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2.
Sci Rep ; 14(1): 7787, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565933

RESUMO

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.


Assuntos
Anticoagulantes , Fibrilação Atrial , Humanos , Anticoagulantes/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/induzido quimicamente , Extração Dentária/efeitos adversos , Fibrilação Atrial/complicações , Administração Oral
3.
J Med Virol ; 96(4): e29600, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38591240

RESUMO

The lower respiratory system serves as the target and barrier for beta-coronavirus (beta-CoV) infections. In this study, we explored beta-CoV infection dynamics in human bronchial epithelial (HBE) organoids, focusing on HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2. Utilizing advanced organoid culture techniques, we observed robust replication for all beta-CoVs, particularly noting that SARS-CoV-2 reached peak viral RNA levels at 72 h postinfection. Through comprehensive transcriptomic analysis, we identified significant shifts in cell population dynamics, marked by an increase in goblet cells and a concurrent decrease in ciliated cells. Furthermore, our cell tropism analysis unveiled distinct preferences in viral targeting: HCoV-OC43 predominantly infected club cells, while SARS-CoV had a dual tropism for goblet and ciliated cells. In contrast, SARS-CoV-2 primarily infected ciliated cells, and MERS-CoV showed a marked affinity for goblet cells. Host factor analysis revealed the upregulation of genes encoding viral receptors and proteases. Notably, HCoV-OC43 induced the unfolded protein response pathway, which may facilitate viral replication. Our study also reveals a complex interplay between inflammatory pathways and the suppression of interferon responses during beta-CoV infections. These findings provide insights into host-virus interactions and antiviral defense mechanisms, contributing to our understanding of beta-CoV infections in the respiratory tract.


Assuntos
Coronavirus Humano OC43 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , Linhagem Celular , Brônquios , SARS-CoV-2 , Interferons , Organoides
4.
Sci Adv ; 10(9): eadk6425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416834

RESUMO

To develop a universal coronavirus (CoV) vaccine, long-term immunity against multiple CoVs, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, Middle East respiratory syndrome (MERS)-CoV, and future CoV strains, is crucial. Following the 2015 Korean MERS outbreak, we conducted a long-term follow-up study and found that although neutralizing antibodies and memory T cells against MERS-CoV declined over 5 years, some recovered patients exhibited increased antibody levels during the COVID-19 pandemic. This likely resulted from cross-reactive immunity induced by SARS-CoV-2 vaccines or infections. A significant correlation in antibody responses across various CoVs indicates shared immunogenic epitopes. Two epitopes-the spike protein's stem helix and intracellular domain-were highly immunogenic after MERS-CoV infection and after SARS-CoV-2 vaccination or infection. In addition, memory T cell responses, especially polyfunctional CD4+ T cells, were enhanced during the pandemic, correlating significantly with MERS-CoV spike-specific antibodies and neutralizing activity. Therefore, incorporating these cross-reactive and immunogenic epitopes into pan-CoV vaccine formulations may facilitate effective vaccine development.


Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , COVID-19/epidemiologia , Vacinas contra COVID-19 , Pandemias , Seguimentos , SARS-CoV-2 , Imunidade Adaptativa , Epitopos
5.
Medicine (Baltimore) ; 103(8): e37232, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394498

RESUMO

Teres minor denervation (TMD) has gained increasing attention in recent years, particularly with the advent of magnetic resonance imaging (MRI). The potential association between TMD and shoulder instability or rotator cuff tear remains a subject of interest in the orthopedic community. In this retrospective and cross-sectional study, authors aim to investigate the potential association between TMD and shoulder instability or rotator cuff tears. Authors retrospectively analyzed MRI findings from 105 patients with TMD, focusing on rotator cuff pathologies, posterior labrocapsular complex (PLCC) tears, and posteroinferior glenohumeral joint capsule alterations. Authors assessed the association between TMD and rotator cuff and PLCC tears. For the multivariate analysis, partial proportional odds models were constructed for subscapularis (SSC) and SSP tears. Rotator cuff tears were present in 82.9% of subjects, with subscapularis (SSC) tears being the most frequent (77.1%). A significant association was observed between TMD and rotator cuff pathology (P = .002). PLCC tears were found in 82.3% of patients, and humeral position relative to the osseous glenoid was noted in 60% of patients with TMD. A significant association was identified between TMD and shoulder instability or labral/capsular abnormalities (P < .001). More than half of the cases exhibited a long tethering appearance toward the axillary neurovascular bundle on T1-weighted sagittal images. Our findings suggest that TMD is significantly associated with rotator cuff tears and shoulder instability. This study highlights the importance of identifying and treating PLCC tears in patients with TMD to address shoulder instability. Further research is needed to elucidate the role of TMD in the pathogenesis of shoulder instability and rotator cuff pathology.


Assuntos
Instabilidade Articular , Lesões do Manguito Rotador , Articulação do Ombro , Humanos , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/patologia , Estudos Transversais , Estudos Retrospectivos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/etiologia , Instabilidade Articular/patologia , Ombro , Articulação do Ombro/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Denervação
6.
J Infect Dis ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114088

RESUMO

Immunocompromised COVID-19 patients were prospectively enrolled from March to November 2022 to understand the association between antibody responses and SARS-CoV-2 shedding. A total of 62 patients were analyzed and the results indicated a faster decline in genomic and subgenomic viral RNA in patients with higher neutralizing and S1-specific IgG antibodies (both P < 0.001). Notably, high neutralizing antibody levels were associated with a significantly faster decrease in viable virus cultures (P = 0.04). Our observations suggest the role of neutralizing antibodies in prolonged virus shedding in immunocompromised patients, highlighting the potential benefits of enhancing their humoral immune response through vaccination or monoclonal antibody treatments.

7.
Antioxidants (Basel) ; 12(12)2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38136157

RESUMO

Merremia umbellata Hallier f. (MU) has been used as an anti-inflammatory agent to treat burns and scales. However, the potential anti-inflammatory mechanisms of action of this plant have not been elucidated. This study aimed to assess the antioxidant and anti-inflammatory effects of the leaf and shoot of MU grown in Bangladesh. The MU extract exhibited antioxidant activities as demonstrated by DPPH and ABTS free-radical-scavenging activities and the total polyphenol and total flavonoid contents. MU extract significantly reduced the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 macrophage. Accordingly, the gene levels of inducible NO synthase and cyclooxygenase-2 were suppressed. The MU extract alleviated the LPS-induced expression of TLR4, NF-κB, and inflammatory cytokines (TNF-α, IL-6, and IL-1ß). The constituents of a MU extract were tentatively identified using UHPLC-PDA-QTOF/MS techniques. The main compounds were identified as 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, quercitrin, and 4,5-dicaffeoylquinic acid. Molecular docking analysis revealed that these compounds interact with TLR4 protein, with quercitrin showing the highest binding affinity among them. Overall, our findings demonstrate the antioxidant and in vitro anti-inflammatory activities of MU and its potential compounds to target the TLR4-NF-κB signaling pathway. These findings are potentially used to further explore promising natural food ingredients that are effective in regulating inflammation.

8.
J Med Virol ; 95(11): e29228, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-38009999

RESUMO

There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID-19). Adult COVID-19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real-time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3-7). Multivariable analysis revealed that B-cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID-19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33-65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85-96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID-19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B-cell-depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.


Assuntos
COVID-19 , Neoplasias Hematológicas , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudos Prospectivos , Vacinas contra COVID-19 , Neoplasias Hematológicas/complicações , Eliminação de Partículas Virais , RNA Viral/análise
9.
Nutrients ; 15(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37960298

RESUMO

Milk is a nutrient-rich food source, and among the various milks, breast milk is a nutrient source provided by mothers to newborns in many mammals. Exosomes are nano-sized membranous extracellular vesicles that play important roles in cell-to-cell communication. Exosomes originate from endogenous synthesis and dietary sources such as milk. Discovered through electron microscopy as floating vesicles, the existence of exosomes in human milk was confirmed owing to a density between 1.10 and 1.18 g/mL in a sucrose gradient corresponding to the known density of exosomes and detection of MHC classes I and II, CD63, CD81, and CD86 on the vesicles. To date, milk exosomes have been used for treating many diseases, including cancers, and are widely proposed as promising carriers for the delivery of chemotherapeutic agents. However, few studies on milk exosomes focus on geriatric health, especially sarcopenia and osteoporosis related to bone and muscle. Therefore, the present study focused on milk exosomes and their cargoes, which are potential candidates for dietary supplements, and when combined with drugs, they can be effective in treating musculoskeletal diseases. In this review, we introduce the basic concepts, including the definition, various sources, and cargoes of milk exosomes, and exosome isolation and characterization methods. Additionally, we review recent literature on the musculoskeletal system and milk exosomes. Since inflammation and oxidative stress underly musculoskeletal disorders, studies reporting the antioxidant and anti-inflammatory properties of milk exosomes are also summarized. Finally, the therapeutic potential of milk exosomes in targeting muscle and bone health is proposed.


Assuntos
Exossomos , Vesículas Extracelulares , Osteoporose , Recém-Nascido , Feminino , Animais , Humanos , Idoso , Leite , Leite Humano , Osso e Ossos , Mamíferos
10.
J Neuroinflammation ; 20(1): 267, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978545

RESUMO

BACKGROUND: Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood-brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis. METHODS: Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease. RESULTS: Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood-brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice. CONCLUSIONS: Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood-brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis.


Assuntos
Meningite Pneumocócica , Humanos , Animais , Camundongos , Barreira Hematoencefálica/metabolismo , Peixe-Zebra/metabolismo , Pericitos/metabolismo , Streptococcus pneumoniae , Citocinas/metabolismo , Quimiocinas/metabolismo , Leucócitos/metabolismo
12.
Int J Mol Sci ; 24(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37834245

RESUMO

Sarcopenia is a progressive muscle disease characterized by the loss of skeletal muscle mass, strength, function, and physical performance. Since the disease code was assigned, attention has been focused on natural products that can protect against muscle atrophy. Cibotium barometz (Cibotium Rhizome) has been used as an herbal medicine for the treatment of bone or joint diseases in Asian countries. However, no studies have identified the mechanism of action of Cibotium Rhizome on muscle atrophy related to sarcopenia at the site of myotubes. The aim of this study was to investigate the improvement effect of the ethanol extract of Cibotium Rhizome (ECR) on dexamethasone-induced muscle atrophy in an in vitro cell model, i.e., the C2C12 myotubes. High-performance liquid chromatography was performed to examine the phytochemicals in ECR. Seven peaks in the ECR were identified, corresponding to the following compounds: protocatechuic acid, (+)-catechin hydrate, p-coumaric acid, ellagic acid, chlorogenic acid, caffeic acid, and ferulic acid. In atrophy-like conditions induced by 100 µM dexamethasone for 24 h in C2C12, ECR increased the expression of the myosin heavy chain, p-Akt, the p-mammalian target of rapamycin (mTOR), p-p70S6K, and repressed the expression of regulated in development and DNA damage responses 1 (REDD1), kruppel-like factor 15 (KLF 15), muscle atrophy F-box, and muscle-specific RING finger protein-1 in C2C12. In addition, ECR alleviated dexamethasone-induced muscle atrophy by repressing REDD1 and KLF15 transcription in C2C12 myotubes, indicating the need for further studies to provide a scientific basis for the development of useful therapeutic agents using ECR to alleviate the effects of skeletal muscle atrophy or sarcopenia.


Assuntos
Sarcopenia , Traqueófitas , Rizoma/metabolismo , Sarcopenia/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Extratos Vegetais/química , Dexametasona/uso terapêutico , Músculo Esquelético/metabolismo
13.
Infect Chemother ; 55(3): 397-402, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37794578

RESUMO

An online survey was conducted in Korea to identify the unmet medical needs of people living with human immunodeficiency virus (HIV) (PLWH). Participants (n = 105) were mostly male (93.3%), aged >40 years (75.2%), and treated for ≥6 years post-diagnosis (61.9%). Most PLWH (71.4%) were very satisfied/satisfied with their HIV management. Areas of concern were quality of life (QoL) and mental health. Characteristics of a long-term therapeutic agent were 'low risk of resistance', 'high long-term viral suppression efficacy', and 'high degree of safety'. Pre-consultation QoL and mental health screening would be beneficial for the long-term success of HIV management.

14.
iScience ; 26(9): 107689, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37680469

RESUMO

SARS-CoV-2 variants have continuously emerged globally, including in South Korea. To characterize the molecular evolution of SARS-CoV-2 in South Korea, we performed phylogenetic and genomic recombination analyses using more than 12,000 complete genome sequences collected until October 2022. The variants in South Korea originated from globally identified variants of concern and harbored genetic clade-common and clade-specific amino acid mutations mainly around the N-terminal domain (NTD) or receptor binding domain (RBD) in the spike protein. Several point mutation residues in key antigenic sites were under positive selection persistently with changing genetic clades of SARS-CoV-2. Furthermore, we detected 17 potential genomic recombinants and 76.4% (13/17) retained the mosaic NTD or RBD genome. Our results suggest that point mutations and genomic recombination in the spike contributed to the molecular evolution of SARS-CoV-2 in South Korea, which will form an integral part of global prevention and control measures against SARS-CoV-2.

15.
Front Endocrinol (Lausanne) ; 14: 1195888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680887

RESUMO

Objective: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods: We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results: The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04-1.19), 28% (95% CI = 1.19-1.37), or 64% (95% CI = 1.41-1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion: The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.


Assuntos
Doenças Cardiovasculares , Gota , Insuficiência Cardíaca , Isquemia Miocárdica , Acidente Vascular Cerebral , Humanos , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Isquemia Miocárdica/complicações , Isquemia Miocárdica/epidemiologia , Gota/complicações , Gota/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , República da Coreia/epidemiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-37552177

RESUMO

AIM: To investigate the dimensional stability and quality of the alveolar ridge augmented using a synthetic bone block (SBB) at damaged extraction sockets. MATERIALS AND METHODS: Four participants were included in whom socket augmentation was performed using SBB and a collagen membrane. Intraoral scan (IOS) was performed before extraction (baseline), immediately postoperative (IP), and at 6 months (6M). Cone-beam computed tomography (CBCT) was performed at IP and 6M. At 6M, a trephine biopsy was obtained during implant placement and the sample was observed using synchrotron. Profilometric change of soft tissue was measured from the IOS data, hard tissue dimensional change was measured from the CBCT data and the bone quality from synchrotron data. RESULTS: There were minimal changes in the soft tissue profile between baseline and IP, baseline and 6M, and IP and 6M (0.11±1.08 and 0.02±0.8, and -0.65±0.82 mm3). Horizontal bone width measured at 1 mm increments from the augmented bone crest to 5 mm apically revealed only slight reduction (less than 1 mm) at all levels between IP and 6M. The augmented bone height was well maintained from IP until 6M (-0.21±0.53 mm). Synchrotron analysis revealed low to moderate bone quality after 6M (percentage new bone = 16.49±4.91). CONCLUSIONS: Augmentation of the damaged extraction socket using SBB is a viable technique, in which the dimensions of the augmented ridge can be maintained up to 6M. Further long term randomized clinical trial is needed.

17.
Antiviral Res ; 216: 105669, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37437781

RESUMO

Even though the World Health Organization announced the end of the COVID-19 pandemic as a global public health emergency on May 5, 2023, SARS-CoV-2 continues to pose a significant health threat worldwide, resulting in substantial numbers of infections and fatalities. This study investigated the antiviral potential of Z-FA-FMK (FMK), a novel host cathepsin L protease inhibitor, against SARS-CoV-2 infection using both in vitro and in vivo models. In vitro assessments of FMK against a diverse set of SARS-CoV-2 strains, including the Wuhan-like strain and nine variants, demonstrated potent inhibition with EC50 values ranging from 0.55 to 2.41 µM, showcasing similar or superior efficacy compared to FDA-approved antivirals nirmatrelvir (NTV) and molnupiravir (MPV). In vivo experiments using orally administered FMK (25 mg/kg) in SARS-CoV-2-infected K18 hACE2 transgenic mice revealed improved survival rates of 60% and accelerated recovery compared to NTV and MPV treatments. Additionally, FMK displayed a longer half-life (17.26 ± 8.89 h) than NTV and MPV in the mouse model. Due to its host-targeting mechanism, FMK offers potential advantages such as reduced drug resistance and broad-spectrum antiviral activity against multiple coronaviruses. These findings indicate that FMK may serve as a promising candidate for further clinical evaluation in the fight against SARS-CoV-2.


Assuntos
Anti-Infecciosos , COVID-19 , Animais , Camundongos , Humanos , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , SARS-CoV-2 , Catepsina L , Pandemias , Antivirais/farmacologia , Antivirais/uso terapêutico , Inibidores Enzimáticos
18.
Nutrients ; 15(11)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37299588

RESUMO

Sarcopenia is characterized by an age-related loss of skeletal muscle mass and function and has been recognized as a clinical disease by the World Health Organization since 2016. Substantial evidence has suggested that dietary modification can be a feasible tool to combat sarcopenia. Among various natural dietary ingredients, the present study focused on botanical and marine extracts, phytochemicals, and probiotics. Aims of this review were (1) to provide basic concepts including the definition, diagnosis, prevalence, and adverse effects of sarcopenia, (2) to describe possible pathological mechanisms including protein homeostasis imbalance, inflammation, mitochondrial dysfunction, and satellite cells dysfunction, and (3) to analyze recent experimental studies reporting potential biological functions against sarcopenia. A recent literature review for dietary ingredients demonstrated that protein homeostasis is maintained via an increase in the PI3K/Akt pathway and/or a decrease in the ubiquitin-proteasome system. Regulation of inflammation has primarily targeted inhibition of NF-κB signaling. Elevated Pgc-1α or Pax7 expression reverses mitochondrial or satellite cell dysfunction. This review provides the current knowledge on dietary components with the potential to assist sarcopenia prevention and/or treatment. Further in-depth studies are required to elucidate the role of and develop various dietary materials for healthier aging, particularly concerning muscle health.


Assuntos
Sarcopenia , Humanos , Sarcopenia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Dieta , Mitocôndrias/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Músculo Esquelético/metabolismo , Envelhecimento/fisiologia
19.
Front Cell Infect Microbiol ; 13: 1192512, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256107

RESUMO

Background: Immune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated. Methods: A nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant-confirmed patients. Results: A total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O2 support (18.4% vs. 27.1%, P < 0.001) and progressed to severe disease (4.0% vs. 8.0%, P < 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O2 support (HR 0.677, 95% CI 0.561-0.816) and progression to severe disease (HR 0.489, 95% CI 0.337-0.709). Among the 939 delta-confirmed patients, O2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O2 support (HR 0.963, 95% CI 0.697-1.329) or progression to severe disease (HR 0.665, 95% CI 0.349-1.268) in delta-confirmed group. Conclusions: Regdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Estudos Retrospectivos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais
20.
Food Nutr Res ; 672023.
Artigo em Inglês | MEDLINE | ID: mdl-37223261

RESUMO

Background: Obesity is a major risk factor for metabolic syndrome and a serious health concern worldwide. Various strategies exist to treat and prevent obesity, including dietary approaches using bioactive ingredients from natural sources. Objective: This study aimed to investigate the anti-obesity effect of whole-plant Allium macrostemon (also called as long-stamen chive) extract (AME) as a potential new functional food. Design: C57BL/6N mice were divided into three groups and fed either a control diet (CD), high-fat diet (HFD), or HFD with AME treatment (200 mg/kg BW daily) for 9 weeks. The mice in the CD and HFD groups were treated with vehicle control. Results: AME supplementation reduced HFD-induced body weight gain, fat mass, and adipocyte size. AME suppressed peroxisome proliferator-activated receptor γ and fatty acid synthase mRNA expression, indicating reduced adipogenesis and lipogenesis in adipose tissue. In addition, AME lowered inflammation in adipose tissue, as demonstrated by the lower number of crown-like structures, mRNA, and/or protein expression of macrophage filtration markers, as well as pro-inflammatory cytokines, including F4/80 and IL-6. Endoplasmic reticulum stress was also alleviated by AME administration in adipose tissue. Several phenolic acids known to have anti-obesity effects, including ellagic acid, protocatechuic acid, and catechin, have been identified in AME. Conclusion: By suppressing adipose tissue expansion and inflammation, AME is a potential functional food for the prevention and/or treatment of obesity and its complications.

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