Bioinformatic Resources for Exploring Human-virus Protein-protein Interactions Based on Binding Modes.

Historically, there have been many outbreaks of viral diseases that have continued to claim millions of lives. Research on human-virus protein-protein interactions (PPIs) is vital to understanding the principles of human-virus relationships, providing an essential foundation for developing virus control strategies to combat diseases. The rapidly accumulating data on human-virus PPIs offer unprecedented opportunities for bioinformatics research around human-virus PPIs. However, available detailed analyses and summaries to help use these resources systematically and efficiently are lacking. Here, we comprehensively review the bioinformatic tools used in human-virus PPIs research, discuss and compare the function, performance, and limitations of these web resources. This study aims to provide researchers with a bioinformatic toolbox that will hopefully better facilitate the exploration of human-virus PPIs based on binding modes.

Refining the Rab7-V1G1 axis to mitigate iron deposition: Protective effects of quercetin in alcoholic liver disease.

Iron overload is a common feature of alcoholic liver disease (ALD) and contributes significantly to disease progression. Quercetin, a flavonoid known for its iron-chelating properties, has emerged as a potential protective compound against ALD. However, research on quercetin's regulatory effects on iron levels in ALD is limited. To address this, we conducted a study using male C57BL/6J mice were subjected to a Lieber De Carli liquid diet containing ethanol (28% energy replacement) with or without quercetin supplementation (100 mg/kg.BW) for 12 weeks. Additionally, HepG2 cells, after transfection with the CYP2E1 plasmid, were incubated with ethanol and/or quercetin. Our findings revealed that ethanol consumption led to iron overload in both hepatocytes and lysosomes. Interestingly, despite the increase in iron levels, cells exhibited impaired iron utilization, disrupting normal iron metabolism. Further analysis identified a potential mechanism involving the Rab7-V1G1 (V-ATPase subunit) axis. Inhibition of V-ATPase by Concanamycin A caused elevated ROS levels, impaired lysosomal and mitochondria function, and increased expression of HIF1α and IRP2. Ultimately, this disruption in cellular processes led to iron overload and mitochondrial iron deficiency. Quercetin supplementation mitigated ethanol-induced hepatocyte damage by reversing iron overload through modulation of the Rab7-V1G1 axis and improving the interaction between lysosomes and mitochondria. In conclusion, this study elucidates a novel pathophysiological mechanism by which quercetin protects against ALD through its regulation of iron homeostasis.

Matricellular proteins: From cardiac homeostasis to immune regulation.

Tissue repair after myocardial injury is a complex process involving changes in all aspects of the myocardial tissue, including the extracellular matrix (ECM). The ECM is composed of large structural proteins such as collagen and elastin and smaller proteins with major regulatory properties called matricellular proteins. Matricellular cell proteins exert their functions and elicit cellular responses by binding to structural proteins not limited to interactions with cell surface receptors, cytokines, or proteases. At the same time, matricellular proteins act as the "bridge" of information exchange between cells and ECM, maintaining the integrity of the cardiac structure and regulating the immune environment, which is a key factor in determining cardiac homeostasis. In this review, we present an overview of the identified matricellular proteins and summarize the current knowledge regarding their roles in maintaining cardiac homeostasis and regulating the immune system.

Impact of social wellbeing on tooth loss and cognition: A scoping review.

OBJECTIVE: The proposed explanations for the association between tooth loss and cognitive function have largely focused on systemic inflammation, mechanoreceptor feedback, and nutritive deficiencies. However, the role of social wellbeing in this relationship remains unknown. The aim of this scoping review is to explore the pathways linking different aspects of social function, collectively grouped under the umbrella of social wellbeing, to tooth loss and cognitive impairment. DATA AND SOURCES: An electronic database search was performed in PubMed, Scopus, and Embase. Reference lists of relevant articles were also searched. Data on the associations between social wellbeing, cognitive function and tooth loss was charted in an extraction form and summarised qualitatively. STUDY SELECTION: From the initial search of 3293 records, 71 studies were included in the present review. Forty-seven studies investigated the relationship between social wellbeing and cognition, 21 studies investigated the relationship between social wellbeing and tooth loss, and only 3 studies investigated all three variables. CONCLUSION: This review demonstrates the need for further research on tooth loss, cognition and social wellbeing in tandem and describes potential psychological, biological, cognitive, and behavioural mechanisms interlinking these factors. While substantial evidence was found for the association between social relationships and cognition, fewer studies explored the potentially bidirectional relationship of social wellbeing and tooth loss. CLINICAL SIGNIFICANCE: The implications of this review may guide clinicians to focus on the social consequences of tooth loss, which may have broader repercussions on cognitive health. The role of social support in helping older people cope with oral disease and the benefits of fostering positive lifestyle habits should not be underestimated.

The Complete Mitochondrial Genome of the Siberian Scoter Melanitta stejnegeri and Its Phylogenetic Relationship in Anseriformes.

The Siberian Scoter (Melanitta stejnegeri) is a medium sea duck distinct from M. deglandi due to the absence of hybridization and differences in morphological characteristics. However, knowledge of its phylogenetic relationships within Anseriformes is limited due to a lack of molecular data. In this study, the complete mitogenome of M. stejnegeri was firstly sequenced, then annotated and used to reconstruct the phylogenetic relationships of 76 Anseriformes species. The complete mitogenome of M. stejnegeri is 16,631 bp and encodes 37 typical genes: 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 1 non-coding control region. Its mitogenome organization is similar to that of other Anseriformes species. The phylogenetic relationships within the genus Melanitta are initially clarified, with M. americana at the base. M. stejnegeri and M. deglandi are sister groups, clustering with M. fusca and M. perspicillata in order. Phylogenetic analysis suggests that Mareca falcata and M. strepera are sister groups, differing from previous studies. Results firstly indicate that Clangula hyemalis and Somateria mollissima are sister groups, suggesting a potentially skewed phylogenetic relationship may have been overlooked in earlier analyses relying solely on mitochondrial genomes. Our results provide new mitogenome data to support further phylogenetic and taxonomic studies of Anseriformes.

Unveiling the seroprevalence of human papillomavirus in Guangdong, China: Implications for vaccination strategies.

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.

Linking Daily Victimization to Daily Affect Among Adolescents: The Mediating Role of Sleep Quality and Disturbance.

Bullying victimization is prevalent among adolescents and often linked to emotional problems. Prior studies have been focused on the concurrent or longitudinal associations between bullying victimization and emotional problems, but the daily associations and the underlying mechanisms remain unclear. Implementing daily diary method, the study aimed to examine the links between daily victimization and positive and negative affect as well as the mediating role of sleep quality and disturbance. A total of 265 Chinese adolescents (Mage = 11.65, SD = 0.74; 32.80% females) participated in this study and completed 7-day daily diaries on bullying victimization (traditional and cyber victimization), sleep quality and disturbance, and affect. As hypothesized, at the between-person level, sleep disturbance mediated the relationships between both traditional and cyber victimization and subsequent negative affect. At the within-person level, sleep quality mediated the pathway between traditional victimization and next-day negative affect; furthermore, sleep disturbance mediated the pathway between traditional victimization and positive affect the following day. These findings highlight the mediating roles of sleep quality and sleep disturbance in the relationships between stressful victimizing experiences and emotional problems and also provide novel insights into these associations.

Effects of self-perception of aging interventions in older adults: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Self-perception of aging (SPA) is associated with various health outcomes in the aging process. This study aimed to conduct a systematic review of existing interventions targeting SPA among older adults, and to synthesize their effects on self-perception of aging, physical performance, and mental health. RESEARCH DESIGN AND METHODS: A systematic search was performed in PubMed, Embase, PsycINFO, CINAHL, Web of Science, CENTRAL, CNKI, SinoMed, VIP, and WanFang databases for randomized controlled trials that reported intervention effects on self-perception of aging, physical performance, and mental health in older adults. Two researchers independently conducted study selection, data extraction and quality assessment. RESULTS: A total of 16 studies were included for qualitative analysis, and 12 studies of them were included for meta-analysis. The results showed a significant impact of interventions on self-perception of aging, with the effect size of -0.56 (95% CI -1.06 to -0.07, P=0.03). And the results also supported a significant improvement in physical performance and mental health among older adults. DISCUSSION AND IMPLICATIONS: Self-perception of aging interventions present a promising approach to enhance positive aging perception for older adults, with potential benefits extending to physical performance and mental health. However, larger-scale and more robust trials are still required to validate these findings and obtain more accurate conclusions.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma.

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

The adhesin RadD enhances Fusobacterium nucleatum tumour colonization and colorectal carcinogenesis.

Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K-AKT-NF-κB-MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD-CD147 interaction could be a potential therapeutic target for CRC.

Lipidomics combined with random forest machine learning algorithms to reveal freshness markers for duck eggs during storage in different rearing systems.

The differences in lipids in duck eggs between the 2 rearing systems during storage have not been fully studied. Herein, we propose untargeted lipidomics combined with a random forest (RF) algorithm to identify potential marker lipids based on ultra-performance liquid chromatography‒mass spectrometry (UPLPC-MS/MS). A total of 106 and 16 differential lipids (DL) were screened in egg yolk and white, respectively. In yolk, metabolic pathway analysis of DLs revealed that glycerophospholipid metabolism and sphingolipid metabolism were the key metabolic pathways in the traditional free-range system (TFS) during storage, glycosylphosphatidylinositol-anchored biosynthesis and glyceride metabolism were the key pathways in the floor-rearing system (FRS). In egg white, the key pathway in both systems is the biosynthesis of unsaturated fatty acids. Combined with RF algorithm, 12 marker lipids were screened during storage. Therefore, this study elucidates the changes in lipids in duck eggs during storage in 2 rearing systems and provides new ideas for screening marker lipids during storage. This approach is highly important for evaluating the quality of egg and egg products and provides guidance for duck egg production.

Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis.

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

Crosstalk of methylation and tamoxifen in breast cancer (Review).

Tamoxifen is a widely used anti­estrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the long­term application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progression­free survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen.

Tensorized and Compressed Multi-view Subspace Clustering via Structured Constraint.

Multi-view learning has raised more and more attention in recent years. However, traditional approaches only focus on the difference while ignoring the consistency among views. It may make some views, with the situation of data abnormality or noise, ineffective in the progress of view learning. Besides, the current datasets have become high-dimensional and large-scale gradually. Therefore, this paper proposes a novel multi-view compressed subspace learning method via low-rank tensor constraint, which incorporates the clustering progress and multi-view learning into a unified framework. First, for each view, we take the partial samples to build a small-size dictionary, which can reduce the effect of both redundancy information and computation cost greatly. Then, to find the consistency and difference among views, we impose a low-rank tensor constraint on these representations and further design an auto-weighted mechanism to learn the optimal representation. Last, due to the non-square of the learned representation, the bipartite graph has been introduced, and under the structured constraint, the clustering results can be obtained directly from this graph without any post-processing. Extensive experiments on synthetic and real-world benchmark datasets demonstrate the efficacy and efficiency of our method, especially for the views with noise or outliers.

Spatial distribution of residential environment, genetic susceptibility, and psoriasis: A prospective cohort study.

Background: Genetic and environmental factors contribute to psoriasis, but the impact of residential environments on this condition remains uncertain. We aimed to investigate the association of residential environments with psoriasis risk and explore its interaction with genes. Methods: We retrieved data on the spatial distribution of residential environments at 300 and 1000 m buffer zones from the UK Biobank, including the proportions of natural environments, domestic gardens, green spaces, and blue spaces within these zones. We then used Cox hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between residential environments and psoriasis risk. Lastly, we constructed polygenic risk scores to determine genetic susceptibility and further analyse the interaction with residential environments. Results: Overall, 3755 incident cases of psoriasis were documented during a median follow-up of 12.45 years. Compared with the lowest exposure quantile (Q1), Q4 exposure to natural environments (1000 m buffer: HR = 1.16, 95% CI = 1.05-1.29; 300 m buffer: HR = 1.12, 95% CI = 1.02-1.24) and green spaces (1000 m buffer: HR = 1.16, 95% CI = 1.04-1.28; 300m buffer: HR = 1.10, 95% CI = 1.00-1.21) increased the risk of psoriasis, while Q4 exposure to domestic gardens (1000 m buffer: HR = 0.85, 95% CI = 0.77-0.93; 300m buffer: HR = 0.91, 95% CI = 0.83-1.00) and Q3 exposure to blue spaces (1000 m buffer: HR = 0.89, 95% CI = 0.81-0.98) were negatively associated with psoriasis risk. Among participants with a high genetic risk, those exposed to high levels of natural environments (1000 m buffer: HR = 1.49, 95% CI = 1.15-1.93; 300 m buffer: HR = 1.39, 95% CI = 1.10-1.77) and green spaces (300 m buffer: HR = 1.30, 95% CI = 1.04-1.64) had a higher risk of psoriasis, while those exposed to blue spaces (1000 m buffer: HR = 0.78, 95% CI = 0.63-0.98) had a lower risk of psoriasis. We also observed joint effects of genetic risk and residential environments and an antagonistic additive interaction between blue spaces and genetic risk (P = 0.011). Conclusions: We observed that residing in natural environments and green areas increased the risk of psoriasis in our sample, while proximity to blue spaces and domestic gardens was associated to reduced risks. The association of residential environments with psoriasis risk was modified by genetic susceptibility.

Colonization Mediated by T6SS-ClpV Disrupts Host Gut Microbiota and Enhances Virulence of Salmonella enterica serovar Typhimurium.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common foodborne enteric pathogen that infects humans or mammals and colonizes the intestinal tract primarily by invading the host following ingestion. Meanwhile, ClpV is a core secreted protein of the bacterial type VI secretion system (T6SS). Because elucidating ClpV's role in the pathogenesis of T6SS is pivotal for revealing the virulence mechanism of Salmonella, in our study, clpV gene deletion mutants were constructed using a λ-red-based recombination system, and the effect of clpV mutation on SL1344's pathogenicity was examined in terms of stress resistance, motility, cytokine secretion, gut microbiota, and a BALB/c mouse model. Among the results, ClpV affected SL1344's motility and was also involved in cell invasion, adhesion, and intracellular survival in the MDBK cell model but did not affect invasion or intracellular survival in the RAW264.7 cell model. Moreover, clpV gene deletion significantly reduced the transcription levels of GBP2b, IFNB1, IL-6, NLRP3, NOS2, and TNF-α proinflammatory factor levels but significantly increased transcription levels of IL-4 and IL-10 anti-inflammatory factors. Last, ClpV appeared to closely relate to the pathogenicity of S. Typhimurium in vivo, which can change the gut environment and cause dysbiosis of gut microbiota. Our findings elucidate the functions of ClpV in S. Typhimurium and illustrating interactions between T6SS and gut microbiota help to clarify the mechanisms of the pathogenesis of foodborne diseases.

Nanomaterial-integrated injectable hydrogels for craniofacial bone reconstruction.

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.

The investigation of potential mechanism of Fuzhengkangfu Decoction against Diabetic myocardial injury based on a combined strategy of network pharmacology, transcriptomics, and experimental verification.

BACKGROUND AND OBJECTIVES: Diabetic cardiomyopathy (DCM) is a cardiac condition resulting from myocardial damage caused by diabetes mellitus (DM), currently lacking specific therapeutic interventions. Fuzhengkangfu decoction (FZK) plays an important role in the prevention and treatment of various cardiovascular diseases. However, the efficacy and potential mechanisms of FZK are not fully understood. This study aims to investigate the protective effect and mechanisms of FZK against DCM. METHODOLOGIES: Rats were given a high-calorie diet along with a low dosage of streptozotocin (STZ) to establish a rat model of DCM. The diabetic rats received FZK or normal saline subcutaneously for 12 weeks. Echocardiography was conducted to evaluate their heart function characteristics. Rat heart morphologies were assessed using Sirius Red staining and H&E staining. Transcriptome sequencing analysis and network pharmacology were used to reveal possible targets and mechanisms. Molecular docking was conducted to validate the association between the primary components of FZK and the essential target molecules. Finally, both in vitro and in vivo studies were conducted on the cardioprotective properties and mechanism of FZK. RESULTS: According to the results of network pharmacology, FZK may prevent DCM by reducing oxidative stress and preventing apoptosis. Transcriptomics confirmed that FZK protected against DCM-induced myocardial fibrosis and remodelling, as predicted by network pharmacology, and suggested that FZK regulated the expression of oxidative stress and apoptosis-related proteins. Integrating network pharmacology and transcriptome analysis results revealed that the AGE-RAGE signalling pathway-associated MMP2, SLC2A1, NOX4, CCND1, and CYP1A1 might be key targets. Molecular docking showed that Poricoic acid A and 5-O-Methylvisammioside had the highest docking activities with these targets. We further conducted in vivo experiments, and the results showed that FZK significantly attenuated left ventricular remodelling, reduced myocardial fibrosis, and improved cardiac contractile function. And, our study demonstrated that FZK effectively reduced oxidative stress and apoptosis of cardiomyocytes. The data showed that Erk, NF-κB, and Caspase 3 phosphorylation was significantly inhibited, and Bcl-2/Bax was significantly increased after FZK treatment. In vitro, FZK significantly reduced AGEs-induced ROS increase and apoptosis in cardiomyocytes. Furthermore, FZK significantly inhibited the phosphorylation of Erk and NF-κB proteins and decreased the expression of MMP2. All the results confirmed that FZK inhibited the activation of the Erk/NF-κB pathway in AGE-RAGE signalling and alleviated oxidative stress and apoptosis of cardiomyocytes. In summary, we verified that FZK protects against DCM by inhibiting myocardial apoptotic remodelling through the suppression of the AGE-RAGE signalling pathway. CONCLUSION: In conclusion, our research indicates that FZK demonstrates anti-cardiac dysfunction properties by reducing oxidative stress and cardiomyocyte apoptosis through the AGE-RAGE pathway in DCM, showing potential for therapeutic use.

Dietary polyunsaturated fatty acids intake is negatively associated with hyperuricemia: The National Health and Nutrition Examination Survey 2003-2015.

BACKGROUND AND AIMS: The objective of this research was to explore the associations between dietary PUFAs intake and hyperuricemia risk. METHODS AND RESULTS: Based on the National Health and Nutrition Examination Survey (NHANES) 2003-2015, all eligible individuals were divided into hyperuricemia and non-hyperuricemia groups based on diagnostic criteria for hyperuricemia (serum uric acid >420 µmol/L for men and >360 µmol/L for women). Multivariate-adjusted logistic regression was employed to explore the relationship between dietary PUFAs intake and hyperuricemia risk. Total PUFAs and their subtypes were modeled to isocalorically replace saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Higher intake of n-3 PUFAs, n-6 PUFAs, linoleic acid (LA), alpha-linoleic acid (ALA), and non-marine PUFAs intake correlated with decreased hyperuricemia risk, with adjusted odds ratio (OR) and 95% confidence interval (95%CIs) were 0.77 (0.63, 0.93), 0.75 (0.61, 0.92), 0.75 (0.61, 0.91), 0.69 (0.55, 0.87), and 0.73 (0.59, 0.91), respectively. Replacing 5% of total energy intake from SFAs with isocaloric PUFAs was associated with decreased odds of hyperuricemia in men (0.69 (0.57, 0.84)) and in individuals (0.81 (0.71, 0.92)). Similar trends were observed in the substitution of SFAs with non-marine PUFAs in men (0.87 (0.80, 0.94)) and in all individuals (0.92 (0.88, 0.98)). Sensitivity analyses exhibited consistent results with primary analyses. CONCLUSION: Higher dietary intake of n-3 PUFAs, n-6 PUFAs, LA, ALA, and non-marine PUFAs was associated with decreased hyperuricemia risk. These results support the recommendation to substitute SFAs with PUFAs in diet.

Managing Cardiovascular Risk in Patients with Autoimmune Diseases: Insights from a Nutritional Perspective.

PURPOSE OF REVIEW: Autoimmune diseases manifest as an immune system response directed against endogenous antigens, exerting a significant influence on a substantial portion of the population. Notably, a leading contributor to morbidity and mortality in this context is cardiovascular disease (CVD). Intriguingly, individuals with autoimmune disorders exhibit a heightened prevalence of CVD compared to the general population. The meticulous management of CV risk factors assumes paramount importance, given the current absence of a standardized solution to this perplexity. This review endeavors to address this challenge from a nutritional perspective. RECENT FINDINGS: Emerging evidence suggests that inflammation, a common thread in autoimmune diseases, also plays a pivotal role in the pathogenesis of CVD. Nutritional interventions aimed at reducing inflammation have shown promise in mitigating cardiovascular risk. The integration of nutritional strategies into the management plans for patients with autoimmune diseases offers a holistic approach to reducing cardiovascular risk. While conventional pharmacological treatments remain foundational, the addition of targeted dietary interventions can provide a complementary pathway to improve cardiovascular outcomes.