Bosnian Journal of Basic Medical Sciences (BJBMS)
Not a member yet
1863 research outputs found
Sort by
The mechanism of high mobility group box-1 protein and its bidirectional regulation in tumors
Get PDFHigh-mobility group box-1 protein (HMGB1) is a nonhistone chromatin-related protein widely found in eukaryotic cells. It is involved in the transcription, replication, and repair of DNA to maintain nuclear homeostasis. It participates in cell growth, differentiation, and signal transduction. Recent studies showed that HMGB1 has a bidirectional regulatory effect on tumors by regulating TLR4/MYD88/NF-κB and RAGE/AMPK/mTOR signaling pathways. On the one hand, it is highly expressed in a variety of tumors, promoting tumor proliferation and invasion, while on the other hand, it induces autophagy and apoptosis of tumor cells and stimulates tumor-infiltrating lymphocytes to produce an anti-tumor immune response. At present, HMGB1 could be used as a target to regulate the drug resistance and prognostication in cancer. Clinical applications of HMGB1 in cancer need further in-depth studies
The value of elastography strain rate ratio in benign and malignant BI-RADS-US 3-4 breast masses
Get PDFIn the realm of breast diagnostics, Breast Imaging Reporting and Data System (BI-RADS) serves as a systematic framework, guiding a methodical exploration into the nuanced narratives of masses. The current study aims to investigate the value of strain rate ratio (SR) of elastography for benign and malignant breast masses categorized by BI-RADS for Ultrasonography (BI-RADS-US) category 3-4. Ultrasonographic data of 1099 breast masses that underwent both elastography and pathological examination were retrospectively analyzed by non-parametric test, consistency analysis and receiver operating characteristic (ROC) curve sequentially. ROC curve was used to evaluate the diagnostic effect of SR method in different BI-RADS categories of breast lesions. The maximum Youden index obtained from the ROC curve was 0.845. At a cut-off value of 3.57, the SR values’ diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value for distinguishing benign and malignant breast lesions were 85.7 %, 98.8 %, 93.6 %, 97.9 % and 91.45 %, respectively. Consistency analysis showed that the consistency between SR value and pathological diagnosis was 93.6 % (κ = 0.864). In addition, the SR values between benign and malignant lesions of BI-RADS 3 and 4 were statistically different (P < 0.001). ROC analysis indicated that the diagnostic area under curve (AUC) for SR value in BI-RADS 3, 4a, 4b and 4c lesions were 0.985, 0.866, 0.793 and 0.916, respectively. In addition, the study observed 58 cases of missed diagnosis and 20 cases of misdiagnosis in evaluating benign and malignant breast lesions. The elastic SR ratio method has a good diagnostic value for the evaluation of breast masses, particularly for lesions with a score of 3-4. The elastic SR ratio method is instrumental in enhancing the accuracy of diagnosis
Nuclear factor erythroid 2-related factor 2 promotes radioresistance by regulating glutamate-cysteine ligase modifier subunit and its unique immunoinvasive pattern
Get PDFThe enzyme glutamate-cysteine ligase modifier subunit (GCLM) serves as the initial rate-limiting factor in glutathione (GSH) synthesis. GSH is the preferred substrate for glutathione peroxidase 4 (GPX4), directly impacting its activity and stability. This study aims to elucidate the expression of GCLM and its correlation with the nuclear factor erythroid 2-related factor 2 (NFE2L2), commonly referred to as NRF2, in esophageal squamous cell carcinoma (ESCC) and further investigate the potential signaling axis of radiotherapy resistance caused by NRF2-mediated regulation of ferroptosis in ESCC. The expression of NRF2, GCLM, and GPX4 in ESCC was analyzed by bioinformatics, and their relationship with ferroptosis was verified through cell function experiments. Their role in radioresistance was then investigated through multiple validation steps. Bioinformatics analysis was employed to determine the immune infiltration pattern of NRF2 in ESCC. Furthermore, the effect of NRF2-mediated massive macrophage M2 infiltration on radiotherapy and ferroptosis was validated through in vivo experiments. In vitro assays demonstrated that overactivated NRF2 promotes radioresistance by directly binding to the promoter region of GCLM. The Tumor Immune Estimation Resource (TIMER) and quanTIseq analyses revealed NRF2 enrichment in M2 macrophages with a positive correlation. Co-culturing KYSE450 cells with M2 macrophages demonstrated that a significant infiltration of macrophages M2 can render ESCC cells resistant to radiotherapy but restore their sensitivity to ferroptosis in the process. Our study elucidates a link between the NRF2-GCLM-GSH-GPX4 signaling axis in ESCC, highlighting its potential as a therapeutic target for antagonistic biomarkers of resistance in the future. Additionally, it provides a novel treatment avenue for ESCC metastasis and radioresistance
Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation
Get PDFThe cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV
Reconsideration of the laminin receptor 67LR in colorectal cancer cells
Get PDFThe 67 kDa laminin receptor (67LR) was identified as the first laminin receptor shown to be involved in the carcinogenesis of various cancers, including colorectal cancer. While the exact composition of this 67 kDa receptor remains unknown, it has been reported to be formed by the 37 kDa ribosomal protein SA (RPSA) covalently attached to another unidentified protein. The goal of this study was to clarify the molecular structure of 67LR to enhance our understanding of its role in malignancies. Using cell fractionation of colorectal cancer cells, the 67 kDa immunoreactive protein corresponding to 67LR was found in the soluble protein fraction, while some of the 37 kDa RPSA exhibited plasma membrane-like properties. Proteomic analysis of the 67 kDa fraction revealed the absence of RPSA but identified the β-galactosidase-related 67 kDa elastin-binding protein (67EBP), another laminin binding receptor which presents amino acid sequence similarities that can explain the immune cross reactivity with RPSA. The downregulation of β-galactosidase through short hairpin RNA (shRNA) led to a reduction in both 67LR and 67EBP immunoreactive proteins, confirming the misidentification of 67LR and 67EBP in colorectal cancer cells. Based on these findings, we propose to redefine the 67LR as the RPSA-containing laminin receptor (RCLR) to avoid confusion with the 67EBP
The predictive role of modified stress hyperglycemia rate in predicting early pneumonia after isolated coronary bypass surgery in patients with diabetes mellitus
Get PDFPostoperative pneumonia (PP) is one of the most serious complications following coronary artery bypass graft (CABG) surgery. The recently developed admission blood glucose (ABG)/estimated average glucose (eAG) ratio has been identified as a prognostic marker in cardiovascular diseases. This study aimed to investigate the predictive role of the modified ABG/eAG (mABG/eAG) ratio in the development of pneumonia during the early postoperative period in diabetic patients undergoing CABG surgery. In this single-center study, diabetic patients who underwent isolated coronary bypass surgery at the Training and Research Hospital between 1 January 2018 and 1 January 2023 were included. Patients who did not develop PP were assigned to the control group, while those who developed PP were assigned to the PP group. A total of 549 patients were included in the study, 478 patients in the control group (median age = 58 years [range 35-81]) and 71 patients in the PP group (median age = 63 years [37-86]). In the multivariate analysis, the use of packed blood products (odds ratio [OR] = 1.685, 95% confidence interval [CI]: 1.453 - 1.892; P = 0.027), mABG/eAG ratio (OR = 1.659, 95% CI: 1.190 - 2.397; P = 0.019), and re-intubation (OR = 1.829, 95% CI: 1.656 - 1.945; P = 0.034) were identified as independent predictors for the development of PP. Our findings demonstrate that the mABG/eAG ratio is an independent predictor of PP in diabetic patients undergoing CABG surgery. Based on our results, high-risk patients can be identified by calculating the mABG/eAG ratio.
Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis
Get PDFIdiopathic pulmonary fibrosis (IPF) is a progressive and chronic disease that significantly impacts patient quality of life, and its incidence is on the rise. The pathogenesis of IPF remains poorly understood. Alveolar type 2 (AT2) cells are crucial in the onset and progression of IPF, yet the specific mechanisms involved are not well defined. Lon protease 1 (LONP1), known for its critical roles in various diseases, has an unclear function in IPF. Our research investigated the impact of Lonp1 gene deletion on AT2 cell functionality and its subsequent effect on IPF development. We generated a bleomycin-induced pulmonary fibrosis mouse model with a targeted Lonp1 knockout in AT2 cells and assessed the consequences on AT2 cell function and fibrosis progression. Additionally, we constructed the MLE12 cells with stable Lonp1 knockdown and utilized transcriptome sequencing to identify pathways altered by the Lonp1 knockdown. Our results indicated that mice with AT2 cell-specific Lonp1 knockout exhibited more severe fibrosis compared to controls. These mice exhibited a reduction in AT2 and AT1 cell populations, along with an increase in p53- and p21-positive AT2 cells. Lonp1 knockdown in MLE12 cells led to the upregulation of aging-associated pathways, with fibroblast growth factor 2 (Fgf2) gene emerging as a central gene interconnecting these pathways. Therefore, loss of Lonp1 appears to promote AT2 cell aging and exacerbate bleomycin-induced pulmonary fibrosis. Fgf2 emerges as a pivotal downstream gene associated with cellular senescence. This study uncovers the role of the Lonp1 gene in pulmonary fibrosis, presenting a novel target for investigating the pathological mechanisms and potential therapeutic approaches for IPF
Naringenin – a potential nephroprotective agent for diabetic kidney disease: A comprehensive review of scientific evidence
Get PDFDiabetes mellitus (DM) is a chronic disease characterized by persistent hyperglycemia, which is a major contributing factor to chronic kidney disease (CKD), end-stage renal disease (ESRD), and cardiovascular-related deaths. There are several mechanisms leading to kidney injury, with hyperglycemia well known to stimulate oxidative stress, inflammation, tissue remodeling, and dysfunction in the vascular system and organs. Increased reactive oxygen species (ROS) decrease the bioavailability of vasodilators while increasing vasoconstrictors, resulting in an imbalance in vascular tone and the development of hypertension. Treatments for diabetes focus on controlling blood glucose levels, but due to the complexity of the disease, multiple drugs are often required to successfully delay the development of microvascular complications, including CKD. In this context, naringenin, a flavonoid found in citrus fruits, has demonstrated anti-inflammatory, anti-fibrotic, and antioxidant effects, suggesting its potential to protect the kidney from deleterious effects of diabetes. This review aims to summarize the scientific evidence of the effects of naringenin as a potential therapeutic option for diabetes-induced CKD
The severity of intrahepatic cholestasis of pregnancy and its association with pregnancy complications and neonatal asphyxia: A single-center case analysis and systematic review
Get PDFIntrahepatic cholestasis of pregnancy (ICP) poses significant risks to maternal and neonatal health. Our study at Jiangxi Provincial Maternal and Child Health Hospital analyzed clinical and biochemical markers in singleton pregnancies diagnosed with ICP from October 2016 to December 2022. This research, supported by a systematic review and meta-analysis of existing studies, highlights the increasing incidence of ICP and its association with elevated levels of total bile acids, transaminases, and bilirubin. Our findings indicate a marked increase in the risk of preterm birth, cesarean delivery, and neonatal asphyxia as the severity of ICP escalates. This underscores the need for vigilant monitoring and management of affected pregnancies. By confirming the relationship between biochemical marker abnormalities and adverse pregnancy outcomes, our study advocates for enhanced clinical strategies and paves the way for future research aimed at improving prevention, diagnosis, and treatment methods for ICP
Development and evaluation of interpretable machine learning regressors for predicting femoral neck bone mineral density in elderly men using NHANES data
Get PDFOsteoporotic femoral neck fractures (OFNFs) pose a significant orthopedic challenge in the elderly population, accounting for up to 40% of all osteoporotic fractures and leading to considerable health deterioration and increased mortality. In addressing the critical need for early identification of osteoporosis through routine screening of femoral neck bone mineral density (FNBMD), this study developed a user-friendly prediction model aimed at men aged 50 years and older, a demographic often overlooked in osteoporosis screening. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study involved outlier detection and handling, missing value imputation via the K nearest neighbor (KNN) algorithm, and data normalization and encoding. The dataset was split into training and test sets with a 7:3 ratio, followed by feature screening through the least absolute shrinkage and selection operator (LASSO) and the Boruta algorithm. Eight different machine learning algorithms were then employed to construct predictive models, with their performance evaluated through a comprehensive metric suite. The random forest regressor (RFR) emerged as the most effective model, characterized by key predictors such as age, body mass index (BMI), poverty income ratio (PIR), serum calcium, and race, achieving a coefficient of determination (R²) of 0.218 and maintaining robustness in sensitivity analyses. Notably, excluding race from the model resulted in sustained high performance, underscoring the model’s adaptability. Interpretations using Shapley additive explanations (SHAP) highlighted the influence of each feature on FNBMD. These findings indicate that our predictive model effectively aids in the early detection of osteoporosis, potentially reducing the incidence of OFNFs in this high-risk population