Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To investigate the impact of olanzapine and risperidone on the cognitive function, sensory gating function and clinical symptoms of patients with first-episode schizophrenia(FES).Additionally, to analyze the correlation between sensory gating inhibitory deficits and cognitive impairment in FES patients.Methods:A total of 71 FES patients were selected in the Third People's Hospital of Zhongshan City from March 2023 to March 2024, and 60 healthy controls were recruited during the same period.The FES patients were divided into olanzapine group and risperidone group by random number table.Olanzapine group was treated with variable doses of olanzapine(10-20 mg/d), and risperidone group was treated with variable doses of risperidone(3-6 mg/d).The MATRICS consensus cognitive battery(MCCB) was used to evaluate the cognitive function of the patients, P50 index was measured by auditory paired condition-stimulus paradigm, and the efficacy was evaluated by positive and negative syndrome scale(PANSS) score reduction rate before and after 6 weeks of treatment.Healthy controls were assessed cognitive function only once with P50.SPSS 25.0 software was used for data processing. Perform statistical analysis using paired sample t-test, Wilcoxon signed rank test, independent sample t-test, Mann Whitney U test, χ2 test and generalized linear model. Results:Before treatment, the S2 amplitude of FES (1.74 (0.91, 2.79) μV) was higher than that of healthy controls (1.70 (1.04, 2.71) μV) (Wald χ2=4.483, P=0.034), the S2/S1 ratio of FES (0.58 (0.43, 0.78)) was higher than that of healthy controls (0.41 (0.31, 0.57)) (Wald χ2=10.909, P=0.001), and the difference of FES amplitude of S1-S2 was (1.22 (0.43, 1.92) μV) was lower than that of healthy controls (2.23 (1.54, 3.07) μV) (Wald χ2=17.679, P<0.001). There was no significant difference in PANSS, MCCB and P50 between olanzapine group and risperidone group before treatment (all P>0.05). After treatment, there was no significant difference in response rate between the two groups ( χ2=0.059, P=0.808), the PANSS scores were lower than those before treatment, the MCCB test results were higher than those before treatment (both P<0.05), and the P50 results were not statistically significant different compared with those before treatment (both P>0.05). The generalized linear model showed that the S1, S2 amplitude of the P50 had positive impact on the connection test score in the MCCB test ( β=0.466, P=0.020; β=0.879, P=0.009), other indicators were not found to have an impact on the test scores of the MCCB test (all P>0.05). Conclusion:Olanzapine and risperidone can significantly improve the cognitive function of FES, but the improvement of sensory gating deficits is limited. The pathogenic mechanism of sensory gating inhibitory deficits in FES may be different from that of cognitive dysfunction.

BackgroundDementia seriously affects the quality of life and lifespan of elderly people， with Alzheimer's disease （AD） being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD， but the causal relationship between the two still requires further research. ObjectiveTo investigate the potential causal relationship between gout and AD through a two-sample Mendelian randomization （MR） analysis， so as to provide references for the prevention and treatment of AD. MethodsData from Genome-Wide Association Studies （GWAS） extracted in 2024 were analyzed， using pooled data on gout （6 810 cases in the case group and 477 788 cases in the control group） published by UK Biobank in 2021 as the exposure variable， and data on AD （3 899 cases in the case group and 214 893 cases in the control group） published by FinnGen in the same year as the outcome variable. The inverse-variance weighted， MR-Egger regression， weighted median estimation， simple model and weighted model were used to analyze the potential causal relationship between gout and AD. Pleiotropic effects were assessed using MR-Egger regression. Heterogeneity assessment was conducted using Cochran's Q test. The leave-one-out analysis was carried out for sensitivity analysis. And a funnel plot was drawn to detect potential publication bias. ResultsThe inverse-variance weighted analysis demonstrated a negative causal relationship between gout and AD （OR=0.004， 95% CI： 0~0.700， P<0.05）. The plot resembled a symmetrical inversed funnel， indicating the absence of publication bias. No heterogeneity was detected by Cochran's Q test. The MR-Egger regression indicated no significant horizontal pleiotropy. Concerning the reverse directions， no significant associations between AD and gout were noted. ConclusionThere is a negative causal relationship between gout and AD， with gout potentially reducing the risk of developing AD. ［Funded by The Third Batch of Social Welfare and Basic Research Projects （Medical and Health） of Zhongshan City in 2022 （number， 2022B3017）］