Liver Organoids From Hepatocytes of Healthy Humans and Non-alcoholic Fatty Liver Disease (NAFLD) Patients Display Multilineage Architecture and can be Used to Develop an Model of Steatohepatitis.

Background/aim: Non-alcoholic fatty liver disease (NAFLD) is a global health concern with limited treatment options. The paucity of predictive   models in preclinical settings seems to be one of the limitations of identifying effective medicines. We therefore aimed to develop an   model that can display the key hallmarks of NAFLD, such as steatosis, inflammation, and fibrosis.

Itaconate mechanism of action and dissimilation in .

Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with increases itaconate levels in lung tissues.

Withaferin A inhibits Chikungunya virus nsP2 protease and shows antiviral activity in the cell culture and mouse model of virus infection.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus causing fever, myalgia, and debilitating joint swelling and pain, which in many patients becomes chronic. The frequent epidemics of CHIKV across the world pose a significant public health burden necessitating the development of effective antiviral therapeutics. A cellular imaging-based high-content screening of natural compounds identified withaferin A (WFA), a steroidal lactone isolated from the plant Withania somnifera, as a potent antiviral against CHIKV.

Receptor Binding Domain-Specific B Cell Memory Responses Among Individuals Vaccinated Against SARS-CoV-2.

: The COVID-19 pandemic prompted unprecedented vaccine development efforts against SARS-CoV-2. India, which was one of the countries most impacted by COVID-19, developed its indigenous vaccine in addition to utilizing the ones developed by other countries. While antibody levels and neutralizing antibody titres are considered initial correlates of immune protection, long-term protection from the pathogen relies on memory B and T cells and their recall responses.

Pandemic-Proofing: Intercepting Zoonotic Spillover Events.

Zoonotic spillover events pose a significant and growing threat to global health. By focusing on preventing these cross-species transmissions, we can significantly mitigate pandemic risks. This review aims to analyze the mechanisms of zoonotic spillover events, identify key risk factors, and propose evidence-based prevention strategies to reduce future pandemic threats.

Placental Proteomics Reveals an Elevated Level of Aldo-Keto Reductase 1-B1, Highlighting Its Potential Role in Spontaneous Preterm Birth.

Preterm birth (PTB) refers to the delivery of a baby before the completion of 37 weeks of gestation. It is a significant global health issue with implications for both mothers and neonates. The placenta is a transient organ crucial in the sustenance of pregnancy until parturition; its dysfunction is associated with different adverse pregnancy outcomes, including PTB.

Seroprevalence and risk factors for Crimean-Congo hemorrhagic fever virus exposure among febrile patients in northern Tanzania.

Background: Crimean-Congo hemorrhagic fever is a tick-borne zoonotic disease that may be severe and is present in many African countries. We aimed to understand the seroprevalence and risk for Crimean-Congo hemorrhagic fever virus in Tanzania by testing archived serum samples from patients enrolled in a prospective cohort study.

Methods: We prospectively enrolled febrile inpatients and outpatients from 2012 through 2014 at two referral hospitals in northern Tanzania.

Integrated proteomics and connectivity map-based analysis reveal compounds with a potential antiviral effect against Japanese encephalitis virus infection in a mouse model.

Japanese encephalitis virus (JEV) is the leading causative agent of viral encephalitis in India and contributes to a significant disease burden in South Asian countries. However, no antiviral treatment is available against JEV-induced encephalitis, highlighting the urgent need for novel therapeutic approaches. Repurposing or repositioning drugs was found to be more economical and practical in the current drug development scenario.

represses type VI secretion system through a manganese-dependent small RNA-mediated regulation.

Type VI secretion system (T6SS) is utilized by many Gram-negative bacteria to eliminate competing bacterial species and manipulate host cells. ATCC 17978 utilizes T6SS at the expense of losing pAB3 plasmid to induce contact-dependent killing of competitor microbes, resulting in the loss of antibiotic resistance carried by pAB3. However, the regulatory network associated with T6SS in remains poorly understood.

Trypanosomatid DRBD9s are likely to be eIF4B orthologues.

Initiation of protein translation is one of the key steps in protein synthesis carried out by translation initiation factors in conjunction with ribosomes. The roles and mechanisms of these initiation factors in prokaryotic and eukaryotic protein synthesis are well understood. However, they are only beginning to be understood in trypanosomatids.

PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs.

The PD-1/PDL-1 immune checkpoint inhibitors revolutionized cancer treatment, yet osteosarcoma remains a therapeutic challenge. In some types of cancer, PD-1 receptor is not solely expressed by immune cells but also by cancer cells, acting either as a tumor suppressor or promoter. While well-characterized in immune cells, little is known about the role and interactome of the PD-1 pathway in cancer.

Epidemiology of chronic and acute pancreatitis in India (EPICAP-India): protocol for a multicentre study.

Introduction: Acute and chronic pancreatitis (CP) are inflammatory conditions of the pancreas that cause local and systemic complications. The epidemiology of these conditions are not well-known in India.

Methods And Analysis: We describe the protocol and procedures of a multicentre study for delineating the epidemiology of pancreatitis in India.

Conformational dynamics of a nicotinic receptor neurotransmitter site.

Agonists enhance receptor activity by providing net-favorable binding energy to active over resting conformations, with efficiency (η) linking binding energy to gating. Previously, we showed that in nicotinic receptors, η-values are grouped into five structural pairs, correlating efficacy and affinity within each class, uniting binding with allosteric activation (Indurthi and Auerbach, 2023). Here, we use molecular dynamics (MD) simulations to investigate the low-to-high affinity transition (L→H) at the Torpedo α-δ nicotinic acetylcholine receptor neurotransmitter site.

From Spores to Suffering: Understanding the Role of Anthrax in Bioterrorism.

Introduction: Anthrax, caused by the bacterium Bacillus anthracis, stands as a formidable threat with both natural and bioterrorism-related implications. Its ability to afflict a wide range of hosts, including humans and animals, coupled with its potential use as a bioweapon, underscores the critical importance of understanding and advancing our capabilities to combat this infectious disease. In this context, exploring futuristic approaches becomes imperative, as they hold the promise of not only addressing current challenges but also ushering in a new era in anthrax management.

Berbamine prevents SARS-CoV-2 entry and transmission.

Effective antiviral drugs are essential to combat COVID-19 and future pandemics. Although many compounds show antiviral activity, only a few retain effectiveness against SARS-CoV-2. Here, we show that berbamine (Berb) is effective against SARS-CoV, MER-CoV, SARS-CoV-2 and its variants, including the XBB.

Autophagy-related gene BECN1 single nucleotide polymorphisms in diseases.

Autophagy is a cytoprotective process that operates within a cell to maintain cellular homeostasis. An array of multiple proteins is involved to mediate this conserved cellular process. Among these, Beclin 1 protein encoded by BECN1 gene plays a crucial role during the initiation of autophagy.

Antimalarial Drug Artemotil Promotes Induction of Type 1 Regulatory T Cells.

Artemisinin and its derivatives, used as front-line anti-malarial drugs, exhibit anti-inflammatory properties. They were found to suppress the generation and function of Th1 and Th17 cells while promoting the generation of Foxp3 + regulatory T cells (Tregs). However, the specific role of Artemotil (β-arteether) in modulating the generation and functions of CD4 + T cells, particularly Type 1 regulatory T cells (Tr1), remains to be explored.

strategies to recognize pharmacological constraints contrary to COX-2 and 5-LOX.

COX-2 and 5-LOX are major enzymes implicated in inflammatory processes and have a crucial role in the pathogenesis of inflammatory disorders and malignancies. Designing antagonists that may concurrently interact with several receptors is a viable technique; thus, blocking these two targets with a single chemical compound might provide an efficient therapeutic approach. In-silico approaches have been employed to find polypharmacological inhibitors, especially for drug repurposing and multitarget drug design.

A compendium of methods: Searching allele specific expression via RNA sequencing.

Diploid mammalian genome has paired alleles for each gene; typically allowing for equal expression of the two alleles within the cell/tissue. However, genetic regulatory elements and epigenetic modifications can disrupt this equality, leading to preferential expression of one allele. Examining high-confidence allele-specific expression (ASE) is vital for understanding genetic variations and their impact on major diseases like cancers and diabetes.

Improved metabolic stability in iNOS knockout mice with Lactobacillus supplementation.

Oxidative and nitrosative stress play pivotal roles in normal physiological processes and the pathogenesis of metabolic disorders. Previous studies from our lab demonstrated insulin resistance (IR), and dyslipidemia in iNOS mice, emphasizing the importance of maintaining optimal redox balance. These mice exhibited altered gut microbiota with decreased Lactobacillus.