Bosnian Journal of Basic Medical Sciences (BJBMS)
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hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination
Get PDFHypoxic-ischemic brain injury (HIBD) is a major cause of neonatal mortality and long-term neurological deficits, with limited treatment options. Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) have shown promise in neuroprotection, but the mechanisms remain unclear. This study explores how hUC-MSC-EVs protect neonatal rats from HIBD. hUC-MSC-EVs were isolated, characterized, and administered to neonatal rats subjected to HIBD. Behavioral reflexes and brain infarction were assessed, along with cellular and molecular analyses of hippocampal tissue. An in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model was used to simulate ischemic conditions in rat primary microglia. Results demonstrated that hUC-MSC-EVs significantly improved neurological outcomes, reduced brain infarction, and decreased microglial activation and pyroptosis. These effects were linked to the inhibition of NLRP3 inflammasome activation and enhanced ubiquitination via the protein kinase A (PKA) pathway. Blocking PKA partially reversed these protective effects. Here we highlight that hUC-MSC-EVs provide neuroprotection by regulating the NLRP3 inflammasome, offering a potential therapeutic strategy for HIBD. These findings expand the understanding of EV-mediated neuroprotection and suggest broader applications for ischemia-related conditions, with potential for clinical translation
Effects of spinal-epidural anesthesia combined with intravenous etomidate on adrenocortical and immune stress in elderly patients undergoing anorectal surgery: A retrospective analysis
Get PDFThe management of anesthesia in elderly patients undergoing surgery presents unique challenges, particularly in mitigating stress responses and ensuring stability. Etomidate may alleviate adrenocortical and immune stress. This study aims to investigate the anesthetic effects of combined spinal-epidural anesthesia (CSEA) supplemented with etomidate during anorectal surgery in elderly patients. The medical records of 49 cases treated with CSEA and etomidate (ETO group) and 48 cases treated with CSEA alone (control group) were reviewed and analyzed. All patients received ropivacaine hydrochloride for anesthesia, with the ETO group additionally receiving an infusion of etomidate for sedation. Parameters such as arterial blood gas, visual analog scale (VAS), Ramsay sedation scale (RSS), serum cortisol and norepinephrine levels, pro-inflammatory cytokines, and lymphocyte ratios were assessed at different time points. Compared to the control group, the ETO group showed increased mean arterial pressure, decreased heart rate, and elevated arterial SpO2 30 minutes after anesthesia. The ETO group also had higher RSS scores, lower VAS scores, and reduced serum cortisol and norepinephrine levels. Additionally, decreased levels of pro-inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-8, were observed, along with an increase in the regulatory cytokine IL-10. An increased proportion of CD4+ T cells and a higher CD4/CD8 ratio were also noted. This study demonstrates the benefits of using etomidate to mitigate adrenocortical and immune stress in elderly patients undergoing anorectal surgery
Letter regarding “The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders”
Get PDFDear Editor,
We have read the article “The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders”, recently published in your esteemed journal.
We are a team dedicated to diagnosing, approaching, and managing patients with connective tissue disorders, particularly hypermobile spectrum disorders (HSD) and Ehlers–Danlos syndromes (EDS). We appreciate the research group’s effort to address the complexity of connective tissue disorders using a multi-panel genetic approach and their analysis of genotype–phenotype associations in a cohort of Mexican patients.
However, we would like to express our concern regarding two specific points that we consider crucial for the comprehensive understanding and management of these disorders.
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Leveraging social media for resident training in developing countries: A case study of Libya
Get PDFSocial media platforms have emerged as invaluable tools for remote training in resource-constrained countries. This study presents the development, implementation, and preliminary assessment of a remote intensive care unit (ICU) training program conducted in Libya utilizing social media platforms. This educational initiative was based on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury (CERTAIN) program, targeting Libyan resident physicians. The initiative comprised a series of live-streamed pulmonary/critical care lectures and asynchronous discussion of clinical cases via a private messaging chat. Participant engagement, satisfaction, and learning outcomes were evaluated using social media analytics and surveys. A total of 323 learners joined the Libyan ICU training program chat group, and two tele-education sessions were broadcast, accumulating a total of 749 views. The majority (72.6%) of learners had graduated from medical school within the past five years and were in residency training. Clinical cases and learning materials were shared through 2,991 messages in the chat group. Learners\u27 objective and subjective clinical knowledge improved after each tele-education session, and 88% of survey respondents rated the remote ICU training program as excellent. This study highlights the potential of using widely available social media platforms for remote ICU education in resource-limited settings
Husref Tahirović: Dr. Isak Samokovlija. The life in a white coat
Get PDFDr. Husref Tahirović, an endocrinologist and professor emeritus of pediatrics at the University of Tuzla School of Medicine and a member of the Academy of Sciences and Arts of Bosnia and Herzegovina, performed many functions and held many appointments during his long professional life, reflecting his various scientific and social interests. Among other roles, he has been the Editor-in-Chief of Acta Medica Academica, the official journal of the Academy. In this journal, he published several historical articles on famous physicians from Bosnia and Herzegovina. His interest in history also led him to spend considerable time during the last few years researching the life and works of Dr. Isak Samokovlija a celebrated writer in former Yugoslavia, who was also a physician recognized for his contributions to medicine and the organization of health care services in Bosnia and Herzegovina before the Second World War. This book contains a wealth of data that Dr. Tahirović has collected about this remarkable physician, who was born in Goražde in 1889 and died in Sarajevo in 1955.
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Is there an association between glomerular hyperfiltration and coronary flow velocity reserve in patients with gestational diabetes history?
Get PDFGlomerular hyperfiltration (GHF) is an early marker of chronic kidney disease (CKD) and may predict coronary microvascular dysfunction, presenting as reduced coronary flow velocity reserve (CFVR) in patients with a history of gestational diabetes (GDM). This study aimed to assess the glomerular filtration rate (GFR) and compare CFVR in patients with a history of GDM. We screened patients referred to the Cardiology Department of Istanbul Medeniyet University for angina pectoris, excluding those with positive treadmill test results. Women with a history of GDM were categorized into three groups based on GFR levels: Group 1 (60-89 ml/min), Group 2 (90-119 ml/min), and Group 3 (≥ 120 ml/min). Coronary diastolic peak velocities were measured at baseline and after dipyridamole administration, with CFVR defined as the ratio of hyperemic to baseline diastolic peak velocities. The homeostasis model assessment of insulin resistance (HOMA-IR) and body mass index were derived from patient files. A total of 166 patients were included: 57 in Group 1, 80 in Group 2, and 29 in Group 3. HOMA-IR was higher in Group 3 compared to Group 2 (P < 0.05). Group 1 had the lowest CFVR (2.3 ± 0.3%), Group 2 had the highest (2.5 ± 0.3%), and Group 3 showed a moderate decrease in CFVR (2.4 ± 0.3%). Multivariate linear regression analysis revealed that HbA1c was independently associated with CFVR. In patients with GDM, GHF is associated with reduced CFVR, linked to metabolic parameters such as HbA1c and HOMA-IR. Interventions to improve metabolic health may prevent cardiovascular disease in these patients
Combined fibrinogen concentration and neutrophil-to-lymphocyte ratio, an integrative model of the inflammatory response and coagulation cascades, for predicting prognosis in patients with upper tract urothelial carcinoma
Get PDFInflammation and coagulation cascades are closely correlated with cancer occurrence and progression. This study investigated the prognostic value of the combination of plasma fibrinogen level and neutrophil-to-lymphocyte ratio (F-NLR) in patients with upper tract urothelial carcinoma (UTUC). The predictive ability of the F-NLR for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) was initially established and then further validated in patients who underwent radical nephroureterectomy (RNU) for UTUC. As a result, patients were divided into three groups following the establishment of cut-off values for the neutrophil-to-lymphocyte ratio (NLR) (≥2.53 vs <2.53) and fibrinogen (≥4.55 vs <4.55) through receiver operating characteristic (ROC) curve analysis: F-NLR score 0 (low fibrinogen and low NLR), 2 (high fibrinogen and high NLR), or 1 (remaining patients). The F-NLR score was then identified as an independent risk factor for OS, CSS, and PFS (all P value <0.05) by multivariate regression analysis in both the training and validation cohorts. In addition, F-NLR-based nomograms for OS, CSS, and PFS were developed and evaluated using the concordance index (C-index) and calibration curves. The integration of the F-NLR into existing nomograms improved predictive accuracy compared to the use of nomograms without the F-NLR score. This suggests that the addition of F-NLR is beneficial for enhancing the accuracy of prognosis prediction in patients with UTUC. The F-NLR score may serve as a powerful predictor for patients with UTUC
Effect of β-1,4-GalTI on the biological function of astrocytes treated by LPS
Get PDFInflammation of the central nervous system (CNS) is a common feature of neurological disorders and infections, playing a crucial role in the development of CNS-related conditions. CNS inflammation is primarily regulated by glial cells, with astrocytes being the most abundant type in the mammalian CNS. Numerous studies have demonstrated that astrocytes, as immunocompetent cells, perform diverse and complex functions in both health and disease. Glycosylation, a critical post-translational modification of proteins, regulates numerous biological functions. The expression and activity of glycosyltransferases, the enzymes responsible for glycosylation, are closely associated with the pathogenesis of various diseases. β-1,4-GalTI, a mammalian glycosyltransferase, plays a significant role in cell-cell interactions, adhesion, and migration. Although many studies have focused on β-1,4-GalTI, few have explored its effects on astrocyte function. In this study, we constructed lentiviral vectors for both interference and overexpression of β-1,4-GalTI and discovered that β-1,4-GalTI knockdown inhibited astrocyte migration and proliferation, while its overexpression promoted these processes. Concurrently, β-1,4-GalTI knockdown reduced the expression of TNF-α, IL-1β, and IL-6, whereas overexpression enhanced the expression of these cytokines. These findings suggest that modulating β-1,4-GalTI activity can influence the molecular functions of astrocytes and provide a theoretical foundation for further research into β-1,4-GalTI as a potential therapeutic target in astrocyte-mediated inflammation
Unveiling the impact of C15orf48 on non-small cell lung cancer through NF-kappa B signaling
Get PDFThe role of the C15orf48 gene in lung cancer is not well understood. This study aimed to investigate the effect of C15orf48 in non-small cell lung cancer (NSCLC). Bioinformatics analyses were performed using Oncomine, The Cancer Genome Atlas (TCGA), Protein-Protein Interaction (PPI) networks, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Immunohistochemical staining was used to detect C15orf48 expression in tissue microarrays. Cellular assays, including CCK8, colony formation, wound healing, transwell migration, flow cytometry, and cell adhesion, were conducted to assess cell viability, proliferation, invasion, and apoptosis. A xenograft tumor model was used to examine tumor growth, and Western blotting was used to detect protein expression. C15orf48 expression was significantly upregulated in tumor tissues compared to normal tissues and was associated with poor prognosis. Knockdown of C15orf48 in A549 and H1299 cells reduced proliferation, invasion, and adhesion while increasing apoptosis. C15orf48 knockdown also inhibited tumor growth in vivo and was associated with immune cell infiltration. Although C15orf48 expression correlated with the epithelial-mesenchymal transition (EMT) score, no significant differences were observed. GSEA identified the NF-κB signaling pathway as a key pathway involved. Proteins PLAUR, IKBα, IL-1RN, ICAM1, and TMPRSS4 showed decreased expression in the shC15orf48 group compared to the shCtrl group. We concluded that C15orf48 promotes NSCLC progression, potentially through immune cell infiltration and the NF-κB signaling pathway
Predicting osteoradionecrosis risk in patients with locoregionally advanced nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: The value of the CARWL index
Get PDFOsteoradionecrosis (ORN) is a severe complication that can arise in patients with nasopharyngeal carcinoma due to the aggressive nature of chemoradiotherapy treatment. The purpose of our study was to assess the utility of the recently introduced CARWL index, which integrates the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in predicting the risk of ORN in patients with locoregionally advanced nasopharyngeal cancer (LA-NPC) undergoing concurrent chemoradiotherapy (CCRT). We conducted a retrospective cohort analysis on 304 patients with LA-NPC treated with CCRT. Patients were categorized into CARWL index groups based on CAR (cut-off: 3.0) and SWL (weight loss > 5% over the past six months): CARWL-0 (CAR < 3.0, SWL ≤ 5%), CARWL-1 (CAR < 3.0 with SWL > 5% or CAR ≥ 3.0 with SWL ≤ 5%), and CARWL-2 (CAR ≥ 3.0 and SWL > 5%). The primary endpoint was the incidence of ORN in each CARWL index group. At a median follow-up of 67.2 months, 28 patients (9.2%) developed ORN. The incidence of ORN was 2.1%, 9.4%, and 16.3% in the CARWL-0, CARWL-1, and CARWL-2 groups, respectively (P < 0.001). Multivariate analysis identified smoking status (HR: 2.58, P = 0.034), N-stage (HR: 1.96, P = 0.008), T-stage (HR: 1.84, P = 0.017), pre-CCRT tooth extraction status (HR: 5.81, P < 0.001), post-CCRT tooth extraction status (HR: 6.82, P < 0.001), mandibular V55.8 Gy (HR: 6.12, P < 0.001), and CARWL score (HR: 5.67, P = 0.002) as significant predictors of ORN. The CARWL index is a reliable predictive tool for evaluating the risk of ORN in LA-NPC patients undergoing CCRT. If further validated, its use in clinical settings could aid in the early identification of high-risk patients and enable the implementation of personalized preventive strategies