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المؤلفون: Xiaozhen Liu, Ruixuan Jia, Xiang Meng, Ying Li, Liping Yang
المصدر: Experimental eye research. 215
مصطلحات موضوعية: Cellular and Molecular Neuroscience, Ophthalmology, Disease Models, Animal, Mice, Rhodopsin, Retinal Rod Photoreceptor Cells, Retinal Degeneration, Electroretinography, Animals, Humans, Mice, Transgenic, Sensory Systems, Retinitis Pigmentosa
الوصف: RHO is one of the most common genetic causes of autosomal dominant retinitis Pigmentosa (adRP) and there is no effective therapy for this disease. While rapidly developed CRISPR/Cas9 gene editing technology presents a promising therapeutic strategy to treat adRP. A large number of studies for treating adRP using CRISPR/Cas9 have been performed based on transgenic mouse models which are affected with adRP caused by mutant mouse rhodopsin allele, the counterpart of human rhodopsin. Recently, some RHO humanized mouse models like T17M, P23H are generated, which permit testing of the therapeutic effect of CRISPR/Cas9 in preclinical in vivo systems, without putting humans at risk. While available humanized mouse models are few compared to the number of known RHO mutations, but it is time-consuming and costly to build humanized mice for each mutation. We wonder whether a humanized mouse model having several mutations simultaneously can be developed, although which rarely occurs in patients, to investigate the therapeutic effect of CRISPR/Cas9 for RHO-mediated adRP in preclinical in vivo systems. Homology directed repair strategy combing with CRISPR/Cas9 was employed to introduce human RHO genomic fragment containing the replacement of mouse exon1(mE1) after the start codon to mE5 before the stop codon and all introns by the human counterparts. The human rhodopsin could express under the control of the endogenous murine promoter both transcriptionally and translationally in vivo. Human rhodopsin in humanized mouse lines (without mutation) could replace murine rhodopsin morphologically and functionally. While human rhodopsin containing T17M, G51D, G114R, R135W and P171R mutations simultaneously in mutant humanized (Mut-Rho
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المؤلفون: Q. L. Dong, Xiang-meng Liu, Xiao-lin Yu, Shan Ma, Shu-ying Liu, Rui-tian Liu, Jie Zhu, Yue Zhang
المصدر: Brain Research. 1697:21-33
مصطلحات موضوعية: Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Movement disorders, Neuropathology, Motor Activity, Pharmacology, medicine.disease_cause, Mice, 03 medical and health sciences, Cognition, Superoxide Dismutase-1, 0302 clinical medicine, Huntington's disease, hemic and lymphatic diseases, mental disorders, medicine, Huntingtin Protein, Animals, Cognitive Dysfunction, Molecular Biology, Neuroinflammation, business.industry, General Neuroscience, NF-kappa B, Brain, Immunoglobulins, Intravenous, medicine.disease, Hedgehog signaling pathway, Disease Models, Animal, Oxidative Stress, Huntington Disease, 030104 developmental biology, Adjunctive treatment, Neurology (clinical), Nervous System Diseases, medicine.symptom, Cognition Disorders, Reactive Oxygen Species, business, 030217 neurology & neurosurgery, Oxidative stress, Signal Transduction, Developmental Biology
الوصف: Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive movement disorders and cognitive deficits, which is caused by a CAG-repeat expansion encoding an extended polyglutamine (polyQ) tract in the huntingtin protein (HTT). Reduction of mutant HTT levels and inhibition of neuroinflammation has been proposed as a major therapeutic strategy in treating HD. Intravenous immunoglobulin (IVIg) therapy has been firmly established for the treatment of several autoimmune or inflammatory neurological diseases, either as adjunctive treatment or as first-line therapy. However, whether IVIg has therapeutic potential on HD remains unclear. Here we for the first time demonstrated that IVIg treatment remarkably rescued motor and cognitive deficits, prevented synaptic degeneration, attenuated neuroinflammation and oxidative stress in R6/2 mouse model. Further investigation showed that the beneficial effects of IVIg resulted from the reduced levels of mutant HTT and inhibition of NF-κB signalling pathway. These findings suggest that IVIg is a promising therapeutic potential for HD.
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المؤلفون: Ning Wen, Ya-Zheng Dang, Yu Wang, Yong Li, Zhen Ren, Guo-Dong Wang, Bo-Xiang Meng, Jing Zhang, Jiao Wu
المصدر: Experimental Cell Research. 370:373-382
مصطلحات موضوعية: 0301 basic medicine, Carcinoma, Hepatocellular, Integrin, Chromosomal translocation, ADAM17 Protein, Metastasis, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, medicine, Animals, Humans, Cell Proliferation, Gene knockdown, Tissue microarray, biology, Cell growth, Integrin beta1, Liver Neoplasms, Cell migration, Cell Biology, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cancer research, biology.protein
الوصف: ADAM17 is believed to promote tumor development by facilitating both cell proliferation and migration. In this study, we investigated the involvement of ADAM17 and the activation of the integrin pathway in the regulation of the malignant properties of hepatocellular carcinoma cells and tissues. ADAM17 was positively correlated with active integrin β1, which was determined using a human tissue microarray and an N-nitrosodiethylamine-induced HCC mouse model. We found elevated ADAM17 and active integrin β1 levels in HCC tissues compared with adjacent liver tissues, and the active integrin β1 levels were associated with tumor size and TNM grade. High ADAM17 and active integrin β1 levels in tumor tissues were significantly associated with poor survival of HCC patients. RNAi-mediated ADAM17 knockdown and integrin β1 blockade significantly attenuated the migration and invasion of HCC cells, and overexpression of ADAM17 showed the reverse effects. ADAM17 interference attenuated the intrahepatic growth and metastasis of HCC cells in an orthotopic xenograft model. ADAM17-knockdown cells showed diminished levels of active integrin β1, p-FAK, p-AKT, MMP-2 and MMP-9. ADAM17 knockdown significantly attenuated the translocation of the Notch1 intracellular domain into the nucleus, whereas overexpression of the Notch1 intracellular domain rescued the translocation and enhanced the activation of integrin β1. Our data provide evidence for ADAM17 as an important determinant of malignant properties via regulation of integrin β1 activation and Notch1 signaling. Inhibition of ADAM17 may provide viable therapeutic potential for preventing HCC metastasis.
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المؤلفون: Lei Zhang, Abigail N. Rankine, Zi-Hao Zhang, Zi-Fei Wang, Wan-Xin Zheng, Xiang Meng, Hao Gu, Qiu-Yue Lou
المصدر: European journal of pharmacology. 902
مصطلحات موضوعية: 0301 basic medicine, Biology, Metastasis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Biomarkers, Tumor, Diagnostic biomarker, Animals, Humans, Multiple tumors, Pharmacology, Advanced stage, RNA, Cancer, medicine.disease, Prognosis, Head and neck squamous-cell carcinoma, Gene Expression Regulation, Neoplastic, 030104 developmental biology, chemistry, Head and Neck Neoplasms, Cancer research, Carcinoma, Squamous Cell, RNA, Long Noncoding, 030217 neurology & neurosurgery, DNA
الوصف: At present, emerging evidences shows that non-coding RNAs (ncRNAs) play crucial roles for development of multiple tumors. Amongst these ncRNAs, long non-coding RNAs (lncRNAs) play prominent roles in physiological and pathological processes. LncRNAs are a type of transcript of more than 200 nucleotides, which are a significant obsession in various types of tumors and have extremely complex regulatory networks with DNA, RNA, and proteins in tumor cells, so that lncRNAs have attracted wide attention from researchers. LncRNAs are RNA transcripts larger than 200 nucleotides and have been shown to serve important regulatory roles in different types of cancer via interactions with DNA, RNA and proteins. Head and neck squamous cell carcinoma (HNSCC) are is one of the most malignant tumors with low survival rates in advanced stages. Recently, lncRNAs have been demonstrated to be involved in a wide range of biological processes, including proliferation, metastasis, and prognosis of HNSCC. Therefore, this review describes molecular mechanisms of up- or down-regulation of lncRNAs and expounds their functions in pathology and clinical practices in HNSCC. It also highlights their potential clinical applications as biomarkers for the diagnosis, prognosis, and treatment of HNSCC. However, studies on lncRNAs are still not comprehensive, and more investigations are needed in the future.
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المؤلفون: Ben, Liu, Yu-Jiao, Liu, Dan-Dan, Liu, Bao-Xia, Zhao, Kai, Zhang, Ru-Nan, Jing, Si-Cong, Dong, Xiu-Xiang, Meng
المصدر: Zhongguo shi yan xue ye xue za zhi. 28(2)
مصطلحات موضوعية: Mice, Doxorubicin, Drug Resistance, Neoplasm, Animals, Humans, Mice, Nude, Apoptosis, K562 Cells, Transfection, Cell Proliferation
الوصف: To investigate the effect of Bmi-1 gene silencing on the proliferation of K562/ADM cells in vitro and in vivo and to explore its possible molecular mechanism.The small interference RNA (siRNA) sequences of Bmi-1 were transfected into K562/ADM cells for decreasing the expression of Bmi-1. The effect of Bmi-1 silencing on the proliferation of K562/ADM cells in vitro and in vivo was detected by using MTT method, cell colony-forming test and tumoriganicity of nude mice; the expression of Bmi-1, PTEN and PAKT proteins was detected by Wertern blot. The immunohistochemistry assay was used to analyze the expression of Bmi-1 and Ki-67.The Bmi-1 silencing could significantly inhibit the proliferation activity of K562/ADM cells, the cell colony-forming ability and tumorigenicity were reduced. LY294002 decreased p-AKT expression, cell colony-forming ability and tumorigenicity. Bpv reduced the PTEN expression but increased p-AKT expression and restored the colony-forming ability and tumorigenesis of K562/ADM-S1-Bpv cells. Bmi-1-siRNA dramatically suppressed the Bmi-1 and Ki-67 protein levels in xenograft tumor tissue.Bmi-1 can mediate the proliferation of K562/ADM cell, the PTEN/p-AKT might be involved in this pathway.沉默Bmi-1表达对K562/ADM细胞体内外增殖能力的影响.观察沉默Bmi-1表达对慢性髓系白血病阿霉素耐药细胞株-K562/ADM细胞增殖的影响并初步探讨其分子机制.将Bmi-1小干扰RNA（siRNA）序列转染到K562/ADM细胞中降低其Bmi-1的表达；采用MTT法、软琼脂集落形成实验、裸鼠成瘤实验检测沉默Bmi-1表达对K562/ADM细胞体内外增殖能力的影响；应用Western blot检测Bmi-1、PTEN、p-AKT等蛋白表达；免疫组织化学实验分析Bmi-1和Ki-67的表达情况.Bmi-1基因的沉默能够抑制K562/ADM细胞的增殖活性、集落形成及裸鼠成瘤能力；Bmi-1基因沉默后，干扰组PTEN表达明显升高，而p-AKT活性明显下降；p-AKT抑制剂-LY294002处理K562/ADM细胞后，p-AKT表达降低，集落形成及裸鼠成瘤能力相比K562/ADM细胞降低；PTEN抑制剂-Bpv处理K562/ADM-S1细胞后，PTEN的表达降低，而p-AKT表达、集落形成及裸鼠成瘤能力得以重塑； Bmi-1基因沉默使得肿瘤组织中Bmi-1与Ki-67表达均下降.Bmi-1基因有可能参与了对K562/ADM的体内外增殖能力的调控，PTEN/pAKT信号通路可能涉及其中.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::8f91475fe6557c5c4c81498373cb08c2
https://pubmed.ncbi.nlm.nih.gov/32319377 -
6
المؤلفون: Peng-xin Xu, Jie Zhu, Rui-tian Liu, Xiao-lin Yu, Yue Zhang, Xiang-meng Liu
المصدر: Br J Pharmacol
مصطلحات موضوعية: 0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, medicine.medical_treatment, Morris water navigation task, Mice, Transgenic, 03 medical and health sciences, Amyloid beta-Protein Precursor, Epitopes, Mice, 0302 clinical medicine, Immune system, Cognition, Alzheimer Disease, medicine, Animals, Amino Acid Sequence, Neuroinflammation, Pharmacology, Vaccines, Amyloid beta-Peptides, biology, business.industry, Experimental autoimmune encephalomyelitis, Immunotherapy, medicine.disease, Research Papers, Peptide Fragments, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Immunization, Immunology, biology.protein, Antibody, business, 030217 neurology & neurosurgery, Conformational epitope
الوصف: Background and purpose Immunotherapeutic intervention is one of the most promising strategies for the prevention and treatment of Alzheimer's disease (AD). Although they showed great success in AD mouse models, the clinical trials of many immune approaches failed due to low efficacy and safety. Thus, an animal model which can show the potential side effects of vaccines or antibodies is urgently needed. In this study, we generated EAE/AD mice by crossing APP/PS1 mice with experimental autoimmune encephalomyelitis (EAE) mice. We then investigated the efficacy and safety of two vaccines: the immunogens of which were Aβ1-42 aggregates (Aβ42 vaccine) and an oligomer-specific conformational epitope (AOE1 vaccine), respectively. Experimental approach EAE/AD mice were immunized with the Aβ42 vaccine or AOE1 vaccine five times at biweekly intervals. After the final immunization, cognitive function was evaluated by the Morris water maze, Y maze, and object recognition tests. Neuropathological changes in the mouse brains were analysed by immunohistochemistry and ELISA. Key results In contrast to previous findings in conventional AD animal models, Aβ42 immunization promoted neuroinflammation, enhanced Aβ levels and plaque burden, and failed to restore cognitive deficits in EAE/AD mice. By contrast, AOE1 immunization dramatically attenuated neuroinflammation, reduced Aβ levels, and improved cognitive performance in EAE/AD mice. Conclusion and implications These results suggest that the EAE/AD mouse model can exhibit the potential side effects of AD immune approaches that conventional AD animal models fail to display. Furthermore, strategies specifically targeting Aβ oligomers may be safe and show clinical benefit for AD treatment.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5117258653711af2c912edc0339d4b77
https://europepmc.org/articles/PMC7236067/ -
7
المؤلفون: Ke Wu, Yu Song, Rong Hua, Xia Qin, Yong-Mei Zhang, Ying Song, Qing-Xiang Meng, Zhi-Jing Song, Jun-Li Cao
المصدر: Psychoneuroendocrinology. 117
مصطلحات موضوعية: Male, endocrine system, Corticotropin-Releasing Hormone, Endocrinology, Diabetes and Metabolism, Optogenetics, Inhibitory postsynaptic potential, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Medicine, Animals, GABAergic Neurons, Biological Psychiatry, Behavior, Animal, Endocrine and Autonomic Systems, business.industry, GABAA receptor, Visceral pain, Neural Inhibition, Visceral Pain, 030227 psychiatry, Rats, Psychiatry and Mental health, Stria terminalis, Disease Models, Animal, nervous system, Muscimol, chemistry, Paraventricular nucleus of hypothalamus, Animals, Newborn, Hyperalgesia, GABAergic, Septal Nuclei, medicine.symptom, business, Neuroscience, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery, Stress, Psychological, Paraventricular Hypothalamic Nucleus
الوصف: Ample evidence suggests that early life stress (ELS) is a high-risk factor for the development of visceral pain disorders, whereas the mechanism underlying neuronal circuit remains elusive. Herein, we employed neonatal colorectal distension (CRD) to induce visceral hypersensitivity in rats. A combination of electrophysiology, pharmacology, behavioral test, molecular biology, chemogenetics and optogenetics confirmed that CRD in neonatal rats could predispose the elevated firing frequency of the parvocellular corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of hypothalamus (PVN) in adulthood, with the CRH neurons activated and the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) diminished, both contributing to chronic visceral hypersensitivity. Moreover, following administration of exogenous GABA (300 mM/0.5 μL) and GABAA receptor agonist muscimol (3 mM/0.5 μL) in PVN, visceral hyperalgesia was abrogated. In addition, the PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), and the excitability of these GABAergic neurons was weakened in visceral hypersensitivity. Specific depletion of the GABAergic neurons in AV region precipitated visceral hyperalgesia. Moreover, chemogenetic activation of the PVN-projecting neurons alleviated the visceral hypersensitivity. Photoactivation of PVN-projecting GABAergic neurons abated the visceral hypersensitivity in neonatal-CRD rats, whereas photoinhibition evoked visceral hyperalgesia in naive rats. Our findings demonstrated that disinhibition of the PVN-projecting GABAergic neurons in AV region contributed to the excitation of CRH neurons, thereby mediating visceral hypersensitivity. Our study might provide a novel insight into the neuronal circuits involved in the ELS-induced visceral hypersensitivity.
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المؤلفون: Xiao-Yun Luo, Hai-Feng Pan, Xiao-Mei Li, Yue-Xin Yang, Dong-Qing Ye, Xiang Meng, Zong-Wen Shuai, Hui-Hui Shen
المصدر: Autoimmunity Reviews. 17:694-702
مصطلحات موضوعية: 0301 basic medicine, Inflammasomes, Immunology, Inflammation, Nod, Inflammatory bowel disease, Autoimmune Diseases, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, Immunology and Allergy, Innate immune system, integumentary system, business.industry, Inflammasome, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Rheumatoid arthritis, medicine.symptom, business, Signal Transduction, medicine.drug
الوصف: NLRP3, a member of nucleotide-binding domain-(NOD) like receptor family, can be found in large varieties of immune and non-immune cells. Upon activation, the NLRP3, apoptosis-associated speck-like protein (ASC) and pro-caspase-1 would assemble into a multimeric protein, called the NLRP3 inflammasome. Then the inflammasome promotes inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. Previous studies have indicated the importance of NLRP3 in regulating innate immunity. Recently, numerous studies have revealed their significance in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and inflammatory bowel disease (IBD). In this review, we will briefly discuss the biological features of NLRP3 and summarize the recent progression of the involvement of NLRP3 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.
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المؤلفون: Xiang-meng Liu, Yue Zhang, Jia-qian Chai, Shu-ying Liu, Q. L. Dong, Rui-tian Liu, Jie Zhu, Xiao-lin Yu
المصدر: International Immunopharmacology. 54:145-152
مصطلحات موضوعية: Male, 0301 basic medicine, Genetically modified mouse, endocrine system, medicine.medical_specialty, endocrine system diseases, Amyloid, Immunology, Apoptosis, Mice, Transgenic, Inflammation, Immunomodulation, Islets of Langerhans, Mice, 03 medical and health sciences, Insulin resistance, Insulin-Secreting Cells, hemic and lymphatic diseases, Internal medicine, Diabetes mellitus, Autophagy, medicine, Animals, Humans, Insulin, Immunology and Allergy, Cells, Cultured, Pharmacology, geography, geography.geographical_feature_category, business.industry, Immunoglobulins, Intravenous, Type 2 Diabetes Mellitus, Islet, medicine.disease, Islet Amyloid Polypeptide, Glucose, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Cytokines, Inflammation Mediators, Protein Multimerization, medicine.symptom, business
الوصف: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by β-cell loss, insulin resistance, islet inflammation and amyloid deposits derived from islet amyloid polypeptide (IAPP). Reducing toxic IAPP oligomers and inhibiting islet inflammation may provide therapeutic benefit in treating T2DM. Intravenous immunoglobulin (IVIg) is an efficient anti-inflammatory and immunomodulatory agent for the treatment of several autoimmune or inflammatory neurological diseases. However, whether IVIg has therapeutic potential on T2DM remains unclear. In present study, we showed that IVIg treatment significantly improved glucose control and insulin sensitivity, and prevented β-cell apoptosis by lowering toxic IAPP oligomer levels, attenuating islet inflammation and activating autophagy in human IAPP transgenic mouse model. These results suggest that IVIg is a promising therapeutic potential for T2DM treatment.
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المؤلفون: Avijit Baidya, Betül Çelebi-Saltik, Xiaochen Wang, Changsheng Wang, Zitong Wang, Jiahua Ni, Nureddin Ashammakhi, Shiming Zhang, Yihang Chen, Xiang Meng, Jadranka Travas-Sejdic, Haonan Ling, Samad Ahadian, Han-Jun Kim, Ali Khademhosseini, Hao Liu, Mehmet R. Dokmeci
المصدر: Adv Mater
مصطلحات موضوعية: Materials science, Biocompatibility, Transistors, Electronic, Nanotechnology, Biocompatible Materials, 02 engineering and technology, Thiophenes, 010402 general chemistry, 01 natural sciences, Article, Cell Line, Mice, PEDOT:PSS, Animals, General Materials Science, Electrodes, Cell Proliferation, Bioelectronics, Muscle Cells, Mechanical Engineering, Temperature, Hydrogels, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Mechanics of Materials, Self-healing hydrogels, Polystyrenes, 0210 nano-technology
الوصف: There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe-injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room-temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large-scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room-temperature-formed PEDOT:PSS hydrogels (RT-PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self-healable hydrogel bioelectronic devices.
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