Chu Y, Zhu J, Liu Z
… +4 more, Liao F, Yao Y, Wu W, Song K
Arch Med Sci
· 2026 Jan · PMID 42110599
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INTRODUCTION: The causal relationship between type 1 diabetes mellitus (T1DM) and osteoporosis has not been clarified in large prospective cohort studies. This study aimed to assess the causal association between T1DM an...INTRODUCTION: The causal relationship between type 1 diabetes mellitus (T1DM) and osteoporosis has not been clarified in large prospective cohort studies. This study aimed to assess the causal association between T1DM and osteoporosis, and further identify eligible mediators. MATERIAL AND METHODS: We explored the causal relationship between T1DM and osteoporosis by two-sample Mendelian randomization (MR), a method that uses genetic variants as instrumental variables for causal inference. We selected five candidate mediators based on their relevance to metabolic processes in T1DM and bone health, including body mass index (BMI), glycated hemoglobin (HbA1c), cholesterol in medium very low-density lipoprotein particles (M-VLDL-C), saturated fatty acids (SFA), and sex hormone-binding globulin (SHBG), and identified eligible mediators by two-step MR. We validated the correlation of T1DM and mediators with osteoporosis in a UK Biobank (UKB) prospective cohort study. RESULTS: In MR analysis, T1DM was related to a significantly increased risk of osteoporosis (OR = 1.046, 95% CI: 1.015 to 1.079, = 0.004). In two-step MR, T1DM was significantly associated with decreased levels of M-VLDL-C and SFA and increased levels of SHBG, but showed no significant effect on BMI or HbA1c. Furthermore, lower levels of M-VLDL-C and higher levels of SHBG, but not SFA, were significantly associated with an elevated risk of osteoporosis. Hence M-VLDL-C and SHBG were identified as eligible mediators. In the UKB cohort study, consistent results were found. CONCLUSIONS: T1DM may cause osteoporosis by reducing M-VLDL-C and increasing SHBG levels in plasma. The identified mediators may serve as important biomarkers for early detection and treatment of osteoporosis in T1DM patients.
Arch Med Sci
· 2026 Jan · PMID 42110596
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Early diagnosis is crucial for improving the prognosis of lung cancer, one of the leading causes of cancer-related deaths. Lung cancer includes small cell lung cancer (SCLC, ~15% of cases) and non-small cell lung cancer...Early diagnosis is crucial for improving the prognosis of lung cancer, one of the leading causes of cancer-related deaths. Lung cancer includes small cell lung cancer (SCLC, ~15% of cases) and non-small cell lung cancer (NSCLC, ~80-85%). Prognosis depends on the stage at diagnosis: the 5-year survival rate is 65% for localized NSCLC but only 9% for distant-stage disease. Radiologists face challenges distinguishing benign from malignant pulmonary nodules on computed tomography scans. This review explores deep learning (DL) methods, including multi-view convolutional neural networks (CNNs) and 3D models for nodule segmentation, emphasizing volumetric assessments for malignancy prediction. CNNs effectively analyze CT data, achieving 94.2% sensitivity with 1.0 false positives per scan in lung nodule detection. DL enhances diagnostic accuracy, reduces radiologist workload, and enables earlier lung cancer detection. Further research is needed to improve model adaptability across diverse clinical settings.
Białecka M, Białecka M, Machoy-Mokrzyńska A
… +2 more, Malinowski D, Rać M
Arch Med Sci
· 2026 Jan · PMID 42110595
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Cytokines are small, membrane-bound, protein-based cell signaling molecules that aid cell-to-cell communication in physiological and pathological processes. TNF-α is a pleiotropic cytokine that is regarded as a principal...Cytokines are small, membrane-bound, protein-based cell signaling molecules that aid cell-to-cell communication in physiological and pathological processes. TNF-α is a pleiotropic cytokine that is regarded as a principal cytokine in the acute and chronic phases of the immune and inflammatory responses. TNF-α has been demonstrated to play a role in neuroplasticity and myelination, as well as excitotoxicity, neuroinflammation, and damage to the blood-brain barrier. The involvement of TNF-α in the etiology of Parkinson's disease, both in its early and late stages, Alzheimer's disease, multiple sclerosis, and coronary artery disease has been substantiated using both experimental models and clinical studies. TNF also plays a key role in cardiovascular disease, initiating a cascade of inflammatory and vascular responses. The aim of this study was to clarify the molecular mechanisms of TNF action and the effects of its secretion in selected diseases.
Naveed MA, Ali A, Ahmed M
… +12 more, Razzak MJ, Muhammad OR, Zafar MNU, Hasan M, Iqbal R, Azeem B, Naveed H, Sandhyavenu H, Munir MB, Almahmeed W, Neppala S, Banach M
Arch Med Sci
· 2026 Jan · PMID 42110594
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INTRODUCTION: Cardiac arrest (CA) is a leading cause of death in the US, with over 600,000 cases annually. People with diabetes mellitus (DM) have higher CA risk and worse outcomes due to factors such as obesity, hyperte...INTRODUCTION: Cardiac arrest (CA) is a leading cause of death in the US, with over 600,000 cases annually. People with diabetes mellitus (DM) have higher CA risk and worse outcomes due to factors such as obesity, hypertension, and dyslipidemia. This study examined the mortality trends of CA among adults with diabetes from 1999 to 2024. MATERIAL AND METHODS: We analyzed data from the CDC WONDER multiple-cause-of-death database, identifying decedents aged ≥ 25 years with both CA and DM listed as underlying or contributing causes of death (ICD-10: I46.0 to I46.9 for CA; E10-E14 for DM). Annual crude and age-adjusted mortality rates were calculated. Joinpoint regression was used to identify trend changes and calculate annual percent changes (APC) and average annual percent changes (AAPC). RESULTS: Between 1999 and 2024, a total of 1,146,259 deaths were recorded. Overall, the age-adjusted mortality rate (AAMR) decreased from 21.3 per 100,000 in 1999 to 18.3 in 2024 with an AAPC of -0.69. However, a significant increase occurred from 2018 to 2021 (APC: +11.02), coinciding with the COVID-19 pandemic. Men exhibited higher AAMRs than women (23.9 and 16.1, respectively), and non-Hispanic Black individuals had the highest racial AAMRs at 37.1. Geographic disparities revealed the Western U.S. to have the highest mortality rate at 29, and urban areas to have slightly higher AAMRs than rural areas (19.4 vs. 18.7). CONCLUSIONS: While CA-related mortality among diabetic adults decreased from 1999 to 2018, a rise between 2018 and 2021 highlights vulnerabilities, especially among men, non-Hispanic Black populations, and high-burden regions. Continued efforts are necessary to address healthcare disparities and enhance emergency responses, thereby reducing mortality gaps.
INTRODUCTION: Chronic respiratory diseases represent a significant global health burden, characterized by high incidence and mortality rates. However, the potential associations between physical activity, leisure sedenta...INTRODUCTION: Chronic respiratory diseases represent a significant global health burden, characterized by high incidence and mortality rates. However, the potential associations between physical activity, leisure sedentary behavior, and susceptibility to chronic respiratory diseases remain uncertain. MATERIAL AND METHODS: A two-sample Mendelian randomization approach was used in this investigation, using physical activity and leisure sedentary behavior as exposures, and common chronic respiratory diseases such as asthma, bronchiectasis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, and obstructive sleep apnea syndrome as outcomes, to explore the genetic causal relationships. We utilized genome-wide association studies to select genetic instrumental variables related to these exposures. These variables were then used to assess the impact of physical activity and leisure sedentary behavior on the susceptibility to chronic respiratory diseases. RESULTS: Our findings indicate that strenuous sports or other exercises and vigorous physical activity are protective factors against asthma, whereas leisure-time television watching is a risk factor. Frequent leisure-time television watching is closely associated with an increased susceptibility to chronic obstructive pulmonary disease. Leisure-time computer use and overall average acceleration in physical activity are inversely related to the risk of developing pulmonary arterial hypertension. Higher engagement in driving and vigorous physical activity are causally associated with a reduced risk of obstructive sleep apnea syndrome. CONCLUSIONS: Our analysis supports the causal relationships between physical activity, sedentary behavior, and chronic respiratory diseases, providing genetic evidence that supports lifestyle modifications to reduce susceptibility to these conditions.
INTRODUCTION: Liver fibrosis is a reversible wound-healing response to acute or chronic liver injury. Liver cirrhosis is the advanced stage of liver fibrosis. This study explored the causal associations of sex hormones -...INTRODUCTION: Liver fibrosis is a reversible wound-healing response to acute or chronic liver injury. Liver cirrhosis is the advanced stage of liver fibrosis. This study explored the causal associations of sex hormones - estradiol, bioavailable testosterone, total testosterone, and sex hormone-binding globulin (SHBG) - and adiponectin with liver fibrosis, cirrhosis, and primary biliary cirrhosis (PBC). MATERIAL AND METHODS: A two-sample Mendelian randomization (MR) study using publicly available data was performed. Causal estimates were calculated by the inverse variance weighted (IVW) method, and additional approaches such as MR-Egger, weighted median, simple mode, and weighted mode were used to complement the IVW approach. Sensitivity analysis was performed employing leave-one-out analysis. RESULTS: The IVW analysis revealed a relationship between genetically predicted total testosterone levels and the likelihood of fibrosis and cirrhosis in females; odds ratio (OR) = 1.537, 95% confidence interval (CI): 1.082-2.182. There was a significant association between genetically predicted estradiol levels and an increased risk of liver fibrosis and cirrhosis (OR = 2.287, 95% CI: 1.403-3.727) and PBC (OR = 3.075, 95%CI: 1.306-7.240) in males. Our findings indicated that genetically predicted adiponectin was causally related to fibrosis and cirrhosis (OR = 1.608, 95% CI: 1.063-2.430) and PBC (OR = 2.631, 95% CI: 1.211-5.715). MR-Egger, weighted median, simple mode and weighted mode consistently yielded similar outcomes. Cochrane's Q test showed no heterogeneity in these instrumental variables, and there was no significant directional pleiotropy. CONCLUSIONS: There were positive causal associations of total testosterone with fibrosis and cirrhosis among females, and of estradiol levels with liver fibrosis and cirrhosis and PBC in males. Higher adiponectin could increase the risk of fibrosis and cirrhosis and PBC.
INTRODUCTION: The study aimed to explore the causal association between genetically predicted sleep traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness, and sleep a...INTRODUCTION: The study aimed to explore the causal association between genetically predicted sleep traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness, and sleep apnea syndrome) and diabetic nephropathy (DN). MATERIAL AND METHODS: A two-sample Mendelian randomization (MR) design was used to analyze summary data from genome-wide association studies of sleep traits and DN. The main analysis was conducted using the inverse variance weighted (IVW) method, and robustness was tested using the weighted median, weighted mode, and MR-Egger regression methods. Heterogeneity was detected using Cochran's Q-test, horizontal pleiotropy using the MR-Egger regression method, potential outliers using MR-PRESSO, and single-nucleotide polymorphisms driving the results using a leave-one-out analysis. RESULTS: The genetic prediction results indicated no statistically significant associations between the sleep traits and DN (all IVW > 0.05). However, the weighted median analysis showed a possible causal association between long sleep and DN (OR < 0.01, 95% CI: 0-0.70, = 0.04) and a borderline possible causal association between sleep apnea syndrome and DN (OR = 2.50, 95% CI: 0.99-6.35, = 0.05). Cochran's Q-test indicated possible heterogeneity for the sleep duration analysis ( = 0.01), but no horizontal pleiotropy or outliers were detected (all > 0.05). CONCLUSIONS: This MR analysis suggested no causal associations between the sleep traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness, and sleep apnea syndrome) and DN. Further in-depth research is needed to examine the relationship between sleep and DN.
This state-of-the-art review surveys the rapidly advancing field of triglyceride-lowering therapies as of 2025, positioning hypertriglyceridemia (HTG) as both a residual driver of atherosclerotic cardiovascular disease (...This state-of-the-art review surveys the rapidly advancing field of triglyceride-lowering therapies as of 2025, positioning hypertriglyceridemia (HTG) as both a residual driver of atherosclerotic cardiovascular disease (ASCVD) and a key precipitant of acute pancreatitis. After outlining the pathophysiological role of elevated triglycerides - via remnant lipoproteins, inflammation and endothelial dysfunction, often within the lipid triad of low high-density lipoprotein-cholesterol (HDL-C) and small, dense low-density lipoprotein (LDL) - we evaluate established and emerging pharmacologic options. Fenofibrate, a PPAR-α activator, remains a cornerstone for mixed dyslipidemia, improving micro- and macrovascular outcomes in diabetes. Purified eicosapentaenoic acid (icosapent ethyl) is highlighted for its robust reduction of major adverse cardiovascular events despite neutral triglyceride thresholds, albeit with a modest increase in atrial fibrillation risk. Novel agents targeting apolipoprotein C-III (volanesorsen, olezarsen, plozasiran) achieve profound triglyceride declines and substantially mitigate pancreatitis in familial chylomicronemia syndrome (FCS), while angiopoietin-like 3 (ANGPTL3) inhibitors and fibroblast growth factor 21 (FGF21) agonists demonstrate early promise in broad atherogenic-lipid reduction and metabolic modulation. The paper emphasizes the importance of genetic testing to differentiate FCS from multifactorial chylomicronemia syndrome, guiding personalized therapy. Current guidelines endorse icosapent ethyl and fenofibrate for high-risk HTG, with apoC-III inhibitors poised to become first-line for FCS as access improves. Ongoing trials of ANGPTL3 inhibitors, FGF21 agonists and gene-editing approaches may soon redefine lifelong lipid management.
INTRODUCTION: Given insulin resistance's (IR) critical role in metabolic pathophysiology, this study aims to identify optimal coffee consumption patterns by timing and dose to improve population health. MATERIAL AND METH...INTRODUCTION: Given insulin resistance's (IR) critical role in metabolic pathophysiology, this study aims to identify optimal coffee consumption patterns by timing and dose to improve population health. MATERIAL AND METHODS: Multivariate logistic regression and restricted cubic splines assessed associations between coffee timing, dosage, and IR (measured by estimated glucose disposal rate) from NHANES data (1999-2018). Interaction and subgroup analyses explored variations across population segments. RESULTS: We analysed 21,138 participants, of whom 46.79% were non-consumers. Among consumers, 76% primarily drank coffee in the morning. Morning consumption at the lowest quartile (Q1) showed significant improvement in IR (odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.16-1.62), although this benefit diminished with higher consumption levels ( < 0.05). While the "all-day" pattern overall showed a non-significant trend toward improved insulin resistance (OR = 1.20, 95% CI: 0.83-1.73), higher consumption within this pattern (Q3: OR = 1.46, 95% CI: 1.13-1.89; Q4: OR = 1.34, 95% CI: 1.11-1.63) proved significantly more beneficial than lower intake. Comparative analysis revealed that morning consumption tended to be more advantageous for low-to-moderate intake (Q1-Q2), whereas all-day distribution showed potential benefits at higher consumption levels (Q3-Q4). The observed benefits were primarily associated with caffeinated coffee, attenuated by sugar addition, and varied across subgroups based on age, sex, and comorbidities. CONCLUSIONS: Both morning and all-day coffee intake improve IR. For moderate consumption (1-2 cups/day), morning intake provides optimal improvement in insulin sensitivity. For higher intake (≥ 3 cups/day), distributed consumption is more effective. These findings support chrono-nutrition principles for optimising metabolic health through coffee consumption.
INTRODUCTION: Osteosarcoma (OS) is a highly malignant bone tumor with limited treatment options. The role of apolipoprotein E () in OS remains unclear. This study explores the impact of overexpression on OS, particularl...INTRODUCTION: Osteosarcoma (OS) is a highly malignant bone tumor with limited treatment options. The role of apolipoprotein E () in OS remains unclear. This study explores the impact of overexpression on OS, particularly its effects on ferroptosis and autophagy. MATERIAL AND METHODS: 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. 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 results. RESULTS: overexpression significantly inhibited OS cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT), with 3-MA partially reversing these effects. overexpression also inhibited the mTOR and Stat3 expression, enhancing autophagy, as shown by increased LC3B-1, LC3B-2, and Beclin1 expression. Additionally, overexpression promoted apoptosis, associated with increased reactive oxygen species (ROS) and intracellular Fe² levels, and altered ferroptosis-related gene expression, including upregulation of and downregulation of , , and . , overexpression in a mouse xenograft model resulted in significantly smaller tumors, with changes in autophagy and ferroptosis markers consistent with findings. CONCLUSIONS: 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: Low back pain (LBP) is a common condition and the leading cause of disability worldwide. Medical students may be at higher risk due to prolonged sitting and stress. The aim of this study was to examine the...INTRODUCTION: Low back pain (LBP) is a common condition and the leading cause of disability worldwide. Medical students may be at higher risk due to prolonged sitting and stress. The aim of this study was to examine the prevalence of LBP and disability among Polish medical students and identify associated risk factors. MATERIAL AND METHODS: In this study, 533 medical students, predominantly female (66.4%), with a median age of 22, were surveyed via an online questionnaire. The survey used the Oswestry Disability Index (ODI) and Patient Health Questionnaire (PHQ-9) to evaluate LBP and depression symptoms. Demographic data and information on smoking, exercise, sitting duration, spine posture, past and present LBP, pain duration, intensity, and analgesic use were also collected. RESULTS: Point prevalence LBP was 70.95%, while 78.26% of participants reported past history of LBP. The median LBP intensity measured with the Numeric Rating Scale (NRS) was 3, and the median ODI score was 10%. Overall, female medical students suffered more from LBP than males (66.4% vs. 33.6%). The following LBP risk factors were identified in the studied group: past episodes of LBP (OR = 2.92), sitting 8 h/day (OR = 2.44), as well as 10 h or more (OR = 2.95), moderate and severe depression symptoms (OR = 2.51, OR = 7.33 respectively). CONCLUSIONS: Prevalence of low back pain among medical students in the studied group is high, resulting in mild disability, with females experiencing more severe symptoms than males. Past LBP episodes, sitting 8 h or more, and depression symptoms are independent risk factors for development of LBP among Polish medical students.
INTRODUCTION: Meningioma, a prevalent intracranial tumor, presents diagnostic and therapeutic challenges due to its heterogeneous nature. Metabolic profiling has emerged as a promising approach to elucidate its underlyin...INTRODUCTION: Meningioma, a prevalent intracranial tumor, presents diagnostic and therapeutic challenges due to its heterogeneous nature. Metabolic profiling has emerged as a promising approach to elucidate its underlying molecular mechanisms and discover potential biomarkers. MATERIAL AND METHODS: This study employed bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between plasma metabolites and meningioma risk. Genetic instruments were used as surrogates for both plasma metabolites and meningioma, allowing MR analysis in both directions to assess the impact of metabolites on meningioma risk and vice versa. This study encompassed data on 1400 plasma metabolites and 314,708 participants (1316 individuals diagnosed with meningioma and 313,392 individuals without meningioma). RESULTS: Initially, 46 plasma metabolites/metabolite ratios were found to be associated with meningioma risk ( < 0.05), with 23 associated with a decreased risk and 23 associated with an increased risk of meningioma. Furthermore, the identified relationships between the 46 plasma metabolites/metabolite ratios and meningioma showed no significant horizontal pleiotropy ( > 0.05), suggesting that the results are not influenced by other confounding factors. Reverse MR analysis revealed that meningioma has no significant impact on the levels of 24 plasma metabolites/metabolite ratios, and is unaffected by confounding factors. In addition, the identified plasma metabolites influence the occurrence of meningioma through nine metabolic pathways. CONCLUSIONS: The findings of this bidirectional MR study indicate that 24 plasma metabolites/metabolite ratios lead to a significantly increased/decreased risk of meningioma, suggesting that the plasma metabolite profile characteristics serve as important serological tools for the early diagnosis of meningioma.
Balwicki Ł, Klimiuk KB, Miller M
… +9 more, Szurowska E, Kasza N, Bidzińska J, Didkowska J, Cedzyńska M, Czajkowska-Malinowska M, Zdrojewski T, Jassem J, Rzyman W
Lung cancer, the leading cause of cancer-related deaths globally and in Poland, accounts for 25% of all cancer-related deaths, with smoking being its predominant cause. While primary prevention through smoking cessation...Lung cancer, the leading cause of cancer-related deaths globally and in Poland, accounts for 25% of all cancer-related deaths, with smoking being its predominant cause. While primary prevention through smoking cessation is crucial, the effectiveness of lung cancer screening (LCS) with low-dose computed tomography in reducing mortality has gained international recognition. This expert consensus, developed through multidisciplinary collaboration, proposes a comprehensive framework for smoking cessation interventions within LCS. Key recommendations include providing participants with educational materials, cognitive-behavioral counseling, and pharmacotherapy. Proactive follow-up, biochemical addiction validation, and teleconsultations are essential to ensure long-term cessation. Besides, participants should be discouraged from using alternative nicotine products, such as heated tobacco or electronic cigarettes due to their limited efficacy, highly probable health risks and potential for nicotine addiction. By integrating evidence-based cessation methods, LCS programs can serve as a model for broader smoking cessation strategies in healthcare.
In recent years, the relationship between microbiota and various aspects of health has become a focal point for scientific investigation. The complex interplay between microbial communities and the development, progressi...In recent years, the relationship between microbiota and various aspects of health has become a focal point for scientific investigation. The complex interplay between microbial communities and the development, progression, and treatment of gynaecological malignancies is a burgeoning field not yet fully understood. Recent research indicates that gut, vaginal, and uterine microbiota play a critical role in the response to treatments of ovarian cancer, and particularly in chemotherapy, anti-angiogenic therapy, and PARP inhibitors. Microbiota and microbial metabolites can modulate immune responses, drug metabolism, and angiogenesis, affecting the outcomes of therapy. This review explores the relationship between microbiota and anticancer therapies, and discusses the connection between dysbiosis and treatment resistance, highlighting the potential of microbiota as biomarkers and therapeutic targets in ovarian cancer treatment.
INTRODUCTION: Type 2 diabetes (T2D) and mild cognitive impairment (MCI) are interrelated conditions that significantly impair quality of life. This study aimed to identify a feasible biomarker for assessing T2D-MCI risk...INTRODUCTION: Type 2 diabetes (T2D) and mild cognitive impairment (MCI) are interrelated conditions that significantly impair quality of life. This study aimed to identify a feasible biomarker for assessing T2D-MCI risk and to evaluate a potential therapeutic strategy. MATERIAL AND METHODS: We integrated data from the National Health and Nutrition Examination Survey (NHANES) with Mendelian randomization (MR) to investigate genetic causal relationships between T2D, MCI, and their shared biomarkers. Transcriptomic analysis identified T2D-associated genes. Clinical trials evaluated the short-term effects of modified fasting therapy (MFT) on glucose regulation and cognitive function. Cellular assays and patient samples were used to validate the regulatory roles of key genes in biochemical markers and downstream signaling pathways. RESULTS: Among 6,356 T2D and 1,138 MCI subjects, vitamin D, high-density lipoprotein cholesterol (HDL-C), globulin, and creatinine were associated with both conditions. MR analysis showed that higher HDL-C levels reduced T2D risk (0.9059, 95% CI: 0.8666-0.9470) but increased MCI risk (OR = 1.0482, 95% CI: 1.0216-1.0755). Nuclear factor I A () was identified as a key HDL-C regulator. In a clinical cohort (17 T2D patients and 23 controls), MFT reduced body mass index fasting glucose and HDL-C, increased expression, and improved Montreal Cognitive Assessment scores, especially in T2D-MCI patients. HDL-C rebounded at 6 months. overexpression increased intracellular HDL-C and suppressed NF-κB signaling, while knockdown reduced APOA1 and APOE. CONCLUSIONS: HDL-C has divergent genetic effects on T2D and MCI. modulates HDL-C and NF-κB activity, supporting metabolic and cognitive improvements. Targeting through MFT may represent a promising strategy for T2D-MCI prevention and treatment.
INTRODUCTION: Bladder cancer is a highly recurrent malignancy and frequently shows drug resistance. Although gemcitabine initially works well for most patients, the majority of treated patients progressively generate res...INTRODUCTION: Bladder cancer is a highly recurrent malignancy and frequently shows drug resistance. Although gemcitabine initially works well for most patients, the majority of treated patients progressively generate resistance after multiple rounds of therapy, eventually leading to tumor recurrence. Recent studies suggest that a small subpopulation of cancer cells with stem cell-like properties - cancer stem cells - may be responsible for chemoresistance and tumor recurrence. Circular RNAs (circRNAs) are novel non-coding RNAs with great potential as cancer therapy. MATERIAL AND METHODS: The levels of circRNA_103809 in bladder cancer cells and a normal urothelial cell line were measured by quantitative polymerase chain reaction (qPCR). Bladder cancer cells were depleted of circRNA_103809, then and cell growth, migration, invasion, sphere formation ability, and resistance to gemcitabine were analyzed. The biomarkers of cell migration, invasion, and stemness were detected by western blotting assay. The interaction between miR-516a with circRNA_103809 or FBXL18 3'UTR was detected by luciferase reporter gene assay and an RNA pulldown experiment. RESULTS: Depletion of circRNA_103809 significantly suppressed the viability of bladder cancer cells, reduced cell migration and invasion, increased sensitivity to gemcitabine, and repressed cancer cell stemness. Further investigation of the molecular mechanism revealed that circRNA_103809 interacted with miR-516a to modulate the expression of FBXL18 in bladder cancer cells. CONCLUSIONS: CircRNA_103809 acts as a potential promoter of bladder cancer through sponging miR-516a to upregulate FBXL18. Our findings identify circRNA_103809 as a potential target for bladder cancer therapy.