MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors.

Objective: Postoperative delirium (POD) has become a critical challenge with severe consequences and increased incidences as the global population ages. However, the underlying mechanism is yet unknown. Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods: Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group. Behavioral tests were conducted 24 h before surgery and 6, 9, and 24 h after surgery. Complement C3 (C3) and S100 calcium-binding protein B protein (S100beta) levels were measured in the hippocampus, and a metabolomics analysis was performed on saliva, hippocampus, cortex, and amygdala samples. Results: In total, 43, 33, 38, and 14 differential metabolites were detected in the saliva, hippocampus, cortex, and amygdala, respectively. "Pyruvate" "alpha-linolenic acid" and "2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine" are enriched in one common pathway and may be potential non-invasive biomarkers for POD. Common changes were observed in the three brain regions, with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion: Dysfunctions in energy metabolism, oxidative stress, and neurotransmitter dysregulation are implicated in the development of POD. The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Characteristic and mechanism of biological nitrogen and phosphorus removal facilitated by biogenic manganese oxides (BioMnOx) at various concentrations of Mn(II).

Biogenic manganese oxides (BioMnOx) have attracted considerable attention as active oxidants, adsorbents, and catalysts. However, characteristics and mechanisms of nitrification-denitrification in biological redox reactions mediated by different concentrations of BioMnOx are still unclear. Fate of nutrients (e.g., NH4+-N, TP, NO3--N) and COD were investigated through different concentrations of BioMnOx produced by Mn(II) in the moving bed biofilm reactor (MBBR). 34% and 89.2%, 37.8% and 89.8%, 57.3% and 88.9%, and 62.1% and 90.4% of TN and COD by MBBR were synchronously removed in four phases, respectively. The result suggested that Mn(II) significantly improved the performance of simultaneous nitrification and denitrification (SND) and TP removal based on manganese (Mn) redox cycling. Characteristics of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and electron transfer system activity (ETSA) were discussed, demonstrating that ROS accumulation reduced the ETSA and GSH-Px activities when Mn(II) concentration increased. Extracellular polymeric substance (EPS) function and metabolic pathway of Mn(II) were explored. Furthermore, effect of cellular components on denitrification was evaluated including BioMnOx performances, indicating that Mn(II) promoted the non-enzymatic action of cell fragments. Finally, mechanism of nitrification and denitrification, denitrifying phosphorus and Mn removal was further elucidated through X-ray photoelectron spectroscopy (XPS), high throughput sequencing, and fourier transform infrared reflection (FTIR). This results can bringing new vision for controlling nutrient pollution in redox process of Mn(II).

Computed tomography-based radiomics diagnostic approach for differential diagnosis between early- and late-stage pancreatic ductal adenocarcinoma.

BACKGROUND: One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma (PDAC) is that most patients are usually diagnosed at late stages. There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages. AIM: To evaluate the potential value of radiomics analysis in the differentiation of early-stage PDAC from late-stage PDAC. METHODS: A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography (CT) within 30 d prior to surgery were included in the study. Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system. Radiomics features were extracted from the region of interest (ROI) for each patient using Analysis Kit software. The most important and predictive radiomics features were selected using Mann-Whitney U test, univariate logistic regression analysis, and minimum redundancy maximum relevance (MRMR) method. Random forest (RF) method was used to construct the radiomics model, and 10-times leave group out cross-validation (LGOCV) method was used to validate the robustness and reproducibility of the model. RESULTS: A total of 792 radiomics features (396 from late arterial phase and 396 from portal venous phase) were extracted from the ROI for each patient using Analysis Kit software. Nine most important and predictive features were selected using Mann-Whitney U test, univariate logistic regression analysis, and MRMR method. RF method was used to construct the radiomics model with the nine most predictive radiomics features, which showed a high discriminative ability with 97.7% accuracy, 97.6% sensitivity, 97.8% specificity, 98.4% positive predictive value, and 96.8% negative predictive value. The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models. CONCLUSION: The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.

Influences of evidence-based nursing intervention on pressure ulcers in intensive care units: A meta-analysis.

A meta-analysis was conducted comprehensively to investigate the impact of evidence-based nursing (EBN) interventions on pressure injury (PI) in the intensive care unit (ICU) patients. Computer searches were performed, from databases inception to November 2023, in Wanfang, PubMed, China National Knowledge Infrastructure, Google Scholar, Embase, and Cochrane Library for randomized controlled trials (RCTs) on the application of EBN interventions in ICU patients. Two independent researchers conducted screenings of the literature, extracted data, and carried out quality evaluations. Stata 17.0 software was employed for data analysis. Overall, 25 RCTs, involving 2494 ICU patients, were included. It was found that compared to conventional care methods, the implementation of EBN interventions in ICU patients markedly decreased the occurrence of PI (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.17-0.30, p < 0.001), delayed the onset time of pressure ulcers (standardized mean difference [SMD]: -1.61, 95% CI: -2.00 to -1.22, p < 0.001), and also improved nursing satisfaction (OR: 1.18, 95% CI: 1.14-1.23, p < 0.001). Our findings suggest the implementation of EBN interventions in the care of PI in ICU patients is highly valuable, can reduce the occurrence of PI, can delay the time of appearance, and is associated with relatively higher nursing satisfaction, making it worthy of promotion.

Correlation Between Anesthesia Methods and Adverse Short-Term Postoperative Outcomes Depending on Frailty: A Prospective Cohort Study.

Purpose: This study aims to investigate how the type of anesthesia used during major orthopedic surgery may impact adverse short-term postoperative outcomes depending on frailty. Methods: To conduct this investigation, we recruited individuals aged 65 years and older who underwent major orthopedic surgery between March 2022 and April 2023 at a single institution. We utilized the FRAIL scale to evaluate frailty. The primary focus was on occurrences of death or the inability to walk 60 days after the surgery. Secondary measures included death within 60 days; inability to walk without human assistance at 60 days; death or the inability to walk without human assistance at 30 days after surgery, the first time out of bed after surgery, postoperative blood transfusion, length of hospital stay, hospital costs, and the occurrence of surgical complications such as dislocation, periprosthetic fracture, infection, reoperation, wound complications/hematoma. Results: In a study of 387 old adult patients who had undergone major orthopedic surgery, 41.3% were found to be in a frail state. Among these patients, 262 had general anesthesia and 125 had neuraxial anesthesia. Multifactorial logistic regression analyses showed that anesthesia type was not linked to complications. Instead, frailty (OR 4.04, 95% CI 1.04 to 8.57, P< 0.001), age (OR 1.05, 95% CI 1.00-1.10, P= 0.017), and aCCI scores, age-adjusted Charlson Comorbidity Index, (OR 1.36, 95% CI 1.12 to 1.66, P= 0.002) were identified as independent risk factors for death or new walking disorders in these patients 60 days after surgery. After adjusting for frailty, anesthesia methods was not associated with the development of death or new walking disorders in these patients (P > 0.05). Conclusion: In different frail populations, neuraxial anesthesia is likely to be comparable to general anesthesia in terms of the incidence of short-term postoperative adverse outcomes.

Study on the treatment of osteoarthritis by acupuncture combined with traditional Chinese medicine based on pathophysiological mechanism: A review.

Osteoarthritis (OA) is a major contributor to disability and social costs in the elderly. As the population ages and becomes increasingly obese, the incidence of the disease is higher than in previous decades. In recent years, important progress has been made in the causes and pathogenesis of OA pain. Modern medical treatment modalities mainly include the specific situation of the patient and focus on the core treatment, including self-management and education, exercise, and related weight loss. As an important part of complementary and alternative medicine, TCM has remarkable curative effect, clinical safety, and diversity of treatment methods in the treatment of OA. Traditional Chinese Medicine treatment of OA has attracted worldwide attention. Therefore, this article will study the pathophysiological mechanism of OA based on modern medicine, and explore the treatment of OA by acupuncture combined with Chinese Medicine.

l-thyroxine attenuates extracellular Hsp90α-induced vascular endothelial calcification in diabetes mellitus, as revealed by parallel metabolic profiles.

BACKGROUND AND AIMS: Diabetic atherosclerotic vascular disease is characterized by extensive vascular calcification. However, an elevated blood glucose level alone does not explain this pathogenesis. We investigated the metabolic markers underlying diabetic atherosclerosis and whether extracellular Hsp90α (eHsp90α) triggers vascular endothelial calcification in this particular metabolic environment. METHODS: A parallel human/animal model metabolomics approach was used. We analyzed 40 serum samples collected from 24 patients with atherosclerosis and from the STZ-induced ApoE-/- mouse model. A multivariate statistical analysis of the data was performed, and mouse aortic tissue was collected for the assessment of plaque formation. In vitro, the effects of eHsp90α on endothelial cell calcification were assessed by serum analysis, Western blotting and immunoelectron microscopy. RESULTS: Diabetic ApoE-/- mice showed more severe plaque lesions and calcification damage. Stearamide, oleamide, l-thyroxine, l-homocitrulline and l-citrulline are biomarkers of diabetic ASVD; l-thyroxine was downregulated in both groups, and the thyroid sensitivity index was correlated with serum Hsp90α concentration. In vitro studies showed that eHsp90α increased Runx2 expression in endothelial cells through the LRP1 receptor. l-thyroxine reduced the increase in Runx2 levels caused by eHsp90α and affected the distribution and expression of LRP1 through hydrogen bonding with glutamine at position 1054 in the extracellular segment of LRP1. CONCLUSIONS: This study provides a mechanistic link between characteristic serum metabolites and diabetic atherosclerosis and thus offers new insight into the role of extracellular Hsp90α in promoting vascular calcification.

Relationship between social isolation and glycaemic control of people previously diagnosed with diabetes: secondary analysis from the CHARLS.

OBJECTIVES: Social isolation may affect diabetes self-management. This study aimed to explore the relations between social isolation and glycaemic control in patients with diabetes and to explore lifestyle differences among individuals with different levels of social isolation. METHODS: The relevant data of 665 people previously diagnosed with diabetes included in the China Health and Retirement Longitudinal Study from 2011 to 2015 were extracted and analysed. The study included patient general information, blood glucose, lipids, glycosylated haemoglobin, social isolation index, health-related lifestyle factors and diabetes-related factors. Differences in metabolic abnormalities and modifiable lifestyles were compared among patients with varying levels of social isolation. RESULTS: Multiple linear regression analysis demonstrated that among men aged 45-64 years, the high social isolation group had significantly higher glycosylated haemoglobin levels compared with the low isolation group (7.29±1.81 vs 6.59±1.63, p=0.026). A positive correlation was observed between social isolation and blood glucose (ß=14.16; 95% CI 2.75 to 25.57; p=0.015) and glycosylated haemoglobin (ß=0.35; 95% CI 0.10 to 0.60; p=0.006), indicating that higher social isolation was associated with higher fasting blood glucose and glycosylated haemoglobin levels. However, no significant associations were observed in other age groups. Notably, men aged 45-65 years with high social isolation had higher depression rates (44.10% vs 24.60%, p=0.024), lower engagement in moderate exercise (5.70% vs 23.50%, p=0.019) and shorter 10-minute walks (17.10% vs 36.80%, p=0.027). Differences in other health-related and diabetes-related factors were not statistically significant. CONCLUSION: Middle-aged men with diabetes with higher social isolation tend to have higher blood glucose and glycosylated haemoglobin levels. This subset of patients requires targeted attention to provide social support from family and friends for improved glycaemic control. If necessary, education on diabetes should be made available to family members and friends.

The Pharmacogenetic Variability Associated With the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Healthy Chinese Subjects: A National Multicenter Exploratory Study.

PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects. METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted. FINDINGS: Sixteen SNPs located on 11 genes influenced the AUC0-t. Among these, the 3 most influential genes were MiR516A2, PARP14, and MIR618. Thirty-six SNPs from 28 genes were associated with the PD of rivaroxaban. The 3 most influential genes were PKNOX2, BRD3, and APOL4 for anti-Xa activity, and GRIP2, PLCE1, and MLX for diluted prothrombin time (dPT). Among them, BRD3 played an important role in both the PK and PD of rivaroxaban. Anti-Xa activity (ng/mL) differed significantly among subjects with BRD3 rs467387: 145.1 ± 55.5 versus 139.9 ± 65.1 versus 164.0 ± 68.6 for GG, GA, and AA carriers, respectively (P = 0.0002). IMPLICATIONS: This study found that that the regulation of the BRD3 gene might affect the PK and PD of rivaroxaban, suggesting that it should be studied as a new pharmacologic target. The correlation between this gene locus and clinical outcomes has yet to be verified in patients undergoing clinical treatment.

Protecting against ferroptosis in hyperuricemic nephropathy: The potential of ferrostatin-1 and its inhibitory effect on URAT1.

Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro. Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC50 value of 7.37 ± 0.66 µM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.

CT Image-Based Radiomic Analysis for Detecting PD-L1 Expression Status in Bladder Cancer Patients.

RATIONALE AND OBJECTIVES: The role of Programmed death-ligand 1 (PD-L1) expression is crucial in guiding immunotherapy selection. This study aims to develop and evaluate a radiomic model, leveraging Computed Tomography (CT) imaging, with the objective of predicting PD-L1 expression status in patients afflicted with bladder cancer. MATERIALS AND METHODS: The study encompassed 183 subjects diagnosed with histologically confirmed bladder cancer, among which the PD-L1(+) cohort constituted 60.1% of the total population. Stratified random sampling was utilized at a 7:3 ratio. We employed five diverse machine learning algorithms-Decision Tree, Random Forest, Linear Support Vector Classification, Support Vector Machine, and Logistic Regression-to establish radiomic models on the training dataset. These models endeavored to predict PD-L1 expression status premised on radiomic features derived from region-of-interest segmentation. Subsequent to this, the predictive performance of these models was examined on a validation set employing the receiver operating characteristic (ROC) curve. The DeLong test was utilized to contrast ROC curves, thereby pinpointing the model with superior predictive accuracy. RESULTS: 16 features were chosen for the model construction. All five models revealed strong performance in the training set (AUC, 0.920-1) and commendable predictive ability in the validation set (AUC, 0.753-0.766). As per the DeLong test, no statistically significant disparities were observed among any of the models (P > 0.05) in the validation set. Additional verification through the calibration curve and decision curve analysis indicated that the Logistic Regression model exhibited extraordinary precision and practicality. CONCLUSION: Our machine learning model, grounded on radiomic features, demonstrated its proficiency in accurately distinguishing bladder cancer patients with high PD-L1 expression. Future research, incorporating more exhaustive datasets, could potentially augment the predictive efficiency of radiomic algorithms, thereby advancing their clinical utility.

Trends and age-period-cohort effect on the incidence of falls from 1990 to 2019 in BRICS.

Background: The increasing burden of falls in BRICS countries warrants a comprehensive investigation to understand the dynamics and trends. This study utilized data from the Global Burden of Disease Study (GBD) 2019 to assess fall incidence rates in Brazil, Russia, India, China, and South Africa (BRICS) to provide valuable insights for the development of targeted prevention and management strategies. Methods: Data from the GBD 2019 were employed to estimate fall incidence rates. The study utilized age-period-cohort (APC) model analysis, implemented using R 4.3.0 software and the R package apc, to examine fall incidence trends from 1990 to 2019. Results: In 2019, the BRICS nations collectively reported 32.32 million fall cases. The overall fall incidence rate increased from 2681.7 per 100,000 people in 1990-2896.3 per 100,000 people in 2019. China and India exhibited escalating trends, with China experiencing the highest growth rate at 21%, followed by India at 5.8%. South Africa displayed a comparatively lower overall incidence rate increase. Notably, the 90-94 age group in China exhibited the most significant deterioration, with men and women experiencing annual increases of 4.23% and 1.77%, respectively. Age effects indicated a higher susceptibility to falls among preschool children and the elderly. Period effects revealed no improvement in the fall state for India (2005-2019) and China (2015-2019). Cohort effects adversely impacted the incidence rate for individuals born earlier in South Africa. Conclusion: The present study highlights a consistent upward trend in fall incidence rates across BRICS countries from 1990 to 2019. With an aging population, the burden of fall-related diseases is on the rise in these nations. Our results underscore the necessity of formulating evidence-based disease prevention and management approaches tailored to the distinctive demographic attributes of each nation. Addressing these trends is crucial for mitigating the growing impact of falls on public health in BRICS countries.

Current status and future trends of the global burden of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD.

Multiple cancer cell types release LIF and Gal3 to hijack neural signals.

Neural signals can significantly influence cancer prognosis. However, how cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screening then identifies leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as the key cytokines released by these cancer cell types to trigger brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that pharmacologic or genetic blockage of cancer cell-derived LIF or Gal3 signaling abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple cancer cell types hijacking the nervous system to promote tumor progression.

A meta-analysis of technology acceptance in healthcare from the consumer's perspective.

Consumer-oriented health care technologies are increasingly available and transforming global health delivery systems. However, there is a paucity of research that systematically investigates health care technology acceptance from the consumer's perspective. This study conducts a literature review and meta-analysis to examine consumers' adoption intentions toward health care technologies. The findings suggest that technology acceptance models are transferable to health care technology with modifications, and factors such as perceived risks, technology performance expectancy, consumer trust, and habit significantly correlate with consumers' adoption intentions. This study provides valuable insights into health care technology management and practical implications for health care service designers, providers, and regulatory authorities.

Correlation between metabolic syndrome and periurethral prostatic fibrosis: results of a prospective study.

BACKGROUND: Prostatic fibrosis, characterized by the accumulation of myofibroblasts and collagen deposition, is closely associated with LUTS and may lead to mechanical obstruction of the urethra. Additionally, Metabolic Syndrome (MetS), characterized by central obesity, high blood sugar, lipid metabolism disorders, and hypertension, is increasingly recognized as a proinflammatory condition linked to prostate inflammation. METHODS: Clinical data from 108 subjects who underwent transurethral resection of the prostate or bipolar plasmakinetic enucleation of the prostate were prospectively collected between June 2021 and August 2022. Patients were divided in two groups according to whether or not they had a diagnosis of MetS. Specimens were stained with Masson trichrome and the periurethral prostatic fibrosis extent was evaluated using quantitative morphometry. RESULTS: Forty-three patients (39.8%) were diagnosed with MetS. Patients with MetS showed a significantly greater extent of prostatic fibrosis than the others (68.1 ± 17.1% vs. 42.5 ± 18.2%, P < 0.001), and there was a positive correlation between the number of positive MetS parameters and the extent of prostatic fibrosis (R2 = 0.4436, P < 0.001). Multivariate regression analysis revealed that central obesity (B = 2.941, 95% confidence interval, 1.700-3.283), elevated fasting glucose (B = 1.036, 95% confidence interval, 0.293-1.780), reduced HDL cholesterol (B = 0.910, 95% confidence interval, 0.183-1.636) and elevated triglycerides (B = 1.666, 95% confidence interval, 0.824-2.508) were positively correlated to prostatic fibrosis. Elevated blood pressure, however, was unrelated to prostatic fibrosis (B = 0.009, 95% confidence interval, -0.664-0.683). CONCLUSIONS: The present findings suggest that prostatic fibrosis is positively correlated with MetS and its components including central obesity, elevated fasting glucose, reduced high density lipoprotein cholesterol and elevated triglycerides.

Transforming growth factor-ß receptors: versatile mechanisms of ligand activation.

Transforming growth factor-ß (TGF-ß) signaling is initiated by activation of transmembrane TGF-ß receptors (TGFBR), which deploys Smad2/3 transcription factors to control cellular responses. Failure or dysregulation in the TGF-ß signaling pathways leads to pathological conditions. TGF-ß signaling is regulated at different levels along the pathways and begins with the liberation of TGF-ß ligand from its latent form. The mechanisms of TGFBR activation display selectivity to cell types, agonists, and TGF-ß isoforms, enabling precise control of TGF-ß signals. In addition, the cell surface compartments used to release active TGF-ß are surprisingly vibrant, using thrombospondins, integrins, matrix metalloproteinases and reactive oxygen species. The scope of TGFBR activation is further unfolded with the discovery of TGFBR activation initiated by other signaling pathways. The unique combination of mechanisms works in series to trigger TGFBR activation, which can be explored as therapeutic targets. This comprehensive review provides valuable insights into the diverse mechanisms underpinning TGFBR activation, shedding light on potential avenues for therapeutic exploration.

Gut microbiota-based discovery of Houttuyniae Herba as a novel prebiotic of Bacteroides thetaiotaomicron with anti-colitis activity.

Ulcerative colitis (UC) represents an inflammatory disease characterized by fluctuations in severity, posing substantial challenges in treatment. The gut microbiota plays a pivotal role in the pathogenesis of UC. This study sought to identify drugs specifically targeting the gut microbiota to mitigate UC. We initiated a meta-analysis on gut microbiota in UC patients to identify UC-associated bacterial strains. Subsequently, we screened 164 dietary herbal medicines in vitro to identify potential prebiotics for the UC-associated bacterium, Bacteroides thetaiotaomicron. The DSS-induced colitis mouse model was utilized to evaluate the anti-colitis efficacy of the identified dietary herbal medicine. Full-length 16 S rRNA amplicon sequencing was employed to observe changes in gut microbiota following dietary herbal medicine intervention. The relative abundance of Bacteroides was notably diminished in UC patients compared to their healthy counterparts. B. thetaiotaomicron exhibited an inverse relationship with UC symptoms, indicating its potential as an anti-colitis agent. In vitro assessments revealed that H. Herba significantly bolstered the proliferation of B. thetaiotaomicron. Further experiments showed that treating DSS-induced mice with an aqueous extract of H. Herba considerably alleviated colitis indicators such as weight loss, colon shortening, disease activity score (DAI), and systemic inflammation. Microbial analysis revealed B. thetaiotaomicron as the sole bacterium substantially augmented by H. Herba in vivo. Overall H. Herba emerges as a promising prebiotic for B. thetaiotaomicron, offering significant anti-colitis benefits. Employing a gut microbiota-centric approach proves valuable in the quest for drug discovery.This study provides a new paradigm for drug discovery that targets the gut microbiota to treat UC.

Acupuncture for response and complete pain relief time of acute renal colic: Secondary analysis of a randomized controlled trial.

Background: The integration of acupuncture with intramuscular injection of diclofenac sodium can expedite the onset of analgesia in treating acute renal colic caused by urolithiasis. However, it remains unclear whether acupuncture can accelerate pain relief constantly until complete remission. This study aimed to explore the extent to which acupuncture can expedite the onset time of response or complete pain relief in treating acute renal colic, and the predictive value of patient characteristics for treatment efficacy. Methods: This secondary analysis utilized data from a prior randomized controlled trial. Eighty patients with acute renal colic were randomly assigned 1:1 to the acupuncture group or the sham acupuncture group. After intramuscular injection of diclofenac sodium, acupuncture or sham acupuncture was delivered to patients. The outcomes included time to response (at least a 50 % reduction in pain) and complete pain relief. Between-group comparison under the 2 events was estimated by Kaplan-Meier methodology. Subgroup analysis was performed utilizing the Cox proportional hazards model. Results: The median response time and complete pain relief time in the acupuncture group were lower than those in the sham acupuncture group (5 vs 30 min, Log Rank P < 0.001; 20 min vs not observed, Log Rank P < 0.001, respectively). Hazard Ratios (HRs) for response across all subgroups favored the acupuncture group. All HRs for complete pain relief favored acupuncture, expect large stone and moderate pain at baseline. No interaction was found in either event. Conclusion: Acupuncture can accelerate the response time and complete pain relief time for patients with acute renal colic, with the efficacy universally. Trial registration: This study has been registered at Chinese Clinical Trial Registry: ChiCTR1900025202.