Publications by authors named "Ravi Vats"

Cigarette smoking is associated with a higher risk of ICU admissions among patients with flu. However, the etiological mechanism by which cigarette smoke (CS) exacerbates flu remains poorly understood. Here, we show that a mild dose of influenza A virus promotes a severe lung injury in mice preexposed to CS but not room air for 4 weeks.

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Lipid droplets (LDs) have drawn much attention in recent years. They serve as the energy reservoir of cells and also play an important role in numerous physiological processes. Furthermore, LDs are found to be associated with several pathological conditions, including cancer and diabetes mellitus.

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Human skeleton requires an adequate supply of many different nutritional factors for optimal growth and development. The role of nutrition in bone growth has piqued interest in recent years, especially in relation to maximizing peak bone mass and reducing the risk of osteoporosis. Protein deficiency-induced bone loss was induced in female growing rats.

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Acute lung injury, referred to as the acute chest syndrome, is a major cause of morbidity and mortality in patients with sickle cell disease (SCD), which often occurs in the setting of a vaso-occlusive painful crisis. P-selectin antibody therapy reduces hospitalization of patients with SCD by ∼50%, suggesting that an unknown P-selectin-independent mechanism promotes remaining vaso-occlusive events. In patients with SCD, intraerythrocytic polymerization of mutant hemoglobin promotes ischemia-reperfusion injury and hemolysis, which leads to the development of sterile inflammation.

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Article Synopsis
  • Hemophilia A is a genetic bleeding disorder caused by low levels of coagulation factor VIII (FVIII), traditionally treated with IV FVIII treatments.
  • Recent research shows gene therapy using a vector called adeno-associated virus (AAV) can help, but challenges like cellular stress and immune response limit its effectiveness.
  • In a study with FVIII-deficient mice, researchers found that a specific type of liver cell's structural changes hindered gene transfer, indicating that the absence of proper liver cell function affects the success of this therapy.
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Powdery mildew (PM) caused by the obligate biotrophic fungal pathogen Erysiphe pisi is an economically important disease of legumes. Legumes are rich in isoflavonoids, a class of secondary metabolites whose role in PM resistance is ambiguous. Here we show that the pterocarpan medicarpin accumulates at fungal infection sites, as analysed by fluorescein-tagged medicarpin, and provides penetration and post-penetration resistance against E.

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Aging is the most significant risk factor for the majority of chronic diseases, including liver disease. The cellular, molecular, and pathophysiological mechanisms that promote age-induced hepatovascular changes are unknown due to our inability to visualize changes in liver pathophysiology in live mice over time. We performed quantitative liver intravital microscopy (qLIM) in live C57BL/6J mice to investigate the impact of aging on the hepatovascular system over a 24-mo period.

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Understanding the kinetics and spatiotemporal interactions of living cells within the tissue environment requires real-time imaging. The introduction of two-photon microscopy has substantially boosted the power of live intravital imaging, making it possible to obtain information of individual cells in near-physiologic conditions within intact tissues nondestructively. Intravital imaging of the liver has proved useful in understanding its 3D structure, function, and dynamic cellular interactions.

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Yes-associated protein 1 (YAP1) regulates cell plasticity during liver injury, regeneration, and cancer, but its role in liver development is unknown. We detect YAP1 activity in biliary cells and in cells at the hepatobiliary bifurcation in single-cell RNA sequencing analysis of developing livers. Deletion of Yap1 in hepatoblasts does not impair Notch-driven SOX9+ ductal plate formation but does prevent the formation of the abutting second layer of SOX9+ ductal cells, blocking the formation of a patent intrahepatic biliary tree.

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The current therapeutic regimen for visceral leishmaniasis is inadequate and unsatisfactory due to toxic side effects, high cost and emergence of drug resistance. Alternative, safe and affordable antileishmanials are, therefore, urgently needed and toward these we synthesized a series of arylpiperazine substituted pyranone derivatives and screened them against both in vitro and in vivo model of visceral leishmaniasis. Among 22 synthesized compounds, 5a and 5g showed better activity against intracellular amastigotes with an IC of 11.

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Background: Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified.

Methods: To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed.

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  • P-selectin inhibition can help reduce episodes where blood flow is blocked in SCD patients, but researchers are still looking into its long-term effects.
  • A study using special mice showed that while chronic lack of P-selectin improves liver blood flow, it doesn’t fully protect the liver from damage due to increased cell aging and lower liver cell reproduction.
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Nanomolar concentrations of drag-reducing polymer (DRP) reduce vaso-occlusion in the liver of sickle cell disease (SCD) mice. The potential for DRP as a rheology-based treatment/therapy for SCD warrants further study.

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  • Patients with hemolytic anemias are at increased risk for developing blood clots in their lungs, but the exact cause of this link is unclear.
  • A study using mice demonstrated that acute hemolysis causes the formation of clots rich in platelets in small pulmonary arteries, which can temporarily block blood flow.
  • The research indicates that the release of ADP from damaged red blood cells is crucial for triggering platelet activation and subsequent clot formation, while thrombin does not significantly contribute to this process.
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  • * Acute chest syndrome (ACS) is a severe complication of SCD that contributes significantly to patient mortality and can develop from VOE.
  • * Recent research shows that a P-selectin monoclonal antibody, specifically a fusion molecule called TSGL-Ig, can reduce lung vaso-occlusion in SCD mice, demonstrating its potential to prevent both VOE and ACS in SCD patients.
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  • Sickle cell disease (SCD) can lead to hepatic crises, but the exact molecular mechanisms of liver injury in SCD are not well understood, prompting research using humanized mouse models and patient blood samples.* -
  • The study found that SCD mice showed liver issues like sinusoidal ischemia and increased liver size due to activation of NF-κB, which disrupted farnesoid X receptor (FXR) function and impaired bile transport and metabolism, causing bile buildup in the liver.* -
  • By blocking NF-κB activation, researchers were able to restore FXR signaling and reduce liver damage in SCD mice, highlighting a potential target for treatments of liver-related complications in sickle cell disease.*
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  • In sickle cell disease, the abnormal polymerization of hemoglobin S leads to hemolysis and blockage of small blood vessels, contributing to complications like acute chest syndrome.
  • Researchers used advanced imaging techniques on SCD mice and blood samples to investigate the role of the immune system in causing lung vasoocclusion and injury.
  • They found that platelet activation linked to an inflammasome response results in the formation of inflammatory molecules and platelet-neutrophil aggregates that hinder blood flow, suggesting new therapeutic targets could help prevent acute chest syndrome.
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Background And Aims: The Wnt/β-catenin signaling pathway has a well-described role in liver pathobiology. Its suppression was recently shown to decrease bile acid (BA) synthesis, thus preventing the development of cholestatic liver injury and fibrosis after bile duct ligation (BDL).

Approach And Results: To generalize these observations, we suppressed β-catenin in Mdr2 knockout (KO) mice, which develop sclerosing cholangitis due to regurgitation of BA from leaky ducts.

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Although commensal flora is involved in the regulation of immunity, the interplay between cytokine signaling and microbiota in atherosclerosis remains unknown. We found that interleukin (IL)-23 and its downstream target IL-22 restricted atherosclerosis by repressing pro-atherogenic microbiota. Inactivation of IL-23-IL-22 signaling led to deterioration of the intestinal barrier, dysbiosis, and expansion of pathogenic bacteria with distinct biosynthetic and metabolic properties, causing systemic increase in pro-atherogenic metabolites such as lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO).

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Background & Aims: Liver fibrosis, hepatocellular necrosis, inflammation, and proliferation of liver progenitor cells are features of chronic liver injury. Mouse models have been used to study the end-stage pathophysiology of chronic liver injury. However, little is known about differences in the mechanisms of liver injury among different mouse models because of our inability to visualize the progression of liver injury in vivo in mice.

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Unlabelled: β-Catenin, the downstream effector of the Wnt signaling, plays important roles in hepatic development, regeneration, and tumorigenesis. However, its role at hepatocyte adherens junctions (AJ) is relatively poorly understood, chiefly due to spontaneous compensation by γ-catenin. We simultaneously ablated β- and γ-catenin expression in mouse liver by interbreeding β-catenin-γ-catenin double-floxed mice and Alb-Cre transgenic mice.

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Article Synopsis
  • This study investigates how sickle cell disease (SCD) causes blockages in lung blood vessels, leading to lung injuries during crises.
  • Researchers used advanced imaging in mice with SCD and found that neutrophils and platelets form clumps that block tiny lung arteries and worsen the condition.
  • Targeting specific molecules on platelets may offer a new treatment approach to prevent lung complications in SCD patients by reducing these harmful aggregates.
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