Bosnian Journal of Basic Medical Sciences (BJBMS)
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miR-542-3p attenuates corticosterone-induced hippocampal neuronal damage in depressive mice by modulating PTEN/AKT/GSK3β/β-catenin pathway
Full text linkDepression is a common psychological disease, and nerve injury is the key link of depression. The molecular mechanism involved in this link needs to be explored. miR-542-3p can reduce the degree of hippocampal neuronal damage in rats, but its mechanism in the neural damage of depression is still unclear. HT-22 cell injury was induced by corticosterone (CORT). After overexpression or knockdown of miR-542-3p, CORT-induced HT-22 cell injury was tested by cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay and flow cytometry. Inflammatory and oxidative stress indicator levels were analyzed by kit and flow cytometry. The target genes of miR-542-3p were obtained by database analysis, and the targeting relationship between miR-542-3p and phosphatase and tensin homolog (PTEN) was explored based on dual luciferase assay. After PTEN overexpression or application of AKT pathway agonist MK-2206, the degree of cell damage, inflammation, and oxidative stress were detected again. CORT was used to induce depression in mice. Pathological changes of brain tissue structure and neuronal survival were observed by pathological staining. The miR-542-3p, PTEN, and AKT/GSK3β/β-catenin pathway protein levels in vivo and in vitro were detected by qRT-PCR and Western blot. Overexpression/knockdown of miR-542-3p alleviated/aggravated CORT-induced cell injury, inflammation, and oxidation levels in HT-22 cells (P < 0.05). Meanwhile, overexpressed miR-542-3p can reduce neurological damage of mice. miR-542-3p can target PTEN, and it can trigger the AKT/GSK3β/β-catenin pathway by targeting PTEN expression to reduce CORT-induced nerve injury (P < 0.05). miR-542-3p can reduce CORT-induced hippocampal neuronal damage by targeting PTEN and activating the AKT/GSK3β/β-catenin pathway
Comparison of robotic, conventional, and endoscopic nipple-sparing mastectomy with immediate prosthetic breast reconstruction for breast cancer: A systematic review and meta-analysis
Full text linkIn this network meta-analysis (NMA), we aimed to evaluate the relative efficacy of robotic nipple-sparing mastectomy (RNSM), conventional nipple-sparing mastectomy (CNSM), and endoscope-assisted nipple-sparing mastectomy (ENSM), each combined with immediate prosthetic breast reconstruction (IPBR), for the treatment of breast cancer. Relevant studies published up to June 15, 2024, were identified through searches of PubMed, Embase, the Cochrane Library, and Web of Science. Data extracted from these studies were analyzed using Stata 15.1 and the Gemtc 1.0.1 package in R 4.2.3. A Bayesian framework and a Markov Chain Monte Carlo model were employed to conduct the NMA. Additionally, a ranking chart was generated to compare the advantages and disadvantages of the surgical methods. Ten studies met the inclusion criteria and were included in the NMA. The results indicated that ENSM with immediate implant-based reconstruction was associated with a smaller incision compared to CNSM. RNSM combined with IPBR was linked to a lower incidence of total complications, Grade 3 complications, and nipple-areola complex necrosis than CNSM. Furthermore, RNSM with IPBR demonstrated a lower recurrence rate than CNSM. However, CNSM with IPBR showed better outcomes in terms of surgical time, hospital stay, and positive margin infiltration. In contrast, RNSM and ENSM, both combined with IPBR, outperformed CNSM in terms of incision length, complication rates, and recurrence outcomes
PF4 in rejuvenation therapy: Neuroprotection and cognitive enhancement
Full text linkPlatelet factor 4 (PF4), a platelet-derived chemokine found in the blood, has been identified as a critical factor in modulating the rejuvenation of the aged brain. Increasing evidence suggests that PF4 secretion is a prerequisite for the cognitive benefits associated with young blood transfusion, the longevity factor klotho, and exercise. Systemic administration of exogenous PF4 has been shown to reduce circulating pro-aging immune factors and restore peripheral immune function in the aged brain by mitigating age-related hippocampal neuroinflammation, promoting molecular changes in synaptic plasticity, and improving cognitive function in aged mice. Clinically, reduced serum PF4 levels have been significantly associated with cognitive decline and core pathological biomarkers in Alzheimer’s disease. Mechanistically, the chemokine receptor CXCR3 partially mediates the cellular, molecular, and cognitive benefits of systemic PF4 administration in the aged brain. However, several critical questions remain, including the potential role of PF4 in blood–brain communication, its interaction with neurotransmitters and neuropharmacological processes, and how these findings might be translated into clinical practice. Further detailed studies are needed to validate and expand upon these insights for therapeutic application
A deep learning model based on chest CT to predict benign and malignant breast masses and axillary lymph node metastasis
Full text linkDifferentiating early-stage breast cancer from benign breast masses is crucial for radiologists. Additionally, accurately assessing axillary lymph node metastasis (ALNM) plays a significant role in clinical management and prognosis for breast cancer patients. Chest computed tomography (CT) is a commonly used imaging modality in physical and preoperative evaluations. This study aims to develop a deep learning model based on chest CT imaging to improve the preliminary assessment of breast lesions, potentially reducing the need for costly follow-up procedures such as magnetic resonance imaging (MRI) or positron emission tomography-CT and alleviating the financial and emotional burden on patients. We retrospectively collected chest CT images from 482 patients with breast masses, classifying them as benign (n = 224) or malignant (n = 258) based on pathological findings. The malignant group was further categorized into ALNM-positive (n = 91) and ALNM-negative (n = 167) subgroups. Patients were randomly divided into training, validation, and test sets in an 8:1:1 ratio, with the test set excluded from model development. All patients underwent non-contrast chest CT before surgery. After preprocessing the images through cropping, scaling, and standardization, we applied ResNet-34, ResNet-50, and ResNet-101 architectures to differentiate between benign and malignant masses and to assess ALNM. Model performance was evaluated using sensitivity, specificity, accuracy, receiver operating characteristic (ROC) curves, and the area under the curve (AUC). The ResNet models effectively distinguished benign from malignant masses, with ResNet-101 achieving the highest performance (AUC: 0.964; 95% CI: 0.948–0.981). It also demonstrated excellent predictive capability for ALNM (AUC: 0.951; 95% CI: 0.926–0.975). In conclusion, these deep learning models show strong diagnostic potential for both breast mass classification and ALNM prediction, offering a valuable tool for improving clinical decision-making
Metagenomic and metabolomic analysis of gut microbiome\u27s role in spinal cord injury recovery in rats
Full text linkSpinal cord injury (SCI) induces profound systemic changes, including disruptions in gut microbiome composition and host metabolism. This study aimed to investigate the impact of SCI on gut microbial diversity and serum metabolites in rats, and to explore potential microbiome–metabolite interactions that may influence recovery. Male Sprague–Dawley (SD) rats were assigned to either SCI or sham-operated groups. Fecal samples were collected for whole-genome metagenomic sequencing, and serum samples were analyzed using untargeted metabolomics. Gut microbial composition and diversity were assessed using α- and β-diversity indices, while Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa. Metabolomic pathway analysis was performed to detect significant changes in serum metabolites, and Spearman’s correlation was used to evaluate associations between gut microbes and metabolites. SCI significantly altered gut microbiota composition, with increased proportions of Ligilactobacillus and Staphylococcus, and decreased proportions of Lactobacillus and Limosilactobacillus. Metabolomic analysis revealed disrupted energy metabolism and elevated oxidative stress in SCI rats, as indicated by increased serum levels of pyruvate and lactic acid. Correlation analysis further identified significant associations between specific gut bacteria and key metabolites, suggesting microbiome-driven metabolic dysregulation following SCI. These findings highlight significant interactions between the gut microbiota and host metabolism after SCI and suggest that microbiome-targeted interventions may hold therapeutic potential for improving recovery by modulating metabolic function and oxidative stress responses
Hormonal predictors of the lean phenotype in humans
Full text linkClinical obesity is characterized by excessive fat accumulation and an increased risk of numerous associated comorbidities. Adipose tissue secretes leptin and other adipokines, which play key roles in regulating energy balance, glucose homeostasis, and body fat mass. Recently, incretin and pancreatic hormones have also been shown to influence these processes. However, the regulatory mechanisms and interactions among these hormones are not yet fully understood. This study investigates hormonal predictors of the lean phenotype (in terms of total body fat) in patients undergoing body contouring surgery, with or without prior bariatric surgery. This prospective quasi-experimental study included patients who underwent body contouring procedures at Hamad General Hospital between January 2021 and December 2023. Patients were assessed at three time points: before surgery, 2–3 weeks post-surgery, and 6–10 weeks post-surgery. Body composition and hormone levels were measured, and statistical analyses—including descriptive statistics and logistic regression models—were used to examine trends and predict the lean phenotype. Among the hormones analyzed, amylin showed a significant association with the lean phenotype while increasing leptin, GIP and spexin levels negatively modulated the amylin effect. History of bariatric surgery weakly predicted the lean phenotype after adjusting for leptin and gut hormone levels. A margins plot demonstrated the interactions between amylin, spexin, GIP, and leptin levels that collectively predicted the probability of exhibiting the lean phenotype. These findings highlight amylin, GIP, leptin, and spexin as key hormonal predictors of fat mass, underscoring the critical role of gut hormones and adipokines in determining body fat distribution and the lean phenotype in humans
Vitamin D and depression in adults: A systematic review
Full text linkDepression is one of the most prevalent psychiatric disorders and a leading cause of disability worldwide. Although the pathogenesis of depression remains far from fully understood, current research suggests a potential role for vitamin D due to its involvement in brain functioning. Moreover, vitamin D supplementation has shown promising results in the treatment of patients with depression. Therefore, the present study aimed to systematically review the available research investigating the association between vitamin D levels and the onset of depression. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered in the PROSPERO database (registration number: CRD42024515918). A search was performed across PubMed/Medline, SCOPUS, and Web of Science databases, yielding a total of 8,052 potentially eligible articles. After the removal of duplicates and ineligible records, and exclusion based on title and abstract screening, 297 original full-text articles were assessed according to the inclusion and exclusion criteria. Ultimately, 66 articles were included in this systematic review. Most of the included studies employed a cross-sectional design (N = 46). Overall, the data analyzed in this review indicate an association between depression and vitamin D serum levels, particularly in studies using cross-sectional designs. Only a few longitudinal studies demonstrated that lower vitamin D levels are associated with an increased risk of developing depressive symptoms or major depressive disorder, highlighting an important research gap. However, it remains to be established through future research whether acute or chronic vitamin D supplementation could have a protective effect against the development of depression
PJ34 prevents cisplatin-induced hair cell loss via inhibition of PARP-1–AIF parthanatos
Full text linkThe poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 acts as an anti-inflammatory and neuroprotective agent by modulating parthanatos. This study aimed to explore the protective effects of PJ34 against cisplatin-induced injury in auditory cells and to elucidate its underlying mechanism of action. Flow cytometry and immunofluorescence were employed to detect apoptosis in HEI-OC1 and ovarian cancer cell lines. Additionally, immunofluorescence and Western blotting were used to assess changes in the expression of related proteins, including cleaved Caspase-3, PARP-1, and cytosolic apoptosis-inducing factor (AIF), across the groups. Mitochondrial membrane potential (MMP) levels were measured using the MMP assays, and reactive oxygen species (ROS) levels were assessed by MitoSox red staining. Our results indicate that treatment with 30 μM cisplatin activates cleaved Caspase-3, promotes PARP-1 overexpression, and facilitates AIF nuclear translocation, leading to decreased MMP and increased ROS accumulation, which ultimately triggers auditory cell death. Treatment with 2.5 μM PJ34 mitigated PARP-1 overexpression and AIF nuclear translocation following cisplatin exposure, reduced the decline in MMP, and decreased ROS accumulation, thereby alleviating damage to auditory cells. Conversely, PJ34 enhanced the damaging effects of cisplatin on ovarian cancer cell lines. In conclusion, our findings suggest that PJ34 may reduce cisplatin-induced hair cell death by regulating PARP-1-mediated parthanatos. Notably, PJ34 shows promise as a potential novel therapeutic agent for the prevention and/or treatment of cisplatin-induced ototoxicity
Pirfenidone reduces ovarian fibrosis and improves PCOS in letrozole-induced rat model
Full text linkPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by cystic ovarian morphology, anovulation, and infertility. Ovarian fibrosis has recently emerged as a key pathological feature of PCOS. This study investigated whether pirfenidone (PFD), an antifibrotic agent, could improve ovarian dysfunction in a letrozole-induced PCOS rat model. Forty-two female Wistar albino rats were divided into six groups (n=7 each): control, PFD, PCOS, PCOS/PFD, PCOS/combined oral contraceptives (COC), and PCOS/PFD/COC. PCOS was induced using letrozole (1 mg/kg/day orally for 21 days). PFD (200 mg/kg/day) and/or COC (0.18 mg/kg cyproterone acetate and 0.00315 mg/kg ethinyl estradiol) were administered for 21 days. Compared to controls, PCOS rats exhibited significant disruptions in estrous cyclicity, ovarian morphology, and fibrosis-related markers (all p<0.0001), despite no significant changes in testosterone (p=0.058) or estrogen (p=0.896) levels. PFD treatment significantly improved estrous cyclicity, follicular profile, and corpora lutea count (all p<0.0001), reduced ovarian fibrosis (p<0.0001), downregulated TGF-β1, CTGF, and MMP-9 (all p<0.0001), and upregulated PPAR-γ and MMP-2 (both p<0.0001), without affecting hormone levels (p=0.945 and p=0.479, respectively). COC treatment also improved estrous cyclicity and ovarian histology (all p<0.0001), reduced fibrosis (p=0.005), and modulated TGF-β1, CTGF, MMP-9, and PPAR-γ expression (p=0.0001 to <0.0001), but had no effect on MMP-2 (p=0.868). Combination therapy (PCOS/PFD/COC) provided additional improvement in corpora lutea count (p<0.0001 vs. PCOS/PFD) and collagen deposition (p=0.002 vs. PCOS/PFD) but did not confer further benefits in fibrosis-related marker expression or folliculogenesis (all p>0.05). These findings suggest that pirfenidone mitigates PCOS pathology by targeting ovarian fibrosis, supporting antifibrotic therapy as a novel and promising approach
First-trimester prediction of early-onset preeclampsia using PAPP-A and mean arterial pressure
Full text linkPredicting early-onset preeclampsia (EOP) during the initial stages of pregnancy is essential for effective clinical management and enhancing maternal-fetal outcomes. Current methodologies, which include clinical and demographic risk factors, biophysical parameters, and serum biomarkers, exhibit limited efficacy in predicting EOP. This study aimed to evaluate whether the incorporation of pregnancy-associated plasma protein-A (PAPP-A) and mean arterial pressure (MAP) significantly enhances EOP detection. We conducted a retrospective case-control study involving 518 gravidas, of whom 202 developed EOP and 316 experienced normal pregnancies. Logistic regression models were employed to assess EOP predictions, and the predictive accuracy of these statistical models was evaluated using receiver-operating characteristic curve analysis. Our findings indicate that lower PAPP-A levels, higher MAP, and increased body mass index (BMI) are associated with EOP. Notably, in pregnant women between 11+0 and 13+6 weeks of gestation, a 1-point decrease in PAPP-A corresponds to an 84% increase in the likelihood of developing EOP. The predictive performance of PAPP-A improves significantly when combined with other factors such as BMI, MAP, and a history of diabetes mellitus (DM). The risk of EOP is substantially heightened (20.410 times, 95% CI: 11.104-37.515) in patients exhibiting low PAPP-A levels (<0.88) and high BMI (≥35 kg/m²). Additionally, low PAPP-A combined with elevated MAP levels significantly increases EOP risk (adjusted odds ratio [OR]: 114.83). However, after adjustment, the association between low PAPP-A and a history of DM was not statistically significant (adjusted OR: 2.30, p = 0.202). In conclusion, employing a combination of multiple variables for predicting EOP yields a significant improvement over traditional methods that rely solely on individual factors