63 results on '"Xiaoli Yao"'
Search Results
2. Analysing the influencing factors on caregivers’ burden among amyotrophic lateral sclerosis patients in China: a cross-sectional study based on data mining
- Author
-
Zhong Pei, Ling Lian, Minying Zheng, Ruojie He, Jianing Lin, Weineng Chen, and Xiaoli Yao
- Subjects
Medicine - Abstract
Objectives There is significant burden on caregivers of patients with amyotrophic lateral sclerosis (ALS). However, only a few studies have focused on caregivers, and traditional research methods have obvious shortcomings in dealing with multiple influencing factors. This study was designed to explore influencing factors on caregiver burden among ALS patients and their caregivers from a new perspective.Design Cross-sectional study.Setting The data were collected at an affiliated hospital in Guangzhou, Guangdong, China.Participants Fifty-seven pairs of patients with ALS and their caregivers were investigated by standardised questionnaires.Main outcome measures This study primarily assessed the influencing factor of caregiver burden including age, gender, education level, economic status, anxiety, depression, social support, fatigue, sleep quality and stage of disease through data mining. Statistical analysis was performed using SPSS 24.0, and least absolute shrinkage and selection operator (LASSO) regression model was established by Python 3.8.1 to minimise the effect of multicollinearity.Results According to LASSO regression model, we found 10 variables had weights. Among them, Milano-Torinos (MITOS) stage (0–1) had the highest weight (−12.235), followed by younger age group (−3.198), lower-educated group (2.136), fatigue (1.687) and social support (-0.455). Variables including sleep quality, anxiety, depression and sex (male) had moderate weights in this model. Economic status (common), economic status (better), household (city), household (village), educational level (high), sex (female), age (older) and MITOS stage (2–4) had a weight of zero.Conclusions Our study demonstrates that the severity of ALS patients is the most influencing factor in caregiver burden. Caregivers of ALS patients may suffer less from caregiver burden when the patients are less severe, and the caregivers are younger. Low educational status could increase caregiver burden. Caregiver burden is positively correlated with the degree of fatigue and negatively correlated with social support. Hopefully, more attention should be paid to caregivers of ALS, and effective interventions can be developed to relieve this burden.
- Published
- 2022
- Full Text
- View/download PDF
3. The role of carbon nanoparticles in guiding central neck dissection and protecting the parathyroid in transoral vestibular endoscopic thyroidectomy for thyroid cancer
- Author
-
Zhiliang Xu, Yanyan Meng, Junlong Song, Yuan Wang, and Xiaoli Yao
- Subjects
parathyroid ,endoscopic thyroidectomy ,carbon nanoparticle ,central lymph node ,transoral vestibular ,Medicine - Published
- 2019
- Full Text
- View/download PDF
4. Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction
- Author
-
Chuanming Luo, Huixia Ren, Xiaoli Yao, Zhe Shi, Fengyin Liang, Jing X. Kang, Jian-bo Wan, Zhong Pei, Kuan-Pin Su, and Huanxing Su
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the “single cortical microinfarct model” generated via occluding a penetrating arteriole by femtosecond laser ablation and the “multiple diffuse microinfarcts model” induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered ω-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of ω-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where ω-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain ω-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of ω-3 PUFAs in the treatment or prophylaxis in vascular dementia. Keywords: Fish oil, Cognitive decline, Vascular dementia, Neuropsychiatric disorders
- Published
- 2018
- Full Text
- View/download PDF
5. Cell Surface GRP78 Accelerated Breast Cancer Cell Proliferation and Migration by Activating STAT3.
- Author
-
Xiaoli Yao, Hua Liu, Xinghua Zhang, Liang Zhang, Xiang Li, Changhua Wang, and Shengrong Sun
- Subjects
Medicine ,Science - Abstract
High levels of cell surface glucose regulated protein 78 (sGRP78) have been implicated in cancer growth, survival, metastasis, and chemotherapy resistance. However, the underlying mechanism remains largely unknown. Here we report that the level of sGRP78 expression in human breast tumors gradually increases during cancer progression. Overexpression of GRP78 significantly enhanced its membrane distribution in human MCF-7 breast cancer cells, but had no effect on endoplasmic reticulum (ER) stress. High levels of sGRP78 facilitated cell proliferation and migration, as well as suppressed cell apoptosis. Neutralization of sGRP78 by a specific antibody against GRP78 alleviated sGRP78-induced cell growth and migration. Importantly, high phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) were found in human breast tumors that express sGRP78 and MCF-7 cells infected with adenovirus encoding human GRP78. Pretreatment with a GRP78 antibody suppressed STAT3 phosphorylation. Furthermore, genetic and pharmacological inhibition of STAT3 reversed the impacts of GRP78 on cell proliferation, apoptosis, and migration. These findings indicate that STAT3 mediates sGRP78-promoted breast cancer cell growth and migration.
- Published
- 2015
- Full Text
- View/download PDF
6. Association studies of MMP-9 in Parkinson's disease and amyotrophic lateral sclerosis.
- Author
-
Xianghua He, Lifang Zhang, Xiaoli Yao, Jing Hu, Lihua Yu, Hua Jia, Ran An, Zhuolin Liu, and Yanming Xu
- Subjects
Medicine ,Science - Abstract
Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) share several clinical and neuropathologic features, and studies suggest that several gene mutations and polymorphisms are involved in both conditions. Matrix metalloproteinase-9 (MMP-9) is implicated in the pathogenesis of PD and ALS, and the C(-1562)T polymorphism in the MMP-9 gene leads to higher promoter activity. We therefore investigated whether this polymorphism predisposes to both PD and sporadic ALS (sALS). Samples from 351 subjects with PD and 351 healthy controls from two major cities in China were compared, while samples from 226 subjects with sALS were compared to the same number of controls from three centers in China. A possible association between the C(-1562)T polymorphism in the MMP-9 gene and PD or sALS was assessed by restriction fragment length polymorphism (RFLP) analysis. Our results show a significant association between the C(-1562)T polymorphism in the MMP-9 gene and risk of PD (odds ratio = 2.268, 95% CI 1.506-3.416, p
- Published
- 2013
- Full Text
- View/download PDF
7. An ultra-rare case of 47,XXY/48,XXXY/49,XXXXY mosaic Klinefelter syndrome associated with diabetic ketosis and foot ulcer
- Author
-
Juan Liu, Chuqi Gao, Wei Qiang, and Xiaoli Yao
- Subjects
Infertility ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Aneuploidy ,030209 endocrinology & metabolism ,Karyotype ,medicine.disease ,Dermatology ,03 medical and health sciences ,0302 clinical medicine ,Palpebral fissure ,Diabetes mellitus ,Internal Medicine ,Medicine ,030212 general & internal medicine ,Differential diagnosis ,Klinefelter syndrome ,business ,X chromosome - Abstract
Klinefelter syndrome (KS) is the most common chromosome aneuploidy and a common cause of infertility in males. KS patients have at least one extra X chromosome, and about 80% of patients have the karyotype 47,XXY. Twenty percent of KS patients have higher-grade aneuploidies (48,XXXY, 48,XXYY, 49,XXXXY) and exert some clinical manifestation different from those with 47,XXY. Here we report the case of a young man who initially presented with diabetic ketosis and foot ulcer and was later diagnosed as having an extremely rare mosaic variant of KS (47,XXY/48,XXXY/49,XXXXY). Clinical and laboratory features are summarized. The patient developed a severe foot ulcer with an 18-month history of diabetes. Learning disability was noted since early childhood. The patient had typical manifestations of KS, including increased height, sparse beard and body hair, and small penis. He also had some characteristic features of patients with additional sex chromosomes, including epicanthal folds, narrow palpebral fissures, prominent elbows, and undescended testicles. Severe myopia and myopic macular degeneration was also found. Lab tests revealed low testosterone and elevated FSH but normal LH levels. Chromosome analysis on lymphocytes revealed an aberration of 47,XXY/48,XXXY/49,XXXXY. This case provides information on KS patients with the extremely rare karyotype 47,XXY/48,XXXY/49,XXXXY, and also emphasizes the importance of considering KS in the differential diagnosis of a sterile male with diabetes.
- Published
- 2021
8. Secondary diabetes mellitus in Prader-Willi syndrome
- Author
-
Xiaoli Yao, Juan Liu, and Chuqi Gao
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Nasal bridge ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,030209 endocrinology & metabolism ,medicine.disease ,Short stature ,Hypotonia ,nervous system diseases ,03 medical and health sciences ,Chromosome 15 ,0302 clinical medicine ,Neonatal hypotonia ,Diabetes mellitus ,Internal Medicine ,medicine ,Feeding disorder ,030212 general & internal medicine ,medicine.symptom ,Differential diagnosis ,business - Abstract
Prader-Willi Syndrome (PWS) is a rare autosomal dominant disorder on the 15q11.2-q13 chromosome. PWS may impact metabolic, endocrine, and neurologic systems and combine with hypotonia, sleep disturbances, cognitive disability, central adrenal insufficiency, hypothyroidism, hypogonadism, short stature, and other diseases. Here ,we report a PWS patient with secondary diabetes mellitus. Clinical and laboratory features are summarized. The patient had typical manifestations of PWS including almond-shaped eyes, narrow temples, narrow nasal bridge, and short hands and feet. Lab test revealed hypogonadism and growth hormone deficiency. SNP array revealed one copy of chromosome 15 q11.2q13.1 was missing, with a length of about 6.4 mbp. This case emphasizes the importance of considering PWS in the differential diagnosis of an adolescent with diabetes. Antenatal history of neonatal hypotonia and childhood history of feeding disorder are the keys to the diagnosis of PWS.
- Published
- 2021
9. Purkinje cell (PC) antibody positivity in a patient with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy
- Author
-
Wenbiao Xian, Li Xu, Youming Long, Xiaoli Yao, and Jin Li
- Subjects
0301 basic medicine ,Purkinje cell ,Autoimmune Diseases ,Purkinje Cells ,03 medical and health sciences ,chemistry.chemical_compound ,Autoimmune Diseases of the Nervous System ,0302 clinical medicine ,Glial Fibrillary Acidic Protein ,medicine ,Humans ,Inositol ,Receptor ,Autoantibodies ,biology ,Glial fibrillary acidic protein ,General Neuroscience ,Meningoencephalitis ,General Medicine ,Middle Aged ,medicine.disease ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Astrocytes ,Immunoglobulin G ,biology.protein ,Female ,Antibody ,030217 neurology & neurosurgery - Abstract
This case report is the first to describe the detection of antibodies against inositol 1,4,5-trisphosphate receptor 1 (ITPR1, I3PR) in a patient diagnosed with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. ITPR1 is known as one of the Purkinje cell antibodies present in autoimmune cerebellar ataxia (ACA). Here, we described the association between autoimmune GFAP astrocytopathy and autoimmune cerebellar disease (ACD).Demographic features, clinical characteristics, cerebrospinal fluid (CSF) parameters and neuroimaging findings were collected from this patient. Specifically, antibodies against GFAP and other proteins associated with neurological disorders were measured by immunofluorescence staining in both serum and CSF samples.A 52-year-old woman was diagnosed with autoimmune inflammatory meningoencephalitis. She presented with cognitive dysfunction, psychiatric/behavioral abnormalities and serious insomnia with subacute onset. Brain magnetic resonance imaging (MRI) showed bilateral hyperintensity in the semioval centers on axial images and perivascular linear enhancement oriented radially to the ventricles on sagittal images. GFAP-IgG, oligoclonal bands (OBs), N-methyl-D-aspartate receptor (NMDAR)-IgG and ITPR1-IgG co-existed in her CSF. She responded well to immunoglobulin and steroid treatments.Here, we describe the case of a patient with autoimmune GFAP astrocytopathy whose CSF was positive for ITPR1-IgG; however, she did not show typical ataxia manifestations or cerebellar lesions on her MRI scan. This suggests that ITPR1-IgG is not pathogenic, and the positivity of this antibody in CSF is probably associated with the presence of autoimmune inflammation.
- Published
- 2020
10. The impacts of ubiquilin 1 (UBQLN1) knockdown on cells viability, proliferation, and apoptosis are mediated by p53 in A549 lung cancer cells
- Author
-
Xiaoli Yao, Huiqing Lin, Yunshu Su, and Xinghua Zhang
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,A549 cell ,Gene knockdown ,biology ,business.industry ,Autophagy ,P70-S6 Kinase 1 ,Cell biology ,Ribosomal s6 kinase ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Medicine ,Original Article ,Viability assay ,business ,PI3K/AKT/mTOR pathway - Abstract
Background Little is known about the relationship between ubiquilin 1 (UBQLN1) and p53, both of them have been implicated in the development and progression of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the role of loss of UBQLN1 in cell viability and proliferation, and cell apoptosis in human lung adenocarcinoma A549 cells. Methods Cell viability, proliferation, and apoptosis were determined by MTT, BrdU, and TUNEL assays, respectively. Adenoviruses carrying cDNA or siRNA were used to overexpress or silence target protein. Dihydroethidium (DHE) staining was performed to measure the real-time formation of intracellular reactive oxygen species (ROS). The chymotrypsin-like activity of 20S proteasome core was determined by using synthetic fluorogenic peptide substrate. Results UBQLN1 silencing led to a reduction of p53 protein levels and overexpression of p53 reversed the effects of UBQLN1 knockdown (KD) on cell viability, proliferation, and apoptosis. Furthermore, deficiency of UBQLN1 activated autophagy activity but did not affect proteasome activity. Inhibition of autophagy restored p53 protein levels in UBQLN1-KD A549 cells. In addition, UBQLN1 KD markedly inhibited phosphorylation of mammalian target of rapamycin (mTOR) and its downstream ribosomal S6 kinase (S6K). Conclusions Our experiments suggested that the regulation of UBQLN1 on cell viability, proliferation, and apoptosis was mediated by mTOR/autophagy/p53 signaling pathway.
- Published
- 2020
11. CircC3P1 attenuated pro‐inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR‐21
- Author
-
Donghang Li, Xinghua Zhang, Jie Ren, Rui Xiong, Zilong Lu, Xiaoli Yao, Qing Geng, Wenyang Jiang, Haojie Feng, and Tao Fan
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,Chemokine ,Necrosis ,medicine.medical_treatment ,Acute Lung Injury ,Down-Regulation ,Inflammation ,Apoptosis ,Punctures ,Pharmacology ,Lung injury ,Proinflammatory cytokine ,Sepsis ,sepsis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Phosphorylation ,Cecum ,Ligation ,Lung ,circC3P1 ,biology ,business.industry ,Endothelial Cells ,Cell Biology ,Original Articles ,RNA, Circular ,medicine.disease ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,Cytokine ,030220 oncology & carcinogenesis ,Microvessels ,biology.protein ,Molecular Medicine ,Cytokines ,Original Article ,medicine.symptom ,Inflammation Mediators ,business ,Proto-Oncogene Proteins c-akt - Abstract
Acute lung injury (ALI) induced by sepsis is characterized by an inflammatory process related to the up‐regulation of inflammatory cytokines and chemokines. In the present study, we explored the role of circC3P1 in sepsis‐induced ALI in vitro and in vivo. The caecal ligation and puncture (CLP)‐induced sepsis model was established through CLP surgery. Forty adult male C57BL/6 mice were randomly assigned into sham, CLP, CLP + vector and CLP + circC3P1 (each n = 10). Primary murine pulmonary microvascular endothelial cells (MPVECs) were transfected with circC3P1 or empty vector 24 hours prior to LPS treatment via Lipofectamine 2000. The expressions of circC3P1, tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and IL‐1β were evaluated after 6‐h LPS treatment. Cell apoptosis was evaluated via flow cytometry. The CLP group demonstrated pulmonary morphological abnormalities, increased concentrations of TNF‐α, IL‐6 and IL‐1β in the lung tissue, compared with the sham group. MPVECs treated with LPS significantly elevated TNF‐α, IL‐6 and IL‐1β levels and increased cell apoptosis than that in the control group. The circC3P1 overexpression in sepsis‐induced ALI mice attenuated pulmonary injury, inflammation and apoptosis. Besides, circC3P1 revealed anti‐inflammatory and anti‐apoptotic effect in MPVEC‐treated LPS. CircC3P1 overexpression reduced cell apoptosis and pro‐inflammatory cytokines levels via down‐regulating miR‐21. CircC3P1 attenuated pro‐inflammatory cytokine production and cell apoptosis in ALI induced by sepsis through modulating miR‐21, indicating that circC3P1 is a promising therapeutic biomarker for sepsis‐induced ALI.
- Published
- 2020
12. The distinct manifestation of young-onset amyotrophic lateral sclerosis in China
- Author
-
Minying Zheng, Weineng Chen, Youna Xie, Xiaoli Yao, Pian Huang, and Jianing Lin
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Young onset ,Disease ,03 medical and health sciences ,Superoxide Dismutase-1 ,0302 clinical medicine ,medicine ,Humans ,Amyotrophic lateral sclerosis ,business.industry ,Amyotrophic Lateral Sclerosis ,DNA Helicases ,High-Throughput Nucleotide Sequencing ,Proteins ,medicine.disease ,Multifunctional Enzymes ,DNA-Binding Proteins ,Neurology ,Mutation ,RNA-Binding Protein FUS ,Neurology (clinical) ,business ,RNA Helicases ,030217 neurology & neurosurgery - Abstract
Young-onset amyotrophic lateral sclerosis (ALS) refers to ALS patients with initial symptoms earlier than 45 years, representing a novel disease pattern. We aim to summarize the clinical and genetic features of 102 young-onset ALS patients in China.
- Published
- 2020
13. Klippel–Trenaunay and Sturge–Weber Overlap Syndrome with KRAS and GNAQ mutations
- Author
-
Ru-xun Huang, Xiaoli Yao, Jinsheng Zeng, Ruojie He, Jian Yu, Song-Jie Liao, and Jian Zhang
- Subjects
Adult ,Male ,0301 basic medicine ,Klippel-Trenaunay-Weber Syndrome ,Pathology ,medicine.medical_specialty ,Somatic cell ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Brief Communication ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,Hemangioma ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Sturge-Weber Syndrome ,Humans ,Medicine ,RC346-429 ,Mutation ,business.industry ,General Neuroscience ,Overlap syndrome ,medicine.disease ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,GTP-Binding Protein alpha Subunits, Gq-G11 ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,KRAS ,Brief Communications ,business ,030217 neurology & neurosurgery ,GNAQ ,RC321-571 ,Blood vessel - Abstract
Patients with combined phenotypes of Sturge–Weber syndrome and Klippel–Trenaunay syndrome have been reported, though the underlying genetic spectrum in these individuals remains to be elucidated. We reported the patient presenting with Klippel–Trenaunay and Sturge–Weber overlap syndrome in mainland China. Histopathologic study confirmed the hemangioma of vein and capillary. Co‐existence of a novel somatic KRAS c.182_183 delins TC mutation and GNAQ c.548G>A mutation was identified in the affected skin tissue rather than paired peripheral blood. The somatic mutations of GNAQ and KRAS may affect MAPK‐ERK signaling pathway, resulting in endothelial anomaly and blood vessel malformation.
- Published
- 2020
14. Clinical and genetic features of patients with amyotrophic lateral sclerosis in southern China
- Author
-
Minying Zheng, Xiaoli Yao, Jianing Lin, Youna Xie, Pian Huang, Weineng Chen, and Zhong Pei
- Subjects
Adult ,Oncology ,China ,medicine.medical_specialty ,SOD1 ,TARDBP ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genotype ,Genetic variation ,medicine ,Humans ,030212 general & internal medicine ,Amyotrophic lateral sclerosis ,ERBB4 ,business.industry ,Amyotrophic Lateral Sclerosis ,DNA Helicases ,Proteins ,Middle Aged ,medicine.disease ,Multifunctional Enzymes ,Phenotype ,DNA-Binding Proteins ,Neurology ,Southern china ,Mutation ,RNA-Binding Protein FUS ,Neurology (clinical) ,business ,RNA Helicases ,030217 neurology & neurosurgery - Abstract
Background and purpose Amyotrophic lateral sclerosis (ALS)-related genes and mutations have been increasingly discovered recently and an improved understanding of genotype-phenotype relationships may help to predict the disease course and refine genetic diagnosis. Methods We collected clinical data and blood samples from 268 patients and used next-generation sequencing to comprehensively assay genetic variations in a panel of known ALS genes from 2015 to 2019. Results Among these patients, the mean age of onset was 52.30 ± 10.42 years with a mean diagnosis delay of 15.90 ± 11.88 months. Patients with SOD1, TARDBP and FUS variants were more likely to suffer from familial ALS. Additionally, carriers of FUS variants displayed the earliest onset, followed by those with SOD1 variants. Patients with NEFH variants showed a closer link to pesticide exposure. Patients with SETX variants were prone to bulbar onset with moderate anxiety problems. No genotype-phenotype relations were found in SPG11 and ERBB4 mutants. Conclusion Our findings uncovered some genotype-phenotype relationships and may help to predict the disease course of patients with ALS in southern China.
- Published
- 2020
15. Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of β-Amyloid in a mouse model with Alzheimer’s disease
- Author
-
Huanxing Su, Xiaoli Yao, Lingli Yan, Qiang Liu, Youna Xie, Yuemeng Ma, Senthil Kumaran Satyanarayanan, Jian-Bo Wan, Miaodan Huang, Haitao Zeng, and Kuan-Pin Su
- Subjects
0301 basic medicine ,Genetically modified mouse ,medicine.medical_specialty ,Immunology ,Mice, Transgenic ,Amyloid beta-Protein Precursor ,Mice ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,medicine ,Extracellular ,Animals ,Senile plaques ,Neuroinflammation ,chemistry.chemical_classification ,Amyloid beta-Peptides ,Endocrine and Autonomic Systems ,Chemistry ,Brain ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Tumor necrosis factor alpha ,Alzheimer's disease ,030217 neurology & neurosurgery ,Lipoprotein ,Polyunsaturated fatty acid - Abstract
Amyloid-β (Aβ) plaques is one of the typical pathological hallmark of Alzheimer disease (AD). Accumulating evidence suggests that the imbalance between Aβ production and clearance leads to extracellular Aβ accumulation in the brain. It is reported that the blood–brain barrier (BBB) transport plays a predominant role in Aβ clearance from brain to blood. In the present study, we investigated dynamic alterations of BBB transport function in the early disease stage of AD using APPswe/PS1dE9 C57BL/6J (APP/PS1) transgenic mice. Our results showed that the expression of lipoprotein receptor-related protein 1 (LRP-1), a main efflux transporter of BBB, started to decrease at the age of 4 months old. Interestingly, supplementing with fish oil which is rich in omega-3 polyunsaturated fatty acids (PUFAs) significantly enhanced the expression level of LRP-1 and promoted Aβ clearance from the bran to circulation, as revealed by reduced soluble/insoluble Aβ levels and senile plaques in the brain parenchyma and a corresponding increase of Aβ levels in plasma. Besides, fish oil supplement significantly inhibited the NF-κB activation, reduced the expression of interleukin-1β and tumor necrosis factor-α, and suppressed the glial activation in APP/PS1 mice. The results of the study provide evidence that BBB transport function could be impaired at a very early disease stage, which might contribute to Aβ pathological accumulation in AD, and omega-3 PUFAs intervention could be an effective strategy for the prevention of the progression of AD through promoting Aβ clearance from brain-to-blood.
- Published
- 2020
16. Experimental alcoholism primes structural and functional impairment of the glymphatic pathway
- Author
-
Miaodan Huang, Huanxing Su, Haitao Zeng, Dingbang Chen, Jia-Hong Lu, Lingli Yan, Xiaoli Yao, Zhe Shi, Senthil Kumaran Satyanarayanan, Zhong Pei, and Qiang Liu
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Functional impairment ,Immunology ,Acute alcohol ,Mice ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Cerebrospinal fluid ,Internal medicine ,Parenchyma ,Animals ,Humans ,Medicine ,Dementia ,Cognitive decline ,Cerebrospinal Fluid ,Amyloid beta-Peptides ,Endocrine and Autonomic Systems ,business.industry ,Brain ,Extracellular Fluid ,medicine.disease ,Mice, Inbred C57BL ,Alcoholism ,030104 developmental biology ,Endocrinology ,Glymphatic system ,business ,Glymphatic System ,Alcohol consumption ,030217 neurology & neurosurgery - Abstract
Alcoholism is a risk factor for the development of cognitive decline and dementia. Here we demonstrated that the glymphatic function in the brain was impaired by alcohol administration. Acute moderate alcohol administration substantially retarded and reduced the entry of subarachnoid cerebrospinal fluid (CSF) via the paravascular space into the cerebral parenchyma, thus impaired CSF-interstitial fluid (ISF) exchange and parenchymal amyloid β (Aβ) peptide clearance. The elevated release of β-endorphin and reduced cerebrovascular pulsatility after acute alcohol administration may account for the impairment of the glymphatic function. Chronic moderate alcohol consumption led to pronounced activation of astrocytes and a widespread loss of perivascular AQP4 polarization in the brain, which results in an irreversible impairment of the glymphatic function. The results of the study suggest that impaired glymphatic functions and reduced parenchymal Aβ clearance found in both acute and chronic alcohol treatment may contribute to the development of cognitive decline and dementia in alcoholism.
- Published
- 2020
17. Islet Function Changes Among the Elderly Population
- Author
-
Yue Wang, Jing Sui, Yinghui Hu, Xiaoli Yao, Jie Ming, Mingqian He, Mei Deng, Bingyin Shi, Qiuhe Ji, and Xinrui Zhao
- Subjects
Male ,0301 basic medicine ,Aging ,medicine.medical_specialty ,endocrine system diseases ,Cross-sectional study ,Type 2 diabetes ,Islets of Langerhans ,03 medical and health sciences ,0302 clinical medicine ,Elderly population ,Diabetes mellitus ,Epidemiology ,medicine ,Humans ,Elderly adults ,Aged ,Glycemic ,geography ,geography.geographical_feature_category ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Islet ,Cross-Sectional Studies ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,030220 oncology & carcinogenesis ,Female ,business ,Demography - Abstract
China is stepping into the aging society. The prevalence of type 2 diabetes among elderly population is increasing in China in the last few decades. However, there is a lack of epidemiological investigations regarding to the aging-related changes of islet function in the elderly population.To investigate the islet function and glycemic conditions in the elderly population of western China.Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a provincial representative sample of 3001 western Chinese elderly adults. A 2 h oral glucose tolerance test (OGTT) was conducted among all study participants, and islet function measurements including HOMA-β, HOMA-IR, HOMA-IS, ΔI30/ΔG30, Ip/I0 were calculated.HOMA-β, HOMA-IR and ΔI30/ΔG30 decreased gradually along with increasing age from age of 55 to age of 80 (p0.05). HOMA-IR, HOMA-β and ΔI30/ΔG30 were significantly higher while HOMA-IS lower among urban residents than rural residents or suburb residents (p0.01). FPG, 2 h plasma glucose (P2hPG) and HbA1C increased with increasing age (p0.05), while fasting insulin level (FINS) and 2 h insulin level (P2hINS) decreased with increasing age (p0.05). FPG, P2hPG and glycated hemoglobin (HbA1C) among suburb residents were lower than among urban residents and among rural residents (p0.05).Islet function decreased gradually along with increasing age with no gender difference among the elderly population in western China. Glycemic outcomes became worse with increasing age. These results indicated that strategies aimed at the prevention of diabetes in the elderly population were needed.
- Published
- 2019
18. Endogenous SO2 Controls Cell Apoptosis: The State-of-the-Art
- Author
-
Xiaoyun Ye, Jiantong Du, Yingjun Feng, Junbao Du, Yaqian Huang, Hanlin Peng, Hongfang Jin, Yingying Li, and Xiaoli Yao
- Subjects
Vascular smooth muscle ,QH301-705.5 ,Mechanism (biology) ,apoptosis ,mechanism ,Retinal ,Endogeny ,Cell Biology ,Biology ,Lung injury ,complex mixtures ,respiratory tract diseases ,Cell biology ,Pathogenesis ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Apoptosis ,medicine ,sulfur dioxide ,Neuron ,Biology (General) ,metabolism ,pathophysiology ,Developmental Biology - Abstract
SO2, previously known as the product of industrial waste, has recently been proven to be a novel gasotransmitter in the cardiovascular system. It is endogenously produced from the metabolism pathway of sulfur-containing amino acids in mammalians. Endogenous SO2 acts as an important controller in the regulation of many biological processes including cardiovascular physiological and pathophysiological events. Recently, the studies on the regulatory effect of endogenous SO2 on cell apoptosis and its pathophysiological significance have attracted great attention. Endogenous SO2 can regulate the apoptosis of vascular smooth muscle cells, endothelial cells, cardiomyocytes, neuron, alveolar macrophages, polymorphonuclear neutrophils and retinal photoreceptor cells, which might be involved in the pathogenesis of hypertension, pulmonary hypertension, myocardial injury, brain injury, acute lung injury, and retinal disease. Therefore, in the present study, we described the current findings on how endogenous SO2 is generated and metabolized, and we summarized its regulatory effects on cell apoptosis, underlying mechanisms, and pathophysiological relevance.
- Published
- 2021
19. Milano–Torino Staging and Long-Term Survival in Chinese Patients with Amyotrophic Lateral Sclerosis
- Author
-
Ling Lian, Minying Zheng, Ruojie He, and Xiaoli Yao
- Subjects
Male ,Longitudinal study ,amyotrophic lateral sclerosis ,Time Factors ,Health Status ,Walking ,Neuropsychological Tests ,Severity of Illness Index ,Disability Evaluation ,0302 clinical medicine ,Medicine ,Health Status Indicators ,030212 general & internal medicine ,Longitudinal Studies ,Amyotrophic lateral sclerosis ,Stage (cooking) ,Biology (General) ,Depression (differential diagnoses) ,Milano–Torino staging ,Communication ,Respiration ,General Medicine ,Middle Aged ,Prognosis ,Mental Health ,Disease Progression ,Anxiety ,Female ,medicine.symptom ,long-term survival ,Adult ,medicine.medical_specialty ,China ,QH301-705.5 ,Article ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,Long term survival ,Humans ,Aged ,business.industry ,Disease progression ,Reproducibility of Results ,medicine.disease ,Deglutition ,Clinical trial ,Self Care ,neuropsychiatric factors ,business ,030217 neurology & neurosurgery - Abstract
(1) Background: The aim of this longitudinal study was to evaluate the association between disease progression according to the Milano–Torino staging (MITOS) system and long-term survival in Chinese patients with amyotrophic lateral sclerosis (ALS). We also examined factors affecting MITOS progression. (2) Methods: Patients were enrolled and underwent follow-up at 6, 12, 18, and 24 months, and their demographic and clinical data, including the Milano–Torino stage, Amyotrophic Lateral Sclerosis Functional Rating Scale—Revised (ALSFRS-R) score and neuropsychiatric data, were evaluated. The sensitivity and specificity of predicting survival outcomes based on MITOS progression and ALSFRS-R score decline from baseline to 6 months were compared. The associations between MITOS progression from baseline to 6 months and survival outcome at 12, 18 and 24 months were examined, and factors associated with disease progression were evaluated with subgroup analyses. (3) Results: Among the 100 patients included, 74% were in stage 0 at baseline, and approximately 95% progressed to a higher stage of the MITOS system at 24 months. MITOS progression from baseline to 6 months and ALSFRS-R decline showed comparable value for predicting survival at 12, 18, and 24 months. MITOS progression from baseline to 6 months is strongly associated with death outcomes. Older age at onset and increased depression and anxiety scores may be related to disease progression. (4) Conclusions: MITOS progression during the early disease course could serve as a prognostic marker of long-term survival and may have utility in clinical trials. Age at onset and diagnosis and neuropsychiatric factors might be associated with disease progression.
- Published
- 2021
20. Key Molecules and Pathways Underlying Sporadic Amyotrophic Lateral Sclerosis: Integrated Analysis on Gene Expression Profiles of Motor Neurons
- Author
-
Chenghui Ye, Pian Huang, Jianing Lin, Weineng Chen, Xiaoli Yao, and Huanxing Su
- Subjects
0301 basic medicine ,bioinformatics analysis ,Bioinformatics analysis ,lcsh:QH426-470 ,Blood vessel morphogenesis ,Biology ,FN1 gene ,Pathogenesis ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,sporadic amyotrophic lateral sclerosis ,Gene expression ,Genetics ,medicine ,motor neurons ,Amyotrophic lateral sclerosis ,Transcription factor ,Genetics (clinical) ,Original Research ,gene expression profiles ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Regulatory Pathway ,Neuroscience - Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor neurons. The complex mechanisms underlying ALS are yet to be elucidated, while the lack of disease biomarkers and therapeutic options are associated with the poor prognosis of ALS patients. In this study, we performed bioinformatics analysis to clarify potential mechanisms in sporadic ALS (sALS). We compared three gene expression profiles (GSE18920, GSE56500, and GSE68605) of motor neurons obtained from sALS patients and healthy controls to discover differentially expressed genes (DEGs), and then performed integrated bioinformatics analyses to identify key molecules and pathways underlying sALS. We found that these DEGs were mainly enriched in the structure and functions of extracellular matrix (ECM), while functional enrichment in blood vessel morphogenesis was less correlated with motor neurons. The clustered subnetworks of the constructed protein-protein interaction network for DEGs and the group of selected hub genes were more significantly involved in the organization of collagen-containing ECM. The transcriptional factors database proposed RelA and NF-κB1 from NF-κB family as the key regulators of these hub genes. These results mainly demonstrated the alternations in ECM-related gene expression in motor neurons and suggested the role of NF-κB regulatory pathway in the pathogenesis of sALS.
- Published
- 2020
21. Muscular involvement and tendon contracture in limb-girdle muscular dystrophy 2Y: a mild adult phenotype and literature review
- Author
-
Songjie Liao, Weixi Zhang, Xuelin Feng, Wenbiao Xian, Jinlang Wu, Xiaoli Yao, and Bing Liao
- Subjects
Adult ,Male ,medicine.medical_specialty ,Weakness ,lcsh:Diseases of the musculoskeletal system ,Contracture ,Case Report ,Nuclear envelopathies ,LGM2Y ,Frameshift mutation ,Tendons ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,Achilles tendon contracture ,Joint Contracture ,Child ,030203 arthritis & rheumatology ,030222 orthopedics ,Muscle Weakness ,business.industry ,Muscle weakness ,Anatomy ,LAP1 ,medicine.disease ,Phenotype ,Muscular Dystrophies, Limb-Girdle ,Mutation ,lcsh:RC925-935 ,medicine.symptom ,business ,Tendon contracture ,Limb-girdle muscular dystrophy - Abstract
Background Limb girdle muscular dystrophy type 2Y (LGMD2Y) is a rare subgroup of limb girdle muscular dystrophy featuring limb-girdle weakness, tendon contracture and cardiac involvement. It is caused by the mutation of TOR1AIP1, which encodes nuclear membrane protein LAP1 (lamina-associated polypeptide 1) and comprises heterogeneous phenotypes. The present study reported a patient with a novel homozygous TOR1AIP1 mutation that presented with selective muscle weakness, which further expanded the phenotype of LGMD2Y- and TOR1AIP1-associated nuclear envelopathies. Case presentation A 40-year-old male presented with Achilles tendon contracture and muscle weakness that bothered him from 8 years old. While the strength of his distal and proximal upper limbs was severely impaired, the function of his lower limbs was relatively spared. Muscle pathology showed dystrophic features, and electron microscopy showed ultrastructural abnormalities of disrupted muscle nuclei envelopes. Whole-exome sequencing showed a frameshift mutation in TOR1AIP1 (c.98dupC). Conclusion We reported a novel mild phenotype of LGMD2Y with relatively selective distal upper limb weakness and joint contracture and revealed the heterogeneity of LGDM2Y and the role of the LAP1 isoform by literature review.
- Published
- 2020
22. Cocaine-induced structural and functional impairments of the glymphatic pathway in mice
- Author
-
Pian Huang, Haitao Zeng, Zhe Shi, Jianing Lin, Xiaoli Yao, and Weineng Chen
- Subjects
0301 basic medicine ,media_common.quotation_subject ,Immunology ,Pharmacology ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Cerebrospinal fluid ,Cocaine ,Parenchyma ,Extracellular ,Medicine ,Animals ,Humans ,media_common ,Aquaporin 4 ,Endocrine and Autonomic Systems ,business.industry ,Addiction ,Brain ,Extracellular Fluid ,medicine.disease ,Astrogliosis ,030104 developmental biology ,Cerebral blood flow ,Glymphatic system ,business ,Neurocognitive ,Glymphatic System ,030217 neurology & neurosurgery - Abstract
The glymphatic system plays a central role in the clearance of extracellular wastes from the brain. Cocaine exposure can lead to pathologies that affect the entire brain, resulting in addictive disorders involving motivational and cognitive impairment. However, it remains unknown whether cocaine exposure impairs glymphatic function. In the present study, using a mouse model of noncontingent cocaine exposure, we evaluated glymphatic function including cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and solute clearance during repeated exposures and withdrawal. We found that cocaine treatment, both during repeated exposure and withdrawal, significantly induced widespread astrogliosis and reduced cerebral blood flow (CBF), cerebrovascular pulsatility, and aquaporin-4 (AQP4) polarity. Glymphatic function was greatly impaired in mice after cocaine treatment, as evidenced by reduced CSF influx from paravascular pathways into the brain parenchyma and decreased efflux of interstitial molecules out of the parenchyma. These findings provide evidence that cocaine exposure impairs the clearance of wastes from the brain, which may contribute to the development of neurocognitive disorders in patients with drug addictions.
- Published
- 2020
23. Fish oil protects the blood–brain barrier integrity in a mouse model of Alzheimer’s disease
- Author
-
Xiaoli Yao, Weineng Chen, Haitao Zeng, Youna Xie, Huanxing Su, Jia-Hong Lu, Jian-Bo Wan, and Lingli Yan
- Subjects
medicine.medical_specialty ,Amyloid beta ,Blood–brain barrier ,NF-κB ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Neuroinflammation ,Internal medicine ,medicine ,030304 developmental biology ,Pharmacology ,chemistry.chemical_classification ,0303 health sciences ,biology ,Omega-3 polyunsaturated fatty acids ,Research ,Aβ-degrading enzymes ,Prodromal Stage ,lcsh:Other systems of medicine ,lcsh:RZ201-999 ,Fish oil ,Pathophysiology ,Endocrinology ,Enzyme ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,biology.protein ,030217 neurology & neurosurgery - Abstract
Background Alzheimer’s disease (AD) is ranked as the most prevalent neurodegenerative disease. However, the exact molecular mechanisms underlying pathophysiological alterations in AD remain unclear, especially at the prodromal stage. The decreased proteolytic degradation of Aβ, blood–brain barrier (BBB) disruption, and neuroinflammation are considered to play key roles in the course of AD. Methods Male APPswe/PS1dE9 C57BL/6 J double-transgenic (APP/PS1) mice in the age range from 1 month to 6 months and age-matched wild type mice were used in this study, intending to investigate the expression profiles of Aβ-degrading enzymes for Aβ degradation activities and zonula occludens-1 (zo-1) for BBB integrity at the prodromal stage. Results Our results showed that there were no significant genotype-related alterations in mRNA expression levels of 4 well-characterized Aβ-degrading enzymes in APP/PS1 mice within the ages of 6 months. Interestingly, a significant decrease in zo-1 expression was observed in APP/PS1 mice starting from the age of 5 months, suggesting that BBB disrupt occurs at an early stage. Moreover, treatment of fish oil (FO) for 4 weeks remarkably increased zo-1 expression and significantly inhibited the glial activation and NF-κB activation in APP/PS1 mice. Conclusion The results of our study suggest that FO supplement could be a potential therapeutic early intervention for AD through protecting the BBB integrity and suppressing glial and NF-κB activation.
- Published
- 2020
24. Simple prosthesis versus prosthesis plus titanium-coated polypropylene mesh for implant-based immediate breast reconstruction after total mastectomy for breast cancer
- Author
-
Xiaoli Yao, Xinghua Zhang, Feng Yao, Yi Tu, Yueyue Guo, Chuang Chen, and Shengrong Sun
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Capsular contracture ,030230 surgery ,medicine.disease ,Prosthesis ,Family life ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Breast cancer ,030220 oncology & carcinogenesis ,medicine ,Original Article ,Implant ,Total Mastectomy ,business ,Breast reconstruction - Abstract
Background: Our study compares the cosmetic effects, postoperative complications, and quality of life of immediate breast reconstruction with simple prosthesis or prosthesis plus titanium-coated polypropylene mesh (TCPM) after total mastectomy for breast cancer. Methods: In total, 69 patients who underwent total mastectomy, sentinel lymph node biopsy, and immediate prosthetic breast reconstruction from January 2015 to December 2018 in our hospital were selected, and their cosmetic effects, complications, and quality of life after reconstruction were recorded immediately after surgery and 6 months after surgery. Results: Of these 69 patients, 29 were in the simple prosthesis group and 40 in the prosthesis + TCPM group. The incidence of surgical complications was 17.2% in the simple prosthesis group (5/29; including 4 cases of capsular contracture and 1 case of infection) 15.0% in the prosthesis + TCPM group (6/40; 1 case of flap necrosis, 2 cases of poor wound healing, 2 cases of hematomas, and 1 case of inadequate blood supply to nipple). The complications were successfully managed after symptomatic treatment in both groups. No prosthesis loss was noted. The incidence of postoperative complications showed there to be no significant differences between these two groups (P=0.06, χ 2 =0.80). The satisfaction rate of patients on cosmetic effects was 95.0% (38/40) in the prosthesis + TCPM group, significantly higher than that in the simple prosthesis group (75.90%, 22/29) (P=0.05, χ 2 =3.87). The quality of life in the simple prosthesis group at 2 weeks and six months after the operation was significantly lower than that in the prosthesis + TCPM group. The incidence rate of arm pain and fatigue at 2 weeks after operation was significantly higher than that in the prosthesis + TCPM group (P=0.04, χ 2 =4.42). The satisfaction of family life and sexual interest 6 months after the operation was also significantly lower in the simple prosthesis group than in the prosthesis + TCPM group (P=0.03, χ 2 =4.95). Conclusions: Breast reconstruction with prosthesis combined with TCPM does not increase surgical complications and has a good cosmetic effect and high patient satisfaction. Thus, it is a safe and reconstruction method.
- Published
- 2020
25. USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis
- Author
-
Yongjie Chen, Naichun Yu, Daguo Zhou, Linlin Zhang, Tianwei Zhang, Guojun Wei, Guangrong Ji, Xiaoli Yao, Zongguang Li, and Xiang Xue
- Subjects
Transcriptional Activation ,Aging ,Carcinogenesis ,miR-934 ,Biology ,medicine.disease_cause ,Downregulation and upregulation ,GAS6-AS2 ,Cell Line, Tumor ,medicine ,Humans ,Transaminases ,Gene knockdown ,Osteosarcoma ,GAS6 ,Melanoma ,Cell Biology ,USF1 ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Apoptosis ,Cell culture ,Cancer research ,Disease Progression ,Intercellular Signaling Peptides and Proteins ,Upstream Stimulatory Factors ,RNA, Long Noncoding ,BCAT1 ,Research Paper - Abstract
Long noncoding RNAs (lncRNAs) have been certified as important regulators in tumorigenesis. LncRNA GAS6-AS2 (GAS6-AS2) was a newly identified tumor-related lncRNA, and its dysregulation and oncogenic effects in melanoma and bladder cancer had been reported in previous studies. However, the expression pattern and potential function of GAS6-AS2 in osteosarcoma (OS) have not been investigated. In this study, we identified a novel OS-related lncRNA GAS6-AS2. We found that GAS6-AS2 was distinctly upregulated in both OS specimens and cell lines. Distinct up-regulation of GAS6-AS2 in OS was correlated with advanced clinical stages and shorter survivals. In addition, USF1 could directly bind to the GAS6-AS2 promoter and contribute to its overexpression. Furthermore, GAS6-AS2 knockdown caused tumor suppressive effects via reducing cellular proliferation, migration and invasion, and promoting OS cell apoptosis. Besides, GAS6-AS2 directly bound to miR-934 and downregulated its expression. Mechanistically, GAS6-AS2 positively regulated the expression of BCAT1 through sponging miR-934. Taken together, our data illustrated how GAS6-AS2 played an oncogenic role in OS and might offer a potential therapeutic target for treating OS.
- Published
- 2019
26. Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction
- Author
-
Zhe Shi, Chuanming Luo, Xiaoli Yao, Huanxing Su, Huixia Ren, Zhong Pei, Jian-Bo Wan, Jing X. Kang, Fengyin Liang, and Kuan-Pin Su
- Subjects
0301 basic medicine ,Pathology ,Cognitive decline ,lcsh:Medicine ,Apoptosis ,Hippocampal formation ,Hippocampus ,Vascular dementia ,Mice ,0302 clinical medicine ,Medicine ,chemistry.chemical_classification ,Cerebral Cortex ,Neurons ,lcsh:R5-920 ,TUNEL assay ,General Medicine ,Cerebral Infarction ,Cadherins ,Neuroprotective Agents ,Receptor-Interacting Protein Serine-Threonine Kinases ,lcsh:Medicine (General) ,Polyunsaturated fatty acid ,Research Paper ,Neuropsychiatric disorders ,Genetically modified mouse ,medicine.medical_specialty ,Mice, Transgenic ,Fish oil ,Neuroprotection ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Fish Oils ,Arteriole ,Alzheimer Disease ,medicine.artery ,Fatty Acids, Omega-3 ,Animals ,Humans ,business.industry ,lcsh:R ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Dietary Supplements ,business ,030217 neurology & neurosurgery - Abstract
Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the “single cortical microinfarct model” generated via occluding a penetrating arteriole by femtosecond laser ablation and the “multiple diffuse microinfarcts model” induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered ω-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of ω-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where ω-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain ω-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of ω-3 PUFAs in the treatment or prophylaxis in vascular dementia., Highlights • Omega-3 PUFAs inhibit the RIPK1-mediated apoptotic pathways in cortical microinfarcts. • Omega-3 PUFAs contribute to anatomically decreasing microinfarct damage. • Omega-3 PUFAs supplements improve functional deficits in a mouse model with multiple diffuse microinfarcts. Cerebral microinfarct is defined as microscopic vascular occlusion
- Published
- 2018
27. Fish oil treatment reduces chronic alcohol exposure induced synaptic changes
- Author
-
Ti-Fei Yuan, Huanxing Su, Youna Xie, Baixuan He, Huixia Ren, Zhe Shi, Jian-Bo Wan, Meng Wang, and Xiaoli Yao
- Subjects
Medicine (miscellaneous) ,Binge drinking ,AMPA receptor ,Nucleus accumbens ,Pharmacology ,Nucleus Accumbens ,Alcohol Withdrawal Seizures ,Mice ,03 medical and health sciences ,Fish Oils ,0302 clinical medicine ,Recurrence ,Animals ,Medicine ,Receptors, AMPA ,chemistry.chemical_classification ,Ethanol ,business.industry ,Alcohol dependence ,Neurotoxicity ,Central Nervous System Depressants ,Dendrites ,Fish oil ,medicine.disease ,030227 psychiatry ,Alcoholism ,Psychiatry and Mental health ,chemistry ,Synapses ,Synaptic plasticity ,business ,Locomotion ,030217 neurology & neurosurgery ,Polyunsaturated fatty acid - Abstract
Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure. Our results demonstrated that fish oil significantly reduced the chronic alcohol exposure-induced aberrant dendritic morphologic changes of the medium-sized spiny neurons in the core and the shell of nucleus accumbens. This inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the post synaptic membranes of medium-sized spiny neurons and eventually alleviated withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3 PUFAs are promising for treating withdrawal symptoms and alcohol dependence.
- Published
- 2018
28. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia
- Author
-
Zhong Pei, Chuanming Luo, Xiaoli Yao, Huixia Ren, Huanxing Su, Ming‐yue Li, Ti-Fei Yuan, Qiang Liu, Fengyin Liang, and Dajiang Qin
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,General Neuroscience ,Penumbra ,Ischemia ,Infarction ,Blood flow ,medicine.disease ,Pathology and Forensic Medicine ,Microcirculation ,Brain ischemia ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Anesthesia ,Internal medicine ,Occlusion ,Cardiology ,medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Blood vessel - Abstract
Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia.
- Published
- 2017
29. Azoramide protects iPSC-derived dopaminergic neurons with PLA2G6 D331Y mutation through restoring ER function and CREB signaling
- Author
-
Cheong-Meng Chong, Jia-Hong Lu, Miaodan Huang, Ke Zhang, Xiaotong Cen, Huanxing Su, Zhijian Huang, Dajiang Qin, Minjing Ke, Haitao Zeng, and Xiaoli Yao
- Subjects
Cancer Research ,Parkinson's disease ,Immunology ,Mutant ,Induced Pluripotent Stem Cells ,Apoptosis ,CREB ,Molecular neuroscience ,Article ,Group VI Phospholipases A2 ,Cellular and Molecular Neuroscience ,Neural Stem Cells ,medicine ,Humans ,Calcium Signaling ,lcsh:QH573-671 ,Induced pluripotent stem cell ,Cyclic AMP Response Element-Binding Protein ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,lcsh:Cytology ,Endoplasmic reticulum ,Dopaminergic Neurons ,Dopaminergic ,Cell Biology ,Endoplasmic Reticulum Stress ,Amides ,Cell biology ,Mitochondria ,Thiazoles ,medicine.anatomical_structure ,Neuroprotective Agents ,chemistry ,Mutation ,biology.protein ,Unfolded protein response ,Unfolded Protein Response ,Calcium ,Neuron ,Reactive Oxygen Species - Abstract
The endoplasmic reticulum (ER)-stress-induced cascade events are implicated in Parkinson’s disease (PD). The discovery of drug candidates to protect dopaminergic (DA) neurons from ER-stress-induced oxidative damage is important to resolve the pathological aspects of PD and modify its progress. In this study, we found that a recently identified unfolded protein response (UPR) modulator, azoramide, showed protective effects on patient induced pluripotent stem cells-derived midbrain DA neurons with the homozygous phospholipase A2 group 6 (PLA2G6) D331Y mutant. A series of PD-related cascade events such as ER stress, abnormal calcium homeostasis, mitochondrial dysfunction, increase of reactive oxygen species, and apoptosis were observed in PLA2G6 D331Y mutant DA neurons, whereas azoramide significantly protected PLA2G6 D331Y mutant DA neurons against these events. The beneficial effects of azoramide were abolished by treatment with a cAMP-response element binding protein (CREB) inhibitor. Our results suggest that azoramide is a potential neuroprotectant against DA neuron damage via restoring ER function and the CREB signaling.
- Published
- 2019
30. Intrathecal AAV9-Neprilysin Protects Against Perivascular Amyloid-β Accumulation in a Mouse Model of Cerebral Amyloid Angiopathy
- Author
-
Senthil Kumaran Satyanarayanan, Lingli Yan, Xiaoli Yao, Kuan-Pin Su, Huanxing Su, Ke Zhang, Qiang Liu, Ge Li, Zhong Pei, Miaodan Huang, and Weineng Chen
- Subjects
Genetically modified mouse ,business.industry ,Genetic enhancement ,Transfection ,Pharmacology ,medicine.disease ,medicine.anatomical_structure ,medicine ,Glymphatic system ,Pericyte ,Cerebral amyloid angiopathy ,Cognitive decline ,business ,Neprilysin - Abstract
Targeting amyloid-β (Aβ) accumulation seems a promising strategy for the treatment of cerebral amyloid angiopathy (CAA) and neurodegenerative diseases. However, it is still challenging to develop a safe and efficient technology for brain-wide perivascular Aβ clearance. Using intrathecally injected adeno-associated virus 9 (AAV9) encoding soluble form of neprilysin (sNEP), we showed that AAV-sNEP reduced Aβ accumulation and improved cognitive deficits in Tg-SwDI transgenic mice. Meningeal cells, adventitial cells and smooth muscle cells in leptomeningeal arteries and penetrating arterioles were transfected by intrathecal injection of AAV9-sNEP, hence generating sufficient sNEP to exert beneficial effects by perivascular Aβ clearance, protecting against smooth muscle cell damage and pericyte loss, maintaining blood-brain barrier (BBB) integrity, and eventually improving cognitive decline in Tg-SwDI mice. This study provides pre-clinical evidence that intrathecal delivery of AAV-mediated sNEP may be a promising therapeutic strategy for the treatment of CAA. Funding Statement: This study was supported by the Science and Technology Development Fund, Macau SAR (020/2017/A1 and 039/2017/AFJ); multi-year research grant, University of Macau, (MYRG2016-00184-ICMS-QRCM and MYRG2018-00242-ICMS); Science and Technology Program of Guangzhou (No. 2014J4500031) and Guangzhou Clinical Research and Translational Center for Major Neurological Disease (No. 201604020010). Declaration of Interests: The authors declared no conflicts of interest. Ethics Approval Statement: All animal experiments were approved by the ethics committee at the University of Macau (Macau, China) and Sun Yat-Sen University, and performed in compliance with the institutional guidelines.
- Published
- 2019
31. Investigation of the molecular mechanisms underlying metastasis in prostate cancer by gene expression profiling
- Author
-
Pengcheng Luo, Xinghua Zhang, Cong Qin, Xiaoli Yao, and Jie Zhang
- Subjects
0301 basic medicine ,differentially expressed genes ,Cancer Research ,genetic structures ,Microarray ,metastatic prostate cancer ,Biology ,regulatory network ,Metastasis ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Immunology and Microbiology (miscellaneous) ,microRNA ,medicine ,Oncogene ,pathway ,Microarray analysis techniques ,Cancer ,Articles ,General Medicine ,medicine.disease ,Gene expression profiling ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research - Abstract
The present study aimed to screen potential genes associated with metastatic prostate cancer (PCa), in order to improve the understanding of the mechanisms underlying PCa metastasis. The GSE3325 microarray dataset, which was downloaded from the Gene Expression Omnibus database, consists of seven clinically localized PCa samples, six hormone-refractory metastatic PCa samples and six benign prostate tissue samples. The Linear Models for Microarray Data package was used to identify differentially-expressed genes (DEGs) and a hierarchical cluster analysis for DEGs was performed with the pheatmap package. Furthermore, potential functions for the DEGs were predicted by a functional enrichment analysis. Subsequently, microRNAs (miRNAs) potentially involved in the regulation of PCa metastasis were identified by WebGestalt software, and the miRNA-DEG regulatory network was visualized using Cytoscape. In addition, a pathway enrichment analysis for DEGs in the regulatory network was performed. A total of 306 and 2,073 genes were differentially expressed in the clinically localized PCa and the metastatic PCa groups, respectively, as compared with the benign prostate group, of which 174 were differentially expressed in both groups. A number of the DEGs, including CAMK2D and SH3BP4, were significantly enriched in the cell cycle, and others, such as MAF, were associated with the regulation of cell proliferation. Furthermore, some DEGs (CAMK2D and PCDH17) were observed to be regulated by miR-30, whereas others (ADCY2, MAF, SH3BP4 and PCDH17) were modulated by miR-182. Additionally, ADCY2 and CAMK2D were distinctly enriched in the calcium signaling pathway. The present study identified novel DEGs, including ADCY2, CAMK2D, MAF, SH3BP4 and PCDH17, that may be involved in the metastasis of PCa.
- Published
- 2016
32. Rare, low-frequency and common coding variants of ARHGEF28 gene and their association with sporadic amyotrophic lateral sclerosis
- Author
-
Huaping Huang, Feng Lin, Yang Song, Xu-Ying Li, Yanming Xu, Xiaoli Yao, Cheng-hui Ye, and Chaodong Wang
- Subjects
Adult ,0301 basic medicine ,Aging ,Genetic counseling ,SOD1 ,Disease ,Biology ,TARDBP ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Loss of Function Mutation ,C9orf72 ,medicine ,Guanine Nucleotide Exchange Factors ,Humans ,Amyotrophic lateral sclerosis ,Gene ,Genetic Association Studies ,Aged ,Genetics ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,Middle Aged ,medicine.disease ,030104 developmental biology ,Neurology (clinical) ,Geriatrics and Gerontology ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Over 90% of cases are sporadic (sALS) and 5%-10% are familial (fALS). So far, more than 20 genes/loci have been linked to ALS. C9orf72, SOD1, TARDBP, and FUS are noted as the most common ALS genes; however, mutations of these genes explain10% of sALS cases. Recently, Rho guanine nucleotide exchange factor, encoded by ARHGEF28, has been linked to the ALS pathogenesis, possibly by binding low-molecular-weight neurofilament mRNA and affects its stability. However, a systemic screening of ARHGEF28 mutations in ALS is lacking. In this study, we sequenced the entire coding sequence of ARHGEF28 in a Chinese cohort of 399 sporadic ALS and 327 elderly controls. A total of 73 coding variants were identified, including 26 synonymous and 47 nonsynonymous. Among the nonsynonymous variants, 33 were rare (minor allele frequency [MAF]0.01), in which 18 were only identified in cases and 12 were only in controls. Three loss-of-function mutations were identified, including 2 truncations (p.Arg231Ter and p.Ser561Ter) and a frameshift deletion (p.Lys1070fs) in 2 cases and 1 control subject. The frequency of total and case-only rare variants was 7.5% (30/399) and 5.0% (20/399), respectively, in the patients. SKAT-O test suggested that the novel coding variants were marginally enriched in the cases (p = 0.049). Single-variant analysis suggested that the p.Asn1046Ser variant had a higher frequency in cases (8/399, 0.02) than in controls (1/327, 0.003) (OR: 6.67, 95% CI: 0.83-53.61; p = 0.046). By contrast, none of the low-frequency (MAF: 0.01-0.05) or common (MAF0.05) variants was associated with ALS (p0.05). Among all patients, 9 (2.3%) carried rare variants predicted to be deleterious, and the age at onset of these carriers (45.6 ± 10.9 years) was marginally younger than noncarriers (51.9 ± 10.7 years) (p = 0.11). Our results supported a possible genetic contribution of rare but not low-frequency and common coding variants to ALS. These data may have implications in the mechanisms and genetic counseling of the disease.
- Published
- 2020
33. Knockdown of B7H6 inhibits tumor progression in triple‑negative breast cancer
- Author
-
Xiaoli Yao, Yi Tu, Feng Yao, Shengrong Sun, Juanjuan Li, Bing Zhang, and Jinzhong Sun
- Subjects
0301 basic medicine ,Cancer Research ,Cell signaling ,Oncogene ,Cell growth ,Apoptosis Regulator ,Cell ,tumor progression ,Articles ,Cell cycle ,Biology ,Natural killer cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,triple-negative breast cancer ,medicine ,Cancer research ,natural killer cell cytotoxicity receptor 3 ligand 1 ,B7 family - Abstract
The B7 family, the most common family of secondary signaling molecules, consists of eight cell-surface proteins, which regulate the T-cell mediated immune response by delivering co-inhibitory or co-stimulatory signals through their corresponding ligands. Among them, natural killer cell cytotoxicity receptor 3 ligand 1 (NCR3LG1, also known as B7H6) has been reported as a new member, and is involved in tumor progression of various types of human cancer. However, the role of B7H6 in triple-negative breast cancer (TNBC) remains unknown. In the present study, western blotting was performed to determine the protein expression levels of B7H6 in a normal mammary epithelial cell line (MCF-10A), non-TNBC breast cancer cell lines (MCF-7 and AU565) and TNBC cell lines (MDA-MB-231 and MDA-MB-468). B7H6 was knocked down using small interfering RNA, and an MTT assay was performed to determine proliferation ability, flow cytometry was used to analyze apoptosis, and Transwell and wound-healing assays were performed to measure migration ability. Expression of proliferation-associated proteins (SMAD family member 4 and β-catenin) and apoptosis-associated proteins (BCL2 associated X, BCL2 apoptosis regulator and caspase-3) were analyzed by western blotting. The results demonstrated that B7H6 was highly expressed in TNBC cells, and that knockdown of B7H6 inhibited cell proliferation and migration, and promoted apoptosis. Furthermore, the results revealed that proliferation and apoptosis-associated proteins were altered in the B7H6-knockdown MDA-MB-231 cells. In conclusion, the present study demonstrated that B7H6 may have significant roles in the regulation of cell proliferation, apoptosis and migration of TNBC cells.
- Published
- 2018
34. Circadian Rhythm Dysfunction Accelerates Disease Progression in a Mouse Model With Amyotrophic Lateral Sclerosis
- Author
-
Qiang Liu, Weineng Chen, Youna Xie, Yu Peng, Xiaoli Yao, Huanxing Su, Simei Long, Jiaying Dai, Zhilin Huang, and Zhong Pei
- Subjects
0301 basic medicine ,amyotrophic lateral sclerosis ,medicine.medical_specialty ,circadian rhythm dysfunction ,Inflammation ,Disease ,cyanobacteria ,NF-κB ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Genetic predisposition ,Circadian rhythm ,Amyotrophic lateral sclerosis ,lcsh:Neurology. Diseases of the nervous system ,Original Research ,business.industry ,Motor neuron ,Spinal cord ,medicine.disease ,eye diseases ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Neurology ,Gliosis ,inflammation ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by interactions between environmental factors and genetic susceptibility. Circadian rhythm dysfunction (CRD) is a significant contributor to neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. However, whether CRD contributes to the progression of ALS remains little known. We performed behavioral and physiological tests on SOD1G93A ALS model mice with and without artificially induced CRD, and on wild-type controls; we also analyzed spinal cord samples histologically for differences between groups. We found that CRD accelerated the disease onset and progression of ALS in model mice, as demonstrated by aggravated functional deficits and weight loss, as well as increased motor neuron loss, activated gliosis, and nuclear factor κB-mediated inflammation in the spinal cord. We also found an increasing abundance of enteric cyanobacteria in the ALS model mice shortly after disease onset that was further enhanced by CRD. Our study provides initial evidence on the CRD as a risk factor for ALS, and intestinal cyanobacteria may be involved.
- Published
- 2018
35. Lapatinib combined with neoadjuvant paclitaxel-trastuzumab-based chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer: A meta-analysis of randomized controlled trials
- Author
-
Shengrong Sun, Jinzhong Sun, Xiaoli Yao, and Chuang Chen
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Neutropenia ,Lapatinib ,Bioinformatics ,law.invention ,breast cancer ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,medicine ,lapatinib ,skin and connective tissue diseases ,Adverse effect ,Neoadjuvant therapy ,business.industry ,neoadjuvant ,Cancer ,Articles ,medicine.disease ,meta-analysis ,Relative risk ,business ,medicine.drug - Abstract
The purpose of the present study was to quantify the cumulative randomized evidence for the efficacy and safety of lapatinib combined with neoadjuvant therapy in human epidermal growth factor receptor (HER) 2-positive breast cancer. Three electronic databases, MEDLINE, Embase and Cochrane Central Register of Controlled Trials, and the abstracts of major international conferences between inception and 15 December 2013 were searched. Two evaluators independently extracted data. The end-points assessed consisted of the pathological complete response (pCR) rate, breast-conserving surgery (BCS) rate and the occurrence of adverse events. Four randomized controlled trials were assessed in the present study, involving a total of 779 participants. Compared with the patients who did not receive lapatinib, the pCR rate was higher in the hormone receptor (HR)-positive [risk ratio (RR), 1.39; 95% confidence interval (CI), 1.12–1.72; P=0.002) and HR-negative (RR, 1.38; 95% CI, 1.14–1.68; P=0.0009) patients that received lapatinib. No significant difference between the BCS rate of the two treatment arms was observed in two trials (n=382; RR, 1.14; 95% CI, 0.89–1.47; P=0.31). The primary adverse events, including diarrhea, dermatological toxicity, hepatic toxicity and neutropenia, were statistically more frequent in patients that received lapatinib (RR, 2.46; 95% CI, 1.97–3.07; P
- Published
- 2015
36. Enriched endogenous omega-3 fatty acids in mice protect against global ischemia injury
- Author
-
Zhong Pei, Jing X. Kang, Huanxing Su, Chuanming Luo, Huixia Ren, Kwok-Fai So, Chengwei He, Xiaoli Yao, Jian-Bo Wan, and Xiao-Jing Zhang
- Subjects
Genetically modified mouse ,medicine.medical_specialty ,Docosahexaenoic Acids ,Ischemia ,Hippocampus ,Endogeny ,QD415-436 ,Hippocampal formation ,Biochemistry ,Brain Ischemia ,Mice ,Endocrinology ,Internal medicine ,medicine ,Animals ,Cognitive Dysfunction ,CA1 Region, Hippocampal ,Research Articles ,Neurons ,chemistry.chemical_classification ,biology ,business.industry ,Cell Biology ,Cadherins ,medicine.disease ,Resolvin d1 ,Mice, Mutant Strains ,Surgery ,Fatty acid desaturase ,chemistry ,biology.protein ,business ,Polyunsaturated fatty acid - Abstract
Transient global cerebral ischemia, one of the consequences of cardiac arrest and cardiovascular surgery, usually leads to delayed death of hippocampal cornu Ammonis1 (CA1) neurons and cognitive deficits. Currently, there are no effective preventions or treatments for this condition. Omega-3 (ω-3) PUFAs have been shown to have therapeutic potential in a variety of neurological disorders. Here, we report that the transgenic mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs, were protected from global cerebral ischemia injury. The results of the study show that the hippocampal CA1 neuronal loss and cognitive deficits induced by global ischemia insult were significantly less severe in fat-1 mice than in WT mice controls. The protection against global cerebral ischemia injury was closely correlated with increased production of resolvin D1, suppressed nuclear factor-kappa B activation, and reduced generation of pro-inflammatory mediators in the hippocampus of fat-1 mice compared with WT mice controls. Our study demonstrates that fat-1 mice with high endogenous ω-3 PUFAs exhibit protective effects on hippocampal CA1 neurons and cognitive functions in a global ischemia injury model.
- Published
- 2014
37. Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells
- Author
-
Minying Zheng, Raymond T.F. Cheung, Xiaoli Yao, Xi-Lin Lu, Huanxing Su, Huixia Ren, Yonggang Wang, Simei Long, Zhong Pei, Weiwei Su, Jinsheng Zeng, Jun-Xiu Liu, and Qi Wu
- Subjects
medicine.medical_specialty ,Angiogenesis ,Neovascularization, Physiologic ,chemistry.chemical_compound ,Enos ,Puerarin ,Internal medicine ,medicine ,Animals ,Humans ,LY294002 ,Vascular Diseases ,Protein kinase B ,Zebrafish ,PI3K/AKT/mTOR pathway ,Respiratory Burst ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,Amyloid beta-Peptides ,biology ,Endothelial Cells ,biology.organism_classification ,Isoflavones ,Vascular endothelial growth factor ,Neuroprotective Agents ,Endocrinology ,chemistry ,Reactive Oxygen Species - Abstract
As40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer׳s disease (AD). In the present study, we investigated the possible protective effects of puerarin against As40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. As40 peptides at 5 μM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aβ40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, As40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of As40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10 μM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways.
- Published
- 2014
38. Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro
- Author
-
Xiong-Ming Luo, Guang-Chun Gao, Huanxing Su, Simei Long, Mian He, Xiaoli Yao, Shuzhong Yao, Yaohua Hu, Min-Qi Luo, Meng Xia, Qi Wu, and Junxiu Liu
- Subjects
Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Embryo, Nonmammalian ,Nitric Oxide Synthase Type III ,Angiogenesis ,anti-angiogenesis ,catunaregin ,VEGF ,zebrafish ,HUVECs ,Catechols ,Pharmaceutical Science ,Angiogenesis Inhibitors ,Lignans ,Article ,Neovascularization ,Cell Movement ,Enos ,Internal medicine ,Drug Discovery ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,Regeneration ,Phosphorylation ,lcsh:QH301-705.5 ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Zebrafish ,Protein kinase B ,Tube formation ,biology ,biology.organism_classification ,Cell biology ,Oncogene Protein v-akt ,Vascular endothelial growth factor A ,Endocrinology ,lcsh:Biology (General) ,embryonic structures ,Animal Fins ,medicine.symptom ,Signal Transduction - Abstract
Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.
- Published
- 2014
39. A comparison of mammography, ultrasonography, and far-infrared thermography with pathological results in screening and early diagnosis of breast cancer
- Author
-
Zhiliang Xu, Xiaoli Yao, Wen Wei, Juanjuan Li, Shengrong Sun, Ying-Wen Wan, Kai-Yang Li, and Lijun Wang
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Geography, Planning and Development ,Management, Monitoring, Policy and Law ,medicine.disease ,030218 nuclear medicine & medical imaging ,Benign breast tumors ,03 medical and health sciences ,Breast cancer screening ,0302 clinical medicine ,Breast cancer ,030220 oncology & carcinogenesis ,Thermography ,medicine ,Mammography ,Radiology ,Breast disease ,Ultrasonography ,business ,Pathological - Abstract
Background: Many breast-imaging techniques have been developed as primary clinical methods for identifying early-stage breast cancers and differentiating them from benign breast tumors. For the large population of China, any screening method that is rapid, economical, and accurate is worthy of evaluation. Objective: To compare the effectiveness of mammography, color Doppler ultrasonography, and far-infrared thermography in the screening and early diagnosis of breast cancer. Methods: Data from 2036 women with breast disease between January 2007 and May 2011 were included in this study. All patients underwent mammography, ultrasonography, and far-infrared thermography imaging. The diagnostic accuracy of the three methods was determined using postoperative pathological results as the diagnostic criterion standard. Results: There were 480 patients found to have breast malignancies on pathological examination. The lesion diameter was Conclusion: Far-infrared thermography is more accurate for breast cancer screening than ultrasonography and mammography for lesions 2 cm in diameter.
- Published
- 2014
40. Thermal tomography for monitoring tumor response to neoadjuvant chemotherapy in women with locally advanced breast cancer
- Author
-
Xiaoli Yao, Si Sun, Shengrong Sun, Xiaojun Ding, Manman Shi, Shan Zhu, Juan Wu, Qi Wu, Juanjuan Li, Kai-Yang Li, and Qian Liu
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Treatment response ,medicine.medical_treatment ,Locally advanced ,Tumor response ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Internal medicine ,Medicine ,Chemotherapy ,business.industry ,medicine.disease ,Predictive value ,thermal tomography ,Surgery ,030104 developmental biology ,Thermal tomography ,030220 oncology & carcinogenesis ,Ultrasonography ,Clinical Research Paper ,business ,neoadjuvant chemotherapy - Abstract
// Qi Wu 1,* , Juanjuan Li 1,* , Si Sun 2 , Xiaoli Yao 1 , Shan Zhu 1 , Juan Wu 3 , Qian Liu 1 , Xiaojun Ding 1 , Manman Shi 1 , Kaiyang Li 4 and Shengrong Sun 1 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 2 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 3 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 4 Department of Electronic Science and Technology, School of Physics and Technology, Wuhan University, Wuhan, Hubei, P. R. China * These authors have contributed equally to this work Correspondence to: Shengrong Sun, email: // Keywords : thermal tomography, neoadjuvant chemotherapy, breast cancer Received : December 16, 2016 Accepted : March 15, 2017 Published : March 25, 2017 Abstract Background & Aims: This study aims to analyze the feasibility and predictive value of thermal tomography (TT) for monitoring early treatment response in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC). Methods: Patients with LABC who were due to receive six cycles of NAC were examined by TT prior to NAC, the second cycle of NAC, the fourth cycle of NAC and surgery. Changes in TT parameters and ultrasonography were correlated with pathologic response to NAC, and the predictive value was assessed. Results: Forty-four patients were evaluable for response (25 pathologic responders and 19 nonresponders). As early as after the first cycle of NAC, changes in the TT parameters ΔTs, ΔTn, and ΔTa correlated significantly with pathologic response ( P < 0.05). The best predictor of pathologic response after the 6th cycle of NAC was TT (area under the receiver operating characteristic curve, 0.794), as opposed to cross-sectional areas and the longest diameter by ultrasonography. Conclusions: TT allows for monitoring early tumor response to NAC and can predict pathologic response in the early stages of therapy. Therefore, TT could be used as a novel imaging modality to monitor NAC treatment.
- Published
- 2016
41. Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease
- Author
-
Dajiang Qin, Xiaotong Cen, Huanxing Su, Zhijian Huang, Cheong-Meng Chong, Xiaoli Yao, Minjing Ke, Jia-Hong Lu, and Yuan Tan
- Subjects
0301 basic medicine ,Parkinson's disease ,Neurite ,induced pluripotent stem cells ,Disease ,Biology ,Orginal Article ,hydroxyurea ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Induced pluripotent stem cell ,Dopaminergic ,Cell Biology ,medicine.disease ,Phenotype ,030104 developmental biology ,Parkinson’s disease ,Unfolded protein response ,Neurology (clinical) ,Geriatrics and Gerontology ,disease phenotypes ,ER stress ,Neuroscience ,Reprogramming ,030217 neurology & neurosurgery - Abstract
Induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons might be reset back to the fetal state due to reprogramming. Thus, it is a compelling challenge to reliably and efficiently induce disease phenotypes of iPSCs-derived dopaminergic neurons to model late-onset Parkinson’s disease (PD). Here, we applied a small molecule, hydroxyurea (HU), to promote the manifestation of disease relevant phenotypes in iPSCs-based modeling of PD. We established two iPS cell lines derived from two sporadic PD patients. Both patients-iPSCs-derived dopaminergic neurons did not display PD relevant phenotypes after 6 weeks culture. HU treatment remarkably induced ER stress on patients-iPSCs-derived dopaminergic neurons. Moreover, HU treatment significantly reduced neurite outgrowth, decreased the expression of p-AKT and its downstream targets (p-4EBP1 and p-ULK1), and increased the expression level of cleaved-Caspase 3 in patients-iPSCs-derived dopaminergic neurons. The findings of the present study suggest that HU administration could be a convenient and reliable approach to induce disease relevant phenotypes in PD-iPSCs-based models, facilitating to study disease mechanisms and test drug effects.
- Published
- 2019
42. Alterations in AQP4 expression and polarization in the course of motor neuron degeneration in SOD1G93A mice
- Author
-
Chuanming Luo, Baixuan He, Jiaying Dai, Minying Zheng, Huanxing Su, Xi-Lin Lu, Xiaoli Yao, Zhong Pei, Weihao Lin, and Qiang Liu
- Subjects
0301 basic medicine ,Genetically modified mouse ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,amyotrophic lateral sclerosis ,aquaporin-4 polarization ,SOD1 ,Central nervous system ,Mice, Transgenic ,Degeneration (medical) ,Biology ,Biochemistry ,glutamate transporter 1 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,astrocyte ,Anterior Horn Cells ,Glial Fibrillary Acidic Protein ,Genetics ,medicine ,Animals ,Homeostasis ,superoxide dismutase 1 G93A mice ,Amyotrophic lateral sclerosis ,Molecular Biology ,Aquaporin 4 ,Motor Neurons ,Superoxide Dismutase ,Articles ,Motor neuron ,medicine.disease ,Spinal cord ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Spinal Cord ,Astrocytes ,Nerve Degeneration ,Disease Progression ,Molecular Medicine ,sense organs ,030217 neurology & neurosurgery ,Immunostaining - Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The disease progression is associated with the astrocytic environment. Aquaporin-4 (AQP4) water channels are the most abundant AQPs expressed in astrocytes, exerting important influences on central nervous system homeostasis. The present study aimed to characterize the alterations in AQP4 expression and loca-lization in superoxide dismutase 1 (SOD1) G93A transgenic mice. SOD1G93A mice were sacrificed during the presymptomatic, disease onset and end stages and immunostaining was performed on spinal cord sections to investigate neuronal loss, glial activation and AQP4 expression in the spinal cord. It was observed that global AQP4 expression increased in the spinal cord of SOD1G93A mice as the disease progressed. However, AQP4 polarization decreased as the disease progressed, and AQP4 polarized localization at the endfeet of astrocytes was decreased in the spinal ventral horn of SOD1G93A mice at the disease onset and end stages. Meanwhile, motor neuron dege-neration and decreased glutamate transporter 1 expression in astrocytes in SOD1G93A mice were observed as the disease progressed. The results of the present study demonstrated that AQP4 depolarization is a widespread pathological condition and may contribute to motor neuron degeneration in ALS.
- Published
- 2016
43. Fish Oil Prevents Lipopolysaccharide-Induced Depressive-Like Behavior by Inhibiting Neuroinflammation
- Author
-
Ti-Fei Yuan, Yu Peng, Baixuan He, Huanxing Su, Huixia Ren, Xiaoli Yao, Zhe Shi, and Zhijian Huang
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Neuroscience (miscellaneous) ,medicine.disease_cause ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Immune system ,Fish Oils ,Internal medicine ,medicine ,Animals ,Neuroinflammation ,chemistry.chemical_classification ,Inflammation ,business.industry ,Depression ,Fish oil ,Mice, Inbred C57BL ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,Neurology ,chemistry ,Hypothalamus ,business ,030217 neurology & neurosurgery ,Oxidative stress ,Polyunsaturated fatty acid ,Hormone - Abstract
Depression is associated with somatic immune changes, and neuroinflammation is now recognized as hallmark for depressive disorders. N-3 (or omega-3) polyunsaturated fatty acids (PUFAs) are well known to suppress neuroinflammation, reduce oxidative stress, and protect neuron from injury. We pretreated animals with fish oil and induced acute depression-like behaviors with systemic lipopolysaccharide (LPS) injection. The levels of cytokines and stress hormones were determined from plasma and different brain areas. The results showed that fish oil treatment prevent LPS-induce depressive behavior by suppression of neuroinflammation. LPS induced acute neuroinflammation in different brain regions, which were prevented in fish oil fed mice. However, neither LPS administration nor fish oil treatment has strong effect on stress hormone secretion in the hypothalamus and adrenal. Fish oil might provide a useful therapy against inflammation-associated depression.
- Published
- 2016
44. Protective effects of xyloketal B against MPP+-induced neurotoxicity in Caenorhabditis elegans and PC12 cells
- Author
-
Wei Li, Zhong Pei, Yongcheng Lin, Xiaoli Yao, Ling Chen, Jiyan Pang, Xi-Lin Lu, Heng Zhang, Guan-Lei Wang, Zhenxing Li, Zhiyong Liu, Jinsheng Zeng, and Zhongliang Xu
- Subjects
1-Methyl-4-phenylpyridinium ,Cell Survival ,Dopamine ,Green Fluorescent Proteins ,Population ,Intracellular Space ,Biology ,Mitochondrion ,medicine.disease_cause ,PC12 Cells ,Neuroprotection ,Animals, Genetically Modified ,chemistry.chemical_compound ,medicine ,Animals ,Caenorhabditis elegans ,education ,Molecular Biology ,Pyrans ,Cell Nucleus ,Membrane Potential, Mitochondrial ,Neurons ,education.field_of_study ,Dose-Response Relationship, Drug ,General Neuroscience ,Neurodegeneration ,Neurotoxicity ,Anatomy ,Glutathione ,medicine.disease ,Rats ,Cell biology ,Neuroprotective Agents ,chemistry ,Nerve Degeneration ,Neurology (clinical) ,Reactive Oxygen Species ,Intracellular ,Oxidative stress ,Developmental Biology - Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population over age 65years. Mitochondrial defect and oxidative stress actively participate in the dopaminergic (DA) neuron degeneration in PD. Xyloketal B is a novel marine compound with unique chemical structure isolated from mangrove fungus Xylaria sp. (no. 2508). Recently, we have demonstrated that Xyloketal B can directly scavenge DPPH free radicals and protects mitochondria against oxidative insult. In the present study, we investigate the neuroprotective action of xyloketal B against MPP+-induced neurotoxicity in Caenorhabditis elegans and PC12 cells. The viability and DA neurodegeneration was assessed in C. elegans selectively expressing green fluorescent protein (GFP) in DA neurons. PC12 cell damage was measured using MTT and nuclear morphology. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential and total GSH were assessed. Xyloketal B dose-dependently protected against MPP+-induced loss of viability and DA neurodegeneration in C. elegans. Similar neuroprotection was replicated in MPP+ PC12 cell model. In addition, xyloketal B attenuated MPP+-induced intracellular ROS accumulation, loss of mitochondrial membrane potential and restored total GSH level in PC12 cells. All together, the present study demonstrates that xyloketal B protects against MPP+-induced neurotoxicity in C. elegans and PC12 cells mainly through its antioxidant property and restoration of total GSH level.
- Published
- 2010
45. Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury
- Author
-
Jian-Bo Wan, Huixia Ren, Ti-Fei Yuan, Peng Li, Chuanming Luo, Jing-X Kang, Xiaoli Yao, Chengwei He, Zhe Shi, and Huanxing Su
- Subjects
0301 basic medicine ,Docosahexaenoic Acids ,Neuroscience (miscellaneous) ,Ischemia ,Endogeny ,Pharmacology ,Brain Ischemia ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Fatty Acids, Omega-3 ,Medicine ,Animals ,Cells, Cultured ,chemistry.chemical_classification ,Cerebral Cortex ,Neurons ,Reactive oxygen species ,business.industry ,Glutathione ,Recovery of Function ,medicine.disease ,Cadherins ,Neuroprotection ,Up-Regulation ,Mice, Inbred C57BL ,Oxygen ,Disease Models, Animal ,030104 developmental biology ,Glucose ,Neuroprotective Agents ,Neurology ,chemistry ,Biochemistry ,Docosahexaenoic acid ,Reperfusion Injury ,Female ,business ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Polyunsaturated fatty acid - Abstract
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.
- Published
- 2015
46. Neuroprotective effects of ginsenosides on neural progenitor cells against oxidative injury
- Author
-
Xu Wang, Jun Ye, Peng Li, Huanxing Su, Minying Zheng, Chengwei He, Jian‑Ping Yao, Jian-Bo Wan, and Xiaoli Yao
- Subjects
0301 basic medicine ,Transcriptional Activation ,Cancer Research ,Antioxidant ,Ginsenosides ,oxidative injury ,medicine.medical_treatment ,neural progenitor cells ,Pharmacology ,Biology ,medicine.disease_cause ,Biochemistry ,Neuroprotection ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Neural Stem Cells ,tert-Butylhydroperoxide ,Genetics ,medicine ,Animals ,Molecular Biology ,Cells, Cultured ,Articles ,Neural stem cell ,Rats ,Oxidative Stress ,030104 developmental biology ,Neuroprotective Agents ,Oncology ,Terminal deoxynucleotidyl transferase ,chemistry ,Gene Expression Regulation ,Apoptosis ,Ginsenoside ,Molecular Medicine ,Female ,030217 neurology & neurosurgery ,Intracellular ,Oxidative stress ,Biomarkers - Abstract
Ginsenosides exhibit various neuroprotective effects against oxidative stress. However, which ginsenoside provides optimal effects for the treatment of neurological disorders as a potent antioxidant remains to be elucidated. Therefore, the present study investigated and compared the neuroprotective effects of the Rb1, Rd, Rg1 and Re ginsenosides on neural progenitor cells (NPCs) following tert-Butylhydroperoxide (t-BHP)-induced oxidative injury. Primary rat embryonic cortical NPCs were prepared from E14.5 embryos of Sprague-Dawley rats. The oxidative injury model was established with t‑BHP. A lactate dehydrogenase assay and terminal deoxynucleotidyl transferase dUTP nick‑end labeling staining were used to measure the viability of the NPCs pre‑treated with ginsenosides under oxidative stress. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the activation of intracellular signaling pathways triggered by the pretreatment of ginsenosides. Among the four ginsenosides, only Rb1 attenuated t‑BHP toxicity in the NPCs, and the nuclear factor (erythroizd‑derived 2)‑like 2/heme oxygenase‑1 pathway was found to be key in the intracellular defense against oxidative stress. The present study demonstrated the anti-oxidative effects of ginsenoside Rb1 on NPCs, and suggested that Rb1 may offer potential as a potent antioxidant for the treatment of neurological disorders.
- Published
- 2015
47. No evidence of association between polymorphisms in four genes and sporadic amyotrophic lateral sclerosis in Han Chinese
- Author
-
Yanming Xu, Xinglong Yang, Ran An, Jing Xi, and Xiaoli Yao
- Subjects
Adult ,Male ,Han chinese ,Genotype ,Single-nucleotide polymorphism ,Subgroup analysis ,Disease ,Polymorphism, Single Nucleotide ,Young Adult ,Asian People ,Gene Frequency ,parasitic diseases ,medicine ,Humans ,Genetic Predisposition to Disease ,Amyotrophic lateral sclerosis ,Gene ,Genetic Association Studies ,Aged ,Genetics ,Aged, 80 and over ,Membrane Glycoproteins ,C9orf72 Protein ,Keratin-18 ,business.industry ,Amyotrophic Lateral Sclerosis ,Proteins ,Middle Aged ,medicine.disease ,Minor allele frequency ,Neurology ,Calcium-Calmodulin-Dependent Protein Kinase Type 1 ,Female ,Neurology (clinical) ,business - Abstract
The four single nucleotide polymorphisms (SNPs) rs34517613, rs3849943, rs8141797 and rs6703183, each located in a different gene, have recently been associated with risk of developing sporadic amyotrophic lateral sclerosis (SALS) in European and northern Chinese populations, but no data are yet available for other ethnic groups. Here we explored the possible association between these four SNPs and SALS in Han Chinese primarily from southern and south-western China. A total of 298 individuals with SALS from three centres in mainland China and 486 unrelated healthy controls were recruited. All subjects were successfully genotyped using the ligase detection reaction (LDR). We found no evidence that any of these SNPs are associated with risk of disease in either heterozygous or homozygous individuals (p > 0.05). Subgroup analysis based on gender showed a similar lack of association. However, subgroup analysis based on spinal- or bulbar-onset SALS revealed significant differences in the genotype distributions (p = 0.009) and minor allele frequencies of rs6703183 (p = 0.004). In conclusion, it may be premature to conclude associations between these four SNPs and SALS, which should be examined in additional ethnic groups.
- Published
- 2015
48. Cell Surface GRP78 Accelerated Breast Cancer Cell Proliferation and Migration by Activating STAT3
- Author
-
Xinghua Zhang, Hua Liu, Liang Zhang, Shengrong Sun, Changhua Wang, Xiaoli Yao, and Li Xiang
- Subjects
Adult ,STAT3 Transcription Factor ,Glucose-regulated protein ,Cell ,Genetic Vectors ,lcsh:Medicine ,Apoptosis ,Breast Neoplasms ,Metastasis ,Adenoviridae ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,STAT3 ,lcsh:Science ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Aged ,Cell Proliferation ,Neoplasm Staging ,Multidisciplinary ,biology ,Cell growth ,business.industry ,Carcinoma, Ductal, Breast ,lcsh:R ,Cancer ,Middle Aged ,medicine.disease ,Antibodies, Neutralizing ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Lymphatic Metastasis ,Immunology ,biology.protein ,Cancer research ,Disease Progression ,Female ,lcsh:Q ,Signal transduction ,Neoplasm Grading ,business ,Signal Transduction ,Research Article - Abstract
High levels of cell surface glucose regulated protein 78 (sGRP78) have been implicated in cancer growth, survival, metastasis, and chemotherapy resistance. However, the underlying mechanism remains largely unknown. Here we report that the level of sGRP78 expression in human breast tumors gradually increases during cancer progression. Overexpression of GRP78 significantly enhanced its membrane distribution in human MCF-7 breast cancer cells, but had no effect on endoplasmic reticulum (ER) stress. High levels of sGRP78 facilitated cell proliferation and migration, as well as suppressed cell apoptosis. Neutralization of sGRP78 by a specific antibody against GRP78 alleviated sGRP78-induced cell growth and migration. Importantly, high phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) were found in human breast tumors that express sGRP78 and MCF-7 cells infected with adenovirus encoding human GRP78. Pretreatment with a GRP78 antibody suppressed STAT3 phosphorylation. Furthermore, genetic and pharmacological inhibition of STAT3 reversed the impacts of GRP78 on cell proliferation, apoptosis, and migration. These findings indicate that STAT3 mediates sGRP78-promoted breast cancer cell growth and migration.
- Published
- 2015
49. H63D polymorphism in the hemochromatosis gene is associated with sporadic amyotrophic lateral sclerosis in China
- Author
-
Yanming Xu, Xianghua He, Xiaoli Yao, Bo Yan, Huifang Shang, Fayun Hu, Jing Xi, Hongmei Zhou, Dong Zhou, Lihua Yu, Li He, J. Hu, Zhuolin Liu, X. Lu, and Lunxu Liu
- Subjects
China ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Genotype ,Hfe gene ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Gastroenterology ,Chinese han population ,Asian People ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Hemochromatosis Gene ,Amyotrophic lateral sclerosis ,Hemochromatosis Protein ,Hemochromatosis ,Genetics ,business.industry ,Amyotrophic Lateral Sclerosis ,Histocompatibility Antigens Class I ,Case-control study ,Membrane Proteins ,nutritional and metabolic diseases ,Odds ratio ,medicine.disease ,Neurology ,Neurology (clinical) ,Restriction fragment length polymorphism ,business ,Polymorphism, Restriction Fragment Length - Abstract
Background and purpose: The H63D polymorphism in the hemochromatosis (HFE) gene has been reported as a risk factor for amyotrophic lateral sclerosis (ALS) in Europe and America, but no data have been reported for Asia. Here, we investigated the possible association between H63D and sporadic ALS (sALS) in a Chinese Han population. Methods: A total of 195 individuals with sALS from three centers in China and 405 unrelated healthy controls were recruited. All subjects were genotyped by restriction fragment length polymorphism (RFLP) analysis. Results: Sporadic ALS was significantly related to the H63D polymorphism in heterozygous carriers (odds ratio 3.10, 95%CI: 1.49–6.47, P = 0.002). Conclusions: The HFE H63D polymorphism may contribute to the development of sALS in Chinese.
- Published
- 2011
50. Associations and indications of Ki67 expression with clinicopathological parameters and molecular subtypes in invasive breast cancer: A population-based study
- Author
-
Xiaoli Yao, Hongmei Zheng, Wen Wei, Feng Yao, Lijun Wang, Juanjuan Li, Yan Li, Yi Tu, Chuang Chen, Shengrong Sun, Jingping Yuan, and Jinzhong Sun
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,business.industry ,Estrogen receptor ,Cancer ,Articles ,medicine.disease ,Molecular medicine ,Breast cancer ,medicine.anatomical_structure ,Internal medicine ,Progesterone receptor ,medicine ,Biomarker (medicine) ,Stage (cooking) ,business ,Lymph node - Abstract
Ki67 has potential prognostic and predictive values for breast cancer patients, and has become an important biomarker in routine clinical practice. The aims of the present study were to investigate the distribution of Ki67 expression and its correlation with other clinicopathological parameters in central China. In total, 1,259 patients with newly-diagnosed invasive breast cancer were included in the present study. The clinical information was obtained from the electronic medical records. The expression levels of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were detected by immunohistochemical analysis. The associations between Ki67 scores and other prognostic factors were evaluated as continuous and categorical variables. The mean value of the Ki67 scores of all patients was 31%. In total, ~36% (456/1,259) of the patients demonstrated a low expression of Ki67. A statistically significant correlation was identified between the mean Ki67 scores and the lymph node status, tumor grade, ER, PR and HER2 status, and clinical stage or molecular subtypes (all P14%) and low (≤14%) level groups, the χ2 test was used to verify these results. The Ki67 scores demonstrated no statistically significant differences between the HER2-positive (non-luminal) and three negative subtypes, with the exception of patients with a tumor size of >2 cm (P=0.02). In conclusion, the results revealed the presence of significant correlations between Ki67 and other clinicopathological parameters.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.