Keratinocyte-derived small extracellular vesicles delay diabetic wound healing by triggering fibroblasts autophagy.

Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.

Diabetic foot ulcers are a serious complication of diabetes and can lead to amputation and death. Therefore, it is crucial to comprehensively elucidate the mechanisms of delayed diabetic wound healing, with emphasis on the role of keratinocyte-derived small extracellular vesicles. In vivo and in vitro experiments showed that keratinocyte-derived small extracellular vesicles suppressed diabetic wound healing, which is partly attributed to the effects of their content (LINC01435) in fibroblasts. This study suggests that LINC01435 could be targeted to regulate diabetic wound healing.

[18F]FDG PET integrated with structural MRI for accurate brain age prediction.

PURPOSE: Brain aging is a complex and heterogeneous process characterized by both structural and functional decline. This study aimed to establish a novel deep learning (DL) method for predicting brain age by utilizing structural and metabolic imaging data. METHODS: The dataset comprised participants from both the Universal Medical Imaging Diagnostic Center (UMIDC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The former recruited 395 normal control (NC) subjects, while the latter included 438 NC subjects, 51 mild cognitive impairment (MCI) subjects, and 56 Alzheimer's disease (AD) subjects. We developed a novel dual-pathway, 3D simple fully convolutional network (Dual-SFCNeXt) to estimate brain age using [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and structural magnetic resonance imaging (sMRI) images of NC subjects as input. Several prevailing DL models were trained and tested using either MRI or PET data for comparison. Model accuracies were evaluated using mean absolute error (MAE) and Pearson's correlation coefficient (r). Brain age gap (BAG), deviations of brain age from chronologic age, was correlated with cognitive assessments in MCI and AD subjects. RESULTS: Both PET- and MRI-based models achieved high prediction accuracy. The leading model was the SFCNeXt (the single-pathway version) for PET (MAE = 2.92, r = 0.96) and MRI (MAE = 3.23, r = 0.95) on all samples. By integrating both PET and MRI images, the Dual-SFCNeXt demonstrated significantly improved accuracy (MAE = 2.37, r = 0.97) compared to all single-modality models. Significantly higher BAG was observed in both the AD (P < 0.0001) and MCI (P < 0.0001) groups compared to the NC group. BAG correlated significantly with Mini-Mental State Examination (MMSE) scores (r=-0.390 for AD, r=-0.436 for MCI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores (r = 0.333 for AD, r = 0.372 for MCI). CONCLUSION: The integration of [18F]FDG PET with structural MRI enhances the accuracy of brain age prediction, potentially introducing a new avenue for related multimodal brain age prediction studies.

DMA-HPCNet: Dual Multi-Level Attention Hybrid Pyramid Convolution Neural Network for Alzheimer's Disease Classification.

Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer's disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.

MnS-BaS Heterostructures as Effective Catalysts for Oxygen Reduction Reaction.

The inadequate electrical conductivity of metal sulfides, along with their tendency to agglomerate, has hindered their use in energy storage and catalysis. The construction of a heterojunction can ameliorate these deficiencies to some extent. In this paper, MnS-BaS heterojunction catalysts were prepared by a hydrothermal method, which is a simple and inexpensive process. The MnS-BaS heterojunction catalysts exhibited superior performance owing to the strong synergistic interaction between MnS and BaS. Density functional theory (DFT) calculations reveal strong interactions at the heterojunction interface and significant electron transfer between MnS and BaS, which further modulates the electronic structure of Mn. The elevation of the center of the d-band enhances the adsorption of oxygen and oxygen-containing intermediates on the catalyst, thus promoting the oxygen reduction reaction (ORR). The practical application of MnS-BaS catalysts was tested by assembling zinc-air batteries. This study provides a rational strategy for designing transition metal catalysts that are efficient and low cost.

Multi-target mechanism of misoprostol in pregnancy termination based on network pharmacology and molecular docking.

Misoprostol is a prostaglandin analogue that contracts the uterus, prompting the expulsion of the embryo. No systematic evaluation of the mechanisms of misoprostol has previously been performed. In this study, known targets of misoprostol were obtained from the DrugBank database; potential targets of misoprostol were predicted using data from the SwissTargetPrediction and PharmMapper databases; and the main targets of pregnancy termination were obtained from the GeneCards database. The protein-protein interaction (PPI) network of the shared genes between misoprostol and pregnancy termination was constructed using data from the STRING database, and the "misoprostol-pregnancy termination-pathway" network was constructed and potential targets was verified through molecular docking. We analyzed 37 shared target genes and obtained a network diagram of 134 potential targets, which the core therapeutic targets were HSP90AA1, EGFR, and MAPK1. GO functional and KEGG pathway enrichment analyses showed that misoprostol can modulate the VEGF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway in pregnancy termination and mainly interferes with protein phosphorylation, cell localization, and protein hydrolysis regulation processes. This research illustrates the mechanism underlying the pharmacological effect of misoprostol, namely pregnancy termination. However, further experimental verification is warranted for optimal use of misoprostol during clinical practice.

Le misoprostol est un analogue des prostaglandines qui contracte l'utérus, provoquant l'expulsion de l'embryon. Aucune évaluation systématique des mécanismes du misoprostol n'a été réalisée auparavant. Dans cette étude, les cibles connues du misoprostol ont été obtenues à partir de la base de données DrugBank ; Les cibles potentielles du misoprostol ont été prédites à l'aide des données des bases de données SwissTargetPrediction et PharmMapper ; et les principales cibles de l'interruption de grossesse ont été obtenues à partir de la base de données GeneCards. Le réseau d'interaction protéine-protéine (IPP) des gènes partagés entre le misoprostol et l'interruption de grossesse a été construit à l'aide des données de la base de données STRING, et le réseau « voie d'interruption de grossesse-misoprostol ¼ a été construit et les cibles potentielles ont été vérifiées par amarrage moléculaire. Nous avons analysé 37 gènes cibles partagés et obtenu un diagramme de réseau de 134 cibles potentielles, dont les principales cibles thérapeutiques étaient HSP90AA1, EGFR et MAPK1. Les analyses d'enrichissement des voies fonctionnelles GO et KEGG ont montré que le misoprostol peut moduler la voie de signalisation VEGF, la voie de signalisation du calcium et la voie de signalisation NF-κB lors de l'interruption de grossesse et interfère principalement avec les processus de phosphorylation des protéines, de localisation cellulaire et de régulation de l'hydrolyse des protéines. Cette recherche illustre le mécanisme sous-jacent à l'effet pharmacologique du misoprostol, à savoir l'interruption de grossesse. Cependant, une vérification expérimentale plus approfondie est justifiée pour une utilisation optimale du misoprostol au cours de la pratique clinique.

Population Genetic Assessment Model Reveals Conservation Priorities for Gymnocypris Species Resources on the Qinghai-Tibetan Plateau.

The Qinghai-Tibetan Plateau (QTP) has nurtured a rich diversity of species because of its unique geographical and environmental conditions. Gymnocypris species (subfamily Schizopygopsinae) are primitive fishes that live in the special environment of the plateau, and their evolution and distribution are inseparable from the historical changes of the QTP. Recently, the resources of Gymnocypris species have been decreasing due to habit deterioration and the intensification of human activities. Therefore, the scientific conservation of the genetic resources of Gymnocypris species is urgently required. In this study, we established two models for the priority conservation assessment of germplasm resources of Gymnocypris species on the basis of the genetic diversity and phylogenetic relationships of 674 individuals from eight Gymnocypris species populations. The results show that the Gymnocypris potanini (GPO), Gymnocypris eckloni (GE), and Gymnocypris przewalskii (GPR) populations are the most genetically diverse in terms of combined genetic diversity values and should be prioritized for conservation. In terms of genetic contribution, the GPO, GE, and GPR populations have a positive impact on maintaining the distinctiveness and diversity of the entire Gymnocypris species population and should be prioritized for conservation. However, in terms of different evolutionary clades, the Gymnocypris namensis, Gymnocypris waddellii, Gymnocypris dobula, and GE populations in clade A should be given priority for protection, the GE population in clade B should be given priority, and the GPR population in clade C should be given priority. In conclusion, the two models and assessment of conservation priorities will provide a scientific basis for the conservation of Gymnocypris species.

Transcatheter Aortic Valve Replacement and Coronary Protection Guided by Deep Learning and 3-Dimensional Printing.

OBJECTIVE: In this case report, the auxiliary role of deep learning and 3-dimensional printing technology in the perioperative period was discussed to guide transcatheter aortic valve replacement and coronary stent implantation simultaneously. CASE PRESENTATION: A 68-year-old man had shortness of breath and chest tightness, accompanied by paroxysmal nocturnal dyspnea, 2 weeks before presenting at our hospital. Echocardiography results obtained in the outpatient department showed severe aortic stenosis combined with regurgitation and pleural effusion. The patient was first treated with closed thoracic drainage. After 800 mL of pleural effusion was collected, the patient's symptoms were relieved and he was admitted to the hospital. Preoperative transthoracic echocardiography showed severe bicuspid aortic valve stenosis combined with calcification and aortic regurgitation (mean pressure gradient, 42 mmHg). Preoperative computed tomography results showed a type I bicuspid aortic valve with severe eccentric calcification. The leaflet could be seen from the left coronary artery plane, which indicated an extremely high possibility of coronary obstruction. After preoperative imaging assessment, deep learning and 3-dimensional printing technology were used for evaluation and simulation. Guided transcatheter aortic valve replacement and a coronary stent implant were completed successfully. Postoperative digital subtraction angiography showed that the bioprosthesis and the chimney coronary stent were in ideal positions. Transesophageal echocardiography showed normal morphology without paravalvular regurgitation. CONCLUSION: The perioperative guidance of deep learning and 3-dimensional printing are of great help for surgical strategy formulation in patients with severe bicuspid aortic valve stenosis with calcification and high-risk coronary obstruction.

SRT1720 inhibits bladder cancer cell progression by impairing autophagic flux.

Bladder cancer (BC) is the most common cancer of the urinary tract, with poor survival, high recurrence rates, and lacking of targeted drugs. In this study, we constructed a library to screen compounds inhibiting bladder cancer cells growth. Among them, SRT1720 was identified to inhibit bladder cancer cell proliferation in vitro and in vivo. SRT1720 treatment also suppressed bladder cancer cells migration, invasion and induced apoptosis. Mechanism studies shown that SRT1720 promoted autophagosomes accumulation by inducing early-stage autophagy but disturbed the late-stage of autophagy by blocking fusion of autophagosomes and lysosomes. SRT1720 appears to induce autophagy related proteins expression and alter autophagy-related proteins acetylation to impede the autophagy flux. LAMP2, an important lysosomal associated membrane protein, may mediate SRT1720-inhibited autophagy flux as SRT1720 treatment significantly deacetylated LAMP2 which may influence its activity. Taken together, our results demonstrated that SRT1720 mediated apoptosis and autophagy flux inhibition may be a novel therapeutic strategy for bladder cancer treatment.

Effect of Tannic Acid on Antioxidant Function, Immunity, and Intestinal Barrier of Broilers Co-Infected with Coccidia and Clostridium perfringens.

The purpose of this study was to determine the efficacy of tannic acid on the antioxidative function, immunity, and intestinal barrier of broilers co-infected with coccidia and Clostridium perfringens (CCP). A total of 294 1-day-old arbor acres(AA) broilers were divided into three groups: control group (CON), CCP co-infected group (CCP), and 1000 mg/kg TA + CCP co-infected group (CTA). This trial lasted for 28 days. The results showed that the CCP group decreased the activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), catalase (CAT), and total antioxidant capacity (T-AOC) levels and increased the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in the jejunum (p < 0.05). The mRNA levels of GSH-Px3 and CAT in the liver and jejunum, and the mRNA levels of GSH-Px3, SOD, HO-1, and NAD(P)H quinone oxidoreductase I (NQO1) in the liver were down-regulated by CCP challenge (p < 0.05). In addition, the Keap1 and Nrf2 mRNA levels in the liver and jejunum, jejunal glutathione S-transferase (GST), and heme-oxygenase-1 (HO-1) were upregulated in the CCP group compared with CON (p < 0.05). The mRNA levels of interleukin 8 (IL-8), IL-1ß, inducible nitric oxide synthase (iNOS), and interferon γ (IFN-γ) in the jejunum were elevated, and jejunal mRNA levels of IL-10, zonula occludens protein1 (ZO-1), claudin-1, claudin-2, and occludin were decreased in the CCP treatment (p < 0.05). Dietary supplementation with 1000 mg/kg TA increased the activity of GSH-Px, T-SOD, CAT, and T-AOC and decreased the contents of H2O2 and MDA in the jejunum (p < 0.05). Compared with the CCP group, TA decreased the mRNA level of Keap1 and Nrf2 in the liver and jejunum, increased the GSH-Px3, SOD, and CAT mRNA in the liver, and alleviated the rise of IL-8, IL-1ß, iNOS, and IFN-γ and decrease in IL-10, occludin gene expression in the jejunum (p < 0.05). In conclusion, the addition of 1000 mg/kg TA to the diet improved the jejunal barrier, mitigated the jejunal inflammation, and increased the antioxidant capacity of the liver and jejunum through the activation of the transcription factor Nrf2 downstream of the Nrf2-Keap1 pathway in broilers with NE condition.

Extraction, purification, structural features, modifications, bioactivities, structure-activity relationships, and applications of polysaccharides from garlic: A review.

Garlic is a common vegetable and spice in people's daily diets, in which garlic polysaccharide (GP) is one of the most important active components with a variety of benefits, such as antioxidant, immune-enhancing, anti-inflammatory, liver-protective and bowel-regulating properties. >20 types of GPs, mainly crude polysaccharides, have been identified. However, the exact chemical composition of GPs or the mechanism underlying their pharmacological activity is still not fully understood. The extraction and purification methods of GPs are compared in this review while providing detailed information on their structural features, identification methods, major biological activities, mechanisms of actions, structural modifications, structure-activity relationships as well as potential applications. Finally, the limitations of GP research and future issues that need to be addressed are discussed in this review. GPs are widely recognized as substances with great potential in the pharmaceutical and food industries. Therefore, this review aims to provide a comprehensive summary of the latest research progresses in the field of GPs, together with scientific insights and a theoretical support for the development of GPs in research and industrialization.

Effectiveness of a 5-year health empowerment programme on promoting cardiovascular health for adults from low-income families in Hong Kong.

OBJECTIVE: This study aimed to evaluate the effectiveness of a health empowerment programme (HEP) to enhance cardiovascular health for adults from low-income families. METHODS: A prospective cohort study (N = 219, Intervention group: n = 103, comparison group: n = 116) was conducted with participants recruited from January 2013 to November 2015 and followed up until January 2022. Throughout the study duration, intervention group were invited to participate in the HEP. The cardiovascular health status of both groups at baseline and follow-up were assessed using the adapted Ideal Cardiovascular Health Index (ICHI) defined by the American Heart Association. After inverse propensity score weighting, multiple linear regression and Poisson regression were employed to examine the effects of the HEP. RESULTS: The HEP was associated with a greater increase in ICHI total score (B = 0.33, p < 0.001), and the increase of proportion of people achieving a normal blood pressure (Incidence rate ratio: 3.39, p < 0.05). CONCLUSION: HEP can be an effective and sustainable strategy to reduce social disparities in cardiovascular health of adults from low-income families, as indicated by improvement in the ICHI total score and blood pressure status. PRACTICAL IMPLICATIONS: The sustainable HEP in the community setting has potential for generalizability and scalability to other financially challenged families.

Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.

OBJECTIVE: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19. METHODS: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase. RESULTS: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses. CONCLUSION: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function.

Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement.

In the study of TAVR, 3-dimensional (3D) printed aortic root models and pulsatile simulators were used for simulation training and teaching before procedures. The study was carried out in the following three parts: (1) experts were selected and equally divided into the 3D-printed simulation group and the non-3D-printed simulation group to conduct four times of TAVR, respectively; (2) another 10 experts and 10 young proceduralists were selected to accomplish three times of TAVR simulations; (3) overall, all the doctors were organized to complete a specific questionnaire, to evaluate the training and teaching effect of 3D printed simulations. For the 3D-printed simulation group, six proceduralists had a less crossing-valve time (8.3 ± 2.1 min vs 11.8 ± 2.7 min, P < 0.001) and total operation time (102.7 ± 15.3 min vs 137.7 ± 15.4 min, P < 0.001). In addition, the results showed that the median crossing-valve time and the total time required were significantly reduced in both the expert group and the young proceduralist group (all P<0.001). The results of the questionnaire showed that 3D-printed simulation training could enhance the understanding of anatomical structure and improve technical skills. Overall, cardiovascular 3D printing may play an important role in assisting TAVR, which can shorten the operation time and reduce potential complications.

Efficacy of physical exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with atrial fibrillation: a systematic review and meta-analysis.

Objective: It is advised that patients engage in physical activity to enhance their quality of life and achieve better results. The purpose of the current study was to measure the efficacy of exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with AF. Method: A comprehensive systematic literature search was performed in PubMed, Embase, and Web of Science from 1991 to 2023 for RCTs comparing physical exercise combined with AF routine treatments to routine treatments alone. The meta-analysis was conducted following PRISMA guidelines. Our main outcomes were physical ability (measured by the 6-min walk test, 6MWT), cardiac function (measured by left ventricular ejection fraction, LVEF) and cardiopulmonary fitness (measured by peak oxygen uptake and resting heart rate). Quality assessments were conducted using the Cochrane Collaboration tool. Results: Thirteen trials involving 672 patients met the criteria for analysis. The results showed that physical exercise increased physical ability by improving the 6MWT (m) performance (MD = 96.99, 95% CI: 25.55-168.43; Z = 2.66; p = 0.008); and enhanced peak VO2 (ml/kg per min) (MD = 4.85, 95% CI: 1.55-8.14; Z = 2.89; p = 0.004) while reducing resting heart rate (beats per minute, bpm) (MD = -6.14, 95% CI: -11.30 to -0.98; Z = 2.33; p = 0.02). However, the results showed that regular exercise could improve LVEF (%) inpatients clinically, which had no statistic difference between experimental and control group (MD = 1.49, 95% CI: -0.25-3.24; Z = 1.68; p = 0.09). Conclusion: Our meta-analysis shows that physical exercise is an effective intervention to improve the exercise ability and cardiopulmonary fitness for AF patients. Meanwhile, we also do not exclude the positive effect of exercise on the improvement of cardiac function (LVEF) in patients with AF. To this end, doctors should consider the positive impact of exercise on patients and give advice on exercise limits in practical clinical practice.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Association of sleep characteristics with cardiovascular disease risk in adults over 40 years of age: a cross-sectional survey.

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

[Retracted] Germacrone cooperates with dexmedetomidine to alleviate high­fat diet­induced type 2 diabetes mellitus via upregulating AMPKα1 expression.

[This retracts the article DOI: 10.3892/etm.2019.7990.].

Raltitrexed induces apoptosis through activating ROS-mediated ER stress by impeding HSPA8 expression in prostate cancer cells.

Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N-acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy.

Traditional Chinese Medicine-based Treatment in Cardiovascular Disease: Potential Mechanisms of Action.

Cardiovascular Disease (CVD) is the leading cause of morbidity and death worldwide and has become a global public health problem. Traditional Chinese medicine (TCM) has been used in China to treat CVD and achieved promising results. Therefore, TCM has aroused significant interest among pharmacologists and medical practitioners. Previous research showed that TCM can regulate the occurrence and development of atherosclerosis (AS), ischemic heart disease, heart failure, myocardial injury, and myocardial fibrosis by inhibiting vascular endothelial injury, inflammation, oxidant stress, ischemia-reperfusion injury, and myocardial remodeling. It is well-known that TCM has the characteristics of multi-component, multi-pathway, and multitarget. Here, we systematically review the bioactive components, pharmacological effects, and clinical application of TCM in preventing and treating CVD.

Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer.

BACKGROUND: Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. METHODS: A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. RESULTS: Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. CONCLUSION: This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells.