Search

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and swelling. Several studies have demonstrated that RA fibroblast-like synovial cells (RA-FLS) play an important role in RA pathogenesis. Activated RA-FLS contribute to synovial inflammation by secreting inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. LMT-28 is derivative of oxazolidone and exerts anti-inflammatory effects on RA via IL-6 signaling pathway regulation. LMT-28 also regulates T cell differentiation in RA condition. However, the effect of LMT-28 on the migration and invasion of RA-FLS remains unknown. Kaempferol has been reported to have pharmacological effects on various diseases, such as inflammatory diseases, autoimmune diseases, and cancer. Additionally, kaempferol has been reported to inhibit RA-FLS migration and invasion, but it is not known about the therapeutic mechanism including molecular mechanism such as receptor. The present study aimed to investigate the synergistic effects of the combined treatment of LMT-28 and kaempferol on RA-FLS activation and RA pathogenesis in mouse model. LMT-28 and kaempferol co-administration inhibited RA disease severity and histological collapse in the joint tissues of CIA mice, as well as downregulated the levels of pro-inflammatory cytokines in mouse serum. Additionally, the combined treatment inhibited excessive differentiation of T helper 17 cells and osteoclasts. Furthermore, compared with single treatments, combined treatment showed enhanced inhibitory effects on the hyperactivation of IL-6-induced signaling pathway in RA-FLS. Combined treatment also inhibited RA-FLS cell proliferation, migration, and invasion and suppressed the expression of matrix metalloproteinase in RA-FLS. Furthermore, we confirmed that the combined treatment inhibited chondrocyte proliferation, migration, and invasion. In conclusion, our results suggest that the combined treatment of LMT-28 and kaempferol exerts a synergistic effect on the RA development via the regulation of IL-6-induced hyperactivation of RA-FLS. Furthermore, this study suggests that combination therapies can be an effective therapeutic option for arthritis.

Early-life malnutrition adversely affects nearly all organ systems, resulting in multiple physiological adaptations, including growth restriction and muscle and bone loss. Although there is growing evidence that probiotics effectively improve systemic growth under malnourished conditions in different animal models, our knowledge of the beneficial effects of probiotics on various organs is limited. Here, we show that Lactobacillus plantarum strain WJL (LpWJL) can mitigate skeletal muscle and bone loss in protein-malnourished juvenile mice. Mice on prenatal day 21 were fed a protein-malnourished (P-MAL) diet with or without LpWJL supplementation for six weeks. Compared to mice on the P-MAL diet alone, LpWJL supplementation significantly increased muscle mass and size, resulting in enhanced muscle strength and endurance capacity. Furthermore, LpWJL supplementation induced the expression of the key growth factor IGF-1 while decreasing muscle atrophy markers such as Atrogin-1 and MuRF-1, indicating potential mechanisms by which protein malnutrition-induced muscle wasting is counteracted. Additionally, LpWJL supplementation alleviated the reduction in cortical bone thickness and the deterioration of trabecular bone microstructure in the femur. Taken together, these results indicate that LpWJL can protect against skeletal muscle atrophy and compromised bone microarchitecture caused by protein malnutrition, providing novel insights into the potential therapeutic applications of probiotics for treating malnutrition-related disorders. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and swelling. Several studies have demonstrated that RA fibroblast-like synovial cells (RA-FLS) play an important role in RA pathogenesis. Activated RA-FLS contribute to synovial inflammation by secreting inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. LMT-28 is derivative of oxazolidone and exerts anti-inflammatory effects on RA via IL-6 signaling pathway regulation. LMT-28 also regulates T cell differentiation in RA condition. However, the effect of LMT-28 on the migration and invasion of RA-FLS remains unknown. Kaempferol has been reported to have pharmacological effects on various diseases, such as inflammatory diseases, autoimmune diseases, and cancer. Additionally, kaempferol has been reported to inhibit RA-FLS migration and invasion, but it is not known about the therapeutic mechanism including molecular mechanism such as receptor. The present study aimed to investigate the synergistic effects of the combined treatment of LMT-28 and kaempferol on RA-FLS activation and RA pathogenesis in mouse model. LMT-28 and kaempferol co-administration inhibited RA disease severity and histological collapse in the joint tissues of CIA mice, as well as downregulated the levels of pro-inflammatory cytokines in mouse serum. Additionally, the combined treatment inhibited excessive differentiation of T helper 17 cells and osteoclasts. Furthermore, compared with single treatments, combined treatment showed enhanced inhibitory effects on the hyperactivation of IL-6-induced signaling pathway in RA-FLS. Combined treatment also inhibited RA-FLS cell proliferation, migration, and invasion and suppressed the expression of matrix metalloproteinase in RA-FLS. Furthermore, we confirmed that the combined treatment inhibited chondrocyte proliferation, migration, and invasion. In conclusion, our results suggest that the combined treatment of LMT-28 and kaempferol exerts a synergistic effect on the RA development via the regulation of IL-6-induced hyperactivation of RA-FLS. Furthermore, this study suggests that combination therapies can be an effective therapeutic option for arthritis. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)–derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the association between methionine (MET) metabolism and endocrine function of the pituitary gland in patients with suprasellar region tumor. Materials and methods: Twenty patients with intracranial germinoma were included in this study. Initial staging and all surveillance MET PET/CT scans and comparable serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH) were analyzed. The patients were divided into two groups according to tumor location, with tumors in the suprasellar region (condition) or not (control). MET uptake of the pituitary gland (i.e., SUVR [standardized uptake value ratio]) and levels of FSH, LH, TSH were compared in the condition and control groups and in the before and after treatment phases of each group. Results: The SUVR in the control group was like that found in normal pituitary glands in previous studies, whereas the SUVR of the untreated condition group was high and that of treated condition group was low with significance compared to the control group. Serum levels of pituitary hormones in before and after treatment condition groups were significantly lower than those in the control group. The FSH and LH levels of curatively treated patients in the control group were positively correlated with SUVR with respective ß values of 3.71 and 0.98 (p <.001). The TSH level of the treated condition group was negatively correlated with SUVR (ß = -1.02, p <.001). Conclusion: This study is the first known investigation to examine the association between MET metabolism and endocrine function of the pituitary gland, and it confirmed that MET metabolism reflects endocrine function. A future study validating the result of correlation analysis is warranted. [ABSTRACT FROM AUTHOR]

PURPOSE:To evaluate the association between spontaneous reporting (SR) and the knowledge, attitude, and needs of community pharmacists (CPs), using a questionnaire following a conceptual model known as the mixed model of knowledge-attitude-practices and the satisfaction of needs. METHODS:Self-administered questionnaires were used with a nationwide convenience sample of CPs between September 1, 2014 and November 25, 2014 in Korea. The association between SR and the predictive factors was evaluated using multivariate logistic regression analysis. RESULTS:In total, 1,001 questionnaires were analyzed. The mean age of the respondents and the number of years spent in community pharmacy practice were 45.6 years and 15.3 years, respectively. CPs with experience of SR was 29.4%. Being older than 60 (ORadj, 0.16; 95% CI, 0.06-0.42), having prior experience with adverse drug reactions (ADR) (ORadj, 6.46; 95% CI, 2.46-16.98), having higher specific knowledge of SR (ORadj, 3.58; 95% CI, 1.96-6.56), and having less concern about the obstacles to SR (ORadj, 0.36; 95% CI, 0.23-0.57) were significant contributing factors to SR. The main obstacles to SR included perception of ADRs as 'not serious ADR' (77.9%), 'already well known ADR' (81.5%), and 'uncertain about causality' (73.3%). CPs without reporting experience had greater concerns related to the reporting method and the liability of the pharmacy than those with reporting experience (p

This document is a correction notice for a study titled "Risk factors for critical COVID-19 illness during Delta- and Omicron-predominant period in Korea; using K-COV-N cohort in the National health insurance service." The correction pertains to the funding statement, which was published incorrectly. The correct funding statement acknowledges that the study was conducted as part of a public-private joint research effort on COVID-19, co-hosted by the KDCA (Korea Disease Control and Prevention Agency) and the NHIS (National Health Insurance Service) in South Korea. The study also received support from the Korea National Institute of Health. The funders did not have any involvement in the study design, data collection and analysis, decision to publish, or manuscript preparation. [Extracted from the article]

Background & aims: Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. Methods: MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. Results: Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. Conclusions: We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms. [ABSTRACT FROM AUTHOR]

Background: Identifying acute ischemic stroke (AIS) among potential stroke cases is crucial for stroke research based on claims data. However, the accuracy of using the diagnostic codes of the International Classification of Diseases 10th revision was less than expected. Methods: From the National Health Insurance Service (NHIS) claims data, stroke cases admitted to the hospitals participating in the multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) during the study period with principal or additional diagnosis codes of I60-I64 on the 10th revision of International Classification of Diseases were extracted. The datasets were randomly divided into development and validation sets with a ratio of 7:3. A stroke identification algorithm using the claims data was developed and validated through the linkage between the extracted datasets and the registry database. Results: Altogether, 40,443 potential cases were extracted from the NHIS claims data, of which 31.7% were certified as AIS through linkage with the CRCS-K database. We selected 17 key identifiers from the claims data and developed 37 conditions through combinations of those key identifiers. The key identifiers comprised brain CT, MRI, use of tissue plasminogen activator, endovascular treatment, carotid endarterectomy or stenting, antithrombotics, anticoagulants, etc. The sensitivity, specificity, and diagnostic accuracy of the algorithm were 81.2%, 82.9%, and 82.4% in the development set, and 80.2%, 82.0%, and 81.4% in the validation set, respectively. Conclusions: Our stroke identification algorithm may be useful to grasp stroke burden in Korea. However, further efforts to refine the algorithm are necessary. [ABSTRACT FROM AUTHOR]