Bosnian Journal of Basic Medical Sciences (BJBMS)
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The impact of MITF expression on tumor-infiltrating lymphocytes in melanoma: Insights into immune microenvironment dynamics
Get PDFMelanoma progression is influenced by complex interactions between tumor cells and the immune microenvironment. This study examined the relationship between microphthalmia-associated transcription factor (MITF) expression and the immune microenvironment in primary melanoma using a modified classification of tumor-infiltrating lymphocytes (TILs) based on conventional BRISK categories. Archival formalin-fixed, paraffin-embedded tissue samples from 81 primary melanoma patients were analyzed via tissue microarray immunohistochemistry to assess MITF protein levels. TIL patterns were categorized into six groups, refining the traditional BRISK classification to distinguish between continuous and discontinuous infiltration, as well as peripheral vs intratumoral distribution. The analysis revealed that melanomas classified under the BRISK B category exhibited the highest MITF expression, often exceeding 50%. In contrast, tumors in the NON-BRISK and ABSENT TIL groups showed significantly lower MITF expression (mean values: 32.73% ± 16.98% and 22.00% ± 10.54%, respectively), with statistically significant differences (Kruskal–Wallis test, P = 0.027; modified classification, P = 0.011). Additionally, the presence of CD20+ B lymphocytes correlated with increased MITF expression (P = 0.009). MITF gene amplification was detected in 29% of cases, though its association with protein expression showed only a trend (P = 0.058). These findings highlight the complex interplay between MITF expression and TIL distribution in melanoma, suggesting that refined TIL classification may offer deeper insights into tumor immunobiology and help predict responses to immunotherapy
Luteolin mitigates hippocampal damage in a rat model of streptozotocin-induced diabetes
Get PDFDiabetes mellitus (DM) is a chronic metabolic disorder that poses a serious threat to human health by causing long-term damage to various vital organs. It leads to insulin resistance and disrupts carbohydrate, fat, and protein metabolism. This study aimed to investigate the protective effects of luteolin (Lut) against diabetes-induced damage in the hippocampus of rats, using immunohistochemical, histopathological, biochemical, and molecular approaches. Lut [20 μg/kg, intraperitoneally (i.p.)] was administered to counteract hippocampal damage induced by diabetes, which was experimentally triggered using streptozotocin at a dose of 50 mg/kg (i.p.). The experiment lasted 28 days and included 48 rats divided into six groups of eight: Control, DM, citrate buffer (solvent), DM+Lut, Lut, and dimethyl sulfoxide (solvent). In the DM group, there was a decrease in Bcl-2 gene expression and an increase in the expression levels of Bax, caspase-3, cytochrome c, activating transcription factor-6, and inositol-requiring enzyme-1, compared to the DM+Lut group. Histological analysis revealed greater neuronal degeneration, neuroinflammation, and apoptosis in the DM group than in the DM+Lut group. Biochemical analysis also supported these findings, as indicated by increased oxidative stress index values. These results suggest that Lut mitigates the toxic effects of oxidative and endoplasmic reticulum stress, enhances antioxidant defenses, and supports hippocampal function. The findings demonstrate Lut’s potential to prevent diabetes-induced hippocampal damage. Consequently, further research is strongly recommended to explore Lut as a therapeutic agent for diabetic neurodegeneration
Role of indocyanine green fluorescence and inferior thyroid artery ligation in hypocalcemia after total-thyroidectomy
Get PDFPostoperative hypocalcemia remains a frequent complication of total thyroidectomy, and identifying intraoperative strategies to prevent it continues to be a key clinical challenge. This retrospective study aims to evaluate the role of indocyanine green (ICG) fluorescence imaging and truncal ligation of the inferior thyroid artery in the development of hypocalcemia following total thyroidectomy. Additionally, it seeks to identify factors associated with or predictive of hypocalcemia measured on postoperative day 1, as well as to determine the prevalence of transient and permanent hypoparathyroidism. The study included 200 patients who underwent total thyroidectomy performed by the same surgical team between January 2023 and March 2024. The surgical technique employed involved ligation of the inferior thyroid artery at its proximal trunk. Serum calcium levels were assessed for all patients during hospitalization, and again at 10 and 30 days post-surgery. Additionally, the relationship between postoperative calcemia and the vascularization of at least one parathyroid gland was evaluated using indocyanine green fluorescence imaging. Hypocalcemia (<8.5 mg/dL) was observed in 81 patients (40.5%) on postoperative day 1. The rate of transient hypoparathyroidism was 31% (62 patients), while permanent postoperative hypoparathyroidism was seen in 2.5% (5 patients). Patients with a positive vascularization index on indocyanine green fluorescence imaging were significantly less likely to experience hypocalcemia (Fisher’s exact test, p = 0.0014). The truncal ligation of the inferior thyroid artery did not significantly influence the occurrence of transient or permanent hypoparathyroidism. In conclusion, indocyanine green fluorescence imaging is confirmed as a useful tool for evaluating parathyroid vascularity, although its associated costs should be carefully considered
The immunotherapy breakthroughs in cervical cancer: Focus on potential biomarkers and further therapy advances
Get PDFDespite the well-established role of human papillomavirus (HPV) as the primary cause of cervical cancer (CC) and the existence of an effective HPV vaccine, over half a million women are diagnosed with CC globally each year, with more than half of them dying from the disease. Immunotherapy has rapidly become a cornerstone of cancer treatment, offering substantial improvements in survival rates and reducing treatment-related side effects compared to traditional therapies. For the past 25 years, chemoradiotherapy (CRT) has been the standard treatment for locally advanced CC (LACC). However, while adjuvant chemotherapy has failed to improve outcomes in LACC, the integration of neoadjuvant chemotherapy (NACT) with CRT, as well as chemoimmunoradiotherapy followed by consolidation immunotherapy, has transformed treatment strategies, demonstrating superior efficacy compared to CRT alone. In the first-line treatment of CC, adding pembrolizumab to platinum-based chemotherapy, either with or without bevacizumab, has significantly improved outcomes compared to platinum-based chemotherapy and bevacizumab alone. This review explores the current landscape of immunotherapy and biomarker advancements in CC. Furthermore, we discuss promising future directions, including the potential of personalized immunotherapy approaches and novel combination therapies to further enhance treatment efficacy and improve prognoses for patients with CC
Serum NPTX2 and cognitive impairment in geriatric diabetes
Get PDFCognitive impairment is an increasingly common complication of diabetes, yet its underlying pathophysiological mechanisms remain poorly understood. Neuronal pentraxin 2 (NPTX2), a recently identified synaptic biomarker linked to cognitive disorders, has not previously been examined in relation to cognitive function in geriatric individuals with diabetes. This cross-sectional study enrolled 90 participants—46 geriatric patients with diabetes and 44 age-matched non-diabetic controls. Demographic and clinical data were collected for all participants. After informed consent, cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Serum NPTX2 levels were measured by ELISA. No significant differences were found between the diabetic and control groups in age, sex, education level, marital status, smoking history, comorbid conditions, or polypharmacy. However, the groups differed significantly in MoCA scores (p < 0.001), MMSE scores (p = 0.028), and NPTX2 levels (p = 0.048); the diabetic group showed lower cognitive scores and biomarker levels. NPTX2 levels correlated positively with MoCA and MMSE scores and negatively with diabetes duration, patient age, and the presence of microvascular complications. In conclusion, cognitive function was significantly lower in geriatric patients with diabetes than in controls, and serum NPTX2 levels were significantly associated with cognitive performance. These findings suggest a possible role for NPTX2 in diabetes-related cognitive decline and support further investigation of its utility within a broader biomarker panel
Beyond BMI: An opinion on the clinical value of AI-powered CT body composition analysis
Get PDFBody Mass Index (BMI) has long been used as a standard measure for assessing population-level health risks, but its clinical adequacy has increasingly been called into question. This opinion paper challenges the clinical adequacy of BMI and presents AI-enhanced CT body composition analysis as a superior alternative for individualized risk assessment. While BMI serves population-level screening, its inability to differentiate between tissue types leads to critical misclassifications, particularly for sarcopenic obesity. AI-powered analysis of CT imaging at the L3 vertebra level provides precise quantification of skeletal muscle index, visceral, and subcutaneous adipose tissues -metrics that consistently outperform BMI in predicting outcomes across oncology, cardiology, and critical care. Recent technological advances have transformed this approach: the "opportunistic" use of existing clinical CT scans eliminates radiation concerns, while AI automation has reduced analysis time from 15-20 minutes to mere seconds. These innovations effectively address previous implementation barriers and enable practical clinical application with minimal resource demands, creating opportunities for targeted interventions and personalized care pathways
Procalcitonin in acute and chronic coronary syndromes: Diagnostic biomarker of coronary inflammation
Get PDFProcalcitonin (PCT) is classically a biomarker of bacterial infection, but its role in cardiovascular inflammation—particularly in coronary artery disease (CAD)—is less well defined. Evidence linking PCT with disease extent and outcomes across acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) remains limited. We compared PCT levels among ACS, CCS, and angiographic controls; examined associations with inflammatory burden and anatomic complexity (SYNTAX score); and evaluated diagnostic performance and short- and intermediate-term prognostic value. In this single-center retrospective study, 477 consecutive adults undergoing diagnostic coronary angiography (December 2019–March 2020) were categorized as ACS (n=190), CCS (n=202), or controls with normal epicardial arteries (n=85). Demographic, laboratory, and angiographic data were collected. PCT was measured within 24 hours of admission. Multivariable logistic regression (using log10-transformed PCT) assessed independent associations with ACS and CCS. Correlations tested relationships with SYNTAX, C-reactive protein (CRP), and troponin-I. Receiver operating characteristic (ROC) analyses quantified discrimination. In ACS, outcomes were compared by PCT ≥0.25 ng/mL. Median PCT was higher in ACS and CCS than in controls (both p<0.001). Log10-PCT independently predicted disease presence in ACS (OR 4.30, 95% CI 2.00–9.20, p<0.001) and CCS (OR 2.81, 95% CI 1.43–5.54, p=0.003). In CCS, PCT correlated weakly but significantly with SYNTAX score (r=0.274, p=0.002); no meaningful correlations with SYNTAX, CRP, or troponin-I were observed in ACS. PCT showed moderate diagnostic accuracy (AUC 0.791 for ACS; optimal cut-off 0.25 ng/mL, sensitivity 82.4%, specificity 65.3%; and AUC 0.763 for CCS; optimal cut-off 0.30 ng/mL, sensitivity 89.4%, specificity 54.0%; all p<0.001). In ACS, PCT ≥0.25 ng/mL was not associated with higher in-hospital mortality, 1-year all-cause mortality, or major adverse cardiovascular events. PCT reflects inflammatory burden and the presence of CAD in both ACS and CCS and remains an independent predictor of disease presence, but its prognostic utility—particularly in ACS—is limited. PCT should complement, not replace, established biomarkers and anatomical scoring systems in clinical decision-making. Prospective, multicenter studies with serial PCT measurements are warranted to refine its clinical role
Correction: Glioblastoma induces CAF-like astrocyte activation via the AKT/mTOR–SERPINH1/COL5A1 axis
Get PDFCorrection to: Glioblastoma induces CAF-like astrocyte activation via the AKT/mTOR–SERPINH1/COL5A1 axis
This corrigendum corrects the authors’ affiliations to:
Jingxian Zhang¹,²#, Yajia Chen¹,²#, and Hongwu Xu¹,²*.
¹Department of Neurosurgery, Tenth Affiliated Hospital, Southern Medical University, Dongguan, Guangdong, China.²Department of Human Anatomy, Shantou University Medical College, Jinping District, Shantou, Guangdong, China.
The authors sincerely apologize for this error and confirm that this correction does not affect the scientific content or conclusions of the article
S-palmitoylation-related genes in Crohn\u27s disease: Bioinformatic identification and validation
Get PDFCrohn\u27s disease (CD) is a complex chronic inflammatory bowel disorder characterized by the absence of reliable biomarkers and effective targeted treatments. Recent evidence has suggested a role for S-palmitoylation, a reversible post-translational modification, in immune regulation and intestinal inflammation. However, a systematic, gene-centric investigation explicitly linking S-palmitoylation to the pathogenesis and diagnosis of CD has not been conducted. To address this gap, our study employs a comprehensive bioinformatic analysis to identify and validate key genes associated with both CD and S-palmitoylation, assessing their potential as diagnostic biomarkers and therapeutic targets. Utilizing data from the Gene Expression Omnibus (GEO, GSE83448) and GeneCards, we identified 23 S-palmitoylation-associated differentially expressed genes (SP-DEGs) in CD. Functional enrichment analysis indicated their significant roles in cysteine-specific S-palmitoylation and immunometabolic regulation. We applied machine learning algorithms, including least absolute shrinkage and selection operator (LASSO) regression and support vector machine–recursive feature elimination (SVM-RFE), to select nine hub genes. Validation in two independent cohorts (GSE16879 and GSE59071) and ROC analysis confirmed ZDHHC23 and IFITM1 as biomarkers with high diagnostic value. These genes also exhibited correlations with immune infiltration patterns, as determined by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), MCPcounter, and QuanTIseq. In vitro experiments corroborated consistent changes in mRNA and protein expression for both ZDHHC23 and IFITM1, reinforcing their involvement in CD. This study offers systematic insights into the functional roles of S-palmitoylation-related genes in CD, providing a novel theoretical foundation for the development of diagnostic and targeted therapeutic strategies
Rare liver diseases — Etiology, diagnosis and management: A review
Get PDFRare liver diseases (RLDs) are diverse and often misdiagnosed conditions that impose significant clinical and public health challenges due to their variable presentations and limited treatment options. This study aims to synthesize contemporary evidence on the etiology, classification, diagnostics, and management of RLDs and to identify near-term research and implementation priorities. We conducted a systematic search of PubMed and Scopus for the years 2015 to 2025 using predefined keywords. We included peer-reviewed human studies, such as guidelines, randomized trials, and large registries, focusing on mechanisms, diagnostic strategies, and treatments. We excluded animal studies and non-peer-reviewed reports, extracting data on disease biology, diagnostic tools, outcomes, and molecular therapies. RLDs can be categorized into genetic/inherited, autoimmune cholestatic, and other vascular/metabolic entities. Care for these diseases is increasingly guided by structured pathways that integrate biochemistry and serology with magnetic resonance cholangiopancreatography (MRCP), elastography, targeted next-generation sequencing (NGS), and selective biopsy. Emerging biomarkers, such as circulating microRNAs, alongside machine learning in imaging techniques, enhance disease staging and prognostication. Key management strategies include the use of bile-acid modulators, surgical interventions, and ileal bile acid transporter (IBAT) inhibitors for progressive familial intrahepatic cholestasis (PFIC). Lifelong copper chelation is recommended for Wilson disease, with trientine preferred for neurologic phenotypes. Supportive care in alpha-1 antitrypsin deficiency (A1ATD) is complemented by the investigation of molecular chaperones. Additionally, gene-directed therapies, gene editing, RNA-based approaches, and cell therapies show early promise but raise concerns regarding durability, safety, and ethical considerations, particularly for pediatric patients. In conclusion, implementing precision medicine frameworks that rely on standardized diagnostics, multicenter registries, and equitable access is crucial for facilitating earlier detection and translating mechanism-targeted therapies into sustainable, globally accessible benefits