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Cancer is a condition in which a few of the body's cells grow beyond its control and spread to other outward regions. Globally, gastric cancer (GC) is third most common cause of cancer-related mortality and the fourth most common kind of cancer. Persistent infection of VacA-positive Helicobacter pylori (H. pylori) modulates cellular physiology and leads to GC. About â¼70% of H. pylori are positive for vacuolating cytotoxin-A (VacA), and it infects â¼80-90% of world populations. Herein, for first time, we repurposed FDA-approved gram-negative antibiotics, which are feasible alternatives to existing regimens and may be used in combinatorial treatment against VacA-positive H. pylori. Out of 110 FDA-approved antibiotics, we retrieved 92 structures, which were screened against the VacA protein. Moreover, we determined that the top eight hit antibiotics viz; cefpiramide, cefiderocol, eravacycline, doxycycline, ceftriaxone, enoxacin, tedizolid, and cefamandole show binding free energies of -9.1, -8.9, -8.1, -8.0, -7.9, -7.8, -7.8 and -7.8 Kcal/mol, respectively, with VacA protein. Finally, we performed 100 ns duplicate MD simulations on the top eight selected antibiotics showing strong VacA binding. Subsequently, five antibiotics, including cefiderocol, cefpiramide, doxycycline, enoxacin, and tedizolid show stable ligand protein distance and good binding affinity revealed by the MM-PBSA scheme. Among the five antibiotics cefiderocol act as the most potent inhibitor (-28.33 kcal/mol). Furthermore, we also identified the hotspot residue like Asn-506, Tyr-529, and Phe-483 which control the interaction. Concisely, we identified antibiotics that can be repurposed against VacA of H. pylori and explored their molecular mechanism of interaction with VacA.Communicated by Ramaswamy H. Sarma.
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Aurora kinase A (AURKA) is one of the crucial cell cycle regulators associated with gastric cancer. Here, we explored Epstein Barr Virus-induced gastric cancer progression through EBV protein EBNA1 with AURKA. We found that EBV infection enhanced cell proliferation and migration of AGS cells and upregulation of AURKA levels. AURKA knockdown markedly reduced the proliferation and migration of the AGS cells even with EBV infection. Moreover, MD-simulation data deciphered the probable connection between EBNA1 and AURKA. The in-vitro analysis through the transcript and protein expression showed that AURKA knockdown reduces the expression of EBNA1. Moreover, EBNA1 alone can enhance AURKA protein expression in AGS cells. Co-immunoprecipitation and NMR analysis between AURKA and EBNA1 depicts the interaction between two proteins. In addition, AURKA knockdown promotes apoptosis in EBV-infected AGS cells through cleavage of Caspase-3, -9, and PARP1. This study demonstrates that EBV oncogenic modulators EBNA1 possibly modulate AURKA in EBV-mediated gastric cancer progression.
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Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/metabolismo , Neoplasias Gástricas/metabolismo , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Antígenos Nucleares do Vírus Epstein-Barr/genética , Antígenos Nucleares do Vírus Epstein-Barr/metabolismoRESUMO
Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps (lmp1, lmp2a, and lmp2B). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory (mmp3 and mmp7); cell-cycle regulator (pcna); antiapoptotic gene (bcl2); increased the expression of the proapoptotic gene (apaf1 and bax); and tumor suppressor (p53, prb, and pten). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-É, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.
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Rab5B is a small monomeric G protein that regulates early endocytosis and controls signaling pathways related to cell growth, survival, and apoptosis. Dysregulation of Rab5B protein expression has been linked to the development of several cancers such as leukemia, lymphoma, kidney, prostate, ovarian, breast cancer, etc. Our research shows the first attempt to identify inhibitors that can target Rab5B GTPase. In this study, we performed molecular docking using Autodock Vina 1.5.6 and identified eight molecules with docking scores ranging from -9.8 to -10.6 kcal/mol. Thereafter, we examined the pharmacological characteristics of these compounds, and selected compounds were further analyzed for their conformational dynamics and thermodynamic stability using molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA)-based free energy calculations. Notably, our findings revealed that strychnine had the highest binding affinity to Rab5B followed by anonaine, helioxanthin, and taiwanin E, with a ΔGbind value of -21.43, -17.11, -15.11, and -14.09 kcal/mol respectively. The binding free energy calculations showed that Van der Waals interactions are the primary contributor to the binding between Rab5B and the inhibitor. The interaction between the inhibitor and Rab5B was shown to be controlled by certain hot spot residues, including Phe45, Tyr48, Ala64, and Ala30. Overall, we believe that these findings could facilitate the exploration and development of potential hits against Rab5B, subject to optimization and further research. Rab5B inhibitory binding affinity of natural plants active compounds.
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Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/ß-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.
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Infecções por Vírus Epstein-Barr , Helicobacter pylori , Neoplasias Gástricas , Humanos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Fosfatidilinositol 3-Quinases , Transdução de SinaisRESUMO
Helicobacter pylori infection is associated with various gastrointestinal diseases and gastric cancer. Our data shows the H. pylori isolates and their associated pathology, isolated from two different stomach niches: gastric epithelium and gastric juice. Gastric adenocarcinoma (AGS) cells were infected with H. pylori juice (HJ1, HJ10 and HJ14) and biopsy (HB1, HB10 and HB14) isolates for 6, 12 and 24 hrs. To determine the cell migration ability of the infected cells, scratch wound assay was performed. The decrease in the wound area was measured by Image J software. Status of cell proliferation accessed by counting the cell number through trypan blue exclusion method. Further assessment of pathogenic potential and carcinogenic ability of the isolates was done by determining the genomic instability in the cell post infection. Cells were stained with DAPI and number of micro and macro nuclei was counted in the acquired images. The data will be helpful in understanding the difference in the carcinogenic ability of H. pylori with respect to their physiological niche.
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The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. This virus has a high mismatch repair proofreading ability due to its unique exonuclease activity, making it knotty to treat. The nucleocapsid protein can serve as a potential antiviral drug target, as this protein is responsible for multiple captious functions during the viral life cycle. Herein, we have investigated the potential to repurpose active antiviral compounds of plant origins for treating the SARS-CoV-2 infection. In the present study, we followed the molecular docking methodology to screen druggable natural plants' active compounds against the nucleocapsid protein of SARS-CoV-2. The virtual screening of all 68 compounds revealed that the top seven active compounds, such as withanolide D, hypericin, silymarin, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein, exhibit good binding affinity with druggable ADME properties, toxicity, and Pass prediction. The stability of the docked complexes was studied by conducting molecular simulations of 100 ns. MM-GBSA calculated the binding free energy uncovered that withanolide D, hypericin, and silymarin result in highly stable binding conformations in three different sites of the nucleocapsid protein. However, further investigation is needed in order to validate the candidacy of these inhibitors for clinical trials.Communicated by Ramaswamy H. Sarma.
Natural plants' active compounds may aid in the inhibition of SARS-CoV-2 replication and COVID-19 therapeutics.Hypericin, silymarin, withanolide D, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein are effective against SARS-CoV-2 N protein.Studied natural plants' active compounds could be useful against COVID-19 and its associated organs comorbidities.ADMET properties of selected compounds favor these compounds as druggable candidates.
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COVID-19 , SARS-CoV-2 , Humanos , Proteínas do Nucleocapsídeo , Simulação de Acoplamento Molecular , Antivirais/farmacologia , Simulação de Dinâmica Molecular , Inibidores de ProteasesRESUMO
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.
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Self-assembled benzoselenadiazole (BSe)-capped tripeptide based nanofibrillar hydrogels have been developed with inherent anticancer and anti-inflammatory activity.
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Anti-Inflamatórios , Hidrogéis , Anti-Inflamatórios/farmacologia , Hidrogéis/farmacologiaRESUMO
Plants are a valued potential source of drugs for a variety of diseases and are often considered less toxic to humans. We investigated antiviral compounds that may potentially target SARS-CoV-2 antigenic spike (S) and host proteins; angiotensin-converting enzyme2 (ACE2), and transmembrane serine protease2 (TMPRSS2). We scrutinized 36 phytochemicals from 15 Indian medicinal plants known to be effective against RNA viruses via molecular docking. Besides, the TMPRSS2 structure was modeled and validated using the SWISS-MODEL. Docking was performed using Autodock Vina and 4.2 followed by visualization of the docking poses on Pymol version 2.4.0 and Discovery Studio Visualizer. Molecular docking showed that 12 out of 36 active compounds interacted efficiently with S, ACE2, and TMPRSS2 proteins. The ADMET profile generated using the swissADME and pkCSM server revealed that these compounds were possessed druggable properties. The Amber 12 simulation package was used to carry out energy minimizations and molecular dynamics (MD) simulations. The total simulation time for both S protein: WFA and S protein: WND complexes was 300 ns (100 ns per replica). A total of 120 structures were extracted from the last 60 ns of each MD simulation for further analysis. MM-PBSA and MM-GBSA were employed to assess the binding energy of each ligand and the receptor-binding domain of the viral S-protein. The methods suggested that WND and WFA showed thermodynamically favorable binding energies, and the S protein had a higher affinity with WND. Interestingly, Leu455 hotspot residue in the S protein, also predicted to participate in binding with ACE2, was engaged by WND and WFA. HighlightsPlants' natural active compounds may aid in the development of COVID-19 therapeutics.MD simulation study revealed stable binding of withanolide D and withaferin A with spike proteinWithanolide D and withaferin A could be effective against SARS-CoV-2 spike protein.Discovery of druggable agents that have less or lack of binding affinity with ACE2 to avoid the organs associated with comorbidities.According to ADMET selected phytochemicals may be used as druggable compounds.Communicated by Ramaswamy H. Sarma.
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COVID-19 , SARS-CoV-2 , Humanos , Simulação de Acoplamento Molecular , Enzima de Conversão de Angiotensina 2 , Simulação de Dinâmica Molecular , Antivirais/farmacologiaRESUMO
Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a global pandemic. Additionally, the SARS-CoV-2 infection in the patients of Gastric Cancer (GC; the third leading cause of death in the world) pose a great challenge for the health management of the patients. Since there have been uncertainties to develop a new drug against COVID-19, there is an urgent need for repurposing drugs that can target key proteins of both SARS-CoV-2 and GC. The SARS-CoV-2-RdRp protein contains the NiRAN domain, which is known to have kinase-like folds. A docking study of the FDA approved drugs against GC was performed using AutoDock 4.2 and Glide Schrodinger suite 2019 against SARS-CoV-2-RdRp protein. MMGBSA and MD simulation studies were performed to investigate the binding and stability of the inhibitors with the target protein. In this study, we have found 12 kinase inhibitors with high binding energies namely Baricitinib, Brepocitinib, Decernotinib, Fasudil, Filgotinib, GSK2606414, Peficitinib, Ruxolitinib, Tofacitinib, Upadacitinib, Pamapimod and Ibrutinib. These FDA approved drugs against GC can play a key role in the treatment of COVID-19 patients along with GC as comorbidity. We also hypothesize that JAK, ITK, Rho-associated kinases, FGFR2, FYN, PERK, TYK2, p38-MAPK and SYK kinases can be considered as key therapeutic targets in COVID-19 treatment. Taken altogether, we have proposed the SARS-CoV-2-RdRp as a potential therapeutic target through in-silico studies. However, further in-vitro and in-vivo studies are required for the validation of the proposed targets and drugs for the treatment of COVID-19 patients already suffering from GC.
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Tratamento Farmacológico da COVID-19 , Preparações Farmacêuticas , Neoplasias Gástricas , Reposicionamento de Medicamentos , Fármacos Gastrointestinais , Humanos , SARS-CoV-2 , Neoplasias Gástricas/tratamento farmacológicoRESUMO
Persistent coinfection with Helicobacter pylori and Epstein-Barr virus (EBV) promotes aggressive gastric carcinoma (GC). The molecular mechanisms underlying the aggressiveness in H. pylori and EBV-mediated GC are not well characterized. We investigated the molecular mechanism involved in H. pylori- and EBV-driven proliferation of gastric epithelial cells. Results showed that the coinfection is significantly more advantageous to the pathogens as coinfection creates a microenvironment favorable to higher pathogen-associated gene expression. The EBV latent genes ebna1 and ebna3c are highly expressed in the coinfection compared to lone EBV infection at 12 and 24 h. The H. pylori-associated genes 16S rRNA, cagA, and babA were also highly expressed during coinfection compared to H. pylori alone. In addition, upregulation of gankyrin, which is a small oncoprotein, modulates various cell signaling pathways, leading to oncogenesis. Notably, the knockdown of gankyrin decreased the cancer properties of gastric epithelial cells. Gankyrin showed a similar expression pattern as that of ebna3c at both transcript and protein levels, suggesting a possible correlation. Further, EBV and H. pylori created a microenvironment that induced cell transformation and oncogenesis through dysregulation of the cell cycle regulatory (ccnd1, dapk3, pcna, and akt), GC marker (abl1, tff-2, and cdx2), cell migration (mmp3 and mmp7), DNA response (pRB, pten, and p53), and antiapoptotic (bcl2) genes in infected gastric epithelial cells through gankyrin. Our study provides a new insight into the interplay of two oncogenic agents (H. pylori and EBV) that leads to an enhanced carcinogenic activity in gastric epithelial cells through overexpression of gankyrin. IMPORTANCE In the present study, we evaluated the synergistic effects of EBV and H. pylori infection on gastric epithelial cells in various coinfection models. These coinfection models were among the first to depict the exposures of gastric epithelial cells to EBV followed by H. pylori; however, coinfection models exist that narrated the scenario upon exposure to H. pylori followed by that to EBV. We determined that a coinfection by EBV and H. pylori enhanced the expression of oncogenic protein gankyrin. The interplay between EBV and H. pylori promoted the oncogenic properties of AGS cells like elevated focus formation, cell migration, and cell proliferation through gankyrin. EBV and H. pylori mediated an enhanced expression of gankyrin, which further dysregulated cancer-associated genes such as cell migratory, tumor suppressor, DNA damage response, and proapoptotic genes.
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Infecções por Vírus Epstein-Barr/genética , Infecções por Helicobacter/genética , Complexo de Endopeptidases do Proteassoma/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Gástricas/microbiologia , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica , Coinfecção/genética , Coinfecção/microbiologia , Coinfecção/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/microbiologia , Infecções por Vírus Epstein-Barr/virologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Mucosa Gástrica/virologia , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/virologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-κB, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.
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Coronaviruses are large positive-sense RNA viruses with spike-like peplomers on their surface. The Coronaviridae family's strains infect different animals and are popularly associated with several outbreaks, namely SARS and MERS epidemic. COVID-19 is one such recent outbreak caused by SARS-CoV-2 identified first in Wuhan, China. COVID-19 was declared a pandemic by WHO on 11th March 2020. Our review provides information covering various facets of the disease starting from its origin, transmission, mutations in the virus to pathophysiological changes in the host upon infection followed by diagnostics and possible therapeutics available to tackle the situation. We have highlighted the zoonotic origin of SARS-CoV-2, known to share 96.2% nucleotide similarity with bat coronavirus. Notably, several mutations in SARS-CoV-2 spike protein, nucleocapsid protein, PLpro, and ORF3a are reported across the globe. These mutations could alter the usual receptor binding function, fusion process with the host cell, virus replication, and the virus's assembly. Therefore, studying these mutations could help understand the virus's virulence properties and design suitable therapeutics. Moreover, the aggravated immune response to COVID-19 can be fatal. Hypertension, diabetes, and cardiovascular diseases are comorbidities substantially associated with SARS-CoV-2 infection. The review article discusses these aspects, stating the importance of various comorbidities in disease outcomes. Furthermore, medications' unavailability compels the clinicians to opt for atypical drugs like remdesivir, chloroquine, etc. The current diagnostics of COVID-19 include qRT-PCR, CT scan, serological tests, etc. We have described these aspects to expose the information to the scientific community and to accelerate the research.
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The pandemic of novel coronavirus disease (COVID-19) caused by the Severe Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) creates an immense menace to public health worldwide. Currently, the World Health Organization (WHO) has recognized the novel coronavirus as the main cause of global pandemic. Patients infected with this virus generally show fever, nausea, and respiratory illness, while some patients also manifest gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea. Traces of SARS-CoV-2 RNA have been found in gastrointestinal cells. Further angiotensin converting enzyme 2 (ACE2) the known receptor for the virus is extensively expressed in these cells. This implies that gastrointestinal tract can be infected and can also present them as a replication site for SARS-CoV-2, but since this infection may lead to multiple organ failure, therefore identification of another receptor is a plausible choice. This review aims to provide comprehensive information about probable receptors such as sialic acid and CD147 which may facilitate the virus entry. Several potential targets are mentioned which can be used as a therapeutic approach for COVID-19 and associated GI disorders. The gut microbiomes are responsible for high levels of interferon-gamma which causes hyper-inflammation and exacerbates the severity of the disease. Briefly, this article highlights the gut microbiome's relation and provides potential diagnostic approaches like RDT and LC-MS for sensitive and specific identification of viral proteins. Altogether, this article reviews epidemiology, probable receptors and put forward the tentative ideas of the therapeutic targets and diagnostic methods for COVID-19 with gastrointestinal aspect of disease.
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Coronavirus disease 2019 (COVID-19) caused by SARS-CoV2 is associated with various comorbidities; cardiovascular diseases, hypertension, diabetes, liver, lung diseases, and neurological ailments. The majority of the dysfunctions mentioned above are often associated with endothelial deterioration, indicating that endothelium can be the target of SARS-CoV2. Our study is an exclusive observational study that quantitatively analyses COVID-19 related comorbidities. We retrieved the data of % population of COVID-19 hospitalized and deceased patients with associated comorbidities from publicly accessible portals of the five European countries. A two tailed t-test enabled us to determine the significant proportions of deaths compared to hospitalized patients with associated comorbidity. Our study revealed that deaths associated with cardiovascular diseases and diabetes are highly significant (p < 0.0001) compared to hospitalized in countries like Italy, France, and Spain unlike the Netherlands. Deaths from kidney diseases (Italy- p < 0.0001; Sweden- p < 0.0001; Netherlands- p = 0.0001; France- p = 0.0033) and neurological ailments (France- p = 0.0001; Netherlands- p < 0.0001) are significantly higher than the total hospitalized patients affected by the particular comorbidity. We have noted that deaths due to liver diseases are least associated with COVID-19 among all comorbidities. Intriguingly, immunodeficiency shows mixed outcomes in death proportions compared to the hospital admitted individuals. Besides, the treatment regime involves drugs like losartan, ACE inhibitors, angiotensin-receptor blockers, Remdesivir, Chloroquine, Hydroxychloroquine, etc. may modulate the severity of the comorbidities. These comorbidities can create chaos in the existing healthcare system and may worsen the disease outcome.
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BACKGROUND: Helicobacter pylori (H. pylori) is well-known for its role in chronic gastritis and gastric cancer. Eradication of these carcinogenic bacteria from the gut is one of the challenges for clinicians. The complexity of treatment mainly owes to antibiotic resistance and relapse due to an additional reservoir in the oral cavity. Our study emphases the isolation of H. pylori from distinct habitats of the gut microenvironment (gastric biopsy and gastric juice) and its subsequent characterization. We have also evaluated the effect of various oral rinses on isolated H. pylori from different anatomical locations of included subjects. RESULTS: The possible strains isolated from two different habitats of the same subject shows a striking difference in their growth pattern. Promisingly, some of the included oral rinses are efficient in growth inhibition as per recommended 30 s treatment. The subsequent evaluation shows that oral rinse B (among A-E) is most effective and down-regulates the expression of one of the potent H. pylori gene, CagA, in the infected gastric adenocarcinoma (AGS) cells. CONCLUSION: Our study, for the first time, revealed that H. pylori, isolated from the different habitat of the same subject, show a different growth pattern. The expression of H. pylori pathogenic gene (CagA) was down-regulated by the use of oral rinses. Hence, oral rinses will reduce the H. pylori in the oral cavity and help to control its migration from oral to the gastric compartment and may be used as an adjuvant treatment option for its re-infection.
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Suco Gástrico/microbiologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Boca/microbiologia , Antissépticos Bucais/farmacologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biópsia , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Mucosa Gástrica/cirurgia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Masculino , Viabilidade Microbiana/efeitos dos fármacos , RNA Ribossômico 16S/genéticaRESUMO
The World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) Asian site was New Delhi, India. Its sample was drawn from 58 affluent neighborhoods in South Delhi. This community was selected to facilitate the recruitment of children who had at least one parent with 17 or more years of education, a key factor associated with unconstrained child growth in this setting. A door-to-door survey was conducted to identify pregnant women whose newborns were subsequently screened for eligibility for the longitudinal study, and children aged 18 to 71 months for the cross-sectional component of the study. A total of 111,084 households were visited over an 18-month period. Newborns were screened at birth at 73 sites. The large number of birthing facilities used by this community, the geographically extensive study area, and difficulties in securing support of pediatricians and obstetricians for the feeding recommendations of the study were among the unique challenges faced by the implementation of the MGRS protocol at this site.