BioMed Research International最新文献

This study presents an integrated computational framework that combines three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling with molecular dynamics (MD) simulations to advance the rational design of triazole-based urease inhibitors. Given the role of urease as a central virulence factor in Helicobacter pylori and its increasing relevance in antibiotic-resistant infections, effective predictive methodologies are essential for early-stage inhibitor development. A dataset of 54 triazole derivatives was examined using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), generating statistically robust and predictive models that elucidate the steric, hydrophobic, and hydrogen-bonding features underlying inhibitory potency. These insights, supported by molecular docking and structure-activity relationship analyses, informed the construction of a pharmacophore model used to screen the ZINC database. Several candidate molecules, including ZINC84668437, ZINC84669798, and ZINC244633273, emerged as computationally promising and demonstrated favorable predicted druglikeness and ADMET characteristics. MD simulations were subsequently employed to evaluate the dynamic stability and conformational behavior of the ligand-urease complexes, reinforcing the coherence of the integrated computational workflow. The primary contribution of this work resides in its methodological integration of complementary in silico approaches rather than in experimental validation. Although the findings offer mechanistic insights and prioritize potential lead compounds, they remain predictive and necessitate future empirical confirmation. Overall, the study establishes a rigorous and academically grounded computational strategy that can guide subsequent efforts in the design of selective urease inhibitors for H. pylori-associated diseases.

[This corrects the article DOI: 10.1155/2023/9416281.].

Liver cirrhosis is one of the most common causes of death for pediatric patients with cholestasis. Because microRNA (miRNA) plays a part in the pathogenesis of the disease, comparing the changes in miRNA expression in cholestatic patients with liver cirrhosis could be helpful for therapeutic or prognostic purposes. miRNA levels in cirrhotic pediatric patients with progressive familial intrahepatic cholestasis (PFIC) and biliary atresia (BA) were studied in this research to comprehend the molecular distinctions and the significance of miRNA regulation in fibrosis and liver cirrhosis. Blood samples were collected from 43 PFIC patients and 84 BA patients, all of whom were confirmed to have liver cirrhosis. The in-house SYBR Green RT-qPCR techniques were established to assess the variations in the expressions of 12 miRNAs. Utilizing bioinformatics tools, the gene targets of the studied miRNAs were examined. Patients' expression of 12 miRNAs was higher than that of the healthy group. However, there was a notable distinction between the miRNAs in PFIC and BA. The levels of miR-34, miR-155, miR-199, miR-200b, and miR-222 were significantly higher in BA than in PFIC. PFIC showed a significantly higher level of miR-223 than BA. The predictive importance of distinct miRNAs in both diseases was revealed by the AUC values. In BA, miR-222 was associated with both liver transplantation and the PELD score. Death was correlated with miR-21, miR-155, miR-199, and miR-200 in BA and miR-34 in PFIC. The analysis showed the significance of the connection between miRNA expression and PI3K/Akt and TGF-β signaling in pediatric liver cirrhosis. Future investigations can evaluate the significance of the studied miRNAs as novel therapeutic targets and diagnostic options.

Introduction: Bee pollen, a natural product rich in polyphenols, exhibits remarkable antioxidant, anti-inflammatory, and hepatoprotective properties.

Aim: This study was aimed at evaluating the hepatoprotective effects of solid lipid nanoparticles (SLNs) loaded with bee pollen.

Materials and methods: SLNs were formulated and optimized by varying surfactant ratios and lipid contents at two different temperatures.

Results and discussion: The optimized bee pollen SLNs demonstrated a particle size of 118.6 nm, a PdI of 0.35, a zeta potential of -22.6 mV, and an entrapment efficiency of 92.7%. The in vitro release study showed minimal release during the initial 120 min, followed by a continuous increase up to 48 h, indicating a sustained and prolonged release profile. Both bee pollen and bee pollen ethanolic extract-loaded SLNs exhibited significant cytoprotective effects against lead-induced cytotoxicity in HepG2 cells. In vivo studies revealed that treatment with bee pollen and especially bee pollen SLNs substantially ameliorated lead-induced hepatic injury. Treatment notably reduced serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, malondialdehyde, and nitric oxide. Additionally, it enhanced the activity of glutathione peroxidase, catalase, superoxide dismutase, and total antioxidant capacity, as well as levels of total thiol, reduced glutathione, and liver tissue proteins. Histopathological analysis further confirmed that treatment, particularly with bee pollen SLNs, significantly improved lead-induced hepatic structural damage.

Conclusion: These findings confirm that bee pollen, and more prominently its SLN formulation, possesses strong hepatoprotective potential.

Introduction: The temporalis muscle is a key masticatory muscle involved in jaw movement, specifically in the elevation and retraction of the mandible. This muscle has a complex anatomical structure, which includes both superficial and deep layers that are vital for its function. Variability in the muscle's morphology can influence its efficiency in chewing and may play a role in several clinical conditions, such as temporomandibular joint disorders (TMDs) and bruxism. Understanding the anatomical variations in the temporalis muscle is essential for improving diagnostic accuracy and treatment approaches.

Material and methods: This study included 34 female participants (age: median 48.5 [36-64] years) and 24 male participants (age: median 47.5 [37-68] years). MRI scans were used to assess the anatomy of the temporalis muscle, focusing on the presence of both superficial and deep muscle layers. The presence of a longitudinal muscle core was also examined to identify anatomical variations. Cases were classified based on the presence of both layers and the extent of hypoplasia in the posterior portion of the superficial layer. Descriptive statistics are reported as median and the first and third quartiles (Q1-Q3), and group differences were assessed with nonparametric tests.

Results: The study revealed that the temporalis muscle exhibited significant anatomical variability across participants. In six cases, only the deep layer was present, with symmetry in one female and one male. In 26 cases, the posterior portion of the superficial layer was hypoplastic, appearing as a thin muscular layer. Hypoplasia was significantly more common in males (p = 0.02168). Based on these observations, the muscle was classified into three groups: (1) muscles with both layers intact (72.4%), (2) muscles with both layers but with a hypoplastic posterior portion of the superficial layer (22.4%), and (3) muscles with only the deep layer (5.2%).

Conclusion: This study provides new insights into the anatomical variability of the temporalis muscle, highlighting differences in the superficial and deep layers and the prevalence of hypoplasia in the posterior portion of the superficial layer. These findings have important clinical implications, as they can improve radiological diagnostics and aid in the accurate identification of muscle variations. Understanding these variations enhances the ability to diagnose and treat temporomandibular disorders and related conditions more effectively, offering more personalized care for patients.

Adipose-derived stem cells (ADSCs) have garnered significant interest in regenerative medicine (RM) due to their abundant availability, ease of isolation, and ability to differentiate into various cell types. The growth of ADSCs is crucial for their therapeutic effectiveness, as it directly influences their ability to repair damaged tissues. MicroRNAs (miRNAs) are recognized as powerful regulators of gene expression and cellular functions, including proliferation, and are believed to play a role in modulating the proliferative potential (PP) of ADSCs. This review is aimed at exploring existing research on how miRNAs influence the PP of ADSCs, focusing on aspects such as the cell cycle, ADSC factors, and various signaling pathways, including STAT3, PI3K-AKT, Hippo, Notch, Wnt/β-catenin, and MAPK pathways that affect ADSC proliferation. We also examined the impact of miRNAs on the migration of ADSCs. Through a review of relevant studies, we identified several miRNAs that influence the PP of ADSCs through various mechanisms. These miRNAs interact with key signaling pathways, cell cycle regulators, and other elements related to cell proliferation, leading to both positive and negative effects on ADSC growth. Additionally, numerous studies have suggested that modifying miRNA expression levels could enhance the PP of ADSCs for therapeutic applications. This review provides valuable insights into the intricate regulatory networks involving miRNAs that govern the PP of ADSCs. A deeper understanding of the roles of miRNAs in ADSC proliferation holds promise for improving the efficacy of ADSC therapies and advancing the field of RM. Further research is warranted to elucidate the specific mechanisms by which miRNAs regulate ADSC proliferation and to identify new therapeutic targets for enhancing the regenerative potential of ADSCs. Exploring new miRNA targets, developing miRNA-based therapies, and creating advanced delivery systems are promising avenues for future research. The role of miRNAs in regulating the PP of ADSCs presents exciting opportunities for the advancement of RM and tissue engineering.

Glaucoma is a chronic neurodegenerative disease of the visual system, and treatment is targeted toward lowering intraocular pressure. However, some patients fail to respond to treatment and their intraocular pressure levels remain high, risking continuous vision loss. Explainable machine learning provides a mechanism for both individual prognostication and the identification of factors associated with treatment outcome. Here, we used explainable machine learning to predict intraocular pressure for glaucoma patients receiving medication treatment. We accessed the UK Biobank to obtain information on 290 eyes from 161 participants who reported a diagnosis of glaucoma and were receiving treatment. Features were divided into three distinct datasets containing demographic data only, physiometabolic parameters and medication prescription data, and all data combined. We evaluated five machine learning techniques for each feature set in terms of their ability to predict intraocular pressure at a follow-up visit in a classification task. We then calculated SHapley Additive exPlanation (SHAP) values for the best performing model to determine feature importance, stability, and interactions. We found that eXtreme Gradient Boosting (XGBoost) outperformed all other models when trained and tested on the combined feature set with an area under receiver operating characteristic curve (AUC) of 0.708. Insulin-like growth factor 1 (IGF-1), low-density lipoprotein (LDL), and lymphocyte count ranked as the three most important features for this model. LDL and IGF-1 exhibited a low degree of global variability in contribution to the model output across all cross-validation repeats. SHAP values demonstrated the strongest interactions being between LDL and IGF-1. In summary, our studies indicated the importance of blood LDL and IGF-1 in contributing to the outcomes of intraocular pressure lowering treatment and demonstrated the ability of XGBoost to predict these outcomes.

The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) and biofilm-producing ability have become a worldwide serious concern. This study is aimed at investigating the clonal relationships, coexistence of carbapenemase-resistant and biofilm-related genes, and biofilm biomass capacity in 57 A. baumannii isolates obtained from patients in intensive care units (ICUs). Antibiotic resistance patterns to 11 antibiotics were determined using the disc diffusion test. The minimum inhibitory concentrations (MICs) of imipenem and colistin were evaluated by the microdilution method. All isolates were subjected to PCR for the detection of carbapenemase- and biofilm-related genes and examined for the biofilm-forming ability using crystal violet staining methods. The clonality relationship was identified by rep-PCR. Overall, 49 (86%) isolates were characterized as extensively drug-resistant (XDR) with a high MIC for imipenem. Eight isolates were resistant to colistin (MIC>64 μg/mL). Additionally, 86.21% of isolates were strong biofilm formers, which correlated with the PDR phenotype. All isolates carried at least three genes related to biofilm formation. Genotypically, 100% of isolates had bla _OXA-51-like, bla _OXA-24-like, and bla _TEM genes, followed by bla _VIM (61.4%), bla _OXA-23-like (24.6%), bla _SHV (1.8%), and bla _KPC (1.8%), whereas bla _CTX-M and bla _OXA-58-like genes were not found in the isolates. The rep-PCR analysis identified 10 distinct genotypes, among which GTG Type 3 showed a significant correlation with strong biofilm formation. Moreover, the greatest number of colistin-resistant isolates (MIC>64 μg/mL) were located in this cluster. This study highlights the emergence of PDR A. baumannii strains carrying a variety of β-lactamase and biofilm-related genes in ICUs, underscoring the urgent need for improved infection control measures and antimicrobial stewardship programs to address the spread of these formidable pathogens.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that significantly increases cardiovascular disease (CVD) risk in women. While insulin resistance and dyslipidemia are established contributors, growing evidence highlights mitochondrial dysfunction and chronic low-grade inflammation as central drivers of cardiovascular pathology in PCOS.

Objective: This narrative review synthesizes current evidence on how mitochondrial dysfunction and inflammation interact to promote cardiovascular complications in women with PCOS while identifying potential therapeutic targets and areas requiring further investigation.

Methods: A comprehensive review of clinical and experimental studies was conducted using PubMed, Scopus, and Web of Science databases. Relevant literature exploring mitochondrial alterations, oxidative stress, inflammatory cytokines, and endothelial function in PCOS, with emphasis on cardiovascular outcomes, was critically evaluated and summarized.

Results: Women with PCOS exhibit altered mitochondrial dynamics, reduced ATP production, and elevated reactive oxygen species (ROS), which collectively impair vascular function. These mitochondrial abnormalities compromise oocyte quality and endometrial receptivity and activate proinflammatory signaling pathways, including the NLRP3 inflammasome, contributing to endothelial dysfunction and atherogenesis, and increased long-term cardiovascular risk, particularly in women with prior pregnancy complications. Elevated levels of cytokines including TNF-α, IL-6, and CRP further exacerbate cardiovascular risk. This bidirectional relationship between mitochondrial dysfunction and inflammation establishes a vicious cycle underlying cardiovascular deterioration in PCOS.

Conclusion: Mitochondrial dysfunction and inflammation are interdependent mechanisms that contribute substantially to cardiovascular risk in women with PCOS. Targeting mitochondrial dysfunction and systemic inflammation presents a promising therapeutic strategy for reducing cardiovascular morbidity in PCOS. Future research should emphasize phenotype-specific interventions, biomarker discovery, and translational trials to improve long-term reproductive and cardiovascular outcomes.

The continued reemergence of Ebola virus epidemics remains a global health concern, largely due to limited therapeutic interventions. This study is aimed at identifying and characterizing antiviral peptides as potential lead candidates against the Sudan Ebola virus. We retrieved antiviral peptides from the AVPdb and designed novel peptides from them using support vector machine, RF, and discriminant analysis algorithms. The toxicity and allergenicity predictions were performed using ToxinPred, ADMETLab 3.0, Allertop, and AllergenFP web servers, respectively. The 3D structures of selected peptides were modeled using PEP-FOLD and I-TASSER and validated using ProSA and PROCHECK web servers. The best peptide models were docked against the Sudan Ebola virus VP-40 protein using HDOCK and ClusPro. Molecular dynamics (MD) simulations were then carried out in GROMACS 2024.2. Out of 170 designed motifs, 30 exhibited antiviral potential with antiviral scores ranging from 0.506 to 1.000. Among the predicted antiviral peptides, five demonstrated favorable stability, nontoxicity, and nonallergenic properties. PEP-FOLD produced more stable peptide structures than I-TASSER, with over 84.6% of their amino acids in the most favorable region. Binding energies ranged from -252.39 to -145.83 kcal/mol (HDOCK) and from -887.7 to -538.7 units (ClusPro). The MD simulations confirmed high stability, with motif A10_M showing the strongest binding and structural compactness. Five peptides show strong potential as therapeutic leads against Sudan Ebola virus; however, further experimental validation is recommended.