BACKGROUND:Niemann-Pick disease type C1 (NPC1) is caused by NPC1 gene mutations, resulting in Purkinje cell degeneration and death, glial cell activation, and progressive neurodegeneration. Menstrual blood-derived endometrial stem cells (MenSCs) have been explored as a promising tool for treating neurodegenerative diseases due to their wide range of sources, non-invasive nature, and regular collection methods. OBJECTIVES:This study aims to investigate whether MenSCs can improve neuroinflammation and apoptosis in NPC1 mutant cell (Npc1KO BV2 cell line) and mice (Npc1-/- mice), and explore their underlying mechanisms. METHODS:MenSCs were transplanted into the 4-week-old Npc1-/- mice cerebellum through stereotaxic injection, and their effects on weight, behavior, and survival were assessed. The activation of glial cells and the survival of neurons were detected by immunofluorescence technology, and the expression level of related inflammatory factors and apoptotic proteins was detected by western blotting. The transcriptome changes in cerebellum after MenSCs transplantation were analyzed by transcriptome sequencing. The mechanism by which MenSCs treat NPC1 was validated at the cellular level using the activator butyzamide. RESULTS:MenSCs transplantation could slow down the rate of weight loss and improve motor coordination in Npc1-/- mice, but had no significant improvement in lifespan. MenSCs could mitigate the activation of glial cells, alleviate neuroinflammation, reduce cell apoptosis, and increase the number of mature neurons and Purkinje cells in the cerebellum. Transcriptome analyses results indicated that the JAK/STAT signaling pathway changed across different groups. Compared with age-matched Npc1+/+ mice, the protein expression levels of P-JAK2 and P-STAT3, the ratios of P-JAK2/JAK2 and P-STAT3/STAT3 were increased in the cerebellum of 5-week-old Npc1-/- mice in the PBS group; compared with age-matched Npc1-/- mice in the PBS group, the protein expression levels of P-JAK2 and P-STAT3, the ratios of P-JAK2/JAK2 and P-STAT3/STAT3 were decreased after MenSCs transplantation. Finally, treating Npc1KO BV2 cells with butyzamide further confirmed that MenSCs relieve inflammation and apoptosis caused by Npc1 gene mutations through JAK2/STAT3 signaling pathway. CONCLUSION:Our study demonstrate that MenSCs ameliorate neuroinflammation and apoptosis in NPC1 mutant cell and mice through JAK2/STAT3 signaling pathway.

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are characterized by the progressive loss of neuronal function and structure, leading to severe morbidity and mortality. Current therapeutic approaches are ineffective at stopping or reversing disease progression. Stem cell therapy has emerged as a promising candidate in research and treatment. Mesenchymal stem cells (MSCs) are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential. MSCs can differentiate into neurons and glial cells, modulate immune responses, and reduce inflammation, and their exosomes can promote neural repair and regulate neuronal function; thus, MSCs offer unique advantages for treating neurodegenerative diseases. However, challenges remain in optimizing cell delivery methods, ensuring the long-term survival and integration of transplanted cells, and fully understanding their therapeutic effects. This article primarily outlines the functions of MSCs in neurodegenerative diseases, with the intention that further research will fully harness their potential and translate these findings into clinical applications, offering new hope for patients suffering from neurodegenerative diseases.

Niemann–Pick disease (NPD) is a rare autosomal recessive neurodegenerative disease characterized by hepatosplenomegaly, neuropathy, and a significantly shortened lifespan. Lipid metabolism disorder is the main pathological feature of NPD. Currently, the exact pathogenesis of NPD remains unclear, and drug therapy is largely palliative, focusing on symptom management, but it has side effects. Mesenchymal stem cells (MSCs) possess several advantageous properties, including their differentiation potential, wide availability, low immunogenicity, and the ability to secrete regulatory factors, which have led to their extensive application in basic research targeting neurodegenerative diseases. Studies have demonstrated that transplantation of MSCs from different sources into animal models of NPD can delay the loss of Purkinje cells in the cerebellum, reduce lipid deposition, improve motor coordination, slow the rate of weight loss, and extend lifespan. This review explores the therapeutic potential of MSCs in the treatment of NPD, highlighting their emerging role in addressing this challenging condition.

The clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein (Cas) system is a gene editing technology guided by RNA endonuclease. The CRISPR-Cas12a (also known as CRISPR-Cpf1) system is extensively utilized in genome editing research due to its accuracy and high efficiency. In this paper, we primarily focus on the application of CRISPR-Cpf1 technology in the construction of disease models and gene therapy. Firstly, the structure and mechanism of the CRISPR-Cas system are introduced. Secondly, the similarities and differences between CRISPR-Cpf1 and CRISPR-Cas9 technologies are compared. Thirdly, the main focus is on the application of the CRISPR-Cpf1 system in cell and animal genome editing. Finally, the challenges faced by CRISPR-Cpf1 technology and corresponding strategies are analyzed. Although CRISPR-Cpf1 technology has certain off-target effects, it can effectively and accurately edit cell and animal genomes, and has significant advantages in the preclinical research.

Depression is a common mental illness in the elderly, which is associated with compromised quality of life, disability, suicide risk and mortality.Drug treatment of late-life depression has large adverse reactions and is prone to drug resistance.Therefore, non-pharmacological interventions have gradually become a research hotspot.This paper reviewed the research progress of non-pharmacological interventions of late-life depression at home and abroad in recent years, and provides a theoretical basis for further research on effective treatment of late-life depression.

研究生群体是高校科研工作的主力军,研究生教育作为我国高等教育的重要组成,需要创新管理模式.地方高校二级学院结合学院特色和优势对于研究生进行个性化的管理和培养拥有较多的自主权,更适合进行研究生管理模式创新研究,以提升研究生个体的科研能力及未来对社会的适应能力.

NPC1 gene encodes a transmembrane glycoprotein on the late endosome/lysosomal membrane. Its mutation leads to a rare and aggravated autosomal recessive neurovisceral condition, termed Niemann-Pick disease type C1 (NPC1), which is characterized by progressive neurodegeneration, visceral symptoms, and premature death. To investigate the influence of NPC1 gene deletion on cell morphology, adhesion, proliferation, and apoptosis, CRISPR-Cas9 technology was used to knockout the NPC1 gene in HEK 293 T cells. Sanger sequencing, western blotting, and immunofluorescence were used to confirm successful NPC1 ablation. Filipin staining results indicated that deletion of NPC1 gene led to accumulation of unesterified cholesterol in HEK 293 T cells. Phalloidin staining results revealed cell aggregation, synapse shortening, nuclear enlargement, and cytoskeleton filamentous actin thinning in HEK 293 T cells with NPC1 gene mutation. Furthermore, NPC1 gene mutated HEK 293 T cell showed enhanced cell adhesion, inhibited cell proliferation, and increased cell apoptosis. In addition, NPC1 gene mutations significantly increased the protein expression levels of E-cadherin and γ-catenin and significantly decreased the protein expression levels of Wnt 3a, c-Myc, and cyclin D1. These results suggest that NPC1 may regulate cell adhesion by affecting the cadherin–catenin complex through E-cadherin, and that the classical Wnt signaling pathway may be inhibited by restricting β-catenin from entering the nucleus to inhibit cell proliferation.

在信息化时代,在线课程是教育信息化发展的产物,在线课程为学习者带来诸多便利,高校如何将在线课程教学资源融入课堂教学来改善教学质量,是高校教师面临的一个课题.文章以课程组建设的精品在线开放课程为研究对象,分析了传统课堂教学的不足及混合式教学模式的必要性.结合医学细胞生物学课程,对任务驱动式混合教学模式的教学设计、教学过程和教学效果进行了分析,旨在为混合式教学模式的开展提供有益参考.

Niemann-Pick disease type C1 (NPC1) is a hereditary neurodegenerative disorder caused by a mutation in the NPC1 gene. This gene encodes a transmembrane protein found in lysosomes. This disease characterized by hepatosplenomegaly, neurological impairments and premature death. Recent preclinical studies have shown promising results in using mesenchymal stem cells (MSCs) to alleviate the symptoms of NPC1. One type of MSCs, known as human menstrual blood-derived endometrial stem cells (MenSCs), has attracted attention due to its accessibility, abundant supply, and strong proliferation and regeneration capabilities. However, it remains uncertain whether the conditioned medium of MenSCs (MenSCs-CM) can effectively relieve the symptoms of NPC1. To investigate this further, we employed the CRISPR-Cas9 technique to successfully create a Npc1 gene knockout N2a cell line (Npc1(KO) N2a). Sanger sequencing confirmed the occurrence of Npc1 gene mutation in these cells, while western blotting revealed a lack of NPC1 protein expression. Filipin staining provided visual evidence of unesterified cholesterol accumulation in Npc1(KO) N2a cells. Moreover, Npc1(KO) N2a cells exhibited significantly decreased viability, increased inflammation, and heightened cell apoptosis. Notably, our study demonstrated that the viability of Npc1(KO) N2a cells was most significantly improved after being cultured by 36 h-collected MenSCs-CM for 0.5 days. Additionally, MenSCs-CM exhibited the ability to effectively reduce inflammation, counteract cell apoptosis, and ameliorate unesterified cholesterol accumulation in Npc1(KO) N2a cells. This groundbreaking finding establishes, for the first time, the protective effect of MenSCs-CM on N2a cells with Npc1 gene deletion. These findings suggest that the potential of MenSCs-CM as a beneficial therapeutic approach for NPC1 and other neurodegenerative diseases.

Niemann-Pick disease type C1 (NPC1) is a lysosomal lipid storage disease caused by NPC1 gene mutation. Our previous study found that, compared with wild-type (Npc1+/+ ) mice, the renal volume and weight of Npc1 gene mutant (Npc1-/- ) mice were significantly reduced. We speculate that Npc1 gene mutations may affect the basic structure of the kidneys of Npc1-/- mice, and thus affect their function. Therefore, we randomly selected postnatal Day 28 (P28) and P56 Npc1+/+ and Npc1-/- mice, and observed the renal structure and pathological changes by haematoxylin-eosin staining. The level of renal fibrosis was detected by immunofluorescence histochemical techniques, and western blotting was used to detect the expression levels of apoptosis-related proteins and canonical Wnt signalling pathway related proteins. The results showed that compared with Npc1+/+ mice, the kidneys of P28 and P56 Npc1-/- mice underwent apoptosis and fibrosis; furthermore, there were obvious vacuoles in the cytoplasm of renal tubular epithelial cells of P56 Npc1-/- mice, the cell bodies were loose and foam-like, and the canonical Wnt signalling pathway was abnormally activated. These results showed that Npc1 gene mutation can cause pathological changes in the kidneys of mice. As age increased, vacuoles developed in the cytoplasm of renal tubular epithelial cells, and apoptosis of renal cells, abnormal activation of the Wnt signalling pathway, and promotion of renal fibrosis increased.

Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.

研究生是具有专业技术的高层次人才,是新时代中国特色社会主义现代化建设的中坚力量.研究生教育是国家高等教育的重要组成部分.高校肩负着培养德才兼备的时代新人的重要使命,推动新时代研究生教育改革发展,加强研究生思想政治教育,可以增强研究生的理论素质、坚定研究生的理想信念、提高研究生的道德品质.文章分析了高校研究生思想政治教育的现状,提出"党建+"的教育新模式,着力提升研究生思想政治教育的质量,培养担当民族复兴大任的新青年.

Aestivation is a special ability possessed by some animals to cope with hot and dry environments utilizing dormancy. At a macroscopic level, dormant animals stop moving and eating. At the microscopic level, the expression of a large number of genes in these animals is strictly controlled. However, little is known about what changes occur during aestivation, especially in fish. In this study, we used transcriptome analysis to examine what changes occur in the gills and lungs of the African lungfish (Protopterus annectens) during the maintenance phase of aestivation and speculated on their causes. We found that aestivating transcriptomes were highly similar between gills and lungs. We also found that some genes showed differential expression or alternative splicing, which may be associated with different organs. In addition, differential expression analysis revealed that the lungs maintained significantly higher bioactivity during aestivation, which suggests that the main respiratory organ in aestivating lungfish can transform. Our study provides a reference point for studying the relationship between aestivation and hibernation and further increases understanding of aestivation.

Niemann–Pick disease type C1 (NPC1) is a neurodegenerative disorder characterized by lysosomal storage of free cholesterol. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a cyclic oligosaccharide derivative that is being developed to treat NPC1. Recently, metformin was reported to be beneficial in various neurodegenerative diseases, such as Alzheimer’s and Huntington’s diseases. In this study, we examined the effects of combined treatment with HPβCD and metformin on Npc1−/− mice. Unfortunately, body weight and survival rates showed that cotreatment with metformin did not extend survival time and increase the body weight of HPβCD-treated Npc1−/− mice. However, cotreatment with metformin reduced inflammatory response and inhibited the proinflammatory cytokine release in the brain, liver and spleen of HPβCD-treated Npc1−/− mice. Furthermore, metformin did not reduce the free cholesterol levels in Npc1−/− brain tissue or fibroblasts. In conclusion, our results demonstrate that metformin does not show beneficial effects on body weight or survival time but reduced the inflammatory response in a mouse model of NPC1 when combined with HPβCD.

起源于英国牛津的本科生导师制已经是我国高校普遍采用的人才培养制度.目前,本科生导师制在创新型人才培养中主要采用创客教育、以赛促培、项目促培三种应用方式.其优势是:个性化培养体现"因材施教";能力提升与综合素质培养结合.但在应用过程中也存在一些瓶颈问题,如导师数量和质量不足、批判性思维培养欠缺、奖励扶持力度不够等.根据本科生导师制在新乡医学院生命科学技术学院的运行实践,提出建议和措施:(一)本科生导师可通过学院择优选聘和学生推荐相结合的方式进行聘任,确保导师的质量.(二)定期举办本科生导师培训,吸纳更多的一线教师加入导师队伍,确保导师的数量.(三)通过制度规范导师的职责、任务和工作量评价标准,切实提高导师的工作积极性和学生培养质量.

Epilepsy is a nervous system disease caused by abnormal discharge of brain neurons, which is characterized by recurrent seizures. The factors that induce epilepsy include genetic and environmental factors. Genetic factors are important pathogenic factors of epilepsy, such as epilepsy caused by protocadherin-19 (PCDH-19) mutation, which is an X-linked genetic disease. It is more common in female heterozygotes, which are caused by mutations in the PCDH-19 gene. Epilepsy caused by environmental factors is mainly caused by brain injury, which is commonly caused by brain tumors, brain surgery, or trauma to the brain. In addition, the pathogenesis of epilepsy is closely related to abnormalities in some signaling pathways. The Wnt/β-catenin signaling pathway is considered a new target for the treatment of epilepsy. This review summarizes these factors inducing epilepsy and the research hypotheses regarding the pathogenesis of epilepsy. The focus of this review centers on cadherins and the pathogenesis of epilepsy. We analyzed the pathogenesis of epilepsy induced by N-cadherin and PCDH-19 in the cadherin family members. Finally, we expect that in the future, new breakthroughs will be made in the study of the pathogenesis and mechanism of epilepsy at the cellular and molecular levels.

生物工程专业是将生物学理论与方法和工程学手段相结合,培养应用型专业人才的新兴专业.面对生物工程产业的迅速发展、专业人才需求激增、生物工程专业本科就业专业对口率不高的现状,优化人才培养方案、凸显专业特色、提高人才竞争力势在必行.因此,文章比较了中美两国6所高校生物工程专业本科人才培养方案,阐述了中美高校在培养目标、课程设置和培养特色方面的特点和差异,提出了新乡医学院生物工程专业人才培养方案优化建议,以期为我国生物工程专业本科人才培养方案优化提供理论依据和参考.

In this study, we established a mouse model of epilepsy and analysed abnormal neuronal damage and inflammation in the hippocampus of mice with kainic acid (KA)‐induced epilepsy to provide the basis for the pathogenesis of epilepsy. C57 mice, aged 4 weeks, were injected intraperitoneally in the KA group with 20 mg/kg of KA and in the sham experimental group with normal saline. The whole brain and hippocampus of mice in the sham experimental group and KA epilepsy model group were collected on days 7, 14, 21 and 28 after injection. The difference in the protein expression in the hippocampus was detected using fluorescence immunohistochemistry. The hippocampal tissue was also collected and frozen to detect protein expression by western blot. The results of the haematoxylin and eosin (HE) and Nissl staining showed that the mouse model of temporal lobe epilepsy could be established by intraperitoneal injection of KA, and the success rate of the model was 53.8%. The expression of DCX‐, β‐catenin‐, GFAP‐ and Iba‐1‐labelled glial cells in the KA‐induced epilepsy model group were higher than those in the sham group. The results of western blotting showed that the expression of DCX and β‐catenin in the KA‐induced epilepsy model group was higher than that in the sham experimental group, while the expression of N‐cadherin and Iba‐1 on days 14 and 28 was significantly (P < .05) higher than that in the sham experimental group. In KA‐induced epilepsy model group, the expression of Bcl‐2 was decreased, while the expression of Bad and PUMA was increased.

本研究以医学细胞生物学MOOC平台线上和我校线下混合式教学模式为研究对象,通过对医学细胞生物学MOOC平台线上学习数据及新乡医学院医学细胞生物学近三年学生考核数据统计分析,提出了基于MOOC的医学细胞生物学线上线下混合式教学模式,为信息化背景下医学细胞生物学教学提供新的教学模式.

规律成簇间隔短回文重复(CRISPR)及CRISPR相关核酸内切酶(Cas)系统是古生菌和细菌中一类重要的获得性免疫系统,可有效抵御噬菌体等外源遗传物质的侵袭、感染.近年来,CRISPR-Cas9系统被发展为一种由RN A指导核酸内切酶的基因编辑技术.本文就该技术在基因组编辑及基因转录调控中的应用进行综述.