Exosomes (Exos) are an essential class of extracellular vesicles enriched with a wide range of biologically active molecules, which gives them a unique advantage in participating in intercellular signaling and communication and serving as carriers for drug delivery. Exo-based diagnostic and therapeutic strategies are currently hot topics in disease research. Owing to their naturally low immunogenicity, good biocompatibility, ability to penetrate the blood‒brain barrier (BBB), and engineered modifications, exos have significant advantages and possible applications in the treatment of nervous system diseases. Due to the serious harm of neurological diseases to human health, they have been widely studied by researchers. Exos can be administered in a variety of ways, including intranasal administration, intracranial administration, local stereotactic injection, and encapsulation in biomaterials, each of which has its own advantages and disadvantages. However, several requirements need to be met before exo-based therapies can be implemented, such as the standardization of isolation and purification techniques, an in-depth understanding of the mechanism of action, and safety assessments and regulation for clinical translation. The aim of this review is to provide a comprehensive overview of the biogenesis, molecular composition, function, and delivery modes of exos and their therapeutic roles and mechanisms in neurological diseases (e.g., multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and stroke) and to discuss the current challenges and future perspectives to support ongoing research and clinical applications.

Ovarian aging is accompanied by a decline in the quantity and quality of follicles, leading to reduced fertility. Ovarian aging encompasses natural aging due to DNA damage, telomere attrition, and mitochondrial dysfunction, as well as a pathological functional failure caused by environmental toxins, known as a premature ovarian failure. Cell therapy is currently a focal point of research, with mesenchymal stem cells (MSCs) being particularly notable due to their wide availability, ease of expansion, strong self-renewal capabilities, multipotent differentiation, and paracrine functions. MSCs have shown great potential in the field of cell therapy, including delaying ovarian aging. MSCs can delay ovarian aging through various mechanisms: antioxidation, differentiation and regeneration, promotion of cell proliferation, inhibition of cell apoptosis, and anti-inflammatory responses. Currently, MSCs transplantation has achieved significant results in animal models, improving ovarian function and enhancing fertility. However, clinical applications still face numerous challenges, such as determining the optimal cell source, transplantation route, dosage, and long-term safety, which require further research. In this review, we will elaborate on the mechanisms of ovarian aging, the modes of action of MSCs, and the mechanisms by which MSCs delay ovarian aging, aiming to provide a theoretical basis for the clinical application of MSCs and to bring breakthroughs in the treatment of diseases such as premature ovarian failure.

Due to exposure factors such as industrial exhaust, sewage discharge, pesticide runoff, automobile exhaust, and fuel combustion, environmental toxicants are widely present in daily life. Organisms are exposed to these environmental toxicants through contaminated air, food, and drinking water, and these environmental toxicants enter the human body and cause cytotoxicity and diseases through various pathways. As a new cell death mode that is different from cell necrosis, apoptosis, and autophagy, ferroptosis are mainly dysregulation of intracellular iron metabolism, lipid metabolism disorders, and the dysregulation of the antioxidant defense system, leading to lipid peroxidation and ultimately to the rupture of the cell membrane, damage, and cell death. Studies have shown that environmental toxicants induce a series of diseases, such as digestive diseases, urinary diseases, respiratory diseases, neurological disorders, and reproductive diseases, through the above mechanisms. We elaborate the mechanism of common environmental toxicants in inducing ferroptosis and the related systemic diseases mediated through the ferroptosis to provide the theoretical basis for preventing and treating environmental toxicant-related diseases. Nonetheless, our understanding of ferroptosis remains incomplete. For example, mechanisms and methods for the selective control of ferroptosis remain elusive, elucidating these mechanisms and strategies may be critical for leveraging knowledge of ferroptosis to treat related diseases.

Reproductive system disorders significantly contribute to infertility, and traditional or conventional treatments often have limited efficacy in addressing this issue. In recent years, stem cell therapy has emerged as an alternative therapeutic strategy owing to its various advantages. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are pivotal in tissue repair owing to their robust proliferative capacity, potent immunomodulatory effects, low immunogenicity, and paracrine actions. Extracellular vesicles (EVs), the primary mediators of paracrine functions, exhibit therapeutic effects similar to those of hUC-MSCs. Consequently, numerous researchers have investigated the application of hUC-MSCs and their EVs in treating reproductive disorders. These cells have the potential to restore fertility by mitigating oxidative stress, excessive autophagy, and ferroptosis in tissues, while promoting the expression of anti-inflammatory factors and vascular remodeling. However, hUC-MSCs present significant limitations compared to EVs, including higher tumorigenicity and low infusion efficiency. Consequently, EVs may emerge as the primary alternative therapy, while hUC-MSCs hold promise as a therapeutic option with potential applications in regenerative medicine.

The impact of environmental pollution on fertility has become an essential issue in global public health. Maturation, fertilisation, and embryonic development of oocytes depend on the energy provided by mitochondria; however, with increased environmental pollution and ageing, mitochondrial dysfunction and its subsequent functional and metabolic abnormalities have become leading causes of female fertility decline. When mitochondrial dysfunction occurs in the oocyte, reduced metabolic efficiency leads to impaired nuclear and cytoplasmic maturation of the oocyte, affecting the quality of the oocyte, which further contributes to decreased female fertility and increased risk of infertility, miscarriage, and aneuploid foetuses due to ovarian dysfunction. Several factors affect mitochondrial function, including excess reactive oxygen species (ROS)-induced mutations in mitochondrial DNA (mtDNA), changes in mtDNA copy number, oxidative stress (OS), damage to key cellular components and organelles, and changes in metabolic intermediates and byproducts at the cellular level, further affecting oocyte developmental competence. Mitochondrial dysfunction leads to problems such as abnormal spindle formation and chromosome misalignment, reducing fertilisation potential and embryonic developmental capacity. Mitochondrial dysfunction plays a key role in oocyte ageing and the decline in germ cell function, and an in-depth study of its molecular mechanisms and intervention strategies is highly important for slowing oocyte ageing, increasing fertility, and improving the success rate of assisted reproduction techniques. Clinical trial number Not applicable.

Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

Alcohol induces neurodevelopmental toxicity through multiple biological processes, including DNA methylation and histone modifications in epigenetic regulation. Epigenetic mechanisms involving DNA chemical modifications represent crucial molecular pathways that regulate gene expression during neurodevelopment, exhibiting high sensitivity to adverse lifestyle factors such as alcohol consumption, smoking, and stress. Prenatal alcohol consumption is a primary cause of fetal neurodevelopmental disorders. Alcohol alters DNA methylation and histone modification levels in the brain, which in turn disrupts the expression levels of related genes. This review focuses on how alcohol mediates neurodevelopmental toxicity by disrupting DNA methylation mechanisms. First, alcohol affects DNA methylation through the following pathways: (1) Inhibiting folate metabolism reduces the production of the methyl donor S-adenosylmethionine (SAM), thereby decreasing DNA methyltransferase (DNMTs) activity; (2) Induces oxidative stress, where reactive oxygen species (ROS) disrupt methylation status at CpG sites; (3) Directly alters the activity of DNMTs and TETs, leading to hypermethylation or hypomethylation in gene promoter regions. These abnormal methylation patterns significantly impact the differentiation neural stem cells (NSCs), neuronal migration and synapse formation, as well as the function of glial cells. Methylation abnormalities in neurodevelopment-related genes can trigger neuronal migration defects and synaptic plasticity disorders. Alcohol-induced methylation-related changes exhibit brain region specificity, involving areas such as the hippocampus, prefrontal cortex, and hypothalamus. Regarding intervention strategies, prenatal supplementation with methyl donors like folate and choline partially reverses alcohol-induced abnormal DNA methylation and improves neurodevelopmental outcomes. This study highlights the role of DNA methylation in alcohol-mediated neurotoxicity, providing a theoretical basis for elucidating the molecular mechanisms of FASD and developing targeted epigenetic therapeutic strategies.

Infertility is a common reproductive disorder affecting millions of couples worldwide. It is estimated that male factors account for about 30%-50% of infertility cases, and some studies have found that the concentration of male sperm gradually decreases over time, a trend that suggests the importance of male fertility. Many factors contribute to the decline of male fertility, among which environmental factors have received widespread attention. After reaching adulthood, spermatogonial stem cells will continue to produce sperm, but these cells exist outside the blood testicular barrier, which makes them highly sensitive to environmental conditions such as air pollution, tobacco smoke, radiation, and heavy metals. It is reported that exposure to these adverse environmental factors not only causes oxidative stress and DNA damage to germ cells, but also leads to abnormal epigenetic modification of sperm DNA, thereby causing a series of diseases. This article reviewed the abnormal methylation changes in DNA associated with exposure to environmental pollutants during spermatogenesis and how these changes affect the quantity, quality, and function of spermatozoa.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are hazardous to human health; can be produced by a variety of pathways; and are widely present in the environment, including air, soil, and water. When PAHs enter the human body, they accelerate cellular senescence and cellular ageing by promoting cell cycle arrest, inducing the excessive production of reactive oxygen species (ROS) and DNA methylation and mitochondrial dysfunction, thereby increasing the likelihood of disease, including reproductive disorders, Alzheimer's disease and cardiovascular diseases. Therefore, studying and combatting diseases caused by PAH exposure is critical. In this work, we elaborate on the mechanism of PAH toxicity and the diseases caused by PAHs from the perspective of the cellular senescence induced by PAHs, their central component benzo(a)pyrene, and their derivatives, with the aim of elucidating the molecular mechanisms of human diseases induced by PAHs through cellular senescence to provide theoretical support for the development of targeted preventive strategies and the maintenance of public health.

Polycyclic aromatic hydrocarbons (PAHs), which are widely present in incompletely combusted air particulate matter <2.5 μm (PM2.5), tobacco and other organic materials, can enter the human body through various routes and are a class of environmental pollutants with neurotoxic effects. PAHs exposure can lead to abnormal development of the nervous system and neurobehavioral abnormalities in animals, including adverse effects on the nervous system of children and adults, such as a reduced learning ability, intellectual decline, and neural tube defects. After PAHs enter cells of the nervous system, they eventually lead to nervous system damage through mechanisms such as oxidative stress, DNA methylation and demethylation, and mitochondrial autophagy, potentially leading to a series of nervous system diseases, such as Alzheimer's disease. Therefore, preventing and treating neurological diseases caused by PAHs exposure are particularly important. From the perspective of the in vitro and in vivo effects of PAHs exposure, as well as its effects on human neurodevelopment, this paper reviews the toxic mechanisms of action of PAHs and the corresponding prevention and treatment methods to provide a relevant theoretical basis for preventing the neurotoxicity caused by PAHs, thereby reducing the incidence of diseases related to the nervous system and protecting human health.

随着干细胞生物学和转化医学的飞速发展,干细胞治疗技术在修复和再生领域已展现出了巨大的应用价值.随着我国不断推出支持干细胞研究的政策利好,干细胞基础研究和临床研究都处于世界技术发展前沿,干细胞疗法在自身免疫性疾病、神经系统疾病、内分泌系统疾病乃至生殖系统疾病等领域都实现了重大突破,已经由基础转向临床试验,未来可期.然而,随着行业的迅猛扩张,干细胞临床研究人才缺口日益凸显,人才需求迫在眉睫,高等医学教育是培养和输送干细胞研究专业人才重中之重的环节,因此在高等医学教育中设立干细胞生物学前沿课程,有助于医学生了解干细胞基本理论、干细胞类型和适应证,把握干细胞治疗前沿方向,加强"医、学、研"联合发展,为培养干细胞转化研究专业技术人才、未来全面推广干细胞临床治疗技术奠定基础.

Benzo(a)pyrene (BaP), the earliest and most significant carcinogen among polycyclic aromatic hydrocarbons (PAHs), has been found in foods, tobacco smoke, and automobiles exhaust, etc. Exposure to BaP induced DNA damage directly, or oxidative stress-related damage, resulting in cell apoptosis and carcinogenesis in human respiratory system, digestive system, reproductive system, etc. Moreover, BaP triggered genome-wide epigenetic alterations by methylation, which might cause disturbances in regulation of gene expression, and thereby induced cancer. It has been proved that BaP reduced genome-wide DNA methylation, and activated proto-oncogene by hypomethylation in the promoter region, but silenced tumor suppressor genes by promoter hypermethylation, resulting in cancer initiation and progression. Here we summarized the changes in DNA methylation in BaP exposure, and revealed the methylation of DNA plays a role in cancer development.

Cellular metabolism in tumor is an important biological process to promote the occurrence and development of tumor, and the genes related to cellular metabolism are gradually becoming the targets of tumor treatment. However, more researches are still needed to explore the abnormal metabolism in tumor progression and its prognostic value. BDH2 gene is a multifunctional gene, participates in a variety of metabolic pathways, plays an important catalytic role in iron metabolism, participates in ketone metabolism and is related to lipid metabolism. In recent years, researchers have found that BDH2 plays distinct roles in various types of tumors. The occurrence and development of a variety of tumors are closely related to BDH2. This paper analyzes, summarizes and prospects the role and mechanism of BDH2 in metabolism and tumorigenesis.

The hair follicle (HF) is an important mini‐organ of the skin, composed of many types of cells. Dermal papilla cells are important signalling components that guide the proliferation, upward migration and differentiation of HF stem cell progenitor cells to form other types of HF cells. Thymosin β4 (Tβ4), a major actin‐sequestering protein, is involved in various cellular responses and has recently been shown to play key roles in HF growth and development. Endogenous Tβ4 can activate the mouse HF cycle transition and affect HF growth and development by promoting the migration and differentiation of HF stem cells and their progeny. In addition, exogenous Tβ4 increases the rate of hair growth in mice and promotes cashmere production by increasing the number of secondary HFs (hair follicles) in cashmere goats. However, the molecular mechanisms through which Tβ4 promotes HF growth and development have rarely been reported. Herein, we review the functions and mechanisms of Tβ4 in HF growth and development and describe the endogenous and exogenous actions of Tβ4 in HFs to provide insights into the roles of Tβ4 in HF growth and development.

目的:探讨STAT3-siRNA对肝癌细胞pim-2基因表达的影响.方法:设计靶向stat3基因的siRNA-SECs,构建重组表达质粒,在体外基于脂质体来实现介导,对SMMC-7721转染,在对转染效果进行分析的过程中所采用的主要方法为Western blot和半定量RT-PCR分析.结果:转染STAT3-siRNA表达载体后,肝癌SMMC-7721细胞株pim-2 mRNA表达和蛋白表达均明显下降,对照组各指标均无明显变化.结论:siRNA明显抑制了pim-2的表达,并抑制肿瘤生长.作为一个重要的基因沉默工具,未来siRNA有希望变成肝癌治疗的一种新的方法.

Increased cashmere yield and improved quality are some goals of cashmere goat breeding. Thymosin beta-4 (Tβ4) plays a key role in the growth and development of hair follicles. For the past ten years, we have evaluated the role of Tβ4 by establishing a flock of 15 cashmere goats that specifically overexpress the Tβ4 gene in the hair follicles. These Tβ4 overexpression (Tβ4-OE) cashmere goats had more secondary hair follicles than the WT goats and produced more cashmere. Meanwhile, combined analysis of the skin transcriptome and proteome in cashmere goats suggested that Tβ4 may affect hair growth by interacting with keratin type II cytoskeletal 4 epidermal (KRT4) to mediate the extracellular signal-regulated protein kinase (ERK) signaling pathway, thereby promoting the development of secondary hair follicles, and consequently, increasing cashmere yield. Thus, the specific overexpression of Tβ4 in the hair follicles of cashmere goats effectively increased the cashmere yield.

OBJECTIVE:To evaluate the proformance of multiplex PCR and capillary electrophoresis(MPCE) in the detection of JAK2V617F and CALR mutation in myeloproliferative neoplasms(MPN).METHODS:The specificity primers of JAK2617F gene mutation and the primers of CALR gene were designed at the same time. The JAK2V617F and CALR gene primers were labeled with Cy5 fluorescence, all the primers were mixed in one tube for multiplex PCR and the PCR prodcuts were analysised by capillary electrophoresis. Then detection limit and sensitivity of MPCE were evaluated, and compared with comercial diagnostic kit.RESULTS:JAK2V617F and CALR gene mutations could be detect by MPCE in one PCR test. JAK2V617F mutation could be detected at 0.01 ng genomic DNA, double positive JAK2V617F and CLAR gene mutations could be detected at 0.1 ng genomic DNA, at least 0.1% JAK2V617F positive mutation could be detected. The consistency between MPCE and commercial diagnostic gene mutation kit was 100%.CONCLUSION:It is developed that a new gene mutation detection method of JAK2 V617F and CLAR gene based on MPCE in our experiment and it can be used as a new reagent for molecular diagnosis of MPN patients.

Connexin 43 (Cx43), known to form gap junction transmembrane channels between the cytoplasm of two adjacent cells, plays a key role in physiological functions, such as regulating cell growth, differentiation, and maintaining tissue homeostasis. Cashmere goat is an important farm animal that provides cashmere, which was produced by secondary hair follicles (SHF), for human consumption; however, there is no report about the role of Cx43 on the growth and development of SHF in cashmere goat. In this study, we investigated the effect of Cx43 on proliferation secondary hair follicle dermal papilla cells (SHF-DPCs) in Albas cashmere goat. In SHF-DPCs, Cx43 overexpression promoted cell proliferation and upregulated the expression of IGF-1, whereas Cx43 knockdown was associated with the opposite effects. These results suggested that Cx43 may promote cell proliferation by inducing IGF-1. Overall, our research not only contributes to a better understanding of the mechanism of the growth and development of SHF in cashmere goat, but also shed light on cashmere quality control in the future.

Paeonol, a major ingredient isolated fromMoutan Cort,has various pharmacological effects. Our previous studies have shown that paeonol can exert antioxidant and anti-inflammatory therapeutic effects on ethanol-induced experimental gastric ulcer (GU). Therefore, in this study, we designed two GU models in rats induced by pyloric ligation (PL) and acetic acid and evaluated the protective effects of paeonol and gastroretention tablets of paeonol (GRT-Ps; 24, 48, and 96 mg/kg) on GU in rats and the effect of paeonol (48 mg/kg) on the intestinal flora.In vivoexperiments showed that paeonol or GRT-Ps remarkably reduced gastric mucosal damage in a dose-dependent manner in the different types of models and improved the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content. And in fact, the sustained-release effect of GRT-Ps is more conducive to the improvement of GU compared with the rapid clearance of free drugs. In the PL-induced model, gastric secretion parameters, that is, pH and total acid, showed significant differences compared with the model group. In addition, paeonol treatment can improve the richness and diversity of the intestinal flora and increase the amount of beneficial bacteria, such asLactobacillus. Paeonol and its stable sustained-release tablet GRT-Ps can promote ulcer healing by inhibiting oxidative stress and regulating the intestinal flora. This study can provide basis for the clinical treatment of GU with paeonol. Graphical Abstract

For decades, researchers have focused on building genetically and phenotypically stable neural stem cell lines designed to restore the irreversible loss of function of nerve tissue to meet clinical needs. Among them, stem cells that maintain their pluripotent state in adults have also become one of the research focuses. With the development of technologies such as induced pluripotent stem cells and direct differentiation of somatic cells into desired cell types, research methods based on the use of allogeneic neural stem cells derived from embryonic or fetal neural tissue have gradually become a thing of the past. This article will review the basic molecular mechanisms surrounding the maintenance of pluripotent states of stem cells and reprogrammed somatic cells, as well as experimental protocols for inducing neural stem cells.