30 results on '"Ran Ran Wang"'
Search Results
2. Delivery of miR‐3529‐3p using MnO2‐SiO2‐APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A
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Ying Zhang, Ran‐Ran Wang, Rui Liu, Shu‐Yang Xie, Fei Jiao, You‐Jie Li, Jiaxuan Xin, Han Zhang, Zhenbo Wang, and Yun‐Fei Yan
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HIGD1A ,lung adenocarcinoma ,miR‐3529‐3p ,MSA ,nanoparticle ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The present study aimed to investigate the function of miR‐3529‐3p in lung adenocarcinoma and MnO2‐SiO2‐APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy. Methods Expression levels of miR‐3529‐3p were evaluated in lung carcinoma cells and tissues by qRT‐PCR. The effects of miR‐3529‐3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK‐8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT‐PCR and mitochondrial complex assay were used to determine the targeting relationship between miR‐3529‐3p and hypoxia‐inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH‐DA staining and FACS. Results MiR‐3529‐3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR‐3529‐3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR‐3529‐3p, HIGD1A expression was downregulated, through which miR‐3529‐3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR‐3529‐3p into cells, but also enhance the antitumor function of miR‐3529‐3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR‐3529‐3p. Conclusions Our results establish the antioncogenic role of miR‐3529‐3p, and demonstrate that miR‐3529‐3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis.
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- 2023
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3. Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession
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Yuan-Rong Liu, Dan-Dan Song, Dong-Min Liang, You-Jie Li, Yun-Fei Yan, Hong-Fang Sun, Mei-Ling Zhang, Jin-Xia Hu, Yu-Long Zhao, Yan Liang, Yan-Mei Li, Zhen Yang, Ran-Ran Wang, Hou-Feng Zheng, Pingyu Wang, and Shu-Yang Xie
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.
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- 2022
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4. Salvianolic acid A improve mitochondrial respiration and cardiac function via inhibiting apoptosis pathway through CRYAB in diabetic cardiomyopathy
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Di-fei Gong, Shu-chan Sun, Ran-ran Wang, Awaguli Dawuti, De-wen Kong, Rui-qi Liu, Li-da Du, Shou-bao Wang, Yang Lu, Tian-yi Yuan, Guan-hua Du, and Lian-hua Fang
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Salvianolic acid A ,Diabetic cardiomyopathy ,Mitochondrial ,Apoptosis ,CRYAB ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.
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- 2023
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5. Increased joint loading induces subchondral bone loss of the temporomandibular joint via the RANTES-CCRs-Akt2 axis
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Shi-Yang Feng, Jie Lei, Yu-Xiang Li, Wen-Ge Shi, Ran-Ran Wang, Adrian Ujin Yap, Yi-Xiang Wang, and Kai-Yuan Fu
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Bone biology ,Medicine - Abstract
Early-stage temporomandibular joint osteoarthritis (TMJOA) is characterized by excessive subchondral bone loss. Emerging evidence suggests that TMJ disc displacement is involved, but the pathogenic mechanism remains unclear. Here, we established a rat model of TMJOA that simulated disc displacement with a capacitance-based force-sensing system to directly measure articular surface pressure in vivo. Micro-CT, histological staining, immunofluorescence staining, IHC staining, and Western blot were used to assess pathological changes and underlying mechanisms of TMJOA in the rat model in vivo as well as in RAW264.7 cells in vitro. We found that disc displacement led to significantly higher pressure on the articular surface, which caused rapid subchondral bone loss via activation of the RANTES–chemokine receptors–Akt2 (RANTES-CCRs-Akt2) axis. Inhibition of RANTES or Akt2 attenuated subchondral bone loss and resulted in improved subchondral bone microstructure. Cytological studies substantiated that RANTES regulated osteoclast formation by binding to its receptor CCRs and activating the Akt2 pathway. The clinical evidence further supported that RANTES was a potential biomarker for predicting subchondral bone loss in early-stage TMJOA. Taken together, this study demonstrates important functions of the RANTES-CCRs-Akt2 axis in the regulation of subchondral bone remodeling and provides further knowledge of how disc displacement causes TMJOA.
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- 2022
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6. WFDC21P promotes triple-negative breast cancer proliferation and migration through WFDC21P/miR-628/SMAD3 axis
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Yu-Bo Wei, Dong-Min Liang, Mei-Ling Zhang, You-Jie Li, Hong-Fang Sun, Qin Wang, Yan Liang, Yan-Mei Li, Ran-Ran Wang, Zhen-Lin Yang, Pingyu Wang, and Shu-Yang Xie
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WFDC21P ,microRNA ,N6-methyladenosine ,epigenetics ,triple-negative breast cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Long non-coding RNAs (lncRNAs) modulate cell proliferation, cycle, and apoptosis. However, the role of lncRNA-WFDC21P in the tumorigenesis of triple-negative breast cancer (TNBC) remains unclear. Results of this study demonstrated that WFDC21P levels significantly increased in TNBC, which was associated with the poor survival of patients. WFDC21P overexpression significantly promoted TNBC cell proliferation and metastasis. WFDC21P interacted with miR-628-5p, which further suppressed cell proliferation and metastasis by negatively regulating Smad3-related gene expression. Recovery of miR-628-5p weakened the roles of WFDC21P in promoting the growth and metastasis of TNBC cells. Moreover,N6-methyladenosine (m6A) modification upregulated WFDC21P expression in the TNBC cells. WFDC21P and its m6A levels were increased after methyltransferase like 3 (METTL3) overexpression but reduced after METTL3 silencing. The proliferation and metastasis of TNBC cells were promoted by METTL3 overexpression but suppressed by METTL3 silencing. This study demonstrated the vital roles of WFDC21P and its m6A in regulating the proliferation and metastasis of TNBC cells via the WFDC21P/miR-628/SMAD3 axis.
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- 2022
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7. miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation
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Qian Zhang, Yun-Fei Yan, Qing Lv, You-Jie Li, Ran-Ran Wang, Guang-Bin Sun, Li Pan, Jin-Xia Hu, Ning Xie, Can Zhang, Bao-Cheng Tian, Fei Jiao, Sen Xu, Ping-Yu Wang, and Shu-Yang Xie
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Cytology ,QH573-671 - Abstract
Abstract Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.
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- 2021
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8. Immunity and inflammation in pulmonary arterial hypertension: From pathophysiology mechanisms to treatment perspective
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Ran-ran Wang, Tian-yi Yuan, Jian-mei Wang, Yu-cai Chen, Jiu-liang Zhao, Meng-tao Li, Lian-hua Fang, and Guan-hua Du
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Inflammation ,Immunity ,Autoimmune disease ,Pulmonary arterial hypertension ,Pathophysiology ,Immunosuppressive therapy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH.
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- 2022
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9. Clinical characteristics and sociodemographic features of psychotic major depression
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Meng-qi Wang, Ran-ran Wang, Yu Hao, Wei-feng Xiong, Ling Han, Dong-dong Qiao, and Juan He
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Psychiatry ,RC435-571 - Abstract
Abstract Background Psychotic major depression (PMD) is a subtype of depression with a poor prognosis. Previous studies have failed to find many differences between patients with PMD and those with non-psychotic major depression (NMD) or schizophrenia (SZ). We compared sociodemographic factors (including season of conception) and clinical characteristics between patients with PMD, NMD, and schizophrenia. Our aim was to provide data to help inform clinical diagnoses and future etiology research. Methods This study used data of all patients admitted to Shandong Mental Health Center from June 1, 2016 to December 31, 2017. We analyzed cases who had experienced an episode of PMD (International Classification of Diseases, Tenth Revision codes F32.3, F33.3), NMD (F32.0–2/9, F33.0–2/9), and SZ (F20–20.9). Data on sex, main discharge diagnosis, date of birth, ethnicity, family history of psychiatric diseases, marital status, age at first onset, education, allergy history, and presence of trigger events were collected. Odds ratios (OR) were calculated using logistic regression analyses. Missing values were filled using the k-nearest neighbor method. Results PMD patients were more likely to have a family history of psychiatric diseases in their first-, second-, and third-degree relatives ([OR] 1.701, 95% confidence interval [CI] 1.019–2.804) and to have obtained a higher level of education (OR 1.451, 95% CI 1.168–1.808) compared with depression patients without psychotic features. Compared to PMD patients, schizophrenia patients had lower education (OR 0.604, 95% CI 0.492–0.741), were more often divorced (OR 3.087, 95% CI 1.168–10.096), had a younger age of onset (OR 0.934, 95% CI 0.914–0.954), less likely to have a history of allergies (OR 0.604, 95% CI 0.492–0.741), and less likely to have experienced a trigger event 1 year before first onset (OR 0.420, 95% CI 0.267–0.661). Season of conception, ethnicity, and sex did not differ significantly between PMD and NMD or schizophrenia and PMD. Conclusions PMD patients have more similarities with NMD patients than SZ patients in terms of demographic and clinical characteristics. The differences found between PMD and SZ, and PMD and NMD correlated with specificity of the diseases. Furthermore, allergy history should be considered in future epidemiological studies of psychotic disorders.
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- 2021
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10. Dan-Shen-Yin Granules Prevent Hypoxia-Induced Pulmonary Hypertension via STAT3/HIF-1α/VEGF and FAK/AKT Signaling Pathways
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Ran-Ran Wang, Tian-Yi Yuan, Di Chen, Yu-Cai Chen, Shu-Chan Sun, Shou-Bao Wang, Ling-Lei Kong, Lian-Hua Fang, and Guan-Hua Du
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traditional chinese medicine ,Dan-Shen-Yin ,hypoxia-induced pulmonary hypertension ,network pharmacology ,mechanism ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Traditional Chinese medicine (TCM) plays an important role in the treatment of complex diseases, especially cardiovascular diseases. However, it is hard to identify their modes of action on account of their multiple components. The present study aims to evaluate the effects of Dan-Shen-Yin (DSY) granules on hypoxia-induced pulmonary hypertension (HPH), and then to decipher the molecular mechanisms of DSY. Systematic pharmacology was employed to identify the targets of DSY on HPH. Furthermore, core genes were identified by constructing a protein-protein interaction (PPI) network and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analysis. Related genes and pathways were verified using a hypoxia-induced mouse model and hypoxia-treated pulmonary artery cells. Based on network pharmacology, 147 potential targets of DSY on HPH were found, constructing a PPI network, and 13 hub genes were predicted. The results showed that the effect of DSY may be closely associated with AKT serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), and HIF-1 signaling pathways, as well as biological processes such as cell proliferation. Consistent with network pharmacology analysis, experiments in vivo demonstrated that DSY could prevent the development of HPH in a hypoxia-induced mouse model and alleviate pulmonary vascular remodeling. In addition, inhibition of STAT3/HIF-1α/VEGF and FAK/AKT signaling pathways might serve as mechanisms. Taken together, the network pharmacology analysis suggested that DSY exhibited therapeutic effects through multiple targets in the treatment of HPH. The inferences were initially confirmed by subsequent in vivo and in vitro studies. This study provides a novel perspective for studying the relevance of TCM and disease processes and illustrates the advantage of this approach and the multitargeted anti-HPH effect of DSY.
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- 2022
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11. Time series analysis of mumps and meteorological factors in Beijing, China
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Yu Hao, Ran-ran Wang, Ling Han, Hong Wang, Xuan Zhang, Qiao-ling Tang, Long Yan, and Juan He
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Beijing ,Meteorological factors ,Mumps ,Time series ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Over the past decades there have been outbreaks of mumps in many countries, even in populations that were vaccinated. Some studies suggest that the incidence of mumps is related to meteorological changes, but the results of these studies vary in different regions. To date there is no reported study on correlations between mumps incidence and meteorological parameters in Beijing, China. Methods A time series analysis incorporating selected weather factors and the number of mumps cases from 1990 to 2012 in Beijing was performed. First, correlations between meteorological variables and the number of mumps cases were assessed. A seasonal autoregressive integrated moving average model with explanatory variables (SARIMAX) was then constructed to predict mumps cases. Results Mean temperature, rainfall, relative humidity, vapor pressure, and wind speed were significantly associated with mumps incidence. After constructing the SARIMAX model, mean temperature at lag 0 (β = 0.016, p
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- 2019
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12. Delivery of <scp>miR</scp> ‐3529‐3p using <scp> MnO 2 ‐SiO 2 ‐APTES </scp> nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting <scp>HIGD1A</scp>
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Ying Zhang, Ran‐Ran Wang, Rui Liu, Shu‐Yang Xie, Fei Jiao, You‐Jie Li, Jiaxuan Xin, Han Zhang, Zhenbo Wang, and Yun‐Fei Yan
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Pulmonary and Respiratory Medicine ,Oncology ,General Medicine - Published
- 2023
13. Chemosensory Gene Families in the Oligophagous Pear Pest Cacopsylla chinensis (Hemiptera: Psyllidae)
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Ji-Wei Xu, Xiu-Yun Zhu, Qiu-Jie Chao, Yong-Jie Zhang, Yu-Xia Yang, Ran-Ran Wang, Yu Zhang, Meng-Zhen Xie, Ya-Ting Ge, Xin-Lai Wu, Fan Zhang, Ya-Nan Zhang, Lei Ji, and Lu Xu
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Cacopsylla chinensis ,oligophagous pest ,chemosensory genes ,transcriptome analysis ,tissue expression ,Science - Abstract
Chemosensory systems play an important role in insect behavior, and some key associated genes have potential as novel targets for pest control. Cacopsylla chinensis is an oligophagous pest and has become one of the main pests of pear trees, but little is known about the molecular-level means by which it locates its hosts. In this study, we assembled the head transcriptome of C. chinensis using Illumina sequencing, and 63,052 Unigenes were identified. A total of 36 candidate chemosensory genes were identified, including five different families: 12 odorant binding proteins (OBPs), 11 chemosensory proteins (CSPs), 7 odorant receptors (ORs), 4 ionotropic receptors (IRs), and 2 gustatory receptors (GRs). The number of chemosensory gene families is consistent with that found in other Hemipteran species, indicating that our approach successfully obtained the chemosensory genes of C. chinensis. The tissue expression of all genes using quantitative real-time PCR (qRT-PCR) found that some genes displayed male head, female head, or nymph-biased specific/expression. Our results enrich the gene inventory of C. chinensis and provide valuable resources for the analysis of the functions of some key genes. This will help in developing molecular targets for disrupting feeding behavior in C. chinensis.
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- 2019
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14. Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats
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Juan He, Ran-Ran Wang, Weifeng Xiong, Ruo-Yun Zheng, Yu Hao, and Xu Wang
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Yunqi recipes ,Decoction ,Pharmacology ,030226 pharmacology & pharmacy ,CUMS ,03 medical and health sciences ,Norepinephrine ,0302 clinical medicine ,Dopamine ,medicine ,Hippocampus (mythology) ,lcsh:Miscellaneous systems and treatments ,030304 developmental biology ,0303 health sciences ,Fluoxetine ,Fuhe decoction ,Depression ,business.industry ,lcsh:RZ409.7-999 ,Tail suspension test ,Monoamine neurotransmitter ,Complementary and alternative medicine ,Antidepressant ,business ,medicine.drug - Abstract
Objective: To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation (CUMS) combined with social isolation. Methods: Fifty male SD rats were randomly divided into a blank group, model group, fluoxetine group, Chaiqinwendan decoction group, and Fuhe decoction group. Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model. After 42 days of administration, a tail suspension test and high-performance liquid electrochemical detection (HPLC-ECD) were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine (NE), dopamine (DA), 5-hydroxytrytamine (5-HT), and metabolites in different brain regions of rats in each group before and after treatment. Results: Compared with the model group, the epinephrine (E) content in the Fuhe decoction group was highly significantly increased (P
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- 2020
15. Puerarin-V prevents the progression of hypoxia- and monocrotaline-induced pulmonary hypertension in rodent models
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Di Chen, Hui-fang Zhang, Tian-yi Yuan, Shu-chan Sun, Ran-ran Wang, Shou-bao Wang, Lian-hua Fang, Yang Lyu, and Guan-hua Du
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Pharmacology ,Monocrotaline ,Hypertension, Pulmonary ,Rodentia ,General Medicine ,Pulmonary Artery ,Vascular Remodeling ,Isoflavones ,Rats ,Disease Models, Animal ,Mice ,Phosphatidylinositol 3-Kinases ,Animals ,Pharmacology (medical) ,Hypoxia - Abstract
Pulmonary hypertension (PH) is a cardiopulmonary disease characterized by a progressive increase in pulmonary vascular resistance. One of the initial pathogenic factors of PH is pulmonary arterial remodeling under various stimuli. Current marketed drugs against PH mainly relieve symptoms without significant improvement in overall prognosis. Discovering and developing new therapeutic drugs that interfere with vascular remodeling is in urgent need. Puerarin is an isoflavone compound extracted from the root of Kudzu vine, which is widely used in the treatment of cardiovascular diseases. In the present study, we evaluated the efficacy of puerarin in the treatment of experimental PH. PH was induced in rats by a single injection of MCT (50 mg/kg, sc), and in mice by exposure to hypoxia (10% O
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- 2021
16. Activation of the Intrinsic Pain Inhibitory Circuit from the Midcingulate Cg2 to Zona Incerta Alleviates Neuropathic Pain
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Shihong Zhang, Yu-Xing Wu, Fang Guo, Yi Wang, Xiang-Yao Li, Shuang Wang, Ran-Ran Wang, Yu Du, Zhong Chen, and Ting-Ting Hu
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Male ,0301 basic medicine ,Analgesic ,Pain ,Inhibitory postsynaptic potential ,Gyrus Cinguli ,03 medical and health sciences ,Glutamatergic ,0302 clinical medicine ,Neural Pathways ,Animals ,Zona Incerta ,Medicine ,GABAergic Neurons ,Research Articles ,business.industry ,General Neuroscience ,food and beverages ,Pain Perception ,Nerve injury ,Mice, Inbred C57BL ,Optogenetics ,030104 developmental biology ,medicine.anatomical_structure ,Nociception ,Allodynia ,Neuropathic pain ,Neuralgia ,Zona incerta ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glubecame hypoactive after nerve injury. Although a brief activation of the MCC Cg2Gluto ZIGABAcircuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Gluconstitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Gluto ZIGABAcircuit may serve as a potential therapeutic strategy for this disease.SIGNIFICANCE STATEMENTGlutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) are tonically involved in the intrinsic pain inhibition via projecting to GABAergic neurons in the zona incerta. They are hypoactive after nerve injury. Selective activation of the circuit compensates the reduction of its analgesic strength and relieves neuropathic pain. Therefore, MCC Cg2Gluand the related analgesic circuit may serve as therapeutic targets for neuropathic pain. In contrast, MCC Cg1Gluhave an opposite role in pain modulation and become hyperactive after nerve injury. The present study provides novel evidence for the concept that neuropathic pain is associated with the dysfunction of endogenous pain modulatory system and new perspective on the treatment of neuropathic pain.
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- 2019
17. Clinical characteristics and sociodemographic features of psychotic major depression
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Yu Hao, Meng-Qi Wang, Juan He, Weifeng Xiong, Ling Han, Dong-dong Qiao, and Ran-Ran Wang
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medicine.medical_specialty ,lcsh:RC435-571 ,business.industry ,Odds ratio ,medicine.disease ,Confidence interval ,Psychiatry and Mental health ,Schizophrenia ,lcsh:Psychiatry ,Internal medicine ,Epidemiology ,medicine ,Etiology ,Marital status ,Family history ,Psychiatry ,business ,Primary Research ,Depression (differential diagnoses) - Abstract
Background Psychotic major depression (PMD) is a subtype of depression with a poor prognosis. Previous studies have failed to find many differences between patients with PMD and those with non-psychotic major depression (NMD) or schizophrenia (SZ). We compared sociodemographic factors (including season of conception) and clinical characteristics between patients with PMD, NMD, and schizophrenia. Our aim was to provide data to help inform clinical diagnoses and future etiology research. Methods This study used data of all patients admitted to Shandong Mental Health Center from June 1, 2016 to December 31, 2017. We analyzed cases who had experienced an episode of PMD (International Classification of Diseases, Tenth Revision codes F32.3, F33.3), NMD (F32.0–2/9, F33.0–2/9), and SZ (F20–20.9). Data on sex, main discharge diagnosis, date of birth, ethnicity, family history of psychiatric diseases, marital status, age at first onset, education, allergy history, and presence of trigger events were collected. Odds ratios (OR) were calculated using logistic regression analyses. Missing values were filled using the k-nearest neighbor method. Results PMD patients were more likely to have a family history of psychiatric diseases in their first-, second-, and third-degree relatives ([OR] 1.701, 95% confidence interval [CI] 1.019–2.804) and to have obtained a higher level of education (OR 1.451, 95% CI 1.168–1.808) compared with depression patients without psychotic features. Compared to PMD patients, schizophrenia patients had lower education (OR 0.604, 95% CI 0.492–0.741), were more often divorced (OR 3.087, 95% CI 1.168–10.096), had a younger age of onset (OR 0.934, 95% CI 0.914–0.954), less likely to have a history of allergies (OR 0.604, 95% CI 0.492–0.741), and less likely to have experienced a trigger event 1 year before first onset (OR 0.420, 95% CI 0.267–0.661). Season of conception, ethnicity, and sex did not differ significantly between PMD and NMD or schizophrenia and PMD. Conclusions PMD patients have more similarities with NMD patients than SZ patients in terms of demographic and clinical characteristics. The differences found between PMD and SZ, and PMD and NMD correlated with specificity of the diseases. Furthermore, allergy history should be considered in future epidemiological studies of psychotic disorders.
- Published
- 2021
18. miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation
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Qian Zhang, Yun-Fei Yan, Qing Lv, You-Jie Li, Ran-Ran Wang, Guang-Bin Sun, Li Pan, Jin-Xia Hu, Ning Xie, Can Zhang, Bao-Cheng Tian, Fei Jiao, Sen Xu, Ping-Yu Wang, and Shu-Yang Xie
- Abstract
Background: Emerging evidence shows that lncRNA WFDC21P could promote STAT3 phosphorylation and microRNA 4293 SNP is associated with the risk of carcinomas, but the oncogenic functions of WFDC21P and miR-4293 in lung carcinoma are unclear.Methods: mRNA sequencing of lung carcinoma and control para-carcinoma tissues was performed to screen the potential targets. WFDC21P and miR-4293 levels were evaluated in lung carcinoma cells and tissues by qRT-PCR. The function of WFDC21P and miR-4293 on proliferation, apoptosis and metastasis were assessed by MTT, FACS, western blot, transwell assays, colony formation assays and xenografts experiment. RNA immunoprecipitation assays were implemented to verify the relationship between WFDC21P and mRNA-decapping enzyme 2 (DCP2). Furthermore, gain/loss of miR-4293 functions were used to determine its targeting relationship of DCP2. Results: WFDC21P expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, WFDC21P promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified DCP2 can directly bind to WFDC21P and down-regulates its expression. DCP2 as a direct target of miR-4293 and its expression is suppressed by miR-4293. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With positive correlation to WFDC21P expression, miR-4293 also plays oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both WFDC21P and miR-4293. Conclusion: Our results establish oncogenic roles for both WFDC21P and miR-4293, and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in lung carcinoma pathogenesis.
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- 2020
19. Targeted galectin-7 inhibition with ultrasound microbubble targeted gene therapy as a sole therapy to prevent acute rejection following heart transplantation in a Rodent model
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Zhuo Wang, Piyu Li, Shouqiang Li, Mingyuan Xu, Yingjie Li, Chen Zhao, Thomas R-Porter, Shuang-quan Jiang, Ran-ran Wang, Jianfeng Chen, Mengmeng Liang, Jiawei Tian, Kai Kang, Xiao-ping Leng, Dandan Yu, Weidong Yu, and Yanmei Ou
- Subjects
medicine.medical_treatment ,Genetic enhancement ,Galectins ,Biophysics ,Bioengineering ,Rodentia ,02 engineering and technology ,Pharmacology ,Biomaterials ,03 medical and health sciences ,medicine ,Animals ,030304 developmental biology ,Galectin ,Heart transplantation ,0303 health sciences ,Gene knockdown ,Microbubbles ,business.industry ,Immunosuppression ,Genetic Therapy ,021001 nanoscience & nanotechnology ,In vitro ,Rats ,Transplantation ,Pharmaceutical Preparations ,Mechanics of Materials ,Ceramics and Composites ,Heart Transplantation ,0210 nano-technology ,business - Abstract
Despite significant advances in transplantation, acute cellular rejection (AR) remains a major obstacle that is most prevalent in the first months post heart transplantation (HT). Current treatments require high doses of immunosuppressive drugs followed by maintenance therapies that have systemic side effects including early infection. In this study, we attempted to prevent AR with a myocardial-targeted galectin-7-siRNA delivery method using cationic microbubbles (CMBs) combined with ultrasound targeted microbubble destruction (UTMD) to create local immunosuppression in a rat abdominal heterotopic heart transplantation acute rejection model.Galectin-7-siRNA (siGal-7) bound to CMBs were synthesized and effective ultrasound-targeted delivery of siGal-7 into target cells confirmed in vitro. Based on these observations, three transplant rat models were tested:①isograft (ISO); ② Allograft (ALLO) +UTMD; and ③ALLO + PBS. UTMD treatments were administered at 1, 3, 5, 7 days after HT. Galectin 7 expression was reduced by 50% compared to ALLO + PBS (p 0.005), and this was associated with significant reductions in both galectin 7 and Interleukin-2 protein levels (p 0.001). The ALLO + UTMD group had Grade II or less inflammatory infiltration and myocyte damage in 11/12 rats using International Society For Heart and Lung Transplantation grading, compared to 0/12 rats with this grading in the ALLO + PBS group at 10 days post HT (p 0.001).Ultrasound-targeted galectin-7-siRNA knockdown with UTMD can prevent acute cellular rejection in the early period after allograft heart transplantation without the need for systemic immunosuppression.Microbubble, Acute Rejection, Heart Transplantation, Galectin-7, RNA.
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- 2020
20. Advances in the research on application of KL-6 in the diagnosis and treatment of interstitial lung disease
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Ran-ran WANG, Jian ZHU, and Jiang-lin ZHANG
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interstitial lung disease ,lcsh:R5-920 ,diagnosis ,KL-6 ,lcsh:R ,lcsh:Medicine ,prognosis ,lcsh:Medicine (General) - Abstract
Interstitial lung disease represents a group of diffuse pulmonary diseases that mainly affects pulmonary mesenchyme and alveolar spaces, resulting in loss of alveolar-capillary functions. It is also a common complication or an important factor that influences the prognosis of rheumatoid arthritis, dermatomyositis, systemic sclerosis. Searching for the biomarkers for the early diagnosis of the disease and/or indicative of the activity of the condition has been a subject of active investigations. KL-6, expressed on type II pneumocytes, is seen as the most promising biomarker for the diagnosis of the disease. This review summarizes the recent researches about the use of KL-6 in the diagnosis and treatment of interstitial lung disease. DOI: 10.11855/j.issn.0577-7402.2017.04.15
- Published
- 2017
21. Chemosensory Gene Families in the Oligophagous Pear Pest Cacopsylla chinensis (Hemiptera: Psyllidae)
- Author
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Yu-Xia Yang, Yong-Jie Zhang, Xin-Lai Wu, Ya-Nan Zhang, Ran-Ran Wang, Fan Zhang, Yu Zhang, Ya-Ting Ge, Ji-Wei Xu, Xiu-Yun Zhu, Meng-Zhen Xie, Lei Ji, Qiu-Jie Chao, and Lu Xu
- Subjects
0106 biological sciences ,Cacopsylla chinensis ,Odorant binding ,01 natural sciences ,Article ,Transcriptome ,03 medical and health sciences ,transcriptome analysis ,Gene family ,lcsh:Science ,Gene ,chemosensory genes ,Illumina dye sequencing ,030304 developmental biology ,Genetics ,0303 health sciences ,biology ,business.industry ,Pest control ,oligophagous pest ,biology.organism_classification ,Hemiptera ,010602 entomology ,tissue expression ,Insect Science ,lcsh:Q ,PEST analysis ,business - Abstract
Chemosensory systems play an important role in insect behavior, and some key associated genes have potential as novel targets for pest control. Cacopsylla chinensis is an oligophagous pest and has become one of the main pests of pear trees, but little is known about the molecular-level means by which it locates its hosts. In this study, we assembled the head transcriptome of C. chinensis using Illumina sequencing, and 63,052 Unigenes were identified. A total of 36 candidate chemosensory genes were identified, including five different families: 12 odorant binding proteins (OBPs), 11 chemosensory proteins (CSPs), 7 odorant receptors (ORs), 4 ionotropic receptors (IRs), and 2 gustatory receptors (GRs). The number of chemosensory gene families is consistent with that found in other Hemipteran species, indicating that our approach successfully obtained the chemosensory genes of C. chinensis. The tissue expression of all genes using quantitative real-time PCR (qRT-PCR) found that some genes displayed male head, female head, or nymph-biased specific/expression. Our results enrich the gene inventory of C. chinensis and provide valuable resources for the analysis of the functions of some key genes. This will help in developing molecular targets for disrupting feeding behavior in C. chinensis.
- Published
- 2019
22. Time series analysis of mumps and meteorological factors in Beijing, China
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Ran Ran Wang, Hong Wang, Qiao Ling Tang, Juan He, Yu Hao, Long Yan, Xuan Zhang, and Ling Han
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0301 basic medicine ,Time series ,Meteorological Concepts ,Vapor Pressure ,Rain ,030106 microbiology ,Wind ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,0302 clinical medicine ,Beijing ,Negatively associated ,Statistics ,Humans ,lcsh:RC109-216 ,030212 general & internal medicine ,Autoregressive integrated moving average ,Weather ,Mumps ,Models, Statistical ,Incidence ,Incidence (epidemiology) ,Temperature ,Humidity ,Interrupted Time Series Analysis ,Meteorological factors ,Confidence interval ,Infectious Diseases ,Environmental science ,Seasons ,Weather factors ,Research Article - Abstract
Background Over the past decades there have been outbreaks of mumps in many countries, even in populations that were vaccinated. Some studies suggest that the incidence of mumps is related to meteorological changes, but the results of these studies vary in different regions. To date there is no reported study on correlations between mumps incidence and meteorological parameters in Beijing, China. Methods A time series analysis incorporating selected weather factors and the number of mumps cases from 1990 to 2012 in Beijing was performed. First, correlations between meteorological variables and the number of mumps cases were assessed. A seasonal autoregressive integrated moving average model with explanatory variables (SARIMAX) was then constructed to predict mumps cases. Results Mean temperature, rainfall, relative humidity, vapor pressure, and wind speed were significantly associated with mumps incidence. After constructing the SARIMAX model, mean temperature at lag 0 (β = 0.016, p
- Published
- 2019
23. Contents Vol. 97, 2016
- Author
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Hiroshi Oka, You-ting Zhang, Cong Hao, Yanling Hu, Wei-Wei Hou, Koushirou Sogawa, Josef Donnerer, Rongping Zhang, Kazuhiko Taguchi, Hui-Ting Jiang, En-Qiang Mao, Ran-Ran Wang, Izzettin Hatip-Al-Khatib, Ruyal F. Tan, Da-feng Zhang, Wan-Hua Yang, Xu Lu, Jie Yu, Kouichi Taura, Kouichi Nakahara, Yasuhiro Takigawa, Feng Jing, Amr A. Fouad, Angela Burian, Iyad Jresat, Makoto Ohigashi, Myung Sook Oh, Wei Zhang, Chao Huang, Takashi Shibata, Markus Zeitlinger, Tetsuo Nakata, Jarogniew J. Luszczki, Miyuki Kobara, Shi-Hong Zhang, Wonil Lee, Öznur Açikalin, Zhong Chen, Ingrid Liebmann, Druckerei Stückle, Bo Jiang, Kazuki Matsubara, Juan He, Robert Sauermann, Gunhyuk Park, Ze'ev Seltzer, Ting-Ting Hu, Guo-Dong Lou, Nobuyoshi Imai, Er-Zhen Chen, Takanori Miura, Yin Zhang, Sang Hyun Sung, Ni-yun Ge, Miyusse Sakasegawa, Yeomoon Sim, Jili Wang, Peter Matzneller, Waleed H. Albuali, Funda F. Bölükbaşi Hatip, Guang-hui Zhu, Rui-jie Chen, Daisuke Kato, Norio Ogata, and Hiroe Toba
- Subjects
Pharmacology ,General Medicine - Published
- 2016
24. Photoluminescent crystalline-assembly of gold nanoclusters: Facile preparation with the mediation of hydroxyl-terminated hyperbranched polyethylenimine and its reversible response to CO2 adsorption and desorption
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Tong-Xian Zhang, Yu Chen, Ran-Ran Wang, and Li-Ping Yu
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Materials science ,Aqueous solution ,Photoluminescence ,General Chemical Engineering ,Quantum yield ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,Industrial and Manufacturing Engineering ,0104 chemical sciences ,Nanoclusters ,Metal ,Adsorption ,X-ray photoelectron spectroscopy ,Desorption ,visual_art ,visual_art.visual_art_medium ,Environmental Chemistry ,0210 nano-technology - Abstract
Stimuli-responsive metal nanoclusters (NCs) are intriguing materials due to their wide applications in photoluminescence (PL) sensors, bioimaging and catalysis. CO2 gas as a green stimulus could arouse the PL variation of certain metal NCs only under high-pressure condition. Metal NCs responding to the normal-pressure CO2 have not been reported yet. In this work, hydroxyl-terminated hyperbranched polyethylenimine (HPEI-OH) was used to mediate the preparation of water-soluble Au NC assemblies (Au NC-As) with crystallization-induced emission (CIE) nature. HPEI-OH played a multifunctional role, such as reducing Au ions, endowing water solubility to Au NC-As, packing thiolated Au NCs closely and enabling CO2-responsiveness to Au NC-As. Controlling the preparation pH at 2.0 or 3.2, red or yellow-emitting Au NC-As with quantum yield of ca. 4.6% or 5.8% were achieved. The as-prepared CIE-type Au NC-As possessed pH-responsive characteristic and strong PL emission was achieved under acidic condition. The CIE nature rendered not only strong PL emission to Au NC-As, but also strong photoelectron emission verified by the X-ray photoelectron spectroscopy. The introduction of Zn2+ ions extended the application range of Au NC-As from acidic condition till to weak basic condition. Under neutral condition, the formed complex of Zn2+/Au NC-As showed reversible PL response to the normal-pressure CO2/N2 cycling through adsorption and desorption process. Finally, the application of the complex in measuring the CO2 concentration of carbonated beverages was presented.
- Published
- 2020
25. Pregnancy Outcomes in Women of Advanced Maternal Age: a Retrospective Cohort Study from China
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Ran-Ran Wang, Peiyuan Qiu, Yu-Xia Wu, Ya-Yi Hu, Dan Shan, Sivakumar Ramadoss, Ai-Lin Li, and Qian Chen
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Adult ,Risk ,medicine.medical_specialty ,China ,Multivariate analysis ,lcsh:Medicine ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,030212 general & internal medicine ,Advanced maternal age ,lcsh:Science ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,Obstetrics ,business.industry ,Medical record ,Confounding ,lcsh:R ,Pregnancy Outcome ,Retrospective cohort study ,medicine.disease ,Cohort ,lcsh:Q ,Female ,business ,Cohort study ,Maternal Age - Abstract
This retrospective cohort study attempts to investigate pregnancy complications and adverse pregnancy outcomes in women of advanced maternal age (AMA). Data were extracted from electronic medical records system at West China Second University Hospital of Sichuan University from January 2013 to July 2016. The study cohort consisted 8 subgroups of women on 4 different age levels (20–29 years, 30–34 years, 35–39 years and ≥40 years) and 2 different parities (primiparity and multiparity). In the study period, 38811 women gave birth at our hospital, a randomized block was used to include 2800 women of singleton pregnancy >28 gestational weeks, with 350 patients in each subgroup. Maternal complications and fetal outcomes were collected and defined according to relevant guidelines. Confounding factors representing maternal demographic characteristics were identified from previous studies and analysed in multivariate analysis. There was an increasing trend for the risks of adverse pregnancy outcomes with increasing age, especially in AMA groups. Our study showed that AMA, primiparity, maternal overweight or obesity, lower educational level and residence in rural area increased pregnancy complications and adverse fetal outcomes. Increased professional care as well as public concern is warranted.
- Published
- 2018
26. Histamine Upregulates Nav1.8 Expression in Primary Afferent Neurons via H2Receptors: Involvement in Neuropathic Pain
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Ran-Ran Wang, Jie Yu, Zhong Chen, Guo-Dong Lou, Ying-Ying Tang, Shihong Zhang, Jiaxing Yue, and Wei-Wei Hou
- Subjects
Male ,Pain Threshold ,Sensory Receptor Cells ,Pharmacology ,Histamine Agonists ,NAV1.8 Voltage-Gated Sodium Channel ,Rats, Sprague-Dawley ,Sciatica ,chemistry.chemical_compound ,Histamine H2 receptor ,Ganglia, Spinal ,Physiology (medical) ,Animals ,Medicine ,Receptors, Histamine H2 ,Pharmacology (medical) ,Cimetidine ,Cells, Cultured ,Pain Measurement ,Thioperamide ,Dose-Response Relationship, Drug ,business.industry ,Original Articles ,Famotidine ,Neuroma ,medicine.disease ,Rats ,Up-Regulation ,Disease Models, Animal ,Psychiatry and Mental health ,Histamine H2 Antagonists ,chemistry ,Hyperalgesia ,Anesthesia ,Neuropathic pain ,Sciatic nerve ,business ,Histamine ,medicine.drug - Abstract
Summary Introduction The upregulation of Nav1.8 in primary afferents plays a critical role in the development and persistence of neuropathic pain. The mechanisms underlying the upregulation are not fully understood. Aims The present study aims to investigate the regulatory effect of histamine on the expression of Nav1.8 in primary afferent neurons and its involvement in neuropathic pain. Results Histamine at 10−8 M increased the expression of Nav1.8 in cultured DRG neurons. This effect could be blocked by H2 receptor antagonist cimetidine or famotidine, but not by H1 receptor antagonist pyrilamine or dual H3/H4 antagonist thioperamide. Peri-sciatic administration of histamine increased Nav1.8 expression in the sciatic nerve and L4/L5 DRG neurons in a dose-dependent manner, accompanied with remarkable mechanical allodynia and heat hyperalgesia in the ipsilateral hindpaw. Famotidine but not pyrilamine or thioperamide inhibited Nav1.8 upregulation and pain hypersensitivity. In addition, famotidine (40 mg/kg, i.p.) not only suppressed autotomy behavior in the rat neuroma model of neuropathic pain but also attenuated mechanical allodynia and thermal hyperalgesia following partial sciatic nerve ligation. Moreover, famotidine inhibited Nav1.8 upregulation in the neuroma and ligated sciatic nerve. Conclusions Our findings indicate that histamine increases Nav1.8 expression in primary afferent neurons via H2 receptor-mediated pathway and thereby contributes to neuropathic pain. H2 receptor antagonists may potentially be used as analgesics for patients with neuropathic pain.
- Published
- 2014
27. Activation of the Intrinsic Pain Inhibitory Circuit from the Midcingulate Cg2 to Zona Incerta Alleviates Neuropathic Pain.
- Author
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Ting-Ting Hu, Ran-Ran Wang, Yu Du, Fang Guo, Yu-Xing Wu, Yi Wang, Shuang Wang, Xiang-Yao Li, Shi-Hong Zhang, and Zhong Chen
- Subjects
- *
GABAERGIC neurons , *NEUROLOGICAL disorders , *PAIN , *HYPOKINESIA , *ALLODYNIA - Abstract
Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glu became hypoactive after nerve injury. Although a brief activation of the MCC Cg2Glu to ZIGABA circuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Glu constitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Glu to ZIGABA circuit may serve as a potential therapeutic strategy for this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
28. A critical time window for the analgesic effect of central histamine in the partial sciatic ligation model of neuropathic pain
- Author
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Wei Wei Hou, Jiaxing Yue, Ying Ying Tang, Zhong Chen, Jie Yu, Guo Dong Lou, Ting Ting Hu, Li Yun Shi, Shi-Hong Zhang, Hiroshi Ohtsu, and Ran Ran Wang
- Subjects
Central Nervous System ,0301 basic medicine ,Histidine Decarboxylase ,Pharmacology ,Neuropathic pain ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Histamine H2 receptor ,Microglial activation ,Mice, Knockout ,Analgesics ,Drug Administration Routes ,General Neuroscience ,Histamine H1 Antagonists ,Histidine decarboxylase ,Histamine H2 Antagonists ,Neurology ,Hyperalgesia ,IL-1β ,Anesthesia ,medicine.symptom ,Cimetidine ,Histamine ,medicine.drug ,Pain Threshold ,Central histamine ,Immunology ,Histamine H1 receptor ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,medicine ,Animals ,Histidine ,Analgesic effect ,Pyrilamine ,business.industry ,Research ,Receptors, Interleukin-1 ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Sciatic Neuropathy ,business ,030217 neurology & neurosurgery - Abstract
Background It is known that histamine participates in pain modulation. However, the effect of central histamine on neuropathic pain is not fully understood. Here, we report a critical time window for the analgesic effect of central histamine in the partial sciatic nerve ligation model of neuropathic pain. Methods Neuropathic pain was induced by partial sciatic nerve ligation (PSL) in rats, wild-type (C57BL/6J) mice and HDC−/− (histidine decarboxylase gene knockout) and IL-1R−/− (interleukin-1 receptor gene knockout) mice. Histidine, a precursor of histamine that can increase the central histamine levels, was administered intraperitoneally (i.p.). Histidine decarboxylase (HDC) enzyme inhibitor α-fluoromethylhistidine was administered intracerebroventricularly (i.c.v.). Histamine H1 receptor antagonist mepyramine and H2 receptor antagonist cimetidine were given intrathecally (i.t.) and intracisternally (i.c.). Withdrawal thresholds to tactile and heat stimuli were measured with a set of von Frey hairs and infrared laser, respectively. Immunohistochemistry and Western blot were carried out to evaluate the morphology of microglia and IL-1β production, respectively. Results Histidine (100 mg/kg, i.p.) administered throughout days 0–3, 0–7, or 0–14 postoperatively (PO) alleviated mechanical allodynia and thermal hyperalgesia in the hindpaw following PSL in rats. Intrathecal histamine reversed PSL-induced thermal hyperalgesia in a dose-dependent manner and intracisternal histamine alleviated both mechanical allodynia and thermal hyperalgesia. Moreover, α-fluoromethylhistidine (i.c.v.) abrogated the analgesic effect of histidine. However, histidine treatment initiated later than the first postoperative day (treatment periods included days 2–3, 4–7, and 8–14 PO) did not show an analgesic effect. In addition, histidine treatment initiated immediately, but not 3 days after PSL, inhibited microglial activation and IL-1β upregulation in the lumbar spinal cord, in parallel with its effects on behavioral hypersensitivity. Moreover, the inhibitory effects on pain hypersensitivity and spinal microglial activation were absent in HDC−/− mice and IL-1R−/− mice. H1 receptor antagonist mepyramine (200 ng/rat i.t. or i.c.), but not H2 receptor antagonist cimetidine (200, 500 ng/rat i.t. or 500 ng/rat i.c.), blocked the effects of histidine on pain behavior and spinal microglia. Conclusions These results demonstrate that central histamine is analgesic within a critical time window in the PSL model of neuropathic pain via histamine H1 receptors. This effect may partly relate to the inhibition of microglial activation and IL-1β production in the spinal cord following nerve injury. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0637-0) contains supplementary material, which is available to authorized users.
- Published
- 2016
29. Deletion of a Helicoverpa armigera nucleopolyhedrovirus gene encoding a virion structural protein (ORF107) increases the budded virion titre and reduces in vivo infectivity
- Author
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Marcel Westenberg, Fei Deng, Xiaoyu Pan, Xiulian Sun, Gang Long, Huiyuan Wang, Ran Ran Wang, Just M. Vlak, Zhihong Hu, Songwang Hou, Hualin Wang, and Yueting Zheng
- Subjects
Genes, Viral ,genome sequence ,viruses ,Immunoelectron microscopy ,Blotting, Western ,Molecular Sequence Data ,Laboratory of Virology ,cloning ,virus ,dna ,Helicoverpa armigera ,medicine.disease_cause ,baculoviruses ,Virus ,Cell Line ,Laboratorium voor Virologie ,Western blot ,Virology ,medicine ,Polyhedrin ,Animals ,Amino Acid Sequence ,Microscopy, Immunoelectron ,Nucleocapsid ,Viral Structural Proteins ,Infectivity ,Mutation ,Virulence ,medicine.diagnostic_test ,biology ,fungi ,Virion ,PE&RC ,biology.organism_classification ,Molecular biology ,Nucleopolyhedroviruses ,Lepidoptera ,Molecular Weight ,Open reading frame ,Larva ,single-nucleocapsid nucleopolyhedrovirus ,escherichia-coli ,Sequence Alignment ,Gene Deletion - Abstract
The open reading frame Ha107 of Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HearNPV) encodes a putative protein of 51 kDa with homologues in a few group II NPVs and a granulovirus. Ha107 was transcribed as polyadenylated transcripts in infected HzAM1 insect cells. The transcripts were initiated at two distinct locations, one upstream of Ha106 (superoxide dismutase gene, sod) and the second upstream of Ha107. By Western blot analysis, two forms of the HA107 protein were detected in infected cells, a major polypeptide of 48 kDa and a minor one of 51 kDa. Western blot and immunoelectron microscopy analyses further showed that the HA107 protein was associated with the nucleocapsids of both budded virions (BVs) and occlusion-derived virions. A Ha107 knockout virus expressing enhanced green fluorescent protein and polyhedrin was constructed using bacmid technology. A one-step virus growth curve indicated that the BV titre of the knockout virus was significantly higher than that of the parental virus and a Ha107 repair virus. Bioassays indicated that the knockout virus was able to infect third-instar H. armigera larvae; however, its median lethal dose (LD50) was significantly higher than those of the parental virus and Ha107 repair virus. These data indicate that Ha107 encodes a non-essential structural protein of HearNPV virions and that deletion of this gene increases the BV titre and LD50 of the occluded virus.
- Published
- 2007
30. A critical time window for the analgesic effect of central histamine in the partial sciatic ligation model of neuropathic pain.
- Author
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Jie Yu, Ying-Ying Tang, Ran-Ran Wang, Guo-Dong Lou, Ting-Ting Hu, Wei-Wei Hou, Jia-Xing Yue, Hiroshi Ohtsu, Li-Yun Shi, Shi-Hong Zhang, Zhong Chen, Yu, Jie, Tang, Ying-Ying, Wang, Ran-Ran, Lou, Guo-Dong, Hu, Ting-Ting, Hou, Wei-Wei, Yue, Jia-Xing, Ohtsu, Hiroshi, and Shi, Li-Yun
- Subjects
ANALGESICS ,NEURALGIA ,HISTAMINE ,PAIN management ,SCIATIC nerve ,DECARBOXYLASE inhibitors ,HYPERALGESIA treatment ,AMINOPYRIDINES ,ANIMAL experimentation ,ANTIHISTAMINES ,BIOLOGICAL models ,CELL receptors ,CENTRAL nervous system ,CIMETIDINE ,DRUG administration ,ENZYMES ,HYPERALGESIA ,MICE ,RATS ,SCIATICA ,H2 receptor antagonists ,HISTIDINE ,PAIN threshold ,PHARMACODYNAMICS ,THERAPEUTICS - Abstract
Background: It is known that histamine participates in pain modulation. However, the effect of central histamine on neuropathic pain is not fully understood. Here, we report a critical time window for the analgesic effect of central histamine in the partial sciatic nerve ligation model of neuropathic pain.Methods: Neuropathic pain was induced by partial sciatic nerve ligation (PSL) in rats, wild-type (C57BL/6J) mice and HDC(-/-) (histidine decarboxylase gene knockout) and IL-1R(-/-) (interleukin-1 receptor gene knockout) mice. Histidine, a precursor of histamine that can increase the central histamine levels, was administered intraperitoneally (i.p.). Histidine decarboxylase (HDC) enzyme inhibitor α-fluoromethylhistidine was administered intracerebroventricularly (i.c.v.). Histamine H1 receptor antagonist mepyramine and H2 receptor antagonist cimetidine were given intrathecally (i.t.) and intracisternally (i.c.). Withdrawal thresholds to tactile and heat stimuli were measured with a set of von Frey hairs and infrared laser, respectively. Immunohistochemistry and Western blot were carried out to evaluate the morphology of microglia and IL-1β production, respectively.Results: Histidine (100 mg/kg, i.p.) administered throughout days 0-3, 0-7, or 0-14 postoperatively (PO) alleviated mechanical allodynia and thermal hyperalgesia in the hindpaw following PSL in rats. Intrathecal histamine reversed PSL-induced thermal hyperalgesia in a dose-dependent manner and intracisternal histamine alleviated both mechanical allodynia and thermal hyperalgesia. Moreover, α-fluoromethylhistidine (i.c.v.) abrogated the analgesic effect of histidine. However, histidine treatment initiated later than the first postoperative day (treatment periods included days 2-3, 4-7, and 8-14 PO) did not show an analgesic effect. In addition, histidine treatment initiated immediately, but not 3 days after PSL, inhibited microglial activation and IL-1β upregulation in the lumbar spinal cord, in parallel with its effects on behavioral hypersensitivity. Moreover, the inhibitory effects on pain hypersensitivity and spinal microglial activation were absent in HDC(-/-) mice and IL-1R(-/-) mice. H1 receptor antagonist mepyramine (200 ng/rat i.t. or i.c.), but not H2 receptor antagonist cimetidine (200, 500 ng/rat i.t. or 500 ng/rat i.c.), blocked the effects of histidine on pain behavior and spinal microglia.Conclusions: These results demonstrate that central histamine is analgesic within a critical time window in the PSL model of neuropathic pain via histamine H1 receptors. This effect may partly relate to the inhibition of microglial activation and IL-1β production in the spinal cord following nerve injury. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
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