Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 56
Filter
1.
Elife ; 122023 04 18.
Article in English | MEDLINE | ID: covidwho-2327355

ABSTRACT

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction with TNF receptor-associated factor 6 (TRAF6) and its ability to methylate asparagine residues in the coiled-coil domain. This interaction was found to inhibit TRAF6 oligomerization and autoubiquitination, which prevented NF-κB transactivation and subsequent expression of endothelial adhesion molecules. Separately, PIMT also suppressed ICAM-1 expression by inhibiting its N-glycosylation, causing effects on protein stability that ultimately translated into reduced EC(endothelial cell)-leukocyte interactions. Our study has identified PIMT as a novel and potent suppressor of endothelial activation. Taken together, these findings suggest that therapeutic targeting of PIMT may be effective in limiting organ injury in inflammatory vascular diseases.


Subject(s)
Lipopolysaccharides , Protein D-Aspartate-L-Isoaspartate Methyltransferase , TNF Receptor-Associated Factor 6 , Animals , Mice , Endothelial Cells/metabolism , Endothelium/metabolism , Lipopolysaccharides/metabolism , Signal Transduction , TNF Receptor-Associated Factor 6/genetics , TNF Receptor-Associated Factor 6/metabolism , Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics , Protein D-Aspartate-L-Isoaspartate Methyltransferase/metabolism
2.
Bioeng Transl Med ; 8(3): e10475, 2023 May.
Article in English | MEDLINE | ID: covidwho-2320823

ABSTRACT

In patients with mild osteoarthritis (OA), two to four monthly injections are required for 6 months due to the degradation of hyaluronic acid (HA) by peroxidative cleavage and hyaluronidase. However, frequent injections may lead to local infection and also cause inconvenience to patients during the COVID-19 pandemic. Herein, we developed a novel HA granular hydrogel (n-HA) with improved degradation resistance. The chemical structure, injectable capability, morphology, rheological properties, biodegradability, and cytocompatibility of the n-HA were investigated. In addition, the effects of the n-HA on the senescence-associated inflammatory responses were studied via flow cytometry, cytochemical staining, Real time quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. Importantly, the treatment outcome of the n-HA with one single injection relative to the commercial HA product with four consecutive injections within one treatment course in an OA mouse model underwent anterior cruciate ligament transection (ACLT) was systematically evaluated. Our developed n-HA exhibited a perfect unification of high crosslink density, good injectability, excellent resistance to enzymatic hydrolysis, satisfactory biocompatibility, and anti-inflammatory responses through a series of in vitro studies. Compared to the commercial HA product with four consecutive injections, a single injection of n-HA contributed to equivalent treatment outcomes in an OA mouse model in terms of histological analysis, radiographic, immunohistological, and molecular analysis results. Furthermore, the amelioration effect of the n-HA on OA development was partially ascribed to the attenuation of chondrocyte senescence, thereby leading to inhibition of TLR-2 expression and then blockade of NF-κB activation. Collectively, the n-HA may be a promising therapeutic alternative to current commercial HA products for OA treatment.

3.
Acta Biomater ; 158: 493-509, 2023 03 01.
Article in English | MEDLINE | ID: covidwho-2245092

ABSTRACT

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. STATEMENT OF SIGNIFICANCE: Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics.


Subject(s)
COVID-19 , Vaccines , Humans , SARS-CoV-2 , COVID-19 Vaccines , Microspheres , Antiviral Agents/pharmacology
4.
Environ Pollut ; 317: 120728, 2022 Nov 22.
Article in English | MEDLINE | ID: covidwho-2246467

ABSTRACT

Wuhan took strict measures to prevent the spread of COVID-19 from January 26 to April 7 in 2020. The lockdown reduced the concentrations of atmospheric pollutants, except ozone (O3). To investigate the increase in O3 during the lockdown, trace gas pollutants were collected. The initial concentrations of volatile organic compounds (VOCs) were calculated based on a photochemical ratio method, and the ozone formation potential (OFP) was obtained using the initial and measured VOC concentrations. The O3 formation regime was NOX-limited based on the VOCs/NOX diurnal ratios during the lockdown period. The reduced nitric oxide (NO) concentrations and lower wind speed (WS) could explain the night-time O3 accumulation. The initial total VOCs (TVOCs) during the lockdown were 47.6 ± 2.9 ppbv, and alkenes contributed 48.1%. The photochemical loss amounts of alkenes were an order of magnitude higher than those of alkenes in the same period in 2019 and increased from 16.6 to 28.0 ppbv in the daytime. The higher initial alkene concentrations sustained higher OFP during the lockdown, reaching between 252.4 and 504.4 ppbv. The initial isoprene contributed approximately 35.0-55.0% to the total OFP and had a positive correlation with the increasing O3 concentrations. Approximately 75.5% of the temperatures were concentrated in the range of 5 and 20 °C, which were higher than those in 2019. In addition to stronger solar radiation, the higher temperatures induced higher isoprene emission rates, partially accounting for the higher isoprene concentrations. Lower isoprene-emitting trees should be considered for future urban vegetation to control O3 episodes.

5.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.02.09.23285515

ABSTRACT

Background. The pandemic of the new coronavirus infection COVID-19 determines the relevance of conducting a study of the gender age structure of hospitalized and deceased among the population of Moscow on the example of one of the city clinical hospitals in 2020 and 2021. The aim of the work is to identify the patterns of the epidemic process of COVID-19 in connection with the gender and age characteristics of hospitalized adults and to establish the sex and age groups most susceptible to hospitalization and mortality from COVID-19. Materials and methods. The analysis of the structure of hospitalized and deceased from COVID-19 in the context of their gender and age composition was carried out. The data of the statistical accounting form F-60u/lech "Journal of infectious diseases" of adults hospitalized in one of the city clinical hospitals of Moscow in 2020 and 2021 were used. Data processing was carried out by a set of standard statistical methods. To identify the true risk groups for hospitalization and mortality, a statistical correction of the sex and age composition of the population of Moscow was used. Results and discussion. Using standard statistical methods in combination with the use of statistical correction of sex and age composition, data on the true risk groups for hospitalization and mortality among the population of Moscow in 2020 and 2021 were obtained. Conclusion. The results obtained in our independent study on the true risk groups for hospitalization and mortality among the population of Moscow complement and introduce new knowledge about the true risk groups for hospitalization and mortality in COVID-19. The patterns identified in this epidemiological analysis are an important component of epidemiological surveillance for making managerial decisions to prevent the spread of SARS-CoV-2 and planning for the provision of inpatient medical care to established gender and age risk groups.


Subject(s)
COVID-19 , Coronavirus Infections , Communicable Diseases
6.
Clin Chim Acta ; 540: 117227, 2023 Feb 01.
Article in English | MEDLINE | ID: covidwho-2177056

ABSTRACT

BACKGROUND: Early stratification of disease progression remains one of the major challenges towards the post-coronavirus disease 2019 (COVID-19) era. The clinical relevance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid load is debated due to the heterogeneity in patients' underlying health conditions. We determined the prognostic value of nasopharyngeal viral load dynamic conversion for COVID-19. METHODS: The cycling threshold (Ct) values of 28,937 nasopharyngeal SARS-CoV-2 RT-PCRs were retrospectively collected from 3,364 COVID-19 patients during hospitalization and coordinated to the onset of disease progression. The ROC curve was utilized to determine the predictive performance of the rate of Ct value alteration between two consecutive RT-PCR runs within 48 h (ΔCt%) for disease transformation across patients with different COVID-19 severity and immune backgrounds, and further validated with 1,860 SARS-CoV-2 RT-PCR results from an independent validation cohort of 262 patients. For the 67 patients with severe COVID-19, Kaplan-Meier analysis was performed to evaluate the difference in survival between patients stratified by the magnitude of Ct value alteration between the late and early stages of hospitalization. RESULTS: The kinetics of viral nucleic acid conversion diversified across COVID-19 patients with different clinical characteristics and disease severities. The ΔCt% is a clinical characteristic- and host immune status-independent indicator for COVID-19 progression prediction (AUC = 0.79, 95 % CI = 0.76 to 0.81), which outperformed the canonical blood test markers, including c-reactive protein (AUC = 0.57, 95 % CI = 0.53 to 0.61), serum amyloid A (AUC = 0.61, 95 % CI = 0.54 to 0.68), lactate dehydrogenase (AUC = 0.61, 95 % CI = 0.56 to 0.67), d-dimer (AUC = 0.56, 95 % CI = 0.46 to 0.66), and lymphocyte count (AUC = 0.62, 95 % CI = 0.58 to 0.66). Patients with persistent high SARS-CoV-2 viral load (an increase of mean Ct value < 50 %) during the first 3 days of hospitalization demonstrated a significantly unfavorable survival (HR = 0.16, 95 % CI = 0.04 to 0.65, P = 2.41 × 10-3). CONCLUSIONS: Viral nucleic acid dynamics of SARS-CoV-2 eliminates the inter-patient variance of basic health conditions and therefore, can serve as a prognostic marker for COVID-19.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , Retrospective Studies , Prognosis , Time Factors , Viral Load , Disease Progression
7.
Environ Sci Pollut Res Int ; 30(14): 40405-40426, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2174826

ABSTRACT

The COVID-19 pandemic has also caused an environmental challenge, especially plastic pollution. This study is aimed to provide a systematic review of the current status and outlook of research on plastic pollution caused by the COVID-19 pandemic using a bibliometrics approach. The results indicate developed countries were the first to pay attention to the impact of plastics on the ocean and ecological environment during COVID-19 and conducted related research, and then developing countries followed up and started research. Research in developed countries is absolutely dominant in plastic pollution induced by the COVID-19, although the plastic pollution faced by developing countries is also very serious. The author's co-occurrence analysis shows the Matthew effect. Keyword clustering shows that plastics have a harsh chain-like impact on the ecological environment from land to ocean to atmosphere. The non-degradable components of plastic bring a serious impact the ocean ecosystems, and then pose a serious threat to the entire ecosystem environment.


Subject(s)
COVID-19 , Plastics , Humans , Ecosystem , Pandemics , COVID-19/epidemiology , Environmental Pollution , Environmental Monitoring/methods
8.
Sci Adv ; 9(2): eade0869, 2023 01 13.
Article in English | MEDLINE | ID: covidwho-2193381

ABSTRACT

Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs) and causes several hematological disorders and fetal hydrops. Amino acid (aa) 5-68 of minor capsid protein VP1 (VP1u5-68aa) is the minimal receptor binding domain for B19V to enter EPCs. Here, we carried out a genome-wide CRISPR-Cas9 guide RNA screen and identified tyrosine protein kinase receptor UFO (AXL) as a proteinaceous receptor for B19V infection of EPCs. AXL gene silencing in ex vivo expanded EPCs remarkably decreased B19V internalization and replication. Additions of the recombinant AXL extracellular domain or a polyclonal antibody against it upon infection efficiently inhibited B19V infection of ex vivo expanded EPCs. Moreover, B19V VP1u interacted with the recombinant AXL extracellular domain in vitro at a relatively high affinity (KD = 103 nM). Collectively, we provide evidence that AXL is a co-receptor for B19V infection of EPCs.


Subject(s)
Axl Receptor Tyrosine Kinase , Erythema Infectiosum , Parvovirus B19, Human , Humans , Capsid Proteins/genetics , Capsid Proteins/metabolism , Erythema Infectiosum/metabolism , Parvovirus B19, Human/genetics , Parvovirus B19, Human/metabolism , Protein Binding , Axl Receptor Tyrosine Kinase/metabolism
9.
Jie Fang Jun Yi Xue Za Zhi ; 47(11):1073-1078, 2022.
Article in Chinese | ProQuest Central | ID: covidwho-2164243

ABSTRACT

Objective To analyze the mental health status of medical staff in the Fourth Branch of National Convention and Exhibition Center Makeshift Hospital during the COVID-19 epidemic in Shanghai to lay a theoretical foundation for the mental health and psychological intervention of medical staff in COVID-19 and other public health emergencies. Methods An online questionnaire survey was conducted with the generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and Athens insomnia scale (AIS) before medical staff entering the makeshift hospital and one month later. Results The detection rates of anxiety, depression and insomnia were 18.4%, 22.1% and 27.0% respectively before entering the makeshift hospital, and 28.8%, 59.3% and 64.2% respectively during the follow-up period one month later. The GAD-7, PHQ-9 and AIS scores of medical staff after working in the makeshift hospital for one month increased significantly compared with those at the baseline period (P<0.01). Female and previous history of using sedative and hypnotic drugs were risk factors for increased depression level among medical staff in the makeshift hospital. Conclusions The anxiety, depression and insomnia levels of the medical staff in Shanghai increased after working in the makeshift hospital for one month. It is of great significance for the front-line support work to identify the medical staff with serious psychological problems and carry out psychological intervention in the early stage.

10.
Mol Cell ; 82(23): 4519-4536.e7, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2120478

ABSTRACT

Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.


Subject(s)
AMP-Activated Protein Kinases , Nucleic Acids , Animals , AMP-Activated Protein Kinases/genetics , Immunity, Innate , Antiviral Agents , Glucose
12.
Trop Med Infect Dis ; 7(10)2022 Oct 02.
Article in English | MEDLINE | ID: covidwho-2066497

ABSTRACT

(1) Background: During the two-year-long siege from the COVID-19 pandemic, a significant proportion of doctor visits transitioned from in-person to virtual. Scare evidence is available to assess the quality of patient-provider communication via the platform of telemedicine, especially for PrEP care within primary care settings. (2) Methods: Participants included 18 primary care providers and 29 PrEP-eligible women. Through content analysis and thematic analysis, facilitators and barriers embedded at different levels of telemedicine were identified and assessed. (3) Results: Women and providers reported pros and cons regarding their telemedicine experiences during the initial wave of COVID-19. Both groups of participants agreed that telemedicine visits were more convenient, efficient, and comfortable than in-person visits. However, without face-to-face interactions, some women felt less empathy, caring, and connected with their providers during virtual visits. Health providers expressed concerns with telemedicine, including patients' privacy, lack of intimacy between patients and providers, and delayed lab work. (4) Conclusions: Our data indicate multi-level factors may affect telemedicine experience among PrEP-eligible women and health providers. Participants expressed concerns that may further entrench these long-existing health disparities in healthcare. Proactive efforts from policymakers, health professionals, researchers, and stakeholders are urgently required to tackle identified barriers and to pave the way for the new infrastructure that ensures health equity in society.

13.
Trials ; 23(1): 797, 2022 Sep 21.
Article in English | MEDLINE | ID: covidwho-2038855

ABSTRACT

BACKGROUND: Depression and anxiety are common among pregnant women. Internet-delivered psychological therapies such as cognitive behavioral therapy (iCBT) have been developed to increase accessibility and address common help-seeking barriers, especially during pandemic period. The objective of this trial is to evaluate the short-term and long-term effects of iCBT on reducing depressive symptoms among pregnant women during the COVID-19 pandemic with the overall goal of preventing depression recurrence in the first 12 months postpartum. METHODS: A multi-site randomized controlled trial will be conducted where 300 pregnant women early in their third trimester will be screened for depression symptoms using the Edinburgh Postnatal Depression Scale (EPDS) during a routine obstetrical visit. Eligible and consenting women with a score greater than 9 will be randomly allocated (1:1) to either intervention group or control group. ICBT involving the completion of 7 weekly online modules will be delivered via a well-designed perinatal mental healthcare app. The primary objective is to evaluate the effect of iCBT on reducing depression symptoms among pregnant Chinese women starting from their third trimester. The secondary objectives are to examine the effect of iCBT on anxiety, sleep quality, social support, parenting stress, co-parenting relationship, and infant development. DISCUSSION: This multi-center randomized controlled trial has been planned in accordance with best practices in behavioral trial design. The internet-based intervention addressed the needs of pregnant women during a major pandemic where face-to-face therapy is not preferable. The trial has a relatively large sample size with sufficient power to evaluate the efficacy of iCBT intervention for the primary and secondary outcomes. One year follow-up evaluation in the study is designed to determine the longer-term effect of the intervention on both maternal and infant outcomes. Although a limitation is the assessment of depression and anxiety using self-report measures, these easily incorporated and maternal-preferred assessments allow for real-life scalability if the intervention is proven to be effective. ETHICS AND DISSEMINATION: Ethics was approved by the institutional review board of International Peace Maternity and Child Health Hospital (GKLW2020-25). Dissemination of results will be published in peer-reviewed academic journals and presented at scientific conferences. TRIAL STATUS: The first patient was enrolled on 19 August 2020. To date, 203 participants have met eligibility requirements and been randomized to either the intervention group or control group. Data collection aims to be complete in September 2022. Date and version identifier: 2020715-version1.0. TRIAL REGISTRATION: ChiCTR2000033433. Registered 31 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=54482 .


Subject(s)
COVID-19 , Cognitive Behavioral Therapy , Child , Cognitive Behavioral Therapy/methods , Depression/diagnosis , Depression/therapy , Female , Humans , Internet , Multicenter Studies as Topic , Pandemics , Pregnancy , Randomized Controlled Trials as Topic , Treatment Outcome
14.
J Clin Med ; 11(17)2022 Aug 30.
Article in English | MEDLINE | ID: covidwho-2006087

ABSTRACT

(1) Purpose: Here, we describe the clinical characteristics and predisposing factors of acute foggy corneal epithelial disease, a rare disease newly found during COVID-19 pandemic; (2) Methods: In this single-arm, ambispective case series study, ten patients with acute foggy corneal epithelial disease admitted between May 2020 and March 2021 were enrolled. Their detailed medical history and clinical and ophthalmic findings were recorded and analyzed; (3) Results: All the patients were female (100%), aged from 28 to 61 years (mean age of 40.4 ± 9.3 years). Seven cases (70%) had excessive eye use, and six cases (60%) had stayed up late and were overworked. Ten subjects (100%) presented with acute onset and a self-healing tendency. There was a mild-to-moderate decrease in the corrected visual acuity (0.35 ± 0.21 (LogMAR)). Slit-lamp examination showed diffuse dust-like opacity and edema in the epithelial layer of the cornea. By in vivo confocal microscope, epithelial cells presented characteristically a "relief-like" appearance. Anterior segment optical coherence tomography examination revealed that the mean epithelial thickness was increased (69.25 ± 4.31 µm, p < 0.01); (4) Conclusions: Acute foggy corneal epithelial disease is a rare disease in clinic, which tends to occur in young and middle-aged females. The typical clinical symptom is sudden foggy vision, which occurs repeatedly and can be relieved without treatment. Sex, an abnormal menstrual cycle, overuse of the eyes, fatigue and pressure might be risk factors. Changes in lifestyle and eye use habit during the COVID-19 pandemic may have possibly contributed to this disease incidence.

15.
Eur J Med Chem ; 238: 114458, 2022 Aug 05.
Article in English | MEDLINE | ID: covidwho-1982956

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as the pathogen of coronavirus disease 2019 (COVID-19), has infected millions of people and took hundreds of thousands of lives. Unfortunately, there is deficiency of effective medicines to prevent or treat COVID-19. 3C like protease (3CLPro) of SARS-CoV-2 is essential to the viral replication and transcription, and is an attractive target to develop anti-SARS-CoV-2 agents. Targeting on the 3CLPro, we screened our protease inhibitor library and obtained compound 10a as hit to weakly inhibit the SARS-CoV-2 3CLPro, and determined the co-crystal structure of 10a and the protease. Based on the deep understanding on the protein-ligand complexes between the hit and SARS-CoV-2 3CLPro, we designed a series of peptidomimetic inhibitors, with outstanding inhibitory activity against SARS-CoV-2 3CLPro and excellent anti-viral potency against SARS-CoV-2. The protein-ligand complexes of the other key inhibitors with SARS-CoV-2 3CLPro were explicitly described by the X-ray co-crystal study. All such results suggest these peptidomimetic inhibitors could be further applied as encouraging drug candidates.


Subject(s)
COVID-19 Drug Treatment , Peptidomimetics , Antiviral Agents/chemistry , Cysteine Endopeptidases/chemistry , Humans , Ligands , Peptide Hydrolases , Peptidomimetics/chemistry , Peptidomimetics/pharmacology , Protease Inhibitors/chemistry , SARS-CoV-2
16.
World J Pediatr ; 18(8): 538-544, 2022 08.
Article in English | MEDLINE | ID: covidwho-1906548

ABSTRACT

BACKGROUND: Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated occurrence. This review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital's previous experiences with the diagnosis and treatment of severe acute hepatitis for reference. DATA SOURCES: Websites including the UK Health Security Agency, European Centre for Disease Prevention and Control, CDC, WHO, and databases including PubMed/Medline, Cochrane Library, Embase and Web of Science were searched for articles on severe acute hepatitis in children. RESULTS: As of May 26, 2022, a total of 650 cases have been reported in 33 countries; at least 38 (6%) children required liver transplantation, and nine (1%) died. Cases are predominantly aged between 3 and 5 years old, and there are no epidemiological links among them. The common manifestations are jaundice, vomiting and pale stools. Adenovirus tested positive in most cases, and SARS-CoV-2 and other viruses were detected in a few cases, but virus particles were not found in liver tissue. Adenovirus immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver samples. The hierarchical treatment includes symptomatic and supportive therapy, management of coagulation disorders and hepatic encephalopathy, artificial liver support, and liver transplantation (approximately 6%-10% of cases require liver transplant). CONCLUSIONS: The etiology of this severe acute hepatitis in children is not clear. The clinical features are severe acute hepatitis with significantly elevated liver enzymes. Clinicians need to be alert to children with hepatitis.


Subject(s)
Hepatitis , Acute Disease , Child , Child, Preschool , Hepatitis/diagnosis , Hepatitis/prevention & control , Hepatitis/therapy , Humans
17.
Molecules ; 27(11)2022 May 26.
Article in English | MEDLINE | ID: covidwho-1866459

ABSTRACT

Dipyridamole, apart from its well-known antiplatelet and phosphodiesterase inhibitory activities, is a promising old drug for the treatment of pulmonary fibrosis. However, dipyridamole shows poor pharmacokinetic properties with a half-life (T1/2) of 7 min in rat liver microsomes (RLM). To improve the metabolic stability of dipyridamole, a series of pyrimidopyrimidine derivatives have been designed with the assistance of molecular docking. Among all the twenty-four synthesized compounds, compound (S)-4h showed outstanding metabolic stability (T1/2 = 67 min) in RLM, with an IC50 of 332 nM against PDE5. Furthermore, some interesting structure-activity relationships (SAR) were explained with the assistance of molecular docking.


Subject(s)
Dipyridamole , Idiopathic Pulmonary Fibrosis , Animals , Dipyridamole/pharmacology , Dipyridamole/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/metabolism , Microsomes, Liver/metabolism , Molecular Docking Simulation , Molecular Structure , Rats , Structure-Activity Relationship
18.
Sci China Life Sci ; 65(10): 1971-1984, 2022 10.
Article in English | MEDLINE | ID: covidwho-1826874

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.


Subject(s)
Agmatine , COVID-19 , Interferon Type I , Animals , Antiviral Agents/therapeutic use , Cytokines/metabolism , Fibroblasts/metabolism , Interferon Regulatory Factors/metabolism , Interferon Type I/metabolism , Interleukin-6/metabolism , Mice , NF-kappa B/metabolism , Putrescine , SARS-CoV-2
19.
Front Immunol ; 13: 856327, 2022.
Article in English | MEDLINE | ID: covidwho-1809401

ABSTRACT

Coronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF-α by partly intervention of NF-κB activity in LPS-induced macrophage model. In vivo, peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-α. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS.


Subject(s)
COVID-19 Drug Treatment , Cytokine Release Syndrome , Acids, Carbocyclic , Animals , Cytokine Release Syndrome/drug therapy , Guanidines , Humans , Leukocytes, Mononuclear , Mice , SARS-CoV-2 , Tumor Necrosis Factor-alpha
20.
Ann Transl Med ; 10(6): 333, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1786446

ABSTRACT

Background: High-throughput population screening for the novel coronavirus disease (COVID-19) is critical to controlling disease transmission. Convolutional neural networks (CNNs) are a cutting-edge technology in the field of computer vision and may prove more effective than humans in medical diagnosis based on computed tomography (CT) images. Chest CT images can show pulmonary abnormalities in patients with COVID-19. Methods: In this study, CT image preprocessing are firstly performed using fuzzy c-means (FCM) algorithm to extracted the region of the pulmonary parenchyma. Through multiscale transformation, the preprocessed image is subjected to multi scale transformation and RGB (red, green, blue) space construction. After then, the performances of GoogLeNet and ResNet, as the most advanced CNN architectures, were compared in COVID-19 detection. In addition, transfer learning (TL) was employed to solve overfitting problems caused by limited CT samples. Finally, the performance of the models were evaluated and compared using the accuracy, recall rate, and F1 score. Results: Our results showed that the ResNet-50 method based on TL (ResNet-50-TL) obtained the highest diagnostic accuracy, with a rate of 82.7% and a recall rate of 79.1% for COVID-19. These results showed that applying deep learning technology to COVID-19 screening based on chest CT images is a very promising approach. This study inspired us to work towards developing an automatic diagnostic system that can quickly and accurately screen large numbers of people with COVID-19. Conclusions: We tested a deep learning algorithm to accurately detect COVID-19 and differentiate between healthy control samples, COVID-19 samples, and common pneumonia samples. We found that TL can significantly increase accuracy when the sample size is limited.

SELECTION OF CITATIONS
SEARCH DETAIL