Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis.

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

The geriatric nutrition risk index is longitudinally associated with incident Sarcopenia: evidence from a 5-year prospective cohort.

BACKGROUND: Previous studies investigating the association between the geriatric nutrition risk index (GNRI) and sarcopenia either lacked longitudinal evidence or narrowly focused on specific populations. AIMS: We aimed to reveal longitudinal associations of GNRI with sarcopenia risk in community-dwelling Chinese. We also investigated interaction effects of potential factors on such associations. METHODS: We included participants aged ≥ 50 years with sufficient data from the WCHAT study who did not have sarcopenia at baseline and completed sarcopenia assessment during follow-up. GNRI was calculated according to the formula based on serum albumin, height and weight. Sarcopenia was diagnosed according to the 2019 AWGS consensus. Longitudinal associations between GNRI and sarcopenia were estimated by logistic regression with GNRI as either a continuous or categorical variable by tertiles, using generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1907 participants without baseline sarcopenia were finally included, of whom 327 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, sarcopenia risk decreased with each one standard deviation increase in GNRI (ORadjusted=0.36, 95% CI 0.31-0.43), and it also decreased successively from the lowest (< 111.2) through middle (111.2-117.7) to the highest (≥ 117.8) tertile of the GNRI level (P for trend < 0.001). Similar results were yielded by GEE. Such associations generally remained robust across subgroups with distinct characteristics, while significant differences were observed between different age groups (≥ 65 vs. <65 years) (interaction P-value < 0.05). CONCLUSION: GNRI is longitudinally associated with sarcopenia risk with possibly age-specific differences in association magnitude, which holds implications for policymakers to conduct population-based risk assessment.

The lncRNA TRG-AS1 promotes the growth of colorectal cancer cells through the regulation of P2RY10/GNA13.

BACKGROUND: The lncRNA TRG-AS1 and its co-expressed gene P2RY10 are important for colorectal cancer (CRC) occurrence and development. The purpose of our research was to explore the roles of TRG-AS1 and P2RY10 in CRC progression. METHODS: The abundance of TRG-AS1 and P2RY10 in CRC cell lines (HT-29 and LoVo) and normal colon cells FHC was determined and difference between CRC cells and normal cells was compared. LoVo cells were transfected with si-TRG-AS1 and si-P2RY10 constructs. Subsequently, the viability, colony formation, and migration of the transfected cells were analyzed using cell counting kit-8, clonogenicity, and scratch-wound/Transwell® assays, respectively. Cells overexpressing GNA13 were used to further explore the relationship between TRG-AS1 and P2RY10 along with their downstream functions. Finally, nude mice were injected with different transfected cell types to observe tumor formation in vivo. RESULTS: TRG-AS1 and P2RY10 were significantly upregulated in HT-29 and LoVo compared to FHC cells. TRG-AS1 knockdown and P2RY10 silencing suppressed the viability, colony formation, and migration of LoVo cells. TRG-AS1 knockdown downregulated the expression of P2RY10, GNA12, and GNA13, while P2RY10 silencing downregulated the expression of TRG-AS1, GNA12, and GNA13. Additionally, GNA13 overexpression reversed the cell growth and gene expression changes in LoVo cells induced by TRG-AS1 knockdown or P2RY10 silencing. In vivo experiments revealed that CRC tumor growth was suppressed by TRG-AS1 knockdown and P2RY10 silencing. CONCLUSIONS: TRG-AS1 knockdown repressed the growth of HT-29 and LoVo by regulating P2RY10 and GNA13 expression.

The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target.

INTRODUCTION: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. RESULTS: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. CONCLUSION: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Longitudinal associations between social support and sarcopenia: findings from a 5-year cohort study in Chinese aged ≥50 years.

OBJECTIVES: We aimed to investigate longitudinal associations of overall social support and its sub-domains with risk of sarcopenia and its related traits in community-dwelling Chinese aged ≥ 50 years. We also explored interaction effects of potential factors on such associations. DESIGN: A prospective cohort study. SETTING: Community-based setting in western China. PARTICIPANTS: We included participants aged ≥50 years with complete information necessary for analysis from the WCHAT study who did not have sarcopenia at baseline (2018) and had sufficient data for sarcopenia assessment during 2021-2023. MEASUREMENTS: Exposures included overall social support, subjective support, objective support and support utilization, which were assessed with the Social Support Rating Scale. Outcomes included sarcopenia, low muscle mass (LMM), low muscle strength and low physical performance, which were diagnosed with the 2019 AWGS consensus. Longitudinal associations between the exposures and outcomes were estimated by logistic regression, with generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1905 participants were finally included in the analytic sample, of whom 326 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, higher degree of overall social support (OR = 0.87, 95%CI 0.76-0.99), subjective support (OR = 0.88, 95%CI 0.77-0.99) and support utilization (OR = 0.87, 95%CI 0.77-0.99) correlated with lower sarcopenia risk, among which higher support utilization degree was indicative of lower risk for LMM (OR = 0.88, 95%CI 0.79-0.98). GEE further revealed that overall support degree was negatively associated with risk for sarcopenia (OR = 0.86, 95%CI 0.76-0.98) and LMM (OR = 0.87, 95%CI 0.77-0.99). Objective support was neither significantly associated with sarcopenia nor its traits. No significant interaction effect was observed between overall support and the concerned confounders on sarcopenia (interaction P-value > 0.05). CONCLUSION: Overall social support degree was negatively associated with sarcopenia risk, possibly primarily through affecting muscle mass rather than muscle strength or physical performance, and such an association remained robust across subgroups with distinct characteristics. This holds implications for policymakers to conduct population-based risk assessment, and supportive strategies against sarcopenia should focus on enhancing subjective support and support utilization rather than objective support alone.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer.

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Multidomain interventions for non-pharmacological enhancement (MINE) program in Chinese older adults with mild cognitive impairment: a multicenter randomized controlled trial protocol.

BACKGROUND: Dementia is characterized by progressive neurodegeneration and therefore early intervention could have the best chance of preserving brain health. There are significant differences in health awareness, living customs, and daily behaviors among Chinese older adults compared to Europeans and Americans. Because the synergistic benefits of multidomain non-pharmacological interventions are consistent with the multifactorial pathogenicity of MCI, such interventions are more appealing, easier to adhere to, and more relevant to daily life than single-mode interventions. One of the aims of this study is to verify the effect of multidomain intervention strategies for MCI patients based on Chinese population characteristics, and the other is to establish a biobank and image database to investigate the pathogenesis and pathways of cognitive impairment. METHODS: Our study was designed as a national multicenter, community-based randomized controlled trial (RCT). Twelve medical institutions in ten Chinese cities will participate in our study from 2020 to 2024, and 1080 community residents aged 50 and above will be enrolled as participants. Each sub-center will be responsible for 90 participants (30 people per community) across three communities (non-contact control group, health education group, and multidomain intervention group). The community will be the basic unit of the present study, and all participants in each community will receive the same intervention/control measure. Three working groups are set up in each sub-center to manage the three communities independently to minimize interference at the implementation level between the groups. The multidomain intervention group will receive integrated interventions including exercise, nutrition, sleep, health education and mindfulness meditation. All data generated by the research will be analyzed and processed by statistical software (such as SPSS 21.0, Python 3.0, etc.), and part of the research data will be displayed in the form of graphs and tables. DISCUSSION: In order to achieve a high-quality community intervention study, it is crucial to have a well-designed experimental protocol that follows rigorous scientific methodology. In addition, effective management of quality control measures and monitoring compliance throughout the study process are essential components. This study provides a detailed discussion of stakeholder compliance, research quality control, potential harm and mitigation, auditing, and future plans in order to better address research issues. TRIAL REGISTRATION: ChiCTR2000035012 (July 27, 2020).

Extracellular matrix-derived mechanical force governs breast cancer cell stemness and quiescence transition through integrin-DDR signaling.

The extracellular matrix (ECM) serves as signals that regulate specific cell states in tumor tissues. Increasing evidence suggests that extracellular biomechanical force signals are critical in tumor progression. In this study, we aimed to explore the influence of ECM-derived biomechanical force on breast cancer cell status. Experiments were conducted using 3D collagen, fibrinogen, and Matrigel matrices to investigate the role of mechanical force in tumor development. Integrin-cytoskeleton-AIRE and DDR-STAT signals were examined using RNA sequencing and western blotting. Data from 1358 patients and 86 clinical specimens were used for ECM signature-prognosis analysis. Our findings revealed that ECM-derived mechanical force regulated tumor stemness and cell quiescence in breast cancer cells. A mechanical force of ~45 Pa derived from the extracellular substrate activated integrin ß1/3 receptors, stimulating stem cell signaling pathways through the cytoskeleton/AIRE axis and promoting tumorigenic potential and stem-like phenotypes. However, excessive mechanical force (450 Pa) could drive stem-like cancer cells into a quiescent state, with the removal of mechanical forces leading to vigorous proliferation in quiescent cancer stem cells. Mechanical force facilitated cell cycle arrest to induce quiescence, dependent on DDR2/STAT1/P27 signaling. Therefore, ECM-derived mechanical force governs breast cancer cell status and proliferative characteristics through stiffness alterations. We further established an ECM signature based on the fibrinogen/fibronectin/vitronectin/elastin axis, which efficiently predicts patient prognosis in breast cancer. Our findings highlight the vital role of ECM-derived mechanical force in governing breast cancer cell stemness/quiescence transition and suggest the novel use of ECM signature in predicting the clinical prognosis of breast cancer.

Immunotherapy combined with chemotherapy in the treatment for rare primary mucoepidermoid carcinoma of the liver: a case report.

Primary mucoepidermoid carcinoma of the liver (PMCL) is rare in the hepatic system, with no standard treatment and poor prognosis with a median overall survival of only 120 days. PMCL with immunotherapy has not been reported yet. Here, we present a case of PMCL treated by immunotherapy and chemotherapy. A 64-year-old male with PMCL underwent partial right hepatectomy and liver lesion resection on 19 June 2020. Two months later, the chest computed tomography indicated the presence of multiple nodules in both lungs with higher tumor markers. Considering the presence of a tumor metastasis, the patient received four courses of immunotherapy plus mGEMOX chemotherapy from 8 September 2020. The patient tolerated the combined therapy well, with red moles on the face and chest which were considered as grade 1 reactive cutaneous capillary endothelial proliferation. He also had grade 2 thrombocytopenia and leucopenia after the first course of chemotherapy, but no neutropenia, fatigue, vomiting or diarrhea. However, his disease progressed. The patient refused further treatment and died on 20 April 2021. The overall survival time after diagnosis was 301 days. We describe here the first case report on immunotherapy treatment for PMCL. That suggested immunotherapy combined with chemotherapy may be an option after a hepatic lobectomy for PMCL.

Identification of TGF-ß signaling-related molecular patterns, construction of a prognostic model, and prediction of immunotherapy response in gastric cancer.

Background: TGF-ß signaling pathway plays an essential role in tumor progression and immune responses. However, the link between TGF-ß signaling pathway-related genes (TSRGs) and clinical prognosis, tumor microenvironment (TME), and immunotherapy in gastric cancer is unclear. Methods: Transcriptome data and related clinical data of gastric cancer were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and 54 TSRGs were obtained from the Molecular Signatures Database (MSigDB). We systematically analyzed the expression profile characteristics of 54 TSRGs in 804 gastric cancer samples and examined the differences in prognosis, clinicopathological features, and TME among different molecular subtypes. Subsequently, TGF-ß-related prognostic models were constructed using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to quantify the degree of risk in each patient. Patients were divided into two high- and low-risk groups based on the median risk score. Finally, sensitivity to immune checkpoint inhibitors (ICIs) and anti-tumor agents was assessed in patients in high- and low-risk groups. Results: We identified two distinct TGF-ß subgroups. Compared to TGF-ß cluster B, TGF-ß cluster A exhibits an immunosuppressive microenvironment with a shorter overall survival (OS). Then, a novel TGF-ß-associated prognostic model, including SRPX2, SGCE, DES, MMP7, and KRT17, was constructed, and the risk score was demonstrated as an independent prognostic factor for gastric cancer patients. Further studies showed that gastric cancer patients in the low-risk group, characterized by higher tumor mutation burden (TMB), the proportion of high microsatellite instability (MSI-H), immunophenoscore (IPS), and lower tumor immune dysfunction and exclusion (TIDE) score, had a better prognosis, and linked to higher response rate to immunotherapy. In addition, the risk score and anti-tumor drug sensitivity were strongly correlated. Conclusion: These findings highlight the importance of TSRGs, deepen the understanding of tumor immune microenvironment, and guide individualized immunotherapy for gastric cancer patients.

Crack Unet: Crack Recognition Algorithm Based on Three-Dimensional Ground Penetrating Radar Images.

Three-dimensional (3D) ground-penetrating radar is an effective method for detecting internal crack damage in pavement structures. Inefficient manual interpretation of radar images and high personnel requirements have substantially restrained the generalization of 3D ground-penetrating radar. An improved Crack Unet model based on the Unet semantic segmentation model is proposed herein for 3D ground-penetrating radar crack image processing. The experiment showed that the MPA, MioU, and accuracy of the model were improved, and it displayed better capacity in the radar image crack segmentation task than current mainstream algorithms do, such as deepLabv3, PSPNet, and Unet. In the test dataset without cracks, Crack Unet is on the same level as deepLabv3 and PSPNet, which can meet engineering requirements and display a significant improvement compared with Unet. According to the ablation experiment, the MPA and MioU of Unet configured with PMDA, MC-FS, and RS modules were larger than those of Unet configured with one or two modules. The PMDA module adopted by the Crack Unet model showed a higher MPA and MioU than the SE module and the CBAM module did, respectively. The results show that the Crack Unet model has a better segmentation ability than the current mainstream algorithms do in the task of the crack segmentation of radar images, and the performance of crack segmentation is significantly improved compared with the Unet model. The Crack Unet model has excellent engineering application value in the task of the crack segmentation of radar images.

Association between the domestic use of solid cooking fuel and increased prevalence of depression and cognitive impairment in a big developing country: A large-scale population-based study.

Background: Previous studies have suggested that air pollution affects physiological and psychological health. Using solid fuel at home is a significant source of indoor air pollution. The associations between solid fuel use and depressive symptoms and cognitive health were unclear among older adults from low- and middle-income countries (LMICs). Methods: To evaluate the association of solid fuel use with depressive symptoms and cognitive health among older adults, we obtained data from the Longitudinal Aging Study in India (LASI) and excluded subjects younger than 60 years and without critical data (solid fuel use, depressive symptoms, and cognitive health). The 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) was used to assess depressive symptoms, with more than ten indicative of depression. Cognitive health was assessed using measures from the Health and Retirement Study (HRS), and subjects with the lowest 10th percentile were considered to have cognitive impairment. The participants' responses defined solid fuel use. Multivariable logistic regression, linear regression, subgroup analysis, and interaction tests were performed to appraise the relationship between solid fuel use and depression and cognitive impairment. Results: A total of 29,789 participants over 60 years old were involved in this study. Almost half of the participants (47.5%) reported using solid fuel for home cooking. Compared with clean fuel use, solid fuel use was related to an increased prevalence of depression [odds ratio (OR) 1.09, 95% CI 1.03-1.16] and higher CES-D-10 scores (ß 0.23, 95% CI 0.12-0.35) after fully adjusted covariables. Using solid fuel was also related to a higher risk of cognitive impairment (OR 1.21, 95% CI 1.11-1.32) and a lower cognitive score (ß -0.63, 95% CI -0.79 to -0.47) compared with those who used clean fuel. In the subgroup analysis, the prevalence of depression increased in females and non-smokers. The association of solid fuel use with depression and cognitive impairment exists in subgroups of BMI, economic status, caste, living area, education, and drinking. Conclusions: The use of solid fuel at home was associated with an increased prevalence of depression and cognitive impairment among older adults in India.

The association between serum soluble Klotho and chronic kidney disease among us adults ages 40 to 79 years: Cross-sectional study.

Background: Chronic kidney disease (CKD) is diagnosed in more than 26 million U.S. people, which increases the risk of many adverse events. α-Klotho was reported to have potential effects on kidney function. The purpose of this study was to investigated whether CKD prevalence is associated with α-Klotho levels in the U.S. people aged 40-79 years. Methods: Thirteen thousand five hundred eighty-nine participates in the National Health and Nutrition Examination Survey 2007-2016 aged 40-79 with information of Klotho and kidney function were included. The association between CKD and Klotho was calculated using multivariate linear or logistic regression models with adjustment of several possibly confounding variables. Subgroup analyses stratified by age, BMI, and diabetes mellitus were conducted. The non-linear relationship between Klotho and dependent variables with a non-normality of residues was assessed using smooth curve fitting and the segmented regression (also known as piece-wise regression) models. Results: Among 13,589 participants, the median of Klotho levels was 803.10 pg/mL, mean eGFR of all participants was 86.96 (SD = 19.88) mL/min/1.73 m2, and CKD was diagnosed in 20.11% of them (N = 2733). In the fully adjusted model, eGFR was positively associated with Klotho (ß = 5.14, 95%CI 4.13-6.15, p < 0.001), while CKD was negatively associated with Klotho (stage ≧ 1, OR = 0.62, 95% CI 0.50-0.76, p < 0.001; stage ≧ 3, OR = 0.31, 95% CI 0.24-0.41, p < 0.001). The non-linear relationship showed that occurrence of CKD stage> 1 and albuminuria were negatively associated with Klotho when Klotho smaller than turning point (for whether CKD stage> 1, turning point K = 6.85, Klotho < K, OR = 0.44, p < 0.001; for albuminuria, turning point K = 6.84, Klotho < K, OR = 0.59, p < 0.001). Conclusion: Serum soluble Klotho levels were positively associated with eGFR and negatively associated with the prevalence of CKD, especially in elderly, obese, and diabetic patients.

Potential association between frailty and pTau in community-dwelling older adults.

BACKGROUND: Frailty is a geriatric syndrome characterized by a decline in physiological reserves, and multiple factors contribute to the occurrence and development of frailty. Growing evidence supports a strong link and overlap between frailty and cognitive impairment, but the mechanisms involved have not yet been fully elucidated. AIM: To identify associations between 12 plasma cognition-related biomarkers and frailty in community-dwelling older adults. METHODS: A total of 375 participants (age 70.9 ± 5.8, 165 men and 210 women) were included in this study. Frailty was assessed using the modified Fried frailty phenotype. Participants were divided into not-frail group (n = 313) and frail group (n = 62). Twelve plasma cognitive biomarkers were detected by enzyme-linked immunosorbent assay (ELISA). Multinomial logistic regression was used to explore the association between different biomarkers and frailty status. RESULTS: Among the 12 biomarkers, only pTau was higher in frail individuals than in their not-frail peers (471.3 ± 58.1 pg/mL vs. 451.9 ± 61.1 pg/mL, p = 0.022). No other biomarkers had any significant association with frailty, including total-Tau (tTau), neurofilament light (NFL), amyloid-ß 40 (Aß40), amyloid-ß 40 (Aß42), S100 calcium binding protein B (S100B), visinin-like protein 1 (VLP-1), Alzheimer-associated neuronal thread protein (AD7cNTP), ß-amyloid precursor protein (ßAPP), chitinase-3-like-1 (CHI3L1), soluble complement receptor 1 (sCR1) and heart-type fatty acid binding protein (hFABP). Furthermore, pTau was compared between negative and positive subject groups for each individual criterion of frailty. Significantly higher levels of pTau were observed in those who were positive for the criteria of low grip strength (451.2 ± 61.4 pg/mL vs. 469.1 ± 57.6 pg/mL, p = 0.019), exhaustion (451.2 ± 61.6 pg/mL vs. 466.4 ± 58.4 pg/mL, p = 0.035) and low physical activity (451.1 ± 60.7 pg/mL vs. 465.7 ± 60.7 pg/mL, p = 0.034) when compared to those who were negative for each corresponding criterion. Finally, in the multivariable-adjusted analysis, the association between pTau and frailty was statistically significantly associated (OR: 1.40, 95% CI: 1.04-1.89), even after adjusting. CONCLUSIONS: The present study found a potential association between pTau and frailty. Future works should monitor the longitudinal trajectory of changes of pTau concentrations in frailty older adults. A better understanding of the molecular mechanisms behind will contribute to biomarker research in frailty.

The Association Between Grip Strength and Depression Among Adults Aged 60 Years and Older: A Large-Scaled Population-Based Study From the Longitudinal Aging Study in India.

Background: The association between grip strength and depression in elderly individuals in low- and middle-income countries (LMICs) has rarely been studied. This study aims to explore the relevance of grip strength and depression in the elderly population using data from a national large-scale population. Methods: This study was conducted using data from seniors over 60 years old in wave 1 of the Longitudinal Aging Study in India (LASI). Grip strength is the maximum of three measurements by the dynamometer. Depression symptoms were assessed using 10 items on the Center for Epidemiologic Studies Depression Scale (CESD-10) with a 10-point boundary. Multivariate linear regression analysis, non-linear analysis, subgroup analysis, interaction tests and sensitivity analysis were performed. Results: There were 27,343 participants in this study, including 19,861 participants with low grip strength and 7,482 participants with normal grip strength. The results revealed that grip strength and depression were negatively correlated in elderly individuals after adequate adjustment for confounding factors [odds ratio (OR) = 1.237, 95% confidence interval (CI) 1.172-1.305, p < 0.00001]. The results remained stable after adjusting for all confounding factors (OR = 1.090, 95% CI 1.030-1.155, p = 0.00307). Regression analysis showed that physical activity (PA), comorbidities and cognition may have an impact on the correlation between grip strength and depression symptoms. Smooth curve fit suggested that grip strength and depressive symptoms were linearly related. The interaction test results of gender in the relationship between grip strength and depression were significant (p for interaction < 0.05). Conclusion: Grip strength and depression were negatively correlated in older Indians, and larger prospective studies are needed in the future to determine this association.

Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells.

Background: Diminished sensitivity towards chemotherapy remains the major impediment to the clinical treatment of bladder cancer. However, the critical elements in control of chemotherapy resistance remain obscure. Methods: We adopted improved collagen gels and performed cytotoxicity analysis of doxorubicin (DOX) and mitomycin C (MMC) of bladder cancer cells in a 3D culture system. We then detected the expression of multidrug resistant gene ABCB1, dormancy-associated functional protein chicken ovalbumin upstream-transcription factor 1 (COUPTF1), cell proliferation marker Ki-67, and cellular senescence marker senescence-associated ß-galactosidase (SA-ß-Gal) in these cells. We further tested the effects of integrin blockade or protein kinase B (AKT) inhibitor on the senescent state of bladder cancer. Also, we examined the tumor growth and survival time of bladder cancer mouse models given the combination treatment of chemotherapeutic agents and integrin α2ß1 ligand peptide TFA (TFA). Results: Collagen gels played a repressive role in bladder cancer cell apoptosis induced by DOX and MMC. In mechanism, collagen activated the integrin ß1/AKT cascade to drive bladder cancer cells into a premature senescence state via the p21/p53 pathway, thus attenuating chemotherapy-induced apoptosis. In addition, TFA had the ability to mediate the switch from senescence to apoptosis of bladder cancer cells in xenograft mice. Meanwhile, TFA combined with chemotherapeutic drugs produced a substantial suppression of tumor growth as well as an extension of survival time in vivo. Conclusions: Based on our finding that integrin ß1/AKT acted primarily to impart premature senescence to bladder cancer cells cultured in collagen gel, we suggest that integrin ß1 might be a feasible target for bladder cancer eradication.

Association between Dietary Inflammatory Index and serum Klotho concentration among adults in the United States.

BACKGROUND: Klotho is a hormone that emerges as an antiaging biomarker. However, the influence of the dietary pattern's inflammatory potential on serum Klotho levels in human populations, especially in a general adult population, remains unknown. This study aimed to evaluate the relationship between the dietary inflammatory index (DII) and serum Klotho concentrations in individuals living in the United States.  METHODS : From the 2007-2016 National Health and Nutrition Examination Survey database, data of participants who completed the full 24-h dietary history and underwent serum Klotho testing were analyzed. The association between DII and serum Klotho concentrations was estimated using multivariable linear regression models. We also conducted segmented regression model to examine the threshold effect of DII on serum Klotho concentrations. RESULTS: A total of 10,928 participants were included, with a median serum Klotho concentration of 805.20 pg/mL (IQR: 657.58 - 1001.12) and a median DII of 1.43 (IQR: - 0.16 - 2.82). Multivariable regression showed that participants with high DII scores were associated with low serum Klotho concentrations; when classifying DII into quartiles, after full adjustment, participants in DII quartiles 3 and 4 showed a decrease in Klotho levels (25.27 and 12.44 pg/ml, respectively) compared with those in the lowest quartile (quartile 1) (95% CI: - 41.80, - 8.73 and - 29.83, 4.95, respectively; P for trend = 0.036). The segmented regression showed that the turning point value of DII was - 1.82 (95% CI: - 2.32, - 0.80). A 1-unit increase in DII was significantly associated with lower Klotho levels by - 33.05 (95% CI: - 52.84, - 13.27; P = 0.001) when DII ranges from - 5.18 to - 1.82; however, the relationship was not significant when DII ranges from - 1.82 to 5.42 (P > 0.05). Furthermore, stratified analyses indicated that the observed associations between DII and serum Klotho concentration were stronger among those aged ≥ 56 years, those with normal weight, and those without chronic kidney disease (P for interaction = 0.003, 0.015, and 0.041, respectively). CONCLUSIONS: In summary, we indicated that there was a dose-response relationship between DII and serum Klotho concentrations, suggesting that adhering to an anti-inflammatory diet has beneficial effects on aging and health by increasing the serum Klotho concentration.

H2O2 down-regulates SIRT7's protective role of endothelial premature dysfunction via microRNA-335-5p.

Endothelial senescence is believed to constitute the initial pathogenesis of the atherosclerotic cardiovascular disease (ASCVD). MicroRNA-335-5p (miR-335-5p) expression is significantly up-regulated in oxidative stress-induced endothelial cells (ECs). Sirtuin7 (SIRT7) is considered to prevent EC senescence, yet data on its response to ASCVD risk factors are limited. The present study analyzed the elevated levels of miR-335-5p and the decreased levels of SIRT7 in human umbilical vein endothelial cells (HUVECs), and found that high glucose, tumor necrosis factor-α (TNF-α), and H2O2 are the three contributing factors that induced cellular senescence. The current study also assessed premature endothelial senescence and decreased proliferation, adhesion, migration, and nitric oxide (NO) secretion in HUVECs with these risk factors together with SIRT7-siRNA transfection. It found that the miR-335-5p inhibitor attenuated the down-regulation of SIRT7 expression induced by oxidative stress in HUVECs, and SIRT7 overexpression exerts a rescue effect against miR-335-5p-induced endothelial dysfunction. Furthermore, the direct binding of miR-335-5p to SIRT7 was observed in human embryonic kidney cells 293T (HEK 293T). Therefore, it can be inferred that miR-335-5p down-regulates the expression of SIRT7 in human cells. Current findings may provide deeper insights into the underlying mechanisms of endothelial senescence and potential therapeutic targets of ASCVD as well as other age-related diseases.