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1.
Signal Transduct Target Ther ; 7(1): 137, 2022 Apr 25.
Article in English | MEDLINE | ID: covidwho-1805598

ABSTRACT

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents , COVID-19/genetics , Humans , Hypothalamo-Hypophyseal System , Immunity, Innate/genetics , Mice , Pituitary-Adrenal System , Progesterone/pharmacology
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334322

ABSTRACT

More than 450 million individuals have recovered from COVID-19, but little is known about the host responses to long COVID. We performed proteomic and metabolomic analyses of 991 blood and urine specimens from 144 COVID-19 patients with comprehensive clinical data and up to 763 days of follow up. Our data showed that the lungs and kidneys are the most vulnerable organs in long COVID patients. Pulmonary and renal long COVID of one-year revisit can be predicted by a machine learning model based on clinical and multi-omics data collected during the first month from the disease onset with an ACC of 87.5%. Serum protein SFTPB and ATR were associated with pulmonary long COVID and might be potential therapeutic targets. Notably, our data show that all the patients with persistent pulmonary ground glass opacity or patchy opacity lesions developed into pulmonary fibrosis at two-year revisit. Together, this study depicts the longitudinal clinical and molecular landscape of COVID-19 with up to two-year follow-up and presents a method to predict pulmonary and renal long COVID.

3.
J Sci Food Agric ; 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1800382

ABSTRACT

BACKGROUND: Nasopharyngeal carcinoma (NPC) is publicly known as a malignant tumor. Our previous study reported that plumbagin exhibits potent anti-cancer actions. Nevertheless, more mechanical details of plumbagin against NPC remain unknown. The present study aimed to unmask the core targets/genes and anti-NPC mechanisms involved in the signaling pathways of plumbagin prior to biochemical validation. METHODS: A network pharmacology approach was employed to respective identification of mutual and core targets/genes in plumbagin and/treating NPC. Molecular docking determination was used to identify core target proteins for biochemical validation using human and cell line samples. RESULTS: In total, 60 anti-NPC genes of plumbagin were screened out, and then nine core target genes of plumbagin against NPC were identified accordingly. The enrichment findings revealed detailed biological functions and pharmacological pathways of plumbagin against NPC. Moreover, in silico analysis using molecular docking had determined the core targets for further experimental validation, comprising protein kinase B (AKT1) and sarcoma gene (SRC). In human sample validation, clinical NPC sections showed increased positive expression of AKT1 and SRC. Additionally, plumbagin-treated NPC cells resulted in inactivated protein expression of AKT1 and SRC. CONCLUSION: The re-identified core targets/genes in the molecular docking report may function as plumbagin-related pharmacological targets for treating NPC via experimental validation. Furthermore, additional anti-NPC molecular mechanisms of plumbagin action were disclosed on the basis of enrichment findings. © 2022 Society of Chemical Industry.

4.
Adv Sci (Weinh) ; 9(14): e2104333, 2022 05.
Article in English | MEDLINE | ID: covidwho-1782562

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.


Subject(s)
COVID-19 Vaccines , COVID-19 , Globulins , Animals , COVID-19/therapy , Globulins/therapeutic use , Humans , Immunization, Passive , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331565

ABSTRACT

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. A recent study found that TRIM7 inhibits human enteroviruses through ubiquitination and proteasomal degradation of viral 2BC protein by targeting the 2C moiety of 2BC protein. Here, we report the crystal structures of TRIM7 in complex with 2C, where the C-terminal region of 2C is inserted into a positively charged groove of the TRIM7 PRY-SPRY domain. Structure-guided biochemical studies revealed the C-terminus glutamine residue of 2C as the primary determinant for TRIM7 binding. Such a glutamine-end motif binding mechanism can be successfully extended to other substrates of TRIM7. More importantly, leveraged by this finding, we were able to identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. We further show that TRIM7 may function as a restriction factor to promote the degradation of the viral proteins of norovirus and SARS-CoV-2, thereby restoring the Type I interferon immune response and inhibiting viral infection. Several crystal structures of TRIM7 in complex with SARS-CoV-2 proteins are also determined, and a conserved C-terminus glutamine-specific interaction is observed. These findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.

6.
Public Health ; 203: 65-74, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1629795

ABSTRACT

OBJECTIVES: This study aimed to evaluate the socio-economic burden imposed on the Chinese healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: A cross-sectional study was used to investigate how COVID-19 impacted health and medical costs in China. Data were derived from a subdivision of the Centers for Disease control and Prevention of China. METHODS: We prospectively collected information from the Centers for Disease Control and Prevention and the designated hospitals to determine the cost of public health care and hospitalisation due to COVID-19. We estimated the resource use and direct medical costs associated with public health. RESULTS: The average costs, per case, for specimen collection and nucleic acid testing (NAT [specifically, polymerase chain reaction {PCR}]) in low-risk populations were $29.49 and $53.44, respectively; however, the average cost of NAT in high-risk populations was $297.94 per capita. The average costs per 1000 population for epidemiological surveys, disinfectant, health education and centralised isolation were $49.54, $247.01, $90.22 and $543.72, respectively. A single hospitalisation for COVID-19 in China cost a median of $2158.06 ($1961.13-$2325.65) in direct medical costs incurred only during hospitalisation, whereas the total costs associated with hospitalisation of patients with COVID-19 were estimated to have reached nearly $373.20 million in China as of 20, May, 2020. The cost of public health care associated with COVID-19 as of 20, May, 2020 ($6.83 billion) was 18.31 times that of hospitalisation. CONCLUSIONS: This study highlights the magnitude of resources needed to treat patients with COVID-19 and control the COVID-19 pandemic. Public health measures implemented by the Chinese government have been valuable in reducing the infection rate and may be cost-effective ways to control emerging infectious diseases.


Subject(s)
COVID-19 , China/epidemiology , Cost of Illness , Cross-Sectional Studies , Financial Stress , Health Care Costs , Hospitalization , Humans , Pandemics , Public Health , SARS-CoV-2
7.
Bioengineered ; 12(2): 12461-12469, 2021 12.
Article in English | MEDLINE | ID: covidwho-1585255

ABSTRACT

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Colorectal Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic/drug effects , Genistein/therapeutic use , Phytoestrogens/therapeutic use , Atlases as Topic , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/virology , Cyclin D1/genetics , Cyclin D1/immunology , ErbB Receptors/genetics , ErbB Receptors/immunology , Humans , Interleukin-1alpha/genetics , Interleukin-1alpha/immunology , Interleukin-2/genetics , Interleukin-2/immunology , Janus Kinases/genetics , Janus Kinases/immunology , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Molecular Targeted Therapy/methods , Multigene Family , PPAR gamma/genetics , PPAR gamma/immunology , Pharmacogenetics/methods , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/immunology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/immunology , Receptors, Interleukin-6/genetics , Receptors, Interleukin-6/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , STAT Transcription Factors/genetics , STAT Transcription Factors/immunology , Signal Transduction
8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-293976

ABSTRACT

Severe COVID-19 patients account for most of the mortality of this disease. Early detection and effective treatment of severe patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model correctly classified severe patients with an accuracy of 93.5%, and was further validated using ten independent patients, seven of which were correctly classified. We identified molecular changes in the sera of COVID-19 patients implicating dysregulation of macrophage, platelet degranulation and complement system pathways, and massive metabolic suppression. This study shows that it is possible to predict progression to severe COVID-19 disease using serum protein and metabolite biomarkers. Our data also uncovered molecular pathophysiology of COVID-19 with potential for developing anti-viral therapies.<br><br>Funding: This work is supported by grants from Westlake Special Program for COVID19 (2020), and Tencent foundation (2020), National Natural Science Foundation of China (81972492, 21904107, 81672086), Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars (LR19C050001), Hangzhou Agriculture and Society Advancement Program (20190101A04). <br><br>Conflict of Interest: The research group of T.G. is partly supported by Tencent, Thermo Fisher Scientific, SCIEX and Pressure Biosciences Inc. C.Z., Z.K., Z.K. and S.Q. are employees of DIAN Diagnostics.

9.
Carbohydr Polym ; 285: 118971, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1549670

ABSTRACT

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.


Subject(s)
COVID-19/drug therapy , Ligusticum/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Carbohydrate Conformation , Carbohydrate Sequence , Drugs, Chinese Herbal , Humans , Polysaccharides/isolation & purification , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
10.
Environ Sci Pollut Res Int ; 29(15): 22012-22030, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1514070

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here, we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman's correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), and cellular component (CC) as well as to pathways, specific organs, cells, and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene, and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally, methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.


Subject(s)
Adenocarcinoma of Lung , COVID-19 , Lung Neoplasms , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , COVID-19/genetics , Computational Biology/methods , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology
11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292233

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman’s correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), cellular component (CC) as well as to pathways, specific organs, cells and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.

12.
Front Endocrinol (Lausanne) ; 12: 714909, 2021.
Article in English | MEDLINE | ID: covidwho-1497067

ABSTRACT

Background: Clinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis. Methods: The clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB. Results: The bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU). Conclusions: Based on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.


Subject(s)
COVID-19 , Carcinoma, Endometrioid , Endometrial Neoplasms , Host-Pathogen Interactions , Naphthoquinones/pharmacology , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/genetics , Calcium-Binding Proteins/drug effects , Calcium-Binding Proteins/metabolism , Carcinoma, Endometrioid/complications , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/genetics , Computational Biology , Drug Screening Assays, Antitumor/methods , Endometrial Neoplasms/complications , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Regulatory Networks/drug effects , Genetic Association Studies , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Membrane Proteins/drug effects , Membrane Proteins/metabolism , Middle Aged , Mitogen-Activated Protein Kinase 3/drug effects , Mitogen-Activated Protein Kinase 3/metabolism , Molecular Docking Simulation/methods , Naphthoquinones/therapeutic use , Prognosis , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Signal Transduction/drug effects , Signal Transduction/genetics , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism , Uterus/drug effects , Uterus/metabolism , Uterus/pathology , Uterus/virology
14.
Brief Bioinform ; 22(2): 1279-1290, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343635

ABSTRACT

OBJECTIVES: Patients with colorectal cancer (CRC) may be susceptible to the coronavirus disease-2019 (COVID-19). However, anti-CRC/COVID-19 treatment options are currently unavailable. Since niacin is a vitamin with cytoprotective and anti-inflammatory functions, this study aimed to evaluate the possible functional roles and underlying mechanisms of action of niacin as an anti-COVID-19 and -CRC therapy. INTERVENTIONS: We used a series of network pharmacology-based and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of niacin in CRC/COVID-19. MEASUREMENTS AND MAIN RESULTS: We revealed the clinical characteristics of CRC patients and COVID-19 patients, including predisposing genes, survival rate and prognosis. Moreover, the results of molecular docking analysis indicated that niacin exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions and signaling pathways of niacin in CRC/COVID-19. The analysis indicated that niacin could help in treating CRC/COVID-19 through cytoprotection, enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of cellular microenvironment. Furthermore, five core pharmacological targets of niacin in CRC/COVID-19 were also identified, including BCL2L1, PTGS2, IL1B, IFNG and SERPINE1. CONCLUSIONS: This study, for the first time, revealed the niacin-associated molecular functions and pharmacological targets for treating CRC/COVID-19, as COVID-19 remains a serious pandemic. But the findings were not validated in actual CRC patients infected with COVID-19, so further investigation is needed to confirm the potential use of niacin for treating CRC/COVID-19.


Subject(s)
COVID-19/drug therapy , Computational Biology , Niacin/therapeutic use , SARS-CoV-2/drug effects , Aged , COVID-19/virology , Colorectal Neoplasms/genetics , Female , Humans , Male , Middle Aged , Molecular Docking Simulation , Niacin/pharmacology
15.
Brief Bioinform ; 22(2): 1161-1174, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343620

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19. METHODS: The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology. RESULTS: We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function. CONCLUSIONS: For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world.


Subject(s)
Ascorbic Acid/administration & dosage , Computational Biology , Glycyrrhizic Acid/administration & dosage , Ascorbic Acid/therapeutic use , COVID-19/drug therapy , Drug Therapy, Combination , Glycyrrhizic Acid/therapeutic use , Humans
16.
Bioengineered ; 12(1): 4757-4767, 2021 12.
Article in English | MEDLINE | ID: covidwho-1337229

ABSTRACT

Metformin, a common clinical drug used to treat diabetes mellitus, is found with potential antiobese actions as reported in increasing evidences. However, the detailed mechanisms of metformin-antiobesity-related hypertension remain unrevealed. We have utilized the bioinformatics strategy, including network pharmacology and molecular docking analyses, to uncover pharmacological targets and molecular pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease 2019. In this report, the in-silico approaches using network pharmacology and molecular docking was utilized to identify the core targets, pharmacological functions and mechanisms of metformin against obesity-related hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, and 21 interaction genes, 6 core genes of metformin treating obesity-related hypertension. As results, molecular docking findings indicated the binding capability of metformin with key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2) expressed in obesity- and hypertension-dependent tissues. Metformin-exerted antihypertension/obesity actions involved in metabolic regulation, inflammatory suppression. And antihypertension/obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for ameliorating microenvironmental homeostasis in targeting tissues. In conclusion, our current bioinformatics findings have uncovered all pharmacological targets, biological functions and signaling pathways of metformin treating obesity-related hypertension, thus promoting its clinical application in future.


Subject(s)
Hypertension/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Computational Biology , Humans , Molecular Docking Simulation , Signal Transduction
17.
Aging (Albany NY) ; 13(12): 15785-15800, 2021 06 27.
Article in English | MEDLINE | ID: covidwho-1285613

ABSTRACT

Recent reports indicate that patients with hepatocholangiocarcinoma (CHOL) have a higher morbidity and mortality rate for coronavirus disease (COVID-19). Anti-CHOL/COVID-19 medicines are inexistent. Vitamin A (VA) refers to a potent nutrient with anti-cytotoxic and anti-inflammatory actions. Therefore, this study aimed to determine the potential functions and molecular mechanisms of VA as a potential treatment for patients with both CHOL and COVID-19 (CHOL/COVID-19). The transcriptome data of CHOL patients were obtained from the Cancer Genome Analysis database. Furthermore, the network pharmacology approach and bioinformatics analysis were used to identify and reveal the molecular functions, therapeutic biotargets, and signaling of VA against CHOL/COVID-19. First, clinical findings identified the medical characteristics of CHOL patients with COVID-19, such as susceptibility gene, prognosis, recurrence, and survival rate. Anti-viral and anti-inflammatory pathways, and immunopotentiation were found as potential targets of VA against CHOL/COVID-19. These findings illustrated that VA may contribute to the clinical management of CHOL/COVID-19 achieved by induction of cell repair, suppression of oxidative stress and inflammatory reaction, and amelioration of immunity. Nine vital therapeutic targets (BRD2, NOS2, GPT, MAPK1, CXCR3, ICAM1, CDK4, CAT, and TMPRSS13) of VA against CHOL/COVID-19 were identified. For the first time, the potential pharmacological biotargets, function, and mechanism of action of VA in CHOL/COVID-19 were elucidated.


Subject(s)
COVID-19/drug therapy , Immunity/drug effects , SARS-CoV-2/drug effects , Vitamin A/pharmacology , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/virology , Carcinoma, Hepatocellular/genetics , Cholangiocarcinoma/genetics , Computational Biology , Female , Humans , Inflammation/drug therapy , Inflammation/etiology , Liver Neoplasms/genetics , Male , Molecular Docking Simulation , Proportional Hazards Models , Signal Transduction/drug effects
18.
Proteomics ; 21(15): e2100002, 2021 08.
Article in English | MEDLINE | ID: covidwho-1227784

ABSTRACT

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.


Subject(s)
COVID-19 , L-Lactate Dehydrogenase/blood , Adult , Aged , COVID-19/blood , Female , Humans , Male , Middle Aged , Prognosis , Proteomics , Severity of Illness Index
20.
Crit Care Med ; 48(11): e1004-e1011, 2020 11.
Article in English | MEDLINE | ID: covidwho-998501

ABSTRACT

OBJECTIVES: To evaluate and compare the efficacy of National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment on predicting in-hospital death in patients with coronavirus disease 2019. DESIGN: A retrospective, observational study. SETTING: Single center, West Campus of Wuhan Union hospital-a temporary center to manage critically ill patients with coronavirus disease 2019. PATIENTS: A total of 673 consecutive adult patients with coronavirus disease 2019 between January 30, 2020, and March 14, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demography, comorbidities, vital signs, mental status, oxygen saturation, and use of supplemental oxygen at admission to the ward were collected from medical records and used to score National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Total number of patients was 673 (51% male) and median (interquartile range) age was 61 years (50-69 yr). One-hundred twenty-one patients died (18%). For predicting in-hospital death, the area under the receiver operating characteristics (95% CI) for National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment were 0.882 (0.847-0.916), 0.880 (0.845-0.914), 0.839 (0.800-0.879), 0.766 (0.718-0.814), and 0.694 (0.641-0.746), respectively. Among the parameters of National Early Warning Score, the oxygen saturation score was found to be the most significant predictor of in-hospital death. The area under the receiver operating characteristic (95% CI) for oxygen saturation score was 0.875 (0.834-0.916). CONCLUSIONS: In this single-center study, the discrimination of National Early Warning Score/National Early Warning Score 2 for predicting mortality in patients with coronavirus disease 2019 admitted to the ward was found to be superior to Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Peripheral oxygen saturation could independently predict in-hospital death in these patients. Further validation of our finding in multiple settings is needed to determine its applicability for coronavirus disease 2019.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Critical Illness/mortality , Early Warning Score , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Aged , Blood Pressure , COVID-19 , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Organ Dysfunction Scores , Pandemics , Prognosis , Retrospective Studies , Risk Assessment , SARS-CoV-2
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