Development Of Disease Research Articles

Direct and indirect effects of hepatitis B vaccination in four low- and middle-income countries

Population-level vaccination effects of the hepatitis B vaccine were investigated in four low- and middle-income countries with different levels of vertical and horizontal transmission. Indirect vaccination effects constitute a large proportion of overall vaccination effects of the vaccination programmes in all four countries (over 70% by 2030 in all four countries). However, countries with higher levels of vertical transmission benefit less from indirect vaccination effects from the infant hepatitis B vaccine series during the first decades of the vaccination programme, making the birth dose vaccine more important in these countries. Vaccination, even at levels that do not fully control transmission, has a great effect on the development of disease as it also increases the average age of infection, thereby causing a decrease in the number of chronic infections relative to the number of acute infections.

Revealing key proteins in comparison of tumor and para-tumor tissues in stage I esophageal squamous cell carcinoma: A combined gene expression clustering and protein interaction network analysis

Esophageal Squamous Cell Carcinoma (ESCC) which is diagnosed in advanced stages and metastasis to the vital organs, remained the sixth fatal malignancy among other types of cancer-related death. Considering the lack of specific clinical symptoms in the early development of the disease, finding suitable biomarkers and tissue-specific alterations for effective screening of ESCC is targeted in this project. Gene expression profiles of tumor tissue and para-tumors of stage I ESCC patients were retrieved from the Gene Expression Omnibus (GEO) database. The significant tissue-specific differentially expressed genes (DEGs) were identified and studied based on fold change distribution and the functional role of genes in the action map. A total number of 11,483 significant DEGs discriminated the tumor tissue from para-tumor tissue. Clustering analysis of significant DEGs led to identifying 220 DEGs as the final significant genes. Protein interaction network and action map analysis of the final gene list showed matrix metallopeptidase-9 (MMP9) as the critical gene related to the development of ESCC diseases in stage I. Significant expression change of MMP9 in esophageal carcinoma was validated in UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal). This study highlighted the pivotal role of MMP9 in combination with SPP1, MMP13, and IL18 as a possible biomarkers panel in studies of tumor invasion and prognosis for stage I ESCC disease.

Endothelial Cell Aging and Autophagy Dysregulation.

Entropy is a natural process that affects all living cells, including senescence, an irreversible physiological process that impairs cell homeostasis. Age is a significant factor in disease development, and the pathogenesis of endothelial cell aging is multifactorial. Autophagy dysfunction accelerates endothelial cell aging and cell death, while autophagy preserves endothelial cell youthfulness through intracellular homeostasis and gene expression regulation. Sirt, mTORC1, and AMPK are youthfulness genes that induce autophagy by inhibiting mTOR and upregulating FIP200/Atg13/ULK1. Aged endothelial cells have decreased levels of Lamin B1, γH2AX, Ki67, BrdU, PCNA, and SA β-Gal. Maintaining healthy young endothelial cells can prevent most cardiovascular diseases. Autophagy targeting is a potential future therapeutic strategy to modify endothelial cell age and potentially slow or reverse the aging process. This article provides state-of-the-art research on the role of autophagy in endothelial cell aging. Hypothesizing that autophagy dysregulation is associated with early endothelial cell dysfunction and further clinical sequelae, including atherosclerosis formation, leading to various cardiovascular diseases.

Investigation of RNA-binding protein NOVA1 in silico: Comparison of the modern human V197 with the archaic I197 variant present in Neanderthals

By comparing the high-coverage archaic genome sequences to those of modern humans, specific genetic differences have been identified. For example, a human-specific substitution has been found in neuro-oncological ventral antigen 1 (NOVA1) – an RNA-binding protein that regulates the alternative splicing of neuronal pre-mRNA. The amino acid substitution results in an isoleucine-to-valine change at position 197 in NOVA1 (archaic: I197, modern human: V197). Previous studies have utilised gene editing technology to compare the archaic and modern human forms of NOVA1 in cortical organoids, however, the structural and molecular details require further investigation. Using an in silico approach, the modern human (WT) and archaic (V197I) structures of NOVA1 were generated. Moreover, the structure of NOVA1 containing a glycine-to-valine substitution at position 68 (G68V), which occurs at the RNA-binding interface, was examined for comparison. Protein-RNA docking was subsequently performed to model the interaction of NOVA1 variants with RNA and the complexes were evaluated further using classical molecular dynamics (MD) simulations. Based on the MM-PBSA analysis, the binding free energies were similar between the WT (−956.8 ± 32.6 kcal/mol), V197I (−975.4 ± 65.6 kcal/mol), and G68V (−946.7 ± 34.3 kcal/mol) complexes. The findings highlight the binding and stability of protein-RNA complexes with only modest structural changes observed in the archaic and G68V variants compared to the WT NOVA1 protein. Further clarification is required to enhance our understanding of the impact of NOVA1 mutations on alternative splicing and disease development. In particular, delineating the effect of multiple mutations in the NOVA1 gene is of importance.

Biological and clinical role of TREM2 in liver diseases

Liver diseases constitute a major health burden worldwide, accounting for more than 4% of all disease-related mortalities. While the incidence of viral hepatitis is expected to decrease, metabolic liver disorders are increasingly diagnosed. Liver pathology is diverse, with functional and molecular alterations in both parenchymal and mesenchymal cells, including immune cells. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and mainly expressed on myeloid cells. Several studies have demonstrated that TREM2 plays a critical role in tissue physiology and various pathological conditions. TREM2 is recognized as being associated with the development of liver diseases by regulating tissue homeostasis and the immune microenvironment. The biological and clinical impact of TREM2 is complex, given its diverse context-dependent functions. This review aims to summarize recent progress in understanding the association between TREM2 and different liver disorders and shed light on the clinical significance of targeting TREM2.

GLIS3: a novel transcriptional regulator of mitochondrial functions and metabolic reprogramming in postnatal kidney and polycystic kidney disease

Background and aimsDeficiency in the transcription factor (TF) GLI-Similar 3 (GLIS3) in humans and mice leads to the development of polycystic kidney disease (PKD). In this study, we investigate the role of GLIS3 in the regulation of energy metabolism and mitochondrial functions in relation to its role in normal kidney and metabolic reprogramming in PKD pathogenesis. Approach and resultsTranscriptomics, cistromics, and metabolomics were used to obtain insights into the role of GLIS3 in the regulation of energy homeostasis and mitochondrial metabolism in normal kidney and PKD pathogenesis using GLIS3-deficient mice. Transcriptome analysis showed that many genes critical for mitochondrial biogenesis, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and the tricarboxylic acid (TCA) cycle, including Tfam, Tfb1m, Tfb2m, Ppargc1a, Ppargc1b, Atp5j2, Hadha, and Sdha, are significantly suppressed in kidneys from both ubiquitous and tissue-specific Glis3-deficient mice. ChIP-Seq analysis demonstrated that GLIS3 is associated with the regulatory region of many of these genes, indicating that their transcription is directly regulated by GLIS3. Cistrome analyses revealed that GLIS3 binding loci frequently located near those of hepatocyte nuclear factor 1-Beta (HNF1B) and nuclear respiratory factor 1 (NRF1) suggesting GLIS3 regulates transcription of many metabolic and mitochondrial function-related genes in coordination with these TFs. Seahorse analysis and untargeted metabolomics corroborated that mitochondrial OXPHOS utilization is suppressed in GLIS3-deficient kidneys and showed that key metabolites in glycolysis, TCA cycle, and glutamine pathways were altered indicating increased reliance on aerobic glycolysis and glutamine anaplerosis. These features of metabolic reprogramming may contribute to a bioenergetic environment that supports renal cyst formation and progression in Glis3-deficient mice kidneys. ConclusionsWe identify GLIS3 as a novel positive regulator of the transition from aerobic glycolysis to OXPHOS in normal early postnatal kidney development by directly regulating the transcription of mitochondrial metabolic genes. Loss of GLIS3 induces several features of renal cell metabolic reprogramming. Our study identifies GLIS3 as a new participant in an interconnected transcription regulatory network, that includes HNF1B and NRF1, critical in the regulation of mitochondrial-related gene expression and energy metabolism in normal postnatal kidneys and PKD pathogenesis in Glis3-deficient mice.

Psychosomatic Disorder: The Current Implications and Challenges.

In recent years, there has been increasing global concern about the rising prevalence and rapid progression of psychosomatic disorders (PD). This surge can be attributed to irregular biological conditions and the increasingly stressful lifestyles that individuals lead, ultimately resulting in functional impairments of vital organs. PD arises from intricate interactions involving the central nervous, endocrine, and immune systems. Notably, the hypothalamic-pituitaryadrenal (HPA) axis plays an essential role, as its dysregulation is influenced by prolonged stress and psychological distress. Consequently, stress hormones, including cortisol, exert detrimental effects on immunological function, inflammation, and homeostatic equilibrium. It emerges as physical symptoms influenced by psychological factors, such as persistent pain, gastrointestinal disturbances, or respiratory complications, and is pertinent to highlight that excessive and chronic stress, anxiety, or emotional distress may engender the onset or exacerbation of cardiovascular disorders, namely hypertension and heart disease. Although several therapeutic strategies have been proposed so far, the precise etiology of PD remains elusive due to the intricate nature of disease progression and the underlying modalities of action. This comprehensive review seeks to elucidate the diverse classifications of psychosomatic disorders, explicate their intricate mechanisms, and shed light on their impact on the human body, which may act as catalysts for the development of various other diseases. Additionally, it explores the inherent medico-clinical challenges posed by PD and also explores the cutting-edge technologies, tools, and data analytics pipelines that are being applied in the contemporary era to effectively analyze psychosomatic data.

Synthesis of Chalcones, Screening In silico and In vitro and Evaluation of Helicobacter pylori Adhesion by Molecular Docking.

We synthetized 10 hydroxylated and methoxylated chalcones and evaluated them targeting MMP-9 inhibition, looking for the rate of adhesion of H. pylori in gastric cells, and then, reduction of the inflammatory response as alternative therapeutic agents for controlling the infection. Helicobacter pylori is a Gram-negative bacterium that chronically infects the human stomach, a risk factor for the development of inflammatory gastrointestinal diseases, including cancer, and is classified as a group I carcinogen. It is estimated that it infects around 45% of the global population and that the persistence of the infection is related to the adhesion of the bacteria in the gastric epithelium. The progression of gastric lesions to cancer is connected to the activation of the NF-κB and MAPK pathways, especially in cagA+ strains, which are related to increased expression of MMP-9. The activation of these metalloproteinases (MMPs) contributes to the adhesion of the bacterium in gastric cells and the evolving stages of cancer, such as enabling metastasis. Due to the increasing resistance to the current therapy protocols, the search for alternative targets and candidate molecules is necessary. In this way, controlling adhesion seems to be a suitable option since it is a crucial step in the installation of the bacterium in the gastric environment. Synthetize ten hydroxylated and methoxylated chalcones. Assess their anti-H. pylori potential, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Evaluate their cytotoxicity in AGS cells and selectivity with L-929 cells. Analyze the results and correlate them with in silico predictions to evaluate potential anti-adhesive properties for the chalcones against H. pylori. The chalcones were synthetized by Claisen-Schmidt condensation using Ba(OH)2 or LiOH as catalysts. Predictive in silico assays in PASS Online, tanimoto similarity, ADME properties and molecular docking in MMP-9 (PDB code: 6ESM) were performed. The in vitro assays carried out were the cell viability in gastric adenocarcinoma cells (AGS) and fibroblasts (L-929) by the MMT method and anti-H. pylori, by the broth microdilution method, through the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Ten chalcones were synthesized through Claisen-Schimdt condensation with yields of 10 to 52% and characterized by 1H and 13C nuclear magnetic resonance (NMR) and mass spectrometry (MS). in silico data revealed the possibility of anti-H. pylori, anti-inflammatory, and MMP-9 inhibition for the chalcones. Chalcone 9 showed the best growth inhibition values for MIC and MBC, at 1 μg/mL and 2 μg/mL, respectively. Chalcones 14 and 15 likewise demonstrated excellent inhibitory results, being 2 μg/mL for both MIC and MBC. Additionally, 15 had the best MMP-9 inhibition score. Despite not corroborating the in silico findings, chalcones 10, 13, and 18 showed good cytotoxicity and the best selectivity indices. All compounds exhibited strong activity against H. pylori, specially 15. The predicted MMP-9 inhibition by molecular docking added to the reasonable SI and CI50 values for 15 and the satisfactory reduction in the rate of survival of the bacteria, reveals that it may be acting synergically to reduce the inflammatory response and the possibilities for developing a tumor by inhibiting both bacteria and malignant cells.

The Multifaceted Roles of Hippo-YAP in Cardiovascular Diseases.

The Hippo-yes-associated protein (YAP) signaling pathway plays a crucial role in cell proliferation, differentiation, and death. It is known to have impact on the progression and development of cardiovascular diseases (CVDs) as well as in the regeneration of cardiomyocytes (CMs). However, further research is needed to understand the molecular mechanisms by which the Hippo-YAP pathway affects the pathological processes of CVDs in order to evaluate its potential clinical applications. In this review, we have summarized the recent findings on the role of the Hippo-YAP pathway in CVDs such as myocardial infarction, heart failure, and cardiomyopathy, as well as its in CM development. This review calls attention to the potential roles of the Hippo-YAP pathway as a relevant target for the future treatment of CVDs.

Prognosis of asymptomatic endolymphatic hydrops in healthy volunteers: A five-year cohort study.

This study aimed to clarify the prognosis of asymptomatic endolymphatic hydrops (EH) in healthy volunteers via five-year follow-ups with inner ear magnetic resonance imaging (MRI). Inner ear MRI was performed on 115 participants recruited as controls in a previous study on Meniere's disease. The endolymphatic space was visualized using Naganawa's method of contrast-enhanced MRI with intravenous gadolinium injection and evaluated using Nakashima's method of 2D imaging analysis. Cochlear or vestibular EH was present in 7.0% of participants (n = 8), with all cases being unilateral (laterality), moderate (severity), and asymptomatic (onset). Only cochlear-localized EH, only vestibular-localized EH, and both EH were present in 1.7% (n = 2) (C group), 4.3% (n = 5) (V group), and 0.9% (n = 1) (CV group) of participants, respectively. Conducting inner ear MRI after 5 years showed that EH had almost disappeared in two participants in the C and V groups (4/8, 50.0%). EH was still present in three participants in the V group and one in the CV group (4/8, 50.0%). One participant in the V group and another in the CV group presented with residual inner ear EH and developed typical symptomatic Meniere's disease (2/8, 25.0%). Approximately 7% of healthy participants showed asymptomatic EH. Therefore, EH is not the definitive marker for making a diagnosis of Meniere's disease or the suitable predictor for the development of Meniere's disease. Among these participants, 25% maintained EH and subsequently developed typical Meniere's disease within the next 5 years. Schellong-positive participants maintained persistent EH in the inner ear, and participants with higher scores on the self-rating depression scale developed Meniere's symptoms after 5 years. 2a.

Microbiota profiling in esophageal diseases: novel insights into molecular staining and clinical outcomes

Gut microbiota is recognized nowadays as one of the key players in the development of several gastro-intestinal diseases. The first studies focused mainly on healthy subjects with staining of main bacterial species via culture-based techniques. Subsequently, lots of studies tried to focus on principal esophageal disease enlarged the knowledge on esophageal microbial environment and its role in pathogenesis.Gastro Esophageal Reflux Disease (GERD), the most widespread esophageal condition, seems related to a certain degree of mucosal inflammation, via interleukin (IL) 8 potentially enhanced by bacterial components, lipopolysaccharide (LPS) above all. Gram- bacteria, producing LPS), such as Campylobacter genus, have been found associated with GERD.Barrett esophagus (BE) seems characterized by a Gram- and microaerophils-shaped microbiota.Esophageal cancer (EC) development leads to an overturn in the esophageal environment with the shift from an oral-like microbiome to a prevalently low-abundant and low-diverse Gram--shaped microbiome.Although underinvestigated, also changes in the esophageal microbiome are associated with rare chronic inflammatory or neuropathic disease pathogenesis.The paucity of knowledge about the microbiota-driven mechanisms in esophageal disease pathogenesis is mainly due to the scarce sensitivity of sequencing technology and culture methods applied so far to study commensals in the esophagus.However, the recent advances in molecular techniques, especially with the advent of non-culture-based genomic sequencing tools and the implementation of multi-omics approaches, have revolutionized the microbiome field, with promises of implementing the current knowledge, discovering more mechanisms underneath, and giving insights into the development of novel therapies aimed to re-establish the microbial equilibrium for ameliorating esophageal diseases.

Brain endothelial cell activation and dysfunction associate with and contribute to the development of enlarged perivascular spaces and cerebral small vessel disease.

Multiple injurious stimuli to the brain's endothelium results in brain endothelial cell activation and dysfunction (BECact/dys) with upregulation of inflammatory signaling cascades and a decrease in bioavailable nitric oxide respectively. These injurious stimuli initiate a brain injury and a response to injury wound healing genetically programed cascade of events, which result in cellular remodeling of the neurovascular unit and blood-brain barrier with increased inflammation and permeability. These remodeling changes also include the perivascular spaces that become dilated to form enlarged perivascular spaces (EPVS) that may be identified noninvasively by magnetic resonance imaging. These EPVS are associated with and considered to be a biomarker for cerebral small vessel disease (SVD) and a dysfunctional glymphatic system with impaired removal of neurotoxic waste, which ultimately results in neurodegeneration with impaired cognition and dementia. The penultimate section discusses the understudied role of venous cerebral circulation in relation to EPVS, SVD, and the vascular contribution to cognitive impairment (VCID). The focus of this review will be primarily on BECact/dys that associates with and contributes to the development of EPVS, SVD, and impaired glymphatic system efflux. Importantly, BECact/dys may be a key piece of the puzzle to unlock this complicated story of EPVS and SVD. Multiple transmission electron micrographs and illustrations will be utilized to depict anatomical ultrastructure and allow for the discussion of multiple functional molecular cascades.

Building a protective shield: The role of wound healing in reducing postharvest decay and preserving quality of citrus fruit1

Postharvest citrus fruit is susceptible to pathogenic infestation and quality reduction through wounds, leading to tremendous commercial losses. Herein, wound healing of citrus fruit was obviously at 25°C for five days to form a barrier effective against the development of infectious diseases and water dissipation. Combined with the results of transcriptional and metabolic levels, wound healing activated the expression of CsKCS4, CsKCS11, CsCYP704B1, CsFAH1, CsGPAT3 and CsGPAT9 genes in suberin biosynthesis pathway, and CsPMEI7, CsCesA-D3, CsXTH2, CsXTH6, CsXTH22, CsXTH23, CsXTH24, CsC4H and CsCAD genes in cell wall metabolism pathway, leading to the accumulation of suberin monomers and cell wall components. The results of microscopic observations proved wound healing promoted suberin deposition and cell wall strengthening. Meanwhile, wound healing required the provision of energy and precursor substances by carbohydrate metabolism and amino acid metabolism. We provide new insights into the regulatory mechanism of wound healing on improving disease resistance and maintaining the quality of citrus fruit.

A New Brain Network Construction Paradigm for Brain Disorder via Diffusion-Based Graph Contrastive Learning.

Brain network analysis plays an increasingly important role in studying brain function and the exploring of disease mechanisms. However, existing brain network construction tools have some limitations, including dependency on empirical users, weak consistency in repeated experiments and time-consuming processes. In this work, a diffusion-based brain network pipeline, DGCL is designed for end-to-end construction of brain networks. Initially, the brain region-aware module (BRAM) precisely determines the spatial locations of brain regions by the diffusion process, avoiding subjective parameter selection. Subsequently, DGCL employs graph contrastive learning to optimize brain connections by eliminating individual differences in redundant connections unrelated to diseases, thereby enhancing the consistency of brain networks within the same group. Finally, the node-graph contrastive loss and classification loss jointly constrain the learning process of the model to obtain the reconstructed brain network, which is then used to analyze important brain connections. Validation on two datasets, ADNI and ABIDE, demonstrates that DGCL surpasses traditional methods and other deep learning models in predicting disease development stages. Significantly, the proposed model improves the efficiency and generalization of brain network construction. In summary, the proposed DGCL can be served as a universal brain network construction scheme, which can effectively identify important brain connections through generative paradigms and has the potential to provide disease interpretability support for neuroscience research.

Interplay of gut microbiota, glucagon-like peptide receptor agonists, and nutrition: New frontiers in metabolic dysfunction-associated steatotic liver disease therapy

The gut-liver axis plays a crucial role in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Key metabolites, including lipopolysaccharides, short-chain fatty acids (SCFAs), bile acids, and beneficial gut bacteria such as Bifidobacterium and Lactobacillus, are pivotal in this process. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise in managing MASLD by promoting weight loss, enhancing insulin secretion, and improving liver health. They restore gut-liver axis functionality, and their effects are amplified through dietary modifications and gut microbiome-targeted therapies. Emerging research highlights the interplay between GLP-1 RAs and gut microbiota, indicating that the gut microbiome significantly influences therapeutic outcomes. Metabolites produced by gut bacteria, can stimulate glucagon-like peptide-1 (GLP-1) secretion, further improving metabolic health. Integrating dietary interventions with GLP-1 RA treatment may enhance liver health by modulating the gut microbiota-SCFAs-GLP-1 pathway. Future research is needed to understand personalized effects, with prebiotics and probiotics offering treatment avenues for MASLD.

The Ascorbic Acid-Modified Fenton System for the Degradation of Bisphenol A: Kinetics, Parameters, and Mechanism

Bisphenol A (BPA) has been extensively used in the commercial production, especially the production of plastic products. It has endocrine-disrupting effects and poses potential risks to health, which is also related to the development of various diseases. Nevertheless, using conventional biological treatment techniques has proved challenging in fully breaking down this particular hazardous substance. The degradation ability of the target substance was explored by investigating the effect of an ascorbic acid (Vc)-modified Fenton-like system. The results showed that the degradation rate of the modified system reached 74.6% after 20 min, which was much higher than the 9.1% degradation rate without Vc. Under different ratios of Vc and Fe(III), when the ratios were 1:1 and 1/2:1, the reaction efficiency was the best, and the degradation rate exceeded 83%. When pH = 6.5 and the ratio of Vc to Fe(III) was 1:1, the optimal conditions were achieved, and 83.5% of the BPA could be degraded within 60 min. The results of the quenching experiment provided evidence that •OH was the main reactive oxidizing species (ROS). Analysis of the BPA degradation pathway and the product toxicity evaluation revealed a reduction in the acute/chronic toxicity of BPA from toxic/very toxic to non-harmful/harmful levels. The presented evidence demonstrates that Vc significantly enhances the performance of the modified Fenton-like system and has definite potential for application.

Activins and Inhibins in Cardiovascular Pathophysiology

Activins and inhibins, members of the transforming growth factor β (TGFβ) superfamily, were initially recognized for their opposing effects on the secretion of follicle-stimulating hormone. Subsequent research has demonstrated their broader biological roles across various tissue types. Primarily, activins and inhibins function through the classical TGFβ SMAD signaling pathway, but studies suggest that they also act through other pathways, with their specific signaling being complex and context-dependent. Recent research has identified significant roles for activins and inhibins in the cardiovascular system. Their actions in other systems and their signaling pathways show strong correlations with the development and progression of cardiovascular diseases, indicating potential broader roles in the cardiovascular system. This review summarizes the progress in research on the biological functions and mechanisms of activins and inhibins and their signaling pathways in cardiovascular diseases, offering new insights for the prevention and treatment of cardiovascular diseases.

An update on the pathogenesis and ethnopharmacological therapeutic approaches of vulvovaginal candidiasis

AbstractIn the era of globalization, the concept of world health needs to be practiced where a significant consideration should be given to women health. Of many issues, the most common and under-rated is vulvovaginal candidiasis (VVC); a superficial to invasive mucosal infection of lower reproductive tract in women, primarily caused by commensal yeast Candida. The inability of conventional drugs in triumphing the VVC has made researchers to review the potential of traditional medicines. The present review aimed to highlight the problem and concerns of women related to VVC, covering all aspects of disease development, host response, conventional drug failure, and possibilities of formulating phytomolecule based VVC therapy. The health and disease issues in women are considerably severe, especially for those living in impoverished conditions. Any dysbiosis in vaginal microbiome disturbs the harmony between residing microbes and leads to commencement of VVC. Lactobacillus is key care-taker microbe that keeps check on over growth of Candida by various means. However, Candida have evolved numerous virulence traits to overcome the governance of Lactobacillus as well as host immune system. The present review comprehensively outlined the virulence, and pathogenicity of Candida along with its interaction with host immune system. The review has also highlighted the current conventional drugs and their drawbacks, along with potential of ethnopharmacological phytoactive molecules as future therapies for defining the therapeutic management of the disease. Graphical Abstract

A special focus on polyadenylation and alternative polyadenylation in neurodegenerative diseases: A systematic review

AbstractNeurodegenerative diseases (NDDs) are one of the prevailing conditions characterized by progressive neuronal loss. Polyadenylation (PA) and alternative polyadenylation (APA) are the two main post‐transcriptional events that regulate neuronal gene expression and protein production. This systematic review analyzed the available literature on the role of PA and APA in NDDs, with an emphasis on their contributions to disease development. A comprehensive literature search was performed using the PubMed, Scopus, Cochrane, Google Scholar, Embase, Web of Science, and ProQuest databases. The search strategy was developed based on the framework introduced by Arksey and O'Malley and supplemented by the inclusion and exclusion criteria. The study selection was performed by two independent reviewers. Extraction and data organization were performed in accordance with the predefined variables. Subsequently, quantitative and qualitative analyses were performed. Forty‐seven studies were included, related to a variety of NDDs, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Disease induction was performed using different models, including human tissues, animal models, and cultured cells. Most investigations were related to PA, although some were related to APA or both. Amyloid precursor protein (APP), Tau, SNCA, and STMN2 were the major genes identified; most of the altered PA patterns were related to mRNA stability and translation efficiency. This review particularly underscores the key roles of PA and APA in the pathogenesis of NDDs through their mechanisms that contribute to gene expression dysregulation, protein aggregation, and neuronal dysfunction. Insights into these mechanisms may lead to new therapeutic strategies focused on the modulation of PA and APA activities. Further research is required to investigate the translational potential of targeting these pathways for NDD treatment. image

Angiotensin II Induces Vascular Endothelial Dysfunction by Promoting Lipid Peroxidation-Mediated Ferroptosis via CD36

Angiotensin II (Ang II) is an effective vasoconstriction peptide, a major effector molecule of the renin–angiotensin–aldosterone system (RAAS) and one of the important causes of endothelial dysfunction. Ferroptosis is considered to be involved in the occurrence and development of cardiovascular diseases. This study is dedicated to exploring the role and mechanism of Ang II-induced ferroptosis in HUVECs and to finding molecular targets for vascular endothelial injury and dysfunction during the progression of hypertension. In this study, we found that with the increase in exposure concentration, the intracellular ROS content and apoptosis rate increased significantly, the NO release decreased significantly in the medium- and high-concentration groups and the ET-1 content in the high-concentration group increased significantly. The expression of ZO-1 protein was significantly decreased in the high-concentration group. The expression of p-eNOS, VE-cadherin and Occludin protein showed a dose-dependent downward trend, while the ICAM-1 protein showed an upward trend. Ang II caused lipid metabolism disorders in HUVECs, and the PL–PUFAs associated with ferroptosis were significantly increased. In addition, Ang II promoted a significant increase in intracellular free Fe2+ content and MDA and a significant decrease in GSH content. Furthermore, the expression of GPX4, SLC7A11 and SLC3A2 was down-regulated, the expression of ACSL4, LPCAT3 and ALOX15 was up-regulated, and the ratio of p-cPLA2/cPLA2 was increased. After the intervention of ferroptosis inhibitor Fer-1, the injury and dysfunction of HUVECs induced by Ang II were significantly rescued. Immunofluorescence results showed that the expression of CD36 showed a significant increasing trend and was localized in the cytoplasm. Over-expression of CD36 promoted Ang II-induced ferroptosis and endothelial dysfunction. In conclusion, Ang II induces the injury of HUVECs, decreases vascular diastole and endothelial barrier-related molecules, and increases vascular constriction and adhesion-related molecules, which may be related to CD36 and its mediated lipid peroxidation and ferroptosis signals.