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2.
Inflamm Res ; 2022 Aug 13.
Article in English | MEDLINE | ID: covidwho-1990592

ABSTRACT

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear. METHODS: We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis. RESULTS: LC-MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1ß, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model. CONCLUSION: This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease.

3.
J Biol Chem ; 298(9): 102280, 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1936718

ABSTRACT

Transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is the pathogen responsible for transmissible gastroenteritis, which results in mitochondrial dysfunction in host cells. Previously, we identified 123 differentially expressed circular RNAs (cRNA)from the TGEV-infected porcine intestinal epithelial cell line jejunum 2 (IPEC-J2). Previous bioinformatics analysis suggested that, of these, circBIRC6 had the potential to regulate mitochondrial function. Furthermore, mitochondrial permeability transition, a key step in the process of mitochondrial dysfunction, is known to be caused by abnormal opening of mitochondrial permeability transition pores (mPTPs) regulated by the voltage-dependent anion-selective channel protein 1 (VDAC)-Cyclophilin D (CypD) complex. Therefore, in the present study, we investigated the effects of circBIRC6-2 on mitochondrial dysfunction and opening of mPTPs. We found that TGEV infection reduced circBIRC6-2 levels, which in turn reduced mitochondrial calcium (Ca2+) levels, the decrease of mitochondrial membrane potential, and opening of mPTPs. In addition, we also identified ORFs and internal ribosomal entrance sites within the circBIRC6-2 RNA. We demonstrate circBIRC6-2 encodes a novel protein, BIRC6-236aa, which we show inhibits TGEV-induced opening of mPTPs during TGEV infection. Mechanistically, we identified an interaction between BIRC6-236aa and VDAC1, suggesting that BIRC6-236aa destabilizes the VDAC1-CypD complex. Taken together, the results suggest that the novel protein BIRC6-236aa encoded by cRNA circBIRC6-2 inhibits mPTP opening and subsequent mitochondrial dysfunction by interacting with VDAC1.

4.
JMIR Serious Games ; 10(3): e37026, 2022 07 08.
Article in English | MEDLINE | ID: covidwho-1933483

ABSTRACT

BACKGROUND: COVID-19 has spread worldwide and generated tremendous stress on human beings. Unfortunately, it is often hard for distressed individuals to access mental health services under conditions of restricted movement or even lockdown. OBJECTIVE: The study first aims to develop an online digital intervention package based on a commercially released coloring game. The second aim is to test the effectiveness of difference intervention packages for players to increase subjective well-being (SWB) and reduce anxiety during the pandemic. METHODS: An evidence-based coloring intervention package was developed and uploaded to an online coloring game covering almost 1.5 million players worldwide in January 2021. Players worldwide participated to color either 4 rounds of images characterized by awe, pink, nature, and blue or 4 rounds of irrelevant images. Participants' SWB and anxiety and the perceived effectiveness of the game in reducing anxiety (subjective effectiveness [SE]) were assessed 1 week before the intervention (T1), after the participants completed pictures in each round (T2-T5), and after the intervention (T6). Independent 2-tailed t tests were conducted to examine the general intervention (GI) effect and the intervention effect of each round. Univariate analysis was used to examine whether these outcome variables were influenced by the number of rounds completed. RESULTS: In total, 1390 players worldwide responded and completed at least 1 assessment. Overall, the GI group showed a statistical significantly greater increase in SWB than the general control (GC) group (N=164, t162=3.59, Cohen d=0.59, 95% CI 0.36-1.24, P<.001). Compared to the control group, the best effectiveness of the intervention group was seen in the awe round, in which the increase in SWB was significant (N=171, t169=2.51, Cohen d=0.39, 95% CI 0.10-0.82, P=.01), and players who colored all 4 pictures had nearly significant improvements in SWB (N=171, F4,170=2.34, partial ŋ2=0.053, P=.06) and a significant decrease in anxiety (N=171, F4,170=3.39, partial ŋ2=0.075, P=.01). CONCLUSIONS: These data indicate the effectiveness of online psychological interventions, such as coloring games, for mental health in the specific period. They also show the feasibility of applying existing commercial games embedded with scientific psychological interventions that can fill the gap in mental crises and services for a wider group of people during the pandemic. The results would inspire innovations to prevent the psychological problems caused by public emergencies and encourage more games, especially the most popular ones, to take more positive action for the common crises of humankind.

5.
Modern Supply Chain Research and Applications ; 4(2):122-140, 2022.
Article in English | ProQuest Central | ID: covidwho-1876993

ABSTRACT

Purpose>In the presence of coronavirus disease 2019 (COVID-19), due to the social distance restriction, consumers' regular consumption behaviors and patterns have been changing fundamentally. Thereafter, an innovative group buying model has emerged and developed explosively with a specific focus on consumer's location, known as community-based group buying (CGB). The purpose of this paper is to investigate the transfer mechanism of user's trust in dyadic contexts of social and commercial role-playing in the CGB program.Design/methodology/approach>This study adopts an empirical research method, with an online and offline questionnaire survey, a total of 382 responses have been obtained. Then, both descriptive analysis and hierarchical regression analysis are conducted to explore the dual roles of group leader and its corresponding effects on consumers' trust (i.e. emotional trust and behavioral trust) and engagement actions (i.e. purchase and share) in the CGB program.Findings>Results indicate that resident's trust and their perception of group leader's friend role can positively enhance their engagement actions in the CGB programs. Meanwhile, for the purpose of profit maximization, the group leader is more willing to play a friend role in transactions no matter whether the role conflict exists.Originality/value>Research findings provide some managerial insights for CGB platform on the selection and training of group leaders and the incentive mechanism design.

6.
Adv Healthc Mater ; 11(14): e2200283, 2022 07.
Article in English | MEDLINE | ID: covidwho-1843840

ABSTRACT

The eye is susceptible to viral infections, causing severe ocular symptoms or even respiratory diseases. Methods capable of protecting the eye from external viral invasion in a long-term and highly effective way are urgently needed but have been proved to be extremely challenging. Here, a strategy of forming a long-acting protective ocular surface is described by instilling adhesive dual-antiviral nanoparticles. Taking pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model virus, antiviral agent-loaded nanoparticles are coated with a "double-lock" hybrid cell membrane abundant with integrin-ß1 and angiotensin converting enzyme II (ACE2). After instillation, the presence of integrin-ß1 endows coated nanoparticles with steady adhesion via specific binding to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium, achieving durable retention on the ocular surface. In addition to loaded inhibitors, the exposure of ACE2 can trap SARS-CoV-2 and subsequently neutralize the associated spike protein, playing a dual antiviral effect of the resulting nanoparticles. Adhesive dual-antiviral nanoparticles enabled by coating with a "double-lock" hybrid cell membrane could be a versatile platform for topical long-acting protection against viral infection of the eye.


Subject(s)
Antiviral Agents , COVID-19 , Eye Diseases , Eye , Nanoparticles , Adhesives/pharmacology , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , COVID-19/drug therapy , Eye/drug effects , Eye/virology , Eye Diseases/prevention & control , Eye Diseases/virology , Humans , Integrins , SARS-CoV-2
7.
J Natl Med Assoc ; 114(2): 218-226, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1635310

ABSTRACT

IMPORTANCE: The increased COVID-19 mortality for Black individuals over White individuals may be explained by the known racial disparities in access to insurance. OBJECTIVE: To determine whether racial disparities in COVID-19 mortality still exist when Blacks and Whites are equally insured. DESIGN: Routinely collected data on race, mortality, type of insurance, known risk factors, and lab results from the EPIC Patient Management System were analyzed using a multivariable logistic regression model. SETTING: Piedmont Healthcare is the largest hospital system in Georgia. Due to its multiple locations across the state of Georgia, it receives a relatively equitably insured population. PARTICIPANTS: All patients hospitalized with a positive COVID-19 status between March 1 and November 30, 2020. MAIN OUTCOMES: We hypothesized that Black patients would not have higher odds of mortality than White patients, and that type of insurance would predict COVID-19 mortality. RESULTS: 6,881 (3,674 Black, 3,207 White; 48% male, mean age = 60) patients were included. Race was not a significant predictor of COVID-19 mortality (p>0.05). When controlling for age and insurance, the mortality rate for Black patients was not statistically significant from that for White patients (p>0.05). Compared to those relying on Medicare, patients with commercial (OR=0.68, 95% CI: 0.48-0.96) or out-of-pocket (self-pay) insurance (OR=0.22, 95% CI: 0.03-0.88) had lower odds of mortality. CONCLUSIONS: National trends of racial disparities in COVID-19 mortality may be partially explained by disparities in insurance.


Subject(s)
COVID-19 , Aged , Blacks , Female , Georgia/epidemiology , Healthcare Disparities , Humans , Male , Medicare , Middle Aged , United States
8.
Nano Today ; 40: 101280, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1386357

ABSTRACT

New vaccine technologies are urgently needed to produce safe and effective vaccines in a more timely manner to prevent future infectious disease pandemics. Here, we describe erythrocyte-mediated systemic antiviral immunization, a versatile vaccination strategy that boosts antiviral immune responses by using erythrocytes decorated with virus-mimetic nanoparticles carrying a viral antigen and a Toll-like receptor (TLR) agonist. As a proof of concept, polydopamine nanoparticles were synthesized via a simple in situ polymerization in which the nanoparticles were conjugated with the SARS-CoV-2 spike protein S1 subunit and the TLR7/8 agonist R848. The resulting SARS-CoV-2 virus-mimetic nanoparticles were attached to erythrocytes via catechol groups on the nanoparticle. Erythrocytes naturally home to the spleen and interact with the immune system. Injection of the nanoparticle-decorated erythrocytes into mice resulted in greater maturation and activation of antigen-presenting cells, humoral and cellular immune responses in the spleen, production of S1-specific immunoglobulin G (IgG) antibodies, and systemic antiviral T cell responses than a control group treated with the nanoparticles alone, with no significant negative side effects. These results show that erythrocyte-mediated systemic antiviral immunization using viral antigen- and TLR agonist-presenting polydopamine nanoparticles-a generalizable method applicable to many viral infections-is effective new approach to developing vaccines against severe infectious diseases.

10.
Risk Manag Healthc Policy ; 14: 1833-1841, 2021.
Article in English | MEDLINE | ID: covidwho-1229116

ABSTRACT

BACKGROUND: To explore the epidemiological characteristics of allergic rhinitis (AR) and allergic conjunctivitis (AC) based on the Internet big data. METHODS: The Baidu index (BDI) of keywords "allergic rhinitis" and "allergic conjunctivitis" in Mandarin, the daily pollen concentration (PC) released by the Beijing Meteorological Bureau and the volumes of outpatient visits (OV) of the Beijing Tongren Hospital (Beijing) and the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou) from 2017 to 2020 were obtained. The temporal and spatial changes of AR and AC were discussed. The correlations between BDI and PC/OV were analyzed by Spearman correlation analysis. RESULTS: The trends of BDI of "AR"/"AC" in Beijing showed obvious seasonal variations, but not in Guangzhou. The BDI of "AR" and "AC" was consistent with the OV in both cities (r1AR-BJ=0.580, P<0.001; r1AR-GZ=0.360, P=0.031; r1AC-BJ=0.885, P<0.001; r1AC-GZ=0.694, P<0.001). The BDI of "AR" and "AC" was highly consistent with the change of the PC in Beijing (r AR-Pollen=0.826, P<0.001; r AC-Pollen=0.564, P<0.001). The OV of AR in Beijing and Guangzhou decreased significantly in the first half of 2020, but there was no significant change in AC. In the first half of 2020, the OV of AC in Beijing was significantly higher than that of AR, while that of AC in Guangzhou was slightly higher than that of AR. CONCLUSION: The BDI could reflect the real-world situation to some extent and has the potential to predict the epidemiological characteristics of AR and AC. The BDI and OV of AR decreased significantly, but those of AC were still at a high level, during the COVID-19 pandemic, in the environment where most people in Beijing and Guangzhou wore masks without eye protection.

11.
International Journal of Social Science and Education Research ; 4(2):75-80, 2021.
Article in English | Airiti Library | ID: covidwho-1100340

ABSTRACT

This study explores what specific factors might influence Chinese college students' information transmission patterns on COVID‐19 pop‐science in China. Based on the risk perception theory and the situational theory of problem solving, an influence mechanism model of health information transmission behaviors online was constructed. This study investigated the public's information transmission behaviors of a particular type of health information on social medias during this global public health emergency, and on, specifically, why and how health information were transferred.

12.
Exp Ther Med ; 20(5): 13, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-771405

ABSTRACT

COVID-19 is caused by a novel coronavirus (2019-nCoV or SARS-CoV-2) and has become a global public health emergency. Rapid and accurate molecular diagnostic technologies are crucial for the screening, isolation, treatment, prevention and control of COVID-19. Currently, nucleic acid detection-based techniques and rapid diagnostic tests that detect antigens or antibodies specific to 2019-nCoV infections are the primary diagnostic tools. China National Medical Products Administration has opened a special channel for approval of new pharmaceuticals owing to urgent clinical needs, with 18 nucleic acid detection kits, 11 protein detection kits and 1 sequencing-related equipment and supporting software having been approved until April 23, 2020. The current review summarizes the application situation, advantages, disadvantages and associated technology improvement trends of molecular diagnostics for COVID-19 in China, identifies knowledge gaps and indicates future priorities for research in this field. The most effective way to prevent and control COVID-19 is early detection, diagnosis, isolation and treatment. In the clinical application of molecular diagnosis technology, it is necessary to combine pathogenic microbiology, immunology and other associated detection technologies, advocate the combination of multiple technologies, determine how they complement each other, enhance practicability and improve the ability of rapid and accurate diagnosis and differential diagnosis of COVID-19.

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