Association between composite dietary antioxidant index and atherosclerosis cardiovascular disease in adults: A cross-sectional study.

BACKGROUND AND AIM: The objective of our study was to examine the association between composite dietary antioxidant index (CDAI) and atherosclerotic cardiovascular disease (ASCVD) in adults. METHODS AND RESULTS: Data was gathered from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. To examine the connection between CDAI and ASCVD, multiple logistic regression analyses were performed. Restricted cubic splines were utilized to examine non-linear correlations, and the inflection point was identified using a two-piecewise linear regression approach. Subgroup analyses were performed to demonstrate stability of results. A total of 44,494 individuals were included in the study. The multivariate logistic regression model was fully adjusted and revealed an odds ratio of 0.968 (95% CI: 0.959-0.978; P < 0.001) for the correlation between CDAI and ASCVD. Furthermore, individuals in the highest quartile of CDAI exhibited a decreased risk of ASCVD compared to those in the lowest quartile [0.716 (0.652-0.787); P < 0.001]. Moreover, restricted cubic spline (RCS) analysis revealed non-linear relationship between CDAI and ASCVD, with inflection point at -0.387. The analysis of subgroups showed that the importance of CDAI remained consistent among various age, sex, race, body mass index (BMI), and physical activity. CONCLUSIONS: Our research revealed an inverse and non-linear relationship between CDAI and ASCVD in adults. The implications of these findings are significant for future studies and the formulation of dietary guidelines.

Care Need, Caregiver Availability, and Care Receipt: Variations Across Countries and Over Time in Three Middle-Income Countries.

BACKGROUND: Dementia is expected to increase more rapidly in low- and middle-income countries (LMIC) than in high-income countries (HIC) in the coming decades. Nevertheless, research on dementia care remains limited for LMIC. This study aims to fill this gap by investigating care needs and care receipt in three LMIC: China, Mexico, and India. METHODS: Using harmonized data from the Gateway to Global Aging Data in China, Mexico, and India and focusing on individuals aged 65 and older with cognitive impairment (N = 15,118), we estimated the proportions of care needs related to difficulties with activities of daily living (ADL) and instrumental activities of daily living (IADL), and care receipt. We then used logistic regressions to examine the association between caregiver availability and informal care receipt. RESULTS: We observed relatively similar patterns in care need measures across countries and over time. In contrast, the association between caregiver availability and informal care receipt showed some cross-country variations. Generally, living with family members was associated with a higher probability of receiving informal care in China and India. However, for Mexico, this association was only evident for men. Additionally, we found that the magnitude of the association between caregiver availability and informal care receipt varied with the care recipient's gender. CONCLUSIONS: While living with family members was generally associated with a higher likelihood of receiving informal care in China, Mexico, and India, there are differences in the association between caregiver availability and informal care receipt across countries and over time.

The mitochondrial protease ClpP is a druggable target that controls VSMC phenotype by a SIRT1-dependent mechanism.

Vascular smooth muscle cells (VSMCs), known for their remarkable lifelong phenotypic plasticity, play a pivotal role in vascular pathologies through their ability to transition between different phenotypes. Our group discovered that the deficiency of the mitochondrial protein Poldip2 induces VSMC differentiation both in vivo and in vitro. Further comprehensive biochemical investigations revealed Poldip2's specific interaction with the mitochondrial ATPase caseinolytic protease chaperone subunit X (CLPX), which is the regulatory subunit for the caseinolytic protease proteolytic subunit (ClpP) that forms part of the ClpXP complex - a proteasome-like protease evolutionarily conserved from bacteria to humans. This interaction limits the protease's activity, and reduced Poldip2 levels lead to ClpXP complex activation. This finding prompted the hypothesis that ClpXP complex activity within the mitochondria may regulate the VSMC phenotype. Employing gain-of-function and loss-of-function strategies, we demonstrated that ClpXP activity significantly influences the VSMC phenotype. Notably, both genetic and pharmacological activation of ClpXP inhibits VSMC plasticity and fosters a quiescent, differentiated, and anti-inflammatory VSMC phenotype. The pharmacological activation of ClpP using TIC10, currently in phase III clinical trials for cancer, successfully replicates this phenotype both in vitro and in vivo and markedly reduces aneurysm development in a mouse model of elastase-induced aortic aneurysms. Our mechanistic exploration indicates that ClpP activation regulates the VSMC phenotype by modifying the cellular NAD+/NADH ratio and activating Sirtuin 1. Our findings reveal the crucial role of mitochondrial proteostasis in the regulation of the VSMC phenotype and propose the ClpP protease as a novel, actionable target for manipulating the VSMC phenotype.

The role of exosome derived miRNAs in inter-cell crosstalk among insulin-related organs in type 2 diabetes mellitus.

Exosomes are small extracellular vesicles secreted by almost all cell types, and carry diverse cargo including RNA, and other substances. Recent studies have focused exosomal microRNAs (miRNAs) on various human diseases, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (METS) which accompany the occurrence of insulin resistance. The regulation of insulin signaling has connected with some miRNA expression which play a significant regulatory character in insulin targeted cells or organs, such as fat, muscle, and liver. The miRNAs carried by exosomes, through the circulation in the body fluids, mediate all kinds of physiological and pathological process involved in the human body. Studies have found that exosome derived miRNAs are abnormally expressed and cross-talked with insulin targeted cells or organs to affect insulin pathways. Further investigations of the mechanisms of exosomal miRNAs in T2DM will be valuable for the diagnostic biomarkers and therapeutic targets of T2DM. This review will summarize the molecular mechanism of action of the miRNAs carried by exosomes which are secreted from insulin signaling related cells, and elucidate the pathogenesis of insulin resistance to provide a new strategy for the potential diagnostic biomarkers and therapeutic targets for the type 2 diabetes.

Molecular Mechanisms and Roles of MiR-136-5p in Human Cancer and Other Disorders.

BACKGROUND: MiR-136-5p plays a vital function in regulating developmental processes as well as in the pathophysiology of diseases, with a notable record in tumor suppression. METHODS: This article summarizes the latest findings on the physiological and pathophysiological processes of miR-136-5p in diseases. We searched for relevant studies and selected research articles from the last five years on PubMed with miR-136-5p as the keyword. RESULTS: MiR-136-5p represents a class of microRNAs (miRNAs) that are involved in various human maladies, encompassing cancers, cardio-cerebrovascular disease, diabetes, inflammatory disease, tuberous sclerosis, idiopathic pulmonary fibrosis, and polycystic ovary syndrome. Altered expression of miR-136-5p in specific ailments results in downstream gene expression imbalance, influencing cellular behaviors, such as migration, proliferation, and invasion. Furthermore, miR-136-5p is implicated in five signaling pathways, where it is critical in the onset and advancement of a number of illnesses. Additionally, it has the potential to promote drug resistance to a variety of medications. CONCLUSION: The current review aims to elucidate the role of miR-136-5p in both cancer progression and non-cancerous disorders, emphasizing dysregulated signaling pathways. It also sheds light on the potential of this miRNA as a prognostic biomarker in cancer, offering valuable insights and directions for future research.

miR-743b-3p promotes hepatic lipogenesis via branched-chain amino acids (BCAA) metabolism by targeting PPM1K in aged mice.

BACKGROUND: Lipid metabolism disorders appear to play an important role in the ageing process, thus understanding the cellular and molecular mechanisms underlying the association of ageing with elevated vulnerability to lipid metabolism related diseases is crucial towards promoting quality of life in old age. MicroRNAs (miRNAs) have emerged as crucial regulators of lipid metabolism, and some miRNAs have key roles in ageing. METHODS: In this study, we investigated changes in liver lipid metabolism of ageing mice and the mechanisms of the altered expression of miRNAs in the ageing liver which contributes to the age-dependent increase in lipid synthesis. Here we found that miR-743b-3p was higher expressed in the liver tissues of ageing mice through the small RNA sequencing and bioinformatics analysis, and its target PPM1K was predicted and confirmed the target relationship of miR-743b-3p with PPM1K in the aged mouse liver tissues and the cultured senescent hepatocytes in vitro. Moreover, using the transfected miR-743b-3p mimics/inhibitors into the senescent hepatocyte AML12. RESULTS: We found that miR-743b-3p inhibition reversed the hepatocyte senescence, and finally decreased the expression of genes involved in lipid synthesis(Chrebp, Fabp4, Acly and Pparγ) through increasing the target gene expression of PPM1K which regulated the expression of branched-chain amino acids (BCAA) metabolism-related genes (Bckdhα, Bckdk, Bcat2, Dbt). CONCLUSIONS: These results identify that age-induced expression of miR-743b-3p inhibits its target PPM1K which induces BCAA metabolic disorder and regulates hepatocyte lipid accumulation during ageing.

Ultrafast magnetization enhancement via the dynamic spin-filter effect of type-II Weyl nodes in a kagome ferromagnet.

The magnetic type-II Weyl semimetal (MWSM) Co3Sn2S2 has recently been found to host a variety of remarkable phenomena including surface Fermi-arcs, giant anomalous Hall effect, and negative flat band magnetism. However, the dynamic magnetic properties remain relatively unexplored. Here, we investigate the ultrafast spin dynamics of Co3Sn2S2 crystal using time-resolved magneto-optical Kerr effect and reflectivity spectroscopies. We observe a transient magnetization behavior, consisting of spin-flipping dominated fast demagnetization, slow demagnetization due to overall half-metallic electronic structures, and an unexpected ultrafast magnetization enhancement lasting hundreds of picoseconds upon femtosecond laser excitation. By combining temperature-, pump fluence-, and pump polarization-dependent measurements, we unambiguously demonstrate the correlation between the ultrafast magnetization enhancement and the Weyl nodes. Our theoretical modelling suggests that the excited electrons are spin-polarized when relaxing, leading to the enhanced spin-up density of states near the Fermi level and the consequently unusual magnetization enhancement. Our results reveal the unique role of the Weyl properties of Co3Sn2S2 in femtosecond laser-induced spin dynamics.

Evaluation of renal tubular function by multiparametric functional MRI in early diabetes.

Purpose To evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI. Methods Twenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests. Results At baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide - pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively). Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

Magnetic Resonance Imaging in Atherosclerotic Renal Artery Stenosis: The Update and Future Directions from Interventional Perspective.

Background: Atherosclerotic renal artery stenosis (ARAS) is a condition where the renal arteries become narrowed due to atherosclerosis, leading to reduced blood flow to the kidneys and various renal complications. The effectiveness of interventional treatments, such as renal artery angioplasty and stenting, remains debated, making patient selection for these procedures challenging. Summary: This review focuses on the diagnosis and management of ARAS, with a particular emphasis on the potential role of functional magnetic resonance imaging (MRI) in evaluating renal function and mechanisms. By summarizing current diagnostic approaches and outcomes of interventional treatments, the review highlights the importance of informed clinical decision-making in ARAS management. Functional MRI emerges as a promising noninvasive tool to assess renal function, aiding in patient stratification and treatment planning. Key Messages: The efficacy of interventional treatments for ARAS requires further investigation and careful patient selection. Functional MRI holds promise as a noninvasive means to assess renal function and mechanisms, potentially guiding more effective clinical decisions in ARAS management. Advancing research in diagnostic methods, particularly functional MRI, can enhance our understanding and improve the treatment outcomes for ARAS patients.

Changing attitudes toward homosexuality in South Korea, 1996-2018.

Women are often considered more liberal than men on controversial social issues, but gender gaps in sociopolitical attitudes across different age groups have not been fully explored. This study challenges the taken-for-granted gender differences in public attitudes toward homosexuality by examining both between-gender gaps and within-gender changes across the life course. Using data from five waves of the World Values Survey in South Korea, we explore gender and age differences in Korean adults' attitudes toward homosexuality from 1996 to 2018. Consistent with previous research, people become more conservative as they get older, and in general, women are more accepting of homosexuality than men, accounting for sociodemographic covariates. However, this gender difference is conditioned by people's life stages. Only among young adults (aged 18-29) were female respondents more accepting of homosexuality than their male counterparts. For people aged 30 and older, there are no significant gender differences in attitudes, and for both women and men, homosexuality is mostly unacceptable during their mid (aged 50-59) and late adulthood (aged 60+). Further mediation investigation has shown gendered mechanisms behind age differences in homosexuality acceptability. For both women and men, traditional family/gender attitudes provide significant explanations about age differences in homosexuality, while for women, not for men, family status, especially the number of children, makes older women more conservative in homosexuality issues. We suggest that heteropatriarchal social structures may lead to a resistance to attitudinal changes in non-traditional family forms, such as homosexuality.

miR-155-5p promotes hepatic steatosis via PICALM-mediated autophagy in aging hepatocytes.

BACKGROUND: Hepatic steatosis, a lipid disorder characterized by the accumulation of intrahepatic fat, is more prevalent in the elderly population. This study investigates the role of miR-155-5p in the autophagy dysregulation of aging hepatic steatosis. METHODS: We established an aging mouse model in vivo and a hepatocellular senescence model induced by low serum and palmitic acid in vitro. The fluctuations of microRNAs were derived from RNA-seq data and confirmed by qPCR in 4- and 18-month-old mouse liver tissues. Hematoxylin-eosin (H&E) staining observed pathological changes. Markers of senescence, autophagy, and lipolysis genes were analyzed using Western blot and qPCR. Bioinformatics analysis predicted miR-155-5p's target gene PICALM, confirmed by dual luciferase reporter assay and transfection of miR-155-5p mimic/inhibitor into senescent hepatocytes. RESULTS: Senescent markers (p21, p16, and p-P53) and miR-155-5p were up-regulated in aging liver tissues and senescent hepatocytes. Bioinformatics analysis identified PICALM as a target gene of miR-155-5p, a finding further supported by dual luciferase reporter assays. Inhibition of miR-155-5p reduced expression of senescent marker genes (p16, p21, p-P53), improved autophagy (evidenced by increased LC3B-II and ATG5, and decreased P62), and enhanced lipolysis (indicated by increased ATGL and p-HSL) in senescent hepatocytes. Oil red O staining confirmed that miR-155-5p inhibition significantly reduced lipid accumulation in these cells. CONCLUSIONS: This study suggests a potential new therapeutic approach for age-related hepatic steatosis through the inhibition of miR-155-5p to enhance autophagy.

CT-based radiomics: predicting early outcomes after percutaneous transluminal renal angioplasty in patients with severe atherosclerotic renal artery stenosis.

This study aimed to comprehensively evaluate non-contrast computed tomography (CT)-based radiomics for predicting early outcomes in patients with severe atherosclerotic renal artery stenosis (ARAS) after percutaneous transluminal renal angioplasty (PTRA). A total of 52 patients were retrospectively recruited, and their clinical characteristics and pretreatment CT images were collected. During a median follow-up period of 3.7 mo, 18 patients were confirmed to have benefited from the treatment, defined as a 20% improvement from baseline in the estimated glomerular filtration rate. A deep learning network trained via self-supervised learning was used to enhance the imaging phenotype characteristics. Radiomics features, comprising 116 handcrafted features and 78 deep learning features, were extracted from the affected renal and perirenal adipose regions. More features from the latter were correlated with early outcomes, as determined by univariate analysis, and were visually represented in radiomics heatmaps and volcano plots. After using consensus clustering and the least absolute shrinkage and selection operator method for feature selection, five machine learning models were evaluated. Logistic regression yielded the highest leave-one-out cross-validation accuracy of 0.780 (95%CI: 0.660-0.880) for the renal signature, while the support vector machine achieved 0.865 (95%CI: 0.769-0.942) for the perirenal adipose signature. SHapley Additive exPlanations was used to visually interpret the prediction mechanism, and a histogram feature and a deep learning feature were identified as the most influential factors for the renal signature and perirenal adipose signature, respectively. Multivariate analysis revealed that both signatures served as independent predictive factors. When combined, they achieved an area under the receiver operating characteristic curve of 0.888 (95%CI: 0.784-0.992), indicating that the imaging phenotypes from both regions complemented each other. In conclusion, non-contrast CT-based radiomics can be leveraged to predict the early outcomes of PTRA, thereby assisting in identifying patients with ARAS suitable for this treatment, with perirenal adipose tissue providing added predictive value.

Race/Ethnicity, Nativity, and Gender Disparities in Unmet Care Needs Among Older Adults in the United States.

BACKGROUND AND OBJECTIVES: Although disparities in disability and the unequal distribution of care resources are widely discussed in the literature, there has been less research on disparities in experiencing unmet care needs among older adults. This study aims to investigate how unmet care needs are unevenly distributed across social groups with various intersecting identities, such as race/ethnicity, nativity, and gender, although considering their care needs and care networks, drawing on the conceptual framework of the pathway to unmet needs. RESEARCH DESIGN AND METHODS: The data for this study came from the National Health and Aging Trends Study (2011-2018), and the study sample consisted of 7,061 Medicare beneficiaries who needed assistance with daily activities. Questions about unmet care needs were in the form of consequences related to difficulty or lack of help with daily activities. Mixed-effects negative binomial regression models were used to predict rates of unmet needs. RESULTS: Older adults of color, especially women, experienced higher rates of unmet care needs compared with their White and male counterparts. Although Black-White and gender differences in unmet needs were mostly explained by unequal exposures to care needs and differential care networks, Hispanic women and foreign-born Hispanic men were still at a disadvantage even after adjusting for these covariates. DISCUSSION AND IMPLICATIONS: These results emphasize the importance of adopting an intersectional approach to enhance the quality of long-term services and support for older adults facing social disadvantages.

Protein Phosphatase 2A Activation Promotes Heart Transplant Acceptance in Mice.

BACKGROUND: Although heart transplantation is the definitive treatment for heart failure in eligible patients, both acute and chronic transplant rejection frequently occur. Protein phosphatase 2A (PP2A) activity is critical in maintaining tissue and organ homeostasis. In this study, we evaluated the effect of a novel class of small molecule activators of PP2A (SMAPs) on allograft rejection in a mouse heterotopic heart transplantation model. METHODS: Recipient mice were administered with DT-061 (a pharmaceutically optimized SMAP) or vehicle by oral gavage beginning 1 d after transplantation. Histological and immunofluorescence analyses were performed to examine allograft rejection. Regulatory T cells (Treg) from recipient spleens were subjected to flow cytometry and RNA sequencing analysis. Finally, the effect of DT-061 on smooth muscle cells (SMCs) migration and proliferation was assessed. RESULTS: DT-061 treatment prolonged cardiac allograft survival. SMAPs effectively suppressed the inflammatory immune response while increasing Treg population in the allografts, findings corroborated by functional analysis of RNA sequencing data derived from Treg of treated splenic tissues. Importantly, SMAPs extended immunosuppressive agent cytotoxic T lymphocyte-associated antigen-4-Ig-induced cardiac transplantation tolerance and allograft survival. SMAPs also strongly mitigated cardiac allograft vasculopathy as evidenced by a marked reduction of neointimal hyperplasia and SMC proliferation. Finally, our in vitro studies implicate suppression of MEK/ERK pathways as a unifying mechanism for the effect of PP2A modulation in Treg and SMCs. CONCLUSIONS: PP2A activation prevents cardiac rejection and prolongs allograft survival in a murine model. Our findings highlight the potential of PP2A activation in improving alloengraftment in heart transplantation.

Parental Death Across the Life Course, Social Isolation, and Health in Later Life: Racial/Ethnic Disadvantage in the U.S.

Bereavement is a risk factor for poor health, yet prior research has not considered how exposure to parental death across the life course may contribute to lasting social isolation and, in turn, poor health among older adults. Moreover, prior research often fails to consider the racial context of bereavement in the United States wherein Black and Hispanic Americans are much more likely than White Americans to experience parental death earlier in life. The present study uses longitudinal data from the Health and Retirement Study (HRS; 1998-2016) to consider linkages of parental death, social isolation, and health (self-rated health, functional limitations) for Black, Hispanic, and White older adults. Findings suggest that exposure to parental death is associated with higher levels of isolation, greater odds of fair/poor self-rated health, and greater odds of functional limitations in later life. Moreover, social isolation partially explains associations between parental bereavement and later-life health. These patterns persist net of psychological distress-an additional psychosocial response to bereavement. Racial inequities in bereavement are central to disadvantage: Black and Hispanic adults are more likely to experience a parent's death earlier in the life course, and this differential exposure to parental death in childhood or young adulthood has implications for racial and ethnic inequities in social isolation and health throughout life.

Race/Ethnicity, Nativity, and Gender Disparities in Mental Health Trajectories from Mid- to Later-Life: A Life Course-Intersectional Approach.

BACKGROUND: Numerous studies have highlighted mental health disparities based on race/ethnicity, nativity, and gender across different life stages. However, few have investigated how the intersectionality of these factors influences mental health trajectories during midlife to late life. This study fills this gap by adopting a life course-intersectional approach, viewing mental health trajectories as dynamic processes shaped by the combined influences of race/ethnicity, nativity, and gender. It explores social, psychological, and physiological pathways contributing to these disparities. DESIGN: Using data from the Health and Retirement Study (2006-2018; N = 38,049 observations) and growth curve models, this study examines how intra-individual trends in depressive symptoms (measured as CES-D scale, 07) are influenced by the intersection of race/ethnicity, nativity, and gender. It also investigates the impact of objective and subjective social isolation and physical health on group disparities in mental health trajectories. RESULTS: The findings reveal that, during mid- to early late-life, most Black and Hispanic Americans experience higher levels of depressive symptoms compared to their White counterparts (disparities ranging from 0.184 to 0.463 for men and 0.117 to 0.439 for women). However, this disadvantage diminishes for US-born Hispanic men and US-born Black women (0.014-0.031 faster decrease rates compared to US-born White), while it intensifies for Hispanic immigrants (0.017-0.018 slower decrease rates compared to US-born White) in advanced ages. Mediation analysis demonstrates that both social isolation and physical health contribute to these disparities, with physical health explaining a larger portion, particularly in differences between immigrant Hispanic women and US-born Whites. CONCLUSION: This study underscores the importance of a life course-intersectional approach in understanding mental health disparities. It emphasizes the need for improved social welfare systems and community-level interventions targeting the specific challenges faced by older Hispanic immigrants, especially women who encounter multiple forms of oppression.

miR-871-5p/PGC1α Regulates Aging-Induced Lipid Deposition in Hepatocytes Through Fatty Acid ß-Oxidation.

This study investigated the role of the miR-871-5p/proliferator-activated receptor α (PGC1α) pathway in ameliorating hepatic steatosis. We examined miR-871-5p expression in liver tissues of aging mice and AML12 senescent cells co-induced by low serum and palmitic acid (PA). Bioinformatics and multiple experiments were employed to validate the expression level of the target gene PGC1α for miR-871-5p. In this study, we aimed to investigate the potential role of miR-871-5p in regulating hepatic lipid deposition associated with aging. To do so, we performed in vitro transfection of both miR-871-5p mimic and inhibitor into senescent hepatocytes. Our results showed that miR-871-5p could inhibit PGC1α expression and cause lipid deposition in the liver due to aging. miR-871-5p controls this process by regulating PGC1α/fatty acid ß-oxidation. H&E staining displayed the appearance of fat vacuoles in the livers of aging mice, and fatty acid ß-oxidation-related genes (acyl-coenzyme A oxidase 1 carnitine palmitoyl transferase 1α and peroxisome proliferator-activated receptor α) expression was significantly reduced. Lipogenic genes (sterol regulatory element binding protein 1C and fatty acid synthase) expression level was increased in the livers of aging mice. In AML12 cells co-induced by low serum and PA, miR-871-5p mimics decreased PGC1α expression and increased lipid droplet accumulation in senescent hepatocytes. Conversely, miR-871-5p inhibitor promoted PGC1α expression and reduced lipid deposition in senescent hepatocytes. Our findings suggest that inhibiting miR-871-5p could be crucial in ameliorating aging-associated hepatic steatosis. These findings offer valuable insights into the molecular mechanisms driving hepatic steatosis in aging.

Global research trends on immunotherapy in cancer: A bibliometric analysis.

Cancer immunotherapy has been gradually introduced and has undergone noteworthy developments in recent years. The number of scientific publications has been expanding, and the progression in this field has been rapidly evolving with time. This study aimed to use bibliometric analysis to examine the past 20 years of research on cancer immunotherapy and identify future hotspots. A literature search for medical publications on immunotherapy in cancer from 2000 to 2021 was conducted in the Web of Science Core Collection on March 1, 2022. Visualization analysis was performed using VOSviewer software (version 1.6.16). From 2000 to 2021, a total of 18,778 publications were retrieved. Annual publication output grew rapidly from 366 in 2000 to 3,194 in 2021. The USA issued the largest number of publications (n = 6,739, 35.89%), with the University of Texas System making the largest contribution (n = 802, 4.27%). A total of 976 meaningful topics were identified and further classified into 4 different clusters (immune mechanism, cancer biology, immunotherapy and clinical trials). The most common research topics included 'expression', 'chemotherapy', 'dendritic cells', 'pembrolizumab' and 'open-label'. Highly identified cancer types included hepatocellular, bladder, breast and lung cancer. A shift in popularity from mechanism research to clinical trials was observed, indicating that clinical application would be the center of attention in the future. Attention has been given to the field of cancer immunotherapy, and this trend will continue in the future. This study provides an unbiased visualization analysis on this topic in a scale-efficient manner for further research.

Fucoidan derived from Sargassum pallidum alleviates metabolism disorders associated with improvement of cardiac injury and oxidative stress in diabetic mice.

Type 2 diabetes mellitus (T2DM) and its complications have become a serious global health epidemic. Cardiovascular complications have considered as a major cause of high mortality in diabetic patients. Fucoidans from brown algae have diverse medicinal activities, however, few studies reported pharmacological activity of Sargassum. pallidum fucoidan (Sp-Fuc). Therefore, the aim of this study was to investigate the effects of Sp-Fuc on diabetic symptoms and cardiac injury in spontaneous diabetic db/db mice. SP-Fuc at 200 mg/(kg/d) was administered intragastrically to db/db mice for 8 weeks, the effects on hyperlipidemia, hyperglycemia, insulin resistance, and cardiac damage, as well as oxidative stress, inflammation, Nrf2/ARE, and NF-κB signaling pathways, were investigated. Our data demonstrated that Sp-Fuc significantly (p < 0.05) decreased body weights, hyperlipidemia, and hyperglycemia in db/db mice, along with improved insulin sensitivity. Additionally, Sp-Fuc significantly (p < 0.05) alleviated cardiac dysfunction and pathological morphology of cardiac tissue. Sp-Fuc also significantly (p < 0.05) decreased lipid peroxidation, increased antioxidant function, as well as reduced cardiac inflammation, possibly through Nrf2/ARE and NF-κB signaling. Sp-Fuc can ameliorate the metabolism disorders of glucose and lipid in diabetic mice by activating Nrf2/ARE antioxidant signaling, simultaneously reducing cardiac redox imbalance and inflammatory damage. The present findings provide a perspective on the therapy strategy for T2DM and its complications.

CCN2 deficiency in smooth muscle cells triggers cell reprogramming and aggravates aneurysm development.

Vascular smooth muscle cell (SMC) phenotypic switching is widely recognized as a key mechanism responsible for the pathogenesis of several aortic diseases, such as aortic aneurysm. Cellular communication network factor 2 (CCN2), often upregulated in human pathologies and animal disease models, exerts myriad context-dependent biological functions. However, current understanding of the role of SMC-CCN2 in SMC phenotypic switching and its function in the pathology of abdominal aortic aneurysm (AAA) is lacking. Here, we show that SMC-restricted CCN2 deficiency causes AAA in the infrarenal aorta of angiotensin II-infused (Ang II-infused) hypercholesterolemic mice at a similar anatomic location to human AAA. Notably, the resistance of naive C57BL/6 WT mice to Ang II-induced AAA formation is lost upon silencing of CCN2 in SMC. Furthermore, the pro-AAA phenotype of SMC-CCN2-KO mice is recapitulated in a different model that involves the application of elastase-ß-aminopropionitrile. Mechanistically, our findings reveal that CCN2 intersects with TGF-ß signaling and regulates SMC marker expression. Deficiency of CCN2 triggers SMC reprograming associated with alterations in Krüppel-like factor 4 and contractile marker expression, and this reprograming likely contributes to the development of AAA in mice. These results identify SMC-CCN2 as potentially a novel regulator of SMC phenotypic switching and AA biology.