Search

For COVID-19 survivors, defeating the virus is just the beginning of a long road to recovery. The inducibility and catastrophic effects of the virus are distributed across multiple organs. The induction of cytokine storms in COVID-19 patients is due to the interaction of the SARS-CoV-2 virus and the host receptor, leading to various immunopathological consequences that may eventually lead to death. So far, COVID-19 has affected tons of people across the world, but there is still no effective treatment. Patients facing complications of COVID-19 after recovery have shown extensive clinical symptoms similar to that of patients recovering from previously circulating coronaviruses. Previous knowledge and literature have opened up ways to treat this disease and manage post-COVID-19 complications, which pose a severe challenge to the health system globally and may exacerbate the fragmentation of diseases. The use of steroids as a treatment has resulted in various health problems and side-effects in COVID-19 patients. This review discusses various post-COVID-19 complications observed and adjunctive therapies used along with common COVID-19 treatment and spotlights their side effects and consequences. This review provides the latest literature on COVID-19, which emphasizes the subsequent complications in various organs, side effects of drugs, and alternative regimens used to treat COVID-19. Key words: COVID-19, cytokine storm, post-COVID-19 complications, corticosteroids, immunotherapy. Pour les survivants de la COVID-19, vaincre le virus n'est que le debut d'un long chemin vers la guerison. L'inductibilite virale et les effets catastrophiques qui en decoulent sont dissemines dans plusieurs organes. L'induction de tempetes de cytokines chez les patients atteints de COVID-19 est due a l'interaction entre le virus SRAS-CoV-2 et le recepteur de l'hote, entrainant diverses consequences immunopathologiques, susceptibles de mener ultimement a la mort. Jusqu'a present, le virus a frappe des millions de personnes partout dans le monde, mais il n'existe toujours pas de traitement efficace. Les patients qui presentent des complications de la COVID-19 apres leur convalescence ont manifeste de nombreux symptomes cliniques semblables a ceux provoques par d'autres coronavirus ayant circule auparavant. Les connaissances anterieures et la litterature ont ouvert une fenetre sur des moyens de traiter la COVID-19 et de prendre en charge les complications qui surviennent apres l'infection, lesquelles posent un grave probleme pour le systeme de sante mondial et ont le potentiel de multiplier les declinaisons de la maladie. L'utilisation de stero'ides comme traitement a revele divers problemes de sante et effets secondaires chez les patients atteints de la COVID-19. Cette revue de litterature dresse un portrait detaille des diverses complications post-COVID-19 observees et des traitements adjuvants utilises en association avec les medicaments couramment employes pour traiter la COVID-19, et met en evidence leurs effets secondaires et leurs consequences. L'article offre une synthese de la plus recente litterature sur la COVID-19, qui se concentre sur les complications subsequentes touchant divers organes, les effets secondaires des medicaments et les autres traitements qui ont ete utilises contre cette maladie. [Traduit par la Redaction] Mots-cles: COVID-19, tempete de cytokines, complications post-COVID-19, corticostero'ides, immunotherapie., 1. Introduction The coronavirus disease 2019 (COVID-19) is the cause of the pandemic due to its transmissibility and lethality worldwide. It has drastically impacted the world's healthcare system and economies. [...]

The application of soft materials, including gels, in different material and biological chemistry domains has gained momentum in the past few years. Environmental remediation, drug resistance, and delivery are significant concerns that are being investigated widely nowadays. In this work, we report the multifunctionality of a gelator molecule A2 (5,5′-((6-(phenylamino)-1,3,5-triazine-2,4-diyl)-bis-(azanediyl))-diisophthalic acid) in the gel state. The gelator molecule A2 was used to fabricate organogel and two metallogels using copper perchlorate and a Ru-based anticancer drug molecule, respectively. The organogel and Cu-metallogel show efficient adsorption capabilities of iodine in the vapor and solution phases. These iodine-loaded gel composites were utilized as efficient antibacterial agents against Escherichia coli and Helicobacter pylori (I10) bacterial strains. Additionally, owing to the pH-responsive nature of the gel material, the Ru-based anticancer drug-loaded metallogel, Ru-A2, was fabricated, and its activity in pH-responsive drug delivery to the cancerous cells was also investigated. [ABSTRACT FROM AUTHOR]

Habitual consumption of areca/betel nut in Southeast Asia has been associated with oral submucous fibrosis (OSMF) and its malignant transformation to oral squamous cell carcinoma. The current study aimed to assess the molecular alterations in fibroblast cell lines after treatment with areca nut. Areca nut extract (ANE) was prepared and characterized for its active ingredient, arecoline. ANE‐treated cells were subjected to cell viability, proliferation, migration, morphologic changes, and transcript of OSMF genes (col1a1, col1a2, hsp47, timp1, timp2, timp3, and timp4). Further, liquid chromatography–mass spectrometry (LCMS) of cell lysate and Raman microspectroscopy (RMS) of fixed cells were performed for metabolomics/lipidomics and biomolecular alterations in the nucleus and periphery of ANE‐treated cells. We compared and integrated the data from both techniques and observed that the cells treated with ANE mimicked OSMF and could be used as an in vitro model. LCMS showed a significant alteration in 17 metabolites and 165 lipid molecules in the cells treated with ANE. Further, 40 molecules in the nucleus and 29 in the periphery were found to be altered in these cells when subjected to RMS. Molecules associated with pathways such as the transfer of acetyl groups into mitochondria, amino sugar metabolism, and the Warburg effect were modulated the most upon ANE treatment. Acetyl CoA was found to be common in most of the altered pathways. Besides, the pathways affecting carbohydrate metabolism were also altered significantly. Targeting these molecules and pathways can help to prevent the malignant transformation of OSMF. [ABSTRACT FROM AUTHOR]

The leaves of Araucaria cunninghamii are known to be nonedible and toxic. Previous studies have identified biflavones in various Araucaria species. This study aimed to investigate the in vitro cytotoxicity of the isolated compounds from Araucaria cunninghamii after metabolomics and network pharmacological analysis. Methanol extract of Araucaria cunninghamii leaves was subjected to bioassay‐guided fractionation. The active fraction was analyzed using LC‐HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta‐sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound‐gene‐pathway network and hierarchical network analysis, protein–protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC50 90.58 μM) exhibits the highest cytotoxicity and monomeric apigenin (IC50 174.5 μM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy ≤−7 Kcal/mol. [ABSTRACT FROM AUTHOR]

Helicobacter pylori and Epstein–Barr Virus (EBV) are Group 1 carcinogens that can enhance gastric cancer progression. Bioactive substances extracted from plants can be effective therapeutic agents in cancer treatment. For example, Withania somnifera extract‐WSE reduces the Gankyrin oncoprotein, which is upregulated in the presence of H. pylori and EBV. The various biochemical and metabolic changes upon 24 hrs post‐infection followed by W. somnifera extract (WSE) treatment on gastric epithelial cells (AGS) can be studied using spectroscopic techniques. In the biomedical sciences, Raman and NMR spectroscopy have been extensively employed to interpret cellular alterations contributing to the onset of infection and the severity of gastric cancer. More specifically, alterations in cellular biochemical homeostasis are linked to the moieties of cholesterol, collagen, choline, carbohydrate, lipids, tyrosine, and phenylalanine. Further, we have found significantly elevated FWHM for carbohydrates, tumor associated protein, collagen, cholesterol, and cholesterol ester in the co‐infection model. We also looked into the potential correlation between these molecules using molecular network analysis and found several related factors that can be modulated through biomolecular levels. These molecules are crucial in several physiological functions, including cell division, cell proliferation, apoptosis, necrosis, cell migration, and lipid transport. Our study paves the pathway to study H. pylori and EBV co‐infection in human gastric epithelial cells and the therapeutic interventions of WSE in this scenario and highlights specific biomolecular alterations, which can be focused for further mechanistic investigations. [ABSTRACT FROM AUTHOR]

Background: EBV infection has long been postulated to trigger multiple sclerosis (MS) and anti-EBV antibodies showed a consistent presence in MS patients. Previous reports from our group have shown that the EBV infects different brain cells. Entry of the virus in neuronal cells is assisted by several host factors including membrane cholesterol. By using an inhibitor, methyl-b-cyclodextrin (MbCD), we evaluated the role of membrane cholesterol in EBV infection and pathogenesis Methodology: The membrane cholesterol depleted cells were infected with EBV and its latent genes expression were assessed. Further, EBV-mediated downstream signalling molecules namely STAT3, RIP, NF-kB and TNF-a levels was checked at protein level along with spatial (periphery and nucleus) and temporal changes in biomolecular fingerprints with Raman microspectroscopy (RS). Results: Upon treatment with MbCD, lmp1 and lmp2a suggested significant downregulation compared to EBV infection. Downstream molecules like STAT3 and RIP, exhibited a decrease in protein levels temporally upon exposure to MbCD while NF-kB levels were found to be increased. Further, the intensity of the Raman spectra exhibited an increase in triglycerides and fatty acids in the cytoplasm of EBV-infected LN-229 cells compared to MbCD+EBV. Likewise, the Raman peak width of cholesterol, lipid and fatty acids were found to be reduced in EBV-infected samples indicates elevation in the cholesterol specific moieties. In contrast, an opposite pattern was observed in the nucleus. Moreover, the ingenuity pathway analysis revealed protein molecules such as VLDLR, MBP and APP that are associated with altered profile of cholesterol, fatty acids and triglycerides with infection-related CNS disorders. Conclusion: Taken together, our results underline the important role of membrane cholesterol over EBV entry/pathogenesis in astroglia cells which further trigger/exacerbate virus-associated neuropathologies. These results likely to aid into the prognosis of neurological disease like MS. [ABSTRACT FROM AUTHOR]

Neurotropic viruses target the central nervous system through various mechanisms: they have the potential to modulate synaptic plasticity, causing cognitive impairments by blocking N-methyl d-aspartate receptors; they alter the Ca2+ ion-signaling pathways modulating long-term potentiation, leading to a severe inflammatory response in brain cells, increased reactive oxygen species and lipid peroxidation through mitochondria and peroxisomes. Inflammatory pathways have a key role in modulating the plasticity of neurons, linked to numerous neurological disorders. Advanced neuroimaging techniques facilitate the early diagnosis of impaired synaptic function in viral infections and neurodegenerative disorders. Here we discuss the understanding of the interplay between neurotropic viral infections and their effects on synaptic plasticity and diagnosis through neuroimaging techniques. The human brain consists of a complex network of cells called neurons. These neurons communicate with each other through chemicals known as neurotransmitters. Changes in these communication networks can cause neurodegenerative disorders such as Alzheimer's or Parkinson's disease. Some viruses, when they infect people, can also infect the central nervous system and cause inflammation that can damage the nervous system. One way they do this is by changing the junctions between neurons, called synapses, causing impaired brain function. Multiple methods can detect these changes through imaging, such as computed tomography and MRI scans. Advances in artificial intelligence also present an opportunity for helping doctors to detect viral infections in the brain in the early stages. This review, therefore, focuses on the changes in synapses because of viral infections and may be useful for doctors to understand how changing the synapse can lead to impaired brain function. [ABSTRACT FROM AUTHOR]

"Herbal electronics" is a very new term tossed for the area where optical and electrical properties of herbal materials are being studied for possible application in electronics. The optical properties of extract solutions obtained from two raw materials namely turmeric, and henna has been studied here using absorption and luminescence spectroscopies. The as‐prepared solutions appear luminescent under UV light and generate two complementary colors, red and green which when mixed together exhibits yellow emission. A careful analysis has been carried out to understand how the two solutions can be mixed to obtain a yellow emission by using a simple Blue/UV LED as excitation source. Obtained emission colors has been qualified using CIE color chart and PL quantum yield have also been calculated. The yellow emission has been demonstrated using a simple set up where a blue led (400 nm) is used as excitation and the mixture solution is used as active luminescent material which emits yellow light with a quantum yield of ∼5 %. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria. On the other hand, dipeptidyl peptidase-IV (DPP-IV) inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis, but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line. We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase (AMPK), which activates the downstream transcription factors PGC-1α,PGC-1β, or FOXO1 for mitochondrial biogenesis; above-mentioned incretin-based therapies are also known to activate AMPK. This study evaluated the effects of sitagliptin, vildagliptin, and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis, were examined. Treatment with sitagliptin (100 µM), vildagliptin (100 µM), and exendin-4 (10 nM) for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay, cell migration by scratch, and transwell migration assays, accompanied with marginal reduction in cell numbers along with the apoptotic appearance, the rate of apoptosis, and decreased lactate content in conditioned medium. These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio, increased MitoTracker green and red staining, and increased expression of transcription factors PGC-1α, NRF-1, NRF-2, TFAM, and HO-1. Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1 µM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay. Thus, sitagliptin, vildagliptin, and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect. Therapeutic response was in the order of: sitagliptin > vildagliptin > exendin-4. [ABSTRACT FROM AUTHOR]

The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding. [ABSTRACT FROM AUTHOR]

Vaccine adjuvants are substances that improve the immune capacity of a recombinant vaccine to a great extent and have been in use since the early 1900s; they are primarily short-lived and initiate antigen activity, mainly an inflammatory response. With the developing technologies and innovation, early options such as alum were modified, yet the inorganic nature of major vaccine adjuvants caused several side effects. Outer membrane vesicles, which respond to the stressed environment, are small nano-sized particles secreted by gram-negative bacteria. The secretory nature of OMV gives us many benefits in terms of infection bioengineering. This article aims to provide a detailed overview of bacteria's outer membrane vesicles (OMV) and their potential usage as adjuvants in making OMV-based vaccines. The OMV adjuvant-based vaccines can be a great benefactor, and there are ongoing trials for formulating OMV adjuvant-based vaccines for SARS-CoV-2. This study emphasizes engineering the OMVs to develop better versions for safety purposes. This article will also provide a gist about the advantages and disadvantages of such vaccines, along with other aspects. [ABSTRACT FROM AUTHOR]

Background/Aims: Cells require regular maintenance of proteostasis. Synthesis of new polypeptides and elimination of damaged or old proteins is an uninterrupted mechanism essential for a healthy cellular environment. Impairment in the removal of misfolded proteins can disturb proteostasis; such toxic aggregation of misfolded proteins can act as a primary risk factor for neurodegenerative diseases and imperfect ageing. The critical challenge is to design effective protein quality control (PQC) based molecular tactics that could potentially eliminate aggregation-prone protein load from the cell. Still, targeting specific components of the PQC pathway for the suppression of proteotoxic insults retains several challenges. Earlier, we had observed that LRSAM1 promotes the degradation of aberrant proteins. Here, we examined the effect of resveratrol, a stilbenoid phytoalexin compound, treatment on LRSAM1 E3 ubiquitin ligase, involved in the spongiform neurodegeneration. Methods: In this study, we reported induction of mRNA and protein levels of LRSAM1 in response to resveratrol treatment via RT-PCR, immunoblotting, and immunofluorescence analysis. The LRSAM1-mediated proteasomal-based clearance of misfolded proteins was also investigated via proteasome activity assays, immunoblotting and immunofluorescence analysis. The increased stability of LRSAM1 by resveratrol was demonstrated by cycloheximide chase analysis. Results: Here, we show that resveratrol treatment induces LRSAM1 E3 ubiquitin ligase expression levels. Further, our findings suggest that overexpression of LRSAM1 significantly elevates proteasome activities and improves the degradation of bona fide heat-denatured luciferase protein. Exposure of resveratrol not only slows down the turnover of LRSAM1 but also effectively degrades abnormal proteinaceous inclusions, which eventually promotes cell viability. Conclusion: Our findings suggest that resveratrol facilitates LRSAM1 endogenous establishment, which consequently promotes the proteasome machinery for effective removal of intracellular accumulated misfolded or proteasomal-designated substrates. Altogether, our study proposes a promising molecular approach to specifically trigger PQC signaling for efficacious rejuvenation of defective proteostasis via activation of overburdened proteolytic machinery. [ABSTRACT FROM AUTHOR]