100 results on '"JI Hu"'
Search Results
2. Discovery of a Carbamoyl Phosphate Synthetase 1–Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis
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Xinyao Qiu, Lei Chen, Jin Gu, Hongyang Wang, Chengjun Sui, Yangqianwen Zhang, Yan Zhao, Jinxia Bao, Qiuyu Lian, Bo Zheng, Siyun Shen, Guijuan Luo, Shan Wang, Jing Tang, Yani Zhang, Wenwen Wang, Shuai Yang, Zhixuan Li, Ji Hu, Zhao Yang, Kaiting Wang, Yanjing Zhu, Xuan Wu, Tong Wu, and Jianmin Wu
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Male ,Carcinoma, Hepatocellular ,Carbamoyl-Phosphate Synthase (Ammonia) ,Mice, Nude ,Biology ,medicine.disease_cause ,Gas Chromatography-Mass Spectrometry ,Mice ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Urea Cycle Disorders, Inborn ,neoplasms ,Gene ,Hepatology ,Cell growth ,Liver Neoplasms ,Cancer ,DNA Methylation ,Carbamoyl phosphate synthetase ,medicine.disease ,digestive system diseases ,Case-Control Studies ,Hepatocellular carcinoma ,Urea cycle ,Neoplastic Stem Cells ,FOXM1 ,Cancer research ,Transcriptome ,Carcinogenesis ,Neoplasm Transplantation - Abstract
BACKGROUND AND AIMS Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack in-depth study. Here, through analysis of big databases and clinical samples, we identified a carbamoyl phosphate synthetase 1 (CPS1)-deficient hepatocellular carcinoma (HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic reprogramming as a target for HCC prevention. APPROACH AND RESULTS A pan-cancer study involving differentially expressed metabolic genes of 7,764 tumor samples in 16 cancer types provided by The Cancer Genome Atlas (TCGA) demonstrated that urea cycle (UC) was liver-specific and was down-regulated in HCC. A large-scale gene expression data analysis including 2,596 HCC cases in 7 HCC cohorts from Database of HCC Expression Atlas and 17,444 HCC cases from in-house hepatectomy cohort identified a specific CPS1-deficent HCC subtype with poor clinical prognosis. In vitro and in vivo validation confirmed the crucial role of CPS1 in HCC. Liquid chromatography-mass spectrometry assay and Seahorse analysis revealed that UC disorder (UCD) led to the deceleration of the tricarboxylic acid cycle, whereas excess ammonia caused by CPS1 deficiency activated fatty acid oxidation (FAO) through phosphorylated adenosine monophosphate-activated protein kinase. Mechanistically, FAO provided sufficient ATP for cell proliferation and enhanced chemoresistance of HCC cells by activating forkhead box protein M1. Subcutaneous xenograft tumor models and patient-derived organoids were employed to identify that blocking FAO by etomoxir may provide therapeutic benefit to HCC patients with CPS1 deficiency. CONCLUSIONS In conclusion, our results prove a direct link between UCD and cancer stemness in HCC, define a CPS1-deficient HCC subtype through big-data mining, and provide insights for therapeutics for this type of HCC through targeting FAO.
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- 2021
3. The effect of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota in mice
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Yangqianwen Zhang, Jinxia Bao, Jianmin Wu, Xuan Wu, Wenwen Wang, Zhixuan Li, Yanjing Zhu, Ji Hu, Xinyao Qiu, Lei Chen, Tong Wu, Shan Wang, Kaiting Wang, Xue-Bing Shi, Rui Wu, Bo Zheng, Shuai Yang, Xiaoqing Jiang, Hongyang Wang, Qingbao Cheng, Yan Zhao, and Yani Zhang
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medicine.medical_specialty ,medicine.drug_class ,Gut flora ,digestive system ,Gastroenterology ,Bile Acids and Salts ,Mice ,Internal medicine ,medicine ,Animals ,Bile ,Feces ,Colon crypt ,Biliary drainage ,Cholestasis ,Hepatology ,biology ,Bile acid ,business.industry ,Ruminococcus ,Perioperative ,biology.organism_classification ,Gastrointestinal Microbiome ,Drainage ,Bile acid metabolism ,business - Abstract
Background & aims Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota. Methods Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion. Results We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T-ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long-term survival. Conclusion We have successfully created a mice bile drainage collection model. Short-term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long-term survival. (247 words).
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- 2021
4. PRMT4 drives post-ischemic angiogenesis via YB1/VEGF signaling
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Zhaohui Wang, Ji Hu, Shu Yan, Yilong Wang, Pengchao Wang, and Jia Li
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Vascular Endothelial Growth Factor A ,Protein-Arginine N-Methyltransferases ,Angiogenesis ,Neovascularization, Physiologic ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Ischemia ,In vivo ,Drug Discovery ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Cells, Cultured ,Genetics (clinical) ,Tube formation ,Gene knockdown ,Chemistry ,In vitro ,Cell biology ,Endothelial stem cell ,Vascular endothelial growth factor ,HEK293 Cells ,Molecular Medicine ,Y-Box-Binding Protein 1 ,Signal Transduction ,030215 immunology - Abstract
Angiogenesis is an integral process in many ischemic disorders, and vascular endothelial growth factor (VEGF) plays an important role in it. Protein arginine methyltransferase 4 (PRMT4), a member of the type I PRMT family, is involved in various biological activities, but its role in endothelial cell (EC) remains elusive. Here, we aimed to investigate the role of PRMT4 in ischemic angiogenesis and explore the possible underlying mechanism. We found that PRMT4 was upregulated in ischemic muscles, and VEGF treatment potentiated its expression in ECs. In vitro, adenovirus-mediated PRMT4 overexpression promoted, while its gene disruption inhibited, EC proliferation, migration, and tube formation. In an in vivo hindlimb ischemia model, forced expression of PRMT4 in ECs showed accelerated blood flow recovery and increased capillary density, whereas its knockdown exhibited the opposite effect. Mechanistically, PRMT4 activated the transcription of VEGF via the interaction with Y-box binding protein-1 (YB1), leading to accelerated angiogenesis. Interestingly, the loss of YB1 partially abolished PRMT4-mediated angiogenesis in vitro. Collectively, our data revealed that PRMT4 promoted angiogenesis through interacting with YB1 and the consequential VEGF upregulation, suggesting that PRMT4 may present as a potential therapeutic target in ischemic angiogenesis. KEY MESSAGES: •PRMT4 is induced by VEGF and upregulated in a hindlimb ischemia model. •PRMT4 promotes angiogenesis both in vitro and in vivo. •PRMT4 regulates VEGF expression through interacting with YB1. •YB1 knockdown retards PRMT4-mediated angiogenic effects in vitro.
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- 2021
5. Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice
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You Ni, Yifan Feng, Dingding Shen, Ming Chen, Xiaona Zhu, Qinming Zhou, Yining Gao, Jun Liu, Qi Zhang, Yuntian Shen, Lisheng Peng, Zike Zeng, Dou Yin, Ji Hu, and Sheng Chen
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Neurons ,Mice ,Cellular and Molecular Neuroscience ,Neurology ,Cell Adhesion Molecules, Neuronal ,Immunoglobulin G ,General Neuroscience ,Immunology ,Animals ,Nervous System Diseases ,Autoantibodies - Abstract
Background Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. Methods We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing. Results These experiments showed that patient’s anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient’s antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice. Conclusions Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.
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- 2022
6. Tactile modulation of memory and anxiety requires dentate granule cells along the dorsoventral axis
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Yan Gu, Chen Wu, Ji Hu, Hao Wang, Chi Wang, Kun Li, Jing-Ying Yu, Ping Fang, Shumin Duan, Qian Gong, Mathias V. Schmidt, Xiao-Dong Wang, Bing-Xing Pan, Zhen-Zhen Wu, Hui Liu, Xing-Xing Wang, and Yi-Jun Liu
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Male ,0301 basic medicine ,Time Factors ,Dendritic Spines ,Science ,General Physics and Astronomy ,Anxiety ,Biology ,Somatosensory system ,Article ,Synaptic plasticity ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Memory ,Neuroplasticity ,Animals ,Entorhinal Cortex ,Effects of sleep deprivation on cognitive performance ,Prefrontal cortex ,Neurons ,Neuronal Plasticity ,Multidisciplinary ,Behavior, Animal ,Integrases ,Dentate gyrus ,Cognition ,General Chemistry ,Entorhinal cortex ,Mice, Inbred C57BL ,030104 developmental biology ,Touch ,Dentate Gyrus ,Synapses ,Female ,Stress and resilience ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Here, we report that tactile experience enrichment improves memory and alleviates anxiety by remodeling neurons along the dorsoventral axis of the dentate gyrus (DG) in adult mice. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experience-tagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Moreover, adulthood tactile enrichment attenuates early-life stress-induced memory deficits and anxiety-related behavior. Our findings demonstrate that enriched tactile experience retunes the pathway from S1 to DG and enhances DG neuronal plasticity to modulate cognition and emotion., Touch can positively modulate cognitive performance and emotional response. Here the authors demonstrate that enriched tactile experience improves memory and reduces anxiety in adult mice by remodelling the pathway from the primary somatosensory cortex to the dentate gyrus.
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- 2020
7. A new species of Rhodambulyx Mell, 1939 (Lepidoptera: Sphingidae) from Southwest Chongqing, China
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ZHEN-BANG XU, TOMÁŠ MELICHAR, JI-BAI HE, CHAO ZHANG, XIN-YU ZHANG, DU FENG, and SHAO-JI HU
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Male ,China ,Insecta ,Arthropoda ,Sphingidae ,Biodiversity ,Genitalia, Male ,Moths ,Lepidoptera ,Animalia ,Animals ,Animal Science and Zoology ,Genitalia ,Animal Distribution ,Ecology, Evolution, Behavior and Systematics ,Taxonomy - Abstract
A new species of the genus Rhodambulyx Mell, 1939, Rhodambulyx xinyuae sp. nov., is described from Simianshan Nature Reserve in Southwest Chongqing, China. This species is similar to R. davidi Mell, 1939 and R. kitchingi Brechlin, 2015 in habitus, but can be distinguished by a different wing pattern, male genitalia structure and DNA barcode sequence. In addition, Rhodambulyx namvui Eitschberger & Nguyen, 2017 is removed from synonymy with R. kitchingi and synonymized instead with R. davidi, although whether it would be better treated as a subspecies of R. davidi requires further investigation.
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- 2022
8. Fluoxetine reverses hyperactivity of anterior cingulate cortex and attenuates chronic stress-induced hyperalgesia
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Meiru Qi, Chenglin Li, Jie Li, Xiao-na Zhu, Chen Lu, Huoqing Luo, Yifan Feng, Fang Cai, Xia Sun, Shi-Ting Li, Ji Hu, and Yanli Luo
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Pharmacology ,Cellular and Molecular Neuroscience ,Mice ,Serotonin ,Hyperalgesia ,Fluoxetine ,Animals ,Pain ,Gyrus Cinguli - Abstract
Somatic symptom disorder (SSD), which occurs in about 5-7 percent of the adult population, involves heightened physical and emotional sensitivity to pain. However, its neural mechanism remains elusive and thus hinders effective clinical intervention. In this study, we employed chronic restraint stress (CRS)-induced hyperalgesia as a mouse model to investigate the neural mechanism underlying SSD and its pharmacological treatment. We found that CRS induced hyperactivity of anterior cingulate cortex (ACC), whereas chemogenetic inhibition of such hyperactivity could prevent CRS-induced hyperalgesia. Systematic application and ACC local infusion of fluoxetine alleviated CRS-induced hyperalgesia. Moreover, we found that fluoxetine exerted its anti-hyperalgesic effects through inhibiting the hyperactivity of ACC and upregulating 5-HT1A receptors. Our study thus uncovers the functional role of 5-HT signaling in modulating pain sensation and provides a neural basis for developing precise clinical intervention for SSD.
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- 2022
9. Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice
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Yiqiao Wang, Hailong Dong, Ying Wu, Wenzhi Sun, Gaolin Qiu, Long Li, Ji Hu, Zeyong Yang, Xiaona Zhu, and Yuanhai Li
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Male ,medicine.medical_specialty ,Microdialysis ,Dopamine ,medicine.medical_treatment ,Intraperitoneal injection ,Mice, Transgenic ,Nucleus accumbens ,Photometry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Organ Culture Techniques ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,Hypnotics and Sedatives ,Dexmedetomidine ,Neurotransmitter ,030304 developmental biology ,0303 health sciences ,business.industry ,Dopaminergic Neurons ,Ventral Tegmental Area ,Dopaminergic ,Electroencephalography ,Mice, Inbred C57BL ,Ventral tegmental area ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Endocrinology ,chemistry ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine. Methods Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca2+ indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography. Results Ca2+ signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, –0.745 [–1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, –0.498 [–0.664; –0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, –0.329 [–1.220; –0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 μg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice). Conclusions Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
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- 2020
10. Alpha‐lipoic acid downregulates TRPV1 receptor via NF‐κB and attenuates neuropathic pain in rats with diabetes
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Qian Sun, Bing-Yu Zhang, Hong-Hong Zhang, Guang-Yin Xu, Yi-Lian Zhang, Ping-An Zhang, Xi-Xi Wang, and Ji Hu
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0301 basic medicine ,dorsal root ganglion ,medicine.medical_treatment ,Intraperitoneal injection ,TRPV1 ,TRPV Cation Channels ,Pharmacology ,Antioxidants ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,03 medical and health sciences ,Transient receptor potential channel ,0302 clinical medicine ,Dorsal root ganglion ,Downregulation and upregulation ,Ganglia, Spinal ,Physiology (medical) ,Diabetes mellitus ,painful diabetic neuropathy ,medicine ,Animals ,Pharmacology (medical) ,Thioctic Acid ,business.industry ,NF‐κB ,NF-kappa B ,Original Articles ,medicine.disease ,Streptozotocin ,Rats ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Neuropathic pain ,Neuralgia ,Original Article ,Female ,lipids (amino acids, peptides, and proteins) ,business ,030217 neurology & neurosurgery ,transient receptor potential vanilloid‐1 ,medicine.drug - Abstract
Aims Painful diabetic neuropathy (PDN) is a refractory complication of diabetes. The study aimed to investigate the role of α‐lipoic acid (ALA) on the regulation of transient receptor potential vanilloid‐1 (TRPV1) in dorsal root ganglion (DRG) neurons of rats with diabetes. Methods Whole‐cell patch‐clamp recordings were employed to measure neuronal excitability in DiI‐labeled DRG neurons of control and streptozotocin (STZ)‐induced diabetic rats. Western blotting and immunofluorescence assays were used to determine the expression and location of NF‐κBp65 and TRPV1. Results STZ‐induced hindpaw pain hypersensitivity and neuronal excitability in L4‐6 DRG neurons were attenuated by intraperitoneal injection with ALA once a day lasted for one week. TRPV1 expression was enhanced in L4‐6 DRGs of diabetic rats compared with age‐matched control rats, which was also suppressed by ALA treatment. In addition, TRPV1 and p65 colocated in the same DRG neurons. The expression of p65 was upregulated in L4‐6 DRGs of diabetic rats. Inhibition of p65 signaling using recombinant lentiviral vectors designated as LV‐NF‐κBp65 siRNA remarkably suppressed TRPV1 expression. Finally, p65 expression was downregulated by ALA treatment. Conclusion Our findings demonstrated that ALA may alleviate neuropathic pain in diabetes by regulating TRPV1 expression via affecting NF‐κB.
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- 2020
11. The expression of Tim-1 and Tim-4 molecules in regulatory T cells in type 1 diabetes
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Ji Hu, Chen Fang, Cuiping Liu, Ying-Hong Kong, Heming Guo, Sicheng Li, Yingxiao Shen, and Rong Jiang
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,chemical and pharmacologic phenomena ,030209 endocrinology & metabolism ,Spleen ,T-Lymphocytes, Regulatory ,Peripheral blood mononuclear cell ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Mice, Inbred NOD ,Internal medicine ,medicine ,Animals ,Humans ,Hepatitis A Virus Cellular Receptor 1 ,IL-2 receptor ,NOD mice ,Autoimmune disease ,Type 1 diabetes ,medicine.diagnostic_test ,business.industry ,Interleukin-2 Receptor alpha Subunit ,Autoantibody ,Membrane Proteins ,Forkhead Transcription Factors ,hemic and immune systems ,medicine.disease ,Diabetes Mellitus, Type 1 ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Leukocytes, Mononuclear ,business - Abstract
The TIM family comprises of eight genes in the mouse, three of which are conserved in humans (TIM-1, TIM-3, and TIM-4). Previous studies have revealed the relationships between Tim3+ Tregs and autoimmune disease. There was little study about the expression of Tim1 and Tim4 surface molecules on Tregs. We evaluated the frequency of the Tim1+Tregs and Tim4+Tregs in type 1 diabetes (T1D) in the present study. A total of 28 patients with T1D and 14 gender-, age-, and ethnically matched healthy volunteers were recruited. PBMCs from these individuals were isolated and analyzed by flow cytometry. Splenocytes from mice were also analyzed by flow cytometry. There is no difference in the frequency of Treg cells in peripheral blood isolated from T1D patients. Tim1 on CD4+CD25+ T cells decreased significantly in PBMC of patients with T1D(1.19 ± 0.17% vs 2.78 ± 0.38%, 95% CI:0.87–2.31, P
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- 2020
12. Stay Active to Cope with Fear: A Cortico-Intrathalamic Pathway for Conditioned Flight Behavior
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Wen Zhang, Ji Hu, Yi-Fan Ding, Xiao-Hong Xu, and Ni Tang
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Cerebral Cortex ,Neurons ,medicine.medical_specialty ,Neurology ,Physiology ,business.industry ,General Neuroscience ,Pain medicine ,Conditioning, Classical ,MEDLINE ,Fear ,General Medicine ,Human physiology ,Research Highlight ,Physical medicine and rehabilitation ,Thalamus ,Flight, Animal ,Anesthesiology ,Adaptation, Psychological ,Neural Pathways ,Animals ,Medicine ,business ,Adaptation (computer science) - Published
- 2019
13. Projecting Suitability and Climate Vulnerability of Bhutanitis thaidina (Blanchard) (Lepidoptera: Papilionidae) with Conservation Implications
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Zhi-Xian Gong, Dong-Hui Xing, Jinming Hu, and Shao-Ji Hu
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0106 biological sciences ,China ,010504 meteorology & atmospheric sciences ,Climate Change ,Science ,Species distribution ,Climate change ,Bhutanitis thaidina ,010603 evolutionary biology ,01 natural sciences ,Article ,Animals ,Ecosystem ,0105 earth and related environmental sciences ,Ecological niche ,Multidisciplinary ,Habitat fragmentation ,Polymorphism, Genetic ,biology ,Ecology ,Conservation biology ,Endangered Species ,Representative Concentration Pathways ,Biodiversity ,biology.organism_classification ,Lepidoptera ,Habitat destruction ,Geography ,Habitat ,Medicine ,Animal Distribution ,Entomology - Abstract
Bhutanitis thaidina is an endemic, rare, and protected swallowtail in China. Deforestation, habitat fragmentation, illegal commercialised capture, and exploitation of larval food plants are believed to be the four major causes of population decline of B. thaidina in the recent decade. However, little attention was paid to the impact of climate change. This study used ecological niche factor analysis and species distribution model to analyse the current suitable areas for B. thaidina with BioClim variables as well as its future suitable areas under four future climate scenarios (represented by four Representative Concentration Pathways: RCP2.6, RCP4.5, RCP6.0, and RCP8.5). Statistical analysis was carried out to compare the possible area and altitude changes to the distribution of B. thaidina under changing climate. Our analyses showed that the suitable areas for B. thaidina are fragmented under the current climate, with four suitable centres in northwestern Yunnan, northeastern Yunnan and northwestern Guizhou, the western margin of Sichuan Basin, and Qinling mountains. Apart from further habitat fragmentation under climate change, slight range expansion (average 6.0–8.9%) was detected under the RCP2.6 and RCP4.5 scenarios, while more range contraction (average 1.3–26.9%) was detected under the RCP6.0 and RCP8.5 scenarios, with the two southern suitable centres suffering most. Also, a tendency of contraction (2,500–3,500 m) and upslope shift (~600 m) in suitable altitude range were detected. The findings of this study supported the climate-vulnerable hypothesis of B. thaidina, especially under future climate like the RCP6.0 and RCP8.5 scenarios, in terms of contraction in suitable areas and altitude ranges. Conservation priority should be given to northwestern Yunnan, northeastern Yunnan, and northwestern Guizhou to alleviate the stress of massive habitat loss and extinction. Refugial areas should be established in all four suitable centres to maintain genetic diversity of B. thaidina in China.
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- 2019
14. Melanopsin retinal ganglion cells mediate light-promoted brain development
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Jiaxi Hu, Yiming Shi, Jiaming Zhang, Xinfeng Huang, Qian Wang, Hang Zhao, Jiawei Shen, Zhiping Chen, Wei Song, Ping Zheng, Shulu Zhan, Yanping Sun, Pengfei Cai, Kai An, Changjie Ouyang, Baizhen Zhao, Qixin Zhou, Lin Xu, Wei Xiong, Zhi Zhang, Jianjun Meng, Jutao Chen, Yuqian Ma, Huan Zhao, Mei Zhang, Kun Qu, Ji Hu, Minhua Luo, Fuqiang Xu, Xiaowei Chen, Ying Xiong, Jin Bao, and Tian Xue
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Retinal Ganglion Cells ,Mice ,Rod Opsins ,Animals ,Brain ,Humans ,Oxytocin ,General Biochemistry, Genetics and Molecular Biology - Abstract
During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.
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- 2021
15. Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state
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Xin Wang, Wang Xiaoli, Ji Hu, Hong-Miao Cai, Huoqing Luo, Juan-Guo, Xiao-Hui Sun, Peilin Cong, Le Yu, Yuan-Jun Qin, Na Sun, Ming Xue, Qingxiu Wang, Zhao Li, Hui Wang, Ai-Lian Zhang, and Ming Chen
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0301 basic medicine ,Biophysics ,Stimulation ,Optogenetics ,Anxiety ,Biochemistry ,Sevoflurane ,Anxiety state ,03 medical and health sciences ,Mice ,0302 clinical medicine ,mental disorders ,medicine ,Animals ,Molecular Biology ,business.industry ,Dopaminergic Neurons ,Ventral Tegmental Area ,Cell Biology ,Mice, Inbred C57BL ,030104 developmental biology ,nervous system ,030220 oncology & carcinogenesis ,Anesthesia ,Anesthetics, Inhalation ,Female ,medicine.symptom ,business ,psychological phenomena and processes ,medicine.drug - Abstract
Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.
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- 2021
16. Dexmedetomidine Preconditioning Ameliorates Inflammation and Blood–Spinal Cord Barrier Damage After Spinal Cord Ischemia-Reperfusion Injury by Down-Regulation High Mobility Group Box 1-Toll-Like Receptor 4-Nuclear Factor κB Signaling Pathway
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Jiao Liu, Xiaona Fan, Ji Hu, Shuang-Shuang Zhang, Fen Yuan, and Jun Dai
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Male ,Cord ,Down-Regulation ,Inflammation ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Adrenergic alpha-2 Receptor Agonists ,polycyclic compounds ,medicine ,Animals ,Orthopedics and Sports Medicine ,HMGB1 Protein ,Dexmedetomidine ,030222 orthopedics ,Spinal Cord Ischemia ,Tumor Necrosis Factor-alpha ,business.industry ,NF-kappa B ,NFKB1 ,Spinal cord ,medicine.disease ,Toll-Like Receptor 4 ,medicine.anatomical_structure ,Reperfusion Injury ,Tumor necrosis factor alpha ,Rabbits ,Neurology (clinical) ,medicine.symptom ,Signal transduction ,business ,Reperfusion injury ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Signal Transduction ,medicine.drug - Abstract
To evaluate the effect of Dexmedetomidine (Dex) on the inflammatory response and the integrity of blood-spinal cord barrier (BSCB) after spinal cord ischemia-reperfusion injury (SCIRI).To investigate the role of Dex in spinal cord I/R, particularly in the high mobility group box 1-toll-like receptor 4-nuclear factor κB (HMGB1-TLR4-NF-κB) pathway and the integrity of BSCB.High mobility group box 1 (HMGB1) has been identified as a key mediator for the inflammatory response after spinal cord injury. Toll-like receptor 4-nuclear factor κB (TLR4-NF-κB) signaling pathway is the downstream of HMGB1. Dex preconditioning could protect the spinal cord from I/R injury by inhibiting HMGB1 and stabilizing the integrity of BSCB. But its underlying mechanism is not fully understood.Forty-eight male Japanese white rabbits were randomly assigned to three groups (16 rabbits/group): sham, I/R, and Dex + I/R. The hind-limb motor function was assessed at 12 hours intervals for 48 hours after reperfusion using the modified Tarlov scale score. The expression of HMGB1, TLR4, NF-κB, and tumor necrosis factor α (TNF-α) was evaluated by real-time polymerase chain reaction (RT-PCR) and Western blot. The permeability of BSCB was examined via Evans blue (EB) extravasation.Compared with sham group, spinal cord I/R increased the expression of HMGB1, TLR4, NF-κB, and TNF-α as well as the permeability of BSCB (P 0.05). Spinal cord I/R induced the decline of the score of hind-limb motor function (P 0.01). Preconditioning with Dex attenuated the up-regulation of the express of HMGB1, TLR4, NF-κB, TNF-α, and stabilized the permeability of BSCB (P 0.05). Dex preconditioning also improved the hiatopathological outcome and the motor function (P 0.01).Dex preconditioning may inhibit the inflammatory response and stabilize the integrity of BSCB at least partially by inhibiting the HMGB1-TLR4-NF-κB signaling pathway to protect spinal cord from ischemia/reperfusion injury.2.
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- 2019
17. Neuron-derived neuropeptide Y fine-tunes the splenic immune responses
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Jinsong Yu, Ke Xiao, Xiaohua Chen, Lulu Deng, Lu Zhang, Yue Li, Anran Gao, Junjun Gao, Chengchao Wu, Xinmei Yang, Qiudi Zhou, Jian Yang, Chenyu Bao, Jiaji Jiao, Sheng Cheng, Zhiqing Guo, Weize Xu, Xiaojian Cao, Zheng Guo, Jinxia Dai, Ji Hu, Zhenfang Fu, and Gang Cao
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Neurons ,Mice ,General Neuroscience ,Immunity ,Animals ,Humans ,Neuropeptide Y ,Spleen ,Autoimmune Diseases ,Rats ,Receptors, Neuropeptide Y - Abstract
The nervous and immune systems are closely entwined to maintain the immune balance in health and disease. Here, we showed that LPS can activate suprarenal and celiac ganglia (SrG-CG) neurons and upregulate NPY expression in rats. Single-cell sequencing analysis revealed that knockdown of the NPY gene in SrG-CG altered the proliferation and activation of splenic lymphocytes. In a neuron and splenocyte coculture system and in vivo experiments, neuronal NPY in SrG-CG attenuated the splenic immune response. Notably, we demonstrated that neuronal NPF in Drosophila exerted a conservative immunomodulatory effect. Moreover, numerous SNPs in NPY and its receptors were significantly associated with human autoimmune diseases, which was further supported by the autoimmune disease patients and mouse model experiments. Together, we demonstrated that NPY is an ancient language for nervous-immune system crosstalk and might be utilized to alleviate inflammatory storms during infection and to modulate immune balance in autoimmune diseases.
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- 2022
18. Decreased expression of programmed death-1 on CD8
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Yimei, Shan, Yinghong, Kong, Yan, Zhou, Jingjing, Guo, Qiyun, Shi, Sicheng, Li, Heming, Guo, Yiting, Huang, Sisi, Ding, Cuiping, Liu, Lei, Cao, Yun, Huang, Chen, Fang, and Ji, Hu
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Mice ,Diabetes Mellitus, Type 1 ,Programmed Cell Death 1 Receptor ,Leukocytes, Mononuclear ,Animals ,Humans ,CD8-Positive T-Lymphocytes ,Diabetes Mellitus, Experimental - Abstract
Chronic inflammation of autoimmune diseases, including type 1 diabetes (T1D), is mainly mediated by memory T(Tm) cells, predominantly effector memory T (Tem) cells. The roles of the programmed death-1 (PD-1) receptor on lymphocytes have been well studied in tumor and other infection models. However, little is known about the relationship between the expression of PD-1 on CD8A total of 52 patients diagnosed with T1D and 39 gender-, age-, and ethnically matched health control individuals were enrolled in this study. Peripheral blood mononuclear cells from these individuals were isolated and analyzed by flow cytometry. We evaluated the frequencies of PD-1Frequencies of PD-1It is the first report of the expression of PD-1 on CD8
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- 2020
19. Multiregional profiling of the brain transmembrane proteome uncovers novel regulators of depression
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Yaoyang Zhang, Cuiping Tian, Yan Liu, Ting Dang, Y. Li, Chengyu Fan, Zhuangzhuang Zhang, Hui Li, Shanshan Li, Fei Xu, Ronghui Lou, Huoqing Luo, Chen Pan, Lisha Xia, Pan Tang, Chen Miao, Wenqing Shui, Guisheng Zhong, Xiaoxiao Duan, and Ji Hu
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0301 basic medicine ,Proteomics ,Proteome ,Computational biology ,Biology ,Neurotransmission ,environment and public health ,Biochemistry ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Interaction network ,Profiling (information science) ,Animals ,Receptor ,Research Articles ,G protein-coupled receptor ,Messenger RNA ,Multidisciplinary ,Depression ,Brain ,SciAdv r-articles ,Transmembrane protein ,030104 developmental biology ,Cellular Neuroscience ,biological phenomena, cell phenomena, and immunity ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,Research Article - Abstract
In-depth profiling of transmembrane proteins in the brain leads to the identification of GPCR regulators in a disease model., Transmembrane proteins play vital roles in mediating synaptic transmission, plasticity, and homeostasis in the brain. However, these proteins, especially the G protein–coupled receptors (GPCRs), are underrepresented in most large-scale proteomic surveys. Here, we present a new proteomic approach aided by deep learning models for comprehensive profiling of transmembrane protein families in multiple mouse brain regions. Our multiregional proteome profiling highlights the considerable discrepancy between messenger RNA and protein distribution, especially for region-enriched GPCRs, and predicts an endogenous GPCR interaction network in the brain. Furthermore, our new approach reveals the transmembrane proteome remodeling landscape in the brain of a mouse depression model, which led to the identification of two previously unknown GPCR regulators of depressive-like behaviors. Our study provides an enabling technology and rich data resource to expand the understanding of transmembrane proteome organization and dynamics in the brain and accelerate the discovery of potential therapeutic targets for depression treatment.
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- 2020
20. Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer
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Kelly Slocum, Jianmei Fan, Michael Dore, Palermo Mark G, Zhan Deng, Bakary-Barry Toure, Jorge Garcia-Fortanet, Dyuti Majumdar, Martin F. Hentemann, Nick Keen, Suzanne Zhu, Christopher Towler, Michael Shultz, William R. Sellers, Simon Mathieu, Denise Grunenfelder, Robert Koenig, Douglas C. Bauer, Shumei Liu, Jay Larrow, Victoriano Tamez, David Dunstan, Andreea Argintaru, Timothy Michael Ramsey, Zhouliang Chen, Gang Liu, Ying-Nan Chen, Rukundo Ntaganda, Bing Yu, Joanna Slisz, Hongyun Wang, Pascal D. Fortin, Christopher Sean Straub, Ji-Hu Zhang, Ping Wang, Laura R. LaBonte, Mitsunori Kato, Matthew J. Meyer, Fan Yang, Patrick James Sarver, Samuel B. Ho, Brant Firestone, Rajesh Karki, John F. Reilly, Troy Smith, Ho Man Chan, Cary Fridrich, John William Giraldes, Julie Boisclair, Chen Christine Hiu-Tung, Meir Glick, Zhao B. Kang, Morvarid Mohseni, Lawrence Blas Perez, Michael G. Acker, Sarah Williams, Matthew J. LaMarche, Martin Sendzik, Michelle Fodor, Huia-Xiang Hao, Peter Fekkes, Minying Pu, Travis Stams, Stanley Spence, and Andriana Jouk
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Drug ,Programmed cell death ,media_common.quotation_subject ,Allosteric regulation ,Antineoplastic Agents ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Protein tyrosine phosphatase ,Pharmacology ,01 natural sciences ,03 medical and health sciences ,Mice ,Dogs ,Allosteric Regulation ,In vivo ,Neoplasms ,Drug Discovery ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Enzyme Inhibitors ,Gene ,030304 developmental biology ,media_common ,0303 health sciences ,Chemistry ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,0104 chemical sciences ,Rats ,PTPN11 ,010404 medicinal & biomolecular chemistry ,Macaca fascicularis ,Molecular Medicine - Abstract
SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein as well as a potential immunomodulator, controlling SHP2 activity is of high therapeutic interest. As part of our comprehensive program targeting SHP2, we identified multiple allosteric binding modes of inhibition and optimized numerous chemical scaffolds in parallel. In this drug annotation report, we detail the identification and optimization of the pyrazine class of allosteric SHP2 inhibitors. Structure and property based drug design enabled the identification of protein-ligand interactions, potent cellular inhibition, control of physicochemical, pharmaceutical and selectivity properties, and potent in vivo antitumor activity. These studies culminated in the discovery of TNO155, (3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine (1), a highly potent, selective, orally efficacious, and first-in-class SHP2 inhibitor currently in clinical trials for cancer.
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- 2020
21. Mechanism of higher risk for COVID-19 in diabetes: a mask to lift
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Yihui Sun, Xuna Bian, Hui Li, Yun Huang, Ji Hu, Chen Fang, Heming Guo, and Haixia Guan
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Endocrinology, Diabetes and Metabolism ,Pneumonia, Viral ,030209 endocrinology & metabolism ,medicine.disease_cause ,Diabetes Complications ,Betacoronavirus ,03 medical and health sciences ,Viewpoint ,Diabetes mellitus ,0302 clinical medicine ,Endocrinology ,medicine ,Animals ,Humans ,Intensive care medicine ,Pandemics ,Coronavirus ,SARS-CoV-2 ,business.industry ,Middle East respiratory syndrome ,COVID-19 ,medicine.disease ,Severe acute respiratory syndrome ,030220 oncology & carcinogenesis ,Mechanism ,Coronavirus Infections ,business - Abstract
Purpose This essay aims to propose suggestions on what we can learn from previous investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19. Methods We reviewed some literature on diabetes and other types of coronavirus infection such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) and made some summaries and comparisons. Results Diabetes affect the occurrence and progression of COVID-19. Conclusions In-depth and comprehensive exploration of the mechanism of diabetes affecting COVID-19 should be carried out.
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- 2020
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22. SNRIs achieve faster antidepressant effects than SSRIs by elevating the concentrations of dopamine in the forebrain
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Xia Sun, Chen Lu, Ji Hu, Jie Li, Zilong Gao, Yifan Feng, Huoqing Luo, Yanli Luo, and Tangsheng Lu
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0301 basic medicine ,Male ,Restraint, Physical ,Dopamine ,Nucleus accumbens ,Pharmacology ,Serotonergic ,behavioral disciplines and activities ,Photometry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Prosencephalon ,Medicine ,Animals ,Serotonin and Noradrenaline Reuptake Inhibitors ,business.industry ,Depression ,Dopaminergic ,medicine.disease ,Antidepressive Agents ,Mice, Inbred C57BL ,030104 developmental biology ,Treatment Outcome ,Dopamine receptor ,Major depressive disorder ,Antidepressant ,Female ,Serotonin ,business ,030217 neurology & neurosurgery ,Injections, Intraperitoneal ,Selective Serotonin Reuptake Inhibitors ,medicine.drug - Abstract
Major depressive disorder (MDD) is a severe mental disorder with a high disability rate worldwide. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are the most common agents for antidepressant use. SSRIs and SNRIs are believed to achieve antidepressant effects through the activation of serotonergic or noradrenergic systems. However, whether the dopaminergic system is involved remains unclear. In our study, a genetically encoded dopamine sensor and in vivo fiber photometry recordings were used to measure the dopamine concentrations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) after acute intraperitoneal injection of SSRIs or SNRIs. Combined with the behavioral tests, we found that SNRIs increased dopamine concentrations in both the mPFC and the NAc and showed faster antidepressant effects than SSRIs. To verify the enhanced dopamine levels induce the faster antidepressant effects of SNRIs, we employed dopamine receptor antagonists to specifically block the dopaminergic function. The results showed that the faster antidepressant effects of SNRIs were weakened by the dopamine receptor antagonists. Altogether, our study reveals that SNRIs achieve faster antidepressant effects than SSRIs by elevating the dopamine concentrations in the mPFC and the NAc. Our work proposes further mechanisms for the first-line antidepressants, which provides more basis for clinical treatments. This article is part of the special issue on Stress, Addiction and Plasticity.
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- 2020
23. Revision of Pazala Moore, 1888: The Graphium (Pazala) alebion and G. (P.) tamerlanus Groups, with Notes on Taxonomic and Distribution Confusions (Lepidoptera: Papilionidae)
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Yu Feng Hsu, Fabien L. Condamine, Adam M. Cotton, Kuang Duan, Rong Jiang Wang, Hui Hong Zhang, Xin Zhang, Shao-Ji Hu, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Yunnan Agricultural University, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)
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0106 biological sciences ,Insecta ,geographic range ,Arthropoda ,Graphium ,Lineage (evolution) ,010607 zoology ,Zoology ,divergence time ,Late Miocene ,female genitalia ,010603 evolutionary biology ,01 natural sciences ,Lepidoptera genitalia ,Ascomycota ,morphological confusion ,Animals ,Animalia ,Ecology, Evolution, Behavior and Systematics ,Taxonomy ,Parus ,biology ,Papilionidae ,Biodiversity ,biology.organism_classification ,[SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology ,Lepidoptera ,Taxon ,Female ,Animal Science and Zoology ,Taxonomy (biology) ,Subgenus ,Butterflies ,male genitalia - Abstract
International audience; Three Graphium species belonging to two species groups of the subgenus Pazala, the alebion and tamerlanus groups,were examined in molecular and morphological studies, and their female genitalia are reported for the first time. Theirrelationship with other species groups within the subgenus is assessed and their divergence times are estimated. We findthat G. (P.) alebion is the first lineage to diverge within Pazala in the early Miocene (20 Ma) and that G. (P.) tamerlanusand G. (P.) parus are sister species and diverged from each other in the late Miocene (7 Ma). A revision of the fourrecognised taxa belonging to three species is presented, and historical misidentification of these taxa and their geographicranges are explained.
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- 2020
24. Circular RNA profile in diabetic peripheral neuropathy: analysis of coexpression networks of circular RNAs and mRNAs
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Yi-Lian Zhang, Bing-Yu Zhang, Ji Hu, Hong-Hong Zhang, Shufen Hu, Xi-Xi Wang, Pan-Pan Yang, and Guang-Yin Xu
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0301 basic medicine ,Cancer Research ,Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Dorsal root ganglion ,Diabetic Neuropathies ,Microscopy, Electron, Transmission ,Circular RNA ,Diabetes mellitus ,Ganglia, Spinal ,Genetics ,medicine ,Animals ,RNA, Messenger ,health care economics and organizations ,Messenger RNA ,Gene Expression Profiling ,RNA ,High-Throughput Nucleotide Sequencing ,RNA, Circular ,medicine.disease ,Molecular biology ,Sciatic Nerve ,Mice, Inbred C57BL ,030104 developmental biology ,Peripheral neuropathy ,medicine.anatomical_structure ,Ultrastructure ,030217 neurology & neurosurgery - Abstract
Aim: To study the expression pattern of circular RNAs in diabetic peripheral neuropathy. Materials & methods: Transmission electron microscopy was used to observe the ultrastructure of sciatic nerves and dorsal root ganglion (DRGs). circRNAs in DRGs were identified with high-throughput RNA sequencing. Whole-genome mRNAs were detected by a chip scan. Results: The ultrastructure of sciatic nerves and DRGs in diabetes mellitus mice changed significantly. A total of 11,004 circRNAs and 15 differentially expressed circRNAs, as well as 35,368 mRNAs and 133 differentially expressed mRNAs were identified in DRGs between wild-type and diabetes mellitus mice. 11 circRNAs and 14 mRNAs have a significant correlation using strict coexpression analysis. The expression of circRNA.4614 was validated to be upregulated significantly. Conclusion: Our study suggested that circRNAs might be involved in the regulation of mRNA expressions in diabetic peripheral neuropathy.
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- 2020
25. Strong genetic differentiation among populations of
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Chen, Yang, En-Jiao, Zhu, Qiu-Ju, He, Chuan-Hui, Yi, Xu-Bo, Wang, Shao-Ji, Hu, and Shu-Jun, Wei
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Gene Flow ,China ,Conservation of Natural Resources ,Geography ,Endangered Species ,Genetic Drift ,Genetic Variation ,DNA, Mitochondrial ,Mitochondria ,Coleoptera ,Genetics, Population ,Haplotypes ,Genome, Mitochondrial ,Animals ,Ecosystem ,Phylogeny ,Microsatellite Repeats - Abstract
The long-armed scarab (
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- 2020
26. PRMT4 overexpression aggravates cardiac remodeling following myocardial infarction by promoting cardiomyocyte apoptosis
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Ling Yang, Ji Hu, Chenhui Ju, Kai Huang, and Yilong Wang
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0301 basic medicine ,Male ,medicine.medical_specialty ,Coronary artery occlusion ,Protein-Arginine N-Methyltransferases ,Biophysics ,Ischemia ,Myocardial Infarction ,Myocardial Ischemia ,Apoptosis ,Biochemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,cardiovascular diseases ,Myocardial infarction ,RNA, Small Interfering ,Molecular Biology ,Cells, Cultured ,Ventricular function ,Ventricular Remodeling ,business.industry ,Cell Biology ,medicine.disease ,Cell Hypoxia ,Rats ,Up-Regulation ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Animals, Newborn ,030220 oncology & carcinogenesis ,Heart failure ,cardiovascular system ,Cardiology ,Ischemic heart ,business ,Cardiomyocyte apoptosis - Abstract
Myocardial infarction due to coronary artery occlusion leads to adverse cardiac remodeling and heart failure. Apoptotic loss of cardiomyocytes near the ischemia area enlarges infarct area and promotes cardiac remodeling. Protein arginine methyltransferase 4 (PRMT4), a type I protein arginine methyltransferase, is involved in many cellular processes. Here we aimed to investigate the role of PRMT4 in cardiomyocyte apoptosis and myocardial infarction. We found that PRMT4 expression was markedly increased in ischemic heart and hypoxic cardiomyocytes. In vivo, cardiac-specific overexpression of PRMT4 in mice resulted in decreased survival rate, reduced left ventricular function, and aggravated cardiac remodeling following myocardial infarction. Mechanistically, PRMT4 overexpression promoted hypoxia-induced cardiomyocytes apoptosis, while its inhibition abolished these effects. Taken together, our work suggested an essential role of PRMT4 in myocardial infarction and cardiomyocyte apoptosis.
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- 2019
27. Citrate‐assisted efficient local delivery of naked oligonucleotide into live mouse brain cells
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Fei Lv, Ji Hu, Jiang Li, Shouhua Zhang, Lihua Wang, Chunhai Fan, Wenzhi Sun, and Haibin Zhou
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0301 basic medicine ,Male ,medicine.medical_treatment ,vector‐free ,Oligonucleotides ,Hippocampus ,Striatum ,Citric Acid ,Cell membrane ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Sodium citrate ,ssDNA ,medicine ,Animals ,Oligonucleotide ,Chemistry ,neuronal transfection ,Cell Membrane ,Brain ,Membrane Proteins ,hemic and immune systems ,Cell Biology ,General Medicine ,Original Articles ,respiratory system ,Cortex (botany) ,stereotaxic injection ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Membrane protein ,Microscopy, Fluorescence ,030220 oncology & carcinogenesis ,Biophysics ,Original Article ,Adjuvant - Abstract
Objectives Synthetic oligonucleotides have shown promise in brain imaging. However, delivery of oligonucleotides into live brain cells remains challenging. In this study, we aim to develop a facile yet efficient strategy for local delivery of oligodeoxynucleotide (ODN) to neural cells in live adult mouse brain. Materials and methods A fluorescence‐labelled ODN was diluted with sodium citrate buffer (100 mmol/L, pH = 3). One microlitre of the mixture was injected into a live adult mouse brain. Six hours later, we sacrificed the mouse and prepared brain slices for microscopic imaging. Results We find that the use of sodium citrate buffer in the one‐shot local delivery can improve the diffusion and cell entry efficiency of the unmodified ODN for dozens of times. Only 1 pmol ODN leads to hundreds of positively transferred brain cells. We reason that this promotion is due to the local acidic condition created by the citrate buffer, which leads to the protonation of the ODN and some membrane proteins, thus reduces the Coulomb repulsion between the ODN and the cell membrane. Based on this strategy, we demonstrate fluorescent microscopic imaging of brain cells in different brain regions including striatum, cortex, hippocampus and midbrain. Conclusions The citrate buffer can be used as an adjuvant for facile and effective local injection delivery of ODNs, which may provide a new tool for brain imaging.
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- 2019
28. Downregulation of glucose-6-phosphate dehydrogenase contributes to diabetic neuropathic pain through upregulation of toll-like receptor 4 in rats
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Ping-An Zhang, Hong-Hong Zhang, Qian Sun, Guang-Yin Xu, Ji Hu, and Bing-Yu Zhang
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0301 basic medicine ,medicine.medical_specialty ,dorsal root ganglion ,toll-like receptor 4 ,Glucosephosphate Dehydrogenase ,Pathogenesis ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Dorsal root ganglion ,Diabetic Neuropathies ,Internal medicine ,Diabetes mellitus ,hemic and lymphatic diseases ,Ganglia, Spinal ,Medicine ,Glucose-6-phosphate dehydrogenase ,Animals ,neuropathic pain ,Toll-like receptor ,Sulfonamides ,business.industry ,Diabetes ,nutritional and metabolic diseases ,medicine.disease ,Rats ,030104 developmental biology ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Neuropathic pain ,glucose-6-phosphate dehydrogenase ,Molecular Medicine ,Female ,business ,Complication ,030217 neurology & neurosurgery ,Research Article ,Signal Transduction - Abstract
Background and aim Diabetic neuropathic pain is a refractory and disabling complication of diabetes mellitus. The pathogenesis of the diabetic neuropathic pain is still unclear, and treatment is insufficient. The aim of this study is to investigate the roles of glucose-6-phosphate dehydrogenase (G6PD) and toll-like receptor 4 (TLR4) in neuropathic pain in rats with diabetes. Methods Type 1 diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 75 mg/kg) in adult female Sprague-Dawley rats. Paw withdrawal threshold and paw withdrawal latency of rats were measured by von Frey filaments and thermal radiation, respectively. The expressions of G6PD and TLR4 in L4-L6 dorsal root ganglions (DRGs) were measured by western blotting and quantitative real-time polymerase chain reaction analysis. Fluorescent immunohistochemistry was employed to detect expressions of G6PD and TLR4 and co-location of G6PD with TLR4. Results The mRNA and protein expression levels of G6PD in DRGs were significantly decreased in diabetic rats when compared with age-matched control rats. Upregulation of G6PD by intrathecal injection of G6PD overexpression adenovirus markedly attenuated hindpaw pain hypersensitivity of diabetic rats. The mRNA and protein expression levels of TLR4 in DRGs of diabetic rats were significantly increased when compared with control rats. Intrathecal injection of TLR4-selective inhibitor CLI-095 attenuated diabetic pain in dose- and time-dependent manners. Furthermore, G6PD and TLR4 were co-localized in DRG neurons. Intrathecal injection of G6PD overexpression adenovirus greatly reduced TLR4 expression, while intrathecal injection of CLI-095 had no significant effect on G6PD expression in diabetic rats. Conclusions Our results suggest that decrease in G6PD expression was involved in diabetic peripheral neuropathic pain, which was most likely through upregulation of TLR4 expression in the DRGs of rats.
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- 2019
29. High glucose-induced ubiquitination of G6PD leads to the injury of podocytes
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Ji Hu, Min He, Linling Yan, Meng Wu, Yang Yang, Qin Li, Yiming Li, Robert Stanton, Yi Wang, Wei Gong, Diane E. Handy, Bin Lu, Ronggui Hu, Meng Wang, Qinghua Wang, Chuanming Hao, Yeping Yang, and Zhaoyun Zhang
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0301 basic medicine ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Small interfering RNA ,Protein subunit ,Apoptosis ,Glucosephosphate Dehydrogenase ,medicine.disease_cause ,Kidney ,Biochemistry ,Podocyte ,Rats, Sprague-Dawley ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Ubiquitin ,hemic and lymphatic diseases ,parasitic diseases ,Genetics ,medicine ,Animals ,Humans ,Diabetic Nephropathies ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Chemistry ,Podocytes ,Ubiquitination ,nutritional and metabolic diseases ,Ubiquitin ligase ,Cell biology ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Glucose ,HEK293 Cells ,Proteasome ,Mice, Inbred DBA ,Von Hippel-Lindau Tumor Suppressor Protein ,biology.protein ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress ,Biotechnology ,Protein Binding - Abstract
Oxidative stress contributes substantially to podocyte injury, which plays an important role in the development of diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase (G6PD) is critical in maintaining NADPH, which is an important cofactor for the antioxidant system. Here, we hypothesized that high glucose induced ubiquitination and degradation of G6PD, which injured podocytes by reactive oxygen species (ROS) accumulation. We found that G6PD protein expression was decreased in kidneys of both diabetic patients and diabetic rodents. G6PD activity was also reduced in diabetic mice. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD with small interfering RNA induced podocyte apoptosis. In kidneys of G6PD-deficient mice, podocyte apoptosis was significantly increased. Interestingly, high glucose had no effect on G6PD mRNA expression. Decreased G6PD protein expression was mediated by the ubiquitin proteasome pathway. We found that the von Hippel-Lindau (VHL) protein, an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on K366 and K403. In summary, our data suggest that high glucose induces ubiquitination of G6PD by VHL E3 ubiquitin ligase, which leads to ROS accumulation and podocyte injury.-Wang, M., Hu, J., Yan, L., Yang, Y., He, M., Wu, M., Li, Q., Gong, W., Yang, Y., Wang, Y., Handy, D. E., Lu, B., Hao, C., Wang, Q., Li, Y., Hu, R., Stanton, R. C., Zhang, Z. High glucose-induced ubiquitination of G6PD leads to the injury of podocytes.
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- 2019
30. A New Species of the Graphium (Pazala) mandarinus Group from Central Vietnam (Lepidoptera: Papilionidae)
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Alexander L. Monastyrskii, Adam M. Cotton, Fabien L. Condamine, Shao-Ji Hu, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)
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0106 biological sciences ,Insecta ,Arthropoda ,Graphium ,Range (biology) ,[SDV]Life Sciences [q-bio] ,mandarinus-group ,010607 zoology ,Zoology ,010603 evolutionary biology ,01 natural sciences ,Lepidoptera genitalia ,Animals ,Animalia ,Pazala ,Clade ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,Taxonomy ,new species ,Leptocircini ,biology ,Papilionidae ,Biodiversity ,biology.organism_classification ,Lepidoptera ,Taxon ,Vietnam ,Molecular phylogenetics ,Animal Science and Zoology ,Butterflies ,Global biodiversity - Abstract
The Graphium (Pazala) mandarinus group was recently defined and the status of taxa as well as the number of species was revised. We report here the discovery of a new species from Kon Tum plateau of the Truong Son (Annamite) Range of Central Vietnam, which we describe based on morphological and molecular evidence. Molecular phylogeny shows that the new taxon, G. (P.) wenlingae Hu, Cotton & Monastyrskii sp. nov., is sister to G. (P.) daiyuanae Hu, Zhang & Cotton, 2018 plus G. (P.) confucius Hu, Duan & Cotton, 2018. Molecular dating analysis further suggests that this new species diverged from its sister clade in the Pliocene (~3.5 million years ago). The new taxon constitutes the eighth and southernmost species of the mandarinus group.
- Published
- 2019
31. Identifying Immigrating Sogatella furcifera (Hemiptera: Delphacidae) Using Field Cages: A Case Study in the Yuanjiang (Red River) Valley of Yunnan, China
- Author
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Shao-Ji Hu, Hui Ye, Wen-Xin Wang, Li-Min Dong, and Sui-Yun Chen
- Subjects
0106 biological sciences ,Nymph ,China ,Population ,01 natural sciences ,Hemiptera ,Planthopper ,demographic structure ,Animals ,education ,population density ,Research Articles ,education.field_of_study ,migratory rice pest ,biology ,Outbreak ,General Medicine ,biology.organism_classification ,010602 entomology ,Agronomy ,Insect Science ,field cage ,Animal Migration ,PEST analysis ,Seasons ,Delphacidae ,planthopper ,Animal Distribution - Abstract
The white-backed planthopper, Sogatella furcifera (Horváth), is a devastating migratory rice pest in South China; lack of effective methods to identify immigrating populations is the main cause of difficulties in outbreak forecasting, active prevention, and control. The current study set up field cages (2 × 2 × 3 m each, US-80 standard nylon mesh) in both early- and mid-season paddies in Yuanjiang (Red River) Valley in Yunnan, China, in 2012 and 2014. The immigrating population was successfully separated from the local population of S. furcifera and identified using statistical comparisons. The findings showed that densities of macropterous adults outside the cages were all significantly higher than those inside the cages on both early- and mid-season rice in both years, whereas the densities of young nymphs and old nymphs showed no significant differences. This indicated that immigrations were occurring, the earliest of which occurred on early-season rice in early May and reached its peak in mid-late May before a rapid collapse in both years. In contrast, the immigration on mid-season rice showed a continuous decline or fluctuation throughout the entire period. Analyses demonstrated that the migration process of S. furcifera in the Yuanjiang Valley features continuous immigration from the adjacent southern parts of Yunnan, which may represent most migration events in Yunnan during the outbreak period of a year. The findings of this case study could benefit our understanding of planthopper migration and outbreaks in other parts of China, especially where the outbreak pattern is very different from Yunnan.
- Published
- 2019
32. Therapeutic Effect of Chitooligosaccharide Tablets on Lipids in High-Fat Diets Induced Hyperlipidemic Rats
- Author
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Can-Ji Hu, Yan Bai, Xiaoyi Deng, Di Yang, Hua Cao, Zhengquan Su, and Jiao Guo
- Subjects
Pharmaceutical Science ,Blood lipids ,Oligosaccharides ,Chitin ,Kidney ,Analytical Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,Hyperlipidemia ,lipid metabolism ,gene difference expression ,Adiposity ,0303 health sciences ,Chemistry ,Lipids ,Adipose Tissue ,Liver ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Oxidation-Reduction ,Tablets ,medicine.medical_specialty ,Hyperlipidemias ,Cholesterol 7 alpha-hydroxylase ,Diet, High-Fat ,Article ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Internal medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,Liver X receptor ,030304 developmental biology ,HMGCR ,Chitosan ,Cholesterol ,chitooligosaccharide ,Organic Chemistry ,Lipid metabolism ,medicine.disease ,Rats ,Disease Models, Animal ,Endocrinology ,Gene Expression Regulation ,LDL receptor ,antihyperlipidemic ,Biomarkers ,Lipoprotein - Abstract
Chitooligosaccharide is beneficial for inhibiting dyslipidemia and reducing atherosclerotic and hyperlipidemic risk. The purpose of this study was to investigate the cholesterol-regulating effects and potential mechanisms of Chitooligosaccharide tablets (CFTs) in high-fat diet-induced hyperlipidemic rats. The results revealed that CFTs can regulate serum lipid levels in hyperlipidemic rats in a dosage-dependent manner. Synchronously, gene expressions related to cholesterol excretion were upregulated in a dosage-dependent manner, including cholesterol 7&alpha, hydroxylase (CYP7A1), liver X receptor &alpha, (LXRA), peroxisome proliferation-activated receptor-&alpha, (PPAR&alpha, ) and low-density lipoprotein receptor (LDLR), whereas cholesterol synthetic gene expressions including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and sterol-responsive element binding protein-2 (SREBP2) were reduced. This work highlights that CFTs have potential as natural products to prevent and treat metabolic hyperlipidemia syndrome, probably due to the reduction of cholesterol biosynthesis and through cholesterol elimination, they also improve the pathological changes of liver tissue in rats, alleviate liver damage, maintain normal lipid metabolism in the liver, ameliorate hepatic glycolipid disorders and accelerate TC operation, and reduce blood lipid levels.
- Published
- 2019
33. Brain control of humoral immune responses amenable to behavioural modulation
- Author
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Xu, Zhang, Bo, Lei, Yuan, Yuan, Li, Zhang, Lu, Hu, Sen, Jin, Bilin, Kang, Xuebin, Liao, Wenzhi, Sun, Fuqiang, Xu, Yi, Zhong, Ji, Hu, and Hai, Qi
- Subjects
Adrenergic Neurons ,Male ,Behavior, Animal ,Corticotropin-Releasing Hormone ,T-Lymphocytes ,Plasma Cells ,Brain ,Receptors, Nicotinic ,Amygdala ,Lymphocyte Activation ,Acetylcholine ,Choline O-Acetyltransferase ,Immunity, Humoral ,Mice ,Immunoglobulin G ,Hemocyanins ,Animals ,Spleen ,Stress, Psychological ,Paraventricular Hypothalamic Nucleus - Abstract
It has been speculated that brain activities might directly control adaptive immune responses in lymphoid organs, although there is little evidence for this. Here we show that splenic denervation in mice specifically compromises the formation of plasma cells during a T cell-dependent but not T cell-independent immune response. Splenic nerve activity enhances plasma cell production in a manner that requires B-cell responsiveness to acetylcholine mediated by the α9 nicotinic receptor, and T cells that express choline acetyl transferase
- Published
- 2018
34. Zona incerta GABAergic neurons integrate prey-related sensory signals and induce an appetitive drive to promote hunting
- Author
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Zheng-Dong, Zhao, Zongming, Chen, Xinkuan, Xiang, Mengna, Hu, Hengchang, Xie, Xiaoning, Jia, Fang, Cai, Yuting, Cui, Zijun, Chen, Lechen, Qian, Jiashu, Liu, Congping, Shang, Yiqing, Yang, Xinyan, Ni, Wenzhi, Sun, Ji, Hu, Peng, Cao, Haohong, Li, and Wei L, Shen
- Subjects
Mice ,Predatory Behavior ,Animals ,Zona Incerta ,GABAergic Neurons - Abstract
The neural substrates for predatory hunting, an evolutionarily conserved appetitive behavior, remain largely undefined. Photoactivation of zona incerta (ZI) GABAergic neurons strongly promotes hunting of both live and artificial prey. Conversely, photoinhibition of these neurons or deletion of their GABA function severely impairs hunting. Here electrophysiological recordings reveal that ZI neurons integrate prey-related multisensory signals and discriminate prey from non-prey targets. Visual or whisker sensory deprivation reduces calcium responses induced by prey introduction and attack and impair hunting. ZI photoactivation largely corrects the hunting impairment caused by sensory deprivations. Motivational and reinforcing assays reveal that ZI photoactivation is associated with a strong appetitive drive, causing repetitive self-stimulatory behaviors. These ZI neurons project to the periaqueductal gray matter to induce hunting and motivation. Thus, we have delineated the function of ZI GABAergic neurons in hunting, which integrates prey-related sensory signals into prey detection and attack and induces a strong appetitive motivational drive.
- Published
- 2018
35. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor
- Author
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Matthew J. LaMarche, Peter Fekkes, Jorge Garcia Fortanet, Michael Shultz, Denise Grunenfelder, Zhouliang Chen, Gang Liu, Chen Christine Hiu-Tung, Minying Pu, Travis Stams, Pascal D. Fortin, Palermo Mark G, Ping Wang, Samuel B. Ho, Brant Firestone, Matthew J. Meyer, Dyuti Majumdar, Laura R. LaBonte, Francois Lenoir, Rajesh Karki, Nick Keen, Cary Fridrich, Michelle Fodor, Jay Larrow, Sarah Williams, Christopher Towler, Timothy Michael Ramsey, Ji-Hu Zhang, Franco Lombardo, Ying-Nan P. Chen, Zhan Deng, Mitsunori Kato, Zhao B. Kang, Lawrence Blas Perez, Shumei Liu, and William R. Sellers
- Subjects
Male ,Models, Molecular ,0301 basic medicine ,Programmed cell death ,Allosteric modulator ,Protein Conformation ,Allosteric regulation ,Administration, Oral ,Mice, Nude ,Antineoplastic Agents ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Protein tyrosine phosphatase ,Crystallography, X-Ray ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Allosteric Regulation ,Piperidines ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Structure–activity relationship ,Chemistry ,Small molecule ,High-Throughput Screening Assays ,Mice, Inbred C57BL ,PTPN11 ,Pyrimidines ,030104 developmental biology ,Biochemistry ,Drug Design ,Pyrazines ,030220 oncology & carcinogenesis ,Heterografts ,Molecular Medicine ,Female ,Allosteric Site ,Neoplasm Transplantation - Abstract
SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programmed cell death pathway (PD-1/PD-L1). Because it is an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest. Recently in our laboratories, a small molecule inhibitor of SHP2 was identified as an allosteric modulator that stabilizes the autoinhibited conformation of SHP2. A high throughput screen was performed to identify progressable chemical matter, and X-ray crystallography revealed the location of binding in a previously undisclosed allosteric binding pocket. Structure-based drug design was employed to optimize for SHP2 inhibition, and several new protein-ligand interactions were characterized. These studies culminated in the discovery of 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine (SHP099, 1), a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor.
- Published
- 2016
36. Advance in spinal cord ischemia reperfusion injury: Blood–spinal cord barrier and remote ischemic preconditioning
- Author
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Qijing Yu, Jin-Xiu Huang, Ji Hu, and Hongfei Zhu
- Subjects
0301 basic medicine ,Cord ,Ischemia ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Ischemic Preconditioning ,Neurological deficit ,Spinal Cord Ischemia ,business.industry ,Spinal cord ischemia ,General Medicine ,Spinal cord ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Anesthesia ,Ischemic preconditioning ,business ,Reperfusion injury ,030217 neurology & neurosurgery ,Homeostasis - Abstract
The blood-spinal cord barrier (BSCB) is the physiological and metabolic substance diffusion barrier between blood circulation and spinal cord tissues. This barrier plays a vital role in maintaining the microenvironment stability of the spinal cord. When the spinal cord is subjected to ischemia/reperfusion (I/R) injury, the structure and function of the BSCB is disrupted, further destroying the spinal cord homeostasis and ultimately leading to neurological deficit. Remote ischemic preconditioning (RIPC) is an approach in which interspersed cycles of preconditioning ischemia is followed by reperfusion to tissues/organs to protect the distant target tissues/organs against subsequent lethal ischemic injuries. RIPC is an innovation of the treatment strategies that protect the organ from I/R injury. In this study, we review the morphological structure and function of the BSCB, the injury mechanism of BSCB resulting from spinal cord I/R, and the effect of RIPC on it.
- Published
- 2016
37. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway
- Author
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Ru Yang, Ji Hu, Lin Bo, Zhichun Liu, Jun Huang, Leixi Xue, Zhiqin Liu, and Jian Wen
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Article Subject ,p38 mitogen-activated protein kinases ,Immunology ,Lupus nephritis ,Dioxoles ,Smad2 Protein ,SMAD ,Biology ,urologic and male genital diseases ,p38 Mitogen-Activated Protein Kinases ,Cell Line ,Transforming Growth Factor beta1 ,Mice ,03 medical and health sciences ,lcsh:Pathology ,medicine ,Renal fibrosis ,Animals ,Humans ,RNA, Small Interfering ,skin and connective tissue diseases ,Cytokine TWEAK ,Cell Biology ,Cadherins ,medicine.disease ,Lupus Nephritis ,Actins ,030104 developmental biology ,Apoptosis ,Benzamides ,Tumor Necrosis Factors ,Cancer research ,Female ,Tumor Necrosis Factor Inhibitors ,Tumor necrosis factor alpha ,lcsh:RB1-214 ,Research Article ,Signal Transduction - Abstract
This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used forin vivoexperiments and human proximal tubular cells (HK2 cells) were used forin vitroexperiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, andα-SMA proteins.In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2,α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway.
- Published
- 2016
38. Central Processing of Itch in the Midbrain Reward Center
- Author
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Ming-Gang Liu, Tian-Le Xu, Chen Huang, Michael X. Zhu, Xin-Yu Su, Ji Hu, Su-Shan Guo, Yong Li, Wenzhi Sun, Ying Li, Huoqing Luo, Ming Chen, and Yuan Yuan
- Subjects
0301 basic medicine ,Optogenetics ,Biology ,Histamine Agonists ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Reward ,Dopamine ,Mesencephalon ,parasitic diseases ,otorhinolaryngologic diseases ,medicine ,Biological neural network ,Animals ,Calcium Signaling ,GABAergic Neurons ,skin and connective tissue diseases ,Behavior, Animal ,General Neuroscience ,Dopaminergic Neurons ,Pruritus ,Dopaminergic ,Ventral Tegmental Area ,Chloroquine ,Scratching ,eye diseases ,Electrophysiological Phenomena ,Ventral tegmental area ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,GABAergic ,Neuron ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug ,Histamine - Abstract
Itch is an aversive sensation that evokes a desire to scratch. Paradoxically, scratching the itch also produces a hedonic experience. The specific brain circuits processing these different aspects of itch, however, remain elusive. Here, we report that GABAergic (GABA) and dopaminergic (DA) neurons in the ventral tegmental area (VTA) are activated with different temporal patterns during acute and chronic itch. DA neuron activation lags behind GABA neurons and is dependent on scratching of the itchy site. Optogenetic manipulations of VTA GABA neurons rapidly modulated scratching behaviors through encoding itch-associated aversion. In contrast, optogenetic manipulations of VTA DA neurons revealed their roles in sustaining recurrent scratching episodes through signaling scratching-induced reward. A similar dichotomy exists for the role of VTA in chronic itch. These findings advance understanding of circuit mechanisms of the unstoppable itch-scratch cycles and shed important insights into chronic itch therapy.
- Published
- 2018
39. Revision of Pazala Moore, 1888: The Graphium (Pazala) mandarinus (Oberthür, 1879) Group, with Treatments of Known Taxa and Descriptions of New Species and New Subspecies (Lepidoptera: Papilionidae)
- Author
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Yu Feng Hsu, Kuang Duan, Shao-Ji Hu, Rong Jiang Wang, Adam M. Cotton, Jun Cao, Xin Zhang, Fabien L. Condamine, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Beijing Research Center of Intelligent Equipment for Agriculture, Department of Microbiology and Immunology, Department of Pathology and Molecular Medicine and Cancer Research Institute, Queen's University [Kingston, Canada], and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)
- Subjects
0106 biological sciences ,0301 basic medicine ,China ,Insecta ,Arthropoda ,[SDV]Life Sciences [q-bio] ,Zoology ,India ,Myanmar ,Papilio ,Subspecies ,010603 evolutionary biology ,01 natural sciences ,Lepidoptera genitalia ,03 medical and health sciences ,Species level ,Animals ,Animalia ,Pazala ,Ecology, Evolution, Behavior and Systematics ,Taxonomy ,Leptocircini ,new species ,Molecular dating ,biology ,Papilionidae ,Biodiversity ,biology.organism_classification ,Lepidoptera ,030104 developmental biology ,Taxon ,Vietnam ,Sympatric speciation ,Animal Science and Zoology ,Animal Distribution ,Butterflies - Abstract
International audience; The previously recognised closely related species Graphium (Pazala) mandarinus (Oberthür, 1879) and G. (P.) sichuanica(Koiwaya, 1993) are shown to comprise seven species as a result of both molecular and morphological analysis. Molecular dating analysis is also performed on the mandarinus group in order to investigate the divergence time of the taxa. Two HU ET AL. 402·Zootaxa 4441 (3) © 2018Magnolia Presstaxa, G. (P.) garhwalica (Katayama, 1988) stat. nov. and G. (P.) paphus (de Nicéville, 1886) stat. nov., are raised from sub-specific to specific status; G. (P.) hoeneanus Cotton & Hu nom. nov., stat. rev. is separated from sichuanica at species level; and two previously unrecognised new species, G. (P.) daiyuanae Hu, Zhang & Cotton sp. nov. and G. (P.) confucius Hu, Duan & Cotton sp. nov. are described from Vietnam and China respectively, the latter being sympatric with nominate G.(P.) mandarinus. The identity of the lectotype of G. (P.) mandarinus is confirmed and a lectotype is designated for the tax-on Papilio Glycerion Gray, 1831. A new subspecies of G. (P.) mandarinus is described from western Yunnan and northern Myanmar, G. (P.) mandarinusstilwelli Cotton & Hu ssp. nov.
- Published
- 2018
40. Lateral habenula in the pathophysiology of depression
- Author
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Yan Yang, Hailan Hu, Ji Hu, and Hao Wang
- Subjects
0301 basic medicine ,endocrine system ,media_common.quotation_subject ,Learned helplessness ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Animals ,Humans ,Depressive symptoms ,Depression (differential diagnoses) ,Lateral habenula ,media_common ,Neurons ,Depressive Disorder ,Habenula ,Human studies ,business.industry ,General Neuroscience ,Anhedonia ,Appetite ,Pathophysiology ,Disease Models, Animal ,030104 developmental biology ,medicine.symptom ,Nerve Net ,business ,Neuroscience ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery - Abstract
Depression is a devastating disorder with a combination of diverse symptoms such as low self-esteem, lack of motivation, anhedonia, loss of appetite, low energy, and discomfort without a clear cause. Depression has been suggested to be the result of maladaptive changes in specific brain circuits. Recently, the lateral habenula (LHb) has emerged as a key brain region in the pathophysiology of depression. Increasing evidence from rodent, non-human primate and human studies indicates that the aberrant activity of the LHb is associated with depressive symptoms such as helplessness, anhedonia, and excessive negative focus. Revealing the molecular, cellular and circuit properties of the LHb will help explain how abnormalities in LHb activity are linked to depressive disorders, and shed light on developing novel strategies for depression treatment.
- Published
- 2017
41. Progress and prospects of circular RNAs in Hepatocellular carcinoma: Novel insights into their function
- Author
-
Jun Li, Peng Li, Ji Hu, Xiao-Ming Meng, Yun-xuan Ge, Cheng Huang, Yang Song, and Tao Xu
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,Physiology ,Clinical Biochemistry ,Biology ,Bioinformatics ,Metastasis ,Pathogenesis ,03 medical and health sciences ,Cell Movement ,microRNA ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Neoplasm Invasiveness ,RNA, Neoplasm ,neoplasms ,Cell Proliferation ,Mechanism (biology) ,Liver Neoplasms ,Cell Biology ,RNA, Circular ,medicine.disease ,Prognosis ,digestive system diseases ,Liver regeneration ,Biomarker (cell) ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Hepatocellular carcinoma ,Disease Progression ,RNA ,Function (biology) ,Signal Transduction - Abstract
Hepatocellular carcinoma (HCC) is one of the most predominant subjects of liver malignancies, which arouses global concern in the recent years. Advanced studies have found that Circular RNAs (circRNAs) are differentially expressed in HCC, with its regulatory capacity in HCC pathogenesis and metastasis. However, the underlying mechanism remains largely unknown. In this review, we summarized the functions and mechanisms of those aberrantly expressed circRNAs in HCC tissues. We hope to enlighten more comprehensive studies on the detailed mechanisms of circRNAs and explore their potential values in clinic applications. It revealed that hsa_circ_0004018 can be used as a potential biomarker in HCC diagnosis, with its superior sensitivity to alpha-fetoprotein (AFP). Notably, the correlation of circRNA abundance in the proliferation of liver regeneration (LR) has recently been clarified and different circRNA profiles served as candidates for nonalcoholic steatohepatitis (NASH) diagnosis also be discussed. Therefore, the improved understanding of circRNAs in HCC pathogenesis and metastasis proposed a novel basis for the early diagnosis in HCC patients, which provides a useful resource to explore the pathogenesis of HCC.
- Published
- 2017
42. Alpha-lipoic Acid suppresses P2X receptor activities and visceral hypersensitivity to colorectal distention in diabetic rats
- Author
-
Qian Sun, Yu Feng, Xin Qin, Zhen-Yuan Song, Hong-Hong Zhang, Pan-Pan Yang, Guang-Yin Xu, and Ji Hu
- Subjects
medicine.medical_specialty ,Colon ,medicine.medical_treatment ,Science ,Intraperitoneal injection ,Withdrawal reflex ,Streptozocin ,Article ,Diabetes Mellitus, Experimental ,Diabetes Complications ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Dorsal root ganglion ,Internal medicine ,Diabetes mellitus ,Ganglia, Spinal ,Physical Stimulation ,Medicine ,Animals ,Patch clamp ,Receptor ,Pain Measurement ,Neurons ,Multidisciplinary ,medicine.diagnostic_test ,Thioctic Acid ,business.industry ,Rectum ,medicine.disease ,Streptozotocin ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Hyperalgesia ,Receptors, Purinergic P2X ,030211 gastroenterology & hepatology ,Female ,business ,030217 neurology & neurosurgery ,Receptors, Purinergic P2X3 ,medicine.drug ,Receptors, Purinergic P2X2 - Abstract
The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ATP-induced current density of colon-specific DRG (T13-L2 DRGs) neurons was measured with whole-cell patch clamp. The expression of P2X3Rs of T13-L2 DRGs was measured by western blot analysis. The results showed that AWR scores significantly increased after STZ injection. P2X3R expression and ATP current density of T13-L2 DRG neurons were enhanced in diabetic rats. Intraperitoneal injection with ALA once a day for 1 week remarkably reduced P2X3R expression and ATP current density in diabetic rats. Importantly, ALA treatment attenuated colonic hypersensitivity in diabetic rats. Our data suggest that STZ injection increases expression and function of P2X3 receptors of colon-specific DRG neurons, thus contributing to colonic hypersensitivity in diabetic rats. Administration of ALA attenuates diabetic colonic hypersensitivity, which is most likely mediated by suppressing expression and function of P2X3 receptors in DRGs of diabetic rats.
- Published
- 2017
43. Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED
- Author
-
Guobin Li, Leying Feng, Fangjun Luo, Justin Gu, Hailong Zhang, En Li, Mengxi Zhao, Andreas Lingel, Ling Li, Ophelia Ardayfio, Wei Qi, Zhenting Gao, Lin Teng, Chris Lu, Ying Huang, Johannes Ottl, Peter Atadja, Hong Fan, Zhengtian Yu, Ying Lin, Yuan Mi, Lijian Feng, Xiao Luo, Dirksen E. Bussiere, Kehao Zhao, Ji-Hu Zhang, Man Zhang, and Lei Liu
- Subjects
0301 basic medicine ,Competitive Inhibitors ,Quantitative Structure-Activity Relationship ,lcsh:Medicine ,Biochemistry ,Mass Spectrometry ,Analytical Chemistry ,Histones ,Binding Analysis ,Mice ,Spectrum Analysis Techniques ,Drug Discovery ,Sulfones ,Enzyme Inhibitors ,Amino Acids ,lcsh:Science ,Regulation of gene expression ,Liquid Chromatography ,Multidisciplinary ,Crystallography ,Drug discovery ,Organic Compounds ,Physics ,Chromatographic Techniques ,Polycomb Repressive Complex 2 ,Condensed Matter Physics ,Molecular Docking Simulation ,Chemistry ,Histone ,Bioassays and Physiological Analysis ,Recombination-Based Assay ,Physical Sciences ,Crystal Structure ,Basic Amino Acids ,PRC2 ,Research Article ,Stereochemistry ,Protein subunit ,Liquid Chromatography-Mass Spectrometry ,Library Screening ,macromolecular substances ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Histone H3 ,DNA-binding proteins ,Solid State Physics ,Animals ,Binding site ,Molecular Biology Techniques ,Molecular Biology ,Chemical Characterization ,Enzyme Assays ,Molecular Biology Assays and Analysis Techniques ,Binding Sites ,Biology and life sciences ,Lysine ,Organic Chemistry ,lcsh:R ,Rational design ,Chemical Compounds ,Proteins ,Triazoles ,High-Throughput Screening Assays ,030104 developmental biology ,biology.protein ,Enzymology ,lcsh:Q ,Biochemical Analysis - Abstract
Polycomb repressive complex 2 (PRC2), a histone H3 lysine 27 methyltransferase, plays a key role in gene regulation and is a known epigenetics drug target for cancer therapy. The WD40 domain-containing protein EED is the regulatory subunit of PRC2. It binds to the tri-methylated lysine 27 of the histone H3 (H3K27me3), and through which stimulates the activity of PRC2 allosterically. Recently, we disclosed a novel PRC2 inhibitor EED226 which binds to the K27me3-pocket on EED and showed strong antitumor activity in xenograft mice model. Here, we further report the identification and validation of four other EED binders along with EED162, the parental compound of EED226. The crystal structures for all these five compounds in complex with EED revealed a common deep pocket induced by the binding of this diverse set of compounds. This pocket was created after significant conformational rearrangement of the aromatic cage residues (Y365, Y148 and F97) in the H3K27me3 binding pocket of EED, the width of which was delineated by the side chains of these rearranged residues. In addition, all five compounds interact with the Arg367 at the bottom of the pocket. Each compound also displays unique features in its interaction with EED, suggesting the dynamics of the H3K27me3 pocket in accommodating the binding of different compounds. Our results provide structural insights for rational design of novel EED binder for the inhibition of PRC2 complex activity.
- Published
- 2017
44. Postsynaptic Potentiation of Corticospinal Projecting Neurons in the Anterior Cingulate Cortex after Nerve Injury
- Author
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Xiao Bin He, Le Shi Zhang, Zhijian Zhang, Jian Wang, Min Zhuo, Giannina Descalzi, Xin Qin, Yun-Qing Li, Shuang Qiu, Kohei Koga, Fuqiang Xu, Richard L. Huganir, Ji Hu, Feng Wei, and Tao Chen
- Subjects
Male ,Stilbamidines ,Long-Term Potentiation ,Pyramidal Tracts ,Mice, Transgenic ,In Vitro Techniques ,Neurotransmission ,Gyrus Cinguli ,Mice ,Viral Proteins ,Cellular and Molecular Neuroscience ,Postsynaptic potential ,Animals ,Medicine ,Receptors, AMPA ,Phytohemagglutinins ,Peroneal Neuropathies ,Neurons ,Pyramidal tracts ,business.industry ,Research ,Long-term potentiation ,Nerve injury ,Mice, Inbred C57BL ,Disease Models, Animal ,Luminescent Proteins ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,nervous system ,Mutation ,Peripheral nerve injury ,Synaptic plasticity ,Excitatory postsynaptic potential ,Molecular Medicine ,medicine.symptom ,business ,Proto-Oncogene Proteins c-fos ,Neuroscience - Abstract
Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.
- Published
- 2014
45. Electroacupuncture Suppresses Mechanical Allodynia and Nuclear Factor Kappa B Signaling in Streptozotocin‐Induced Diabetic Rats
- Author
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Hong-Hong Zhang, Guang-Yin Xu, Ying Xiao, Lei Shi, and Ji Hu
- Subjects
medicine.medical_specialty ,Electroacupuncture ,medicine.medical_treatment ,Intraperitoneal injection ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Pyrrolidine dithiocarbamate ,Dorsal root ganglion ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Pharmacology (medical) ,Pain Measurement ,Pharmacology ,biology ,business.industry ,NF-kappa B ,nutritional and metabolic diseases ,Original Articles ,Streptozotocin ,Cystathionine beta synthase ,Rats ,Psychiatry and Mental health ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Hyperalgesia ,Anesthesia ,Neuropathic pain ,biology.protein ,Female ,medicine.symptom ,business ,Signal Transduction ,medicine.drug - Abstract
Summary Aims To investigate whether electroacupuncture (EA) produced analgesic effect and whether nuclear factor kappa B (NF-κB) and cystathionine β synthase (CBS) involved in EA-mediated analgesia in painful diabetic neuropathy in rats. Methods Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) in adult female rats. Mechanical pain threshold was measured by von Frey filaments. EA was applied at acupoint Zu-San-Li (ST-36) in both hindlimbs. Western blot analysis was employed to detect changes in protein levels of NF-κB and CBS in spinal dorsal root ganglion (DRGs). Results Mechanical allodynia was developed 2 weeks after STZ injection and lasted for another 4 weeks. STZ injection significantly enhanced expression of p65 and CBS in lumbar L4-6 DRGs when compared with age-matched controls. EA markedly attenuated mechanical allodynia. Importantly, EA treatment remarkably inhibited p65 and CBS expression in DRGs. Additionally, intrathecal injection of the p65 antagonist pyrrolidine dithiocarbamate attenuated mechanical allodynia and markedly inhibited CBS expression in DRGs in STZ rats. Conclusions These data indicate that EA produced an analgesic effect, which might be mediated at least in a part by inhibition of NF-κB signaling pathway in primary sensory neurons in rats with diabetes.
- Published
- 2012
46. Quantifying the effect of nanoparticles on As(V) ecotoxicity exemplified by nano-Fe2O3(magnetic) and nano-Al2O3
- Author
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Ji Hu, Brett E. Forthaus, Demin Wang, and Jianmin Wang
- Subjects
inorganic chemicals ,Health, Toxicology and Mutagenesis ,Nanoparticle ,chemistry.chemical_element ,Aluminum Hydroxide ,Nanotechnology ,Nano al2o3 ,Ferric Compounds ,Risk Assessment ,Arsenic ,Lethal Dose 50 ,Magnetics ,Drug Delivery Systems ,Nano ,Animals ,Environmental Chemistry ,biology ,Chemistry ,technology, industry, and agriculture ,Ceriodaphnia dubia ,biology.organism_classification ,Daphnia ,Models, Chemical ,Environmental chemistry ,Drug delivery ,Toxicity ,Nanoparticles ,Environmental Pollutants ,Ecotoxicity - Abstract
Nano-Fe2O3 (magnetic) and nano-Al2O3 are increasingly used in biomedical fields for cellular labeling and drug delivery, and in the industry as catalysts. However, they may also serve as carriers of toxic contaminants and negatively impact the environment and human health. In the present study, Ceriodaphnia dubia was used to assess the toxicity of these nanoparticles (NPs) with and without the presence of background arsenic(V) (As[V]). The results showed that although these NPs alone did not exhibit significant toxicity in the experimental concentration range, they could significantly enhance the toxicity of As(V). The accumulation of As(V) on nano-Fe2O3 (m) and nano-Al2O3, as well as the uptake of these NPs in C. dubia, were verified. An inverse relationship between the median lethal concentration (LC50) of the soluble As(V) and the accumulation of NPs in C. dubia was developed. Therefore, the uptake of As(V)-loaded NPs in C. dubia played a key role in enhancing As(V) toxicity. Environ. Toxicol. Chem. 2012; 31: 2870–2876. © 2012 SETAC
- Published
- 2012
47. Toxicity of lead on Ceriodaphnia dubia in the presence of nano-CeO2 and nano-TiO2
- Author
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Jianmin Wang, Jiangtao Wang, Ji Hu, and Demin Wang
- Subjects
inorganic chemicals ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,education ,Nano tio2 ,Ecotoxicology ,Crustacea ,Animals ,Environmental Chemistry ,health care economics and organizations ,Titanium ,biology ,Chemistry ,technology, industry, and agriculture ,Public Health, Environmental and Occupational Health ,Ceriodaphnia dubia ,Drug Synergism ,Cerium ,General Medicine ,General Chemistry ,Hydrogen-Ion Concentration ,respiratory system ,biology.organism_classification ,Pollution ,Engineered nanoparticles ,Lead ,Solubility ,Environmental chemistry ,Toxicity ,Nanoparticles ,Environmental Pollutants - Abstract
Although engineered nanoparticles (NPs) could negatively impact environmental organisms, the synergistic effect of NPs and other toxic substances, which could be more significant than that of NP alone, have seldom been examined. The effect of two common NPs, nano-CeO2 and nano-TiO2, on the toxicity of Pb was evaluated using Ceriodaphnia dubia (C. dubia) as the model organism. Standard EPA procedures were followed in the toxicity evaluation. The toxicity of bare NPs (without Pb) was first evaluated and safe doses (levels without causing lethal effect) of NPs were used in the synergistic studies. It was found that the overall toxicity of Pb in the system containing NPs was greater than that of Pb alone, as indicted by the reduced median lethal concentration (LC50) of soluble Pb. The sorption of Pb onto the NP, and the uptake of NPs in the gastrointestinal tract of C. dubia were validated. Therefore, the uptake of Pb-loaded NPs increased the exposure of C. dubia to Pb, resulting in the enhanced toxicity. Reducing the solution pH could shift Pb speciation and enhance the overall toxicity of Pb, with or without the presence of NPs.
- Published
- 2012
48. Response Patterns of GABAergic Neurons in the Anterior Piriform Cortex of Awake Mice
- Author
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Ji Hu, Minmin Luo, Rongfeng Hu, and Juen Zhang
- Subjects
0301 basic medicine ,Sensory processing ,Light ,Vesicular Inhibitory Amino Acid Transport Proteins ,Cognitive Neuroscience ,medicine.medical_treatment ,Green Fluorescent Proteins ,Action Potentials ,Stimulation ,Sensory system ,Mice, Transgenic ,Piriform Cortex ,Biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Channelrhodopsins ,Piriform cortex ,medicine ,Animals ,GABAergic Neurons ,Wakefulness ,Principal Component Analysis ,Glutamate Decarboxylase ,Neural Inhibition ,Olfactory Perception ,Optogenetics ,Smell ,030104 developmental biology ,nervous system ,Odorants ,Excitatory postsynaptic potential ,GABAergic ,Neuroscience ,030217 neurology & neurosurgery ,Sensory information processing - Abstract
Local inhibition by γ-amino butyric acid (GABA)-containing neurons is of vital importance for the operation of sensory cortices. However, the physiological response patterns of cortical GABAergic neurons are poorly understood, especially in the awake condition. Here, we utilized the recently developed optical tagging technique to specifically record GABAergic neurons in the anterior piriform cortex (aPC) in awake mice. The identified aPC GABAergic neurons were stimulated with robotic delivery of 32 distinct odorants, which covered a broad range of functional groups. We found that aPC GABAergic neurons could be divided into 4 types based on their response patterns. Type I, type II, and type III neurons displayed broad excitatory responses to test odorants with different dynamics. Type I neurons were constantly activated during odorant stimulation, whereas type II neurons were only transiently activated at the onset of odorant delivery. In addition, type III neurons displayed transient excitatory responses both at the onset and termination of odorant presentation. Interestingly, type IV neurons were broadly inhibited by most of the odorants. Taken together, aPC GABAergic neurons adopt different strategies to affect the cortical circuitry. Our results will allow for better understanding of the role of cortical GABAergic interneurons in sensory information processing.
- Published
- 2016
49. De novo mutation of PHEX in a type 1 diabetes patient
- Author
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Wenjin Xiao, Hui Li, Chen Fang, Yun Huang, Wu Cai, Yi Yang, Ji Hu, and Xiaozhen Li
- Subjects
Adult ,Male ,0301 basic medicine ,Proband ,Endocrinology, Diabetes and Metabolism ,Polymerase Chain Reaction ,Mice ,Young Adult ,03 medical and health sciences ,Exon ,Endocrinology ,Genotype ,Animals ,Humans ,Medicine ,Missense mutation ,Amino Acid Sequence ,X chromosome ,Genetics ,Sequence Homology, Amino Acid ,business.industry ,PHEX ,Exons ,Sequence Analysis, DNA ,Prognosis ,PHEX Phosphate Regulating Neutral Endopeptidase ,Introns ,Pedigree ,Rats ,Hypophosphatemic Rickets ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,Mutation ,Pediatrics, Perinatology and Child Health ,Mutation (genetic algorithm) ,Cattle ,Female ,business ,Chickens - Abstract
A new missense mutation on the X chromosome (PHEX) at exon 4(c.442C>T) in a 4-generation Chinese Han pedigree is reported. The proband and four family members were clinically identified as the X-linked hypophosphatemic rickets (XLH) which is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. The proband is identified as hemizygous with the four female family members to be heterozygous genotypes. The discovery was made through the complete sequencing of the exons and the intron-exon boundaries of the PHEX gene of this family. The mutation caused the S141 residue to change to Phe from Ser which is perfectly conserved among humans, mice, rats, cows and chickens. PolyPhen-2 software analysis of the mutation indicated it was probably damaging. The proband was also diagnosed with type 1 diabetes (T1D) and the relationship between XLH and diabetes phenotypes was discussed in the paper.
- Published
- 2016
50. Bioaccumulation of Fe2O3(magnetic) nanoparticles in Ceriodaphnia dubia
- Author
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Demin Wang, Ji Hu, Jianmin Wang, and Jiangtao Wang
- Subjects
Health, Toxicology and Mutagenesis ,technology, industry, and agriculture ,Ceriodaphnia dubia ,Clean environment ,General Medicine ,Biology ,Cladocera ,Toxicology ,biology.organism_classification ,Ferric Compounds ,Pollution ,Arsenic ,Bioaccumulation ,Environmental chemistry ,Toxicity ,Ph range ,Animals ,Nanoparticles ,Ingestion ,Magnetic nanoparticles - Abstract
While nano-Fe(2)O(3)(magnetic) is generally considered non-toxic, it could serve as a carrier of other toxic chemicals such as As(V) and enhance their toxicity. The bioaccumulation of nano-Fe(2)O(3)(m) with different exposure times, NP concentrations, and pH conditions was investigated using Ceriodaphnia dubia (C. dubia) as the model organism. Under natural pH conditions, C. dubia significantly accumulated nano-Fe(2)O(3)(m) in the gut, with the maximum accumulation being achieved after 6 h of exposure. The concentration of nano-Fe(2)O(3) also impacted its accumulation, with the maximum uptake occurring at 20 mg/L or more. In addition, the highest bioaccumulation occurred in a pH range of 7-8 where the highest feeding rate was reported, confirming that the ingestion of NPs is the main route of nano-Fe(2)O(3)(m) bioaccumulation. In a clean environment without NPs, depuration of nano-Fe(2)O(3)(m) occurred, and food addition accelerated the depuration process.
- Published
- 2012
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