Localized apelin-17 analogue-bicelle interactions as a facilitator of membrane-catalyzed receptor recognition and binding.

The apelinergic system encompasses two peptide ligand families, apelin and apela, along with the apelin receptor (AR or APJ), a class A G-protein-coupled receptor. This system has diverse physiological effects, including modulating heart contraction, vasodilation/constriction, glucose regulation, and vascular development, with involvement in a variety of pathological conditions. Apelin peptides have been previously shown to interact with and become structured upon binding to anionic micelles, consistent with a membrane-catalyzed mechanism of ligand-receptor binding. To overcome the challenges of observing nuclear magnetic resonance (NMR) spectroscopy signals of a dilute peptide in biological environments, 19F NMR spectroscopy, including diffusion ordered spectroscopy (DOSY) and saturation transfer difference (STD) experiments, was used herein to explore the membrane-interactive behaviour of apelin. NMR-optimized apelin-17 analogues with 4-trifluoromethyl-phenylalanine at various positions were designed and tested for bioactivity through ERK activation in stably-AR transfected HEK 293 T cells. Far-UV circular dichroism (CD) spectropolarimetry and 19F NMR spectroscopy were used to compare the membrane interactions of these analogues with unlabelled apelin-17 in both zwitterionic/neutral and net-negative bicelle conditions. Each analogue binds to bicelles with relatively weak affinity (i.e., in fast exchange on the NMR timescale), with preferential interactions observed at the cationic residue-rich N-terminal and mid-length regions of the peptide leaving the C-terminal end unencumbered for receptor recognition, enabling a membrane-anchored fly-casting mechanism of peptide search for the receptor. In all, this study provides further insight into the membrane-interactive behaviour of an important bioactive peptide, demonstrating interactions and biophysical behaviour that cannot be neglected in therapeutic design.

Avenanthramide-C Shows Potential to Alleviate Gingival Inflammation and Alveolar Bone Loss in Experimental Periodontitis.

Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1ß, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1ß or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

Avenanthramide C as a novel candidate to alleviate osteoarthritic pathogenesis.

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1ß), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OAlike condition of chondrocytes in vitro. Avn-C restrained IL-1ß- mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1ß, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1ß treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis. [BMB Reports 2021; 54(10): 528-533].

Environmental tobacco smoke exposure and health disparities: 8-year longitudinal findings from a large cohort of Thai adults.

BACKGROUND: In rich countries, smokers, active or passive, often belong to disadvantaged groups. Less is known of tobacco patterns in the developing world. Hence, we seek out to investigate mental and physical health consequences of smoke exposure as well as tobacco-related inequality in transitional middle-income Thailand. METHODS: We studied a nationwide cohort of 87,151 middle-aged and older adults that we have been following for eight years (2005-2013) for emerging chronic diseases. Logistic regression was used to identify attributes associated with passive smoke exposure. Longitudinal associations between smoke exposure and wellbeing (SF-8) or psychological distress (Kessler 6) were investigated with multiple linear regression or multivariate logistic regression analysis. RESULTS: A high proportion of cohort members, especially females, were passive smokers at home and at public transport stations; males were more exposed at workplace and recreational places. We observed a social gradient with more passive smoking in poorer people. We also observed a dose response relationship linking graded smoke exposures (current, former, passive, non-exposed) to less wellbeing and more psychological distress (p-trend < 0.001). Female smokers in general had less wellbeing and more distress. CONCLUSION: Our findings add to current knowledge on the impact of active and passive smoking on health in a transitional economy. Promotion of smoking cessation programs both in public and at home could also potentially reduce adverse disparities in health and wellbeing in middle and lower income settings such as Thailand.

Health-Risk Factors and the Prevalence of Chronic Kidney Disease: Cross-Sectional Findings from a National Cohort of 87,143 Thai Open University Students.

BACKGROUND: Chronic kidney disease (CKD) is becoming a major health challenge worldwide as its aetiology has transferred from predominantly infectious disease to emerging chronic diseases, especially diabetes and hypertension. A rapid health-risk transition driven by economic development is transforming Thailand which is now becoming an ageing country where chronic diseases are a major health burden. METHODS: This study used the 2005 baseline cross-sectional dataset of 87,143 Thai Cohort Study members to investigate risk factors associated with CKD. Using multivariate logistic regression, we looked into the relationship between CKD and demographic and socioeconomic factors, personal health status and various health-related behaviours. RESULTS: The prevalence of CKD in men was lower than that in women (2.5% vs 2.7%). In both sexes, CKD is associated with ageing, cigarette smoking and drinking alcohol, having diabetes, high lipids and hypertension. In men, CKD was associated with living in rural areas, having a low income, a higher BMI, short sleeping and having Western fast food. In women, marriage is associated with a higher risk of CKD. CONCLUSIONS: CKD is strongly associated with ageing, underlying diseases, smoking and drinking. Hypertension, elevated lipids, or diabetes are all risk factors that could be prevented or detected and treated. The Ministry of Public Health should encourage Thai people to consume healthy food, maintain a normal weight, stop smoking and drink alcohol in moderation, all of which will help prevent CKD.