Effect of tremella polysaccharides on the quality of collagen jelly: insight into the improvement of the gel properties and the antioxidant activity of yak skin gelatin.

BACKGROUND: The present study aimed to investigate the effects of tremella polysaccharides on the gel properties and antioxidant activity of yak skin gelatin with a view to improving the quality of collagen jellies. The preparation of composite gels were performed by yak skin gelatin (66.7 mg mL-1) and tremella polysaccharides with different concentrations (0, 2, 4, 6, 8 mg mL-1), and finally the collagen jelly was prepared by composite gel (yak skin gelatin: 66.7 mg mL-1; tremella polysaccharides:6 mg mL-1) with the best performance. RESULTS: Tremella polysaccharides not only improved the hardness, springiness, gel strength, water holding capacity and melting temperature of yak skin gelatin, but also enhanced the composite gel's scavenging activity against ABTS radicals, DPPH radicals, O2 and OH radicals. The filling of tremella polysaccharides into the gelatin network increased the number of crosslinking sites inside the gel, which resulted in the gel network structure becoming dense and orderly. The gel particles became finer and more uniform, and the thermal stability was improved. Furthermore, the sensory score of commercially available gelatin jelly decreased more rapidly during storage compared to the composite gel jelly. CONCLUSION: The gel properties and antioxidant activity of yak skin gelatin were improved by adding tremella polysaccharides, and then the quality and storage properties of the jelly were improved, which also provided technical reference for the development of functional gel food. © 2024 Society of Chemical Industry.

Investigation of temperature effects on wide steel box girder of suspension bridge based on long-term monitoring data.

The time-varying temperature distributions on bridge structures may remarkably change structural performance, which may result in differential strain/stress responses on structural members compared with the design conditions. Therefore, it is crucial to have a comprehensive understanding of temperature distributions and its effects on bridges. In this study, taking advantage of structural health monitoring technology, 1-year field monitoring data collected from a long-span suspension bridge were used to investigate the temperature distributions and their effects on the steel box girder. Specifically, the distributions and probability statistics of temperatures on the top and bottom plates were firstly analyzed. Based on which, the transverse and vertical temperature differences on the box girder were further examined, moreover, the representative values of temperature differences for various return periods were calculated by exceedance probability method. At end, a temperature prediction method was proposed to simulated the temperature field distributions during bridge life cycle, to provide substantial temperature data for estimating future operation condition. The results of this study were beneficial to structural evaluation of in-service bridges to ensure their serviceability and integrity in the life cycle.

MSMTSeg: Multi-Stained Multi-Tissue Segmentation of Kidney Histology Images via Generative Self-Supervised Meta-Learning Framework.

Accurately diagnosing chronic kidney disease requires pathologists to assess the structure of multiple tissues under different stains, a process that is timeconsuming and labor-intensive. Current AI-based methods for automatic structure assessment, like segmentation, often demand extensive manual annotation and focus on single stain domain. To address these challenges, we introduce MSMTSeg, a generative self-supervised meta-learning framework for multi-stained multi-tissue segmentation in renal biopsy whole slide images (WSIs). MSMTSeg incorporates multiple stain transform models for style translation of inter-stain domains, a self-supervision module for obtaining pre-trained models with the domain-specific feature representation, and a meta-learning strategy that leverages generated virtual data and pre-trained models to learn the domain-invariant feature representation across multiple stains, thereby enhancing segmentation performance. Experimental results demonstrate that MSMTSeg achieves superior and robust performance, with mDSC of 0.836 and mIoU of 0.718 for multiple tissues under different stains, using only one annotated training sample for each stain. Our ablation study confirms the effectiveness of each component, positioning MSMTSeg ahead of classic advanced segmentation networks, recent few-shot segmentation methods, and unsupervised domain adaptation methods. In conclusion, our proposed few-shot cross-domain technology offers a feasible and cost-effective solution for multi-stained renal histology segmentation, providing convenient assistance to pathologists in clinical practice. The source code and conditionally accessible data are available at https://github.com/SnowRain510/MSMTSeg.

Association of urinary calcium excretion with chronic kidney disease in patients with type 2 diabetes.

PURPOSE: Herein, we investigated the correlation between urinary calcium excretion (UCaE) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: From August 2018 to January 2023, a total of 2031 T2DM patients providing 24-h urine samples were included in the final analyses. Patients were separated into four cohorts, based on the UCaE quartiles. We then analyzed renal functional indicators like estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE) among the four groups. Lastly, we utilized multivariable logistic regression models to investigate the correlation between UCaE and CKD. RESULTS: After adjusting for confounding factors, we observed a decreasing trend in CKD prevalence (36.3%, 13.0%, 7.5%, and 6.6%, respectively, P < 0.001) across the UCaE quartiles. Albuminuria (55.5% vs. 40.0%, 36.5%, 37.4%) and macroalbuminuria prevalence (20.0% vs. 9.3%, 5.2%, 5.7%) in the lowest quartile were markedly elevated, compared to the remaining three quartiles (P < 0.001). Meanwhile, the eGFR level (P < 0.001) showed a clearly increasing trend across the UCaE quartiles, and patients with moderate-to-severe decreases in eGFR levels (with cutoff limits at 30-59, 15-30, and < 15 mL/min/1.73m2) were mostly found in the lowest quartile (P < 0.001). Logistic regression analysis revealed that patients in the lowest quartile experienced an enhanced prevalence of CKD, relative to those in the highest quartile (odds ratio: 5.90, 95% confidence interval: 3.60-9.67, P < 0.001). CONCLUSION: Decreased UCaE was independently associated with the CKD prevalence in T2DM patients.

Optimizing waste molasses utilization to enhance electron transfer via micromagnetic carriers: Mechanisms and high-nitrate wastewater denitrification performance.

The biological denitrification of high-nitrate wastewater (HNW) is primarily hindered by insufficient carbon sources and excessive nitrite accumulation. In this study, micromagnetic carriers with varying micromagnetic field (MMF) strengths (0.0, 0.3, 0.6, 0.9 mT) were employed to enhance the denitrification of HNW using waste molasses (WMs) as a carbon source. The results revealed that 0.6 mT MMF significantly improved the total nitrogen removal (TN) efficiency at 96.3%. A high nitrate (NO3--N) removal efficiency at 99.3% with a low nitrite (NO2--N) accumulation at 25.5 mg/L was achieved at 0.6 mT MMF. The application of MMF facilitated the synthesis of adenosine triphosphate (ATP) and stimulated denitrifying enzymes (e.g., nitrate reductase (NAR), nitrite reductase (NIR), and nitric oxide reductase (NOR)), which thereby promoting denitrification. Moreover, the effluent chemical oxygen demand (COD), tryptophan and fulvic-like substances exhibited their lowest levels at 0.6 mT MMF. Analysis through 16S ribosomal ribonucleic acid gene sequencing indicated a significant enrichment of denitrifying bacteria including Castellaniella Klebsiella under the influence of MMF. Besides, the proliferation of Acholeplasma, Klebsiella and Proteiniphilum at 0.6 mT MMF promoted the hydrolysis and acidification of WMs. This study offers new insights into the enhanced utilization of WMs and the denitrification of HNW through the application of MMF.

Liuwei Dihuang pills attenuate ovariectomy-induced bone loss by alleviating bone marrow mesenchymal stem cell (BMSC) senescence via the Yes-associated protein (YAP)-autophagy axis.

CONTEXT: Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP). OBJECTIVE: To explore the effects and mechanisms of action of LWDH in PMOP. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated. RESULTS: LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62. DISCUSSION AND CONCLUSIONS: LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.

One new prenylated flavonoid with cytotoxic activity from Epimedium brevicornu maxim.

One previously undescribed prenylated flavonoid (1) and three known ones (2-4) were isolated from leaves of Epimedium brevicornu maxim. Their structures were determined through extensive spectroscopic analysis and comparison with the NMR data in the literature. Compound 1 showed a moderate cytotoxicity with an IC50 value of 18.7 µM, while known compounds 2 and 3 elicited weak cytotoxicities with IC50 values of 29.2 and 32.8 µM against Lewis Lung cancer cells (LLC cells), respectively.

Efficacy of non-conventional synthetic DMARDs for patients with rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). METHODS: PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI. RESULTS: A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV1 and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=-4.62, 95% CI -8.90 to -0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively. CONCLUSION: ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD. PROSPERO REGISTRATION NUMBER: CRD42022356816.

Prognostic prediction of idiopathic membranous nephropathy using interpretable machine learning.

BACKGROUND: Established prognostic models of idiopathic membranous nephropathy (IMN) were limited to traditional modeling methods and did not comprehensively consider clinical and pathological patient data. Based on the electronic medical record (EMR) system, machine learning (ML) was used to construct a risk prediction model for the prognosis of IMN. METHODS: Data from 418 patients with IMN were diagnosed by renal biopsy at the Fifth Clinical Medical College of Shanxi Medical University. Fifty-nine medical features of the patients could be obtained from EMR, and prediction models were established based on five ML algorithms. The area under the curve, recall rate, accuracy, and F1 were used to evaluate and compare the performances of the models. Shapley additive explanation (SHAP) was used to explain the results of the best-performing model. RESULTS: One hundred and seventeen patients (28.0%) with IMN experienced adverse events, 28 of them had compound outcomes (ESRD or double serum creatinine (SCr)), and 89 had relapsed. The gradient boosting machine (LightGBM) model had the best performance, with the highest AUC (0.892 ± 0.052, 95% CI 0.840-0.945), accuracy (0.909 ± 0.016), recall (0.741 ± 0.092), precision (0.906 ± 0.027), and F1 (0.905 ± 0.020). Recursive feature elimination with random forest and SHAP plots based on LightGBM showed that anti-phospholipase A2 receptor (anti-PLA2R), immunohistochemical immunoglobulin G4 (IHC IgG4), D-dimer (D-DIMER), triglyceride (TG), serum albumin (ALB), aspartate transaminase (AST), ß2-microglobulin (BMG), SCr, and fasting plasma glucose (FPG) were important risk factors for the prognosis of IMN. Increased risk of adverse events in IMN patients was correlated with high anti-PLA2R and low IHC IgG4. CONCLUSIONS: This study established a risk prediction model for the prognosis of IMN using ML based on clinical and pathological patient data. The LightGBM model may become a tool for personalized management of IMN patients.

To study the protective effect of Huangqi Baihe Granules on Radiation brain injury based on network pharmacology and experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi baihe Granules (HQBHG), which is a key Chinese medical prescription, has a remarkable efficacy in oxidative stress and inflammation. Nevertheless, the therapeutic effect on Radiation brain injury (RBI) has rarely been studied. AIM OF THE STUDY: The study aimed to verify the effect of HQBHG against RBI and explore its potential mechanism. METHODS: The potential targets and mechanisms of HQBHG against RBI were predicted by network pharmacology and verified by established rat model of RBI Firstly, the therapeutic effect of HQBHG in RBI was confirmed by water maze test, HE staining and Enzyme-linked immunosorbent assay (ELISA). Secondly, the potential critical anti-RBI pathway of HQBHG was further explored by water maze, HE staining, immunofluorescence assays, ELISA and western blot. RESULTS: A total of 43 HQBHG anti-RBI targets were obtained. Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations showed that the treatment of HQBHG in RBI might be mainly related to oxidative stress, inflammation and PI3K/AKT pathway. Experimental studies have indicated that HQBHG can improve spatial learning and memory ability, alleviate pathological damage of brain tissue in RBI of rats. HQBHG also can down-regulate the levels of IL-1ß, TNF-α, ROS and MDA, meanwhile, GSH was significantly up-regulated. In addition, the HQBHG can increase the protein expression phosphorylations PI3K (p-PI3K), phosphorylations AKT(p-AKT) and Nrf2 in the brain tissue of RBI. CONCLUSION: HQBHG may alleviated RBI by regulated oxidative stress and inflammatory response through PI3K/AKT/Nrf2 pathway.

Three-year hospital-wide pain management system implementation at a tertiary medical center: Pain prevalence analysis.

We developed a pain management system over a 3-year period. In this project, "Towards a pain-free hospital", we combined evidence-based medicine and medical expertise to develop a series of policies. The intervention mainly included the development of standard procedures for inpatient pain management, the implementation of hospital-wide pain medicine education and training, the establishment of a dashboard system to track pain status, and regular audits and feedback. This study aimed to gain an understanding of the changes in the prevalence of pain in inpatients under the care of the pain management system. The subjects of the survey are inpatients over 20 years old, and who had been hospitalized in the general ward for at least 3 days. The patients would be excluded if they were unable to respond to the questions. We randomly selected eligible patients in the general ward. Our trained interviewers visited inpatients to complete the questionnaires designed by our pain care specialists. A total of 3,094 inpatients completed the survey from 2018 to 2020. During the three-year period, the prevalence of pain was 69.5% (2018) (reference), 63.3% (2019) (OR:0.768, p<0.01), and 60.1% (2020) (OR:0.662, p <0.001). The prevalence rates of pain in patients undergoing surgery during the 3-year period were 81.4% (2018), 74.3% (2019), and 68.8% (2020), respectively. As for care-related causes of pain, injection, change in position/chest percussion, and rehabilitation showed a decreasing trend over the 3-year period of study. Our pain management system provided immediate professional pain management, and achieved a good result in the management of acute moderate to severe pain, especially perioperative pain. Studies on pain prevalence and Pain-Free Hospitals are scarce in Asia. With the aid of the policies based on evidence-based medicine and the dashboard information system, from 2018 to 2020, the prevalence of pain has decreased year by year.

Synergistic modification of collagen structure using ionic liquid and ultrasound to promote the production of DPP-IV inhibitory peptides.

BACKGROUND: Dual modification of collagen was performed using ionic liquid (IL) and ultrasound (US) to modulate the activity of collagen hydrolyzed peptides and reveal the production mechanism of cowhide-derived dipeptidyl peptidase (DPP-IV) inhibitory peptides. RESULTS: The results revealed that dual modification (IL + US) significantly improved the hydrolytic degree of collagen (P < 0.05). Meanwhile, IL and US tended to promote the break of hydrogen bonds, but inhibit the crosslinking between collagens. The double modification reduced the thermal stability and accelerated the exposure of tyrosine and phenylalanine of collagen, and improved the proportion of small molecular (< 1 kDa) peptides in collagen hydrolysates. Interestingly, the hydrophobic amino acid residues and DPP-IV inhibitory activity of collagen peptides with small molecular weight (< 1 kDa) was increased further under the combination of IL and US. CONCLUSION: Enhanced hypoglycemic activity of collagen peptides can be attained through the dual modification of IL and US. © 2023 Society of Chemical Industry.

Syrian hamster as an ideal animal model for evaluation of cancer immunotherapy.

Cancer immunotherapy (CIT) has emerged as an exciting new pillar of cancer treatment. Although benefits have been achieved in individual patients, the overall response rate is still not satisfactory. To address this, an ideal preclinical animal model for evaluating CIT is urgently needed. Syrian hamsters present similar features to humans with regard to their anatomy, physiology, and pathology. Notably, the histological features and pathological progression of tumors and the complexity of the tumor microenvironment are equivalent to the human scenario. This article reviews the current tumor models in Syrian hamster and the latest progress in their application to development of tumor treatments including immune checkpoint inhibitors, cytokines, adoptive cell therapy, cancer vaccines, and oncolytic viruses. This progress strongly advocates Syrian hamster as an ideal animal model for development and assessment of CIT for human cancer treatments. Additionally, the challenges of the Syrian hamster as an animal model for CIT are also discussed.

Influences of environment, human activity, and climate on the invasion of Ageratina adenophora (Spreng.) in Southwest China.

With economic and social globalization, invasive alien species have significantly threatened local ecological security. Identifying the invasive mechanisms of invasive alien species can aid in preventing species invasions and protecting local ecological and economic security. As a globally invasive plant, Ageratina adenophora (Asteraceae) has spread to many parts of the world and had a seriously impacted the ecology and economy of its invaded areas. Using observational data and Landsat OLI images in an arid valley region in southwest China, this study examined how climate, human activity and environmental factors influence the invasion of A. adenophora and its underlying mechanism. Our results showed that the invasion abundance of A. adenophora was significantly affected by environmental factors (the relative importance was 87.2%), but was less influenced by human activity and climate factors (the relative importance was 2% and 10.8%, respectively). The A. adenophora abundance significantly decreased with aspect, community canopy density, shrub layer coverage, herb layer coverage, Simpson diversity index of shrub and herb layers, the shortest distance to residential areas and temperature seasonality, whereas it increased with soil moisture, temperature annual range, precipitation of wettest month and precipitation of driest month. We conclude that biotic competition is the most influential factor in the invasion of this plant in the arid valley regions. Our results are of great significance for invasion prevention and forest conservation and management in southwest China. Our work emphasized that optimizing the community structure, such as by increasing canopy and shrub coverage and species biodiversity, may help control and mitigate the A. adenophora invasion in southwest China.

RNA profiling of sEV (small extracellular vesicles)/exosomes reveals biomarkers and vascular endothelial dysplasia with moyamoya disease.

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD.

Production and identification of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from discarded cowhide collagen.

The present study focused on the effects of different preparation conditions on the activity and peptide sequence identification of DPP-IV inhibitory peptides based on discarded cowhide collagen and its regulation mechanism. The highest DPP-IV inhibitory activity (IC50 of 3.04 ± 0.13 mg/mL) was obtained by the combination of double enzymatic hydrolysis (papain and compound protease) and optimized IL-US (ultrasound-assisted ionic liquids) pretreatment. The optimal pretreatment condition for ultrasonic power, ultrasonic time, ionic liquid/collagen ratio, and collagen concentration were 389 W, 25 min, 0.7, and 0.3 %, respectively. IL-US pretreatment induced the exposure of active sites and hydrophobic amino acids of collagen peptide, promoted the partial transformation of ß-sheet to ß-turn, and enhanced the stability of gastrointestinal digestion. Seven new peptides with DPP-IV inhibitory ability were identified. Importantly, further molecular docking showed that five peptides (GPVG, FGPGP, APGGAP, GPPGPT, and GPVGPPG) were proposed to be antidiabetic peptides from cowhide collagens.

Rheumatoid arthritis drug sinomenine induces apoptosis of cervical tumor cells by targeting thioredoxin reductase in vitro and in vivo.

Overexpression of thioredoxin reductase (TrxR) has been linked to tumorigenesis and phenotypic maintenance of malignant tumors. Thus, targeting TrxR with natural molecules is a promising strategy for developing anticancer drugs. Sinomenine is a naturally occurring alkaloid isolated from Sinomenium acutum. The drug, Zhengqing Fengtongning made from sinomenine, has been universally applied in rheumatoid arthritis treatment in China as well as other Asian countries for decades. Recently, increasing evidence indicates that sinomenine appears to be a promising therapeutic agent against various cancer cells. However, the exact mechanism underlying the anticancer activity of sinomenine remains unclear. In this study, we identified sinomenine as a kind of new inhibitor for TrxR. Pharmacological inhibition of TrxR by sinomenine results in the decrease of thiols content, increases the levels of reactive oxygen species, and finally facilitates oxidative stress-mediated cancer cell apoptosis. It is vital that knockdown in TrxR1 by shRNA can increase cell sensitivity to sinomenine. Treatment with sinomenine in vivo leads to a decrease in TrxR activity and tumor growth, and an increase in apoptosis. Our findings provide a novel action mechanism related to sinomenine and presents an insight on how to develop sinomenine as a chemotherapeutic agent for cancer therapy.

Oridonin Induces Oxidative Stress-mediated Cancer Cells Apoptosis via Targeting Thioredoxin Reductase.

BACKGROUND: Thioredoxin reductase (TrxR) plays vital role in regulating cellular redox balance as well as redox-mediated signal transduction. Accumulating evidence supports that overactivation of TrxR is closely related to tumorigenesis and that targeting TrxR ablation reverses the growth of numerous malignant tumors, making TrxR a promising target for cancer chemotherapy. Thus, the discovery and development of molecules as promising anticancer agents that target TrxR is of great significance. Oridonin was shown to inhibit TrxR activity, but the detailed cellular mechanism is largely unknown. OBJECTIVE: The study investigated the mechanism of action and underlying inhibitory properties of oridonin on TrxR in HeLa cells. METHODS: A covalent docking was performed to reveal the possible interaction between oridonin and TrxR by Schrödinger Software Suite. TrxR activity was determined by 5,5'-dithiobis-2- nitrobenzoic acid reduction assay and endpoint insulin reduction assay. Sulforhodamine B and colony formation assay were employed to assess the viability and growth of cells. Reactive oxygen species level was measured by probe 2', 7'-dichlorfluorescein diacetate, and dihydroethidium. Hoechst 33342 staining, caspase 3 activation, and fluorescein-5-isothiocyanate-conjugated Annexin V and propidium iodide double staining were used to evaluate apoptosis. RESULTS: Here, we reported the oridonin as a potent inhibitor of TrxR. Inhibition of TrxR results in a decrease of thiols content and total glutathione, elevates reactive oxygen species levels, and finally promotes oxidative stress-mediated apoptosis of cancer cells. CONCLUSION: Targeting TrxR by oridonin discloses a novel molecular mechanism underlying the biological action of oridonin and sheds light on developing oridonin as a potential tumor therapeutic agent.

Amelioration of cognitive impairment using epigallocatechin-3-gallate in ovariectomized mice fed a high-fat diet involves remodeling with Prevotella and Bifidobacteriales.

Background: Estrogen deficiency and a high-fat diet (HFD) are both risk factors for Alzheimer's disease (AD). HFD can accelerate cognitive impairment in estrogen-deficient patients, but there is currently no effective treatment. Epigallocatechin-3-galate (EGCG) is widely studied for its anti-inflammatory, anti-cancer, and anti-neurodegeneration effects. Nevertheless, whether EGCG can ameliorate cognitive impairment in HFD-fed estrogen-deficient mice has not been studied. Methods and Results: Ovariectomized (OVX) mice fed an HFD (HFOVX) for 8 weeks experienced impaired object recognition and spatial memory, but this damage was significantly attenuated by the administration of EGCG at a dose of 45 mg/kg. Through 16S rRNA gene sequencing, we found that HFOVX changed the diversity and structure of the gut microbiota in mice, which could be restored with EGCG. Further analysis showed that HFOVX exposure not only resulted in a decrease of Alloprevotella in Bacteroidetes, Lactobacillaceae in Firmicutes, and Prevotella in Bacteroidetes but also in an increase of Bifidobacteriales in Actinobacteria. EGCG effectively reversed the decrease of Prevotella and inhibited the increase of Bifidobacteriales but had no effect on the decrease of Alloprevotella or Lactobacillaceae or on the increase of Enterorhabdus in HFOVX mice. Additionally, using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we found that EGCG significantly reversed the five functional gut microbiota genes elevated by HFOVX, including iron complex transport system substrate-binding protein, iron complex transport system permease protein, 3-oxoacyl- [acyl-carrier protein] reductase, transketolase, and 8-oxo-dGTP diphosphatase. Conclusions: We concluded that EGCG improved cognitive impairment in mice with estrogen deficiency exacerbated by an HFD involved a rebuilding of the disrupted gut microbiota composition.