bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospects for thermochemi-cal processing of salty coals in Ukraine
Authors: Bryk D.V. , Kulchytska-Zhygaylo D.Z. , Hvozdevych O.V. , Gerlevskyi Yu.Ya.
Published: December 2024

The article shows that the need for a comprehensive study of salty coal (SC) is largely determined by the technological challenges of using it for energy purposes. The combustion of salty coal causes slagging of boilers with subsequent destruction of metal parts and heat-insulating carborundum materials. From the experience of salty coal combustion, it is known that the presence of sodium in coal leads to a decrease in the slagging temperature of 750-850 °C. In addition, the combustion of SC causes sodium condensation on the walls of pipelines and heat exchange surfaces. Specific characteristics of the SC, on which its thermochemical processing depends, are formulated. It is shown that currently, for the use of SC in different countries, it is proposed to burn it together with other coal; the possibilities of creating new equipment and reconstruction of existing boiler plants for burning coal without preliminary cleaning are considered. It is noted that the use of various fluxes and rocks containing kaolin was also studied, and methods of salty coal gasification were developed. Attention is paid to the developments of the Institute of Geology and Geochemistry of Combustible Minerals of the National Academy of Sciences of Ukraine (Lviv), where a bench-scale installation for studying the processes of thermochemical processing of lump coal has been created. A promising process for the thermochemical conversion of salty coal can also be the patented methods of gasification of water-coal pulp developed at the Institute, which involves both sodium leaching at the initial stage of the process when the pulp is introduced into the reactor and its rapid transition to a water-vapour extract directly during the high-temperature process of pulp gasification. The article presents the principle technological schemes of the method of SC conversion, in particular, thermochemical processing of salty coal pulp, patented by IGGGK NAS of Ukraine. In addition to the surface processing of SC, salty coal deposits may be suitable for the use of underground gasification technology. It has been determined that the most promising areas of thermochemical conversion of salty coal will be the gasification of water-coal pulp and underground gasification processes. Therefore, the problem of salty coal requires further scientific research. Keywords: salty coal, energy purposes, combustion, slagging, thermochemical processing, coal pulp, underground coal gasification. Corresponding author D.V. Bryk, e-mail: dmytrobryk@ukr.net
Alpha Lipoic Acid Supplementation and Iron Homeostasis: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Sharifi-Zahabi Elham , Abdollahzad Hadi
Published: December 2024

Background: A growing body of evidence indicates the regulating effects of alpha-lipoic acid on iron metabolism. However, findings from clinical trials are equivocal. This systematic review and meta-analysis aimed to evaluate the quantitative effect of alpha lipoic acid (ALA) supplementation on iron metabolism parameters including serum iron, total iron binding capacity, hemoglobin, and ferritin. Methodology: Online databases, including PubMed, Scopus, and Web of Science were searched, up to 29 May 2022, to obtain all relevant studies. Results: A total of 1901 publications were identified in the systematic search; of which, 10 studies with a total of 529 participants were included in this meta-analysis. Pooled analysis of the studies showed no statistically significant effects of ALA on ferritin (weighted mean difference (WMD) = –11.01 ng/mL; 95% CI: –40.07, 18.05 ng/mL; I2 = 0.0%, p = 0.670), serum iron (WMD = –0.47 μ/dL; 95% CI: –24.48, 23.54 μ/dL; I2 = 94.7%, p < 0.001), hemoglobin (WMD = 0.49 g/dL; 95% CI: –0.54, 1.52 g/dL; I2 = 95.7%, p < 0.001), and total iron binding capacity (TIBC) (WMD = 3.95 μ/dL; 95% CI: –21.3, 29.2 μ/dL; I2 = 53.1%, p = 0.094). In subgroup analysis, ALA significantly increased hemoglobin in patients with hematological disorders (WMD = 1.23 g/dL; 95% CI: 1.00, 1.45 g/dL; I2 = 96.6%, p < 0.001) and in studies with durations longer than 8 weeks (WMD = 1.03 g/dL; 95% CI: 0.82, 1.25 g/dL; I2 = 96.5%, p = 0.02). Conclusion: ALA supplementation had no statistically significant effect on iron-related parameters. Subgroup analysis revealed a significant increasing effect of ALA on hemoglobin in patients with hematological disorders and in studies with durations >8 weeks.
Fat Distribution as a Determinant of Vitamin D Status: A Cross-Sectional Study of Adults in the United States
Authors: Bai Yu
Published: December 2024

Background: This study aimed to elucidate correlations between obesity-related indicators and vitamin D (VD) status in a nationally representative sample of U.S. adults. Methods: We analysed data from 9168 adults aged 20–59 years obtained from the 2011–2018 National Health and Nutrition Examination Survey. Serum 25 hydroxyvitamin D [25(OH)D] levels were measured and categorised into quartiles. Anthropometric measurements, including weight, waist circumference, and fat mass in various body regions quantified through dual-energy X-ray absorptiometry, were collected. Multiple imputation was employed to replace missing data. The importance of obesity-related indicators and serum 25(OH)D concentration was explored using multiple linear regression adjusted for demographics, lifestyle factors, dietary intake, and clinical biomarkers, and stepwise regression. Results: Weight, waist circumference, and fat mass across all body regions were inversely associated with serum 25(OH)D levels (all p < 0.001). Notable differences were observed between men and women. Stepwise regression revealed a strong inverse correlation between visceral adipose tissue and serum 25(OH)D concentration in men [β 95% CI: –13.04 (–18.10, –7.99), p < 0.001], whereas in women, only weight was significantly correlated with serum 25(OH)D concentration [β 95% CI: –0.20 (–0.28, –0.12), p < 0.001]. Demographic attributes, seasonal sunlight exposure, dietary VD, calcium, phosphorus, and magnesium intake, and biomarkers including alkaline phosphatase and creatinine also emerged as significant predictors. Conclusions: Besides conventional obesity measures, abdominal fat metrics exhibit robust associations with VD deficiency, especially in men. Public health initiatives and clinical management strategies for hypovitaminosis D in obese populations should consider nuanced aspects of adiposity distribution alongside other demographic, lifestyle, and dietary factors influencing VD.
Role of Lutein Supplements in the Management of Dry Eye Syndrome: A Systematic Review
Authors: Chu Yi-Ching , Huang Chao-Chun
Published: December 2024

Background: Dry Eye Disease (DED) significantly impacts global populations, causing discomfort and vision problems. This review explores the effects of lutein supplementation on DED symptoms and signs. Methods: A systematic review was conducted following PRISMA guidelines, examining clinical trials from databases including PubMed, Web of Science, EMBASE, and the Cochrane Library. Six randomized controlled trials (RCTs) involving 584 subjects were included. Meta-analysis was not conducted due to heterogeneity in study designs, dosages, and outcome measures. Results: Lutein dosages ranged from 3 mg/day to 20 mg/day, with treatment durations from 4 to 12 weeks. Improvements were observed in subjective symptoms, with significant reductions in Ocular Surface Disease Index (OSDI) scores in some studies. Objective measures also showed positive results: tear break-up time (TBUT) increased significantly in some trials. However, other studies reported no significant differences between treatment and control groups, reflecting heterogeneity in outcomes. Schirmer’s test and corneal-conjunctival staining results varied, with some showing significant improvements and others not. Conclusions: Lutein supplementation may benefit DED patients by improving symptoms and tear film stability. However, due to study heterogeneity, larger, well-designed RCTs are needed to establish standardized dosing and confirm these findings.
The Utility of Maternal Adiponectin and Triglyceride-Glycemic Index for Gestational Diabetes Mellitus Screening: A Cross-Sectional Study
Authors: Al-Rawi H.A.G. , Nori Wassan , Salman Dina Akeel , Issa Abdulkareem H. , Akram Wisam
Published: December 2024

Background: Gestational diabetes mellitus (GDM) is one of the most prominent diseases seen in pregnancy that adversely affects materno-fetal welfare. It is usually screened by an oral glucose tolerance test (GTT), which has some limitations. Adiponectin and triglyceride-glycemic (TyG) index were two biomarkers examined in the GDM context with inconclusive effectiveness. This study aimed to examine both markers' performance in screening for GDM among Iraqi women. Methods: An observational cross-sectional study recruited gestational age and body mass index (BMI) matched pregnant at 26–28 weeks into two groups: healthy controls (n = 44/88) and GDM cases (n = 44/88). Participants' demographics, biochemical [FBS (fasting blood sugar), 2hr_GTT (2-hour glucose tolerance test), HDL (high-density lipoprotein), LDL (low-density lipoprotein), total cholesterol, TG (triglyceride), and TyG index], and hormonal (adiponectin) were recorded. Results: Serum adiponectin was significantly higher among healthy pregnant (8.44 ± 1.12 ng/mL vs. 5.28 ± 0.89 ng/mL); p < 0.0001. In contrast, the TyG index was significantly higher among GDM cases (4.02 ± 0.04 vs. 3.96 ± 0.02; p < 0.0001). Adiponectin showed strong inverse links with FBS, 2hr_GTT with r = (–0.76, –0.80); p < 0.0001, respectively. TyG index was moderately, inversely, and significantly linked to serum adiponectin as r = –0.58; p < 0.0001. Adiponectin and TyG index reliably predicted GDM with a high area under the curve of 0.83 vs. 0.88; p < 0.001, respectively. Conclusions: Both biomarkers correlated well to GDM parameters and showed high sensitivity and specificity in screening for GDM. Their efficiency, easy integrations in practice, and promising therapeutic application suggested by researchers warrant further studies.
Polycystic Ovary Syndrome and Reproductive Health: A Comprehensive Review
Authors: Hussein Ramadan S. , Dayel Salman Bin , Abahussein Othman
Published: December 2024

Objectives: Polycystic ovary syndrome (PCOS) is a prevalent and intricate endocrine disorder that impacts women of reproductive age. It is marked by various symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunctions, with significant implications for reproductive and overall health. This review aims to provide a comprehensive analysis of the impact of PCOS on reproductive health, highlighting the underlying pathophysiology, clinical manifestations, and emerging therapeutic approaches. Mechanism: The current literature was detailed, focusing on the hormonal imbalances associated with PCOS, including androgen excess, insulin resistance, and dysregulation of the hypothalamic-pituitary-ovarian (HPO) axis. The review also explored genetic and environmental factors contributing to PCOS and described the characteristic ovarian morphology. Findings in Brief: The findings reveal that PCOS is not only a leading cause of infertility but also contributes to a spectrum of metabolic and psychological issues. Recent research highlights the role of inflammation, the gut microbiome, and novel therapies in managing PCOS. Despite advances, gaps in understanding the long-term implications of PCOS on reproductive health remain. Conclusions: The review underscores the need for individualized and holistic treatment strategies in managing PCOS, integrating emerging therapies and mental health support. Continued research is vital to improving patient outcomes and advancing the management of this multifaceted condition.
Improvement of Diagnosis by Transvaginal Ultrasound and Prognosis of Endometrial Cancer using miR-222-3p: A Prospective Cohort Study
Authors: Feng Shengrong , Huang Yinping , Liao Juan , Huang Chunlv , Zhao Ruojun , Zeng Min
Published: December 2024

Background: Noninvasive biomarkers need identification to enhance the diagnostic accuracy of endometrial cancer (EC) detection. The diagnostic and prognostic significance of serum miR-222-3p in EC was investigated in this study to provide a reference for clinical diagnosis and treatment. Methods: This prospective cohort study comprised 128 patients with EC and 65 patients with benign endometrial lesions (benign endometrial hyperplasia or polyps) admitted to Qionglai Medical Centre Hospital from January 2016 to December 2018. EC diagnosis was confirmed through endometrial biopsy and postoperative pathology. Serum miR-222-3p levels were quantified using the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Pearson’s method was utilized to assess correlations between miR-222-3p and the resistance index (RI), pulsation index (PI), and mean blood flow velocity (MBFV). Diagnostic and prognostic assessments of miR-222-3p were conducted using receiver operating characteristic (ROC) curve analysis, Cox regression analysis, and Kaplan‒Meier curve analysis. Results: Serum miR-222-3p levels were higher in EC patients compared to controls and were correlated with RI, PI, and MBFV (p < 0.001). Serum miR-222-3p enhanced the sensitivity (69.53% vs. 96.88%) and specificity (92.31% vs. 96.92%) of transvaginal ultrasound for EC diagnosis. Furthermore, serum miR-222-3p showed significant associations with lymph node metastasis (p = 0.002), degree of differentiation (p = 0.023), and the International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.001) in EC patients. It also predicted poor prognosis and served as an independent prognostic predictor (p = 0.036). Conclusions: The combination of miR-222-3p with transvaginal ultrasound enhanced the diagnostic efficiency of EC. Additionally, miR-222-3p holds promise as a biomarker for predicting the prognosis of EC patients.
Shining a Spotlight on RNA m6A Modifications and Potential Targeted Immunotherapy in Ovarian Cancer
Authors: Pang Huaqin , Zheng Weiping , Lu Qiyun , Zhang Huiya
Published: December 2024

Objective: Ovarian cancer is one of the major gynecologic malignancies worldwide. Evidence indicates that N6-methyladenosine (m6A) modification is strongly related to cancer immunity. This review aims to demonstrate the role and function of m6A modification in ovarian cancer tumorigenesis and its potential targeted immunotherapy. Mechanism: Searching the literature for articles related to the m6A modification and ovarian cancer and immunotherapy. Conducting a comprehensive analysis and summarizing the content logically. Findings in Brief: In this review, we summarized the latest research on the function of m6A regulators in ovarian cancer tumorigenesis and targeted immunotherapy. Firstly, we found the function and underlying molecular mechanism of m6A regulators (writers, erasers and readers) in the development and progress of ovarian cancer. Then, we discovered that m6A regulators play a pivotal role in cancer immune responses and efficacy, serving as potential therapeutic targets for cancer immunotherapy. Additionally, m6A related long noncoding RNAs (lncRNAs) have a strong impact on ovarian cancer survival and immunotherapy. Finally, deeply analyzing of m6A modification and targeted genes are needed to improve the potential immunotherapy of ovarian cancer. Conclusions: m6A modification has strong potential in ovarian cancer carcinogenesis and immunotherapy.
Artificial Intelligence-Driven Precision Medicine: Multi-Omics and Spatial Multi-Omics Approaches in Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Shao Yanping , Lv Xiuyan , Ying Shuangwei , Guo Qunyi
Published: December 2024

In this comprehensive review, we delve into the transformative role of artificial intelligence (AI) in refining the application of multi-omics and spatial multi-omics within the realm of diffuse large B-cell lymphoma (DLBCL) research. We scrutinized the current landscape of multi-omics and spatial multi-omics technologies, accentuating their combined potential with AI to provide unparalleled insights into the molecular intricacies and spatial heterogeneity inherent to DLBCL. Despite current progress, we acknowledge the hurdles that impede the full utilization of these technologies, such as the integration and sophisticated analysis of complex datasets, the necessity for standardized protocols, the reproducibility of findings, and the interpretation of their biological significance. We proceeded to pinpoint crucial research voids and advocated for a trajectory that incorporates the development of advanced AI-driven data integration and analytical frameworks. The evolution of these technologies is crucial for enhancing resolution and depth in multi-omics studies. We also emphasized the importance of amassing extensive, meticulously annotated multi-omics datasets and fostering translational research efforts to connect laboratory discoveries with clinical applications seamlessly. Our review concluded that the synergistic integration of multi-omics, spatial multi-omics, and AI holds immense promise for propelling precision medicine forward in DLBCL. By surmounting the present challenges and steering towards the outlined futuristic pathways, we can harness these potent investigative tools to decipher the molecular and spatial conundrums of DLBCL. This will pave the way for refined diagnostic precision, nuanced risk stratification, and individualized therapeutic regimens, ushering in a new era of patient-centric oncology care.
Circadian Disruption in Glaucoma: Causes, Consequences, and Countermeasures
Authors: Gubin Denis , Malishevskaya Tatyana , Weinert Dietmar , Zakharova Ekaterina , Astakhov Sergey , Cornelissen Germaine
Published: December 2024

This review explores the intricate relationship between glaucoma and circadian rhythm disturbances. As a principal organ for photic signal reception and transduction, the eye plays a pivotal role in coordinating the body's circadian rhythms through specialized retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs). These cells are critical in transmitting light signals to the suprachiasmatic nucleus (SCN), the central circadian clock that synchronizes physiological processes to the 24-hour light-dark cycle. The review delves into the central circadian body clock, highlighting the importance of the retino-hypothalamic tract in conveying light information from the eyes to the SCN. It underscores the role of melanopsin in ipRGCs in absorbing light and initiating biochemical reactions that culminate in the synchronization of the SCN's firing patterns with the external environment. Furthermore, the review discusses local circadian rhythms within the eye, such as those affecting photoreceptor sensitivity, corneal thickness, and intraocular fluid outflow. It emphasizes the potential of optical coherence tomography (OCT) in studying structural losses of RGCs in glaucoma and the associated circadian rhythm disruption. Glaucomatous retinal damage is identified as a cause of circadian disruption, with mechanisms including oxidative stress, neuroinflammation, and direct damage to RGCs. The consequences of such disruption are complex, affecting systemic and local circadian rhythms, sleep patterns, mood, and metabolism. Countermeasures, with implications for glaucoma management, are proposed that focus on strategies to improve circadian health through balanced melatonin timing, daylight exposure, and potential chronotherapeutic approaches. The review calls for further research to elucidate the mechanisms linking glaucoma and circadian disruption and to develop effective interventions to address this critical aspect of the disease.
The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples
Authors: Bograya Maria , Vulf Maria , Minchenko Anastasia , Gazatova Natalia , Kuznetsov Georgy , Todosenko Natalia , Volkova Larisa , Ivanov Pavel , Litvinova Larisa
Published: December 2024

Background: Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NAFLD) in humans. This study is the first to investigate the expression of ERBB4 and NRG4 mRNAs and their role in lipid metabolism in the livers of individuals with obesity, type 2 diabetes and biopsy-proven NAFLD. Methods: Liver biospecimens were obtained intraoperatively from 80 individuals. Quantitative reverse transcription polymerase chain reaction was used to measure the expression levels of mRNAs ERBB4 and NRG4, as well as key lipogenesis genes in the liver tissue of the donors. Histological analysis was conducted on liver biopsies from 36 subjects, and the levels of the examined transcripts were compared with the stage of NAFLD. Results: In individuals with elevated body mass index (BMI), ERBB4 and NRG4 levels decreased, while ACACA levels increased. A strong negative correlation was observed between NRG4 and ACACA levels. No deregulation of the analyzed transcripts was detected in NAFLD. Conclusions: The study demonstrates a decrease in ERBB4 and NRG4 mRNA expression in the livers of subjects with high BMI but not in those with NAFLD. The correlation of the studied transcripts with major lipogenesis genes was assessed, and on this basis a putative scheme for NRG4-mediated suppression of hepatic de novo lipogenesis was hypothesised, offering new research vectors in this field.
The PKM2/HIF-1α Axis is Involved in the Pathogenesis of Endometriosis via TGF-β1 under Endometrial Polyps
Authors: Li Jianjuan , Liu Li , Fan Ruiqi
Published: December 2024

Background: Endometriosis patients exhibit a cancer-like glycolytic phenotype. The pyruvate kinase M2 (PKM2)/hypoxia-inducible factor-1 alpha (HIF-1α) axis plays important roles in glycolysis-related diseases, but its role in patients with endometrial polyps (EPs) combined with endometriosis has not been validated. Methods: EP samples were collected from patients with and without endometriosis. PKM2, HIF-1α, and transforming growth factor-beta 1 (TGF-β1) levels were detected by immunohistochemistry (IHC), quantitative polymerase chain reaction, western blotting, and/or immunofluorescence. Primary endometrial stromal cells (ESCs) and non-endometriotic patient-derived ESCs (NESCs) were isolated from patients with EP with or without endometriosis. PKM2 loss-of-function assays in ESCs and gain-of-function assays in NESCs were performed to assess the function of PKM2. The effects of PKM2 and TGF-β1 on the promoter activity of HIF-1α were determined by dual-luciferase reporter assay. Results: PKM2 was overexpressed in ESCs compared to NESCs. Furthermore, PKM2 knockdown repressed viability, decreased migration and invasion, and restrained glycolysis of ESCs, accompanied by reduced HIF-1α levels and weakened promoter activity of HIF-1α. In addition, PKM2 overexpression had the opposite effect on these indicators in NESCs. Of note, an anti-TGF-β1 Ab reversed the PKM2-overexpression-mediated effects on cell viability, migration, and invasion, but not glycolysis or HIF-1α promoter activity, in NESCs. Additionally, PKM2, HIF-1α, and TGF-β1 levels were higher in EP samples with endometriosis than in EP samples without endometriosis, and there were positive correlations between PKM2, HIF-1α, and TGF-β1 IHC scores in all EP samples. Conclusions: PKM2/HIF-1α-axis-dependent glycolysis participates in the pathogenesis of EP combined with endometriosis by mediating TGF-β1 signaling.
Combined Use of Intranasal Methylprednisolone and Allopregnanolone: Revisiting Anti-inflammatory and Remyelinating Treatment in a Murine Model of Multiple Sclerosis
Authors: Pérez-Osorio Iván Nicolás , Espinosa-Cerón José Alejandro , Álvarez-Gutiérrez Camila , Gonzalez-Flores Rodrigo , Besedovsky Hugo , Fragoso Gladis , Torres-Ramos Mónica A. , Sciutto Edda
Published: December 2024

Background: Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, progressive disease that severely affects human health of young adults. Neuroinflammation (NI) and demyelination, as well as their interactions, are key therapeutic targets to halt or slow disease progression. Potent steroidal anti-inflammatory drugs such as methylprednisolone (MP) and remyelinating neurosteroids such as allopregnanolone (ALLO) could be co-administered intranasally to enhance their efficacy by providing direct access to the central nervous system (CNS). Methods: The individual and combined effects of MP and ALLO to control the clinical score of murine experimental autoimmune encephalitis (EAE), to preserve spinal cord tissue integrity, modulate cellular infiltration and gliosis, promote remyelination, and modify the expression of Aryl hydrocarbon receptor (AhR) were evaluated. In silico studies, to deep insight into the mechanisms involved for the treatments, were also conducted. Results: MP was the only treatment that significantly reduced the EAE severity, infiltration of inflammatory cells and ionized calcium-binding adapter molecule 1 (Iba-1) expression respect to those EAE non-treated mice but with no-significant differences between the three treatments. MP, ALLO and MP+ALLO significantly reduced tissue damage, AhR expression, and promoted remyelination. Overall, these results suggest that MP, with or without the co-administration with ALLO is an effective and safe strategy to reduce the inflammatory status and the progression of EAE. Despite the expectations of the use of ALLO to reduce the inflammation in EAE, its effect in the dose-scheme used herein is limited only to improve myelination, an effect that supports its usefulness in demyelinating diseases. These results indicate the interest in exploring different doses of ALLO to recommend its use. Conclusions: ALLO treatment mainly maintain the integrity of the spinal cord tissue and the presence of myelin without affecting NI and the clinical outcome. AhR could be involved in the effect observed in both, MP and ALLO treatments. These results will help in the development of a more efficient therapy for MS patients.
Downregulated METTL3 Accumulates TERT Expression that Promote the Progression of Ovarian Endometriosis
Authors: Li Fang , Tao Hua , Wei Yini , Meng Ru , Li Yushan , Nie Lifang , Zhang Yu , Chang Jinjun
Published: December 2024

Background: Endometriosis is a complicated and enigmatic disease that significantly diminishes the quality of life for women affected by this condition. Increased levels of human telomerase reverse transcriptase (TERT) mRNA and telomerase activity have been found in the endometrium of these patients. However, the precise function of TERT in endometriosis and the associated biological mechanisms remain poorly understood. Methods: We analyzed TERT expression in ectopic endometrial (EC), eutopic endometrial (EU), and normal endometrial (NC) tissues. Human endometrial stromal cells (HESCs) were used to study the effects of TERT depletion and knockdown on cell behavior. We also assessed methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification in TERT transcripts and its impact on mRNA stability and cell functions. Results: The current results indicate that TERT expression is elevated in EC tissue compared to both EU and NC. Depletion of TERT suppressed the proliferation and migration of HESCs, while TERT overexpression had the opposite effect. We found high levels of METTL3-mediated m6A modification in TERT transcripts, particularly in the coding sequence region, resulting in increased translation. However, EC tissues had lower m6A levels due to the downregulation of METTL3. Mechanistically, m6A modification mediated by METTL3 negatively regulates the stability of TERT mRNA in a YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-dependent manner. Furthermore, METTL3 negatively regulated the proliferation and migration of HESCs. Conclusions: Together, our study identified a new molecular mechanism that underlies the pathogenesis of endometriosis. Inhibition of m6A modification and of the METTL3/TERT axis may enhance cellular proliferation and migration, thereby contributing to the progression of endometriosis.
Effect of 2-Aminoethoxydiphenyl Borate on the State of Skeletal Muscles in Dystrophin-Deficient mdx Mice
Authors: Dubinin Mikhail V. , Stepanova Anastasia E. , Igoshkina Anastasia D. , Mikheeva Irina B. , Talanov Eugeny Yu. , Cherepanova Alena A. , Belosludtsev Konstantin N.
Published: December 2024

Objective: Ca2+ overload of muscle fibers is one of the factors that secondarily aggravate the development of Duchenne muscular dystrophy (DMD). The purpose of this study is to evaluate the effects of the Ca2+ channel modulator 2-aminoethoxydiphenyl borate (APB) on skeletal muscle pathology in dystrophin-deficient mdx mice. Methods: Mice were randomly divided into six groups: wild type (WT), WT+3 mg/kg APB, WT+10 mg/kg APB, mdx, mdx+3 mg/kg APB, mdx+10 mg/kg APB. APB was administered intraperitoneally daily for 28 days. Finally, we assessed the grip strength and hanging time of mice, the histology and ultrastructure of the quadriceps, as well as the parameters reflecting quadricep mitochondrial function. Results: 3 mg/kg APB was shown to reduce creatine kinase activity in the serum, intensity of degeneration and the level of fibrosis in the quadriceps of mdx mice, and improved tissue ultrastructure. However, this effect of APB was not sufficient to improve grip strength and hanging time of mdx mice. The effect of 3 mg/kg APB may be due to improve Ca2+ homeostasis in skeletal muscles, as evidenced by a trend toward decreased Ca2+ overload of quadricep mitochondria. High dose of APB (10 mg/kg body weight) showed less pronounced effect on the pathological phenotype of mdx mice. Moreover, 10 mg/kg APB disrupted the ultrastructure of the quadriceps and caused a decrease in grip strength in WT mice. Conclusions: APB is able to improve the phenotype in mdx mouse DMD model. However, the effect of APB is quite limited, which may be due to its multitargeting of Ca2+ channels in the membranes of muscle fibers and intracellular organelles, differentially expressed in DMD.
HSP90 Family Members, Their Regulators and Ischemic Stroke Risk: A Comprehensive Molecular-Genetics and Bioinformatics Analysis
Authors: Kobzeva Ksenia , Ivenkov Maxim , Gromov Rostislav , Bushueva Olga
Published: December 2024

Background: Disruptions in proteostasis are recognized as key drivers in cerebro- and cardiovascular disease progression. Heat shock proteins (HSPs), essential for maintaining protein stability and cellular homeostasis, are pivotal in neuroperotection. Consequently, deepening the understanding the role of HSPs in ischemic stroke (IS) risk is crucial for identifying novel therapeutic targets and advancing neuroprotective strategies. Aim: Our objective was to examine the potential correlation between single nucleotide polymorphisms (SNPs) in genes that encode members of the Heat shock protein 90 (HSP90), small heat shock proteins (HSPB), and heat shock factors (HSF) families, and the risk and clinical characteristics of IS. Methods: 953 IS patients and 1265 controls from Central Russia were genotyped for nine SNPs in genes encoding HSP90AA1, HSFs, and HSPBs using the MassArray-4 system and probe-based polymerase chain reaction (PCR). Results: In smokers, SNP rs1133026 HSPB8 increased the risk of IS (risk allele A, odds ratio (OR) = 1.43, 95% Confidence Interval (CI) 1.02–2.02, p = 0.035), and rs556439 HSF2 increased the brain infarct size (risk allele A, p = 0.02). In non-smokers, SNPs rs4279640 HSF1 (protective allele T, OR = 0.58, 95% CI 0.37–0.92, p = 0.02) and rs4264324 HSP90AA1 (protective allele C, OR = 0.11, 95% CI 0.01–0.78, p = 0.001) lowered the risk of recurrent stroke; SNP rs7303637 HSPB8 increased the age of onset of IS (protective allele T, p = 0.04). In patients with body mass index (BMI) ≥25, SNPs rs556439 HSF2 (risk allele A, OR = 1.33, 95% CI 1.04–1.69, p = 0.02) and rs549302 HSF2 (risk allele G, OR = 1.34, 95% CI 1.02–1.75, p = 0.03) were linked to a higher risk of IS. Conclusions: The primary molecular mechanisms through which the studied SNPs contribute to IS pathogenesis were found to be the regulation of cell death, inflammatory and oxidative stress responses.
InPAS: An R/Bioconductor Package for Identifying Novel Polyadenylation Sites and Alternative Polyadenylation from Bulk RNA-seq Data
Authors: Ou Jianhong , Liu Haibo , Park Sungmi , Green Michael R. , Zhu Lihua Julie
Published: December 2024

Background: Alternative cleavage and polyadenylation (APA) is a crucial post-transcriptional gene regulation mechanism that regulates gene expression in eukaryotes by increasing the diversity and complexity of both the transcriptome and proteome. Despite the development of more than a dozen experimental methods over the last decade to identify and quantify APA events, widespread adoption of these methods has been limited by technical, financial, and time constraints. Consequently, APA remains poorly understood in most eukaryotes. However, RNA sequencing (RNA-seq) technology has revolutionized transcriptome profiling and recent studies have shown that RNA-seq data can be leveraged to identify and quantify APA events. Results: To fully capitalize on the exponentially growing RNA-seq data, we developed InPAS (Identification of Novel alternative PolyAdenylation Sites), an R/Bioconductor package for accurate identification of novel and known cleavage and polyadenylation sites (CPSs), as well as quantification of APA from RNA-seq data of various experimental designs. Compared to other APA analysis tools, InPAS offers several important advantages, including the ability to detect both novel proximal and distal CPSs, to fine tune positions of CPSs using a naïve Bayes classifier based on flanking sequence features, and to identify APA events from RNA-seq data of complex experimental designs using linear models. We benchmarked the performance of InPAS and other leading tools using simulated and experimental RNA-seq data with matched 3′-end RNA-seq data. Our results reveal that InPAS frequently outperforms existing tools in terms of precision, sensitivity, and specificity. Furthermore, we demonstrate its scalability and versatility by applying it to large, diverse RNA-seq datasets. Conclusions: InPAS is an efficient and robust tool for identifying and quantifying APA events using readily accessible conventional RNA-seq data. Its versatility opens doors to explore APA regulation across diverse eukaryotic systems with various experimental designs. We believe that InPAS will drive APA research forward, deepening our understanding of its role in regulating gene expression, and potentially leading to the discovery of biomarkers or therapeutics for diseases.
Gone with the Species: From Gene Loss to Gene Extinction
Authors: Khan Ammad Aslam , Fatima Anees
Published: December 2024

Background: Vertebrae protein-coding genes exhibit remarkable diversity and are organized into many gene families. These gene families have emerged through various gene duplication events, the most prominent being the two rounds of whole-genome duplication (WGD). The current research project analyzed a unique class of genes called “singletons”. Notably, we introduce the concept of “super-singletons”: genes that stand as the last representatives of their ancestral families and the sole representatives of their genetic makeup with no ortholog in any other species. Methods: We used the Ensembl/Biomart pipeline to identify duplicated and unduplicated protein-coding genes in different vertebrate species and found orthologs of human genes. Results: We showed the frequency of duplicated genes and singletons, demonstrating that singletons are more vulnerable to evolutionary loss than duplicated genes. Additionally, we found that contractions in vertebrate gene families are more prevalent than expansion. Conclusion: Our study provides insight into the evolution of gene families and presents a novel scenario where the extinction of species would lead to the extinction of a gene, ultimately shifting the narrative from the impact of genetics on species extinction to the extinction of genes.
Evaluation of Reference Gene Stability for Investigations of Intracellular Signalling in Human Cancer and Non-Malignant Mesenchymal Stromal Cells
Authors: Kosheverova Vera , Schwarz Alexander , Kamentseva Rimma , Kharchenko Marianna , Kornilova Elena
Published: December 2024

Background: Real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) is a powerful tool for analysing target gene expression in biological samples. To achieve reliable results by RT-qPCR, the most stable reference genes must be selected for proper data normalisation, particularly when comparing cells of different types. We aimed to choose the least variable candidate reference genes among eight housekeeping genes tested within a set of human cancer cell lines (HeLa, MCF-7, SK-UT-1B, A549, A431, SK-BR-3), as well as four lines of normal, non-malignant mesenchymal stromal cells (MSCs) of different origins. Methods: The reference gene stability was evaluated using four algorithms (BestKeeper, NormFinder, geNorm and the comparative ΔCt method) and ranked with the RefFinder web-based tool. Results: We found increased variability in the housekeeping genes’ expression in the cancer cell lines compared to that in normal MSCs. POP4 and GAPDH were identified as the most suitable reference genes in cancer cells, while 18S and B2M were the most suitable in MSCs. POP4 and EIF2B1 were shown to be the least variable genes when analysing normal and cancer cell lines together. Epidermal growth factor receptor (EGFR) mRNA relative expression was normalised by the three most stable or three least stable reference genes to demonstrate the reliability of reference genes validation. Conclusion: We analysed and selected stable reference genes for RT-qPCR analysis in the wide panel of cancer cell lines and MSCs. The study provides a reliable tool for future research concerning the expression of genes involved in various intracellular signalling pathways and emphasises the need for careful selection of suitable references before analysing target gene expression.
Research Progress on the Role of the Interleukin Family in the Pathogenesis of Cerebral Palsy in Children
Authors: Hu Mingbo , Bai Chao , Zhao Hong , Wu Junjie , Luan Xinping
Published: December 2024

Cerebral palsy (CP), a common neurological disorder in children, remains a significant research focus. The interleukin (IL) family, pivotal mediators in inflammatory responses, shows increased expression in various neuroinflammatory diseases, markedly influencing their onset and progression. Elevated IL levels in the brains of children with CP, in contrast to healthy peers, reflect similar elevations in neurological conditions linked to CP, indicating a strong association between CP and the IL family. Anti-inflammatory therapies, particularly those targeting ILs, have shown effectiveness in animal models, diverging from traditional CP management methods. This shift suggests IL modulation as a promising therapeutic strategy in pediatric CP. This review consolidates recent findings on the IL family’s role in CP, illuminating their evolving relationship.
Effectiveness of Angiotensin Receptor Blockers (ARB) and Hydrochlorothiazide Compared to ARB Monotherapy in the Control of Hypertension among Adult Patients: A Systematic Review and Meta-Analysis
Authors: Agwu Anthony O. , Egwu Chinedu O. , Chukwu Jennifer , Oyinloye Inigbehe Babatunde
Published: December 2024

Background: Hypertension (HTN) is a global disease of public health concern. It is considered a major cause of morbidity and mortality worldwide. The global and regional recommendations for the management of high blood pressure are complicated, with an increasing call for several adequate measures to commence treatment, increase the dosage, or introduce a new class of medication. Evidence suggests that most people with HTN require more than one drug regime to achieve blood pressure goals, with a greater percentage of patients reporting only having access to monotherapy. This work evaluated the combined effectiveness of angiotensin receptor blockers (ARBs) and hydrochlorothiazide (HCTZ) compared to ARB monotherapy in an uncontrolled hypertensive patients. Methods: The search involved screening through databases such as Cochrane Library, PubMed, CINAHL, Embase, Medline, and the Web of Science, medical journals, and international registry on clinicals from the WHO were searched for primary studies not older than 13 years. Randomized control trials (RCTs) comparing the effectiveness of ARB/HCTZ versus ARB monotherapy in hypertensive patients were selected. Care was taken to include only studies that lasted at least four weeks. Meta-analysis was conducted on RevMan 5.3 statistical application software, following data extraction. Data quality and risk of bias assessment were also all assessed. A total of seven RCTs were considered for this study involving 4814 participants. Results: The result from the intervention arm revealed that ARB/HCTZ combination resulted in a higher rate of target blood pressure achievement when compared to ARB monotherapy relative risk (RR) = 1.53, 95% confidence interval (CI) (1.42, 1.65), with p < 0.00007. The adverse effects observed in the intervention arm were not significant. Conclusion: The ARB/HCTZ combination therapy was more effective in lowering and controlling blood pressure when compared to ARB monotherapy without significant adverse drug effects reported by the participants. Health workers should therefore recommend ARB/HCTZ combination therapy for patients with uncontrolled hypertension.
Comprehensive Insights into Mechanisms for Ventricular Remodeling in Right Heart Failure
Authors: Jiang Dongmei , Wang Jie , Wang Rui , Wu Yun
Published: December 2024

Ventricular remodeling in right heart failure is a complex pathological process involving interactions between multiple mechanisms. Overactivation of the neuro-hormonal pathways, activation of the oxidative stress response, expression of cytokines, apoptosis of cardiomyocytes, and alterations of the extracellular matrix (ECM) are among the major mechanisms involved in the development of ventricular remodeling in right heart failure. These mechanisms are involved in ventricular remodeling, such as myocardial hypertrophy and fibrosis, leading to the deterioration of myocardial systolic and diastolic function. A deeper understanding of these mechanisms can help develop more effective therapeutic strategies in patients with right heart failure (RHF) to improve patient survival and quality of life. Despite the importance of ventricular remodeling in RHF, there are a limited number of studies in this field. This article explores in-depth historical and current information about the specific mechanisms in ventricular remodeling in RHF, providing a theoretical rationale for recognizing its importance in health and disease.
Adding Insult to Injury: When Atrial Fibrillation Encounters Left Bundle Branch Block
Authors: Zhao Dong-sheng , Yadav Nishant , Dong Yan , Chen Qiu-shi , Yang Di , Zhang Feng-xiang
Published: December 2024

Background: It is not uncommon that atrial fibrillation (AF) coexists with left bundle branch block (LBBB). Whether LBBB is an independent predictor of poor prognosis in AF patients remains undetermined. This study aims to investigate the impact of LBBB on the AF-related outcomes in non-valvular AF patients. Methods: The clinical data of AF patients were collected from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. The frequencies of acute arterial embolism events (AEE) and in-hospital cardiac death were compared between the non-LBBB and LBBB groups. And, their 1-year mortality was assessed through a survival analysis model. Additionally, the two groups were matched in a 1:2 ratio by a propensity score matching (PSM) method according to the CHA2DS2VASc score and AF type. Results: 5051 patients diagnosed with non-valvular AF without apparent structural heart disease were enrolled in this study, among them, there were 65 with LBBB which had more AEE (13.8% vs 6.8%, p = 0.04). After PSM, with balanced CHA2DS2VASc score and AF type, LBBB was still related with AEE (13.8% vs 3.8%, p = 0.02) significantly, and it was also independent of heart failure (HF) (odds ratios (OR) 6.38, 95% confidence intervals (CI) [1.10, 36.93], p = 0.04). LBBB was also correlated with in-hospital cardiac death (OR 5.33, 95% CI [1.01, 28.28], p = 0.04). And, the LBBB patients had a lower 1-year survival rate in the subgroup of HF (67.6% vs 83.0%, p = 0.06). Conclusions: The LBBB was an independent risk factor of AEE and related to in-hospital cardiac death and 1-year all-cause mortality in this non-valvular AF cohort from MIMIC-III.
A New Semi-Quantitative Parameter to Assess Functionally Significant Coronary Disease Using Myocardial Contrast Echocardiography
Authors: Long Jili , Lin Jingru , Tao Jia , Wang Hao
Published: December 2024

Background: Quantitative flow ratio (QFR) can identify functionally significant coronary disease non-invasively. Myocardial contrast echocardiography (MCE) is a non-invasive and effective procedure for detecting abnormalities in hemodynamic coronary artery stenosis. Currently, there is no research confirming the correlation between MCE and QFR. This study aims to compare the capacity of the perfusion index (PI) from MCE to diagnose functionally significant coronary disease in patients with chest pain. The investigators use QFR as the gold standard for comparison. Methods: 112 patients referred for coronary angiography (CAG) due to suspicion of coronary artery disease (CAD) were included. 64 patients with functionally significant coronary disease were diagnosed. 48 patients were defined as CAD without functionally significant coronary disease. MCE was performed 24 h before angiography. PI was calculated for each triggering interval by adding the perfusion scores of segments and dividing by the number of segments. Logistic regression analyses were performed to evaluate the association among functionally significant coronary disease, echocardiographic and clinical parameters. Spearman correlation analysis was used to investigate the correlation between PI and QFR. A receiver operating characteristic (ROC) curve was used to assess the capability of echocardiographic and clinical parameters to diagnose functionally significant coronary disease. Results: Patients with functionally significant coronary disease had the worse perfusion in MCE compared with those without functionally significant coronary disease. In multivariable logistic regression analysis, global perfusion index (GPI) (OR: 43.409, p < 0.001) was associated with functionally significant coronary disease in patients with CAD. Based on the Spearman correlation analysis. Left anterior descending artery (LAD)-PI showed a strong negative correlation with LAD-QFR (r = –0.652, p < 0.01). ROC curves showed LAD-PI to be superior to GPI, left circumflex artery PI (LCX-PI) and right coronary artery PI (RCA-PI) in identifying functionally significant coronary disease. Conclusions: The PI derived from MCE has diagnostic value for functionally significant coronary disease with QFR ≤0.80 in 1 or more vessels, with LAD-PI showing the highest diagnostic efficiency. GPI is independently associated with functionally significant coronary disease, but among the branch PIs, LAD-PI has the highest diagnostic efficiency.