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Rheumatoid arthritis (RA) and associated inflammatory complications are the most prevalent illnesses and can turn into fatal conditions if left untreated. Allopathic medicine is not satisfactory for curing RA. Scientific literature reports reveal that several phyto-compounds viz. flavonoids, saponins, and terpenoids, can heal joints and organs from auto-inflammatory rheumatoid arthritis and pain. Gene ontology, gene network analysis, molecular clustering, and literature review were used to optimise RA-specific highly expressed genes. In-silico molecular docking was performed to short-out potential phytomolecules (Neohesperidin dihydrochalcone (NHDC)) from 1000 datasets-library against RA and validate using MD simulation running at 100 ns. In-vitro anti-inflammatory assays of NHDC inhibited egg-albumin denaturation, IC50 of 47.739 ± 0.51 µg/ml. The ex-vivo MTT assay with NHDC rendered 67.209% inhibition at 100 µM against fd-FLS-cells. NHDC downregulated pro-inflammatory cytokine IL-17A production by 61.11% and 50% at 300 and 200 µM, respectively. Thus, this Studies recommend that NHDC may be highlighted as a novel multi-target PADI4 and JAK3 inhibitor with better efficacy and minimal toxicity in RA warranted to In-Vivo and clinical investigation. The current findings have uncovered remarkable genes and signalling pathways linked to RA, which could enhance our existing comprehension of the molecular mechanisms that drive its development and progression.
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Exopolysaccharides (EPSs), originating from various microbes, and mushrooms, excel in their conventional role in bioremediation to showcase diverse applications emphasizing nanobiotechnology including nano-drug carriers, nano-excipients, medication and/or cell encapsulation, gene delivery, tissue engineering, diagnostics, and associated treatments. Acknowledged for contributions to adsorption, nutrition, and biomedicine, EPSs are emerging as appealing alternatives to traditional polymers, for biodegradability and biocompatibility. This article shifts away from the conventional utility to delve deeply into the expansive landscape of EPS applications, particularly highlighting their integration into cutting-edge nanobiotechnological methods. Exploring EPS synthesis, extraction, composition, and properties, the discussion emphasizes their structural diversity with molecular weight and heteropolymer compositions. Their role as raw materials for value-added products takes center stage, with critical insights into recent applications in nanobiotechnology. The multifaceted potential, biological relevance, and commercial applicability of EPSs in contemporary research and industry align with the nanotechnological advancements coupled with biotechnological nano-cleansing agents are highlighted. EPS-based nanostructures for biological applications have a bright future ahead of them. Providing crucial information for present and future practices, this review sheds light on how eco-friendly EPSs derived from microbial biomass of terrestrial and aquatic environments can be used to better understand contemporary nanobiotechnology for the benefit of society.
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Nanoestruturas , Polissacarídeos Bacterianos , Polissacarídeos Bacterianos/química , Biotecnologia , Portadores de Fármacos , NanotecnologiaRESUMO
The outbreak of COVID-19 has caused great havoc and affected many parts of the world. It has imposed a great challenge to the medical and health fraternity with its ability to continue mutating and increasing the transmission rate. Some challenges include the availability of current knowledge of active drugs against the virus, mode of delivery of the medicaments, its diagnosis, which are relatively limited and do not suffice for further prognosis. One recently developed drug delivery system called nanoparticles is currently being utilized in combating COVID-19. This article highlights the existing methods for diagnosis of COVID-19 such as computed tomography scan, reverse transcription-polymerase chain reaction, nucleic acid sequencing, immunoassay, point-of-care test, detection from breath, nanotechnology-based bio-sensors, viral antigen detection, microfluidic device, magnetic nanosensor, magnetic resonance platform and internet-of-things biosensors. The latest detection strategy based on nanotechnology, biosensor, is said to produce satisfactory results in recognizing SARS-CoV-2 virus. It also highlights the successes in the research and development of COVID-19 treatments and vaccines that are already in use. In addition, there are a number of nanovaccines and nanomedicines currently in clinical trials that have the potential to target COVID-19.
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Peptidyl arginine deiminases (PADs) are a family of post-translational modification enzymes that irreversibly citrullinate (deiminate) arginine residues of protein and convert them to a non-classical amino acid citrulline in the presence of calcium ions. It has five isotypes, such as PAD1, PAD2, PAD3, PAD4, and PAD6, found in mammalian species. It has been suggested that increased PAD expression in various tissues contributes to the development of multiple inflammatory diseases, including rheumatoid arthritis (RA), cancer, diabetes, and neurological disorders. Elevation of PAD enzyme expression depends on several factors like rising intracellular Ca2+ levels, oxidative stress, and proinflammatory cytokines. PAD inhibitors originating from natural or synthetic sources can be used as a novel therapeutic approach concerning inflammatory disorders. Here, we review the pathological role of PAD in several inflammatory disorders, factors that trigger PAD expression, epigenetic role and finally, decipher the therapeutic approach of PAD inhibitors in multiple inflammatory disorders.
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Hidrolases , Proteínas , Animais , Desiminases de Arginina em Proteínas/química , Desiminases de Arginina em Proteínas/metabolismo , Hidrolases/metabolismo , Arginina , Mamíferos/metabolismoRESUMO
The epigallocatechin-rich polyphenolic fraction of Assam variety white tea, traditionally used for the management of diverse inflammatory ailments and health drink, was investigated through eco-friendly green aqueous extraction, TLC, and HPLC characterization, phytochemical screening, in vitro DPPH assay, anti-proteinase, MTT assay on synovial fibroblast and colon cancer cells, apoptotic FACS analysis, cytokine ELISA, p-STAT3 western blotting, and in silico docking analysis. HPLC-TLC standardized white tea fraction (WT-F) rendered higher extractive-yield (21%, w/w), than green tea fraction(GT-F) (12%, w/w). WT-F containing flavonoids and non-hydrolysable polyphenols showed better antioxidant activity, rather than equivalent GT-F. WT-F demonstrated remarkable anti-rheumatoid-arthritis activity via killing of synovial fibroblast cells (66.1%), downregulation of TNF-α (93.33%), IL-6 (87.97%), and p-STAT3 inhibition (77.75%). Furthermore, WT-F demonstrated better anti-proliferative activity against colon cancer cells (HCT-116). Collectively, our study revealed that the white tea fraction has boundless potential as anti-rheumatoid arthritis and anti-proliferative agent coupled with apoptotic, antioxidant anti-proteinase, and anti-inflammatory properties. PRACTICAL APPLICATIONS: Our eco-friendly extracted bioactive aqueous fraction of white tea, characterized by TLC-HPLC study and phytochemical screening have demonstrated remarkable anti-rheumatoid arthritis property and anti-proliferative action on colon cancer cells including potential anti-oxidant, anti-inflammatory, and anti-proteinase efficacy. The test WT-F sample has shown impressive safety on normal mammalian cells. WT-F has demonstrated better efficacy against rheumatoid arthritis and cancer model compared to equivalent green tea fraction. Traditionally, it is extensively used for boosting immunity, and energy, with cosmetic, and agricultural applications by the native inhabitants. So, the aqueous fraction of WT is suggested to be used as a prophylactic nutraceutical supplement and or therapeutic agent in commercial polyherbal formulation to attenuate and management of auto-inflammatory rheumatoid arthritis and carcinogenesis of colon. It is additionally suggested to establish in vivo rheumatoid arthritis animal and clinical study to validate their pharmacokinetic stability and dose optimization coupled with anti-inflammatory, cytotoxicity, and anti-oxidant property.
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Artrite Reumatoide , Camellia sinensis , Catequina , Neoplasias do Colo , Animais , Camellia sinensis/química , Chá/química , Antioxidantes/química , Catequina/farmacologia , Anti-Inflamatórios/química , Artrite Reumatoide/tratamento farmacológico , Compostos Fitoquímicos , Neoplasias do Colo/tratamento farmacológico , MamíferosRESUMO
INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the biggest global health issues. Spike protein (S) and nucleoprotein (N), the major immunogenic components of SARS-CoV-2, have been shown to be involved in the attachment and replication of the virus inside the host cell. AREAS COVERED: Several investigations have shown that the SARS-CoV-2 nucleoprotein can elicit a cell-mediated immune response capable of regulating viral replication and lowering viral burden. However, the development of an effective vaccine that can stop the transmission of SARS-CoV-2 remains a matter of concern. Literature was retrieved using the keywords COVID-19 vaccine, role of nucleoprotein as vaccine candidate, spike protein, nucleoprotein immune responses against SARS-CoV-2, and chimera vaccine in PubMed, Google Scholar, and Google. EXPERT OPINION: We have focussed on the use of chimera protein, consisting of N and S-1 protein components of SARS-CoV-2, as a potential vaccine candidate. This may act as a polyvalent mixed recombinant protein vaccine to elicit a strong T and B cell immune response, which will be capable of neutralizing the wild and mutated variants of SARS-CoV-2, and also restricting its attachment, replication, and budding in the host cell.
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COVID-19 , Proteínas Virais de Fusão , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Nucleoproteínas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.
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The SARS-CoV-2 outbreak is the COVID-19 disease, which has caused massive health devastation, prompting the World Health Organization to declare a worldwide health emergency. The corona virus infected millions of people worldwide, and many died as a result of a lack of particular medications. The current emergency necessitates extensive therapy in order to stop the spread of the coronavirus. There are various vaccinations available, but no validated COVID-19 treatments. Since its outbreak, many therapeutics have been tested, including the use of repurposed medications, nucleoside inhibitors, protease inhibitors, broad spectrum antivirals, convalescence plasma therapies, immune-modulators, and monoclonal antibodies. However, these approaches have not yielded any outcomes and are mostly used to alleviate symptoms associated with potentially fatal adverse drug reactions. Nanoparticles, on the other hand, may prove to be an effective treatment for COVID-19. They can be designed to boost the efficacy of currently available antiviral medications or to trigger a rapid immune response against COVID-19. In the last decade, there has been significant progress in nanotechnology. This review focuses on the virus's basic structure, pathogenesis, and current treatment options for COVID-19. This study addresses nanotechnology and its applications in diagnosis, prevention, treatment, and targeted vaccine delivery, laying the groundwork for a successful pandemic fight.