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Our skin serves as the primary barrier against external environmental insults, the latter of which can cause oxidative stress within cells, while various bioactive peptides sourced from natural resources hold promise in protecting cells against such oxidative stress. In this study, we investigate the efficacy of a low molecular weight extract from the sea cucumber Apostichopus japonicus, denoted as Sample-P, in facilitating cell migration and wound healing under oxidative stress conditions in skin cells. The naturally derived compound is a highly complex mix of peptides exhibiting antioxidative properties, as highlighted through liquid chromatography-mass spectrometry peptide screening and an in vitro antioxidant assay. Our results demonstrate that Sample-P is capable of promoting cell migration while preventing severe stress responses such as visible through mTOR expression. To further identify the molecular pathways underpinning the overall protective mechanism of Sample-P, we have utilised a proteomics approach. Our data reveal that Sample-P regulates protein expression associated with ribosomal pathways, glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum (ER), which help in preserving DNA integrity and safeguarding cellular organelles, such as mitochondria and the ER, under oxidative stress conditions in skin cells. In summary, in the presence of H2O2, Sample-P exhibits antioxidative properties at both molecular and cellular levels, rendering it a promising candidate for topical skin treatment to wound healing and to address age-related skin conditions.

Summary: Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown. Here, we conduct genome-wide analysis of AD in multiplex CH families from the Alzheimer Disease Sequencing Project (ADSP). We developed, validated, and applied an implementation of a logistic mixed model for admixture mapping with binary traits that leverages genetic ancestry to identify ancestry-of-origin loci contributing to AD. We identified three loci on chromosome 13q33.3 associated with reduced risk of AD, where associations were driven by Native American (NAM) ancestry. This AD admixture mapping signal spans the FAM155A, ABHD13, TNFSF13B, LIG4, and MYO16 genes and was supported by evidence for association in an independent sample from the Alzheimer’s Genetics in Argentina—Alzheimer Argentina consortium (AGA-ALZAR) study with considerable NAM ancestry. We also provide evidence of NAM haplotypes and key variants within 13q33.3 that segregate with AD in the ADSP whole-genome sequencing data. Interestingly, the widely used genome-wide association study approach failed to identify associations in this region. Our findings underscore the potential of leveraging genetic ancestry diversity in recently admixed populations to improve genetic mapping, in this case for AD-relevant loci.

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

Chemical safety assessment begins with defining the lowest level of chemical that alters one or more measured endpoints. This critical effect level, along with factors to account for uncertainty, is used to derive limits for human exposure. In the absence of data regarding the specific mechanisms or biological pathways affected, non-specific endpoints such as body weight and non-target organ weight changes are used to set critical effect levels. Specific apical endpoints such as impaired reproductive function or altered neurodevelopment have also been used to set chemical safety limits; however, in test guidelines designed for specific apical effect(s), concurrently measured non-specific endpoints may be equally or more sensitive than specific endpoints. This means that rather than predicting a specific toxicological response, animal data are often used to develop protective critical effect levels, without assuming the same change would be observed in humans. This manuscript is intended to encourage a rethinking of how adverse chemical effects are interpreted: non-specific endpoints from in vivo toxicological studies data are often used to derive points of departure for use with safety assessment factors to create recommended exposure levels that are broadly protective but not necessarily target-specific., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mulberry fruit is widely consumed either fresh or in processed food products such as juice, mulberry jelly and jam. Conversely, mulberry marc, the solid component after juicing, is primarily a waste product or used in animal fodder, despite being rich in anthocyanins. Anthocyanins have been reported to have hepatoprotective, hypolipidaemic and antioxidant activities. In this study, the protective effect of mulberry marc anthocyanins (MMA) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats was investigated. Male Sprague Dawley rats were injected with CCl4 to induce liver fibrosis. Compared with the model group, the contents of alanine aminotransferase, aspartate amino transferase, hyaluronidase acid, hydroxyproline and collagen type-III in the MMA 200 mg/kg group were decreased. Moreover, pathological examination and immunohistochemical showed that CCl4-induced liver fibrosis was alleviated by administration of MMA. These results demonstrate that MMA has a potent protective effect on CCl4-induced liver fibrosis in rats.

Background and Aims: Lipoprotein particle size is associated with increased atherosclerosis and cardiovascular disease risk. Certain lifestyle behaviours may be cardioprotective. We examined lipoprotein particle size and concentration relationships with a protective lifestyle behaviour (PLB) score., Methods: This was a cross-sectional analysis of 2045 middle-to older-aged adults. Lipoprotein particle subclass size and concentrations were determined using nuclear magnetic resonance spectroscopy. Five protective behaviours included never smoking, moderate alcohol intake, moderate to vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5-24.9 kg/m 2 ). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with lipoprotein subclasses., Results: Individual behaviour associations varied according to lipoprotein subclass, with normal BMI showing the greatest number of significant relationships. Logistic regression analyses revealed that subjects with the fewest number of protective behaviours had 1.4-2.8 increased odds of having less favourable lipoprotein profiles defined as above or below median level lipoprotein particle subclass size or concentration. Following additional adjustment for BMI, significant trend relationships were observed between the PLB score and large and medium very low-density lipoprotein (p = 0.001 and p < 0.001), total and smaller low-density lipoprotein (LDL) concentrations (p = 0.008 and p < 0.001), LDL size (p = 0.003) and a lipoprotein insulin resistance score (p = 0.003)., Conclusions: Results show a cumulative protective effect of healthy lifestyle behaviours against an unfavourable potentially pro-atherogenic lipoprotein profile in middle-to older-aged adults, highlighting the importance of lifestyle promotion in healthy ageing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective of Study: Alcohol use disorder is one of the most important factors contributing to dementia. This study examined the protective effect of thiamine administration on the incidence of dementia among patients with alcohol use disorder in Taiwan by evaluating a nationwide database., Methods: We retrieved data for this retrospective cohort study from the Longitudinal Health Insurance Database 1995-2000. Patients receiving thiamine therapy after the diagnosis of alcohol use disorder were recruited as the thiamine therapy (TT) group, and the comparison group without TT (NTT group) included randomly assigned and age-, sex-, and index year-matched individuals with alcohol use disorder. Demographic data, comorbid medical disorders, and psychotropic medication use were evaluated and controlled. The cumulative defined daily dose (DDD) was analyzed to demonstrate the dose effect., Results: Each group had 5059 patients. The TT group had a lower crude hazard ratio (0.76; 95% confidence interval: 0.60-0.96) of dementia than the NTT group. After adjusting for demographic data, comorbidity, and psychotropic medication use, the adjusted hazard ratio was 0.54 (95% confidence interval: 0.43-0.69). The significance existed among TT subjects with cumulative DDD higher than 23. The Kaplan-Meier analysis demonstrated a lower cumulative incidence of dementia in the TT group than in the NTT group., Conclusion: The results indicated that thiamine therapy could be a protective factor for dementia development in patients with alcohol use disorder. Thiamine therapy should be a crucial part of the treatment plan and health policies to prevent dementia development or progression among patients with alcohol use disorder., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Bullying is common and harms all involved, yet there is no clarity regarding factors that influence bullying and victimisation for adolescent samples. This meta-analysis aims to synthesise the literature and identify reliable risk and protective factors to adolescent bullying and victimisation. A systematic search of the literature using databases; PsycINFO and Scopus, was undertaken to identify relevant publications from 1985 until July 2014. Inclusion criteria included longitudinal data, an adolescent sample and a focus on predictive factors of bullying or victimisation. From 4698 articles identified, 18 were included. Four predictors of victimisation (prior victimisation, conduct problems, social problems and internalising problems) and four predictors of bullying (conduct problems, social problems, school problems and age) were identified. The literature provides little consistency in predictors assessed and replication is needed for clarification, however, social problems and conduct problems are consistent risk factors and a potential focus for future interventions., (Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

The Democratic Republic of the Congo (DRC) has one of the lowest HIV prevalence in sub-Saharan Africa, estimated at 1.1% [0.9-1.3] of adults aged 15-49 in 2013 (UNAIDS). Within the 2 million km(2) country, however, there exists spatial variation in HIV prevalence, with the highest HIV prevalence observed in the large cities of Kinshasa and Lubumbashi. Globally, HIV is an increasingly rural disease, diffusing outwards from urban centers of high HIV prevalence to places where HIV was previously absent or present at very low levels. Utilizing data collected during Demographic and Health Surveillance (DHS) in 2007 and 2013 in the DRC, we sought to update the map of HIV prevalence in the DRC as well as to explore whether HIV in the DRC is an increasingly rural disease or remains confined to urban areas. Bayesian kriging and regression indicate that HIV prevalence in rural areas of the DRC is higher in 2013 than in 2007 and that increased distance to an urban area is no longer protective against HIV as it was in 2007. These findings suggest that HIV education, testing and prevention efforts need to diffuse from urban to rural areas just as HIV is doing., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS) and/or silymarine against cyclophosphamide (CP) toxicity in male albino rats. The MPS and/or silymarin significantly decreased the activities of serum ASAT and ALAT. However, MPS (1000 mg/kg) normalized their activities towards the normal levels recording 28.75 and 78.75 U/ml respectively. The recorded data also showed the antioxidant effect of MPS by decreasing the level of malondialdehyde (MDA) and increasing the level of reduced glutathione (GSH) as well as normalized the activities of the antioxidant enzyme GST and SOD. Histopathological examinations also confirmed the protective efficacy of MPS against liver toxicity of CP. In conclusion, the recorded results of the present study support the protective role of MPS and/or silymarin against CP-induced hepatic damage., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)