The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study.

BACKGROUND: This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). METHODS: Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. RESULTS: Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (ß= - 0.060, 95% CI - 0.044 to - 0.076; P = 2.416e-14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (ß= - 0.021, 95% CI - 0.003 to - 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. CONCLUSIONS: Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.

Neuroprotective properties of the Lilium brownii extracts in the experimental model of Parkinson's disease.

Lilium brownii (L. brownii) is a plant that can be used for both medicine and food. Its bulbs are commonly used to treat neurological disorders like depression, insomnia, and Parkinson's disease (PD). However, the mechanism by which it treats PD is not yet fully understood. This study aims to investigate the possible mechanism of L. brownii extract in treating PD and to compare the efficacy of ethanol and aqueous extracts of L. brownii. In this study, mice with PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) were given L. brownii extracts for 30 days, and the effects of both extracts were then evaluated. Our study demonstrated that both extracts of L. brownii effectively improved motor dysfunction in PD mice induced by MPTP. Additionally, they increased the number of neurons in the substantia nigra region of the mice. Moreover, both extracts reduced levels of malondialdehyde (MDA) and ferrous ion (Fe2+), while increasing levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum. They also influenced the expression of proteins associated with the p62-Keap1-Nrf2 pathway. Interestingly, while both extracts had similar behavioral effects, the ethanol extract appeared to have a more significant impact on individual proteins in the p62-Keap1-Nrf2 pathway compared to the aqueous extract, possibly due to its higher phenolic acid glyceride content. In conclusion, L. brownii shows promise as an effective and safe treatment for PD.

Associations of 24-hour movement behaviors with emotional and behavioral problems among Chinese adolescents.

PURPOSE: The role of adherence to the recommendations for 24-hour movement behaviors (24-HMB), including physical activity (PA), screen time (ST), and sleep duration (SLP), in relation to emotional and behavioral problems in Chinese adolescents remains uncertain. This study aimed to investigate these associations and explore potential sex differences. METHODS: This school-based cross-sectional study included 15,071 Chinese adolescents with a mean age of 14.53 (SD: 1.65) years. Data on emotional and behavioral problems and 24-HMB (including PA, ST, and SLP) were collected. Analysis was performed using general linear mixed models, with additional sex-stratified analyses conducted. RESULTS: The number of 24-HMB recommendations met was negatively associated with total difficulties (ß estimate=-0.96, 95% CI: -1.07 to -0.85) and positively related to prosocial behavior (ß estimate = 0.41, 95% CI: 0.37 to 0.46) among adolescents. Compared with none of the recommendations met, meeting all recommendations (total difficulties: ß estimate=-2.98, 95% CI: -3.41 to -2.55; prosocial behaviors: ß estimate = 1.05, 95%CI: 0.87 to 1.24) demonstrated the strongest association with both difficulties and prosocial behaviors, followed by meeting recommendations for PA + ST (total difficulties: ß estimate=-2.15, 95% CI: -2.41 to -1.90; prosocial behaviors: ß estimate = 0.98, 95% CI: 0.87 to 1.09). These associations were consistently significant in both boys and girls. CONCLUSION: Adherence to more 24-HMB recommendations, particularly meeting all recommendations or combined PA + ST recommendations, could improve emotional and behavioral well-being among adolescent girls and boys. The significance of balanced movement behaviors for promoting adolescent mental health merits increased attention.

Two New Isospirostanol-Type Saponins from the Bulbs of Lilium Brownii and Their Anti-Hepatocarcinogenic Activity.

Bulbs of Lilium brownii, commonly known as "Bai-he" in China, serve both edible and medicinal purposes in clinical practice. In this study, two new isospirostanol-type saponins were isolated from L. brownii, and their structures were identified by spectroscopic method, and absolute configurations were elucidated by comprehensive analysis of spectral data obtained from combined acid hydrolysis. Two compounds were finally identified as 3-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside]-(22R,25R)-5α-spirosolane-3ß-ol (1) and 3-O-{α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside}-(22R,25R)-5α-spirosolane-3ß-ol (2), respectively. Further, we found that compound 2 significantly suppressed the proliferation of SMMC-7721 and HepG2 cells with IC50 values of 26.3±1.08 µM and 30.9±1.59 µM, whereas compound 1 didn't inhibit both of the two hepatocellular carcinoma. Subsequently, compound 2 effectively decreased the levels of interleukin-1ß and tumor necrosis factor-α and the expression of Bcl-2, and increased the expression of Bax and Caspase-3 proteins. Which indicated that the anti-hepatocellular carcinoma effect of compound 2 involves reducing the level of inflammation and inducing apoptosis.

Generation of an induced pluripotent stem cell line (SYSUSCi004-A) from a patient with Infantile Malignant Osteopetrosis.

Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from a patient with IMO carrying a compound heterozygous mutation in T cell immune regulator 1, ATPase H + transporting V0 subunit a3 (TCIRG1) gene (c.242delC; c.1114C > T) were successfully reprogrammed using Sendai virus encoding the four Yamanaka factors. The generated hiPSCs, IMO-hiPSCs, displayed typical embryonic stem cell-like morphology and were verified by expression of pluripotency markers such as OCT4, SOX2, NANOG, TRA-1-60 and SSEA4, as well as in vivo and in vitro differentiation into derivatives of three germ layers.

TMEM147: A Promising Cancer Biomarker Associated with Immune Cell Infiltration and Prognosis in LIHC-Insights from a Comprehensive Pan-Cancer Genomic Analysis.

Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer analyses investigating the role of TMEM147 in diagnosis, prognosis, and immunological prediction are lacking. An analysis of data from The Cancer Genome Atlas (TCGA) revealed differential TMEM147 expression across various types of cancer as well as within immune and molecular cancer subtypes. Moreover, high TMEM147 expression was associated with poor disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) across cancers, suggesting its potential as a prognostic biomarker. Our study further revealed a significant correlation between TMEM147 expression and T helper cell and Tcm cell infiltration in most cancer types. In the case of liver hepatocellular carcinoma (LIHC), the effect of TMEM147 on prognosis varied among different clinical subtypes. Additionally, functional enrichment analysis revealed an association between TMEM147 and metabolic pathways. Finally, experiments on the MIHA cell line and four LIHC cell lines confirmed the role of TMEM147 in promoting liver cancer cell proliferation, further confirming the clinical value of TMEM147 in liver cancer diagnosis. Our findings suggest that TMEM147 may serve as a diagnostic and prognostic biomarker across cancers while also playing a significant role in LIHC.

Breakfast skipping and risk of all-cause, cardiovascular and cancer mortality among adults: a systematic review and meta-analysis of prospective cohort studies.

Background: Numerous studies reported inconsistent association between breakfast skipping and all-cause, cardiovascular disease (CVD) and cancer mortality. Therefore, we conducted a systematic review and meta-analysis to elucidate these associations. Methods: PubMed, Embase, and Web of Science databases were searched up to July 2023 for prospective cohort studies that assessed the association between breakfast skipping and all-cause, CVD and cancer mortality in general adults. A random effect model was used to estimate the pooled hazard ratio (HR) and 95% confidence intervals (CIs), with subgroup analysis and sensitivity analysis performed. The Newcastle-Ottawa Scale (NOS) was used to assess the study and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: The final analysis included 9 cohort studies including 242 095 participants, with 6 studies for all-cause mortality, 4 studies for CVD mortality, and 2 studies for cancer mortality. Compared to regular breakfast consumption, skipping breakfast was associated with a higher risk of all-cause (HR: 1.27, 95% CI, 1.07-1.51, I2 = 77%), CVD (HR 1.28, 95% CI 1.10-1.50, I2 = 0), and cancer (HR: 1.34, 95% CI: 1.11-1.61, I2 = 0%) mortality. Sensitivity analysis revealed inconsistent results in all-cause and CVD mortality. Subgroup analysis showed significant association in studies with larger participants, longer follow-up, adjustments for energy intake, and high-quality articles. GRADE showed very low evidence for all-cause mortality and low evidence for CVD and cancer mortality. Conclusion: The findings underscore the importance of regular breakfast habits for health and longevity. However, these results require careful interpretation due to geographic limitations, potential heterogeneity, and instability.

Large-pore covalent organic framework as solid phase extraction absorbentforefficientdetermination of polypeptide antibiotics in animal-derived foods.

The precise determination of polypeptide antibiotics (PPTs) in foods has been always challenging because of the interference of various endogenous peptides in complex matrix. Herin, a novel large-pore covalent organic framework (TABPT-SPDA-COF) with accessible pore size of 7.9 nm was synthesized as a solid phase extraction (SPE) absorbent for efficiently enriching four PPTs existed in foods originating from animals. The parameters of SPE process were systematically optimized. Subsequently, four PPTs were determined by UHPLC-MS/MS. Under the optimal conditions, TABPT-SPDA-COF shows outstanding enrichment capacity for PPTs in contrast to commercial absorbents ascribed to size selectivity and multiple interaction effects. The method exhibits excellent linear range (0.005-100 ng mL-1), satisfactory limits of detection (0.1 pg mL-1) as well as relative recoveries (86.2-116 %). This work offers a practicable platform to monitor trace PPTs from complex animal-derived foodstuffs.

A new multifunctional phenanthroline-derived probe for colorimetric sensing of Fe2+ and fluorometric sensing of Zn2.

A new phenanthroline derivative bearing imidazole group, (2-(3,5-di(pyridin-4-yl)phenyl)-1-p-tolyl-1H-imidazo[4,5-f][1,10]phenanthroline) (1), has been devised. 1 can be used as a multifunctional probe exhibiting a highly sensitive colorimetric response to Fe2+ and a selectively ratiometric fluorescent response to Zn2+ in a buffer-ethanol solution. The absorption enhancement accompanied by a visual color change from colorless to red upon addition of Fe2+, makes 1 a suitable naked-eye sensor for Fe2+. Moreover, 1 displayed a Zn2+-induced red-shift of emission (44 nm) showing a color change from blue to light cyan under a 365-nm UV lamp. Its practical imaging applicability for intracellular Zn2+ was confirmed in HeLa cells using a confocal microscope. The improved emission properties and cell imaging capability would provide a new approach for fluorescence sensation for Zn2+.

Tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease: a systematic review and meta-analysis of cohort studies.

Background: Limited and conflicting evidence exists for the associations between tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease (AD). This meta-analysis aimed to elucidate these associations and quantify potential dose-response relationships. Methods: PubMed, EMBASE, and Web of Science were searched up to 11 June 2024 for cohort studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs), with the dose-response relationship assessed using restricted cubic splines. The Grading of Recommendations Assessment Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: Our analysis encompassed 38 cohorts, totalling 751 824 participants and 13 017 dementia and 17 341 AD cases. For dementia, compared with the lowest category, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine were 0.84 (0.74-0.96, n = 6), 0.95 (0.87-1.02, n = 9), and 0.94 (0.70-1.25, n = 5), with all rated as low certainty in GRADE. For AD, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine compared to the lowest category were 0.93 (0.87-1.00, n = 6), 1.01 (0.90-1.12, n = 10), and 1.34 (1.04-1.74, n = 2), with certainty ratings of low, low, and very low, respectively. Dose-response analysis indicated a non-linear relationship between coffee intake (Poverall = 0.04 and Pnonlinear = 0.01) and dementia risk, showing the protective association of risk of dementia with 1 to 3 cups per day of coffee intake. There is a linear association between tea intake and risk of dementia, with a significantly decreased risk of dementia for each 1 cup per day increase in tea consumption (0.96, 95% CI 0.94-0.99, Poverall = 0.01 and Pnonlinear = 0.68). Conclusion: Increased tea consumption was associated with a decreased risk of dementia and AD, and a non-linear relationship was found between coffee and dementia, supporting public health recommendations for dementia prevention.

Discovery of Novel Ortho-Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

CBS promoter hypermethylation increases the risk of hypertension and stroke

OBJECTIVES: Cystathionine β-synthase is a major enzyme in the metabolism of plasma homocysteine. Hyperhomocysteinemia is positively associated with hypertension and stroke. The present study was performed to examine the possible effects of Cystathionine β-synthase promoter methylation on the development of hypertension and stroke. METHODS: Using quantitative methylation-specific PCR, we determined the Cystathionine β-synthase methylation levels in 218 healthy individuals and 132 and 243 age- and gender-matched stroke and hypertensive patients, respectively. The relative changes in Cystathionine β-synthase promoter methylation were analyzed using the 2-ΔΔCt method. The percent of the methylated reference of Cystathionine β-synthase was used to represent the Cystathionine β-synthase promoter methylation levels. RESULTS: In this study, the Cystathionine β-synthase promoter methylation levels of hypertensive and stroke participants were both higher than that of the healthy individuals (median percentages of the methylated reference were 50.61%, 38.05% and 30.53%, respectively, all p<0.001). Multivariable analysis showed that Cystathionine β-synthase promoter hypermethylation increased the risk of hypertension [odds ratio, OR (95% confidence interval, CI)=1.035 (1.025-1.045)] and stroke [OR (95% CI)=1.015 (1.003-1.028)]. The area under the curve of Cystathionine β-synthase promoter methylation was 0.844 (95% CI: 0.796-0.892) in male patients with hypertension and 0.722 (95% CI: 0.653-0.799) in male patients with stroke. CONCLUSION: Cystathionine β-synthase promoter hypermethylation increases the risk of hypertension and stroke, especially in male patients.

Comparisons of serum miRNA expression profiles in patients with diabetic retinopathy and type 2 diabetes mellitus

OBJECTIVES: The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. METHODS: Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. RESULTS: A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. CONCLUSION: Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings.