Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.

BACKGROUND:The stemness index may be associated with the prognosis and immune infiltration of sarcoma,but the specific regulatory mechanism and characteristic genes have yet to be fully elucidated. OBJECTIVE:To investigate the correlation between stem cells and prognosis as well as immune infiltration in sarcoma employing the gene stemness index model and to identify the ferroptosis signature genes associated with sarcoma stem cells. METHODS:The sarcoma RNA sequencing data and related clinical information were obtained from the Cancer Genome Atlas(TCGA).The sarcoma RNA sequencing data were grouped using the sarcoma stemness index.Survival data were used to analyze prognosis between groups.Differentially expressed genes were obtained for pathway enrichment and immune infiltration analysis.Ferroptosis-related differential genes were used to construct a protein interaction network and analyze prognostic correlation.Rhabdomyosarcoma cell lines were cultured and divided into adherent cell group and stem cell group.The adherent cell group received no intervention,while the stem cell group was treated with serum-free culture to enrich stem cells in rhabdomyosarcoma cells.qRT-PCR was used to evaluate stemness markers,ferroptosis-related genes,and mRNA expression of ferroptosis-related markers in the cells. RESULTS AND CONCLUSION:(1)Patients were divided into high and low stemness index groups based on the median stemness index.The progression-free survival of patients in the high stemness index group was lower than that in the low stemness index group by disease risk prediction,suggesting poor prognosis.(2)According to GO and KEGG analysis,the groups with high and low stemness indices differed from one another.There were differences in immune infiltration between the high and low stemness index groups.Nine of the 23 ferroptosis-related genes in the differential genes have the potential to establish a highly correlated network of protein interactions.Patients with high expression of IDO1,IFNG,and AQP5 have a better prognosis,while those with high expression of CA9 have a poor prognosis.(3)The qRT-PCR results demonstrated a significant upregulation of stem cell-related markers NANOG,SOX2,and OCT4 mRNA expressions in the stem cell group compared to the adherent cell group(P<0.05).Compared to the adherent cell group,the stem cell group exhibited decreased mRNA expression level of ferroptosis-related marker SLC7A11(P<0.05)while showing increased levels of ACSL4,GPX4,FTH1,and COX2(P<0.05).Compared to the adherent cell group,the stem cell group displayed decreased mRNA expression level of differentially expressed gene CA9 alongside elevated levels of IDO1,IFNG,and AQP5(P<0.05).Stem cells were strongly associated with sarcoma survival and ferroptosis by bioinformatics analysis and experimental verification.Sarcoma stem cells have aberrant expression of CA9,IDO1,IFNG,and AQP5,which may serve as new targets for sarcoma therapy as well as diagnostic indicators.

Objective To develop and evaluate dietary and exercise intervention program for over-weight/obese patients with polycystic ovary syndrome(PCOS).Methods Seventy patients with over-weight/obese PCOS were prospectively selected as research subjects and divided into intervention group(n=35)and control group(n=35)according to random number table method.According to the completion of the intervention plan,29 cases were finally included in the intervention group and 28 cases in the control group.The control group was given conventional nursing intervention,while the intervention group was applied with the diet and exercise intervention program for overweight/obese patients with PCOS.Both groups were intervened for 3 months.The physical indicators,PCOS sign scores,natural pregnancy rate,degree of self-body image distress(Multidimensional Self-body Im-age Relationship Questionnaire-Appearance Subscale)and self-efficacy level(Self-efficacy Scale)before and after the intervention were compared between the two groups.The occurrence of adverse reactions during the intervention period between the two groups were compared.Results After 1 month and 3 months of intervention,the body mass index(BMI)and PC OS sign score of the pa-tients in the intervention group were significantly lower than those in the control group(P＜0.05).The natural conception rate of the intervention group was 34.48％(10/29),which was significantly higher than 10.71％(3/28)of the control group(P＜0.05).After 1 month and 3 months of inter-vention,the scores of the self-body image relationship-appearance subscale of the patients in the inter-vention group were significantly higher than those in the control group(P＜0.001).After 3 months of intervention,the score of the Self-efficacy Scale of patients in the intervention group was significantly higher than that in the control group(P＜0.001).During the intervention period,no adverse reac-tions caused by diet and exercise intervention occurred in either group.Conclusion Implementing a diet and exercise intervention program for overweight/obese patients with PCOS is beneficial for re-ducing patients' BMI,increasing the natural pregnancy rate,improving self-body image disorders,and enhancing self-efficacy.

Isavuconazole represents a novel gen-eration of triazole antifungal agents for the treat-ment of invasive trichothecenes in adults.The phar-macokinetic profile of isavuconazole differs in spe-cial populations,including children,patients with ex-tracorporeal membrane oxygenation,those with he-patic or renal injury,patients undergoing blood puri-fication,and critically ill individuals and solid organ transplant recipients.These differences impact the safety and efficacy of patient treatment.This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

Isavuconazole represents a novel gen-eration of triazole antifungal agents for the treat-ment of invasive trichothecenes in adults.The phar-macokinetic profile of isavuconazole differs in spe-cial populations,including children,patients with ex-tracorporeal membrane oxygenation,those with he-patic or renal injury,patients undergoing blood puri-fication,and critically ill individuals and solid organ transplant recipients.These differences impact the safety and efficacy of patient treatment.This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations.

Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.

AIM:To explore the impact of sphingosine 1-phosphate receptor 5(S1PR5)on lipopolysaccha-ride(LPS)-induced neuroinflammation and cognitive-behavioral impairments in mice,alongside the anti-inflammatory im-pacts on BV2 cells and associated mechanisms.METHODS:(1)C57BL/6 wild-type(WT)mice and homozygous S1PR5 knockout(KO)mice were utilized and categorized into WT control,WT-LPS,S1PR5 KO control,and S1PR5 KO-LPS groups using the random number method.Neuroinflammatory models in mice were induced by a single intraperitoneal injection of 5 mg/kg LPS in the WT-LPS and S1PR5 KO-LPS groups,while an equivalent volume of saline was injected in-to the WT control and S1PR5 KO control groups.Following 7 days of modeling,the Morris water maze test was conducted,followed by the collection of brain tissues from each group of mice.Hippocampal tissue sections were stained with Nissl.The mRNA expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in hippocampal tis-sues were determined using RT-qPCR.Western blot and tissue immunofluorescence techniques were employed to assess the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in hippocampal tissues.(2)The BV2 cells underwent LPS stimulation to induce an inflammatory response and were treated with either the S1PR5 ago-nist A971432 or lentiviral overexpression of S1PR5.The effects of S1PR5 agonism or overexpression on S1PR5,IL-1β,IL-6,TNF-α,and CD206 were assessed using RT-qPCR.Additionally,CD206 expression was examined via cellular im-munofluorescence.Western blot was employed to analyze the protein levels of microglia polarization markers CD206,in-ducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX2),and NLRP3,as well as p-NF-κB,cleaved caspase-1,and IκBα.RESULTS:(1)Findings from in vivo experiments indicated that S1PR5 KO notably exacerbated LPS-induced memory impairments in mice,alongside increased mRNA levels of IL-1β and IL-6,and increased protein levels of NLRP3 in the hippocampus.(2)The presence of S1PR5 in BV2 cells remained unaffected by variations in A971432 concentration and exposure duration.(3)Activation of S1PR5 or its overexpression significantly mitigated LPS-induced expression of IL-1β,IL-6,and TNF-α,while concurrently enhancing CD206 expression in BV2 cells at the mRNA level.At the protein level,it led to a noteworthy increase in CD206 expression,indicative of M2-type macrophages,and a reduction in the ex-pression of iNOS and COX2,markers of M1-type macrophages.Furthermore,it downregulated NLRP3,p-NF-κB,and cleaved caspase-1 expression,while upregulating IκBα expression.CONCLUSION:S1PR5 deficiency exacerbates cog-nitive deficits in mice by promoting neuroinflammatory responses induced by LPS.

Ferroptosis is a novel form of programmed cell death that relies on the accumulation of intracellular iron ions,causing irreversible damage to cell membranes through extensive lipid peroxidation,ultimately leading to cell death.Ferroptosis is closely associated with various neurodegenerative diseases.The ferroptosis of glial cells can regulate neuronal death by inducing neuroinflammation and affecting oxidative stress,thereby exacerbating the progression of neu-rodegenerative diseases.This review summarizes how ferroptosis occurs in different types of glial cells and its impact on neurons,aiming to deeply understand the effects of glial cell ferroptosis on neurodegenerative diseases and explore the po-tential therapeutic applications of inhibiting this process in treatment.