Effects of soy protein-rich meals on muscle health of older adults in long-term care: A randomized clinical trial.

OBJECTIVE: This study investigated the effects of a soy protein-rich meal intervention on the muscle health of older adults in long-term care facilities. METHODS: A 12-week single-center randomized controlled trial with a control-group and open-label design was conducted. Eighty-four older adults from a long-term care facility participated in the study. The chefs at the facility cooked three meals using soy protein-rich recipes designed by dieticians. For 12 weeks, the intervention group participants consumed three meals with 30 g of soy protein (10 g/meal) per day, and the control group participants maintained their habitual diets. RESULTS: The 84 participants (mean age, 84.9 ± 7.0 years; 61.9% female) were randomly assigned to an intervention group (43 participants) and a control group (41 participants). The intervention group exhibited significant increases in several lean mass indicators, namely soft lean mass (mean, 1.43 kg; 95% confidence interval [CI]: 0.20-1.65 kg), skeletal muscle mass (mean, 1.20 kg; 95% CI: 0.43-1.96 kg), appendicular skeletal muscle mass (mean, 0.79 kg; 95% CI: 0.07-1.52 kg), and skeletal muscle index (mean, 0.37 kg/m2; 95% CI: 0.05-0.68 kg/m2) (all P < 0.05). These changes were not observed in the control group (all P > 0.05). Notably, calf circumference decreased significantly in the control group (mean, -0.98 cm; 95% CI: -1.61 to -0.36 cm) but was maintained in the intervention group. The differences in the calf circumference and 6-m walk performance of the two groups were significant (P < 0.05). CONCLUSIONS: The 12-week soy protein-rich meal intervention improved the muscle mass and 6-m walk performance of older adults in a long-term care facility.

9-O-monoethyl succinate berberine effectively blocks the PI3K/AKT signaling pathway by targeting Wnt5a protein in inhibiting osteosarcoma growth.

BACKGROUND: Osteosarcoma (OS) is the most common primary bone malignancy, mainly affecting children, adolescents, and young adults, followed by the elderly, with a high propensity for local invasion and metastasis. Although surgery combined with chemotherapy has greatly improved the prognosis of patients with OS, the prognosis for metastatic or recurrent OS is still unsatisfactory. The research community has struggled to develop an effective chemotherapy treatment regimen for this tumor. For the creation of an OS drug, our research team has effectively developed and manufactured a new drug named 9-O-monoethyl succinate berberine (B2). PURPOSE: In this study, we aimed to investigate the roles and functions of B2 in the treatment of OS. METHODS: Human OS cell lines and mouse OS cell lines were used in vitro cell experiments, while BALB/c mice and BALB/c nude mice were used in vivo animal experiments. To investigate the molecular mechanism of B2 treatment, antibody microarray analysis, proteomic analysis, quantitative real-time PCR, immunohistochemical labeling, and western blotting analysis were mostly carried out. We assessed the impact of B2 on OS therapy and the underlying molecular pathways based on in vivo and in vitro studies. RESULTS: Our findings demonstrated that B2 has the ability to inhibit the proliferation, migration, and invasion of OS cell lines, while also induce apoptosis in vitro. Additionally, our results suggested that B2 could effectively impede the growth of OS and has less heart and lung damage than cisplatin in vivo. In terms of mechanism, we discovered that the Wnt5a protein is significantly expressed in OS cell lines. Knockdown of Wnt5a can restrict OS cell lines proliferation, and overexpression of Wnt5a had the opposite results. B2 also had a strong affinity with Wnt5a and can inhibit the PI3K/AKT signaling pathway by targeting Wnt5a. Tumor cells proliferation can be inhibited by blocking the PI3K/AKT signaling pathway, and Wnt5a-mediated inactivation of the PI3K/AKT signaling pathway after B2 treatment. In vitro and in vivo experiments with Wnt5a overexpression, B2 significantly inhibited tumor growth, migration, and invasion. Moreover, B2 and Wnt5a also have a strong structural binding ability (binding energy of -7.567 ± 0.084 kcal/mol, binding values of 2.860 ± 0.434 µM), and three hydrogen bonds are generated at the docking positions of amino acids GLN286, ASN288, and ASN292. CONCLUSION: In summary, our study confirmed for the first time that the growth of OS is related to abnormal overexpression of Wnt5a protein, and designed a novel small molecule inhibitor named B2 targeting Wnt5a protein, which inhibits OS growth by mediating PI3K/AKT signaling pathway by targeting Wnt5a protein. Our research laid the groundwork for the promotion of B2 as a new anticancer drug and revealed an innovative chemotherapeutic strategy for OS therapy.

Cobalt(III)-Macrocyclic Scaffolds with Anti-Cancer Stem Cell Activity.

Cobalt(III) compounds with tetradentate ligands have been widely employed to deliver cytotoxic and imaging agents into cells. A large body of work has focused on using cobalt(III)-cyclam scaffolds for this purpose. Here, we investigate the cytotoxic properties of cobalt(III) complexes containing 14-membered macrocycles related to cyclam. A breast cancer stem cell (CSC) in vitro model was used to gauge efficacy. Specifically, [Co(1,4,7,11-tetraazacyclotetradecane)Cl2]+ (1) and [Co(1-oxa-4,8,12-triazacyclotetradecane)Cl2]+ (2) were synthesised and characterised, and their breast CSC activity was determined. The cobalt(III) complexes 1 and 2 displayed micromolar potency towards bulk breast cancer cells and breast CSCs grown in monolayers. Notably, 1 and 2 displayed selective potency towards breast CSCs over bulk breast cancer cells (up to 4.5-fold), which was similar to salinomycin (an established breast CSC-selective agent). The cobalt(III) complexes 1 and 2 were also able to inhibit mammosphere formation at low micromolar doses (with respect to size and number). The mammopshere inhibitory effect of 2 was similar to that of salinomycin. Our studies show that cobalt(III) complexes with 1,4,7,11-tetraazacyclotetradecane and 1-oxa-4,8,12-triazacyclotetradecane macrocycles could be useful starting points for the development of new cobalt-based delivery systems that can transport cytotoxic and imaging agents into breast CSCs.

Interaction between depression and non-essential heavy metals (Cd, Pb, and Hg) on metabolic diseases.

OBJECTIVES: Metal exposure and depression have each been associated with adverse metabolic diseases, but no study has examined the potential interaction between them. We examined the interaction of depression on the association between metals and metabolic diseases among adults. STUDY DESIGN: The interaction of depression in the relationship between metal and metabolic disease in adults was investigated using NHANES, a cross-sectional survey design. METHODS: By employing data from the NHANES database spanning the years 2007-2018, regression models were employed to investigate the independent impacts of heavy metals (cadmium, lead, and mercury) and depression on metabolic diseases (type 2 diabetes, hypertension, hyperlipidemia, metabolic syndrome). Subsequently, the association between metals and metabolic diseases was explored stratified by depression, and the interaction between heavy metals and depression was explored. Because of the complex NHANES design, statistical evaluations were adjusted through weighting to represent the populace of the United States. RESULTS: We found log transformed-urinary lead was significantly associated with type 2 diabetes (OR: 2.33; 95 % CI: 1.23, 4.41) in adults with depression. Log transformed-urinary lead was not associated with type 2 diabetes (OR: 0.84; 95 % CI: 0.56, 1.27) in adults without depression. The interaction between Pb and depression in type 2 diabetes was significant (P for interaction = 0.033). Log transformed-urinary lead * depression was significantly associated with type 2 diabetes (OR: 1.82; 95 % CI: 1.01, 3.34) in adults. There was no significant interaction between cadmium and mercury exposure and depression in patients with type 2 diabetes, hypertension, hyperlipidemia, and metabolic syndrome (P for interaction > 0.05). CONCLUSIONS: The presence of depression positively modified the adverse associations between urinary lead and type 2 diabetes.

An immunogenic anti-cancer stem cell bi-nuclear copper(II)-flufenamic acid complex.

An asymmetric bi-nuclear copper(II) complex with both cytotoxic and immunogenic activity towards breast cancer stem cells (CSCs) is reported. The bi-nuclear copper(II) complex comprises of two copper(II) centres bound to flufenamic acid and 3,4,7,8-tetramethyl-1,10-phenanthroline. The bi-nuclear copper(II) complex exhibits sub-micromolar potency towards breast CSCs grown in monolayers and three-dimensional cultures. Remarkably, the bi-nuclear copper(II) complex is up to 25-fold more potent toward breast CSC mammospheres than salinomycin (a gold standard anti-breast CSC agent) and cisplatin (a clinically administered metallodrug). Mechanistic studies showed that the bi-nuclear copper(II) complex readily enters breast CSCs, elevates intracellular reactive oxygen species levels, induces apoptosis, and promotes damage-associated molecular pattern release. The latter triggers phagocytosis of breast CSCs by macrophages. As far as we are aware, this is the first report of a bi-nuclear copper(II) complex to induce engulfment of breast CSCs by immune cells.

The miR166 targets CsHDZ3 genes to negatively regulate drought tolerance in tea plant (Camellia sinensis).

Drought is the stressor with a significant adverse impact on the yield stability of tea plants. HD-ZIP III transcription factors (TFs) play important regulatory roles in plant growth, development, and stress responses. However, whether and how HD-ZIP III TFs are involved in drought response and tolerance in tea plants remains unclear. Here, we identified seven HD-ZIP III genes (CsHDZ3-1 to CsHDZ3-7) in tea plant genome. The evolutionary analysis demonstrated that CsHDZ3 members were subjected to purify selection. Subcellular localization analysis revealed that all seven CsHDZ3s located in the nucleus. Yeast self-activation and dual-luciferase reporter assays demonstrated that CsHDZ3-1 to CsHDZ3-4 have trans-activation ability whereas CsHDZ3-5 to CsHDZ3-7 served as transcriptional inhibitors. The qRT-PCR assay showed that all seven CsHDZ3 genes could respond to simulated natural drought stress and polyethylene glycol treatment. Further assays verified that all CsHDZ3 genes can be cleaved by csn-miR166. Overexpression of csn-miR166 inhibited the expression of seven CsHDZ3 genes and weakened drought tolerance of tea leaves. In contrast, suppression of csn-miR166 promoted the expression of seven CsHDZ3 genes and enhanced drought tolerance of tea leaves. These findings established the foundation for further understanding the mechanism of CsHDZ3-miR166 modules' participation in drought responses and tolerance.

Association of macronutrient consumption quality, food source and timing with depression among US adults: A cross-sectional study.

BACKGROUND: Growing evidence suggests that meal timing may influence dietary choices and mental health. Thus, this study examined the association between macronutrient consumption quality, food source, meal timing, and depression prevalence in Americans. METHODS: 23,313 National Health and Nutrition Survey participants from 2007 to 2016 were included in this cross-sectional study. Macronutrient intake was calculated for all day, dinner, and breakfast and subtypes into 4 classes. Based on the Patient Health Questionnaire, depression was defined as a 9-item score ≥ 10 on the PHQ-9. The correlation between macronutrients and depression prevalence was estimated with multivariable logistic regression models and isocaloric substitution effects. RESULTS: Low-quality carbohydrates (OR = 1.54, 95 % CI: 1.11, 2.12) were positively linked to depression compared with the lowest quartile, after adjusting for age and other covariates. In contrast, total high-quality carbohydrate (OR = 0.52, 95 % CI: 0.40, 0.66), total animal protein (OR = 0.60, 95 % CI: 0.45, 0.80), and total vegetable protein (OR = 0.61, 95 % CI: 0.43, 0.85) were negatively associated with depression was negatively associated. Replacing low-quality carbohydrates with high-quality carbohydrates throughout the day reduced the risk of depression by approximately 15 %. LIMITATIONS: Cross-sectional data. CONCLUSION: All in all, diet plays a crucial role in the prevention and treatment of depression. Especially in terms of macronutrient intake, high-quality, moderate intake can reduce the risk of depression. However, different subtypes of macronutrient consumption may have different effects on depression, so it becomes crucial to carefully consider the selection and combination of macronutrients.

Identification of novel serum metabolic signatures to predict chronic kidney disease among Chinese elders using UPLC-Orbitrap-MS.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern. However, validated and broadly applicable biomarkers for early CKD diagnosis are currently not available. We aimed to identify serum metabolic signatures at an early stage of CKD to provide a reference for future investigations into the early diagnostic biomarkers. METHODS: Serum metabolites were extracted from 65 renal dysfunction (RD) patients and 121 healthy controls (discovery cohort: 12 RD patients and 55 health participants; validation cohort: 53 RD patients and 66 health participants). Metabolite extracts were analyzed by ultraperformance liquid chromatography coupled with quadrupole-electrostatic field orbital trap mass spectrometry (UPLC-QE-Orbitrap MS) for untargeted metabolomics. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to detect different compounds between groups. Receiver operating characteristic (ROC) curve analysis was carried out to determine the diagnostic value of the validated differential metabolites between groups. We referred to the Kyoto Encyclopedia of Gene and Genomes (KEGG) to elucidate the metabolic pathways of the validated differential metabolites. RESULTS: A total of 22 and 23 metabolites had significantly different abundances in the discovery and validation cohort, respectively. Six of them (creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine) in the RD group was more abundant than that of the health group in both cohorts. The combination of the six validated differential metabolites were able to accurately detect RD (AUC 0.86). Three of the six metabolites are involved in the metabolism of arginine and proline. CONCLUSIONS: The present study highlights that creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine are metabolite indicators with potential predictive value for CKD.

Associations of dietary inflammatory index with low estimated glomerular filtration rate, albuminuria and chronic kidney disease in U.S adults: Results from the NHANES 2011-2018.

BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is characterized by a high inflammation status with ever-increasing prevalence, and defined as low estimated glomerular filtration rate (eGFR) or albuminuria. Both low eGFR and albuminuria can have independent effects on the body. The dietary inflammatory index (DII) is a validated tool used to assess the inflammatory potential of the diet. We aim to explore not only the association between DII and CKD, but also the associations of DII with low eGFR and albuminuria, respectively. In addition, their associations in different subgroups remain to be explored. METHODS AND RESULTS: 18,070 participants from the 2011-2018 NHANES with complete data of dietary intake and laboratory data were involved in our study. The data of 24-hour dietary recall interview was used to calculate DII, CKD could be reflected by laboratory data of creatinine and albumin. Then weighted multivariate logistic regression models and subgroup analyses were performed. The prevalence of low eGFR, albuminuria and CKD were 6.8%, 9.8% and 14.5%, respectively. A positive association between DII and low eGFR was observed (OR=1.12, 95%CI: 1.05-1.21), Q2, Q3 and Q4 are positively associated with a significant 39%, 65% and 71% increased risk of low eGFR compared with Q1 (P for trend<0.05). DII was also associated with CKD (OR=1.06, 95%CI: 1.01-1.11). CONCLUSION: Significant positive associations of DII with CKD and low eGFR were observed. But we didn't find such association between DII and albuminuria.

Associations of the magnesium depletion score and magnesium intake with diabetes among US adults: an analysis of the National Health and Nutrition Examination Survey 2011-2018.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS: MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Exposure to cadmium and lead is associated with diabetic kidney disease in diabetic patients.

BACKGROUND: Cadmium (Cd) and lead (Pb) exhibit nephrotoxic activity and may accelerate kidney disease complications in diabetic patients, but studies investigating the relation to diabetic kidney disease (DKD) have been limited. We aimed to examine the associations of Cd and Pb with DKD in diabetic patients. METHODS: 3763 adults with blood metal measurements and 1604 adults with urinary ones who were diabetic from National Health and Nutrition Examination Survey (NHANES) 2007-2016 were involved. Multivariate logistic regression models were used to analyze the associations of blood Cd (BCd), blood Pb (BPb), urinary Cd (UCd), and urinary Pb (UPb) with DKD. RESULTS: BPb, BCd, and UCd levels were higher among participants with DKD than diabetics without nephropathy, but UPb performed the opposite result. BPb and UCd were significantly associated with DKD in the adjusted models (aOR, 1.17 (1.06, 1.29);1.52 (1.06, 2.02)). Participants in the 2nd and 3rd tertiles of BPb and BCd levels had higher odds of DKD, with a significant trend across tertiles, respectively (all P-trend < 0.005). Multiplication interaction was also identified for BPb and BCd (P for interaction = 0.044). CONCLUSION: BPb, BCd, and UCd were positively associated with the risk of DKD among diabetic patients. Furthermore, there were the dose-response relationship and multiplication interaction in the associations of BPb, BCd with DKD.

Baduanjin exercise intervention trial: research protocol of a randomised controlled trial for frail kidney transplant recipients.

INTRODUCTION: Frailty is one of the most common comorbidities in kidney transplant recipients (KTRs). Physical, psychological and social frailty could be improved by exercise intervention. Baduanjin, also known as Eight-section Brocades, is a type of traditional Chinese medicine exercise characterised by the interplay between physical postures and movements, breathing and mind. It can help frail patients strengthen their upper and lower body muscles, improve their mood, quality of life and frailty. However, the effectiveness of Baduanjin on frail KTRs remains unknown. Therefore, we will conduct a randomised controlled trial (RCT) to evaluate the effectiveness of Baduanjin on frail KTRs. METHODS AND ANALYSIS: This protocol describes an assessor and analyst blinded, parallel RCT for frail KTRs comparing Baduanjin group (n=72) with care-as-usual group (n=72). The primary outcomes are frailty assessed by Frailty Phenotype scale and Tilburg Frailty Indicator scale, and muscle strength assessed by a grip strength metre. The secondary outcomes are quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) and depression assessed by the Hospital Anxiety and Depression Scale. All these data will be collected at the baseline, after 3, 6, 9 and 12 months, respectively. Two-way mixed analysis of variance (ANOVA) will be used to test the effectiveness of Baduanjin exercise. Qualitative interviews with participants in the intervention group will also be performed after 6 months. Themes will be extracted from interview transcripts using NVivo software. ETHICS AND DISSEMINATION: The Ethics Committees of Beijing University of Chinese Medicine (2022BZYLL1018) and China-Japan Friendship Hospital (2022-KY-250) had approved the study. The organ donors were all from China-Japan Friendship Hospital. They provided informed consent and they were not executed prisoners. We have provided BMJ Open with documentation from the hospital that indicates that the organs will be harvested ethically. The findings of this study will be disseminated through peer-reviewed journals, international conferences, media reports and briefings. TRIAL REGISTRATION NUMBER: ChiCTR2100041730.

Associations between dietary magnesium intake and hypertension, diabetes, and hyperlipidemia.

Hypertension, diabetes, and hyperlipidemia significantly impact chronic diseases and mortality. Magnesium is an essential nutrient for maintaining critical physiological functions, and magnesium deficiency is often associated with adverse health outcomes. In a cross-sectional study of US adults, we aimed to explore dietary magnesium intake and its association with the prevalence of hypertension, diabetes, and hyperlipidemia in US adults over 20 years of age in NHANES 2007-2018. We obtained data on 24,171 samples of hypertension, 9950 samples of diabetes, and 12,149 samples of hyperlipidemia. We used multivariable logistic regression models adjusted for multiple sociodemographic, anthropometric, and lifestyle factors, with participants subdivided into five groups based on quintiles of daily dietary magnesium. After adjusting for the major lifestyle and dietary variables, an independent and significant inverse relationship between dietary magnesium and hypertension, diabetes, and hyperlipidemia was observed. Compared with the lowest quintile of magnesium intake, the prevalence of hypertension, diabetes, and hyperlipidemia was significantly reduced in the highest magnesium quintile. The OR of hypertension in the highest quintile was 0.66 (95% CI: 0.51-0.87; P trend < 0.001), the OR of diabetes was 0.56 (95% CI: 0.39-0.81; P trend < 0.001), and the OR of hyperlipidemia was 0.68 (95% confidence interval: 0.53-0.86; P trend = 0.007). In the subgroup analysis, most of the inverse relationships persisted. Our findings highlight the potential of magnesium-rich foods to prevent hypertension, diabetes, and hyperlipidemia in US adults. This article summarizes and discuss recent findings on: 1) A high dietary magnesium intake was associated with a lower prevalence of hypertension; 2) An inverse relationship between dietary magnesium with diabetes hyperlipidemia; 3) Monitoring and management of magnesium was important.

A Breast Cancer Stem Active Cobalt(III)-Cyclam Complex Containing Flufenamic Acid with Immunogenic Potential.

The cytotoxic and immunogenic-activating properties of a cobalt(III)-cyclam complex bearing the non-steroidal anti-inflammatory drug, flufenamic acid is reported within the context of anti-cancer stem cell (CSC) drug discovery. The cobalt(III)-cyclam complex 1 displays sub-micromolar potency towards breast CSCs grown in monolayers, 24-fold and 31-fold greater than salinomycin (an established anti-breast CSC agent) and cisplatin (an anticancer metallopharmaceutical), respectively. Strikingly, the cobalt(III)-cyclam complex 1 is 69-fold and 50-fold more potent than salinomycin and cisplatin towards three-dimensionally cultured breast CSC mammospheres. Mechanistic studies reveal that 1 induces DNA damage, inhibits cyclooxygenase-2 expression, and prompts caspase-dependent apoptosis. Breast CSCs treated with 1 exhibit damage-associated molecular patterns characteristic of immunogenic cell death and are phagocytosed by macrophages. As far as we are aware, 1 is the first cobalt complex of any oxidation state or geometry to display both cytotoxic and immunogenic-activating effects on breast CSCs.

Adverse childhood experiences and human immunodeficiency virus testing among adults with human immunodeficiency virus risk behaviours.

Adverse childhood experiences (ACEs) have been associated with poor HIV testing in adulthood yet, they have not been extensively described in those at increased risk for HIV. Cross-sectional analysis data (n = 204,231) on ACEs and HIV testing were obtained from the 2019-2020 Behavioural Risk Factor Surveillance Survey. Weighted logistic regression models were used to access the association of ACEs exposure, ACEs score, and ACEs type with HIV testing among adults with HIV risk behaviours, and stratified analysis was also performed to examine gender differences. The results indicated the overall rate of HIV testing was 38.8% and was higher among those with HIV risk behaviours (64.6%) than those without (37.2%). In populations with HIV risk behaviours, the negative association of HIV testing with ACEs exposure, ACEs score, and ACEs type was identified. Relative to those without ACEs, adults who were exposed to ACEs might decrease the rate of HIV testing, participants with ≥4 ACEs scores were less likely to have HIV testing, and childhood exposure to sexual abuse had the greatest impact on HIV testing. For both males and females, childhood exposure to ACEs was associated with lower odds of HIV testing and ACEs score ≥4 had the most robust associations with HIV testing. For males, those who experienced witnessed domestic violence had the lowest odds of HIV testing but the odds of engaging in HIV testing for females were the lowest among those who experienced childhood sexual abuse.

The Relationship Between Adverse Childhood Experiences and Subjective Cognitive Decline Based on Sexual Orientation.

OBJECTIVES: Research indicates adverse childhood experiences (ACEs) were associated with subjective cognitive decline (SCD), with higher ACEs reported by sexual minoritized individuals (i.e. lesbian, gay, and bisexual; LGB). This study aimed to explore the relationships between ACEs and SCD based on sexual orientation in middle-aged and older adults. METHODS: The study included 76,592 participants from the 2019-2020 Behavioral Risk Factor Surveillance Survey (BRFSS). Multivariate logistic regressions analyzed ACEs status, score, and type associations with SCD. RESULTS: 2.18% of the participants identified as sexual minoritized individuals. More sexual minoritized individuals reported SCD compared to heterosexual individuals (10.70% for heterosexuals; 17.27% for sexual minoritized individuals). Positive association between SCD and ACEs status (OR = 2.18, 95%CI: 1.09-4.40) was identified among sexual minoritized individuals. CONCLUSIONS: The association between ACEs and SCD was strong in both heterosexual and sexual minoritized populations. Given the higher experience of ACEs among sexual minoritized adults, the subsequent frequency of SCD among these adults also may be higher. CLINICAL IMPLICATIONS: Sexual minoritized older adults may have a history of numerous ACEs, which could contribute to a greater burden of SCD. Clinicians and other stakeholders may wish to consider relationships between ACEs and SCD based on sexual orientation.

The causal associations between growth factors and constipation: a two-sample Mendelian randomization study.

Introduction: Certain growth factors (GFs) are associated with constipation, but few studies has analyzed the causal associations between the two. Therefore, this study used two-sample Mendelian randomization (MR) to systematically analyze the causal associations between GF levels and constipation based on data from genome-wide association studies (GWAS). Methods: Both GF and constipation data were obtained from European populations. GFs, as an exposure variable, were obtained from a genetic map of the human plasma proteome containing 3,301 samples, another GWAS dataset on 90 circulating proteins containing 30,931 samples, and a GWAS dataset containing 3,788 samples. Constipation, as an outcome variable, was obtained from the FinnGen project containing 26,919 cases and 282,235 controls and another UK Biobank dataset containing 3,328 cases and 459,682 controls. Single-nucleotide polymorphisms strongly associated with GFs were regarded as instrumental variables. Inverse-variance weighting, MR-Egger regression, weight median, simple mode, and weight mode methods were used to determine genetic associations. Cochran's Q test, Egger intercept, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier tests were used to analyze sensitivity. Results: The IVW analysis based on FinnGen showed that NGFI-A-binding protein 2 and vascular endothelial growth factor receptor 2 were inversely associated with constipation, and that fibroblast growth factor 7 and transforming growth factor beta receptor II levels were positively associated with constipation. The IVW analysis based on UK Biobank showed that proheparin-binding epidermal growth factor, platelet-derived growth factor AA, and vascular endothelial growth factor121 were inversely associated with constipation. Conclusion: This study showed that some GFs are genetically associated with the risk of constipation.

The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)-Phenanthroline Complexes.

Mononuclear copper(II)-phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)-phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)-phenanthroline complexes 1 and 2 is reported, comprising of 2,9-dimethyl-1,10-phenanthroline or 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9-dimethyl-1,10-phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50-fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold-standard anti-CSC agent). Spectacularly, 1 exhibits >100-fold greater potency toward three-dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti-breast CSC properties of binuclear copper(II)-phenanthroline complexes.

Trends in colorectal cancer screening in the United States, 2012 to 2020.

OBJECTIVES: Despite recommendations to increase the uptake of colorectal cancer (CRC) screening, trends in CRC screening vary with sociodemographic status. We aimed to evaluate trends in CRC screening in the US population and subpopulations. METHODS: A total of 1,082,924 participants aged 50 to 75 from five cycles (2012, 2014, 2016, 2018, and 2020) of the Behavioral Risk Factor Surveillance System were involved. Multivariable logistic regression models were performed to evaluate linear trends in CRC screening utilization from 2012 to 2018. Rao-Scott chi-square tests were used to assess the differences in CRC screening utilization between 2018 and 2020. RESULTS: The estimated percentage reporting up-to-date with CRC screening increased significantly (P for trend <0.001), from 62.8% (95% CI, 62.4%-63.2%) in 2012 to 66.7% (95% CI, 66.3%-67.2%) in 2018 and 70.4% (95% CI, 69.8%-71.0%) in 2020, in accordance with 2008 US Preventive Services Task Force recommendations. Trends followed similar patterns in most subgroups, although with different magnitudes in several subgroups, primarily those underweight showed a stable percentage over time (P for trend = 0.170). In 2020, 72.4% of participants reported they were up to date with CRC screening, including the utilization of stool DNA tests and virtual colonoscopy. Colonoscopy was the most commonly used test in 2020 (64.5%), followed by FOBT (12.6%), stool DNA test (5.8%), sigmoidoscopy (3.8%), and virtual colonoscopy (2.7%). CONCLUSIONS: In this nationally representative survey of the US population from 2012 through 2020, the percentage reporting up to date with CRC screening has increased, but not equally among all subgroups.

Association of the dietary inflammatory index with phenotypic age in the United States adults.

OBJECTIVES: One of the underlying mechanisms of aging is chronic inflammation, which has been closely associated with daily diet. Phenotypic age (PhenoAge) has been used as an index to track the aging process before diseases show clinical symptoms. The present study aimed to explore the association between the dietary inflammatory index (DII) and PhenoAge. METHODS: In total, 9,275 adults aged 20 years old and over in the National Health and Nutrition Examination Survey were involved in this study. Dietary patterns were classified as pro-inflammatory or anti-inflammatory according to the DII. PhenoAge was regarded as a continuous variable, and linear regression was used to explore its association with dietary inflammation. Stratified analyses by sex, age, race, physical exercise, smoking status, drinking status, and body mass index were used to test the sensitivity of these associations. RESULTS: The median value of PhenoAge was 38.60 years and 39.76 years for the participants with anti-inflammatory and pro-inflammatory diets, respectively. A pro-inflammatory diet was positively associated with PhenoAge (ß=0.73; 95% confidence interval, 0.31 to 1.14), compared with participants who had an anti-inflammatory diet. There was an interaction between dietary inflammation and age for PhenoAge (pinteraction<0.001). The strength of the association between a pro-inflammatory diet and PhenoAge was stronger as age increased. CONCLUSIONS: A pro-inflammatory diet was associated with a higher PhenoAge, and the association was strongest in the elderly. We recommended reducing dietary inflammation to delay phenotypic aging, especially for the elderly.