The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.

A deep cut into early cryptococcal pathogenesis.

Dissemination from one organ system to another is common to many pathogens and often the key process separating simple illness from fatal infection. The pathogenic Cryptococcus species offer a prime example. Cryptococcal infection is thought to begin in the lungs, as a mild or asymptomatic pneumonia. However, bloodborne dissemination from the lungs to the brain is responsible for the most devastating forms of infection. As with other disseminating infections, the transition likely depends on rare but crucial events, such as the crossing of a tissue barrier. By their nature, these events are difficult to study. Francis et al. (mBio 15:e03078-23, 2024, https://doi.org/10.1128/mbio.03078-23) have addressed this difficulty by developing a powerful imaging pipeline to scan through unprecedented volumes of tissue from mice infected with Cryptococcus at multiple stages of infection. Their observations challenge some of our basic assumptions about cryptococcal pathogenesis, including when and how the organism reaches the bloodstream and the central nervous system.

[The viral protein NS1: a major player in the pathogenesis of orthoflaviviruses]. / La protéine virale NS1 : un acteur majeur de la pathogenèse des orthoflavivirus.

Orthoflaviviruses are enveloped positive-sense RNA viruses comprising numerous human pathogens transmitted by hematophagous arthropods. This includes viruses such as dengue virus, Zika virus, and yellow fever virus. The viral nonstructural protein NS1 plays a central role in the pathogenesis and cycle of these viruses by acting in two different forms: associated with the plasma membrane (NS1m) or secreted outside the cell (NS1s). The versatility of NS1 is evident in its ability to modulate various aspects of the infectious process, from immune evasion to pathogenesis. As an intracellular protein, it disrupts many processes, interfering with signaling pathways and facilitating viral replication in concert with other viral proteins. As a secreted protein, NS1 actively participates in immune evasion, interfering with the host immune system, inhibiting the complement system, facilitating viral dissemination, and disrupting the integrity of endothelial barriers. This review primarily aims to address the role of NS1 in viral pathogenesis associated with orthoflaviviruses.

Functions of methyltransferase-like 3 in breast cancer: pathogenesis, drug resistance, and therapeutic target.

Breast cancer (BC) is a highly prevalent malignancy worldwide, with complex pathogenesis and treatment challenges. Research reveals that methyltransferase-like 3 (METTL3) is widely involved in the pathogenesis of several tumors through methylation of its target RNAs, and its role and mechanisms in BC are also extensively studied. In this review, we aim to provide a comprehensive interpretation of available studies and elucidate the relationship between METTL3 and BC. This review suggests that high levels of METTL3 are associated with the pathogenesis, poor prognosis, and drug resistance of BC, suggesting METTL3 as a potential diagnostic or prognostic biomarker and therapeutic target. Collectively, this review provides a comprehensive understanding of how METTL3 functions through RNA methylation, which provides a valuable reference for future fundamental studies and clinical applications.

Pathogenic genes implicated in sleep-related hypermotor epilepsy: a research progress update.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by a variable age of onset and heterogeneous etiology. Current literature suggests a prevalence rate of approximately 1.8 per 100,000 persons. The discovery of additional pathogenic genes associated with SHE in recent years has significantly expanded the knowledge and understanding of its pathophysiological mechanisms. Identified SHE pathogenic genes include those related to neuronal ligand- and ion-gated channels (CHRNA4, CHRNB2, CHRNA2, GABRG2, and KCNT1), genes upstream of the mammalian target of rapamycin complex 1 signal transduction pathway (DEPDC5, NPRL2, NPRL3, TSC1, and TSC2), and other genes (CRH, CaBP4, STX1B, and PRIMA1). These genes encode proteins associated with ion channels, neurotransmitter receptors, cell signal transduction, and synaptic transmission. Mutations in these genes can result in the dysregulation of encoded cellular functional proteins and downstream neuronal dysfunction, ultimately leading to epileptic seizures. However, the associations between most genes and the SHE phenotype remain unclear. This article presents a literature review on the research progress of SHE-related pathogenic genes to contribute evidence to genotype-phenotype correlations in SHE and establish the necessary theoretical basis for future SHE treatments.

Pediatric dilated cardiomyopathy: a review of current clinical approaches and pathogenesis.

Pediatric dilated cardiomyopathy (DCM) is a rare, yet life-threatening cardiovascular condition characterized by systolic dysfunction with biventricular dilatation and reduced myocardial contractility. Therapeutic options are limited with nearly 40% of children undergoing heart transplant or death within 2 years of diagnosis. Pediatric patients are currently diagnosed based on correlating the clinical picture with echocardiographic findings. Patient age, etiology of disease, and parameters of cardiac function significantly impact prognosis. Treatments for pediatric DCM aim to ameliorate symptoms, reduce progression of disease, and prevent life-threatening arrhythmias. Many therapeutic agents with known efficacy in adults lack the same evidence in children. Unlike adult DCM, the pathogenesis of pediatric DCM is not well understood as approximately two thirds of cases are classified as idiopathic disease. Children experience unique gene expression changes and molecular pathway activation in response to DCM. Studies have pointed to a significant genetic component in pediatric DCM, with variants in genes related to sarcomere and cytoskeleton structure implicated. In this regard, pediatric DCM can be considered pediatric manifestations of inherited cardiomyopathy syndromes. Yet exciting recent studies in infantile DCM suggest that this subset has a distinct etiology involving defective postnatal cardiac maturation, such as the failure of programmed centrosome breakdown in cardiomyocytes. Improved knowledge of pathogenesis is central to developing child-specific treatment approaches. This review aims to discuss the established biological pathogenesis of pediatric DCM, current clinical guidelines, and promising therapeutic avenues, highlighting differences from adult disease. The overarching goal is to unravel the complexities surrounding this condition to facilitate the advancement of novel therapeutic interventions and improve prognosis and overall quality of life for pediatric patients affected by DCM.

Molecular biomarkers in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma is a unique B-cell derived malignancy featuring rare malignant Hodgkin and Reed Sternberg (HRS) cells that are embedded in a quantitively dominant tumor microenvironment (TME). Treatment of classic Hodgkin lymphoma has significantly evolved in the past decade with improving treatment outcomes for newly diagnosed patients and the minority of patients suffering from disease progression. However, the burden of toxicity and treatment-related long-term sequelae remains high in a typically young patient population. This highlights the need for better molecular biomarkers aiding in risk-adapted treatment strategies and predicting response to an increasing number of available treatments that now prominently involve multiple immunotherapy options. Here, we review modern molecular biomarker approaches that reflect both the biology of the malignant HRS cells and cellular components in the TME, while holding the promise to improve diagnostic frameworks for clinical decision-making and be feasible in clinical trials and routine practice. In particular, technical advances in sequencing and analytic pipelines using liquid biopsies, as well as deep phenotypic characterization of tissue architecture at single-cell resolution, have emerged as the new frontier of biomarker development awaiting further validation and implementation in routine diagnostic procedures.

Pathogenesis of depression and the potential for traditional Chinese medicine treatment.

Depression is a prevalent mental disorder that significantly diminishes quality of life and longevity, ranking as one of the primary causes of disability globally. Contemporary research has explored the potential pathogenesis of depression from various angles, encompassing genetics, neurotransmitter systems, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, inflammation, and intestinal flora, among other contributing factors. In addition, conventional chemical medications are plagued by delayed onset of action, persistent adverse effects, and restricted therapeutic efficacy. In light of these limitations, the therapeutic approach of traditional Chinese medicine (TCM) has gained increasing recognition for its superior effectiveness. Numerous pharmacological and clinical studies have substantiated TCM's capacity to mitigate depressive symptoms through diverse mechanisms. This article attempts to summarize the mechanisms involved in the pathogenesis of depression and to describe the characteristics of herbal medicines (including compounded formulas and active ingredients) for the treatment of depression. It further evaluates their effectiveness by correlating with the multifaceted pathogenesis of depression, thereby furnishing a reference for future research endeavors.

Mechanism and treatment of secondary glaucoma after corneal transplantation: a review.

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

Ischemic Stroke and Autophagy: The Roles of Long Non-Coding RNAs.

Ischemic stroke is a significant cause of morbidity and mortality worldwide. Autophagy, a process of intracellular degradation, has been shown to play a crucial role in the pathogenesis of ischemic stroke. Long non-coding RNAs (lncRNAs) have emerged as essential regulators of autophagy in various diseases, including ischemic stroke. Recent studies have identified several lncRNAs that modulate autophagy in ischemic stroke, including MALAT1, MIAT, SNHG12, H19, AC136007. 2, C2dat2, MEG3, KCNQ1OT1, SNHG3, and RMRP. These lncRNAs regulate autophagy by interacting with key proteins involved in the autophagic process, such as Beclin-1, ATG7, and LC3. Understanding the role of lncRNAs in regulating autophagy in ischemic stroke may provide new insights into the pathogenesis of this disease and identify potential therapeutic targets for its treatment.

The correlation between corona virus disease 2019 and alopecia areata: a literature review.

Corona virus disease 2019(COVID-19) is one of the most serious respiratory pandemic diseases threatening human health for centuries. Alopecia areata (AA) is a sudden patchy hair loss, an autoimmune disease, which seriously affects the image and mental health of patients. Evidence shows that the risk of autoimmune diseases significantly increases after COVID-19, and is positively correlated with the severity, with a significant increase in the risk of alopecia in those over 40 years old. The relationship between COVID-19 and AA has become a hot topic of current research. Strengthening the research on the correlation between COVID-19 and AA can help to identify and protect susceptible populations at an early stage. This article reviews the research progress on the epidemiological background of COVID-19 and AA, the situation and possible mechanisms of AA induced by COVID-19 or COVID-19 vaccination, and potential treatment methods.

Synaptic cell adhesion molecules contribute to the pathogenesis and progression of fragile X syndrome.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a monogenic cause of autism spectrum disorders. Deficiencies in the fragile X messenger ribonucleoprotein, encoded by the FMR1 gene, lead to various anatomical and pathophysiological abnormalities and behavioral deficits, such as spine dysmorphogenesis and learning and memory impairments. Synaptic cell adhesion molecules (CAMs) play crucial roles in synapse formation and neural signal transmission by promoting the formation of new synaptic contacts, accurately organizing presynaptic and postsynaptic protein complexes, and ensuring the accuracy of signal transmission. Recent studies have implicated synaptic CAMs such as the immunoglobulin superfamily, N-cadherin, leucine-rich repeat proteins, and neuroligin-1 in the pathogenesis of FXS and found that they contribute to defects in dendritic spines and synaptic plasticity in FXS animal models. This review systematically summarizes the biological associations between nine representative synaptic CAMs and FMRP, as well as the functional consequences of the interaction, to provide new insights into the mechanisms of abnormal synaptic development in FXS.

Functional Analysis of Genes in Mycobacterium tuberculosis Action Against Autophagosome-Lysosome Fusion.

Tuberculosis is a lethal disease that is one of the world's top ten death-associated infections in humans; Mycobacterium tuberculosis causes tuberculosis, and this bacterium is linked to the lysis of autophagolysosomal fusion action, a self-defense mechanism of its own. Thus, Cytoplasmic bacilli are sequestered by autophagy and transported to lysosomes to be inactivated to destroy intracellular bacteria. Besides this, a macrophage can limit intracellular Mycobacterium by using a type of autophagy, selective autophagy, a cell that marks undesirable ubiquitin existence in cytosolic cargo, acting as a "eat me" sensor in conjunction with cellular homeostasis. Mycobacterium tuberculosis genes of the PE_PGRS protein family inhibit autophagy, increase mycobacterial survival, and lead to latent tuberculosis infection associated with miRNAs. In addition, the family of autophagy-regulated (ATG) gene members are involved in autophagy and controls the initiation, expansion, maturation, and fusion of autophagosomes with lysosomes, among other signaling events that control autophagy flux and reduce inflammatory responses and forward to promote cellular proliferation. In line with the formation of caseous necrosis in macrophages by Mycobacterium tuberculosis and their action on the lysis of autophagosome fusion, it leads to latent tuberculosis infection. Therefore, we aimed to comprehensively analyses the autophagy and self-defense mechanism of Mycobacterium tuberculosis, which is to be gratified future research on novel therapeutic tools and diagnostic markers against tuberculosis.

A Systemic Review on Fitness and Survival of Salmonella in Dynamic Environment and Conceivable Ways of Its Mitigation.

Gastroenteritis caused by non-typhoidal Salmonella still prevails resulting in several recent outbreaks affecting many people worldwide. The presence of invasive non-typhoidal Salmonella is exemplified by several characteristic symptoms and their severity relies on prominent risk factors. The persistence of this pathogen can be attributed to its broad host range, complex pathogenicity and virulence and adeptness in survival under challenging conditions inside the host. Moreover, a peculiar aid of the ever-changing climatic conditions grants this organism with remarkable potential to survive within the environment. Abusive use of antibiotics for the treatment of gastroenteritis has led to the emergence of multiple drug resistance, making the infections difficult to treat. This review emphasizes the importance of early detection of Salmonella, along with strategies for accomplishing it, as well as exploring alternative treatment approaches. The exceptional characteristics exhibited by Salmonella, like strategies of infection, persistence, and survival parallelly with multiple drug resistance, make this pathogen a prominent concern to human health.

Membranous nephropathy: pathogenesis and treatments.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.

Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Bioinformatics and systems biology approaches to identify potential common pathogeneses for sarcopenia and osteoarthritis.

Sarcopenia, a geriatric syndrome characterized by progressive loss of muscle mass and strength, and osteoarthritis, a common degenerative joint disease, are both prevalent in elderly individuals. However, the relationship and molecular mechanisms underlying these two diseases have not been fully elucidated. In this study, we screened microarray data from the Gene Expression Omnibus to identify associations between sarcopenia and osteoarthritis. We employed multiple statistical methods and bioinformatics tools to analyze the shared DEGs (differentially expressed genes). Additionally, we identified 8 hub genes through functional enrichment analysis, protein-protein interaction analysis, transcription factor-gene interaction network analysis, and TF-miRNA coregulatory network analysis. We also discovered potential shared pathways between the two diseases, such as transcriptional misregulation in cancer, the FOXO signalling pathway, and endometrial cancer. Furthermore, based on common DEGs, we found that strophanthidin may be an optimal drug for treating sarcopenia and osteoarthritis, as indicated by the Drug Signatures database. Immune infiltration analysis was also performed on the sarcopenia and osteoarthritis datasets. Finally, receiver operating characteristic (ROC) curves were plotted to verify the reliability of our results. Our findings provide a theoretical foundation for future research on the potential common pathogenesis and molecular mechanisms of sarcopenia and osteoarthritis.

Roles of non-coding RNA in diabetic cardiomyopathy.

In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM.

Virus as the cause of type 1 diabetes.

Type 1 diabetes (T1D), a severe disease requiring intensive insulin treatment, carries an increased risk for complications and reduced lifespan. Certain viruses have been implicated in T1D's etiology, with 'live', replicating enteroviruses (EVs) recently found in the pancreas at diagnosis. This discovery prompted a trial to slow down disease progression using antiviral drugs. A 6-month treatment combining pleconaril and ribavirin in new-onset T1D patients preserved residual insulin production after 1 year, unlike placebo. The results support the theory that viruses may cause T1D in genetically susceptible individuals. A low-grade, persistent viral infection may initiate a cascade of pathogenic mechanisms initially involving the innate immune system, inducing ß-cell stress and neoantigen release, leading to autoimmunity, and eventually the destruction of insulin-producing ß-cells.