搜索结果：Journal of clinical biochemistry and nutrition

Violence against women and against children are human rights violations with lasting harms to survivors and societies at large. Intimate partner violence (IPV) and sexual violence against children (SVAC) are two major forms of such abuse. Despite their wide-reaching effects on individual and community health, these risk factors have not been adequately prioritised as key drivers of global health burden. Comprehensive x§and reliable estimates of the comparative health burden of IPV and SVAC are urgently needed to inform investments in prevention and support for survivors at both national and global levels. We estimated the prevalence and attributable burden of IPV among females and SVAC among males and females for 204 countries and territories, by age and sex, from 1990 to 2023, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023. We searched several global databases for data on self-reported exposure to IPV and SVAC and undertook a systematic review to identify the health outcomes associated with each of these risk factors. We modelled IPV and SVAC prevalence using spatiotemporal Gaussian process regression, applying data adjustments to account for measurement heterogeneity. We employed burden-of-proof methodology to estimate relative risks for outcomes associated with IPV and SVAC. These estimates informed the calculation of population attributable fractions, which were then used to quantify disability-adjusted life-years (DALYs) attributable to each risk factor. Globally, in 2023, we estimated that 608 million (95% uncertainty interval 518-724) females aged 15 years and older had ever been exposed to IPV, and 1·01 billion (0·764-1·48) individuals aged 15 years and older had experienced sexual violence during childhood. 18·5 million (8·74-30·0) DALYs were attributed to IPV among females and 32·2 million (16·4-52·5) DALYs were attributed to SVAC among males and females in 2023. IPV and SVAC were among the top contributors to the global disease burden in 2023, particularly among females aged 15-49 years, ranking as the fourth and fifth leading risk factors, respectively, for DALYs in this group. Among the eight health outcomes found to be associated with IPV, anxiety disorders and major depressive disorder were the leading causes of IPV-attributed DALYs, accounting for 5·43 million (-1·25 to 14·6) and 3·96 million (1·71 to 6·92) DALYs in 2023, respectively. SVAC was associated with 14 health outcomes, including mental health disorder, substance use disorder, and chronic and infectious disease outcomes. Self-harm and schizophrenia were the leading causes of SVAC-attributed burden, with SVAC accounting for 6·71 million (2·00 to 12·7) DALYs due to self-harm and 4·15 million (-1·92 to 13·1) DALYs due to schizophrenia in 2023. IPV and SVAC are substantial contributors to global health burden, and their health consequences span a variety of individual health outcomes. Importantly, mental health disorders account for the greatest share of disease burden among survivors. Investing in prevention of these avoidable risk factors has the potential to avert millions of DALYs and considerable premature mortality each year. Our findings represent strong evidence for global and national leaders to elevate IPV and SVAC among public health priorities. Sustained investments are needed to prevent IPV and SVAC and to implement interventions focused on supporting the complex social and health needs of survivors. Gates Foundation.

Climate change, driven by both natural processes and anthropogenic activities, exerts profound effects on atmospheric and environmental conditions. Maternal nutrition plays a critical role in fetal growth, development, and pregnancy outcomes; thus, disruptions in food systems caused by climate change pose significant risks to maternal and child health, particularly in low-income regions already burdened by malnutrition. Environmental stressors associated with climate change can compromise dietary quality and reduce the availability of essential micronutrients, thereby exacerbating adverse health outcomes in mothers and their offspring. Many of these outcomes are mediated through epigenetic mechanisms, suggesting that climate change may indirectly influence the epigenetic programming of diseases across generations. Understanding these links is crucial for elucidating how climate-driven alterations in maternal nutrition contribute to poor pregnancy outcomes and long-term metabolic disorders in offspring. This narrative review examines the epigenetic implications of climate change on maternal nutrition and fetal development. It explores the impact of climate variability on agricultural productivity and nutrient composition, the consequences of food insecurity for maternal and neonatal health, and the influence of temperature extremes and air pollution on pregnancy outcomes. The review also discusses potential mitigation and adaptation strategies to reduce climate-induced risks to maternal and fetal health. Ultimately, climate change threatens maternal and fetal well-being by diminishing food quality and micronutrient availability, with enduring effects mediated through epigenetic pathways. Addressing these challenges requires longitudinal, population-specific studies and integrated nutrition-environment frameworks to inform effective public health interventions and policy responses.

BACKGROUND: Palliative Care (PC) aims to improve the quality of life of individuals with life-threatening illnesses through the early identification and management of holistic needs. Many Colombians in need of PC die without having access to it. When we previously adapted and validated the Sheffield Profile for Assessment and Referral to Care for Spanish-speaking populations (SPARC-Sp), users reported unmet needs and challenges in comprehension and self-administration, particularly among those with lower literacy levels. We designed, culturally adapted, and validated a Colombia-specific module, SPARC-Sp-Col, as an enhancement to SPARC-Sp, to better capture the holistic PC needs of Colombian patients. METHODS: We used a five-step qualitative methodology: (1) preliminary adaptation of a Colombia-specific module as add-on to SPARC-Sp for the Colombian context; (2) online expert panel review; (3) integration of feedback and iterative refinement; (4) cognitive interviews with patients; and (5) focus groups with healthcare professionals, patients, and caregivers from across Colombia. RESULTS: The iterative adaptation process led to the refinement of item language for improved clarity and cultural resonance, while maintaining semantic equivalence with its original version. We included 17 new items to reinforce existing domains and a dedicated Colombia-specific module to address unmet local needs (5 of them) including housing conditions, violence and navigating the health care system. The evaluation of the resulting tool, SPARC-Sp-Col, demonstrated good content validity according to Aiken’s V (> 0.5), reflective of feedback from expert consensus, allied and social healthcare professionals, patient and caregivers. CONCLUSIONS: SPARC-Sp-Col is a culturally adapted, content-validated instrument that expands SPARC-Sp by incorporating a Colombian-specific module. It enables a more accurate and context-sensitive assessment of the holistic care needs of cancer patients in Colombia. Its development marks a key step toward improving the timely and equitable delivery of PC in a country where access to appropriate support is often lacking.

Given excellent prostate cancer outcomes, comorbidity management is critical to survivorship. While hormone therapy or androgen deprivation therapy (ADT) is a mainstay of treatment, they can negatively impact quality of life and survivorship through cardiovascular, sexual, and metabolic effects. ADT-induced metabolic syndrome causes impaired glucose tolerance, muscle mass loss, and weight gain. This systematic review examined recent randomized clinical trials (RCTs) investigating the impact of diet and weight management strategies on mitigating ADT-related adverse effects. A systematic review of RCTs (2015-2025) was performed using PubMed/Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. To identify how diet and weight management impacts ADT symptoms, search terms included: "prostate cancer," "diet," "nutrition," "glucagon-like peptide-1 receptor agonists" (GLP-1RA), and "ADT." Risk of Bias 2 (ROB2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools evaluated RCT quality. Of 2799 publications, 16 met inclusion/exclusion criteria (range, 23-96 patients/RCT). No RCTs had a high risk of bias or evaluated GLP-1RA. Outcomes included metabolic labs, body composition, and quality of life. Mediterranean and low-carbohydrate diets with exercise reduced cardiovascular and metabolic risk factors, with variable durability. Creatine trended toward increasing lean muscle mass. Multidisciplinary care and community involvement improved accountability and outcome durability. This comprehensive review of diet and ADT in prostate cancer identified nutritional interventions that were safe, feasible, and may be recommended as part of prostate cancer treatment and survivorship. Future RCTs should evaluate optimal diet duration, longer follow-up, multidisciplinary patient support, and novel anti-metabolic therapies like GLP-1RA.

Osteoporosis increases fracture risk in older adults and is associated with impaired health-related quality of life (HRQoL). Osteoporosis-specific HRQoL instruments are widely used, but their measurement performance in older populations has not been comprehensively synthesised. To systematically identify and synthesise development and validation studies of osteoporosis-specific HRQoL instruments for older adults, and to appraise their measurement properties using COSMIN criteria and a modified GRADE approach to inform instrument selection for clinical trials, routine care, and research. Systematic review. Community-dwelling; Long-term care facility; Primary care facility. Older persons aged 60 years or over. We searched Medline (Ovid), Embase, PsycINFO (Ovid), and AMED (Ovid) from inception to August 2024. We extracted and appraised evidence for COSMIN-defined measurement properties: content validity, structural validity, internal consistency, cross-cultural validity or measurement invariance, reliability, measurement error, criterion validity, hypothesis testing for construct validity, and responsiveness. Methodological quality was assessed using the COSMIN Risk of Bias checklist, measurement properties were rated against COSMIN criteria for good measurement properties, and certainty of evidence was graded using a modified GRADE approach. Forty-three studies reported the development and/or validation of nine osteoporosis-specific HRQoL instruments; language and version adaptations resulted in 15 instrument variants. Content validity was the most prominent limitation: only OPTQoL and the English Mini-OQLQ demonstrated sufficient evidence for multiple content validity components, while most widely used instruments lacked adequate evidence on item relevance, comprehensiveness, or comprehensibility. Evidence for internal structure was limited, with structural validity sufficient for ECOS-16 and QoLOS-NVFX, insufficient for QUALEFFO-41, and indeterminate for most other instruments. Cross-cultural validity and measurement invariance were almost entirely unexamined. By contrast, reliability and hypothesis testing for construct validity were more consistently supported, often with moderate-to-high certainty. Measurement error, interpretability, and responsiveness were poorly reported across instruments. The evidence base supports purpose-driven selection of osteoporosis-specific HRQoL instruments rather than a single preferred instrument. Across included studies, ECOS-16 shows the most consistently supported measurement properties in older adults for longitudinal assessment, although important evidence gaps remain (notably measurement error and cross-cultural validity). When brevity is the primary feasibility constraint in routine care, the Mini-OQLQ may be considered; however, evidence for responsiveness is limited.

Consuming a diet high in antioxidants can help lower the risk of stroke. Although the association between the comprehensive dietary antioxidant index (CDAI) and stroke has not been extensively researched, it is a useful tool for evaluating the antioxidant capacity of the diet. To look at any possible processes that may be at play in the association between stroke risk and CDAI. The National Health and Nutrition Examination Survey (NHANES) database, which collected data on stroke patients between 2003 and 2018, was utilized. The study involved three independent variables: CDAI, stroke, serum albumin, and gamma-glutamyltransferase (GGT) as mediating factors. The association between CDAI and stroke was examined using logistic regression models, and the non-linear relationship between the two was investigated using restricted cubic splines (RCS). Furthermore, the possible mediating function of serum albumin and GGT in the connection between CDAI and stroke was examined by the use of mediation analysis. Spearman correlation coefficients were used to evaluate the relationship between the stroke risk and the CDAI component parts. 31,313 non-stroke participants and 1,215 stroke patients were included in this research. The data revealed a negative connection between CDAI and stroke (OR: 0.96, 95% CI: 0.93-0.99, p<0.01) after controlling for all confounding factors. A 38% reduction in the risk of stroke was linked to the highest quartile level of CDAI (OR: 0.62, 95% CI: 0.48-0.80, p<0.001). A non-linear negative connection (P-non-linear&#x2005;=&#x2005;0.0346) between CDAI and stroke was revealed using RCS analysis. Significant mediation effects on the link between CDAI and stroke are attributed to serum albumin (10.98%; p<0.001) and GGT (0.33%; p<0.024), respectively. The Spearman correlation coefficient results showed that vitamin A (r&#x2005;=&#x2005;0.76) and vitamin E (r&#x2005;=&#x2005;0.75) in CDAI were most strongly correlated with stroke, while carotenoids reduce the risk of stroke by mediating serum albumin (Proportion of mediation&#x2005;=&#x2005;25.16%). There was a negative correlation found between CDAI and stroke risk. It could be advantageous to consume more vitamin A and E to help avoid cardiovascular illnesses.

Obesity and overweight in pregnant women increase pregnancy and neonatal morbidity with a risk of metabolic syndrome for children in later life. Maternal preconceptional bariatric surgery reduces maternal and paediatric outcomes but may induce fetal nutritional deficiencies and intrauterine growth restriction through placental reprogramming. The aim of this study was to describe feto-placental unit modifications induced by obesity, and the effect of bariatric surgery performed before gestation, on a diet-induced obese rat model. One month after surgery, rats of 'control', 'obese' and 'bariatric surgery' groups were mated and then sacrificed at D19 of gestation. Clinical description, immuno-histochemistry and molecular analyses were performed on feto-placental units. Obesity induces placental modifications including lipid accumulations, increased inflammation and oxidative stress. Some of these modifications are partially restored by maternal preconceptional bariatric surgery. On the other hand, a reduction in the expression of markers of glucose transport, insulin function and amino acid transport, after bariatric surgery was observed. This phenotype may lead to fetal caloric restriction, adoption of a 'thrifty phenotype' and subsequently fetal growth restriction. These preliminary findings highlight the importance of a close follow-up of women who have undergone bariatric surgery and their children.

This study investigates the nutritional applicability of balanced therapeutic diets for elderly individuals (aged 65 and above) with dysphagia, using the International Dysphagia Diet Standardization Initiative (IDDSI) and the 2022 Chinese Dietary Guidelines as dual frameworks. Ingredient data were collected from "Meishichina", a Chinese culinary database, and processed into dishes complying with IDDSI levels 1-7. Nutritional values were calculated using West China Hospital Nutrition Software, and statistical analyses, including ANOVA and Spearman correlation, were conducted to compare nutrients across IDDSI levels. Results showed significant variation in protein, fat, and carbohydrate content among food categories and IDDSI levels (p&#x2264;0.05), with meats and eggs contributing mainly to protein and fat, while fruits and grains contributed carbohydrates. Spearman analysis revealed positive correlations between IDDSI levels and energy, protein, and fat intake (p&#x2264;0.05). Only IDDSI level 7 met the elderly-specific target of 1,000&#x2005;&#x200d;kcal and 60&#x2005;&#x200d;g protein per meal. To address the nutritional gaps in other levels, supplementation with "Yi Quan Su" enteral nutrition powder was calculated based on the deficits. These findings highlight the nutritional limitations of texture-modified diets at lower IDDSI levels and emphasize the importance of targeted supplementation to meet the needs of older adults with dysphagia.

To investigate the impact of serum vitamin {25-hydroxyvitamin D3 [25(OH)D3] and vitamin B12} and trace element [iron (Fe), zinc (Zn), and copper (Cu)] levels on major adverse cardiovascular events (MACE) and prognosis in patients with first-onset ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). A total of 202 first-onset STEMI patients undergoing emergency PCI were prospectively enrolled and divided into MACE (n&#x2005;=&#x2005;72) and non-MACE (n&#x2005;=&#x2005;130) groups according to 12-month postoperative MACE occurrence. Baseline characteristics, cardiac function parameters, and serum levels of 25(OH)D3, vitamin B12, Fe, Zn, and Cu were measured. Multivariate logistic regression was performed to identify independent influencing factors. Receiver operating characteristic curves were used to evaluate predictive value for MACE. Kaplan-Meier analysis was conducted to assess associations with rehospitalization rates and quality of life (SF-36 scale). The MACE group exhibited significantly lower serum 25(OH)D3, vitamin B12, and Zn levels but higher Fe and Cu levels compared with the non-MACE group. Multivariate analysis identified 25(OH)D3, vitamin B12, and Zn were independently associated with a lower risk of MACE, while Fe and Cu were independently associated with a higher risk of MACE. The combined predictive AUC of 25(OH)D3 and vitamin B12 for MACE was 0.79, which was superior to individual indicators. Moreover, abnormal levels were associated with higher 12-month rehospitalization rates and lower SF-36 scores. Decreased serum 25(OH)D3, vitamin B12, and Zn levels and elevated Fe/Cu levels are significantly associated with MACE occurrence and poor prognosis in first-onset STEMI patients post-PCI.

This study explores the association between urinary lignan metabolites (enterolactone and enterodiol) and prevalent stroke (self-reported history of stroke), as well as the long-term likelihood of all-cause mortality (ACM) in patients with a history of stroke. This study employed a mixed-methods design integrating cross-sectional and retrospective cohort analyses, leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning the period 1999-2010. Eligible participants were those with complete data on urinary lignan metabolites (enterolactone and enterodiol), stroke status assessment, and long-term survival outcomes. Weighted logistic regression models were utilized to elucidate the association between enterolactone, enterodiol, and the likelihood of prevalent stroke, with subgroup analyses stratified by age and gender; effect sizes were quantified as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). The study included 9,752 participants, among whom 194 were dead patients. Follow-up was conducted through December 2019, with a total duration of 164.97&#x2005;&#xb1;&#x2005;0.87 months. The analysis revealed no statistical association between enterodiol and prevalent stroke or ACM in patients with a history of stroke. Using the first quartile of enterolactone as a reference, the fourth quartile group of enterolactone was significantly associated with a lower likelihood of prevalent stroke [OR: 0.64 (0.42-0.98)], particularly in males [OR: 0.43 (0.20-0.91)] and those under the age of 65 years [OR: 0.43 (0.19-0.97)]. Higher urinary enterolactone levels were associated with a lower likelihood of prevalent stroke and reduced ACM likelihood in patients with a history of stroke.

The Sarcopenia and Quality of Life (SarQoL) questionnaire is recognized as the only disease-specific patient-reported outcome measure (PROM) for assessing sarcopenia-related HRQoL. This systematic review and meta-analysis aimed to provide a quantitative summary of all evidence reported on the reliability, validity, responsiveness and floor/ceiling effects of SarQoL in older adults. Following PRISMA-COSMIN guidelines, a systematic search for studies evaluating the psychometric properties of SarQoL (i.e., reliability, validity, responsiveness and floor and ceiling effects) in older people was conducted on MEDLINE (via OVID), PsycINFO, Scopus and EMBASE. Studies published between 2013 and November 2024 using a consensual definition of sarcopenia were included. Study selection and data extraction were made by two independent reviewers. A random-effects model meta-analysis was applied. PROSPERO registration: CRD42024546880. From 411 studies identified by the search strategy, 25 fulfilled the inclusion criteria, including 4585 community-dwelling individuals, of which 1311 were diagnosed as sarcopenic. SarQoL demonstrated high reliability (pooled Cronbach's alpha values consistently exceeding 0.80) and excellent test-retest reliability (pooled ICC&#x2009;=&#x2009;0.98). Construct validity was confirmed with strong convergent correlations (pooled r&#x2009;>&#x2009;0.54) with related dimensions of generic SF-36 and EQ-5D and weaker divergent correlations (pooled r&#x2009;<&#x2009;0.47). Responsiveness, evaluated in two studies using different methodologies, supported the ability of SarQoL to detect meaningful changes in HRQoL. The certainty of evidence was rated as high for reliability, validity and responsiveness. This meta-analysis consolidates a decade of evidence and confirms the strong psychometric properties of SarQoL, with a high level of evidence.

Background/Objectives: Mitochondrial dysfunction, often reflected by a decline in mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells (PMBCs), is a key hallmark of biological aging and is linked to numerous adverse health outcomes, including frailty and cardiovascular disease. Furthermore, emerging evidence suggests that vitamin D may influence mitochondrial dysfunction. This cross-sectional study aims to investigate the associations of mtDNA-CN with muscular strength, self-rated health, and serum 25-hydroxyvitamin D3 (25(OH)D3) levels in a community-dwelling elderly population. Methods: A total of 149 elderly outpatients (&#x2265;65 years) from Soria, Spain, were included in this cross-sectional study. Muscular strength was assessed using the hand grip strength (HGS) test, and self-rated health-related quality of life (QoL) was measured using the EuroQoL five-dimension questionnaire (EQ-5D). Genomic DNA was extracted from peripheral blood, and mtDNA-CN was quantified using quantitative real-time PCR (qPCR). Serum 25(OH)D3, intact parathyroid hormone (iPTH), phosphorus, calcium, albumin and other mineral metabolism markers were measured. Statistical analyses, including Spearman correlations and multivariate logistic regression, were performed to assess associations, with stratification by sex. Results: In the total population, a marginally significant positive correlation was observed between mtDNA copy number (mtDNA-CN) and serum 25(OH)D3 levels (r = 0.210; p = 0.010), which did not remain significant after Bonferroni correction. Among women, lower mtDNA-CN was significantly linked to muscle weakness (p = 0.005), mobility problems (p = 0.009), and a trend toward self-care difficulties (p = 0.016). Multivariate analysis confirmed an independent association with increased mobility impairment risk (adjusted OR = 0.983; 95% CI: 0.97-1.00; p = 0.009). No significant associations were observed between mtDNA-CN and dynapenia or QoL components in the male group. Conclusions: This study identified a marginally significant positive correlation between serum 25(OH)D3 levels and mtDNA-CN in the total population (r = 0.210; p = 0.010), which did not persist after Bonferroni correction, suggesting an exploratory link between vitamin D status and mitochondrial homeostasis in older adults. In addition, these results highlight sex-specific differences in mtDNA-CN as a potential biomarker of functional decline, particularly of mobility, in women. These findings support the idea that mtDNA-CN could serve as an integrated biomarker and that sex-specific nutrition could be used to promote healthy aging.

Misconceptions in pharmacology can undermine learning and compromise both clinical and scientific reasoning, yet few validated tools exist to identify them. Consequently, we developed and validated the Pharmacology Concept Inventory (PCI), which can be used to identify misconceptions, assess learning gains, and evaluate teaching effectiveness. This PCI was designed based on the IUPHAR-Education Section (IUPHAR-Ed) Core Concepts of Pharmacology Project, addressing eight core concepts: drug efficacy, drug-target interaction, steady-state concentration, structure-activity relationship, drug tolerance, drug bioavailability, volume of distribution, and drug clearance. A triangulated design strategy integrated theoretical frameworks, expert review, and student perspectives. Experts examined quality, content validity, and cognitive alignment. The pilot PCI was then administered to a student cohort to evaluate its psychometric properties, providing preliminary evidence for further refinement. Item-level content validity indices ranged from 0.67 to 1.00, with a scale-level average of 0.93. Seventy students completed the pilot survey, leading to the exclusion of items with low discrimination and reliability. Items on drug-target interaction were removed due to consistently poor performance. The final PCI included 26 items covering seven concepts, with strong discrimination indices (0.36-0.75) and difficulty indices (0.26-0.71). Internal consistency was high (Cronbach's alpha&#x2009;=&#x2009;0.91), and concept-level reliability ranged from 0.64 to 0.85. The PCI provides strong evidence for identifying misconceptions and assessing learning outcomes through a pre-post-test approach. Although the PCI currently addresses only a subset of concepts, continued refinements informed by surveys and interviews will enhance its utility and expand its scope for concept-based learning and curriculum evaluation.

Allergic rhinitis (AR) impacts quality of life, work and school productivity. Over the last years, an important body of evidence resulting from mHealth data has led to a better understanding of AR. Such advances have motivated an EAACI-endorsed update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (ARIA 2024-2025). This manuscript presents the ARIA 2024-2025 recommendations for intranasal treatments, one of the mainstays for AR management. The ARIA 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgments and recommendations, including systematic reviews, evaluation of mHealth and pharmacovigilance data, as well as a survey of experts on costs. Eleven guideline questions concerning intranasal treatments for AR were prioritized, leading to recommendations. Overall, these questions concern the choice between different classes of intranasal medications-most notably, intranasal corticosteroids (INCS), antihistamines (INAH), fixed combinations of INAH+INCS and decongestants-or between different individual medications within each class. Four questions had not been evaluated in previous ARIA guidelines, while for the other three there was a change in the strength or directionality of recommendations. Overall, recommendations point to the suggested use of INAH+INCS over INAH or INCS and INCS over INAH. This ARIA 2024-2025 article supports patients, their caregivers, and healthcare professionals in choosing an intranasal treatment. However, decisions on AR treatment should consider the clinical variability of the disease, patients' values, and the affordability of medications.

The hyperphosphorylation of &#x3b1;-synuclein (&#x3b1;-Syn) at serine 129 is associated with in its aggregation, culminating in the formation of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs. Plasma homocysteine (Hcy) levels are typically high in PD, particularly in those treated with Levodopa. Therefore, we aimed to investigate the effects of Hcy on phosphorylation and aggregation of &#x3b1;-Syn. The human neuroblastoma cell line 3D5 expressing wild-type &#x3b1;-Syn under the control of a tetracycline-off system was treated with Hcy, and aggregation and phosphorylation of &#x3b1;-Syn were examined. Hcy was cytotoxic to 3D5 cells, and Hcy induced cell shrinkage at a concentration >100&#x2005;&#x200d;&#x3bc;M. Treatment with Hcy upregulated the levels of &#x3b1;-Syn, increased its phosphorylation at serine 129, and increased casein kinase 2A. Moreover, Hcy treatment significantly increased the level of aggregated form of &#x3b1;-Syn, including oligomers in 3D5 cells. However, folate significantly reversed the Hcy-mediated increase in the levels of total &#x3b1;-Syn and its phosphorylation. In conclusion, Hcy enhances the total &#x3b1;-Syn level, and phosphorylated and oligomeric &#x3b1;-Syn formation, thereby promoting LBs formation.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopamine (DA) neurons and presence of Lewy bodies, with prion-like propagation of &#x3b1;-synuclein (&#x3b1;-syn) also attracting attention recently. However, the specific causes for PD-related pathogenesis, including cell vulnerability and &#x3b1;-syn propagation, occurring only in selective neurons remain unclear. Therefore, we aimed to investigate the interactions between DA and &#x3b1;-syn protein to clarify its effects on &#x3b1;-syn degradation, secretion, and toxicity. We generated PC12 cells expressing human &#x3b1;-syn and M127A mutant in a tetracycline-inducible manner. In these cells, intracellular &#x3b1;-syn levels were controlled via autophagic/lysosomal degradation and secretion to extracellular space. Notably, M127A mutation decreased the intracellular degradation and secretion of &#x3b1;-syn. Using the generated cells, we investigated the association between cell viability and oxidized methionine [Met(O)] in &#x3b1;-syn. We also investigated the effects of Met(O) on &#x3b1;-syn toxicity and stability upon DA induction. Wildtype &#x3b1;-syn overexpression decreased the cell viability, and inhibition of methionine sulfoxide reductase, a methionine sulfoxide-reducing enzyme, further amplified this effect, suggesting that &#x3b1;-syn cytotoxicity is associated with methionine oxidation. Notably, vulnerabilities of M127A mutant cells were lower than those of wildtype &#x3b1;-syn-expressing cells. Overall, our results suggest M127 as the major target for oxidative modification by DA and that this modification is associated with both cell vulnerability and &#x3b1;-syn intracellular stability and secretion in PD pathogenesis.

Lactylation, a novel post-translational histone modification, has emerged as a critical regulatory mechanism in various metabolic disorders. However, its role in the pathogenesis of type 2 diabetes (T2D) remains poorly understood. This study aims to investigate the potential of lactylation-related genes as diagnostic biomarkers for T2D. Differential analysis and weighted gene co-expression network analysis (WGCNA) were performed on the GSE164416 dataset. Genes obtained from these analyses were intersected with the lactylation-related genes to screen candidate genes. The LASSO, SVM-RFE and random forest algorithms were applied to screen the characteristic genes, and their diagnostic efficacy was verified in the independent cohort. The functions and immune associations were analyzed by GSVA, ssGSEA, and TF-miRNA regulatory network analysis, and qRT-PCR, Western blot and CCK-8 experiments were conducted in the T2D cell model for verification. Lactylation-related IKZF1, S100A4, and VIM were identified as potential diagnostic markers for T2D. These three genes were significantly upregulated in T2D samples and exhibited excellent diagnostic performance (AUC >0.80) in both the training set and validation set. The GSVA analysis revealed that these three genes were involved in key biological processes such as immune regulation, transcriptional modification, metabolic homeostasis and cytoskeleton remodeling. Cell experiments demonstrated that the three genes were upregulated in T2D cell models and knockdown of their expression could promote cell viability. This study identified and validated three potential diagnostic markers related to lactylation for T2D, providing new molecular evidence for the early diagnosis and mechanism research of this disease.

The rising incidence of chronic metabolic diseases places a significant economic burden on healthcare systems. Although the efficacy of lifestyle interventions has been reported, clinical nutrition typically emphasizes total energy and macronutrient intake without consensus on ideal dietary patterns. The Dietary Inflammatory Index (DII) assesses the inflammatory potential of diets and has been linked to diseases like cardiovascular disease, cancer, and type 2 diabetes. However, DII use in clinical practice is limited by its complexity. In this study, we developed a method to calculate DII scores using a clinically available food frequency questionnaire (FFQ). Thirty healthy volunteers provided 3-day dietary records (DR) and completed the FFQ. Dietitians calculated the intake of 29 nutrients from the DR. A created table of nutrient content per FFQ item enabled nutrient intake and DII score calculation from the FFQ. Statistical analysis showed significant correlations between 27 of 29 nutrient intakes and DII scores from the DR and FFQ. Regression equations were developed to predict actual nutrient intakes from the FFQ. The estimated DII (eDII) calculated using the equations correlated strongly with the DR-derived DII (r&#x2005;=&#x2005;0.716, p<0.0001). With low bias and variance, our method supports individualized and inflammation-targeted dietary interventions.

To analyze the relationship between serum Vitamin D (VD) and Vitamin C (VC) levels and melanoma risk in American adults using NHANES data. The exposure variables were serum VD and VC. The outcome variable was melanoma presence. Covariates included sex, age, race, BMI, poverty-income ratio, alcohol consumption, smoking, diabetes, hypertension, sunscreen use, and sunburn history. We use weighted logistic regression and restricted cubic spline (RCS) analyses to evaluate the relationship and receiver operating characteristic (ROC) curve to assess the prediction performance. Data from 12,743 (VD) and 12,615 (VC) participants were included. Higher serum VD levels (&#x2265;75 nmol/L) and the highest VC quartile levels (OR&#x2005;=&#x2005;1.91, 95% CI: 1.24-2.97) were associated with an increased melanoma risk. The ROC analysis indicated that the combination of VC or VD with covariates exhibited excellent predictive efficacy (VD and VC model 3: AUC&#x2005;=&#x2005;0.863). RCS analysis revealed a non-linear correlation between VD and melanoma, and a significant non-linear dose-response relationship between serum VC levels and melanoma. Stratified analysis indicated the adverse effect of higher VD on melanoma was more pronounced in men (OR&#x2005;=&#x2005;3.55, 95% CI: 1.99-6.33; p<0.001), non-Hispanic white individuals (95% CI: 1.19-2.95; p&#x2005;=&#x2005;0.009), and diabetic patients (OR&#x2005;=&#x2005;18.81, 95% CI: 3.44-102.79; p&#x2005;=&#x2005;0.002). Sensitivity analysis confirmed results stability. High serum VD and VC levels are associated with increased melanoma risk. Personalized prevention considering ultraviolet exposure and genetic factors are recommended to avoid excessive supplementation.