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1.
J Clin Med ; 11(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35054037

RESUMO

BACKGROUND: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. RESULT: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. INTERPRETATION: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years.

3.
Ann Lab Med ; 42(1): 36-46, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374347

RESUMO

Background: The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem. Recently, the occurrence of CPE has increased globally, but epidemiological patterns vary across region. We report the trends in the genotypic distribution and antimicrobial susceptibility of CPE isolated from rectal and clinical samples during a four-year period. Methods: Between January 2016 and December 2019, 1,254 nonduplicated CPE isolates were obtained from four university hospitals in Korea. Carbapenemase genotypes were determined by multiplex real-time PCR. Antimicrobial susceptibility was profiled using the Vitek 2 system (bioMérieux, Hazelwood, MO, USA) or MicroScan Walkaway-96 system (Siemens West Sacramento, CA, USA). The proportions of carbapenemase genotypes and nonsusceptibility were analyzed using Pearson's chi-square test. Results: Among the 1,254 CPE isolates, 486 (38.8%), 371 (29.6%), 357 (28.5%), 8 (0.6%), 8 (0.6%), and 24 (1.9%) were Klebsiella pneumoniae carbapenemase (KPC), oxacillinase (OXA)-48-like, New Delhi metallo-ß-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-ß-lactamase (VIM), and multiple producers, respectively. The predominant species was K. pneumoniae (72.6%), followed by Escherichia coli (6.5%). More than 90% of the isolates harboring KPC, NDM, and OXA-48-like were nonsusceptible to cephalosporins, aztreonam, and carbapenems. Conclusions: The impact of CPE is primarily due to KPC-, NDM-, and OXA-48-like-producing K. pneumoniae isolates. Isolates carrying these carbapenemase are mostly multidrug-resistant. Control strategies based on these genotypic distributions and antimicrobial susceptibilities of CPE isolates are required.


Assuntos
Anti-Infecciosos , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/epidemiologia , Genótipo , Hospitais Universitários , Humanos , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , República da Coreia , beta-Lactamases/genética
4.
Ann Lab Med ; 42(1): 96-99, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374354

RESUMO

The sensitivity of molecular diagnostics could be affected by nucleotide variants in pathogen genes, and the sites affected by such variants should be monitored. We report a single-nucleotide variant (SNV) in the nucleocapsid (N) gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., G29179T, which impairs the diagnostic sensitivity of the Xpert Xpress SARS-CoV-2 assay (Cepheid, Sunnyvale, CA, USA). We observed significant differences between the threshold cycle (Ct) values for envelope (E) and N genes and confirmed the SNV as the cause of the differences using Sanger sequencing. This SNV, G29179T, is the most prevalent in Korea and is associated with the B.1.497 virus lineage, which is dominant in Korea. Clinical laboratories should be aware of the various SNVs in the SARS-CoV-2 genome and consider their potential effects on the diagnosis of coronavirus disease 2019.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Técnicas de Diagnóstico Molecular , Nasofaringe , Nucleotídeos , Prevalência , República da Coreia , Sensibilidade e Especificidade
6.
Sci Rep ; 11(1): 20740, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671046

RESUMO

Assembling high-quality microbial genomes using only cost-effective Nanopore long-read systems such as Flongle is important to accelerate research on the microbial genome and the most critical point for this is the polishing process. In this study, we performed an evaluation based on BUSCO and Prokka gene prediction in terms of microbial genome assembly for eight state-of-the-art Nanopore polishing tools and combinations available. In the evaluation of individual tools, Homopolish, PEPPER, and Medaka demonstrated better results than others. In combination polishing, the second round Homopolish, and the PEPPER × medaka combination also showed better results than others. However, individual tools and combinations have specific limitations on usage and results. Depending on the target organism and the purpose of the downstream research, it is confirmed that there remain some difficulties in perfectly replacing the hybrid polishing carried out by the addition of a short-read. Nevertheless, through continuous improvement of the protein pores, related base-calling algorithms, and polishing tools based on improved error models, a high-quality microbial genome can be achieved using only Nanopore reads without the production of additional short-read data. The polishing strategy proposed in this study is expected to provide useful information for assembling the microbial genome using only Nanopore reads depending on the target microorganism and the purpose of the research.

7.
Int J Med Sci ; 18(15): 3395-3402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522166

RESUMO

Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.


Assuntos
COVID-19/diagnóstico por imagem , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , COVID-19/sangue , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Contagem de Linfócitos , Oxigênio/uso terapêutico , Prognóstico
8.
Jpn J Infect Dis ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34588372

RESUMO

Using bacterial pan-genome obtained through whole genome sequencing (WGS), coding DNA sequences (CDSs) can be clustered into pan-genome orthologous groups (POGs). We aimed to investigate comparative genomic features of Streptococcus canis based on POG analysis and to determine CDSs specific to prevalent sequence type (ST) 9. Twenty WGS datasets on S. canis strains from invasive and non-invasive specimens were retrieved from the National Center for Biotechnology Information Assembly database. Based on the WGS data, we performed comparative genome hybridization (CGH), pan- and core-genome prediction, Venn diagram test with five ST9 strains, and phylogenetic analysis, with ST determination. We compared the CDSs between seven ST9 and 13 non-ST9 strains. We observed genomic diversity based on CGH and Venn diagram. The predicted pan- and core-genomes contained 4,772 and 1,403 genes, respectively. We found five clades consisting of different STs (ST1, ST44/2, ST13/14, ST21/15/41, and ST9) based on phylogenetic tree. There were differences in four pathways (DNA restriction-modification system, DNA-mediated transposition, extracellular region, and response to oxidative stress) regulated by CDSs specific to ST9. Our findings describe genomic diversity in CGH and Venn diagram, pan- and core-genomes, five clades of genomes consisting of different STs, and unique CDS features associated to ST9.

9.
Diagnostics (Basel) ; 11(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34574024

RESUMO

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been widely used for microbial identification, because of its speed and accuracy, since its introduction to clinical microbiology laboratories. In this study, we evaluated the performance of ASTA MicroIDSys, a newly developed MALDI-TOF, and compared it with the widely used Bruker Biotyper. Microbial identification with the Bruker Biotyper system was performed by using a direct smear method and the Bruker Biotyper database (reference library version 6.0.0.0). The isolates were also tested in parallel, using the ASTA MicroIDSys system with a direct smear method and the MicroIDSys database, CoreDB v1.26. A total of 914 clinical isolates were recovered from the clinical specimens. Identical results with confidence scores (≥2.0, for the Bruker Biotyper) and acceptable scores (≥140 for the ASTA MicroIDSys) were obtained for 840 (91.9%) isolates. The minor errors were defined as misidentification at the species level, and the rate was 1.1% (9/792) for Bruker Biotyper and 1.6% (13/792) for ASTA MicroIDSys. Major errors were defined as misidentification at the genus level, and the rate was 0.3% (2/792) for both Bruker Biotyper and ASTA MicroIDSys. ASTA MicroIDSys showed reliable performance for microbial identification, which was comparable to that of the Bruker Biotyper. Therefore, ASTA MicroIDSys can be applied for the identification of microorganisms in clinical microbiology laboratories.

10.
Vaccines (Basel) ; 9(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199359

RESUMO

South Korea has experienced FMD outbreaks almost every year since 2014. Therefore, a novel local vaccine that can cover various topotypes of viruses is required. Two virus strains, O/Boeun/SKR/2017 and A/Yeoncheon/SKR/2017, were cultured up to the pilot scale based on the optimized conditions set up on the flask scale. FMDV particles (146S) of 2 µg/mL or more were obtained from the virus culture supernatant using a 100 L bioreactor. The viruses were fully inactivated using binary ethylenimine within 16 h through two inactivation cycles and mixed with an adjuvant into a bivalent vaccine (types O and A) consisting of 15 µg viruses per strain. The experimental bivalent vaccine showed a broad spectrum of high neutralizing antibody titers against heterologous viruses, including type O Cathay strain and type A Asia topotypes, except for GVII. The 50% protective dose was determined as 12.5 for O/Boeun/SKR/2017 and 15.6 for A/Yeoncheon/SKR/2017. Collectively, we expect that the bivalent vaccine could protect against FMDV types O and A circulating in South Korea and neighboring countries. To our knowledge, this is the first report demonstrating that the vaccine strains could be successfully scaled-up to a 100 L bioreactor, with the determination of its protective efficacy in pigs.

11.
Int J Biol Sci ; 17(8): 2112-2123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34131410

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.

12.
Int J Biol Macromol ; 183: 1669-1675, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34023371

RESUMO

Polyhydroxybutyrate (PHB) is a biodegradable plastic with physical properties similar to petrochemically derived plastics. Here, Shewanella marisflavi BBL25 was engineered by inserting the pLW487 vector containing polyhydroxyalkanoates synthesis genes from Ralstonia eutropha H16. Under optimal conditions, the engineered S. marisflavi BBL25 produced 1.99 ± 0.05 g/L PHB from galactose. The strain showed high tolerance to various inhibitors and could utilize lignocellulosic biomass for PHB production. When barley straw hydrolysates were used as a carbon source, PHB production was 3.27 ± 0.19 g/L. In addition, PHB production under the microbial fuel cell system was performed to confirm electricity coproduction. The maximum electricity current output density was 1.71 mA/cm2, and dry cell weight (DCW) and PHB production were 11.4 g/L and 6.31 g/L, respectively. Our results demonstrated PHB production using various lignocellulosic biomass and the feasibility of PHB and electricity production, simultaneously, and it is the first example of PHB production in engineered Shewanella.


Assuntos
Cupriavidus necator/genética , Engenharia Genética/métodos , Hidroxibutiratos/metabolismo , Poli-Hidroxialcanoatos/genética , Shewanella/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biomassa , Galactose/metabolismo , Hordeum/química , Hidrólise , Plasmídeos/genética , Poli-Hidroxialcanoatos/biossíntese , Shewanella/genética
13.
Biomolecules ; 11(3)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807121

RESUMO

Gonorrhea is one of the most common, but still hidden and insidious, sexually transmitted diseases caused by Neisseria gonorrhoeae (gonococci). However, the diagnosis and treatment of gonorrhea are hampered by antigenic variability among gonococci, the lack of acquired immunity, and antimicrobial resistance. Further, strains resistant to cephalosporins, including ceftriaxone, the last line of defense, represent a growing threat, which prompted us to develop gonococci-specific diagnostic antibodies with broad-spectrum binding to gonococci strains to generate gonorrhea-detecting reagents. This study reports the identification of gonococci antibodies via bio-panning on gonococci cells using scFv-phage libraries. Reformatting the lead scFv-phage Clones 1 and 4 to a multivalent scFv1-Fc-scFv4 maxibody increased the sensitivity by up to 20-fold compared to the single scFv-Fc (maxibody) alone. Moreover, the multivalent maxibody showed broader cross-reactivity with clinical isolates and the ceftriaxone antibiotic-resistant World Health Organization (WHO) reference strain L. In contrast, the selected antibodies in the scFv-phage, maxibody, and multivalent maxibody did not bind to N. sicca, N. meningitides, and N. lactamica, suggesting the clinical and pharmaceutical diagnostic value of these selected antibodies for gonorrheal infections. The present study illustrates the advantages and potential application of multivalent maxibodies to develop rapid and sensitive diagnostic reagents for infectious diseases and cancer.


Assuntos
Gonorreia/diagnóstico , Gonorreia/microbiologia , Neisseria gonorrhoeae/patogenicidade , Humanos , Neisseria gonorrhoeae/imunologia
14.
Vaccines (Basel) ; 9(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809252

RESUMO

A local virus isolate, O/SKR/JC/2014 (O JC), has been considered as a candidate vaccine strain in the development of a domestic foot-and-mouth disease (FMD) vaccine in Korea. However, producing and preserving a sufficient quantity of intact vaccine antigens from the O JC strain was difficult owing to its distinctive structural instability compared to other candidate vaccine strains. Based on this feature, the O JC strain was adopted as a model virus for the stabilization study to determine the optimal stabilizer composition, which enables long-term storage of the FMD vaccine antigen in both aqueous and frozen phases. In contrast to O JC vaccine antigens stored in routinely used Tris-buffered or phosphate-buffered saline, those stored in Tris-KCl buffer showed extended shelf-life at both 4 °C and -70 °C. Additionally, the combined application of 10% sucrose and 5% lactalbumin hydrolysate could protect O JC 146S particles from massive structural breakdown in an aqueous state for up to one year. The stabilizer composition was also effective for other FMDV strains, including serotypes A and Asia 1. With this stabilizer composition, FMD vaccine antigens could be flexibly preserved during the general production process, pending status under refrigeration and banking under ultrafreezing.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33871217

RESUMO

BACKGROUND: Erythema nodosum and erythema induratum of Bazin are similar inflammatory diseases of the lower extremities. These are clinically distinguishable entities, though overlap can occur. Both diseases are reported to be related to Mycobacterium tuberculosis infection, but it is very difficult to identify Mycobacterium tuberculosis in skin lesions. AIM: This study aimed to develop a new nested polymerase chain reaction targeting the IS6110 insertion sequence of M. tuberculosis to improve the M. tuberculosis detection rate in skin lesions of erythema nodosum or erythema induratum of Bazin. METHODS: From May 2016 to Jan 2018, 14 patients with clinically suspicious erythema nodosum or erythema induratum were enrolled in the study. Two cases were classified as erythema nodosum and 12 as erythema induratum. Individual patients were subjected to a 4-mm punch biopsy, and their venous whole blood was sampled immediately after diagnosis. RESULTS: Eight patients were tested for M. tuberculosis using QuantiFERON, of which seven (87.5%) were positive. IS6110-nested polymerase chain reaction on all 14 patients identified 11 (78.6%) positive cases. Four of the eight (50%) individuals tested with QuantiFERON were also positive in the IS6110 nested polymerase chain reaction. The difference between the outcomes of the QuantiFERON and the IS6110-nested polymerase chain reaction tests was not statistically significant. There was also no significant agreement between the results of both assays. Sequencing the IS6110-nested polymerase chain reaction products showed a 97%-100% nucleotide sequence identity with the H37Rv genome. CONCLUSION: It is important to test for tuberculosis in patients with multiple tender subcutaneous nodules on their lower extremities in high-burden tuberculosis countries like Korea. LIMITATIONS: We need to register more suspicious patients to verify the association between erythema nodosum/erythema induratum of Bazin and M. tuberculosis. Furthermore, it is necessary to improve the more sensitive polymerase chain reaction technique to identify M. tuberculosis directly in cutaneous lesions.

16.
Antibiotics (Basel) ; 10(4)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917043

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent bacterial pathogens and continues to be a leading cause of morbidity and mortality worldwide. MRSA is a commensal bacterium in humans and is transmitted in both community and healthcare settings. Successful treatment remains a challenge, and a search for new targets of antibiotics is required to ensure that MRSA infections can be effectively treated in the future. Most antibiotics in clinical use selectively target one or more biochemical processes essential for S. aureus viability, e.g., cell wall synthesis, protein synthesis (translation), DNA replication, RNA synthesis (transcription), or metabolic processes, such as folic acid synthesis. In this review, we briefly describe the mechanism of action of antibiotics from different classes and discuss insights into the well-established primary targets in S. aureus. Further, several components of bacterial cellular processes, such as teichoic acid, aminoacyl-tRNA synthetases, the lipid II cycle, auxiliary factors of ß-lactam resistance, two-component systems, and the accessory gene regulator quorum sensing system, are discussed as promising targets for novel antibiotics. A greater molecular understanding of the bacterial targets of antibiotics has the potential to reveal novel therapeutic strategies or identify agents against antibiotic-resistant pathogens.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33666028

RESUMO

BACKGROUND: Erythema nodosum and erythema induratum of Bazin are similar inflammatory diseases of the lower extremities. These are clinically distinguishable entities, though overlap can occur. Both diseases are reported to be related to Mycobacterium tuberculosis infection, but it is very difficult to identify Mycobacterium tuberculosis in skin lesions. AIM: This study aimed to develop a new nested polymerase chain reaction targeting the IS6110 insertion sequence of M. tuberculosis to improve the M. tuberculosis detection rate in skin lesions of erythema nodosum or erythema induratum of Bazin. METHODS: From May 2016 to Jan 2018, 14 patients with clinically suspicious erythema nodosum or erythema induratum were enrolled in the study. Two cases were classified as erythema nodosum and 12 as erythema induratum. Individual patients were subjected to a 4-mm punch biopsy, and their venous whole blood was sampled immediately after diagnosis. RESULTS: Eight patients were tested for M. tuberculosis using QuantiFERON, of which seven (87.5%) were positive. IS6110-nested polymerase chain reaction on all 14 patients identified 11 (78.6%) positive cases. Four of the eight (50%) individuals tested with QuantiFERON were also positive in the IS6110 nested polymerase chain reaction. The difference between the outcomes of the QuantiFERON and the IS6110-nested polymerase chain reaction tests was not statistically significant. There was also no significant agreement between the results of both assays. Sequencing the IS6110-nested polymerase chain reaction products showed a 97%-100% nucleotide sequence identity with the H37Rv genome. CONCLUSION: It is important to test for tuberculosis in patients with multiple tender subcutaneous nodules on their lower extremities in high-burden tuberculosis countries like Korea. LIMITATIONS: We need to register more suspicious patients to verify the association between erythema nodosum/erythema induratum of Bazin and M. tuberculosis. Furthermore, it is necessary to improve the more sensitive polymerase chain reaction technique to identify M. tuberculosis directly in cutaneous lesions.

18.
Cells ; 10(2)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572945

RESUMO

Foot-and-mouth disease (FMD) is a highly contagious disease caused by FMD virus (FMDV) in cloven-hoofed animals. Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are representative receptors in the cytoplasm for the detection of viral RNA and trigger antiviral responses, leading to the production of type I interferon. Although MDA5 is a crucial receptor for sensing picornavirus RNA, the interplay between MDA5 and FMDV is relatively unknown compared to the interplay between RIG-I and FMDV. Here, we observed that the FMDV infection inhibits MDA5 protein expression. Of the non-structural proteins, the Lb and 3C proteinases (Lbpro and 3Cpro) were identified to be primarily responsible for this inhibition. However, the inhibition by 3Cpro was independent of proteasome, lysosome and caspase-dependent pathway and was by 3C protease activity. A direct interaction between 3Cpro and MDA5 protein was observed. In conclusion, this is the first report that 3Cpro inhibits MDA5 protein expression as a mechanism to evade the innate immune response during FMDV infection. These results elucidate the pathogenesis of FMDV and provide fundamental insights for the development of a novel vaccine or therapeutic agent.


Assuntos
Proteases Virais 3C/metabolismo , Vírus da Febre Aftosa/imunologia , Evasão da Resposta Imune , Imunidade Inata , Helicase IFIH1 Induzida por Interferon/metabolismo , Animais , Caspases/metabolismo , Catálise , Proteína DEAD-box 58/metabolismo , Regulação para Baixo , Células HEK293 , Humanos , Interferons/genética , Interferons/metabolismo , Lisossomos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Transdução de Sinais , Suínos , Transcrição Genética
19.
Theranostics ; 11(1): 316-329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391477

RESUMO

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/complicações , Síndrome da Liberação de Citocina/imunologia , Citocinas/metabolismo , Imunossupressores/uso terapêutico , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Azetidinas/farmacologia , Azetidinas/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/virologia , Ensaios Clínicos como Assunto , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Humanos , Imunossupressores/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Purinas/farmacologia , Purinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , SARS-CoV-2/imunologia , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resultado do Tratamento
20.
Theranostics ; 11(3): 1207-1231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391531

RESUMO

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.


Assuntos
Antivirais/uso terapêutico , COVID-19/terapia , Infecções por Coronavirus/terapia , Síndrome Respiratória Aguda Grave/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Animais , COVID-19/mortalidade , Carbamatos/uso terapêutico , Infecções por Coronavirus/mortalidade , Modelos Animais de Doenças , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Imidazóis/uso terapêutico , Imunização Passiva/métodos , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome Respiratória Aguda Grave/mortalidade , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Valina/uso terapêutico
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