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.

Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss.

Oral diseases exhibit a significant association with metabolic syndrome, including dyslipidemia. However, direct evidence supporting this relationship is lacking, and the involvement of cholesterol metabolism in the pathogenesis of periodontitis (PD) has yet to be determined. In this study, we showed that high cholesterol caused periodontal inflammation in mice. Cholesterol homeostasis in human gingival fibroblasts was disrupted by enhanced uptake through C-X-C motif chemokine ligand 16 (CXCL16), upregulation of cholesterol hydroxylase (CH25H), and the production of 25-hydroxycholesterol (an oxysterol metabolite of CH25H). Retinoid-related orphan receptor α (RORα) mediated the transcriptional upregulation of inflammatory mediators; consequently, PD pathogenesis mechanisms, including alveolar bone loss, were stimulated. Our collective data provided direct evidence that hyperlipidemia is a risk factor for PD and supported that inhibition of the CXCL16-CH25H-RORα axis is a potential treatment mechanism for PD as a systemic disorder manifestation.

Cu2O/Fe3O4/UiO-66 nanocomposite as an efficient fenton-like catalyst: Performance in organic pollutant degradation and influencing factors based machinelearning.

The persistent presence of organic pollutants like dyes in water environment necessitates innovative approaches for efficient degradation. In this research, we developed an advanced hybrid catalyst by combining metal oxides (Cu2O, Fe3O4) with UiO-66, serving as a heterogeneous Fenton catalyst for for efficient RB19 breakdown in water with H2O2. The control factors to the catalytic behavior were also quantified by machine learning. Experimental results show that the catalytic performance was much better than its individual components (P < 0.05 & non-zero 95% C.I). The improved catalytic efficiency was linked to the occurrence of active metal centers (Fe, Cu, and Zr), with Cu(I) from Cu2O playing a crucial role in promoting increased production of HO•. Also, UiO-66 served as a catalyst support, attracting pollutants to the reaction center, while magnetic Fe3O4 aids catalyst recovery. The optimal experimental parameters for best performance were pH at 7, catalyst loading of 1.6 g/L, H2O2 strength of 0.16 M, and reaction temperature of 25 °C. The catalyst can be magnetically separated and regenerated after five recycling times without significantly reducing catalytic activity. The reaction time and pH were ranked as the most influencing factors on catalytic efficiency via Random Forest and SHapley Additive exPlanations models. The findings show that developed catalyst is a suitable candidate to remove dyes in water by Fenton heterogeneous reaction.

Assessment of the Chemical Profile and Potential Medical Effects of a Flavonoid-Rich Extract of Eclipta prostrata L. Collected in the Central Highlands of Vietnam.

Eclipta prostrata L. (EPL), a medicinal plant, is widely utilized in the central highlands of Vietnam. This study aims to assess the chemical profile and potential medical effects of an EPL extract rich in flavonoids. A total of 36 secondary metabolites were identified from the EPL extract through GC-MS and UHPLC-UV analysis. Among them, 15 volatile compounds and several phenolic and flavonoid chemicals, including salicylic acid, epicatechin gallate, isovitexin, and apigetrin, were reported in EPL extract for the first time. This herbal extract demonstrated moderate inhibition against α-amylase and α-glucosidase, and high anti-oxidant and anti-acetylcholinesterase activities (IC50 = 76.8 ± 0.8 µg/mL). These promising attributes can be likely attributed to the high levels of major compounds, including wedelolactone (1), chlorogenic acid (3), epicatechin gallate (6), salicylic acid (8), isovitexin (9), apigetrin (11), and myricetin (12). These findings align with the traditional use of EPL for enhancing memory and cognitive function, as well as its potential benefits in diabetes management. The results of the molecular docking study reveal that the major identified compounds (1, 6, 9, and 11) showed a more effective acetylcholinesterase inhibitory effect than berberine chloride, with good binding energy (DS values, -12.3 to -14.3 kcal/mol) and acceptable values of RMSD (1.02-1.67 Å). Additionally, almost all the identified major compounds exhibited good ADMET properties within the required limits.

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.

Differential pulse voltammetry determination of salbutamol using disulfite tungsten/activated carbon modified glassy carbon electrode.

In the present article, the disulfide tungsten/activated carbon derived from Eichhornia crassipes (WS2/AC) was synthesized by the hydrothermal process. The received materials were examined by X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray - mapping, and nitrogen adsorption/desorption isotherms. The morphology of WS2/AC was tailored to have a micro/meso/macro structure that facilized large electric conductivity and quick ion diffusion. The WS2/AC sample was used as an electrode modifier for developing an electrochemical sensor for salbutamol detection. WS2/AC exhibited excellent oxidation toward salbutamol. Through some optimized conditions, the electrochemical signal of the proposed sensor varied linearly to the salbutamol concentration ranging from 1 to 210 µM with a low LOD (detection limit) of 0.52 µM. The developed sensor showed several merits: easy producing, convenient usage, fabulous selectivity, and good repeatability as well as reproducibility. Finally, the suggested technique can be applied to determine salbutamol in people's biological fluid with satisfactory recoveries of 98.5-104.4% and without statistics different from standard HPLC.

A review on the determination of veterinary drug residues in food products.

In this paper, we discuss veterinary medicine and its applications in the food industry as well as the risk to the health of humans and animals caused by these residues. We review how the veterinary residues enter and cause some detrimental effects. We also mention two techniques to determine the residue of veterinary medications that exist in food originating from animals, including classic and advanced techniques. Finally, we discuss the potential of various developed methods and compare them with some traditional techniques.

A state-of-the-art review on the nanomaterial-based sensor for detection of venlafaxine.

Venlafaxine (denoted as VFX), a member of the most extensively prescribed antidepressants, is used to handle major depressive disorder, panic disorder and anxiety. This medication affects brain chemistry, which could cause an imbalance in depressed people. VFX and its metabolites, on the other hand, are pollutants in the water environment. Through movement and transformation in several procedures like adsorption, photolysis, hydrolysis and biodegradation, they have harmed living creatures, resulting in the enhancement of diverse active chemicals found in the environment. As a result, determining VFX at modest concentrations with excellent sensitivity, specificity and repeatability are critical. To quantify VFX, various analytical methodologies have been developed. Electroanalytical processes, on the other hand, have piqued interest because of their superior benefits over traditional techniques such as speed, sensitivity, directness and affordability. Subsequently, the purpose of this article is to show how to determine VFX electrochemically using a wide range of electrodes, including CPE, GCE, MCE, SPE, PGE and ISE.

A state-of-the-art review on graphene-based nanomaterials to determine antibiotics by electrochemical techniques.

Antibiotics might build up into the human body by foodstuff metabolism, posing a serious threat to human health and safety. Establishing simple and sensitive technology for quick antibiotic evaluation is thus extremely important. Nanomaterials (or NMTs) with the advantage of possessing merits such as remarkable optical, thermal, mechanical, and electrical capabilities have been highlighted as a piece of the best promising materials for rising new paths in the creation of the future generation biosensors. This paper presents the most recent advances in the use of graphene NMTs-based biosensors to determine antibiotics. Gr-NMTs (or graphene nanomaterials) have been used in the development of a biosensor for the electrochemical signal-transducing process. The rising issues and potential chances of this field are contained to give a plan for forthcoming research orientations. As a result, this review provides a comprehensive evaluation of the nanostructured electrochemical sensing approach for antibiotic residues in various systems. In this review, various electrochemical techniques such as CV, DPV, Stripping, EIS, LSV, chronoamperometry, SWV were employed to determine antibiotics. Additionally, this also demonstrates how graphene nanomaterials are employed to detect antibiotics.

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].

On-cell nuclear magnetic resonance spectroscopy to probe cell surface interactions.

Nuclear magnetic resonance (NMR) spectroscopy allows the determination of atomic-level information on intermolecular interactions, molecular structure, and molecular dynamics in the cellular environment. This may be broadly divided into studies focused on obtaining detailed molecular information in the intracellular context ("in-cell") or those focused on characterizing molecules or events at the cell surface ("on-cell"). In this review, we outline some key NMR techniques applied for on-cell NMR studies through both solution- and solid-state NMR and survey studies that have used these techniques to uncover key information. In particular, we focus on the application of on-cell NMR spectroscopy to characterize ligand interactions with cell surface membrane proteins such as G-protein coupled receptors (GPCRs) and receptor tyrosine kinases. These techniques allow for quantification of binding affinities, competitive binding assays, delineation of ligands involved in binding, ligand bound-state conformational determination, evaluation of receptor structuring and dynamics, and inference of distance constraints characteristic of the ligand-receptor bound state. Interestingly, it is possible to avoid the barriers of production and purification of membrane proteins while obtaining directly physiologically relevant information through on-cell NMR. We also provide a brief survey of the applicability of on-cell NMR approaches to other classes of cell surface molecules.

Pathways to care: a case study of traffic injury in Vietnam.

BACKGROUND: Traffic injuries place a significant burden on mortality, morbidity and health services worldwide. Qualitative factors are important determinants of health but they are often ignored in the study of injury and corresponding development of prehospital Emergency Medical Services (EMS), especially in developing country settings. Here we report our research on sociocultural factors shaping pathways to hospital care for those injured on the roads and streets of Vietnam. METHODS: Qualitative fieldwork on pathways to emergency care of traffic injury was carried out from March to August 2016 in four hospitals in Vietnam, two in Ho Chi Minh City and two in Hanoi. Forty-eight traffic injured patients and their families were interviewed at length using a semi-structured topic guide regarding their journey to the hospital, help received, personal beliefs and other matters that they thought important. Transcribed interviews were analysed thematically guided by the three-delay model of emergency care. RESULTS: Seeking care was the first delay and reflected concerns over money and possessions. The family was central for transporting and caring for the patient but their late arrival prolonged time spent at the scene. Reaching care was the second delay and detours to inappropriate primary care services had postponed the eventual trip to the hospital. Ambulance services were misunderstood and believed to be suboptimal, making taxis the preferred form of transport. Receiving care at the hospital was the third delay and both patients and families distrusted service quality. Request to transfer to other hospitals often created more conflict. Overall, sociocultural beliefs of groups of people were very influential. CONCLUSIONS: Analysis using the three-delay model for road traffic injury in Vietnam has revealed important barriers to emergency care. Hospital care needs to improve to enhance patient experiences and trust. Socioculture affects each of the three delays and needs to inform thinking of future developments of the EMS system, especially for countries with limited resources.

Structure, amphipathy, and topology of the membrane-proximal helix 8 influence apelin receptor plasma membrane localization.

G-protein coupled receptors (GPCRs) typically have an amphipathic helix ("helix 8") immediately C-terminal to the transmembrane helical bundle. To date, a number of functional roles have been associated with GPCR helix 8 segments, but structure-function analysis for this region remains limited. Here, we examine helix 8 of the apelin receptor (AR or APJ), a class A GPCR with wide physiological and pathophysiological relevance. The 71 residue C-terminal tail of the AR is primarily intrinsically disordered, with a detergent micelle-induced increase in helical character. This helicity was localized to the helix 8 region, in good agreement with the recent AR crystal structure. A series of helix 8 mutants were made to reduce helicity, remove amphipathy, or flip the hydrophobic and hydrophilic faces. Each mutant AR was tested both biophysically, in the isolated C-terminal tail, and functionally in HEK 293 T cells, for full-length AR. In all instances, micelle interactions were maintained, and steady-state AR expression was efficient. However, removal of amphipathy or helical character led to a significant decrease in cell surface localization. Flipping of helix 8 amphipathic topology restored cell surface localization to some degree, but still was significantly reduced relative to wild-type. Structural integrity, amphipathy to drive membrane association, and correct topology of helix 8 membrane association all thus appear important for cell surface localization of the AR. This behavior correlates well to GPCR C-terminal tail sequence motifs, implying that these serve to specify key topological features of helix 8 and its proximity to the transmembrane domain.

Putting Culture into Prehospital Emergency Care: A Systematic Narrative Review of Literature from Lower Middle-Income Countries.

BACKGROUND: Prehospital emergency care is cost-effective for improving morbidity and mortality of emergency conditions. However, such care has been discounted in the public health system of many lower middle-income countries (LMICs). Where it exists, the Emergency Medical Service (EMS) system is grossly inadequate, unpopular, and misrepresented. Many EMS reviews in developing countries have identified systemic problems with infrastructure and human resources, but they neglected impacts of sociocultural factors. This study examines the sociocultural dimensions of LMICs' prehospital emergency systems in order to improve the quality and impact of emergency care in those countries. METHODS: Qualitative studies on EMS systems in LMICs were systematically reviewed and analyzed using Kleinman's health system theory of folk, popular, and professional health sectors. Also, the three-delay model of emergency care - seeking, reaching, and receiving - provided a guiding framework. RESULTS: The search yielded over 3,000 papers and the inclusion criteria eventually selected 14, with duplicates and irrelevant papers as the most frequent exclusion. Both user and provider experiences with emergency conditions and the processes of prehospital care were described. Sociocultural factors such as trust and beliefs underlay the way emergency care was experienced. Attitudes of family and community shaped service-seeking behaviors. Traditional medicine was often the first point of care. Private vehicles were the main transportation for accessing care due to distrust and misunderstanding of ambulance services. CONCLUSION: The findings led to the discussion on how culture is woven into the patients' pathway to care, and the recommendation for any future development to place a far greater emphasis on this aspect. Instead of relying purely on the biomedical sector, the health system should acknowledge and show respect for popular knowledge and folk belief. Such strategies will improve trust, facilitate information exchange, and enable stronger healer-patient relationships.

Psychological Distress following Injury in a Large Cohort of Thai Adults.

INTRODUCTION: Injury and psychological distress are public health priorities because of their high occurrence in the population. This study examines the longitudinal effects of injury characteristics on psychological distress. METHODS: Study participants were enrolled distance learning Thai adults (N = 42,785 at 2013 follow-up) residing nationwide. We analysed 2009 and 2013 data. Injury questions included injury prevalence, causes and levels of severity. Distress was measured using the standard Kessler-6. To assess the risk for post-injury distress, we used multinomial logistic regression investigating psychological distress in 2013 as an outcome including injury categories in both 2009 and 2013 as predictors, adjusted for sociodemographic factors. RESULTS: Overall injury was predictive of psychological distress. Both types of injury (traffic and non- traffic) associated with increasing psychological distress. Those that had experienced both types of injuries in the previous year had higher odds of developing psychological distress compared to those who experienced just one type. In 2013, adjusted psychological distress odds ratios were 1.46 [95% Confidence Interval 1.14-1.87] for traffic injury only; 1.26 [1.13-1.40] for non-traffic injury only; and 2.71 [2.19-3.35] for both traffic and non-traffic injuries. Increasing frequency of injury and increasing injury severity were also linked to elevated psychological distress among our Thai cohort members. CONCLUSIONS: Our results revealed a significantly high risk of psychological distress following injury. With increasing occurrence of injury, especially traffic injuries in low and middle income countries such as Thailand, future policies should not only focus on physical care but also address psychological distress as an important consequence of injury.

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.

Social sustainability of Mesocyclops biological control for dengue in South Vietnam.

Copepod Mesocyclops as biological control agents for dengue was previously proven to be effective and sustainable in the Northern and Central provinces of Vietnam. We aim to study social sustainability of Mesocyclops intervention in south Vietnam. Both quantitative and qualitative approaches were used. An entomological survey was carried out in 100 random households of Chanh An commune, Vinh Long Province. Aedes larval indices and Mesocyclops prevalence were compared with historical pre- and post-intervention values. In the same commune, using purposeful sampling, sixteen semi-structured interviews (1 villager leader, 1 local doctor, 10 villagers, 2 teachers, 2 entomology officials), and a focus group discussion (6 Mesocyclops program collaborators) explored water storage habits, beliefs about dengue prevention and behaviour related to Mesocyclops. Thematic analysis was conducted to interpret the qualitative findings. Aedes abundance increased after responsibility for Mesocyclops intervention moved from government to community in 2010, with post-transfer surges in Breteau Index, Container Index, and Larval Density Index. Larval increments coincided with decrease in Mesocyclops prevalence. Villagers had some knowledge of dengue but it was conflated with other mosquito borne diseases and understanding of Mesocyclops was incomplete. Program adoption among the villagers was limited. With reduced government support program collaborators reported limited capacity to conduct population monitoring, and instead targeted 'problem' households. Although the Mesocyclops program was highly sustainable in northern and central provinces of Vietnam, the intervention has not been consistently adopted by southern households in Chanh An commune. Limited education, household monitoring and government support are affecting sustainability. Findings were based on a small household sample visited over a short time period, so other evaluations are needed. However, our results suggest that government support for the Mesocyclops program is still required in this part of Vietnam.

Statistical experimental design of protein crystallization screening revisited.

A statistical experimental design approach was used to prepare a set of solutions for the screening of protein crystallization conditions. This approach is shown to be amenable to quantitative evaluation and therefore to the rational optimization of the screening results. All solutions contain a cryoprotectant, thus eliminating the need for subsequent optimization of crystal freezing conditions.