Bosnian Journal of Basic Medical Sciences (BJBMS)
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Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation
Full text linkST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1), a crucial enzyme for tumor-associated sialic acid modification, has been reported to positively correlate with colorectal cancer (CRC) tumorigenesis; however, the underlying mechanism remains unclear. To elucidate the protumor mechanisms of ST6GAL1, we performed transcriptomic and N-glycoproteomic analyses and in vitro assays. We found that ST6GAL1 was significantly upregulated in tumor samples than in matched normal samples by analyzing fresh clinical samples from public databases (mean mRNA expression level: tumor vs. normal samples = 0.002712:0.000966, P < 0.05, n = 22). The in vitro results revealed that ST6GAL1 overexpression promoted CRC cell proliferation, migration, and chemoresistance, which were significantly blocked by its knockdown. Transcriptomic data showed that many genes related to the four modules (proliferation/cell cycle, migration, motility, and epithelial–mesenchymal transition (EMT) were upregulated after ST6GAL1 overexpression but downregulated after ST6GAL1 knockdown. Furthermore, the N-glycoproteomic data revealed that 25 substrates that were sialylated upon ST6GAL1 overexpression were related to protumor activity. Importantly, we found that knockdown of lectin galactoside-binding soluble 3-binding protein (LGALS3BP), a newly identified secreted substrate of ST6GAL1, significantly blocked the proliferation, invasion, and chemoresistance of CRC cells induced by ST6GAL1 overexpression. Treatment with sialidases (neuraminidases, NAs) also blocked the protumor activity of ST6GAL1. Thus, ST6GAL1-induced increased sialylation of substrates, such as LGALS3BP and upregulation of protumor genes promote CRC tumorigenesis and chemoresistance, which provides important perspectives and new targets for the treatment of CRC
Fecal microbiota transplantation alleviates radiation enteritis by modulating gut microbiota and metabolite profiles
Full text linkThis study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail
The influence of sodium-glucose co-transporter-2 inhibitors on the risk of cancer therapy-related cardiac dysfunction: A meta-analysis
Full text linkCancer therapy-related cardiac dysfunction (CTRCD) is a major concern for patients undergoing cardiotoxic cancer treatments. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown cardioprotective effects in both diabetic and non-diabetic populations. However, their impact on CTRCD risk remains uncertain. This meta-analysis aimed to assess the association between SGLT2 inhibitor use and CTRCD in cancer patients receiving cardiotoxic treatments. A systematic search of PubMed, Embase, and Web of Science was conducted to identify relevant studies. Cohort studies comparing CTRCD incidence in cancer patients with and without SGLT2 inhibitor use were included. Risk ratios (RRs) were pooled using a random-effects model, and subgroup and meta-regression analyses were performed to explore potential effect modifiers. Ten cohort studies involving 34,847 cancer patients met the inclusion criteria. Overall, SGLT2 inhibitor use was associated with a significantly reduced risk of CTRCD (RR: 0.47, 95% confidence interval: 0.33–0.68, P < 0.001), though significant heterogeneity was observed (I² = 70%). Subgroup analysis indicated a stronger protective effect in patients receiving anthracyclines (RR: 0.26) compared to those undergoing other treatments (RR: 0.73, P for subgroup difference = 0.001). Additionally, the cardioprotective effect was more pronounced in cohorts with a lower proportion of men (<55%, RR: 0.27) compared to those with a higher proportion (≥55%, RR: 0.75, P < 0.001). Sensitivity analyses, conducted by excluding one study at a time, consistently supported these findings, reinforcing their robustness. In conclusion, SGLT2 inhibitor use is associated with a lower risk of CTRCD in cancer patients, particularly those receiving anthracyclines. These findings highlight the potential role of SGLT2 inhibitors in mitigating cardiotoxicity during cancer therapy
Genomic correlation, shared loci, and causal link between obesity and diabetic microvascular complications: A genome-wide pleiotropic analysis
Full text linkObservational studies have identified a connection between obesity and microvascular complications in diabetes, yet the genetic contributions to their co-occurrence remain incompletely understood. Our research aims to explore the shared genetic architecture underlying both conditions. We employed linkage disequilibrium score regression (LDSC) and Local Analysis of [co]Variant Association (LAVA) to assess genetic correlations between obesity and diabetic microvascular complications. To validate shared genetic regions, we conducted pleiotropic analysis under the composite null hypothesis (PLACO), functional mapping and annotation (FUMA), and colocalization analysis. Additionally, we applied Multimarker Analysis of GenoMic Annotation (MAGMA), Summary-based Mendelian Randomization (MR), multi-trait colocalization, and enrichment analysis to identify potential functional genes and pathways. Finally, MR and latent causal variable (LCV) analysis were used to clarify causal and pleiotropic relationships across trait pairs. Among 21 trait pairs analyzed, 15 exhibited significant global genetic correlations, and 97 regions showed significant local correlations. PLACO identified 3659–20,489 potentially pleiotropic single nucleotide polymorphisms (SNPs) across 15 trait pairs, with 828 lead SNPs detected via FUMA. Colocalization analysis confirmed 52 shared loci. Gene-based analysis identified seven unique candidate pleiotropic genes, with ribosomal protein S26 (RPS26) emerging as the strongest shared gene. MR and LCV analyses supported a causal relationship between BMI and diabetic kidney disease (DKD). Our findings highlight a shared genetic basis linking obesity with diabetic microvascular complications. These insights offer potential pathways for understanding the mechanisms driving their comorbidity and may inform more integrated therapeutic approaches
Low expression of CADPS predicts poor prognosis in pediatric acute lymphoblastic leukemia without fusion genes
Full text linkPediatric acute lymphoblastic leukemia (ALL) is among the most prevalent hematological malignancies in children. Despite an overall cure rate approaching 90%, a subset of patients still experiences relapse, even with advanced therapeutic interventions. Research into the molecular characteristics and prognostic markers of fusion gene-negative (FG-negative) pediatric ALL remains limited. To address this gap, we performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on 54 FG-negative ALL cases from our center. Our results indicated that neither specific mutations nor tumor mutational burden significantly influenced relapse risk. Notably, we identified a significant downregulation of CADPS in FG-negative pediatric ALL patients who relapsed. The expression levels and prognostic significance of CADPS were further validated using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohort, where lower CADPS expression was associated with reduced event-free survival (EFS) and overall survival (OS) (P < 0.001 for both). Cox regression analyses were subsequently employed to identify OS-related factors and to construct a prognostic prediction model. Notably, this model demonstrated a significant correlation with therapeutic targets. In conclusion, our findings support the potential of CADPS expression as a novel biomarker for prognostic stratification in FG-negative pediatric ALL patients
Clinical significance of a novel inflammatory-nutritional index in glaucoma severity evaluation
Full text linkThis study investigated the association between glaucoma and serum albumin (Alb), lymphocyte percentage (LYMPH%), and their combined index (LAP = LYMPH% × Alb), to evaluate their potential as biomarkers for systemic inflammation and disease progression in glaucoma. We enrolled 161 glaucoma patients and 181 healthy controls. Serum Alb and LYMPH% were measured using standard blood biochemistry and routine tests, and LAP was calculated accordingly. Statistical analyses were performed to compare these markers between groups and assess their correlation with disease severity. Both the median serum Alb level and peripheral blood LYMPH% were significantly lower in the glaucoma group compared to controls (Alb: 43.48 g/L vs 44.63 g/L, P < 0.001; LYMPH%: 24.25% vs 29.12%, P < 0.001). Correspondingly, LAP levels were also significantly reduced in glaucoma patients (1053 vs 1298, P < 0.001). Lower LYMPH% and LAP levels were associated with more severe glaucomatous visual impairment (LAP, healthy controls vs glaucoma: AUC = 0.7080, P < 0.001, Max Youden = 0.3621; early vs severe glaucoma: AUC = 0.8061, P < 0.001, Max Youden = 0.5377). In summary, LAP may serve as a supportive biomarker of systemic inflammation in glaucoma. It demonstrates good accuracy in reflecting glaucoma severity and shows potential for monitoring disease progression
Review of roles of RNA-binding proteins on NAFLD and the related pharmaceutical measures
Full text linkNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and poses a serious threat to public health. NAFLD is considered a risk factor for metabolic syndrome (MS) and is closely associated with type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease. Recently, increasing attention has been paid to the role of RNA-binding proteins (RBPs) in the pathogenesis of NAFLD. A growing body of research has linked RBPs—such as human antigen R (HuR), sequestosome 1 (p62), polypyrimidine tract-binding protein 1 (PTBP1), and heterogeneous nuclear ribonucleoproteins (hnRNPs)—to lipogenesis and inflammation, both of which contribute to NAFLD through mechanisms involving transcriptional regulation, alternative splicing, RNA stability, polyadenylation, and subcellular localization. However, these findings are often fragmented and lack a comprehensive synthesis. The interactions and mechanisms between RBPs and NAFLD have not yet been thoroughly reviewed. This article provides an overview of the roles and mechanisms of various RBPs in NAFLD, summarizing current knowledge with the aid of figures and tables. In particular, it highlights the influence of HuR on NAFLD through multiple pathways, categorizing its effects based on increased or decreased expression. Furthermore, it reviews drugs that alleviate NAFLD by modulating RBPs, aiming to offer valuable insights for drug-targeted therapies based on RBP regulatory networks
Correction: LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis
Full text linkCorrected article: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7225
In the published article [Qu S, et al. LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis. Bosn J Basic Med Sci. 2022; DOI: 10.17305/bjbms.2021.7225], an error was identified in Figure 4D1. Specifically, the immunofluorescence image originally belonging to the "vector" group was mistakenly used for the "LKB1 OE" group during figure preparation. This was an inadvertent error in image placement.The corrected version of Figure 4 is shown below. This correction does not affect the statistical analysis, interpretation, or the overall conclusions of the study
Drosophila melanogaster models for investigating inflammatory bowel disease: Methods, pathology, mechanisms, and therapeutic approaches
Full text linkInflammatory bowel disease (IBD) is a complex disorder characterized by chronic gastrointestinal inflammation. This paper examines the use of Drosophila melanogaster as a model organism to investigate interactions among the gut microbiota, intestinal stem cells (ISCs), and signaling pathways involved in IBD pathogenesis. Key findings indicate that dysbiosis of the gut microbiota significantly contributes to IBD by altering immune responses and inflammatory signaling, leading to increased intestinal damage. Additionally, ISCs are crucial for intestinal regeneration; their dysregulation exacerbates injury, highlighting their role in maintaining gut homeostasis. Natural compounds, particularly those derived from traditional herbal medicines, show promise in alleviating IBD symptoms by targeting oxidative stress, regulating inflammation, and modulating autophagy, thus promoting ISC homeostasis and restoring microbial balance. This review underscores the intricate relationships among the gut microbiota, ISCs, and inflammatory pathways in IBD, as elucidated through Drosophila studies. The studies summarized here emphasize the need to address microbial imbalances, ISC dysregulation, and inflammatory mechanisms to develop effective therapeutic strategies. Further research is essential to fully elucidate these interactions and inform innovative treatments that improve patient outcomes in IBD management
Effectiveness of SGLT2 inhibitors compared to sulphonylureas for long-term glycemic control in type 2 diabetes: A meta-analysis
Full text linkSulphonylureas (SUs) are common glucose-lowering agents used for managing type 2 diabetes mellitus (T2DM). However, their long-term effectiveness is often limited due to declining β-cell function. Sodium-glucose co-transporter 2 (SGLT2) inhibitors act independently of insulin, potentially providing more sustained glycemic control. Nonetheless, comparative data regarding the long-term glycemic durability of these two drug classes are limited. We performed a meta-analysis of head-to-head randomized controlled trials (RCTs) comparing the efficacy of SGLT2 inhibitors versus SUs in patients with T2DM already receiving metformin therapy. Eligible studies reported HbA1c values at intermediate (24–28 weeks or 48–52 weeks) and final (96–104 weeks or 208 weeks) time points, with a minimum follow-up duration of 96 weeks. Pooled mean differences (MD) and their 95% confidence intervals (CIs) were calculated using random-effects models. Seven comparisons from five RCTs were included in our analysis. Compared with SUs, SGLT2 inhibitors were associated with significantly smaller increases in HbA1c over time. From 24–28 weeks to 96–104 weeks, the pooled MD was −0.28% (95% CI: −0.35 to −0.20; p < 0.001; I² = 0%). From 48–52 weeks to 96–104 weeks, the MD was −0.11% (95% CI: −0.19 to −0.04; p = 0.004; I² = 0%). In longer-term analyses, SGLT2 inhibitors demonstrated sustained benefits from 52 weeks to 208 weeks (MD: −0.22%; 95% CI: −0.34 to −0.10; p < 0.001) and from 104 weeks to 208 weeks (MD: −0.12%; 95% CI: −0.25 to −0.01; p = 0.04). Overall, SGLT2 inhibitors provide superior glycemic durability compared to SUs in patients with T2DM, supporting their preferential use as a second-line therapy after metformin