Bosnian Journal of Basic Medical Sciences (BJBMS)
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Piperine inhibits the proliferation of colorectal adenocarcinoma by regulating ARL3-mediated endoplasmic reticulum stress
Get PDFColorectal adenocarcinoma (COAD) is a significant cause of cancer-related mortality worldwide, necessitating the identification of novel therapeutic targets and treatments. This research aimed to investigate the role of ARL3 in COAD progression and to explore the effects of Piperine on ARL3 expression, cell proliferation, epithelial–mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress. Bioinformatics analysis of The Cancer Genome Atlas (TCGA)–COAD, GSE39582, and GSE44861 datasets assessed ARL3 expression levels. Immunohistochemical data from the Human Protein Atlas (HPA) database confirmed ARL3 overexpression in COAD. The association of ARL3 with COAD clinical parameters and prognosis was also examined. COAD cells were treated with Piperine, and in vitro assays evaluated cell proliferation, apoptosis, EMT marker expression, and ER stress (ERS) responses. ARL3 overexpression in COAD correlated with poor prognosis and varied across pathological stages. Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, as indicated by reduced Ki-67 levels and decreased colony-forming ability. Piperine induced S-phase cell cycle arrest and facilitated apoptosis in COAD cells, evidenced by changes in Bax, Bcl-2, cleaved caspase-3, and cleaved Poly (ADP-ribose) polymerase (PARP) levels. Moreover, Piperine downregulated ARL3 expression in COAD cells, thereby suppressing transforming growth factor beta (TGF-β)-induced EMT. Additionally, Piperine attenuated the ARL3-mediated ER stress response, significantly reducing binding immunoglobulin protein (BiP), inositol-requiring enzyme 1 alpha (p-IRE1α), activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) levels. Piperine exerts anti-cancer effects in COAD by modulating ARL3 expression, disrupting cell cycle progression, inhibiting the EMT pathway, and regulating ERS. These findings suggest that Piperine holds promise as a therapeutic agent for COAD through its targeting of ARL3
Cuproptosis-related gene ATOX1 promotes MAPK signaling and diffuse large B-cell lymphoma proliferation via modulating copper transport
Get PDFDiffuse Large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin lymphoma, highlighting the importance of studying susceptibility genes to develop personalized treatment strategies. While cuproptosis, caused by high levels of copper ions induced by ionophores, has been shown to affect cancer survival, its specific role in lymphoma is not yet clear. To investigate the involvement of upregulation-related genes in DLBCL, we employed bioinformatics techniques. Specifically, we analyzed the differentially expressed genes (DEGs) in the GSE25638 dataset using Weighted Gene Co-expression Network Analysis (WGCNA) and performed functional enrichment analysis. By building a Protein-Protein Interaction (PPI) network, candidate genes were identified. Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curve analysis were used to confirm the clinical diagnostic use of these genes. The effects of Antioxidant 1 (ATOX1) knockdown, CuCl2, and DCAC50 treatments on DLBCL cells and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway were investigated by conducting in vitro experiments. Bioinformatics and in vitro experiments confirmed elevated expression of ATOX1 in DLBCL cells and tumor samples. ATOX1 knockdown led to decreased cell proliferation and G2 cell cycle arrest in vitro. Additionally, Phosphorylated Extracellular Signal-Regulated Kinases 1 and 2 (P-ERK1/2) protein levels within the MAPK pathway were reduced as a result of ATOX1 knockdown, but these levels were recovered by CuCl2. Treatment with DCAC50 showed a dose-dependent antiproliferative effect in DLBCL cells, which was strengthened by ATOX1 knockdown. Our study demonstrated that ATOX1 may be important in DLBCL via controlling the MAPK pathway through copper transport, providing new insights into potential therapeutic strategies for DLBCL
Research progress on miRNAs function in the interaction between human infectious viruses and hosts: A review
Get PDFMicroRNAs (miRNAs) represent a class of non-coding small RNAs that are prevalent in eukaryotes, typically comprising approximately 22 nucleotides, and have the ability to post-transcriptionally regulate gene expression. miRNAs exhibit diverse types and functions, with mechanisms of action that include cell differentiation, proliferation, apoptosis, and regulation of signaling pathways. Both viruses and their hosts can encode miRNAs, which serve as crucial effector molecules in the complex interaction between viruses and host cells. Host miRNAs can either directly interact with the virus genome to inhibit virus replication or facilitate virus replication by providing necessary substances. Viral miRNAs can directly bind to host mRNAs, thereby influencing translation efficiency, suppressing the immune response, and ultimately enhancing virus replication. This article comprehensively reviews the roles of miRNAs in virus-host interactions, aiming to provide valuable insights into viral pathogenic mechanisms and potential therapeutic approaches
Prognostic value of immunotherapy in advanced NSCLC based on baseline and dynamic changes in HALP
Get PDFImmune checkpoint inhibitors (ICIs) enhance the tumor-killing ability of T-cells in non-small cell lung cancer (NSCLC), improving overall survival (OS) and revolutionizing treatment for advanced stages. However, challenges remain, such as low response rates and the lack of effective markers for selecting candidates. This study evaluated the impact of hemoglobin, albumin, and platelet (HALP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the efficacy of immunotherapy and survival outcomes in advanced NSCLC. Additionally, it aimed to develop a nomogram based on these parameters. Clinical and hematological data from NSCLC patients who received immunotherapy were analyzed. Efficacy was assessed using the immune Response Evaluation Criteria in Solid Tumors (iRECIST), and progression-free survival (PFS) and OS were evaluated. Prediction models incorporated baseline and post-treatment HALP, NLR, and PLR values. The 203 patients had a median follow-up of 16 months, a median PFS (mPFS) of seven months (6.0–8.0), while the median OS (mOS) was not reached (24.0–not available). Pretreatment PLR (PLR0) was associated with a higher disease control rate (DCR) (odds ratio [OR] = 0.258), while initial immunotherapy and NLR after four treatment cycles (NLR4C) significantly improved the objective response rate (ORR). Cox regression analysis showed that pretreatment HALP (HALP0), HALP after four cycles of treatment (HALP4C), and pretreatment NLR (NLR0) significantly impacted PFS. Additionally, HALP0, NLR0, and PLR after four treatment cycles (PLR4C) were associated with OS. The C-indices for PFS and OS were 0.823 and 0.878, respectively, indicating good predictive accuracy. HALP, NLR, and PLR at various time points effectively predicted immunotherapy response in advanced NSCLC patients, with low HALP combined with high NLR and PLR indicating a poor prognosis. These findings could serve as the basis for stratified randomized controlled trials (RCTs) in the future
Quercetin regulates sensitivity to X-ray radiation of hepatocellular carcinoma through miR-216a-3p
Get PDFHepatocellular carcinoma (HCC) is a highly aggressive liver cancer with limited therapeutic options, and enhancing radiosensitivity remains a key challenge in improving treatment outcomes. Quercetin (Que) can inhibit the progression of HCC; however, its effect on HCC radiosensitivity remains unclear. This research investigates the role of Que in regulating HCC growth and radiosensitivity, aiming to provide a scientific foundation for enhancing the clinical efficacy of radiation therapy in HCC. The CCK-8 assay was used to determine the optimal treatment conditions for Que and X-rays. Changes in cell growth, cycle arrest, invasion, migration, the relative proportion of JC-1 red and green fluorescence (mitochondrial membrane potential), and the levels of ROS, malondialdehyde, superoxide dismutase, and glutathione peroxidase (oxidative stress) were assessed using flow cytometry, Transwell assays, JC-1 staining, Western blot, and ELISA, respectively, under Que, X-ray, and co-treatment conditions. The effect of miR-216a-3p knockdown on the action of Que was also explored, and the potential pathways by which Que regulates HCC growth and radiosensitivity were investigated in conjunction with in vivo subcutaneous transplantation tumor experiments. The in vitro treatment parameters for Que and X-rays were 100 μM and 4 Gy. Que combined with X-ray therapy enhanced HCC cell radiosensitivity, reduced proliferation, invasion, and migration, and promoted oxidative stress and apoptosis. Que was found to upregulate miR-216a-3p in HCC cells. Rescue experiments with miR-216a-3p knockdowns demonstrated that Que regulates HCC cell radiosensitivity via miR-216a-3p. In vivo research further showed that Que increased tumor sensitivity to X-rays by upregulating miR-216a-3p, thereby inhibiting HCC growth. In conclusion, Que has been shown to enhance HCC radiosensitization by upregulating miR-216a-3p and inhibiting HCC progression. Que may be a promising agent for increasing the radiosensitivity of HCC
The association between plasma levels of Sestrin2 and risk factors of cardiovascular diseases in healthy and diabetic adults: A study of Qatar Biobank data
Get PDFThis study examines the association between serum Sestrin2 (SESN2) levels and cardiovascular disease (CVD) risk factors in healthy and diabetic adults, using data from the Qatar Biobank (QBB). A total of 844 participants were included, with 518 in the diabetic cohort and 326 in the healthy cohort. Clinical characteristics, cardiometabolic markers, and SESN2 levels were measured, and binomial logistic regression analyses were conducted to assess the associations between SESN2 and various health indices. Diabetic patients had significantly lower SESN2 levels compared to healthy controls (5.49 ± 5.94 vs 8.25 ± 7.57 ng/mL, P < 0.001). A significant negative correlation was observed between SESN2 and HbA1c (−0.19, P = 0.0006), insulin (−0.19, P = 0.0006), HOMA-IR (−0.17, P = 0.0024), C-peptide (−0.18, P = 0.0012), triglycerides (TG)/HDL ratio (−0.12, P = 0.0283), and the pulsatility index (PI) (−0.15, P = 0.006). In healthy individuals, higher SESN2 levels were associated with lower odds of elevated HbA1c (adjusted odds ratio [AOR] = 0.33, P = 0.00), insulin (AOR = 0.23, P = 0.00), HOMA-IR (AOR = 0.58, P = 0.06), C-peptide (AOR = 0.56, P = 0.04), and TG (AOR = 0.37, P = 0.03). In contrast, diabetic patients showed a positive correlation between SESN2 and insulin (0.15, P = 0.0005), HOMA-IR (0.11, P = 0.0106), and C-peptide (0.12, P = 0.0048). Participants in the highest SESN2 tertile had increased risks for high BMI (AOR = 1.96, P = 0.05), high TG (AOR = 1.57, P = 0.04), high NT-proBNP (AOR = 7.27, P = 0.01), and high fibrinogen (AOR = 1.92, P = 0.03). These findings suggest that while high SESN2 levels are cardioprotective in healthy individuals, they may indicate higher cellular stress in diabetics. Determining optimal SESN2 levels could help assess CVD risk, particularly in diabetic patients
Clinical characteristics associated with recurrent viral RNA positivity in patients within two weeks after recovering from the first SARS-CoV-2 infection
Get PDFMany studies have shown that recovered coronavirus disease 2019 (COVID-19) patients frequently exhibit recurrent viral RNA positivity (RP) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study aimed to summarize the clinical characteristics of these patients and explore potential reasons for RP occurrence. We divided 439 participants into four groups based on the severity of illness prior to the COVID-19 recovery and age: mild-child group, moderate-child group, mild-adult group, and moderate-adult group. Laboratory data were collected and statistically analyzed using the SPSS software, version 24.0. Significant differences were observed in age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), interleukin 6 (IL-6), and neutrophil to lymphocyte ratio (NLR) levels between the mild-adult group and the moderate-adult group (P < 0.05). Additionally, AST levels differed significantly between the mild-child group and the moderate-child group (P < 0.05). The proportion of RP patients within the four groups varied from 7.95% to 26.13% within a 2-week period. Logistic regression analysis revealed that younger age and moderate symptoms were risk factors for RP in children, while the presence of comorbidities (such as chronic heart, lung, liver, and kidney diseases), elevated IL-6 levels, and NLR were risk factors for RP in adults. We constructed two predictive models containing these relevant parameters, and the results of the receiver operating characteristic (ROC) curves indicated strong predictive utility. Our findings suggest that younger children with more severe symptoms, as well as adult patients with elevated levels of IL-6 and NLR and underlying diseases, are at higher risk of RP occurrence
A systematic review of blunt abdominal aortic injury and analysis of predictors of death
Get PDFAt present, research on blunt abdominal aortic injury (BAAI) is limited, with the majority being case reports. Consequently, there is a significant knowledge gap concerning this condition. To address this, we conducted a systematic review by extensively searching major databases. We included all literature that provided individual (non-identifiable) data on BAAI patients, irrespective of the study design. Furthermore, we undertook regression analyses to identify predictors of death after BAAI. The search yielded 2,099 results, leading to the inclusion of 102 case reports and one conference abstract. Using the Joanna Briggs Institute (JBI) checklist for assessment, all studies were deemed of medium to high quality. In total, 133 patients were included, with a median age of 34 years, and 73.7% being male. The predominant clinical manifestation was pain, reported in 65.6% of patients. The most frequently observed aortic lesion severity was grade A (intimal tear or intramural hematoma) at 46.9%, and the most common lesion location was zone III (infrarenal aorta) in 88.3% of cases. The overall mortality after BAAI was 15.3%. Multivariate regression analyses revealed the following predictors of death after BAAI: lower limb ischemia (relative risk [RR] = 7.137, 95% confidence interval [CI] 1.154 - 44.161), cardiopulmonary arrest (RR = 10.250, 95% CI 1.452 - 72.344), and injuries to body parts other than the abdomen and lumbar spine (RR = 2.593, 95% CI 1.189 - 5.655). In conclusion, this review provides a detailed quantitative summary of BAAI\u27s clinical manifestations, diagnosis, treatment, and prognosis, emphasizing its high mortality rate and identifying three critical variables as predictors of death
Changes in attitudes, beliefs, and experiences related to pregnancy during graduate medical education training from 2005 to 2021
Get PDFToday, 50% of medical students are women, and residency and fellowship training years overlap with peak times for starting families. The authors describe attitudes toward pregnancy during residency and fellowship and report pregnancy rates and complications for female residents and resident partners across several decades. A web-based survey was emailed to 1,057 residents in 2005 (period 1) and 1,860 residents in 2021 (period 2). Anonymous surveys were sent to all trainees including pregnant trainees, affected co-trainees and trainee partners. Resident attitudes and pregnancy characteristics were compared between groups using the chi-square (χ2) test for categorical variables and the Kruskal-Wallis test for ordinal variables. A total of 442 residents (41.8%) responded to the 2005 survey, and 525 (28.2%) responded to the 2021 survey. Most residents who covered for a pregnant resident had positive feelings about covering for their colleagues during both time periods, although more positive attitudes were present during the period 2. Only about 10% of residents received compensation for their coverage during both time periods. Among residents with a pregnancy during training (i.e., themselves or partners), most characterized having a baby in training as “somewhat difficult” or “very difficult” at both time periods. Pregnancy complication rates were 33% and 44% for training years 2005 and 2021. As medical education evolves, training programs should be proactive in creating structured support systems for pregnant residents and resident partners to minimize adverse maternal and fetal outcomes and to improve training programs. Future studies are needed to elucidate the causality of higher-than-expected pregnancy complication rates
Exosome miR-4738-3p-mediated regulation of COL1A2 through the NF-κB and inflammation signaling pathway alleviates osteoarthritis low-grade inflammation symptoms
Get PDFThis study aimed to elucidate the roles of microRNA (miR)-4738-3p and the collagen type I alpha 2 chain (COL1A2) gene in the pathogenesis of osteoarthritis (OA) through bioinformatics analysis and cellular assays. The GSE55235 dataset was analyzed using the weighted gene co-expression network analysis (WGCNA) method to identify gene modules associated with OA. Key overlapping genes were identified from these modules and the GSE55235-differential expressed genes (DEGs). The expression levels of selected genes were determined in C28/I2 cells using the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-4738-3p and COL1A2 was examined in the context of interleukin 1 beta (IL-1β) induction. Exosome characterization was achieved through transmission electron microscopy (TEM), western blotting (WB), and other analyses. The study also investigated the functional relevance of miR-4738-3p in OA pathology through various molecular and cellular assays. Our findings revealed that the green module exhibited a strong correlation with the OA phenotype in the GSE55235 dataset, with COL1A2 emerging as a hub gene and miR-4738-3p as its key downstream target. IL-1β induction suggested that COL1A2 is involved in inflammation and apoptosis, while miR-4738-3p appeared to play an antagonistic role. The analysis of exosomes underscored the significance of miR-4738-3p in cellular communication, with an enhanced level of exo-miR-4738-3p antagonizing IL-1β-induced inflammation and promoting cell survival. Conversely, a reduction in exo-miR-4738-3p led to increased cell damage. This study established a clear regulatory relationship between miR-4738-3p and COL1A2, with the nuclear factor kappa B (NF-κB) signaling pathway playing a central role in this regulation. The miR-4738-3p significantly influences the OA-associated inflammation, primarily through modulation of COL1A2 and the NF-κB pathway. Therefore, targeting miR-4738-3p offers a potential therapeutic approach for OA, with exosome miR-4738-3p presenting a promising strategy