International Journal of Medical Sciences最新文献

Excessive exercise can lead to fatigue, consequently affect exercise performance, and further have an adverse impact to human health. The synergistic effects of ginsenosides, salidroside, and syringin on improving exercise performance remain unknown. Hence, the effects of Chinese herb powder (CHP) which consisted of bioactive compounds such as ginsenosides (Rg1, Re, and Rb1), salidroside, and syringin on exercise performance, energy metabolism, tissue damage, antioxidant activity, and inflammatory cytokine were investigated in exhaustive exercise rats. Male Sprague-Dawley rats aged of 8-week-old were randomly assigned into four groups: control (normal, N), low-dose (L, 310 mg/kg bw), medium-dose (M, 620 mg/kg bw), and high-dose (H, 1550 mg/kg bw) groups. The intervention groups were orally given CHP daily for successive 30 days. Abdominal arterial blood, liver, and gastrocnemius muscles were collected 4 hours after exhaustive exercise for further analysis. The high-dose CHP group increased the time to exhaustion, decreased serum lactate level, increased serum superoxide dismutase activity, and decreased liver interleukin-6 concentration. Therefore, CHP exhibits an anti-fatigue effect for prolonging the time to exhaustion through improving lactate clearance, and to a lesser extent, enhancing the capacity of antioxidation and anti-inflammation.

Background: Evidence increasingly indicates that HPV infection plays a pivotal role in the initiation and progression of bladder cancer (BC). Yet, determining the predictive value of HPV-associated genes in BC remains challenging. Methods: We identified differentially expressed HPV-associated genes of BC patients from the TCGA and GEO databases. We screened prognostic genes using COX and LASSO regression, subsequently establishing a risk prediction model. The model's precision and clinical relevance were gauged using Kaplan-Meier survival analyses and ROC curves. Functional enrichment, immune cell infiltration, and drug sensitivity analyses were performed across both high-risk and low-risk sets. PCR assays were utilized to measure the expression levels of genes. Results: We identified 13 HPV-associated genes for our risk model. Among these, FLRT2, HOXC5, LDLR, SCD, GRM7, DSC1, EMP1, and HMGA1 were identified as risk contributors, while LPA, SERPINA6, ZNF124, ETV7, and SCO2 were deemed protective. Cox regression analysis verified that our model provides an independent prediction of overall survival (OS) in bladder cancer (BC) patients. Gene Ontology (GO) analysis revealed predominant gene enrichment in wound healing, extracellular matrix composition, and collagen-rich extracellular matrices. KEGG pathway analysis highlighted primary enrichment areas, including focal adhesion, the PI3K-Akt signalling pathway, and ECM-receptor interaction. Risk scores were correlated with tumor microenvironment (TME) scores, immune cell infiltration, and sensitivities to both chemotherapy and immunotherapy. Conclusion: We have formulated a risk-assessment model pinpointing 13 central HPV-associated genes in BC. These genes present potential as prognostic indicators and therapeutic targets, emphasizing the intertwined relationship between HPV-induced BC progression and the immune landscape.

Coronary microembolization (CME) is defined as atherosclerotic plaque erosion, spontaneous rupture, or rupture of the plaque while undergoing interventional therapy resulting in the formation of tiny emboli that obstruct the coronary microcirculatory system. For percutaneous coronary intervention, CME is a major complication, with a periprocedural incidence of up to 25%. Recent studies have demonstrated that regulatory cell death (RCD) exerts a profound influence on CME through its modulation of inflammatory responses, oxidative stress, cell death, and angiogenesis. RCD, including apoptosis, autophagy, and pyroptosis, is a unique class of genetically highly regulated death patterns pervasive in instances of coronary microembolization. The aim of this review is to summarize the currently known molecular mechanisms underlying CME. Further investigations of the RCD mechanisms may unravel new avenues for the prevention and treatment of CME.

Allergic diseases are a group of chronic inflammatory disorders driven by abnormal immune responses. Dendritic cells (DCs) play a pivotal role in the initiation and progression of allergic diseases by modulating T cell responses. Extensive progress has been made in characterizing crucial roles of metabolic reprogramming in the regulation of immune cell functions. As the critical upstream regulators and effectors in allergic responses, the activation, migration, and function of DCs are reliant on metabolic reprogramming. In this review, we summarize the metabolic characteristics of DCs, and how the cellular microenvironment shapes DC function. We also elucidate the metabolic regulation of DC biology in the context of allergic diseases and targeted therapeutic strategies based on DC metabolism regulation. Understanding the functional alterations in DCs during allergic responses and the underlying mechanisms governing its metabolic regulation is crucial for the development of effective strategies for the prevention and treatment of allergic diseases.

Background: Worldwide, approximately 1.7 billion people are afflicted with musculoskeletal (MSK) diseases, posing significant health challenges. The introduction of single-cell RNA sequencing (scRNA-seq) technology provides novel insights and approaches to comprehend the onset, progression, and treatment of MSK diseases. Nevertheless, there is a remarkable lack of analytical and descriptive studies regarding the trajectory, essential research directions, current research situation, pivotal research focuses, and upcoming perspectives. Therefore, the aim of this research is to present a comprehensive overview of the advancements made in scRNA-seq for MSK disorders over the past 15 years. Methods: It utilizes a robust dataset derived from the Web of Science Core Collection, encompassing January 1, 2009, through September 6, 2024. To achieve this, advanced analytical methodologies were applied to conduct thorough scientometric and visual analyses. Results: The findings underscore the preeminent role of China, which contributes 63.49% of the total publications, thereby exerting a substantial impact within this research domain. Notable contributions came from institutions such as Shanghai Jiao Tong University, Sun Yat-sen University, and Harvard Medical School, with Liu Yun being the leading contributor. Frontiers in Immunology published the greatest number of research papers in this field. This study identified joint diseases, bone neoplasms, bone fractures, and intervertebral disc degeneration as the main research focuses. Conclusion: This extensive scientometric analysis provides substantial benefits to both experienced and novice researchers by facilitating immediate access to critical data, thereby fostering innovation within this field.

Objective: Chronic kidney disease (CKD) is a global health concern, and recent clinical evidence suggests the potential of traditional Chinese medicine (TCM) to slow CKD progression. This offers alternative strategies for CKD patients, mitigating risks related to polypharmacy and adverse drug reactions. Our self-controlled, prospective study aims to assess the impact of Eefooton (EFT), a TCM-based regimen, on kidney health in stage 3-5 CKD patients. Additionally, we conduct a cell culture study to explore the potential mechanisms of EFT in protecting renal function. Materials and methods: Between 2021 and 2022, 75 stage 3-5 CKD patients (56% males; mean age 68.20y) at Kaohsiung Veterans General Hospital and Wu San-Chiang Medical Clinic received six months of EFT treatment alongside conventional CKD medications. The primary outcome assessed was the change in estimated glomerular filtration rate (eGFR) at 6 months, with secondary outcomes including kidney size and blood biomarker changes. Adverse events were monitored. In an in vitro study, EFT effects on HK-2 cell viability and clonogenicity, as well as analysis of apoptosis and fibrosis-related proteins through Western blot, were investigated. Results: Median eGFR significantly improved from 34.37 ± 13.58 to 42.47 ± 18.82 mL/min/1.73 m² (p < 0.001) at month 6 post-treatment. Notably, improvements were observed across different baseline CKD stages (stage 3: p < 0.001, stage 4: p = 0.037). Ultrasonography scans indicated a slight increase in mean kidney size. In vitro, EFT enhanced HK-2 cell viability and increased clonogenicity. Indoxyl sulfate exposure raised cleaved and total PARP-1 activity. Co-treatment with EFT and IS reduced cleaved PARP-1 activity. EFT decreased IS-induced expression of fibrosis-related proteins (α-smooth muscle actin) without affecting apoptosis-related proteins (Caspase 3). Conclusions: When combined with conventional CKD medications, EFT has shown effectiveness in enhancing kidney function in individuals with stage 3-5 CKD, with no reported safety concerns. The PARP-1 inhibition and anti-fibrosis properties of EFT present potential benefits in the context of CKD.

While NUSAP1's association with various tumors is established, its predictive value for prognosis and immunotherapy in lung adenocarcinoma (LUAD) remains unconfirmed. We analyzed Nucleolar Spindle-Associated Protein 1 (NUSAP1) gene expression in TCGA and GTEx datasets and validated it in clinicopathological tissues using qRT-PCR and immunohistochemistry. Additionally, we investigated NUSAP1's relationship with patient prognosis across TCGA and five GEO cohorts. The IMvigor210 cohort was utilized to explore NUSAP1's association with immunotherapy efficacy. Furthermore, single-cell RNA-sequencing data was used to examine the correlation between NUSAP1 and immune cell infiltration. Finally, we analyzed the relationship between NUSAP1 and m6A methylation. NUSAP1 expression was significantly elevated in tumor tissues, correlating with poorer prognosis in LUAD patients. It exhibited a significant correlation with immune cell infiltration in the tumor microenvironment, predominantly expressed in Tprolif cells. LUAD patients with heightened NUSAP1 expression may derive greater benefit from anti-PD-L1 treatment. Additionally, NUSAP1 was tightly linked with m6A methylation. Enrichment analysis revealed its association with key biological functions, including lipid metabolism and cell cycle regulation. Our comprehensive analysis underscores NUSAP1's potential as a prognostic and immunotherapeutic biomarker for LUAD, warranting further investigation.

While the gluten-free diet (GFD) is primarily used to treat celiac disease (CD), recent research suggests it may also offer benefits for autoimmune-related diseases (ARDs), though findings remain inconsistent. This study aimed to investigate the potential protective effect of a GFD against ARDs by Mendelian Randomization (MR) analysis. Utilizing data from over 500,000 samples from the UK Biobank and other publicly available genome-wide association studies (GWAS), MR analysis revealed a significant negative causal relationship between GFD and the risk of developing rheumatoid arthritis (RA) (OR = 0.782, 95% CI = [0.727-0.841], p < 0.001). Mediation analysis identified immune cells such as CD14+ CD16+ monocyte absolute count (mediating 2.441% of the effect), CD14+ CD16+ monocyte percentage (2.346%), and CD20 on IgD+ CD38^dim B cells (3.119%) as potential mediators in the protective effect of GFD on RA. These findings suggest that GFD may help reduce RA risk by modulating specific immune cell populations. However, further research is necessary to clarify the exact mechanisms underlying these associations.

Background: Doublecortin-like kinase 1 (DCLK1) has been revealed to be involved in modulating cancer stemness and tumor progression, but its role in prostate cancer (PCa) remains obscure. Castration-resistant and metastatic PCa exhibit aggressive behaviors, and current therapeutic approaches have shown limited beneficial effects on the overall survival rate of patients with advanced PCa. This study aimed to investigate the biological role and potential molecular mechanism of DCLK1 in the progression of PCa. Methods: The role of DCLK1 in maintaining PCa stem cell-like properties was explored via gain- and loss-of-function studies, including colony formation assays, sphere formation assays and measurement of stemness-related marker expression. A set of transcriptomic data for patients with PCa was downloaded from The Cancer Genome Atlas to analyze the correlations between DCLK1 and Hippo pathway gene expression. The mechanism by which DCLK1 regulates Hippo signaling and cancer stemness was further investigated in vitro by methods such as Western blot analysis, quantitative real-time PCR analysis, immunofluorescence staining, and luciferase reporter assays and in vivo by animal studies. Results: The gain- and loss-of-function studies demonstrated that upregulating DCLK1 promoted but downregulating DCLK1 suppressed aspects of the PCa stem cell-like phenotype, including colony formation, sphere formation and the expression of stemness-related markers (c-Myc, OCT4, CD44, NANOG, SOX2, and KLF4). Importantly, bioinformatics analysis indicated that DCLK1 is closely correlated with the Hippo signaling pathway in PCa. Further in vitro assays revealed that DCLK1 inhibits the Hippo signaling pathway, leading to yes-associated protein (YAP) activation via large tumor suppressor homolog 1 (LATS1). Moreover, the effect of DCLK1 on abolishing stemness traits in PCa was observed after treatment with verteporfin, a small molecule inhibitor of YAP. Consistent with the in vitro findings, the in vivo findings confirmed that DCLK1 promoted the tumorigenicity and stem cell-like traits of PCa cells via Hippo-YAP signaling. Conclusion: DCLK1 promotes stem cell-like characteristics by inducing LATS1-mediated YAP signaling activation, ultimately leading to PCa tumor growth and progression. Thus, our findings identify an attractive candidate for the development of cancer stem cell-targeted therapies to improve treatment outcomes in advanced PCa.

Aim: To investigate the effects of 12-week Lepidium Meyenii extract supplementation on immune responses and inflammatory cytokines after exhaustive endurance exercise (EEE), emphasizing its novel focus on peripheral blood mononuclear cells (PBMCs) cytokine secretion and the implications of interferon-γ (IFN-γ) as a marker for immune modulation. Methods: Twenty healthy men were recruited and assigned into maca and placebo groups using a matched-pair design based on their maximal oxygen consumption (V̇O_2max). All participants consumed 2.25 g of maca or placebo twice per day for 12 weeks, and they then performed EEE. Researchers collected blood samples before exercise, immediately after exercise, and at 2, 4, and 24 hours post-exercise to analyze immune functions and inflammatory markers. Results: No significant differences were observed in the variables between the two groups before supplementation. However, interferon-γ levels from peripheral blood mononuclear cells were significantly higher in the maca group than in the placebo group immediately and at 24 hours after exercise. Regarding the main time effect, the number of lymphocytes in all participants was significantly lower at 2 and 4 hours after exercise than before supplementation. The CD4⁺/CD8⁺ ratio in the groups was significantly lower immediately after exercise than before supplementation, and the ratio retuned to baseline levels at 2 hours after exercise. Conclusion: A 60-minute EEE session induces the open window phenomenon, characterized by immune suppression. Moreover, 12-week maca supplementation had positive effects only on interferon-γ levels from peripheral blood mononuclear cells.