Archives of Medical Science最新文献

Introduction: Cuproptosis is an emerging form of programmed cell death that has been implicated in tumor progression. Nevertheless, the relationship between cuproptosis and the metastatic process in colorectal cancer (CRC) remains obscure, as are the underlying molecular mechanisms that drive CRC progression in this process.

Material and methods: Bioinformatics, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and Western blot (WB) were leveraged to analyze the expression levels of RBM24 in CRC. Cell Counting Kit-8 (CCK-8) assay, Transwell, and WB assays were conducted to determine the cell proliferation, migration, and invasive potential, alongside the expression analysis of metastasis-related proteins. Intracellular Cu²⁺ levels were quantified using a Copper Assay Kit. Additionally, the expression of mitogen-activated protein kinase (MAPK) pathway and cuproptosis-related proteins were probed via WB.

Results: RBM24 was under-expressed in CRC, and its forced expression inhibited the metastatic abilities of CRC cells, including migration, invasion, and epithelial-mesenchymal transition (EMT). The use of a MAPK pathway inhibitor could temper the pro-metastatic effects associated with low RBM24 levels. At the molecular level, the combination of copper ionophores with copper ions (Es-Cu) upregulated RBM24, leading to the inhibition of CRC cell spread. The effects of cuproptosis on CRC cells were abolished by knocking down RBM24.

Conclusions: Elevated levels of cuproptosis-induced cell death disrupt the MAPK signaling cascade, thus suppressing the metastasis of CRC. This discovery sheds new light on the potential application of cuproptosis in oncological treatments.

Introduction: Osteosarcoma (OS) is a highly malignant bone tumor with limited treatment options. The role of apolipoprotein E (APOE) in OS remains unclear. This study explores the impact of APOE overexpression on OS, particularly its effects on ferroptosis and autophagy.

Material and methods: APOE was identified as a key gene through weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis of the GSE28424 dataset. APOE was overexpressed in OS cell lines to evaluate its effects on cell behavior. The role of autophagy was investigated using the autophagy inhibitor 3-methyladenine (3-MA). The involvement of ferroptosis and the mTOR/Stat3 signaling pathway was investigated utilizing quantitative real-time reverse transcription PCR (qRT-PCR), Western blot (WB), and flow cytometry. A mouse xenograft model was employed to validate the in vitro results.

Results: APOE overexpression significantly inhibited OS cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT), with 3-MA partially reversing these effects. APOE overexpression also inhibited the mTOR and Stat3 expression, enhancing autophagy, as shown by increased LC3B-1, LC3B-2, and Beclin1 expression. Additionally, APOE overexpression promoted apoptosis, associated with increased reactive oxygen species (ROS) and intracellular Fe²⁺ levels, and altered ferroptosis-related gene expression, including upregulation of TfR1 and downregulation of FPN, GPX4, and SLC7A11. In vivo, APOE overexpression in a mouse xenograft model resulted in significantly smaller tumors, with changes in autophagy and ferroptosis markers consistent with in vitro findings.

Conclusions: APOE overexpression suppresses osteosarcoma growth by promoting ferroptosis and autophagy through the mTOR/Stat3 signaling pathway, highlighting its promise as a target for OS therapeutic intervention.

Introduction: Lipid metabolism is pivotal in diabetic retinopathy (DR) development. Nevertheless, the relationship between lipid-lowering drugs and the risk of DR remains a topic of debate. This study employed Mendelian randomization (MR) to investigate the potential effects of pharmacological lipid-lowering targets on DR and to clarify the causal association between blood lipid characteristics and DR.

Material and methods: The data comprised genetic variations related to lipid traits and genetic variations associated with lipid-lowering drug targets obtained from the Global Lipid Consortium. Total DR, non-proliferative DR (NPDR), and proliferative DR (PDR) were sourced from the Finnish R9 database. Lipid-lowering drug targets were tested using inverse variance-weighted MR (IVW-MR) and statistics-based MR (SMR). Colocalization and mediation analysis were conducted to validate the results and explore potential mediating factors.

Results: A reduced risk of total DR and NPDR was associated with genetically improved 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (OR = 0.62; 95% CI: 0.46-0.83; p = 1.30 × 10^-2; OR = 0.49; 95% CI: 0.34-0.70; p = 9.70 × 10^-4). Strong colocalization (PP.H4 = 0.85) was observed between whole blood tissue HMGCR expression and a significant MR relationship with total DR (OR = 0.66; ‌95% CI: 0.52-0.85; p = 7.31 × 10^-4). Furthermore, body mass index (BMI) and glycated hemoglobin (HbA_1c) are critical factors that mediate the impact of HMGCR and apolipoprotein B (APOB) on DR risk.

Conclusions: This Mendelian randomization study suggests that abnormalities in triglyceride (TG) levels serve as a pathogenic element in DR. Of the nine lipid-lowering drug targets assessed, HMGCR and APOB have emerged as potential promising targets for managing NPDR. These findings underscore the importance of controlling both BMI and HbA_1c levels to optimize outcomes in diabetic patients at risk for DR. The therapeutic mechanisms of HMGCR and APOB in DR go beyond lipid lowering alone, and a multimodal lipid-lowering strategy should be selected early and comprehensively to address the patient's medical conditions.

Introduction: Single-bundle autologous hamstring tendon reconstruction is a surgical procedure used primarily in orthopedics. The aim of the study was to investigate the impact of using autologous hamstring tendon single-bundle restoration in conjunction with braided threads on both joint stability and clinical efficacy in patients suffering from posterior cruciate ligament (PCL) rupture.

Material and methods: In total, 106 patients diagnosed with PCL rupture were randomly assigned to the control group and study group, each group consisting of 53 patients. The control group received autologous hamstring tendon single-bundle reconstruction, whereas the study group received autologous hamstring tendon single-bundle reconstruction together with braided thread treatment. The comparative rates of treatment success and satisfaction, complication occurrence, pre-and post-surgery joint activity indicators, gait parameters, knee joint function, and joint stability were assessed.

Results: The study group showed a significantly higher rate of excellent and good treatment outcomes compared to the control group (p < 0.05). Twelve months after surgery, the study group showed significantly higher joint activity index, stride length, stride speed, and Rasmussen score compared to the control group.

Conclusions: The single-bundle reconstruction combined with braided thread has good clinical efficacy in patients with PCL rupture and more effectively improves the patient's joint stability.

Introduction: This study aimed to investigate the relationship between serum cytokine levels, particularly interleukin 6 (IL-6), and diabetic nephropathy (DN) in patients with type 1 (T1D) and type 2 diabetes (T2D).

Material and methods: A cross-sectional study was conducted among 200 patients diagnosed with either T1D or T2D from January 2022 to December 2023 at the Endocrinology and Diabetes Department of Madinah Hospital, Saudi Arabia.

Results: A total of 200 individuals with T1D (n = 100) or T2D (n = 100) were enrolled in this research. Male patients (54%) and those aged 30-50 (67.5%) dominated the cohort. About 50% had diabetes for less than 10 years, and 49.5% were overweight. 63.5% (n = 117) had a reduced glomerular filtration rate (GFR), whereas 46% (n = 92) had albuminuria. T1D patients were mostly normal weight, while T2D patients were overweight or obese. Both diabetes types had identical kidney damage stages. T1D patients were more likely to have moderately elevated albuminuria (53% vs. 37%, p < 0.05) than T2D individuals. T1D patients had considerably lower serum cytokine levels than T2D patients. IL-6 levels were moderately correlated with fasting blood glucose (FBG) (r = -0.318, p < 0.01) and HbA_1c (r = -0.319, p < 0.01) in T1D patients. IL-6 had a modest correlation with renal dysfunction markers including GFR and urine albumin-creatinine ratio (UACR) (r = -0.250, p < 0.05 and r = 0.338, p < 0.001, respectively). In T1D patients there was a weak but significant correlation between GFR and IL6.

Conclusions: Lower serum IL-6 levels in T1D patients are linked to delayed onset of kidney damage. The pro-inflammatory role of IL-6 may contribute to the development of DN in T1D patients, as indicated by its association with albuminuria and renal function markers. Further research is warranted to explore IL-6 as a potential therapeutic target in diabetic nephropathy.

Introduction: Withaferin-A (WA) derived from natural products can inhibit the growth and metastasis of colorectal cancer (CRC) in vitro and in vivo.

Material and methods: WA effects on colorectal cancer cells were studied using HCT116 and SW480 lines. In vitro we used shRNA knockdown, plasmid overexpression, viability, proliferation, colony, migration, and invasion assays. And Xenograft and metastasis mouse models evaluated tumor growth and toxicity. Molecular analysis used qRT-PCR, Western blot, IHC, immunoprecipitation, and RNA sequencing.

Results: Transcriptome analysis showed WA suppressed EMT, HSP90, and HIF-1α in CRC. WA inhibited HSP90, HIF-1α, E-cadherin, and their interaction. HIF-1α knockdown reduced CRC migration, invasion, and lung metastasis. 17-AAG similarly inhibited HSP90/HIF-1α and metastasis. HSP90 overexpression rescued HIF-1α expression, binding, and migratory ability in HIF-1α knockdown cells.

Conclusions: These findings indicate that WA inhibits CRC's growth, migration, and invasion by inhibiting the HSP90/HIF-1α/EMT axis. And showed that WA could be a potential therapeutic agent for CRC.