Bosnian Journal of Basic Medical Sciences
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NEIL3 and TOP2A as key drivers of esophageal cancer through WNT signaling
Full text linkEsophageal cancer (EC) is a highly aggressive malignancy with limited treatment options. Nei like DNA glycosylase 3 (NEIL3) and DNA topoisomerase II alpha (TOP2A) have been identified as potential therapeutic targets, though their roles in EC remain unclear. This study investigates the effects of NEIL3 overexpression and TOP2A knockdown, focusing on the WNT signaling pathway. ECA109 esophageal cancer cells were used to assess the impact of NEIL3 overexpression and TOP2A knockdown on proliferation, colony formation, migration, invasion, and apoptosis. The involvement of the WNT signaling pathway was also explored. NEIL3 overexpression significantly enhanced proliferation, colony formation, migration, and invasion while reducing apoptosis. In contrast, TOP2A knockdown suppressed these functions and promoted apoptosis, independent of NEIL3. NEIL3 overexpression could not reverse the effects of TOP2A knockdown. Both NEIL3 and TOP2A acted through the WNT signaling pathway. In vivo, NEIL3 knockdown reduced tumor size and weight via WNT pathway modulation. NEIL3 and TOP2A play key roles in EC progression through the WNT signaling pathway. Targeting these molecules may offer promising therapeutic strategies for EC
Letrozole versus coenzyme Q10 plus Clomiphene citrate for women with Polycystic Ovarian Syndrome: An efficacy and safety analysis
Full text linkClomiphene citrate is a well-established treatment for Polycystic Ovarian Syndrome (PCOS) but has poor efficacy and adverse effects. Coenzyme Q10 supplementation improves mitochondrial function. Letrozole has been reported to be effective with fewer adverse effects but is not approved for PCOS by the USFDA. This is a retrospective study in women diagnosed with PCOS to assess treatment with either 2.5 mg/day letrozole (LO cohort, n = 103) for 5 days per cycle (for 9 cycles). The QC group received additional doses of 50 mg coenzyme Q10 three times daily (QC cohort, n = 123). A third group received only 100 mg/day clomiphene citrate (CC cohort, n = 155) from the second day of the menstrual cycle for 5 days. After treatment, the duration of the menstrual cycle decreased across all cohorts (P < 0.001 for all), with a smaller reduction observed in the LTZ cohort compared to the QC and CC cohorts (P < 0.05 for all). The number of conceived pregnancies in the LTZ cohort (P < 0.0001) and the CC + QC cohort (P < 0.0001) was significantly higher than in the CC only group. Similarly, conception was higher in the CC + Q10 group than in the CC only group (P < 0.0001 for both groups). Letrozole versus clomiphene citrate plus coenzyme Q10 showed similar efficacy in achieving pregnancy in women with PCOS
APOC1 knockdown induces apoptosis and decreases angiogenesis in diffuse large B-cell lymphoma cells through blocking the PI3K/AKT/mTOR pathway
Full text linkDiffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous metastatic lymphoma that can be treated by targeting angiogenesis. Apolipoprotein C1 (APOC1) plays a significant role in the proliferation and metastasis of various malignant tumors; however, its role in DLBCL—particularly its effects on angiogenesis—remains largely unexplored. This study investigates the correlation between APOC1 expression and patient prognosis in DLBCL. Using APOC1 gene knockdown, apoptosis, migration, and invasion were assessed through flow cytometry, the EDU assay, wound healing, and Transwell assays. Additionally, human umbilical vein endothelial cells (HUVEC) angiogenesis was evaluated. Advanced techniques, such as immunofluorescence, TUNEL assay, and immunohistochemical labeling were employed to analyze the effects of APOC1 knockdown on the PI3K/AKT/mTOR signaling pathway and tumor formation in nude mice. Results showed that APOC1 is overexpressed in DLBCL tissues and cells, with high APOC1 levels associated with poor patient prognosis. In vitro experiments revealed that APOC1 knockdown increased apoptosis and inhibited cell proliferation, migration, invasion, HUVEC angiogenesis, and PI3K/AKT/mTOR signaling pathway protein expression in DLBCL cells. Similarly, in vivo studies demonstrated that APOC1 knockdown significantly reduced tumor growth, angiogenesis-related proteins, and phosphorylated PI3K/AKT/mTOR pathway proteins in nude mice. APOC1 knockdown promotes apoptosis and suppresses angiogenesis in DLBCL cells by inhibiting the PI3K/AKT/mTOR pathway
Glioblastoma induces CAF-like astrocyte activation via the AKT/mTOR–SERPINH1/COL5A1 axis
Full text linkGlioblastoma multiforme (GBM), the most aggressive form of glioma, remains the most malignant tumor of the central nervous system. Despite a range of therapeutic strategies, the prognosis for GBM patients remains poor, underscoring the urgent need for novel treatments to inhibit GBM progression. The tumor microenvironment (TME) plays a critical role in tumor development, with cancer-associated fibroblasts (CAFs) acting as key components. However, the origin, composition, and spatial distribution of CAFs within the GBM microenvironment remain poorly understood. To address this gap, our research aims to investigate the etiology, cellular composition, and precise localization of CAFs in GBM, with the goal of elucidating their role in oncogenesis and tumor progression, thereby providing new avenues for therapeutic intervention. In this study, we developed a novel CAF-related prognostic model using data from the TCGA and GEO databases and identified SERPINH1 and COL5A1 as CAF-related genes in GBM. We established a GBM mouse model as well as a GBM cell and astrocyte co-culture system to examine the expression of SERPINH1 and COL5A1 in astrocytes under a simulated tumor microenvironment. Our findings revealed that these genes were more highly expressed in peritumoral tissue compared to normal brain tissue and showed strong co-localization with astrocytes. Furthermore, we found that normal astrocytes can be induced by GBM cells to activate the AKT/mTOR signaling pathway, migrate to the peritumoral region, and upregulate CAF-associated proteins (SERPINH1/COL5A1). These results suggest that astrocytes may serve as a potential source of CAF precursor cells within the GBM tumor microenvironment
Association of serum Netrin-1, NSE, and S100β with brain injury severity and prognosis in patients with sepsis-associated encephalopathy
Full text linkSepsis-associated encephalopathy (SAE) represents the most prevalent neurological complication of sepsis and is frequently linked to unfavorable patient outcomes. This study aimed to evaluate the prognostic significance of serum Netrin-1, neuron-specific enolase (NSE), and S100β levels in patients diagnosed with SAE. A retrospective analysis was performed on 120 SAE patients, measuring serum levels of Netrin-1, NSE, and S100β and correlating these with Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores. Independent risk factors for short-term mortality were identified, and the predictive values of these biomarkers were assessed both individually and in combination. Kaplan-Meier analysis was utilized to compare short-term mortality based on biomarker levels. Netrin-1 was found to be significantly downregulated, while NSE and S100β levels were upregulated in SAE patients. Lower levels of Netrin-1, alongside higher levels of NSE and S100β, correlated with elevated APACHE-II scores and increased short-term mortality. Multivariate analysis confirmed that all three biomarkers serve as independent predictors of short-term mortality. The combined assessment of Netrin-1, NSE, and S100β demonstrated superior prognostic value compared to individual biomarker. Therefore, serum levels of Netrin-1, NSE, and S100β are closely associated with the severity of brain injury in SAE and serve as effective predictors of short-term mortality, enhancing prognostic accuracy in clinical practice
Passenger lymphocyte syndrome – Epidemiology, pathogenesis, diagnosis, treatment and future directions: A review
Full text linkPassenger lymphocyte syndrome (PLS) is a hematological complication that can occur following transplantation, characterized by donor-derived memory B lymphocytes producing antibodies against the recipient\u27s blood cells. This review examines the pathophysiology, diagnostic approaches, and treatment strategies aimed at enhancing clinical management and standardizing therapeutic protocols for PLS. A literature search was conducted using Web of Science and PubMed to identify relevant publications on PLS, resulting in 79 studies. Studies were selected based on predefined criteria, including a focus on human donor-derived alloimmunity, documented blood group antigen-antibody interactions, transplantation context, clinical data on outcomes or management, and methodological validity. Only studies containing actual patient data and substantive discussions about PLS were included. PLS commonly presents as hemolytic anemia, accompanied by elevated lactate dehydrogenase (LDH) levels, indirect hyperbilirubinemia, and reduced haptoglobin levels. Diagnosis is primarily based on clinical manifestations and laboratory tests, including the direct antiglobulin test (DAT) and antibody screening. Differential diagnosis is crucial for excluding drug-induced hemolytic anemia and thrombotic microangiopathy. Current treatment strategies for PLS focus on halting hemolysis and restoring hematological balance. First-line treatment includes donor-compatible red blood cell transfusions and high-dose corticosteroids, while refractory cases may necessitate rituximab or plasmapheresis. Despite advancements in PLS management, challenges persist, including delayed diagnosis due to self-limiting cases and a lack of standardized treatment protocols. Future research should incorporate genomic and proteomic biomarkers for accurate diagnosis and risk prediction. Developing mechanism-driven therapies targeting donor lymphocytes and establishing global consensus frameworks can enhance monitoring, improve graft survival, and optimize transplant recipient outcomes.
Correction: Synthesis, characterization, and in vitro–in ovo toxicological screening of silibinin fatty acids conjugates as prodrugs with potential biomedical applications
Full text linkCorrected article: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10600
The affiliation of the first author, Cristina Adriana Dehelean, was incomplete in the originally published version of this article. One of the authors asked to add her third institutional affiliation.
The correct affiliations for Cristina Adriana Dehelean are as follows:
1Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Timișoara, Romania2Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Timișoara, Romania3Faculty of Food Engineering, University of Life Sciences “King Michael I” from Timișoara, Timișoara, Romania.
We apologize to the readership for any inconvenience caused
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
Remimazolam vs propofol for postoperative delirium in adults undergoing general anesthesia: A meta-analysis
Full text linkPostoperative delirium (POD) is a prevalent and serious complication in adults undergoing surgery with general anesthesia. Remimazolam, an innovative ultra-short-acting benzodiazepine, has been identified as a potential alternative to propofol due to its advantageous pharmacological properties. However, its impact on POD remains uncertain. This study conducted a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of the PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang databases was performed up to March 29, 2025. Randomized controlled trials (RCTs) comparing remimazolam and propofol in adult surgical patients under general anesthesia, specifically reporting on POD incidence, were included. A random-effects model was utilized to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs), accounting for heterogeneity. The analysis included seventeen RCTs encompassing 3,133 patients. Overall, remimazolam significantly decreased the risk of POD compared to propofol (OR: 0.71, 95% CI: 0.52–0.97, p = 0.03; I² = 36%). Sensitivity analyses, which involved excluding one study at a time, yielded consistent results, reinforcing the robustness of the findings. Subgroup analyses revealed uniform effects across different study designs (single-blind vs. double-blind; OR: 0.73 vs. 0.64; p = 0.71) and age groups (adults vs. elderly; OR: 0.64 vs. 0.72; p = 0.79). A trend toward greater benefit was observed in studies with longer follow-up periods (7 days: OR: 0.42) and in those employing the CAM or CAM-ICU for POD diagnosis, although subgroup differences were not statistically significant. In conclusion, remimazolam is associated with a significantly reduced risk of POD compared to propofol in adults undergoing general anesthesia
Mitochondrial dysfunction triggers Zbp1-mediated necroptosis and inflammation in acute lung injury
Full text linkAcute lung injury (ALI) is driven by dysregulated inflammation, but how mitochondrial damage engages necroptosis in alveolar macrophages remains unclear. We aimed to define the mechanistic link between mitochondrial impairment and Zinc finger protein 1 (Zbp1)–mediated necroptosis in the murine alveolar macrophage–like cell line (MH-S). MH-S cells were stimulated with lipopolysaccharide (LPS) and profiled by RNA sequencing; necroptotic death was quantified by Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release, Zbp1 localization was examined by immunofluorescence microscopy, and Zbp1, receptor-interacting protein kinase 3 (RIPK3)/phospho-RIPK3 (p-RIPK3) and mixed lineage kinase domain-like protein (MLKL)/phospho-MLKL (p-MLKL) were measured by Western blotting. Mitochondrial status was assessed by mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (ΔΨm; JC-1), mitochondrial permeability transition pore (MPTP) opening, adenosine triphosphate (ATP) content, and the markers ATP synthase F1 subunit alpha (ATP5a1), mitochondrial transcription factor A (TFAM), and translocase of outer mitochondrial membrane 20 (TOMM20); inflammatory responses were quantified by flow cytometry and qPCR. The mitochondria-targeted antioxidant Mito-TEMPO was used to interrogate the role of oxidative stress. LPS markedly increased Zbp1 transcription, coincident with upregulation of pro-inflammatory genes and activation of necroptosis; mitochondrial damage and elevated mtROS were critical upstream events for Zbp1 induction, driving RIPK3 and MLKL phosphorylation, necroptosis, and cytokine release. Mito-TEMPO restored mitochondrial function, lowered mtROS, downregulated Zbp1 and its necroptotic effectors (p-RIPK3, p-MLKL), and significantly reduced both necroptotic injury and inflammatory output. Collectively, mitochondrial dysfunction–driven mtROS initiates the Zbp1/RIPK3/MLKL necroptotic axis in alveolar macrophages, thereby amplifying pulmonary inflammation in ALI; targeting mtROS may mitigate necroptosis and protect against lung injury