Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

Exploring the multi-targeting phytoestrogen potential of Calycosin for cancer treatment: A review.

Cancer remains a significant challenge in the field of oncology, with the search for novel and effective treatments ongoing. Calycosin (CA), a phytoestrogen derived from traditional Chinese medicine, has garnered attention as a promising candidate. With its high targeting and low toxicity profile, CA has demonstrated medicinal potential across various diseases, including cancers, inflammation, and cardiovascular disease. Studies have revealed that CA possesses inhibitory effects against a diverse array of cancers. The underlying mechanism of action involves a reduction in tumor cell proliferation, induction of tumor cell apoptosis, and suppression of tumor cell migration and invasion. Furthermore, CA has been shown to enhance the efficacy of certain chemotherapeutic drugs, making it a potential component in treating malignant tumors. Given its high efficacy, low toxicity, and multi-targeting characteristics, CA holds considerable promise as a therapeutic agent for cancer treatment. The objective of this review is to present a synthesis of the current understanding of the antitumor mechanism of CA and its research progress.

Metabolic diseases and healthy aging: identifying environmental and behavioral risk factors and promoting public health.

Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue and cellular functions, along with a significant increase in the risk of various aging-related diseases, including metabolic diseases. While advances in modern medicine have significantly promoted human health and extended human lifespan, metabolic diseases such as obesity and type 2 diabetes among the older adults pose a major challenge to global public health as societies age. Therefore, understanding the complex interaction between risk factors and metabolic diseases is crucial for promoting well-being and healthy aging. This review article explores the environmental and behavioral risk factors associated with metabolic diseases and their impact on healthy aging. The environment, including an obesogenic environment and exposure to environmental toxins, is strongly correlated with the rising prevalence of obesity and its comorbidities. Behavioral factors, such as diet, physical activity, smoking, alcohol consumption, and sleep patterns, significantly influence the risk of metabolic diseases throughout aging. Public health interventions targeting modifiable risk factors can effectively promote healthier lifestyles and prevent metabolic diseases. Collaboration between government agencies, healthcare providers and community organizations is essential for implementing these interventions and creating supportive environments that foster healthy aging.

Explainable ensemble machine learning model for prediction of 28-day mortality risk in patients with sepsis-associated acute kidney injury.

Background: Sepsis-associated acute kidney injury (S-AKI) is a major contributor to mortality in intensive care units (ICU). Early prediction of mortality risk is crucial to enhance prognosis and optimize clinical decisions. This study aims to develop a 28-day mortality risk prediction model for S-AKI utilizing an explainable ensemble machine learning (ML) algorithm. Methods: This study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.0) database to gather information on patients with S-AKI. Univariate regression, correlation analysis and Boruta were combined for feature selection. To construct the four ML models, hyperparameters were tuned via random search and five-fold cross-validation. To evaluate the performance of all models, ROC, K-S, and LIFT curves were used. The discrimination of ML models and traditional scoring systems was compared using area under the receiver operating characteristic curve (AUC). Additionally, the SHapley Additive exPlanation (SHAP) was utilized to interpret the ML model and identify essential variables. To investigate the relationship between the top nine continuous variables and the risk of 28-day mortality. COX regression-restricted cubic splines were utilized while controlling for age and comorbidities. Results: The study analyzed data from 9,158 patients with S-AKI, dividing them into a 28-day mortality group of 1,940 and a survival group of 7,578. The results showed that XGBoost was the best performing model of the four ML models with AUC of 0.873. All models outperformed APS-III 0.713 and SAPS-II 0.681. The K-S and LIFT curves indicated XGBoost as the most effective predictor for 28-day mortality risk. The model's performance was evaluated using ROCpr curves, calibration curves, accuracy, precision, and F1 scores. SHAP force plots were utilized to interpret and visualize the personalized predictive power of the 28-day mortality risk model. Additionally, COX regression restricted cubic splines revealed an interesting non-linear relationship between the top nine variables and 28-day mortality. Conclusion: The use of ensemble ML models has shown to be more effective than the LR model and conventional scoring systems in predicting 28-day mortality risk in S-AKI patients. By visualizing the XGBoost model with the best predictive performance, clinicians are able to identify high-risk patients early on and improve prognosis.

Irisin protects against obesity-related chronic kidney disease by regulating perirenal adipose tissue function in obese mice.

BACKGROUND: Compared with typical visceral fat deposits in obesity and metabolic syndrome, perirenal adipose tissue (PRAT) dysfunction is more closely linked to obesity-related chronic kidney disease (OB-CKD). The myokine irisin reportedly promotes positive outcomes in metabolic disease. This study investigated whether irisin could reduce urinary albumin excretion and demonstrate renoprotective effects through the regulation of PRAT function in obese mice. METHODS: C57BL/6 J mice received a high-fat diet (HFD) with or without concurrent administration of irisin. Glucose tolerance, plasma levels of free fatty acids, and urinary albumin excretion were assessed, along with renal morphology. The vascular endothelial growth factor and nitric oxide in glomeruli were also analyzed, in addition to PRAT function-associated proteins. RESULTS: Irisin administration significantly reduced the final body weight, fat mass, and free fatty acids, without reducing PRAT mass, in HFD mice. Furthermore, irisin decreased urinary albumin excretion and attenuated both renal fibrosis and lipid accumulation. Irisin administration led to increases in PRAT function-associated proteins, including sirtuin1, uncoupling protein-1, and heme-oxygenase-1. Ex vivo treatment of PRAT and glomeruli with irisin also restored PRAT function. Finally, irisin treatment restored the vascular endothelial growth factor-nitric oxide axis. CONCLUSIONS: Irisin attenuated metabolic disorders and protected against OB-CKD by normalizing the PRAT-kidney axis. These results suggest that agents targeting PRAT activation might be useful for treatment of OB-CKD.

Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.

Background: Cardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60-89 years at the global, regional, and national levels in 204 countries from 1990 to 2019. Methods: Detailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%. Results: Globally, there were 475,458 (339,942-638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13-19.3) per 100,000 person-years. And there were 185,308 (154,610-200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7-4.8). CM-MC resulted in 3,372,716 (2,931,247-3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7-126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924-24,241)] and disability-adjusted life years [407,712 (370,234-470,165)]. And China had the highest number of incident cases [122, 266 (85,925-166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths. Conclusion: CM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.

The promotion of active aging through older adult education in the context of population aging.

We have entered an era of population aging, and many public health problems associated with aging are becoming more serious. Older adults have earlier onset of chronic diseases and suffer more disability. Therefore, it is extremely important to promote active aging and enhance health literacy. These involves full consideration of the need for education and the provision of solutions to problems associated with aging. The development of OAE is an important measure for implementing the strategy of active aging, and curriculum construction is a fundamental component of achieving OAE. Various subjective and objective factors have limited the development of OAE. To overcome these difficulties and ensure both active and healthy aging, the requirements for active aging should be implemented, the limitations of current OAE should be addressed, system integration should be increased, and the curriculum system should be improved. These approaches will help to achieve the goal of active aging. This paper discusses OAE from the perspective of active aging, based on the promotion of health literacy and provides suggestions to protect physical and mental health among older adults, while promoting their social participation. The provision of various social guarantees for normal life in older adults is a new educational concept.

Diagnostic segregation of human breast tumours using Fourier-transform infrared spectroscopy coupled with multivariate analysis: Classifying cancer subtypes.

The present study aimed to investigate whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy coupled with multivariate analysis could be applied to discriminate and classify among breast tumour molecular subtypes based on the unique spectral "fingerprints" of their biochemical composition. The different breast cancer tissues and normal breast tissues were collected and identified by pathology and ATR-FTIR spectroscopy respectively. The study indicates that the levels of the lipid-to-protein, nucleic acid-to-lipid, phosphate-to-carbohydrate and their secondary structure ratio, including RNA-to-DNA, Amide I-to-Amide II, and RNA-to-lipid ratios were significantly altered among the molecular subtype of breast tumour compared with normal breast tissues, which helps explain the changes in the biochemical structure of different molecular phenotypes of breast cancer. Tentatively-assigned characteristic peak ratios of infrared (IR) spectra reflect the changes of the macromolecule structure in different issues to a great extent and can be used as a potential biomarker to predict the molecular subtype of breast tumour. The present study acts as the first case study to show the successful application of IR spectroscopy in classifying subtypes of breast cancer with biochemical alterations. Therefore, the present study is likely to help to provide a new diagnostic approach for the accurate diagnosis of breast tumours and differential molecular subtypes and has the potential to be used for further intraoperative management.

Spectrochemical determination of effects on rat liver of binary exposure to benzo[a]pyrene and 2,2',4,4'-tetrabromodiphenyl ether.

Benzo[a]pyrene (B[a]P) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants. The effects in organisms of exposures to binary mixtures of such contaminants remain obscure. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive analytical technique allowing spectrochemical analysis of macromolecular components, and alterations thereof, within tissue samples. Herein, we employed ATR-FTIR spectroscopy to identify biomolecular changes in rat liver post-exposure to B[a]P and BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) congener mixtures. Our results demonstrate that significant separation occurs between spectra of tissue samples derived from control versus exposure categories (accuracy = 87%; sensitivity = 95%; specificity = 79%). Additionally, there is significant spectral separation between exposed categories (accuracy = 91%; sensitivity = 98%; specificity = 90%). Segregation between control and all exposure categories were primarily associated with wavenumbers ranging from 1600 to 1700 cm-1 . B[a]P and BDE-47 alone, or in combination, induces liver damage in female rats. However, it is suggested that binary exposure apparently attenuates the toxic effects in rat liver of the individual contaminants. This is supported by morphological observations of liver tissue architecture on hematoxylin and eosin (H&E)-stained liver sections. Such observations highlight the difficulties in predicting the endpoint effects in target tissues of exposures to mixtures of environmental contaminants.

Evaluation of the benefit of post-mastectomy radiotherapy in patients with early-stage breast cancer: A propensity score matching study.

The present study aimed to evaluate the significance of post-mastectomy radiotherapy (PMRT) in patients with early stage (T1-2) breast cancer. The Surveillance, Epidemiology, and End Results database was searched, and data on female patients with early stage (T1-2) breast cancer with 1-3 positive axillary lymph nodes (LNs) were extracted. Patients were subdivided into two groups: Those who had received PMRT and those who had not (no PMRT). Data from the two groups were analyzed in order to identify associations between PMRT status, breast cancer-specific survival (BCSS) probability and overall survival (OS) probability using multivariate Cox proportional hazards regression and propensity score matching models. A total of 7,316 patients were included in the analysis. Prior to propensity score matching, outcome probabilities were increased in the PMRT group, compared with the no PMRT group (BCSS probabilities: 92.0 vs. 90.1%, respectively, P=0.015; OS probabilities: 89.8 vs. 86.0%, respectively, P<0.001). In multivariate analyses, tumor location was not identified as being a risk factor for BCSS (hazard ratio, 0.917; 95% confidence interval, 0.772-1.090; P=0.326). Following propensity score matching, differences between the two treatment groups (PMRT and no PMRT) in terms of their BCSS scores remained significant (93.7 vs. 90.1%, respectively; P=0.007). Compared with the no PMRT group, the OS probabilities of the PMRT group were increased (89.4 vs. 86.0%; P=0.025). In conclusion, the present results indicated that PMRT may benefit the prognosis of patients with breast cancer with early stage disease (T1-2), and those with one to three positive axillary LNs.