Bosnian Journal of Basic Medical Sciences (BJBMS)
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Fiber-type composition and 3D capillary analysis of the human splenius capitis muscle
Get PDFDespite the significance of neck muscles in musculoskeletal disorders, their microscopic anatomy remains poorly characterized. This study examined the splenius capitis muscle, focusing on its fiber-type composition, fiber size, and capillary network characteristics. For comparison and validation, the vastus lateralis muscle was also analyzed. Muscle samples from 13 young male subjects (mean age ± SD: 35.7 ± 8.6 years) were collected within 24-h post-mortem during autopsy. Myosin heavy chain (MyHC) isoform expression was characterized immunohistochemically in 10 μm sections, while the capillary network architecture was assessed in 100 μm sections. Immunofluorescence staining, confocal microscopy, and 3D image analysis were employed to quantify capillary tortuosity, anisotropy, branch density (Br dens), and the length of capillaries per muscle volume (LV), per muscle fiber length (LL), per fiber surface area (LS), and per fiber volume (LVf). Compared to the vastus lateralis muscle, the splenius capitis muscle had a higher percentage of type 1 fibers (51.2% vs 39.7%), fewer type 2a fibers (16.2% vs 31.4%), and smaller fiber diameters (35.5–40.9 μm vs 47–56.1 μm). It also displayed lower Br dens (P = 0.0069), higher anisotropy (P = 0.0004), and lower LL (P < 0.0001) but higher LVf (P = 0.0486). In the splenius capitis muscle, body mass index (BMI) negatively correlated with LV (P = 0.0155), LS (P = 0.0091), LVf (P = 0.0137), and anisotropy (P = 0.0425), and positively correlated with tortuosity (P = 0.0473), indicating a reduction in the capillary network. In the vastus lateralis muscle, only LV (P = 0.0161) decreased with high BMI. This study characterized the fiber-type composition, fiber size, and 3D capillary network of the splenius capitis muscle, establishing a baseline for investigations into pathological muscle alterations
Neuromodulation guide for the non-neuromodulator clinician: What it is and how it can benefit patients?
Get PDFNeuromodulation is being utilized across a variety of medical subspecialties to treat both painful and non-painful medical conditions. However, publications on neuromodulation topics infrequently occur in journals targeting generalists and medical specialties outside of pain medicine and neurosurgery. This study reviewed implantable neuromodulation devices, their respective Food and Drug Administration-approved indications for use, as well as off-label usage, and the associated potential risks and benefits for each device. PubMed and Medline databases were queried for systematic reviews with or without meta-analyses and randomized controlled trials of implantable neuromodulation devices. The literature review resulted in 106 studies eligible for inclusion, and 67 were included in the final review. In conclusion, as the clinical volume of neuromodulation continues to grow, supporting and educating medical professionals who care for patients that receive implanted neuromodulation devices is paramount. It is likely the use of neuromodulation will continue to expand across all medical subspecialties, and as such, every clinician should have a baseline understanding of this treatment
Detecting cell types and densities in the tumor microenvironment improves prognostic risk assessment for breast cancer
Get PDFA comprehensive evaluation of the relationship between the densities of various cell types in the breast cancer tumor microenvironment and patient prognosis is currently lacking. Additionally, the absence of a large patch-level whole slide imaging (WSI) dataset of breast cancer with annotated cell types hinders the ability of artificial intelligence to evaluate cell density in breast cancer WSI. We first employed Lasso-Cox regression to build a breast cancer prognosis assessment model based on cell density in a population study. Pathology experts manually annotated a dataset containing over 70,000 patches and used transfer learning based on ResNet152 to develop an artificial intelligence model for identifying different cell types in these patches. The results showed that significant prognostic differences were observed among breast cancer patients stratified by cell density score (P = 0.0018), with the cell density score identified as an independent prognostic factor for breast cancer patients (P < 0.05). In the validation cohort, the predictive performance for overall survival (OS) was satisfactory, with area under the curve (AUC) values of 0.893 (OS) at 1-year, 0.823 (OS) at 3-year, and 0.861 (OS) at 5-year intervals. We trained a robust model based on ResNet152, achieving over 99% classification accuracy for different cell types in patches. These achievements offer new public resources and tools for personalized treatment and prognosis assessment
Effect of parecoxib on postoperative cognitive function and analgesic safety in elderly patients undergoing gastrointestinal tumor resection: A retrospective study
Get PDFNeuroinflammation is associated with the development of postoperative cognitive dysfunction (POCD). Parecoxib has powerful anti-inflammatory and analgesic effects, which may reduce the occurrence of POCD. We hypothesized that parecoxib could reduce the incidence of POCD and relieve postoperative pain without increasing postoperative complications in elderly patients with gastrointestinal cancer. The study analyzed the effect of parecoxib on elderly patients undergoing elective radical resection of gastrointestinal tumors. Patients were divided into the NSAIDs group and the non-NSAIDs group according to whether parecoxib was administered. Demographic and clinical data were collected and compared. The incidence of POCD was set as the primary outcome, and postoperative pain as the secondary outcome. Among the 440 enrolled patients, the POCD incidence rates within 7 days after surgery in the NSAIDs and non-NSAIDs groups were 42.60% and 40.30%, respectively, with no statistically significant difference (P > 0.05). Patients in the NSAIDs group experienced significantly less pain on the first and second days after surgery compared to the non-NSAIDs group (P < 0.05). There were no statistically significant differences in postoperative adverse events between the two groups (P > 0.05). Parecoxib had no significant negative effect on early postoperative cognitive function, effectively alleviating early postoperative acute pain without increasing postoperative complications. The findings have implications for the broader use of parecoxib in postoperative pain management in elderly patients undergoing major surgery
Gene polymorphisms of miR-323b and miR-1343 that regulate kininogen L are associated with schizophrenia susceptibility: A preliminary population‑based study
Get PDFmiR-SNP is a type of functional single nucleotide polymorphism (SNP) that affects the regulatory functions of miRNA genes, miRNA binding sites, or components of miRNA biogenesis. This study aimed to explore the relationship between miRNA gene polymorphisms that regulate the kininogen L protein and schizophrenia (SCZ). Bioinformatics methods predicted miRNA gene polymorphism sites regulating the kininogen L protein. The polymorphisms of rs56103835, rs6513496, rs651349, and rs2986407 were detected using imLDR multiple SNP typing technologies in 513 SCZ patients and 509 controls. The association of miR-SNP variations with SCZ susceptibility and symptoms was evaluated using SNPstat to determine the optimal inheritance model. Generalized multifactor dimensionality reduction (GMDR) analysis and logistic regression were used to calculate miR-SNP interactions. The association between hsa-miR-323b-rs56103835 and SCZ was statistically significant under the dominant model. The result of gene-gene interaction showed that the three-factor model (rs56103835 / rs2986407 / rs2155248) was the best, but it could not be considered significantly related to SCZ. Additionally, SCZ patients with the CC or CT genotype on rs2986407 were more likely to experience auditory hallucinations than those with the TT genotype. Our data revealed that the mutation of hsa-miR-323b-rs56103835 from C to T was associated with susceptibility to SCZ. The mutation of hsa-miR-1343-rs2986407 from T to C increases the risk of auditory hallucinations in SCZ patients
Inhibition of the long non-coding RNA MALAT1 downregulates MAP2K1, suppressing the progression of hypopharyngeal squamous cell carcinoma
Get PDFThis study aimed to explore the role of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript (lncRNA MALAT1), and its underlying mechanisms in hypopharyngeal squamous cell carcinoma (HSCC). Quantitative real-time PCR (qRT-PCR) was employed to measure lncRNA MALAT1 expression in HSCC and adjacent non-cancerous tissues, along with the expression of the downstream target mitogen-activated protein kinase kinase 1 (MAP2K1). The independent prognostic significance of lncRNA MALAT1 was assessed using Cox regression analysis. Potential downstream targets of MALAT1 were identified through parallel reaction monitoring (PRM) analysis and validated using the TCGA-HNSC database, Western blotting, and immunohistochemistry. CCK-8, flow cytometry, and Transwell assays were conducted to assess the effects of the lncRNA MALAT1/MAP2K1 axis on FaDu cells. Additionally, a nude mouse xenograft model was used to confirm the role of lncRNA MALAT1/MAP2K1 in tumor growth. LncRNA MALAT1 was significantly upregulated in HSCC tissues and closely associated with poor prognosis. Bioinformatics analysis, including PRM screening and TCGA-HNSC data, identified FERMT2, CSNK2A2, and MAP2K1 as potential downstream targets of MALAT1. Validation through qPCR, Western blotting, and immunohistochemistry confirmed MAP2K1 as a downstream target. In vitro and in vivo experiments demonstrated that inhibiting lncRNA MALAT1 suppressed cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) by downregulating MAP2K1 expression. Additionally, it induced apoptosis, affected the cell cycle, and inhibited tumor growth. Our study uniquely demonstrates that targeting MALAT1 significantly impedes HSCC progression by downregulating its novel downstream target, MAP2K1, offering new insights into potential therapeutic strategies
miR-149-3p targeting TMPRSS4 regulates the sensitivity to cisplatin to inhibit the progression of lung cancer
Get PDFLung cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung cancer cells’ sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited cancer progression, promoted apoptosis, and enhanced the chemosensitivity of lung cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung cancer cells to DDP
The diagnostic accuracy of exosomes for glioma: A meta-analysis
Get PDFGlioma is one of the most prevalent primary intracranial tumors, and biomarker testing offers a non-invasive modality with high diagnostic efficiency. The aim of this meta-analysis is to evaluate the diagnostic effectiveness of exosomes as biomarkers for glioma. We included 16 studies on exosomes as biomarkers for gliomas. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for 25 biomarkers across these 16 studies were as follows: 82% (95% CI: 0.77-0.86), 91% (95% CI: 0.86-0.94), 9.10 (95% CI: 5.64-14.68), 0.20 (95% CI: 0.16-0.25), 45.94 (95% CI: 25.40-83.09), and 0.92 (95% CI: 0.89-0.94), respectively. Meta-regression indicated that biomarker analysis, biomarker type, and sample size may be sources of heterogeneity. Subgroup analysis suggested that ultracentrifugation (UC) was a better method for extracting exosomes. miRNA and other RNA groups (sncRNA, lncRNA, circRNA) provided higher SEN (0.88 vs. 0.84 vs. 0.78) compared to proteins. This study demonstrates the superior diagnostic efficacy of exosomes as biomarkers for gliomas, with high accuracy in diagnosing gliomas
Dapagliflozin and Sirtuin-1 interaction and mechanism for ameliorating atrial fibrillation in a streptozotocin-induced rodent diabetic model
Get PDFThe incidence of atrial fibrillation (AF) increases with age and is particularly high in individuals with diabetes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), such as dapagliflozin, show promise in treating heart failure (HF) and reducing the risk of AF. Sirtuin 1 (SIRT1), a key enzyme in metabolic regulation, may be influenced by SGLT2i and play a role in the development of AF. This study investigates the relationship between dapagliflozin therapy and atrial tachyarrhythmia in diabetic cardiomyopathy, with a focus on the role of SIRT1. A streptozotocin (STZ)-induced diabetes mellitus (DM) rat model was used to assess AF across four groups: sham, STZ, STZ with dapagliflozin, and STZ with dapagliflozin + sirtinol (a SIRT1 inhibitor). Additionally, HL-1 cardiomyocytes were cultured under high glucose (HG) conditions and treated with dapagliflozin, with or without sirtinol. In the rat model, dapagliflozin improved atrial fibrosis and reduced AF inducibility and duration—effects that were partially reversed by sirtinol. These findings suggest that dapagliflozin may alleviate cardiac fibrosis and atrial arrhythmia by modulating SIRT1. In HL-1 cells under HG conditions, dapagliflozin reduced apoptosis, restored autophagy and mitophagy, and improved calcium channel activity. However, sirtinol negated these protective effects. Dapagliflozin helped normalize autophagy, mitophagy, and calcium handling, while sirtinol diminished its protective effects, highlighting the key role of SIRT1 in regulating calcium handling under HG conditions. Overall, SIRT1 plays a protective role in diabetic cardiomyopathy by reducing apoptosis, regulating autophagy and mitophagy, and modulating calcium channel activity. Dapagliflozin reduces AF duration and inducibility in the STZ model, likely through SIRT1 upregulation and calcium channel modulation
Comprehensive analysis of a NAD+ metabolism-derived gene signature to predict the prognosis and immune landscape in endometrial cancer
Get PDFAs a crucial regulator influencing tumor progression, nicotinamide adenine dinucleotide (NAD+) is widely acknowledged. However, its role in endometrial cancer (EC) is not completely understood. In this study, we aimed to develop an NAD+metabolic-related genes (NMRGs) risk signature that could reflect the prognosis of EC patients and their responsiveness to immunotherapy and chemotherapy. Data from The Cancer Genome Atlas (TCGA) databases and the Molecular Signatures Database (MSigDB) confirmed two distinct NMRG subtypes in EC patients using consensus clustering, and a risk score was constructed utilizing an NAD+-related prognostic signature depending on the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Receiver operating characteristic (ROC) curves were employed to assess the model’s precision. Additionally, we used Gene Set Enrichment Analysis (GSEA) to predict the biological signaling pathways that might be involved. We also explored the role of the risk score in immune cell infiltration, tumor mutation burden (TMB), immunotherapy, and chemotherapy. Our study established a prognostic risk signature based on six NMRGs, and we observed that the high-risk group was associated with a poorer prognosis. Furthermore, we identified a strong correlation between the high-risk group and several pathways, including DNA replication, cell cycle, and mismatch repair. Lastly, our findings highlighted the influence of NMRGs on the regulation of immune infiltration in EC. Therefore, this signature holds potential value in predicting the prognosis of EC patients and guiding their management, including decisions regarding immunotherapy and chemotherapy, ultimately improving the accuracy of EC patient care