Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

The interaction between Mycobacterium tuberculosis and host, as well as the regulation of some signaling pathways in the host, were involved in pathogen latency in macrophages. microRNAs (miRNAs) regulate the gene expression and biological functions, indicating that miRNAs played a regulatory role in bacterial infections. However, whether the host's miRNAs were also involved in the process of Mycobacterium tuberculosis infection had not been thoroughly studied. This study infected macrophages with pathogenic Mycobacterium tuberculosis strain H37Rv and low virulence strain H37Ra to explore the functional miRNAs. By identifying the expression profile of miRNAs in host cells after infection, the expression of 17 miRNAs significantly changed (P < 0.05) in the human macrophage THP-1 infected with highly pathogenic H37Rv strain (Rv), H37Rv inactivated strain (Rv-), and non-pathogenic H37Ra (Ra) strains respectively, indicating that host miRNAs may be involved in the interaction of Mycobacterium tuberculosis and host. Meanwhile, 10 types of miRNAs showed significant differences in cells infected with pathogenic and non-pathogenic Mycobacterium tuberculosis, suggesting that host miRNAs may play an important role in the pathogenicity and intracellular survival of Mycobacterium tuberculosis. Further study had found that miR-449a, miR-502-5p, and miR-708 were downregulated in cells infected with Mycobacterium marinum. Overexpression of these three miRNAs displayed the significant inhibitory effect on the growth of Mycobacterium marinum, indicating that miRNAs played a pivotal role in the interaction between the host and Mycobacterium marinum. This study provided the new insights into the pathogenesis of Mycobacterium tuberculosis and the treatment of tuberculosis.

HDAC(histone deacetylase)is a class of epigenetic modifying enzymes that can deacetylate proteins by altering the acetylation status of histones in the nucleus,regulating promoter activation levels,and thereby affecting downstream gene expression.However,expression changes of HDACs during endo-thelial differentiation are still unclear.This study used a three-stage method to induce human induced pluripotent stem cells(hiPSCs)to differentiate into endothelial cells,and qRT-PCR was used to detect the expression changes of class I HDAC(HDAC1,2)and class Ⅱ HDAC(HDAC4,5)genes.It was found that HDAC5 exhibits significant expression changes during endothelial differentiation.It is downreg-ulated by 90％during the mesodermal differentiation stage(P＜0.01),upregulated by 3.7-fold during the vascular precursor stage(P＜0.01),and subsequently downregulated by 70％during the late stage of endothelial differentiation(P＜0.01).Immunoblotting experiments further confirmed that HDAC5 under-goes periodic expression changes during endothelial differentiation.Mechanistic studies have shown that HDAC5 downregulation during the differentiation stage of the mesoderm is mediated by Wnt signaling.CHIR99021 treatment and overexpression of Wnt3a can activate the Wnt signaling pathway,leading to HDAC5 downregulation.Inhibiting the Wnt signaling pathway through IWP-2 promotes the recovery of HDAC5 expression.In addition,it was found that HDAC5 is mainly localized in the nucleus,and IWP-2 restores HDAC5 expression,but it remains in the cytoplasm.Further research suggests that downregu-lation of HDAC5 during mesodermal differentiation may contribute to the expression of the mesodermal marker BraT.Treatment with the HDAC inhibitor BML210 can promote early mesodermal differentiation,interfere with endothelial differentiation of vascular precursor cells,and enhance late-stage endothelial differentiation.In conclusion,HDAC5 displays a stage-specific expression during endothelial differentia-tion,and Wnt signaling activation is the main mechanism regulating the downregulation of HDAC5 during the mesoderm stage.

The microbiome plays a role in the development of lower urinary tract diseases, but the impact of viruses on these conditions remains unclear. In recent years, research has emerged demonstrating a potential link between viruses and lower urinary tract diseases, including bladder cancer, prostate cancer, and overactive bladder. In this paper, the research of the correlation between viruses and lower urinary tract diseases and the related mechanisms were reviewed.

Purpose::Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.Methods::Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization.Results::Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. Conclusion::This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

Objective To explore the mechanism of quercetin in the treatment of breast cancer with depressive features using network pharmacology and animal experiments.Methods Network pharmacology and bioinformatics methods were used to predict the key targets and mechanisms of quercetin in the treatment of breast cancer with depressive characteristics.The predicted results were verified by animal experiments.A mouse model of breast cancer with depressive characteristics was constructed,and quercetin intervention was performed after grouping.The depression of mice was evaluated by open field test.The tumor volume and tumor mass were measured.The expression of Ki-67 in tumor tissue was detected by immunohistochemical staining.The expressions of tumor necrosis factor α(TNF-α),interleukin 6(IL-6),p53,Caspase-3 and B-cell lymphoma/leukemia 2(Bcl-2)in tumor tissue were detected by Western Blot.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis of tumor cells.Results In the breast cancer model group with depressive characteristics,the total movement distance in the open field test and the ratio of residence time in the central area of the open field test were decreased,the tumor volume and tumor mass were significantly increased,and Ki-67 expression level in the tumor tissue was significantly increased,the expression levels of TNF-α,IL-6,p53 and Caspase-3 in the tumor tissue were decreased and the expression level of Bcl-2 was increased,as well as the rate of TUNEL positive cells was decreased,the differences being statistically significant compared with the control group(P＜0.01 or P＜0.001).Compared with the model group,the above indexes were significantly reversed in the quercetin group(P＜0.01 or P＜0.001).Conclusion Quercetin can effectively inhibit the progression of breast cancer with depressive characteristics in mice,and its mechanism is related to the regulation of TNF,IL6,TP53,CASP3,BCL2 and other targets to promote tumor cell apoptosis.

Osteoporosis(OP)is a systemic bone disease characterized by low bone mass and damage to the microstructure of bone tissue,leading to increased bone fragility and susceptibility to fracture.Owing to its high prevalence,disability and mortality rates,as well as more sequelae,it brings heavy burden to patients and society.In recent years,as the research on the chemical and pharmacological effects of Psoralea corylifolia has made great progress,scholars have isolated compounds such as coumarins,flavonoids and monoterpene phenols,which have anti-OP,anti-oxidation,and anti-inflammatory properties,Psoralea corylifolia has been widely used in the treatment of OP.This article reviews the regulatory mechanism of active ingredients of Psoralea corylifolia in OP lipid metabolism,bone metabolism and oxidative stress,as well as related therapeutic strategies targeting Wnt/β-catenin,PI3K/Akt,PPAR-γ/Wnt,RANKL/RANK/MAPK and NF-κB signaling pathways,in order to provide further reference for the prevention and treatment of OP.

Objective To investigate the influences and mechanism of X chromosome inactivation specific transcript(XIST)on the proliferation and extracellular matrix synthesis of nucleus pulposus cells in rats with intervertebral disc degeneration(IDD).Methods SD rat intervertebral disc nucleus pulposus cells were isolated and cultured in vitro,and then randomly divided cells into control group,model group,XIST knockdown group,empty plasmid group,and XIST knockdown+miR-132-3p knockdown group.Except for control group,the cells in other groups were induced by interleukin(IL)-1β to establish IDD models.After nucleus pulposus cells were grouped and treated,the expressions of XIST and miR-132-3p in the nucleus pulposus cells of rats were detected by qRT-PCR;the proliferation of intervertebral disc nucleus pulposus cells was detected by MTS method and EdU staining;ELISA was used to measure the levels of inflammatory factors IL-6 and IL-18 in the intervertebral disc nucleus pulposus cells;Immunoblotting was used to detect the expression of extracellular matrix labeled proteins Collagen Ⅱ and Aggrecan in rat nucleus pulposus cells.The targeted regulation of miR-132-3p by XIST in rat nucleus pulposus cells was detected by dual-luciferase reporter gene assay.IDD rat models were established by intramuscular injection of IL-1β and divided into sham operation group,model group,XIST knockdown group,no-load plasmid group,XIST knockdown+miR-132-3p knockdown group,with 12 rats in each group.After treatment in each group,the expressions of XIST and miR-132-3p in intervertebral disc tissues were detected by qRT-PCR;TUNEL staining was used to detect apoptosis of nucleus pulposus cells in intervertebral disc tissue of rats;the morphology of intervertebral disc cartilage was observed by saffron O staining;serum levels of inflammatory factors IL-6 and IL-18 were determined by ELISA;the expressions of Collagen Ⅱ and Aggrecan in intervertebral disc tissues were detected by Western blotting.Results Compared with control group(cells)/sham operation group(rats),XIST expression in intervertebral disc tissue and nucleus pulposus cells,apoptosis rate of intervertebral disc nucleus pulposus cells,levels of inflammatory factors IL-6 and IL-18 in intervertebral disc nucleus pulposus cells culture medium and serum were increased in model group(P＜0.05),the activity and proliferation rate of nucleus pulposus cells and the expressions of miR-132-3p,Collagen Ⅱ and Aggrecan protein in nucleus pulposus cells and intervertebral disc tissues decreased(P＜0.05);compared with model group,the apoptosis rate of nucleus pulposus cells,the levels of inflammatory factors IL-6 and IL-18 in intervertebral disc nucleus pulposus cells culture medium and serum,and the expression of XIST in nucleus pulposus cells and intervertebral disc tissues of rats in XIST knockdown group decreased(P＜0.05),the activity and proliferation rate of nucleus pulposus cells and the expressions of miR-132-3p,Collagen Ⅱ and Aggrecan protein in nucleus pulposus cells and intervertebral disc tissues increased(P＜0.05).Down-regulation of miR-132-3p attenuates the ameliorative effect of knockdown XIST on IL-1β-induced intervertebral disc injury and cartilage matrix loss.XIST was able to target and down-regulate the expression of miR-132-3p in rat nucleus pulposus cells.Conclusion Knockdown of XIST can inhibit inflammation by up-regulating miR-132-3p,thereby inhibiting the apoptosis of IDD nucleus pulposus cells and promoting their proliferation and extracellular matrix synthesis.