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51 pages, 2918 KiB  
Review
Therapeutic Applications and Mechanisms of Superoxide Dismutase (SOD) in Different Pathogenesis
by Shehwaz Anwar, Tarique Sarwar, Amjad Ali Khan and Arshad Husain Rahmani
Biomolecules 2025, 15(8), 1130; https://doi.org/10.3390/biom15081130 - 5 Aug 2025
Abstract
An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O2– is produced by numerous biochemically relevant redox processes and is thought [...] Read more.
An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O2– is produced by numerous biochemically relevant redox processes and is thought to play role in diseases and pathological processes, such as aging, cancer, membrane or DNA damage, etc.; SOD, or superoxide dismutase, is essential for reducing oxidative stress. As a result, the elimination of ROS by SOD may be a useful disease prevention tactic. There have been reports of protective effects against neurodegeneration, apoptosis, carcinogenesis, and radiation. Exogenous SODs’ low bioavailability has drawn criticism. However, this restriction might be removed, and interest in SOD’s medicinal qualities increased with advancements in its formulation. This review discusses the findings of human and animal studies that support the benefits of SOD enzyme regulation in reducing oxidative stress in various ways. Additionally, this review summarizes contemporary understandings of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics and its therapeutic potential. Full article
(This article belongs to the Topic Enzymes and Enzyme Inhibitors in Drug Research)
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14 pages, 614 KiB  
Article
Development of Cut Scores for Feigning Spectrum Behavior on the Orebro Musculoskeletal Pain Screening Questionnaire and the Perceived Stress Scale: A Simulation Study
by John Edward McMahon, Ashley Craig and Ian Douglas Cameron
J. Clin. Med. 2025, 14(15), 5504; https://doi.org/10.3390/jcm14155504 - 5 Aug 2025
Abstract
Background/Objectives: Feigning spectrum behavior (FSB) is the exaggeration, fabrication, or false imputation of symptoms. It occurs in compensable injury with great cost to society by way of loss of productivity and excessive costs. The aim of this study is to identify feigning [...] Read more.
Background/Objectives: Feigning spectrum behavior (FSB) is the exaggeration, fabrication, or false imputation of symptoms. It occurs in compensable injury with great cost to society by way of loss of productivity and excessive costs. The aim of this study is to identify feigning by developing cut scores on the long and short forms (SF) of the Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ and OMPSQ-SF) and the Perceived Stress Scale (PSS and PSS-4). Methods: As part of pre-screening for a support program, 40 injured workers who had been certified unfit for work for more than 2 weeks were screened once with the OMPSQ and PSS by telephone by a mental health professional. A control sample comprised of 40 non-injured community members were screened by a mental health professional on four occasions under different aliases, twice responding genuinely and twice simulating an injury. Results: Differences between the workplace injured people and the community sample were compared using ANCOVA with age and gender as covariates, and then receiver operator characteristics (ROCs) were calculated. The OMPSQ and OMPSQ-SF discriminated (ρ < 0.001) between all conditions. All measures discriminated between the simulation condition and workplace injured people (ρ < 0.001). Intraclass correlation demonstrated the PSS, PSS-4, OMPSQ, and OMPSQ-SF were reliable (ρ < 0.001). Area Under the Curve (AUC) was 0.750 for OMPSQ and 0.835 for OMPSQ-SF for work-injured versus simulators. Conclusions: The measures discriminated between injured and non-injured people and non-injured people instructed to simulate injury. Non-injured simulators produced similar scores when they had multiple exposures to the test materials, showing the uniformity of feigning spectrum behavior on these measures. The OMPSQ-SF has adequate discriminant validity and sensitivity to feigning spectrum behavior, making it optimal for telephone screening in clinical practice. Full article
(This article belongs to the Section Clinical Rehabilitation)
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14 pages, 1058 KiB  
Article
Sex- and Age-Specific Utilization Patterns of Nuclear Medicine Procedures at a Public Tertiary Hospital in Jamaica
by Tracia-Gay Kennedy-Dixon, Mellanie Didier, Fedrica Paul, Andre Gordon, Marvin Reid and Maxine Gossell-Williams
Hospitals 2025, 2(3), 21; https://doi.org/10.3390/hospitals2030021 - 5 Aug 2025
Abstract
Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in [...] Read more.
Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in Jamaica. This was a non-experimental, retrospective study of NM scans that were completed at the University Hospital of the West Indies from 1 June 2022 to 31 May 2024. While all scans were reported in the descriptive totals, for patients with multiple scans during the study period, only the data from the first visit was used in the inferential statistical analysis. This was performed with the IBM SPSS (version 29.0) software and involved the use of chi-square goodness of fit and multinomial logistic regression. A total of 1135 NM scans for 1098 patients were completed (37 patients had more than one scan); 596 (54.3%) were female and 502 (45.7%) were male, with the ages ranging from 3 days to 94 years old. Among the female patients, there was a greater demand in the ≥60 years age group for cardiac amyloid scans (χ2 = 6.40, p < 0.05), while females 18–59 years had a greater demand for thyroid scans (χ2 = 7.714, p < 0.05) and bone scans (χ2 = 3.904, p < 0.05). On the other hand, significantly more males in the ≥60 age group presented for cardiac amyloid (χ2 = 4.167; p < 0.05) and bone scans (χ2 = 145.79, p < 0.01). Males were significantly less likely to undergo a thyroid scan than females (p < 0.01, OR = 0.072, 95% CI: 0.021, 0.243) while individuals aged 18–59 years were more likely to undergo this scan than patients aged 60 or older (p = 0.02, OR = 3.565, 95% CI: 1.258, 10.104). Males were more likely to do a cardiac amyloid scan (p < 0.05, OR = 2.237, 95% CI: 1.023, 4.891) but less likely to undergo a cardiac rest/stress test than females (p = 0.02, OR = 0.307, 95% CI: 0.114, 0.828). Prolonged life expectancy and an aging population have the potential to impact NM utilization, thus requiring planning for infrastructure, equipment, work force, and supplies. Cancer-related and cardiovascular indications are a top priority at this facility; hence, age- and sex-specific analysis are useful in establishing models for policy makers with regard to the allocation of economic and human resources for the sustainability of this specialized service. Full article
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18 pages, 8203 KiB  
Article
Puerarin Enhances Eggshell Quality by Mitigating Uterine Senescence in Late-Phase Laying Breeder Hens
by Zhenwu Huang, Guangju Wang, Mengjie Xu, Yanru Shi, Jinghai Feng, Minhong Zhang and Chunmei Li
Antioxidants 2025, 14(8), 960; https://doi.org/10.3390/antiox14080960 (registering DOI) - 5 Aug 2025
Abstract
The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell [...] Read more.
The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca2+-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article
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37 pages, 5366 KiB  
Article
Oral Microbiota Composition and Its Association with Gastrointestinal and Developmental Abnormalities in Children with Autism Spectrum Disorder
by Zuzanna Lewandowska-Pietruszka, Magdalena Figlerowicz and Katarzyna Mazur-Melewska
Microorganisms 2025, 13(8), 1822; https://doi.org/10.3390/microorganisms13081822 - 4 Aug 2025
Abstract
Autism Spectrum Disorder (ASD) is frequently accompanied by gastrointestinal disturbances, dietary selectivity, and altered stress responses, with growing evidence pointing to gut–brain axis involvement. While intestinal microbiota has been extensively studied, the role of the oral microbiota remains underexplored. This study investigates the [...] Read more.
Autism Spectrum Disorder (ASD) is frequently accompanied by gastrointestinal disturbances, dietary selectivity, and altered stress responses, with growing evidence pointing to gut–brain axis involvement. While intestinal microbiota has been extensively studied, the role of the oral microbiota remains underexplored. This study investigates the associations between oral microbiota composition and behavioral, gastrointestinal, dietary, and neuroendocrine parameters in children with ASD. A total of 45 children aged 2–18 years comprised the study group. Data collection included oral swabs for 16S rRNA gene sequencing, salivary cortisol sampling, dietary records, and standardized behavioral assessments using the Vineland Adaptive Behavior Scale. A total of 363 microbial species across 11 phyla were identified. Significant correlations were observed between specific bacterial taxa and functional gastrointestinal disorders (FGIDs), dietary patterns, salivary cortisol rhythms, and functioning. Children with FGIDs, food selectivity, or macronutrient imbalances exhibited enriched pro-inflammatory taxa (e.g., Selenomonas, Megasphaera), whereas those with typical cortisol secretion or higher adaptive functioning showed greater microbial diversity and abundance of health-associated genera (e.g., Bifidobacterium dentium). These findings suggest that oral microbiota profiles may reflect systemic physiological and neurobehavioral traits in children with ASD. Further longitudinal studies are needed to clarify causal relationships and support the development of microbiota-targeted interventions. Full article
(This article belongs to the Special Issue Focus on Pediatric Infectious Diseases)
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37 pages, 1202 KiB  
Article
Exploring Service Needs and Development Strategies for the Healthcare Tourism Industry Through the APA-NRM Technique
by Chung-Ling Kuo and Chia-Li Lin
Sustainability 2025, 17(15), 7068; https://doi.org/10.3390/su17157068 - 4 Aug 2025
Abstract
With the arrival of an aging society and the continuous extension of the human lifespan, the quality of life has not improved in a corresponding manner. People’s demand for happiness and health is increasing. As a result, a model emerged that integrates tourism [...] Read more.
With the arrival of an aging society and the continuous extension of the human lifespan, the quality of life has not improved in a corresponding manner. People’s demand for happiness and health is increasing. As a result, a model emerged that integrates tourism and medical services, which is health tourism. This growing demand has prompted many service providers to see it as a business opportunity and enter the market. Tourism can help travelers release work stress and restore physical and mental balance; meanwhile, health check-ups and disease treatment can help them regain health. Consumers have long favored health and medical tourism because it helps relieve stress and promotes overall well-being. As people age, some consumers experience a gradual decline in physical functions, making it difficult for them to participate in regular travel services provided by traditional travel agencies. Therefore, this study aims to explore the service needs of health and medical tourism customers (tourists/patients) and the interrelationships among these service needs, so that health and medical tourism service providers can develop more customized and diversified services. This study identifies four key drivers of medical tourism services: medical services, medical facilities, tour planning, and hospitality facilities. This study uses the APA (attention and performance analysis) method to assess each dimension and criterion and utilizes the DEMATEL method with the NRM (network relationship map) to identify network relationships. By combining APA and NRM techniques, this study develops the APA-NRM technique to evaluate adoption strategies and identify suitable paths for health tourism services, providing tailored development strategies and recommendations for service providers to enhance the service experience. Full article
(This article belongs to the Special Issue Inclusive Tourism and Its Place in Sustainable Development Concepts)
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16 pages, 4328 KiB  
Article
High-Throughput Study on Nanoindentation Deformation of Al-Mg-Si Alloys
by Tong Shen, Guanglong Xu, Fuwen Chen, Shuaishuai Zhu and Yuwen Cui
Materials 2025, 18(15), 3663; https://doi.org/10.3390/ma18153663 - 4 Aug 2025
Abstract
Al-Mg-Si (6XXX) series aluminum alloys are widely applied in aerospace and transportation industries. However, exploring how varying compositions affect alloy properties and deformation mechanisms is often time-consuming and labor-intensive due to the complexity of the multicomponent composition space and the diversity of processing [...] Read more.
Al-Mg-Si (6XXX) series aluminum alloys are widely applied in aerospace and transportation industries. However, exploring how varying compositions affect alloy properties and deformation mechanisms is often time-consuming and labor-intensive due to the complexity of the multicomponent composition space and the diversity of processing and heat treatments. This study, inspired by the Materials Genome Initiative, employs high-throughput experimentation—specifically the kinetic diffusion multiple (KDM) method—to systematically investigate how the pop-in effect, indentation size effect (ISE), and creep behavior vary with the composition of Al-Mg-Si alloys at room temperature. To this end, a 6016/Al-3Si/Al-1.2Mg/Al KDM material was designed and fabricated. After diffusion annealing at 530 °C for 72 h, two junction areas were formed with compositional and microstructural gradients extending over more than one thousand micrometers. Subsequent solution treatment (530 °C for 30 min) and artificial aging (185 °C for 20 min) were applied to simulate industrial processing conditions. Comprehensive characterization using electron probe microanalysis (EPMA), nanoindentation with continuous stiffness measurement (CSM), and nanoindentation creep tests across these gradient regions revealed key insights. The results show that increasing Mg and Si content progressively suppresses the pop-in effect. When the alloy composition exceeds 1.0 wt.%, the pop-in events are nearly eliminated due to strong interactions between solute atoms and mobile dislocations. In addition, adjustments in the ISE enabled rapid evaluation of the strengthening contributions from Mg and Si in the microscale compositional array, demonstrating that the optimum strengthening occurs when the Mg-to-Si atomic ratio is approximately 1 under a fixed total alloy content. Furthermore, analysis of the creep stress exponent and activation volume indicated that dislocation motion is the dominant creep mechanism. Overall, this enhanced KDM method proves to be an effective conceptual tool for accelerating the study of composition–deformation relationships in Al-Mg-Si alloys. Full article
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16 pages, 875 KiB  
Review
Cardiorenal Syndrome in the Elderly: Challenges and Considerations
by Matthew Jarocki, Sophie Green, Henry H. L. Wu and Rajkumar Chinnadurai
Geriatrics 2025, 10(4), 104; https://doi.org/10.3390/geriatrics10040104 - 4 Aug 2025
Abstract
Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due [...] Read more.
Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article
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26 pages, 20835 KiB  
Article
Reverse Mortgages and Pension Sustainability: An Agent-Based and Actuarial Approach
by Francesco Rania
Risks 2025, 13(8), 147; https://doi.org/10.3390/risks13080147 - 4 Aug 2025
Abstract
Population aging poses significant challenges to the sustainability of pension systems. This study presents an integrated methodological approach that uniquely combines actuarial life-cycle modeling with agent-based simulation to assess the potential of Reverse Mortgage Loans (RMLs) as a dual lever for enhancing retiree [...] Read more.
Population aging poses significant challenges to the sustainability of pension systems. This study presents an integrated methodological approach that uniquely combines actuarial life-cycle modeling with agent-based simulation to assess the potential of Reverse Mortgage Loans (RMLs) as a dual lever for enhancing retiree welfare and supporting pension system resilience under demographic and financial uncertainty. We explore Reverse Mortgage Loans (RMLs) as a potential financial instrument to support retirees while alleviating pressure on public pensions. Unlike prior research that treats individual decisions or policy outcomes in isolation, our hybrid model explicitly captures feedback loops between household-level behavior and system-wide financial stability. To test our hypothesis that RMLs can improve individual consumption outcomes and bolster systemic solvency, we develop a hybrid model combining actuarial techniques and agent-based simulations, incorporating stochastic housing prices, longevity risk, regulatory capital requirements, and demographic shifts. This dual-framework enables a structured investigation of how micro-level financial decisions propagate through market dynamics, influencing solvency, pricing, and adoption trends. Our central hypothesis is that reverse mortgages, when actuarially calibrated and macroprudentially regulated, enhance individual financial well-being while preserving long-run solvency at the system level. Simulation results indicate that RMLs can improve consumption smoothing, raise expected utility for retirees, and contribute to long-term fiscal sustainability. Moreover, we introduce a dynamic regulatory mechanism that adjusts capital buffers based on evolving market and demographic conditions, enhancing system resilience. Our simulation design supports multi-scenario testing of financial robustness and policy outcomes, providing a transparent tool for stress-testing RML adoption at scale. These findings suggest that, when well-regulated, RMLs can serve as a viable supplement to traditional retirement financing. Rather than offering prescriptive guidance, this framework provides insights to policymakers, financial institutions, and regulators seeking to integrate RMLs into broader pension strategies. Full article
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36 pages, 6047 KiB  
Review
Prevalence and Levels of Thyroid Autoantibodies in Polycystic Ovary Syndrome—Impact of TSH- and BMI-Matched Comparisons: A Systematic Review and Meta-Analysis
by Jakub Kwiatkowski, Nicole Akpang, Lucja Zaborowska and Artur Ludwin
Int. J. Mol. Sci. 2025, 26(15), 7525; https://doi.org/10.3390/ijms26157525 (registering DOI) - 4 Aug 2025
Abstract
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article
(This article belongs to the Section Molecular Oncology)
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27 pages, 2005 KiB  
Article
Glyoxalase 1 Inducer, trans-Resveratrol and Hesperetin–Dietary Supplement with Multi-Modal Health Benefits
by Mingzhan Xue, Naila Rabbani and Paul J. Thornalley
Antioxidants 2025, 14(8), 956; https://doi.org/10.3390/antiox14080956 (registering DOI) - 4 Aug 2025
Abstract
A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose [...] Read more.
A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article
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19 pages, 1016 KiB  
Article
Genetic Associations of ITGB3, FGG, GP1BA, PECAM1, and PEAR1 Polymorphisms and the Platelet Activation Pathway with Recurrent Pregnancy Loss in the Korean Population
by Eun Ju Ko, Eun Hee Ahn, Hyeon Woo Park, Jae Hyun Lee, Da Hwan Kim, Young Ran Kim, Ji Hyang Kim and Nam Keun Kim
Int. J. Mol. Sci. 2025, 26(15), 7505; https://doi.org/10.3390/ijms26157505 (registering DOI) - 3 Aug 2025
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Abstract
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women [...] Read more.
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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29 pages, 2132 KiB  
Review
Polyphenol-Based Therapeutic Strategies for Mitochondrial Dysfunction in Aging
by Tamara Maksimović, Carmen Gădău, Gabriela Antal, Mihaela Čoban, Oana Eșanu, Elisabeta Atyim, Alexandra Mioc and Codruța Șoica
Biomolecules 2025, 15(8), 1116; https://doi.org/10.3390/biom15081116 - 3 Aug 2025
Viewed by 179
Abstract
Aging, a progressive and time-dependent decline in physiological functions, is driven by interconnected hallmarks, among which mitochondrial dysfunction plays a central role. Mitochondria not only regulate energy production but also play key roles in other cellular processes, including ROS generation, apoptosis, and metabolic [...] Read more.
Aging, a progressive and time-dependent decline in physiological functions, is driven by interconnected hallmarks, among which mitochondrial dysfunction plays a central role. Mitochondria not only regulate energy production but also play key roles in other cellular processes, including ROS generation, apoptosis, and metabolic signaling—all of which decline with aging. Polyphenols are a diverse group of natural compounds found in fruits, vegetables, tea, and wine; they emerged as promising anti-aging agents due to their ability to modulate several hallmarks of aging, particularly mitochondrial dysfunction. This review explores how various polyphenolic classes influence mitochondrial function and mitigate aging-related decline. These natural compounds have been shown to reduce oxidative stress, increase energy production, and help maintain normal mitochondrial structure. Moreover, in vitro and in vivo studies suggest that polyphenols can delay signs of aging and improve physical and cognitive functions. Overall, polyphenols show great potential to promote healthy aging and even delay the decline in physiological functions by protecting and enhancing mitochondrial health. Full article
(This article belongs to the Special Issue Bioactive Compounds as Modifiers of Mitochondrial Function)
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33 pages, 938 KiB  
Review
Exploring the Antioxidant Roles of Cysteine and Selenocysteine in Cellular Aging and Redox Regulation
by Marta Pace, Chiara Giorgi, Giorgia Lombardozzi, Annamaria Cimini, Vanessa Castelli and Michele d’Angelo
Biomolecules 2025, 15(8), 1115; https://doi.org/10.3390/biom15081115 - 3 Aug 2025
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Abstract
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, [...] Read more.
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, first proposed by Denham Harman in 1956, highlights the role of reactive oxygen species (ROS), byproducts of normal metabolism, in driving oxidative stress and age-related degeneration. Emerging evidence emphasizes the importance of redox imbalance in the onset of neurodegenerative diseases and aging. Among the critical cellular defenses against oxidative stress are sulfur-containing amino acids, namely cysteine (Cys) and selenocysteine (Sec). Cysteine serves as a precursor for glutathione (GSH), a central intracellular antioxidant, while selenocysteine is incorporated into key antioxidant enzymes such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). These molecules play pivotal roles in neutralizing ROS and maintaining redox homeostasis. This review aims to provide an updated and critical overview of the role of thiol-containing amino acids, specifically cysteine and selenocysteine, in the regulation of redox homeostasis during aging. Full article
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19 pages, 582 KiB  
Article
Xylitol Antioxidant Properties: A Potential Effect for Inflammation Reduction in Menopausal Women?—A Pilot Study
by Ilona Górna, Magdalena Kowalówka, Barbara Więckowska, Michalina Banaszak, Grzegorz Kosewski, Olivia Grządzielska, Juliusz Przysławski and Sławomira Drzymała-Czyż
Curr. Issues Mol. Biol. 2025, 47(8), 611; https://doi.org/10.3390/cimb47080611 - 2 Aug 2025
Viewed by 141
Abstract
Introduction: Oxidative stress is a key factor in the pathogenesis of many chronic diseases, especially in postmenopausal women. Xylitol, a sugar alcohol with potential antioxidant properties, may affect oxidative balance when used as a sugar substitute. Aim: This pilot study aimed to assess [...] Read more.
Introduction: Oxidative stress is a key factor in the pathogenesis of many chronic diseases, especially in postmenopausal women. Xylitol, a sugar alcohol with potential antioxidant properties, may affect oxidative balance when used as a sugar substitute. Aim: This pilot study aimed to assess the effect of replacing sucrose with xylitol on serum antioxidant capacity in postmenopausal women. Methods: This study included 34 women aged 50 to 65 years who successively consumed 5 g/d, 10 g/d, and 15 g/d of xylitol. The dietary intervention lasted a total of 6 weeks, with each phase covering a 2-week period. Diet was assessed twice based on a 7-day dietary interview (Diet 6.0, NIZP–PZH, Warsaw). The material for this study was venous blood. Antioxidant capacity was determined using the DPPH radical scavenging method and the ABTS cation radical scavenging method. Results: In both methods, a significant increase in serum antioxidant potential was observed after replacing sugar with xylitol (p < 0.0001). An increase in the ability to neutralize free radicals was observed in almost all women studied. Additional analysis of the effect of selected nutrients on the obtained effects of the nutritional intervention showed that the most significant effect could potentially be exerted by manganese, maltose, sucrose, and mercury, and the strongest positive correlation was exerted by vitamin A, retinol, and vitamin E. Although the values obtained in the constructed models were not statistically significant, the large effect indicates potentially significant relationships that could have a significant impact on serum antioxidant potential in the studied group of women. Conclusions: The results suggest a potential role of xylitol in enhancing antioxidant defense mechanisms in menopausal women. Although the sample size was relatively small, this study was powered at approximately 80% to detect large effects, supporting the reliability of the observed results. Nevertheless, given the pilot nature of this study, further research with larger cohorts is warranted to confirm these preliminary observations and to clarify the clinical significance of xylitol supplementation in populations exposed to oxidative stress. Full article
(This article belongs to the Special Issue Role of Natural Products in Inflammatory Diseases)
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