Sarcopenic obesity (SOB), which is closely related to being elderly as a feature of aging, is recently gaining attention because it is associated with many other age-related diseases that present as ...altered intercellular communication, dysregulated nutrient sensing, and mitochondrial dysfunction. Along with insulin resistance and inflammation as the core pathogenesis of SOB, autophagy has recently gained attention as a significant mechanism of muscle aging in SOB. Known as important cellular metabolic regulators, the AMP-activated protein kinase (AMPK) and the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) signaling pathways play an important role in autophagy, inflammation, and insulin resistance, as well as mutual communication between skeletal muscle, adipose tissue, and the liver. Furthermore, AMPK and PGC-1α signaling pathways are implicated in the gut microbiome-muscle axis. In this review, we describe the pathological link between SOB and its associated complications such as metabolic, cardiovascular, and liver disease, falls and fractures, osteoarthritis, pulmonary disease, and mental health via dysregulated autophagy controlled by AMPK and/or PGC-1α signaling pathways. Here, we propose potential treatments for SOB by modulating autophagy activity and gut dysbiosis based on plausible pathological links.
Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains ...poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.
Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become a worldwide pandemic. Symptoms range from mild fever to cough, fatigue, severe pneumonia, acute respiratory distress ...syndrome (ARDS), and organ failure, with a mortality rate of 2.2%. However, there are no licensed drugs or definitive treatment strategies for patients with severe COVID-19. Only antiviral or anti-inflammatory drugs are used as symptomatic treatments based on clinician experience. Basic medical researchers are also trying to develop COVID-19 therapeutics. However, there is limited systematic information about the pathogenesis of COVID-19 symptoms that cause tissue damage or death and the mechanisms by which the virus infects and replicates in cells. Here, we introduce recent knowledge of time course changes in viral titers, delayed virus clearance, and persistent systemic inflammation in patients with severe COVID-19. Based on the concept of drug reposition, we review which antiviral or anti-inflammatory drugs can effectively treat COVID-19 patients based on progressive symptoms and the mechanisms inhibiting virus infection and replication.
This study was conducted to evaluate the anti-obesity effects of long-term taurine supplementation in a mild obese ICR mouse model and to study the mechanism by which taurine induces weight loss. ...Three groups of male ICR mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with 2% taurine in drinking water for 28 weeks. Body weight was measured every week. Metabolic, behavioral, and physiological monitoring were carried out using PhenoMaster at 28 weeks. Interscapular brown fat (BAT), inguinal white fat tissue (WAT), and quadriceps muscle were analyzed and compared to assess the change of gene expression related to adipogenesis. Taurine supplementation showed the trend of anti-obesity effect in ICR mice fed an HFD for 28 weeks. HFD-fed mice did not show significant difference of oxygen consumption (VO
2
), energy expenditure (EE), respiratory exchange rate (RER), and locomotive activity compared with those of normal chow diet fed mice. The expression of adipogenesis-related genes such as PPAR-α, PPAR-γ, C/EBP-α, C/EBP-β, and AP2 increased in BAT and WAT, but not in muscle tissue. Taurine supplementation showed the downregulation of these genes in WAT but not in BAT or muscle. Consistently, the expression of taurine transporter (TauT) and adipocyte-specific genes such as adiponectin, leptin, and IL-6 was regulated in a similar pattern by taurine supplementation. Long-term taurine supplementation causes weight loss, most likely by inhibiting adipogenesis in WAT. TauT expression may be involved in the expression of various genes regulated by taurine supplementation.
Different adiponectin isoforms appear to be differentially involved in the pathogenesis of various diseases. The purpose of this study was to generate monoclonal antibodies (mAbs) specific to ...different adiponectin isoforms and investigate whether these mAbs have potential as therapeutic agents for such diseases.
Hybridoma cells producing monoclonal antibodies were generated and screened using enzyme-linked immunosorbent assay and Western blotting for the production of mAbs recognizing human adiponectin isoforms.
The mAb from hybridoma clone KH7-41 recognized both the middle molecular weight (MMW) (hexamer) and low molecular weight (LMW) (trimer) isoforms of adiponectin in human serum, whereas the KH7-33 mAb detected only MMW (hexamer) adiponectin. The KH4-8 clone recognized both the high molecular weight (HMW) (multimer) and MMW adiponectin isoforms. However, in mouse and rat sera, the abovementioned antibodies recognized only the MMW isomer. These mAbs also recognized adiponectin in various human tissues, such as lung, kidney, and adipose tissues, although the three mAbs had different staining intensities. The mAb from clone KH4-8 effectively inhibited increases in interleukin-6 (IL-6) and IL-8 expression in recombinant adiponectin-stimulated human osteoblasts and human umbilical vein endothelial cells. Also, the mAbs KH7-33 and KH4-8 significantly ameliorated rheumatic symptoms in a collagen-induced arthritis mouse model. This result suggests that these mAb treatments may ameliorate adiponectin-mediated inflammatory response.
mAbs against human adiponectin isomers can potentially be developed as therapeutic antibodies to target specific detrimental isoforms of adiponectin while maintaining the functions of beneficial isoforms.
Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of ...recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX).
This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period.
In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated.
This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks.
Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.
INTRODUCTION: The objective of this study was to determine the anti-inflammatory, nociceptive, and antiarthritic effects of piperine, the active phenolic component in black pepper extract. METHODS: ...The in vitro anti-inflammatory activity of piperine was tested on interleukin 1β (IL1β)-stimulated fibroblast-like synoviocytes derived form patients with rheumatoid arthritis. The levels of IL6, matrix metalloproteinase (MMPs), cyclo-oxygenase 2 (COX-2), and prostaglandin E2 (PGE2) were investigated by ELISA and RT-PCR analysis. The analgesic and antiarthritic activities of piperine were investigated on rat models of carrageenan-induced acute paw pain and arthritis. The former were evaluated with a paw pressure test, and the latter by measuring the squeaking score, paw volume, and weight distribution ratio. Piperine was administrated orally to rats at 20 and 100 mg/kg/day for 8 days. RESULTS: Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE2 in a dose dependant manner at concentrations of 10 to 100 μg/ml. In particular, the production of PGE2 was significantly inhibited even at 10 μg/ml of piperine. Piperine inhibited the migration of activator protein 1 (AP-1), but not nuclear factor (NF)κB, into the nucleus in IL1β-treated synoviocytes. In rats, piperine significantly reduced nociceptive and arthritic symptoms at days 8 and 4, respectively. Histological staining showed that piperine significantly reduced the inflammatory area in the ankle joints. CONCLUSIONS: These results suggest that piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Thus, piperine should be further studied with regard to use either as a pharmaceutical or as a dietary supplement for the treatment of arthritis.
Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm ...whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction.
Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed.
A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05).
Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.
Introduction
Accurate clinical decision‐making of dentists should be based on their knowledge and experience. In the past 10 years, interest in competency‐based dentistry education has rapidly ...increased, but there has been little attention paid to methods of improving dental education competency. The purpose of this study was to develop a clinical presentation education model that provides opportunities for students to practice problem‐solving from the moment they greet the patient so that students can obtain the practical experience of competency‐based education and the effectiveness of this model can be confirmed through pilot test.
Methods
This article is divided two parts: First, developing the clinical presentation dental education model (CPDEM) and Second, a pilot study adopted CPDEM. To confirm the effectiveness of this model, the students' satisfaction, their perception of self‐achievement were analysed.
Results
Clinical presentation dental education model has been developed to provide practice‐related education experience and provide linkage between basic science and clinical science. The result of applying this education model to 10 students as a pilot test was shown an overall high satisfaction level. In addition, self‐achievement students’ reported of all intended competencies was higher than for non‐participating students of this model.
Conclusions
This study focuses on practical education centring on clinical presentation. This model could get a meaningful and realistic experiences through the practice using clinical presentation of patients, use their metacognition for organizing and memorizing the patient's case by using concept map. It can be used as a future instructional method to enhance students' competency.
To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with ...rheumatoid arthritis (RA).
This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100.
A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively).
Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101.
ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.
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