Viral and fibrosis

Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation's delicate balance, spanning innate and adaptive immunity. Viral factors' disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression...

Hepatitis C virus (HCV), despite the availability of effective direct-acting antivirals (DAAs) that clear the virus from >95% of individuals treated, continues to cause significant health care burden due to disease progression that can lead to fibrosis, cirrhosis, and/or hepatocellular carcinoma. The fact that some people who are treated with DAAs still go on to develop worsening liver disease warrants further study into the immunopathogenesis of HCV. Many viral infections, including HCV, have been associated with activation of the inflammasome/pyroptosis pathway...

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic liver injury. Exploring potential therapeutic targets and understanding the molecular mechanisms involved in liver fibrosis are essential for the development of effective interventions. The goal of this comprehensive review is to explain how the PI3K/AKT signaling pathway contributes to the reduction of liver fibrosis...

The adult mammalian heart contains a large population of pericytes that play important roles in homeostasis and disease. In the normal heart, pericytes regulate microvascular permeability and flow. Myocardial diseases are associated with marked alterations in pericyte phenotype and function. This review manuscript discusses the role of pericytes in cardiac homeostasis and disease. Following myocardial infarction (MI), cardiac pericytes participate in all phases of cardiac repair. During the inflammatory phase, pericytes may secrete cytokines and chemokines and may regulate leukocyte trafficking, through formation of intercellular gaps that serve as exit points for inflammatory cells...

Alpha-1-antitrypsin (A1AT) is a multifunctional, clinically important, high value therapeutic glycoprotein that can be used for the treatment of many diseases such as alpha-1-antitrypsin deficiency, diabetes, graft-versus-host-disease, cystic fibrosis and various viral infections. Currently, the only FDA-approved treatment for A1AT disorders is intravenous augmentation therapy with human plasma-derived A1AT. In addition to its limited supply, this approach poses a risk of infection transmission, since it uses therapeutic A1AT harvested from donors...

Studies showed that the respiratory is not the only system affected by coronavirus 2, while cardiovascular, digestive, and nervous systems, as well as essential organs such as the kidneys, can be affected by this virus. In this review, we have studied the epidemiology, clinical, and laboratory findings on COVID-19 infection renal involvement, mortality, physiopathology, remaining renal sequels after recovery, underlying renal disease, and renal injury due to its treatment. Also, protective measures for kidney injury are explained in three levels...

Despite antiviral treatment, some patients with chronic hepatitis B (CHB) progress to cirrhosis. Enhancement of autophagy was implicated in the proliferation of hepatitis B in hepatocytes. This study aimed to evaluate the potential role of autophagy in the progression of liver fibrosis in patients receiving antiviral treatments and having completely inhibited viral replication. This descriptive-analytical study was designed and conducted in 2020 at Mottahhari Hepatitis Clinic affiliated with Shiraz University of Medical Science (Shiraz, Iran)...

Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes...

INTRODUCTION: Fibrosis and cirrhosis are associated with worse outcomes after hepatectomy. Aspartate transaminase to platelet ratio index (APRI) is associated with fibrosis and cirrhosis in hepatitis C patients. However, APRI has not been studied to predict outcomes after hepatectomy in patients without viral hepatitis. METHODS: We reviewed the ACS-NSQIP dataset to identify patients who underwent a minor hepatectomy between 2014 and 2021. We excluded patients with viral hepatitis or ascites as well as patients who underwent emergent operations or biliary reconstruction...

The current World Health Organization (WHO) Hepatitis Elimination Strategy suffers from lack of a target for diagnosing or expunging occult HBV infection. A sizable segment of the global population has an undetected HBV infection, particularly the high-risk populations and those residing in countries like India with intermediate endemicity. There is growing proof that people with hidden HBV infection can infect others, and that these infections are linked to serious chronic hepatic complications, especially hepatocellular carcinoma...

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively...

Patients with pulmonary fibrosis (PF) often experience exacerbations of their disease, characterised by a rapid, severe deterioration in lung function that is associated with high mortality. Whilst the pathobiology of such exacerbations is poorly understood, virus infection is a trigger.  This study investigated virus-induced injury responses of alveolar and bronchial epithelial cells (AECs and BECs respectively) from patients with PF and age-matched controls (Ctrls).  Air liquid interface (ALI) cultures of AECs, comprising type I and II pneumocytes or BECs were inoculated with influenza A virus (H1N1) at 0...

INTRODUCTION: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS: We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa...

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerged as versatile non-viral gene delivery systems that could help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics simulations...

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy...

Pyroptosis, a novel programmed cell death mediated by NOD-like receptor protein 3 (NLRP3) inflammasome, is a critical pathogenic process in acute viral myocarditis (AVMC). Mitsugumin 53 (MG53) is predominantly expressed in myocardial tissues and has been reported to exert cardioprotective effects through multiple pathways. Herein, we aimed to investigate the biological function of MG53 in AVMC and its underlying regulatory mechanism in pyroptosis. BALB/c mice and HL-1 cells were infected with Coxsackievirus B3 (CVB3) to establish animal and cellular models of AVMC...

BACKGROUND: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8+ T-cell response. AIMS: To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8+ T-cell response. METHODS: We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8+ cell effector function were correlated with HBsAg level...

Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a mouse model for two virus-induced organ-specific immune-mediated diseases. TMEV-induced demyelinating disease (TMEV-IDD) in the central nervous system (CNS) is a chronic inflammatory disease with viral persistence and an animal model of multiple sclerosis (MS) in humans. TMEV infection can also cause acute myocarditis with viral replication and immune cell infiltration in the heart, leading to cardiac fibrosis. Since platelets have been reported to modulate immune responses, we aimed to determine the role of platelets in TMEV infection...

The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system...

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19"...