A calcium and zinc composite alginate hydrogel for pre-hospital hemostasis and wound care

Carbohydrate Polymers, Год журнала: 2022, Номер 299, С. 120186 - 120186

Опубликована: Окт. 6, 2022

Язык: Английский

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Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight

Molecular and Cellular Biochemistry, Год журнала: 2022, Номер 478(6), С. 1325 - 1343

Опубликована: Окт. 29, 2022

SARS-CoV-2 is a positive-strand RNA virus that infects humans through the nasopharyngeal and oral route causing COVID-19. Scientists left no stone unturned to explore targetable key player in COVID-19 pathogenesis against which therapeutic interventions can be initiated. This article has attempted review, coordinate accumulate most recent observations support of hypothesis predicting altered state mitochondria concerning mitochondrial redox homeostasis, inflammatory regulations, morphology, bioenergetics antiviral signalling infection. Mitochondria extremely susceptible physiological as well pathological stimuli, including viral infections. Recent studies suggest pathogeneses alter integrity, turn modulate cellular response M protein inhibited (MAVS) aggregation hinders innate response. Viral open reading frames (ORFs) also play an instrumental role altering regulation immune Notably, ORF-9b ORF-6 impair MAVS activation. In aged persons, NLRP3 inflammasome over-activated due impaired function, increased reactive oxygen species (mtROS), and/or circulating free DNA, resulting hyper-response classically activated macrophages. tries understand how fission–fusion dynamics affected by virus. review comprehends overall attribute prognosis patients infected with taking into account pertinent vitro, pre-clinical clinical data encompassing subjects broad range severity morbidity. endeavour may help exploring novel non-canonical strategies disease associated complications.

Язык: Английский

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Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июнь 7, 2023

Abstract The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden our society. Most patients infected are asymptomatic or have mild symptoms. Although only small proportion of progressed severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, cardiovascular disorders, is accompanied mortality rates near 7 million deaths. Nowadays, effective therapeutic patterns for still lacking. It been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate avoid immunity, facilitate their own replication, initiate pathological response. Targeting interaction between holds promise developing strategies. In this review, we summarize discuss recent studies dedicated uncovering role life cycle aspects entry, assembly, pathogenesis an emphasis on glucose lipid metabolism. Microbiota long also discussed. Ultimately, recapitulate metabolism-modulating drugs repurposed statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, metformin.

Язык: Английский

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Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I

PLoS Pathogens, Год журнала: 2023, Номер 19(5), С. e1011371 - e1011371

Опубликована: Май 1, 2023

Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, impact of virus on glucose cells and subsequent effects are still unknown. Here, glycolysis induced by shown to facilitate replication promoting lactate production, which then attenuates interaction between mitochondrial antiviral-signaling protein (MAVS) retinoic acid-inducible gene I (RIG-I). induces PK-15 cells, as indicated significantly increased expression hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), superoxide dismutase-2 (SOD2) a dose-and replication-dependent manner, enhanced while reducing ATP generation. Overexpression PKM, PGK1, HIF-1α, PDK3 high concentrations promote replication, glycolytic inhibitors decrease it. Inhibition RLR signaling allowed better production attenuate MAVS RIG-I, regulatory effect was mainly via RIG-I signaling. infection mice PKM PGK1 tissues serum yields lactate. Mice treated with administered sodium showed elevated levels well suppressed induction interferon beta (IFNβ), IFNα, interferon-stimulated 15 (ISG15), interleukin 6 (IL-6). The inhibitory interferons lower oxamate low compared glucose, indicating that inhibited through vitro vivo . These results provide new perspective relationship innate immunity infection, suggesting or may be targets against virus.

Язык: Английский

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SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19

Pharmacological Research, Год журнала: 2024, Номер 204, С. 107170 - 107170

Опубликована: Апрель 12, 2024

To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey metabolic pathways modulated by and confirmed their importance for propagation cataloging specific pathway inhibitors. This revealed that strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from oxidation through glycolysis pentose phosphate (PPP) to provide substrates viral biogenesis. also induces release DNA (mtDNA) activates innate immunity. restructuring energy metabolism is mediated part Orf8 Orf10 whose expression restructures nuclear (nDNA) mtDNA OXPHOS gene expression. These proteins likely alter epigenome, either directly altering histone modifications or modulating metabolite epigenome modification enzymes, potentially silencing contributing long-COVID.

Язык: Английский

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SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Язык: Английский

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2-deoxy-d-glucose as an adjunct to standard of care in the medical management of COVID-19: a proof-of-concept and dose-ranging randomised phase II clinical trial

BMC Infectious Diseases, Год журнала: 2022, Номер 22(1)

Опубликована: Авг. 4, 2022

At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-D-glucose (2-DG) is metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy safety 2-DG as adjunct standard care in treatment moderate severe patients.We conducted randomized, open-label, phase II, clinical study evaluate efficacy, safety, tolerability administered (SOC). A total 110 patients between ages 18 65 years with were included. Patients randomized receive 63, 90, or 126 mg/kg/day addition SOC only. Times maintaining SpO2 ≥ 94% on room air, discharge, recovery, vital signs normalisation, improvement by 1 2 points WHO progression scale, negative conversion RT-PCR, requirement intensive care, mortality analyzed assess efficacy.Patients treated 90 plus showed better outcomes. Time was significantly shorter mg compared (median 2.5 days vs. 5 days, Hazard ratio [95% confidence interval] = 2.3 [1.14, 4.64], p 0.0201). discharge from isolation ward, normalization group. All three doses well tolerated. Thirty-three (30.3%) reported adverse events mostly (86%) mild.2-DG benefit over alone COVID-19. The promising trends observed current II encouraging confirmatory evaluation larger III trial.CTRI, CTRI/2020/06/025664. Registered 5th June 2020, http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27 .

Язык: Английский

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Host mitochondria: more than an organelle in SARS-CoV-2 infection

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Авг. 25, 2023

Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. patients may present with wide range of symptoms, from asymptomatic to requiring intensive care support. The form is often marked an altered immune response and cytokine storm. Advanced age, age-related underlying diseases, including metabolic syndromes, appear contribute increased severity mortality suggesting role for mitochondria in pathogenesis. Furthermore, since system associated its damage-related molecular patterns (mtDAMPs), host mitochondrial play important during infections. Viruses have evolved modulate function survival proliferation, which turn could lead cellular stress progression. Recent studies focused on possible roles SARS-CoV-2 infection. It suggested that hijacking be key factor In this review, we discuss infections infection based past knowledge. Paying attention will help better understand pathophysiology achieve effective methods prevention, diagnosis, treatment.

Язык: Английский

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Virus‐induced host cell metabolic alteration

Reviews in Medical Virology, Год журнала: 2024, Номер 34(1)

Опубликована: Янв. 1, 2024

Abstract Viruses change the host cell metabolism to produce infectious particles and create optimal conditions for replication reproduction . Numerous pathways have been modified ensure available biomolecules sufficient energy. Metabolomics studies conducted over past decade revealed that eukaryotic viruses alter of their cells on a large scale. Modifying like glycolysis, fatty acid synthesis glutaminolysis could provide potential energy virus multiplication. Thus, almost every has unique metabolic signature different relationship between viral life cycle individual processes. There are enormous research in induced reprogramming is being through numerous approaches using vaccine candidates antiviral drug substances. This review provides an overview interference improved monitoring this area will open up new ways more effective therapies combating oncogenesis.

Язык: Английский

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SARS-CoV-2 Nsp6 damages Drosophila heart and mouse cardiomyocytes through MGA/MAX complex-mediated increased glycolysis

Communications Biology, Год журнала: 2022, Номер 5(1)

Опубликована: Сен. 30, 2022

Abstract SARS-CoV-2 infection causes COVID-19, a severe acute respiratory disease associated with cardiovascular complications including long-term outcomes. The presence of virus in cardiac tissue patients COVID-19 suggests this is direct, rather than secondary, effect infection. Here, by expressing individual proteins the Drosophila heart, we demonstrate interaction Nsp6 host MGA/MAX complex (MGA, PCGF6 and TFDP1). Complementing transcriptomic data from fly heart reveal that blocks antagonistic complex, which shifts balance towards MYC/MAX activates glycolysis—with similar findings mouse cardiomyocytes. Further, -induced glycolysis disrupts mitochondrial function, known to increase reactive oxygen species (ROS) failure; could explain COVID-19-associated pathology. Inhibiting pathway 2-deoxy-D-glucose (2DG) treatment attenuates phenotype flies mice. These point as potential pharmacological target for treating failure.

Язык: Английский

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