Bosnian Journal of Basic Medical Sciences (BJBMS)
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The landscape of N1-methyladenosine (m1A) modification in mRNA of the decidua in severe preeclampsia
Get PDFRecent discoveries in mRNA modification have highlighted N1-methyladenosine (m1A), but its role in preeclampsia (PE) pathogenesis remains unclear. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify m1A peaks and the expression profile of mRNA in the decidua of humans with early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). We assessed the m1A modification patterns in preeclamptic decidua using 10 m1A modulators. Our bioinformatic analysis focused on differentially methylated mRNAs (DMGs) and differentially expressed mRNAs (DEGs) in pairwise comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE, as well as m1A-related DEGs. The comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE identified 3110, 2801, and 2818 DMGs, respectively. We discerned three different m1A modification patterns from this data. Further analysis revealed that key PE-related DMGs and m1A-related DEGs predominantly influence signaling pathways critical for decidualization, including cAMP, MAPK, PI3K-Akt, Notch, and TGF-β pathways. Additionally, these modifications impact pathways related to vascular smooth muscle contraction, estrogen signaling, and relaxin signaling, contributing to vascular dysfunction. Our findings demonstrate that preeclamptic decidua exhibits unique mRNA m1A modification patterns and gene expression profiles that significantly alter signaling pathways essential for both decidualization and vascular dysfunction. These differences in m1A modification patterns provide valuable insights into the molecular mechanisms influencing the decidualization process and vascular function in the pathogenesis of PE. These m1A modification regulators could potentially serve as potent biomarkers or therapeutic targets for PE, warranting further investigation
A repeated strike loading organ culture model for studying compression-associated chronic disc degeneration
Get PDFMechanical stress has been viewed as one of the key risk factors in accelerating the intervertebral disc degeneration process. The goal of the present study was to employ a repeated strike loading bovine caudal disc system to elucidate the pathophysiological impacts of cumulative mechanical stress on the disc. The discs in the model groups were subjected to two different mechanical stresses: one strike loading or repeated strike loading. The following indices were analyzed: histological morphology, glycosaminoglycan release, disc height, cell viability, apoptosis-related protein expression, and catabolism-related gene expression. Both mechanical stress modes induced degenerative changes in the discs by day 11, such as clefts and delamination of the annulus fibrosus; they increased glycosaminoglycan release. Cell viability was significantly decreased and catabolic gene expression was significantly up-regulated in the degenerative loading group and repeated strike loading group by day 9. These alterations remained evident in the annulus fibrosus tissue of the repeated strike loading group on day 11. Our data suggests that the repeated strike loading model adopted in this study could lead to degenerative changes in the disc organ model. Annulus fibrosus cells displayed a more noticeable response to mechanical stress damage and a slower recovery process, suggesting that the annulus fibrosus serves as a pivotal factor in disc degeneration due to mechanical stress injuries. The study also indicates that due to the gradual self-repair of intervertebral disc cells after injury, it is necessary to apply repeated strike loading on the disc at specific intervals when researching the repair of chronic disc injuries
Circulating soluble suppression of tumorigenicity-2 and the recurrence of atrial fibrillation after catheter ablation: A meta-analysis
Get PDFSoluble suppression of tumorigenicity-2 (sST-2), a marker of myocardial fibrosis and remodeling, has been related to the development of atrial fibrillation (AF). The aim of this meta-analysis was to evaluate the relationship between baseline serum sST-2 levels and the risk of AF recurrence after ablation. Relevant observational studies were retrieved from PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, accounting for between-study heterogeneity. Fourteen prospective cohorts were included. Pooled results showed higher sST-2 levels before ablation in patients with AF recurrence compared to those without AF recurrence (standardized mean difference = 1.15, 95% confidence interval [CI] = 0.67 to 1.63, P < 0.001; I2 = 92%). Meta-regression analysis suggested that the proportion of patients with paroxysmal AF (PaAF) was positively related to the difference in serum sST-2 levels between patients with and without AF recurrence (coefficient = 0.033, P < 0.001). Subgroup analysis showed a more remarkable difference in serum sST-2 levels between patients with and without AF recurrence in studies where PaAF was ≥ 60% compared to those where it was < 60% (P = 0.007). Further analyses showed that high sST-2 levels before ablation were associated with an increased risk of AF recurrence (odds ratio [OR] per 1 ng/mL increment of sST-2 =1.05, OR for high versus low sST-2 = 1.73, both P values < 0.05). In conclusion, high sST-2 baseline levels may be associated with an increased risk of AF recurrence after catheter ablation
Development of a clinical diagnostic model for Bell\u27s palsy in patients with facial muscle weakness
Get PDFEarly diagnosis of Bell\u27s palsy is crucial for effective patient management in primary care settings. This study aimed to develop a simplified diagnostic tool to enhance the accuracy of identifying Bell\u27s palsy among patients with facial muscle weakness. Data from 240 patients were analyzed using seven potential clinical evaluation indicators. Two diagnostic benchmarks were established: one based on clinical assessment and the other incorporating magnetic resonance imaging (MRI) findings. A multivariate logistic regression model was developed based on these benchmarks, resulting in the construction of a predictive tool evaluated through latent class models. Both models retained four key clinical indicators: absence of forehead wrinkles, accumulation of food and saliva inside the mouth on the affected side, presence of vesicular rash in the ear or pharynx, and lack of pain or symptoms associated with tick exposure, rash, or joint pain. The first model demonstrated excellent discriminative ability (area under the curve [AUC] = 0.96, 95% confidence interval [CI] 0.94 - 0.99) and calibration (P < 0.001), while the second model also showed good performance (AUC = 0.88, 95% CI 0.83 - 0.92) and calibration (P = 0.005). Bootstrap validation indicated no significant overfitting. The latent class defined by the first model significantly aligned with the clinical diagnosis group, while the second model showed lower consistency
The efficacy of Salvia-ligustrazine and Ligustrazine in treating gestational hypertension: A systematic review and meta-analysis
Get PDFPregnancy-induced hypertension syndrome (PIH), a prevalent and critical condition, has garnered increasing attention due to its significant impact on maternal and fetal health outcomes. The conventional treatment approaches rely on magnesium sulfate and various antihypertensive drugs; however, the clinical efficacy of these treatments is limited, highlighting the need to explore alternative avenues for improvement. Recently, a growing number of clinical studies have investigated the use of Salvia-ligustrazine or Ligustrazine in combination with conventional therapy. A comprehensive synthesis and critical analysis of these studies is necessary to evaluate the efficacy and safety of Salvia-ligustrazine or Ligustrazine in treating PIH. We sought all articles published prior to December 2, 2023, from seven databases to identify randomized controlled trials (RCTs) that involved traditional Chinese medicine Salvia-ligustrazine or Ligustrazine in combination with Western medicines for the conventional treatment of PIH, according to predefined inclusion criteria. The studies were assessed using the Cochrane Risk of Bias tool (ROB2.0), and meta-analyses were conducted using Stata 15.0 statistical software. We analyzed 47 RCTs encompassing 4,517 patients. The results demonstrated that combining Salvia-ligustrazine or Ligustrazine with Western medications was more efficacious than using Western medications alone. This combination improved the overall response rate, reduced the incidence of adverse pregnancy outcomes for mothers and infants, and decreased the occurrence of side effects associated with PIH treatment. While we evaluated the efficacy of traditional Chinese medicine injections of Salvia-ligustrazine or Ligustrazine alongside conventional Western treatments, our conclusions must be considered provisional due to potential bias and the limited availability of RCTs
Total glucosides of paeony inhibit NLRP3/caspase-1/GSDMD-mediated inflammation and pyroptosis in C3H/HeJ mice with alopecia areata
Get PDFOne of the most prominent causes of alopecia areata (AA) is chronic inflammation of the hair follicles. Inhibiting cellular pyroptosis, a form of inflammatory programmed cell death, is crucial for reducing follicular inflammation in the skin. Total glucosides of paeony (TGP) possess anti-inflammatory properties across a broad range of illnesses. However, the role of TGP in AA and its relationship to pyroptosis remain unclear. A chronic unpredictable mild stress (CUMS) approach was used to create an AA mouse model. TGP suspension and MCC950 were administered to AA mice via gavage. HE staining, ELISA, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blotting were performed to detect pathological changes in the skin and investigate the levels of inflammatory factors and pyroptosis-related proteins, as well as the potential mechanisms of TGP’s effects. TGP reduced hair loss, increased the number of hair follicles in skin tissues, and decreased inflammatory markers (IL-6, TNF-α, IL-18, and IL-1β) in AA mice. MCC950 significantly reduced the levels of NLRP3/caspase-1/Gasdermin D (GSDMD)-mediated pyroptosis-related proteins (NLRP3, ASC, caspase-1 p10, and GSDMD-N), as well as inflammatory factors. TGP markedly inhibited NLRP3/caspase-1/GSDMD-mediated cellular pyroptosis in a concentration-dependent manner. TGP suppresses the NLRP3/caspase-1/GSDMD signaling cascade in the skin tissues of AA mice, thereby reducing cellular pyroptosis and inflammation. TGP may be a potential therapeutic agent for AA
Study on the mechanism of liver cancer immune escape mediated by MINDY1 through regulation of PD-L1 ubiquitination level
Get PDFThe novel deubiquitinase enzyme, motif interacting with ubiquitin-containing novel DUB family-1 (MINDY1), is highly expressed in liver cancer tissues and plays a crucial role in maintaining the stemness of liver cancer cells. Programmed death ligand-1 (PD-L1) is an immunosuppressive molecule overexpressed by tumour cells. The potential role of MINDY1 in inhibiting the stemness of liver cancer cells by deubiquitinating PD-L1 has not yet been reported. To investigate the mechanism by which MINDY1 mediates immune escape in liver cancer through the regulation of PD-L1 ubiquitination, we examined the expression levels of MINDY1 and PD-L1 in liver cancer and adjacent tissues from 50 hepatocellular carcinoma (HCC) patients using protein imprinting and immunohistochemistry. We analyzed the relationship between the expression levels of MINDY1 and PD-L1 in liver cancer tissues and their correlation with the 5-year tumor-free survival rates of patients. Subsequently, MINDY1 expression was knocked down in Huh7 cells using small interfering RNA (siRNA) interference or upregulated through transfection with a MINDY1 overexpression plasmid. The effects of MINDY1 knockdown or overexpression on the proliferation, apoptosis, migration, and invasion of HCC cells, as well as the regulation of PD-L1 binding and ubiquitination, were assessed. The 5-year tumor-free survival rates were significantly lower in both the high MINDY1 expression group and the high PD-L1 expression group (χ2 = 4.919 and 13.158, respectively). A significant difference in survival was observed between the high and low MINDY1 expression groups (χ2= 27.415). MINDY1 was found to directly interact with PD-L1, with MINDY1 gene knockdown promoting PD-L1 ubiquitination and MINDY1 overexpression inhibiting PD-L1 ubiquitination. All comparisons yielded statistically significant results (P < 0.05). In conclusion, MINDY1 inhibits the malignant progression of liver cancer by inhibiting PD-L1 ubiquitination and mediating immune escape
Epiplakin expression dynamics during colon carcinogenesis: Correlation with proliferation
Get PDFColorectal cancer poses a significant global health challenge, with a considerable proportion arising from colon adenomas. Understanding the molecules involved in the carcinogenesis process is crucial for improving colon cancer diagnosis and prognosis. While research on the role of epiplakin in cancer remains limited compared to other plakin group proteins, comprehending its expression patterns and correlations can offer valuable insights into colon carcinogenesis. In this study, we analyzed 60 tissue samples, including colon adenocarcinomas, tubular adenomas (low malignancy risk group), tubulovillous adenomas (high malignancy risk group), and adjacent normal colon tissues. Classification and grading were reevaluated by histological examination. Immunohistochemistry was performed to assess epiplakin and Ki67 expression. Epiplakin optical density and the Ki67 proliferation index were calculated using ImageJ. Statistical analyses were conducted to evaluate correlations and significance. Epiplakin expression was significantly decreased in colon adenocarcinomas [optical density median 4.04 (95% CI, 3.98 to 4.24)] and tubulovillous adenomas [4.32 (95% CI, 4.08 to 4.32)] compared to normal colon tissues [4.61 (95% CI, 4.50 to 4.67)] and tubular adenomas [4.87 (95% CI, 4.67 to 4.88)] (P < 0.05). Moreover, adenoma groups exhibited higher proliferation indices (P < 0.05), and a positive correlation was found between epiplakin expression and the Ki67 proliferation index (r = 0.317, P < 0.05). Our study highlights the potential significance of epiplakin in colorectal cancer. Decreased epiplakin expression is associated with colon malignancy progression, suggesting its role as a potential marker
Research progress on pathogenesis of skin pigmentation in chronic liver disease
Get PDFChronic liver disease (CLD) is a significant global health concern that leads to increased morbidity and mortality, and is associated with skin pigmentation changes. Excessive facial pigmentation is a common characteristic of patients with CLD, although the exact mechanism underlying this phenomenon remains unclear. Melanin, which consists of eumelanin and pheomelanin, is synthesized in melanocytes. Its production is influenced by cysteine levels and is regulated by key enzymes, such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2). The transport of melanosomes within melanocytes relies primarily on the coordinated action of F-actin and microtubules. However, the mechanism of melanin transfer from melanocytes to surrounding dendritic cells requires further investigation. Several factors contribute to liver fibrosis, including oxidative stress and inflammatory cytokines. This article discusses the factors that are elevated in the serum of patients with chronic liver disease, which may increase melanin deposition. It also introduces the signaling pathways related to melanin synthesis, providing indirect evidence for the pathological mechanisms underlying increased melanin synthesis in CLD. Additionally, the article points out that pigmentation may serve as an important indicator of liver disease deterioration and suggests the formation of a scoring system that combines related factors to enhance the predictive accuracy. In terms of treatment, antioxidants and anti-inflammatory drugs, such as silymarin and vitamin E, may improve CLD and reduce skin pigmentation, but their specific effects still require further investigation. Future research should focus on validating the mechanisms linking pigmentation changes with CLD progression, and exploring therapeutic methods that can simultaneously improve liver function and skin pigmentation, ultimately aiming for better patient outcomes
MiR-509-3p promotes gastric cancer development by activating FOXM1-mediated p38/MK2 pathway
Get PDFGastric cancer (GC), a malignant tumor, is highly prevalent, particularly in Asia. miR-509-3p plays a crucial role in regulating tumorigenesis, but its mechanism in GC remains unclear. Potential targets of miR-509-3p were identified through database analyses (miRWalk, TargetScan, ENCORI, and TCGA). The binding site between miR-509-3p and forkhead box protein M1 (FOXM1) was confirmed using a dual-luciferase assay. CCK-8, EdU, Transwell, wound healing assays, flow cytometry, and Western blot analysis were employed to examine changes in proliferation, migration, invasion, apoptosis, FOXM1, and the p38 MAPK (p38)/MAPK-activated protein kinase 2 (MK2) pathway in GC cells (MNK-45 and HGC-27) after miR-509-3p overexpression or knockdown, FOXM1 overexpression, and application of the p38 pathway agonist Anisomycin. The size and weight of subcutaneous xenografts were measured, and the effects of miR-509-3p overexpression were analyzed through histopathological staining (Tunel immunofluorescence, HE staining, Ki67, and FOXM1 immunohistochemistry). The results showed that overexpression of miR-509-3p suppressed proliferation, migration, and invasion, while accelerating apoptosis. Knockdown of miR-509-3p promoted malignant progression. miR-509-3p inhibited GC by regulating FOXM1-mediated p38/MK2 pathway activation, and miR-509-3p mimics restrained tumor growth in vivo through this pathway. In conclusion, miR-509-3p suppresses GC malignant progression by regulating FOXM1-mediated p38/MK2 pathway activation