[Study on multiple organ injury induced by Haematitum in mice].

Haematitum is a commonly used mineral medicine. It is toxic, as recorded in the second volume of Chinese Materia Medica. Therefore, it should not be taken for a long time. In this study, the effects of Haematitum and calcined Haematitum on multiple organ injuries in mice were investigated, and the mechanism of the toxicity of the related organs was explored by metabolomics. The mice were randomly divided into the control group, Haematitum low-dose group(ZS-L group), Haematitum high-dose group(ZS-H group), and calcined Haematitum high-dose group(DZS-H group), with 12 mice in each group. Haematitum decoction was given by continuous intragastric administration for 10 days. Then the life situation was observed, and samples were taken to detect various indicators. The results showed that the ZS-H group showed obvious toxicity, with different degrees of toxicity damage in the intestinal tract,liver, spleen, and lung. ZS-L group had no toxic reaction. The toxicity of the DZS-H group was significantly reduced, and only the lung was damaged. Metabolomics technology was used to detect the lung tissue of mice in the control group and the ZS-H group, and a total of 15 kinds of significant difference metabolites were detected, mainly involved in choline metabolism in cancer, sphingolipid metabolism, and glycerophospholipid metabolism. Immunohistochemical results showed that the INSIG1 protein expression level in the lung tissue of mice in the ZS-H group was significantly higher than that in the control group. In summary, large doses and long-time use of Haematitum decoction will cause a variety of organ damage, and the same dose of calcined Haematitum is less toxic than Haematitum. In addition, a low dose of Haematitum has no obvious toxic effect. The dysfunction of lipid metabolic pathways such as sphingolipid and glycerophospholipid metabolism may be an important factor in Haematitum-induced pulmonary toxicity. This study provides a reference for further research on the mechanism of Haematitum pulmonary toxicity.

Toxicity study of mineral medicine haematitum.

ETHNOPHARMACOLOGICAL RELEVANCE: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms. AIM OF THE STUDY: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug. MATERIALS AND METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels. RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum. CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.

Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial.

Background: Oxidative stress and chronic inflammation play an important role in the pathogenesis process of cognitive frailty (CF). Regular Baduanjin exercise could improve cognitive frailty in older adults, but it is unclear whether the effect of Baduanjin exercise on improving CF is mediated by modulating circulating oxidative stress and inflammatory process. Method: A total of 102 community-dwelling older adults with CF were recruited and randomly allocated into a 24-week Baduanjin exercise training group or no specific exercise intervention control group at an equal rate. Cognitive function and physical frailty index were assessed using the Montreal Cognitive Assessment (MoCA) and the Edmonton Frail Scale (EFS), as well as the oxidative stress and inflammatory cytokines were measured at baseline and after intervention. Result: After 24 weeks of intervention, the increased MoCA score (2.51 ± 0.32 points, p < 0.001) and the decreased EFS scores (1.94 ± 0.20 points, p = 0.012) in the Baduanjin group were significantly higher than those in the control group. Serum antioxidant SOD levels were increased by 10.03 ± 4.73 U/mL (p < 0.001), and the prooxidative MDA and 8-iso-PGF2α levels were decreased by -1.08 ± 0.80 nmol/mL (p = 0.030) and -86.61 ± 15.03 ng/L (p < 0.001) in the Baduanjin training group; while inflammatory cytokines IFN-γ, IL-2 and IL-4 levels were increased (1.08 ± 0.33 pg./mL, p = 0.034, 2.74 ± 0.75 pg./mL, p = 0.04 and 1.48 ± 0.35 pg./mL, p = 0.042). In addition, a mediation effect that Baduanjin training improved cognitive ability mediated by an increase of circulating IFN-γ and IL-2 levels were observed in this study. Conclusion: Regular Baduanjin exercise training could improve the cognitive frailty of the community-dwelling older adults with CF, and modulate oxidative stress and inflammatory processes by reducing circulating pro-oxidative MDA and 8-iso-PGF2α levels and increasing anti-oxidative SOD levels, as well as impacting inflammatory cytokines IFN-γ, IL-2, and IL-4 levels. Nevertheless, the mechanism of Baduanjin exercise mediating oxidative stress and inflammatory processes should be cautious to be explained. Clinical trial registration: http://www.chictr.org.cn/index.aspx, ChiCTR1800020341.

Flavobacterium poyangense sp. nov., an ammonifying bacterium isolated from a freshwater lake.

A Gram-stain-negative, aerobic, non-spore-forming, nonmotile, rod-shaped, and yellow-pigmented bacterium, designated strain JXAS1T, was isolated from a freshwater sample collected from Poyang Lake in China. Phylogenetic analysis based on 16S rRNA gene sequence revealed that the isolate belonged to the genus Flavobacterium, being closest to Flavobacterium pectinovorum DSM 6368T (98.61 %). The genome size of strain JXAS1T was 4.66 Mb with DNA G+C content 35.7 mol%. The average nucleotide identity and in silico DNA-DNA hybridization values between strain JXAS1T and its closest relatives were below the threshold values of 95 and 70 %, respectively. The strain contained menaquinone 6 (MK-6) as the predominant menaquinone and the major polar lipids were phosphatidylethanolamine, one unidentified glycolipid, and one unidentified polar lipid. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C15 : 0, iso-C17 : 0 3OH, iso-C15 : 0 3OH, and summed feature 9 (iso-C17 : 1 ω9c and/or 10-methyl C16 : 0). Based on phylogenetic, genotypic, and phenotypic evidence, the isolated strain represents a new species in the genus Flavobacterium, and the name Flavobacterium poyangense is proposed. The type strain is JXAS1T (=GDMCC 1.1378T=KCTC 62719T).

Estimating winning percentage of the fourth quarter in close NBA games using Bayesian logistic modeling.

This study examined the fourth quarters in the close games in the regular NBA games in the last decade, ranging from the 2013-14 season to the 2022-2023 season. A close game is categorically defined by a scenario where the point differential is confined within a 10-point margin at the onset of the fourth quarter and narrows further to a 5-point disparity by the end of the game. In total, 2,295 close games were identified in this study. Advanced game statistics, including offensive rate, defensive rate, assistance ratio, pace of game, and true shooting percentage, etc., are obtained from the NBA box scores using a python script. Understanding key factors that determine the outcome of the basketball games is critical, as such can be used to develop predictive models for coaches to design game strategies. This study developed a Bayesian Logistic Modeling approach to estimate the winning probability of a basketball team in the fourth quarter, using the pace of the last quarter and a team's shooting percentage. The accuracy of the model is used to evaluate if the model can correctly classify game outcome based on the identified game statistics in the fourth quarter of a game. The binary outcome of the close game is modeled as a Bernoulli distribution. Results reveal that the True Positive Rate and False Positive Rate is 0.93 and 0.07, respectively. Insights from this study can be used to help design coaching strategies in basketball games, illuminating potential tactical pivots that could tilt the game in their favor.

Integration of network pharmacology, lipidomics, and transcriptomics analysis to reveal the mechanisms underlying the amelioration of AKT-induced nonalcoholic fatty liver disease by total flavonoids in vine tea.

Nonalcoholic fatty liver disease (NAFLD) is the main reason for chronic liver diseases and malignancies. Currently, there is a lack of approved drugs for the prevention or treatment of NAFLD. Vine tea (Ampelopsis grossedentata) has been used as a traditional Chinese beverage for centuries. Vine tea carries out several biological activities including the regulation of plasma lipids and blood glucose, hepato-protective function, and anti-tumor activity and contains the highest content of flavonoids. However, the underlying mechanisms of total flavonoids from vine tea (TF) in the attenuation of NAFLD remain unclear. Therefore, we investigated the interventions and mechanisms of TF in mice with NAFLD using an integrated analysis of network pharmacology, lipidomics, and transcriptomics. Staining and biochemical tests revealed a significant increase in AKT-overexpression-induced (abbreviated as AKT-induced) NAFLD in mice. Lipid accumulation in hepatic intracellular vacuoles was alleviated after TF treatment. In addition, TF reduced the hepatic and serum triglyceride levels in mice with AKT-induced NAFLD. Lipidomics results showed 32 differential lipids in the liver, mainly including triglycerides (TG), diglycerides (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Transcriptomic analysis revealed that 314 differentially expressed genes were commonly upregulated in the AKT group and downregulated in the TF group. The differential regulation of lipids by the genes Pparg, Scd1, Chpt1, Dgkz, and Pla2g12b was further revealed by network enrichment analysis and confirmed by RT-qPCR. Furthermore, we used immunohistochemistry (IHC) to detect changes in the protein levels of the key proteins PPARγ and SCD1. In summary, TF can improve hepatic steatosis by targeting the PPAR signaling pathway, thereby reducing de novo fatty acid synthesis and modulating the glycerophospholipid metabolism.

Vine tea total flavonoids activate the AMPK/mTOR pathway to amelioration hepatic steatosis in mice fed a high-fat diet.

Vine tea (Ampelopsis grossedentata), a traditional Chinese tea, is rich in flavonoids with various biological activities. Our study found that Vine tea total flavonoids (TFs) treatment reduced the body mass and blood lipid levels and improved the hepatic tissue morphology in mice fed the high-fat diet (HFD). In vivo, TF treatment activated the hepatic adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, initiated autophagy, and regulated the expression levels of proteins for lipid metabolism in those HFD-fed mice. In vitro, TF treatment dramatically reduced the lipid droplets and triacylglycerol content in HepG2 and L02 cells treated with oleic acid (OA). These were associated with the activation of the AMPK/mTOR pathway and autophagy initiation in OA-treated hepatocytes. This phenotype was abolished in the presence of 3-methyladenine, an autophagy inhibitor. Our results indicated that the TF activation of AMPK/mTOR leads to the stimulation of autophagy and a decrease in the buildup of intracellular lipids in hepatocytes, showing the potential of TF as a therapeutic agent for nonalcoholic fatty liver disease. PRACTICAL APPLICATION: Vine tea, a tea drink, has been consumed by Chinese folk for over a thousand years. The result of this study will provide evidence that vine tea total flavonoids have potential use as a functional material for the prevention and amelioration of nonalcoholic fatty liver disease.

Screening of Key Components for Melanogenesis Inhibition of Polygonum cuspidatum Extract Based on the Spectrum-Effect Relationship and Molecular Docking.

Polygonum cuspidatum (PC) extract has been listed in the "Catalog of Used Cosmetic Ingredients (2021 Edition)", which can inhibit melanogenesis, thus exerting a whitening effect, and has been widely used in cosmetics. However, there are currently no quality standards for PC extract used in cosmetics, and the bioactive components associated with anti-melanogenesis remain unclear. In view of this, the present study was the first to investigate the spectrum-effect relationship between fingerprints of PC extract and melanogenesis inhibition. Ten batches of PC extract fingerprints were established by HPLC. Pearson's correlation analysis, gray correlation analysis (GRA) and orthogonal partial least squares regression analysis (OPLSR) were used to screen out resveratrol, emodin and physcion as the main whitening active ingredients using the inhibition of tyrosinase in B16F10 cells as the pharmacological index. Then, the melanogenesis inhibitory effects of the above three components were verified by tyrosinase inhibition and a melanin content assay in B16F10 cells. The interaction between small molecules and proteins was investigated by the molecular docking method, and it was confirmed by quantitative real-time PCR (qRT-PCR) that resveratrol, emodin and physcion significantly down-regulated the transcript levels of melanogenesis-related factors. In conclusion, this study established a general model combining HPLC fingerprinting and melanogenesis inhibition and also analyzed the spectrum-effect relationship of PC extract, which provided theoretical support for the quality control of PC extract in whitening cosmetics.

Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease.

Excessive hepatic lipid droplets (LDs) accumulation-induced lipid metabolism disorder contributes to the development of non-alcoholic fatty liver disease (NAFLD). Exercise is a promising therapeutic strategy for NAFLD. However, the mechanism by which exercise ameliorates NAFLD through regulating the catabolism of hepatic LDs remains unclear. In the present study, we investigated the effect of perilipin2 (PLIN2)-lysosomal acid lipase (LIPA) axis mediating exercise-triggered lipophagy in a high-fat diet (HFD)-induced NAFLD mouse model. Our results showed that exercise could reduce HFD-induced hepatic LDs accumulation and change the expression of lipolysis-related enzymes. Moreover, exercise upregulated the expression of microtubule associated protein 1 light chain 3 (LC3) and autophagy-related proteins, and downregulated sequestosome 1 (P62) expression and promoted autophagosomes formation. Interestingly, exercise downregulated PLIN2 expression, upregulated LIPA expression, and increased the activity of hepatic LIPA and serum levels of LIPA in the NAFLD mouse model. Further mechanistic studies demonstrated that adenosine monophosphate-activated protein kinase (AMPK) activator-5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) treatment significantly increased mRNA levels and protein expression of LIPA and LC3II and decreased levels of PLIN2 and P62 in palmitic acid (PA)-treated HepG2 cells. PLIN2 silencing and LIPA overexpression notably increased the mRNA level and protein expression of LC3II and decreased the mRNA level and protein expression of p62, respectively. In summary, our findings reveal novel insights into the effect of exercise on improving lipid droplet metabolism disorder in NAFLD. Enhancing the PLIN2-LIPA axis-mediated lipophagy may be one of the key mechanisms involved in NAFLD alleviation by exercise.

Effect of Baduanjin exercise on executive function in older adults with cognitive frailty: A randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of Baduanjin exercise on executive function in community-dwelling older adults with cognitive frailty. DESIGN: Randomized controlled trial. SETTING: Community residential centers. SUBJECTS: 120 eligible older adults. INTERVENTIONS: Baduanjin training group received supervised Baduanjin training, 60 min sessions three times per week for 24 weeks. The control group did not receive any exercise intervention. MAIN MEASURES: Primary outcome was executive function, assessed using Clock Drawing Test. Secondary outcomes included the subcomponents of executive function (working memory, inhibitory control and cognitive flexibility), attention and cognitive frailty (global cognitive function, physical frailty) assessed using Verbal Fluency Test, Trail Making Test-A/B, Stroop Test, Montreal Cognitive Assessment and Edmonton Frailty Scale, respectively, at baseline and 24 weeks after intervention. RESULTS: After the 24-week intervention, the scores of Clock Drawing Test and Verbal Fluency Test, the Trail Making Test-B time and the Card correct numbers of Stroop Test in Baduanjin training group showed significant improvement compared with control group (all P < 0.05) with small to moderate effect sizes and the significant interaction effect of group by time in the Clock Drawing Test and Trail Making Test-B test (P = 0.003 and P = 0.043); cognitive frailty variables, including Montreal Cognitive Assessment and Edmonton Frail Scale scores, also showed significant improvement (P = 0.002 and P = 0.004) with a moderate effect sizes and a significant interaction effect (P < 0.001, P = 0.013). No adverse events were reported. CONCLUSION: Regular Baduanjin training may be an effective and safe intervention to improve cognitive frailty and executive function in community-dwelling older adults with cognitive frailty. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100050857. Data of registration: 8/5/2020, https://www.chictr.org.cn/showproj.html?proj = 133037.

Selenium Nanoparticles Stabilized by ß-Glucan Nanotubes from Black Fungus and Their Effects on the Proliferation, Apoptosis, and Cell Cycle of HepG2 Cells.

Selenium nanoparticles (Se NPs) have significant anticancer effects, but their poor water solubility and dispersibility limit their further applications in biomedical fields. Biomacromolecules have often been used as dispersants or stabilizers in synthesized Se NPs because they can enhance the dispersibility of Se NPs and reduce their side effects. Our previous studies reported a triple-helix ß-glucan (BFP) from the fruiting bodies of black fungus, which showed a good self-assembly ability in constructing hollow nanotubes for loading metal nanoparticles. Therefore, in the present work, BFP nanotubes were designed as carriers to entrap large amounts of Se NPs in order to enhance their stability and anticancer effects. The results showed that Se NPs were successfully synthesized and loaded inside the BFP nanotubes, and the composite (BFP-Se) exhibited high stability and dispersibility due to the covalent Se-O bonds between the Se NPs and the hydroxyl groups on the BFP nanotubes. Moreover, BFP-Se showed significant effects on the proliferation, apoptosis, and cell cycle of HepG2 cells compared to those exhibited by Se NPs. The mechanism was associated with BFP, which acted as a dispersant or stabilizer, resulting in the enhanced cellular uptake of the Se NPs. BFP also activated the death receptor-mediated and mitochondria-mediated apoptotic pathways in HepG2 cells. These results suggest that BFP-Se has potential applications in biomedical fields, especially for the treatment of human liver cancers.

Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder.

Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

The extraction, structure characterization and hydrogel construction of a water-insoluble ß-glucan from Poria cocos.

Most reported polysaccharides from Poria cocos (PCPs) in traditional Chinese medicine decoctions were water-soluble heteropolysaccharides while the water-insoluble PCPs were scarcely researched due to the poor water-solubility. In this study, a water-insoluble polysaccharide with high yield of 59%, and high purity with a glucan content of 98.8%, was isolated by diluted sodium hydroxide at low temperature and coded as PCPA. The chemical structure of PCPA was identified as a liner ß-glucan with 1, 3-linked glycosidic bond by the fourier infrared spectrum (FT-IR), ion chromatography (ICP), gas chromatography and mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) measurements. Importantly, PCPA was successfully used to construct hydrogels (PCPA-Gs) with good thermal stability, water retention ability and swelling property through simple physical cross-linking, due to the abundance of hydroxyl groups on glucan chains. Moreover, the rheology analysis of PCPA-Gs showed a rapid transition between gel and sol as well as the shear-thinning property. The hydrogel developed in this study holds promise for applications in the food, pharmaceutical, and cosmetic fields.

A positive feedback between cholesterol synthesis and the pentose phosphate pathway rather than glycolysis promotes hepatocellular carcinoma.

Hepatic cholesterol accumulation and hypercholesterolemia are implicated in hepatocellular carcinoma (HCC). However, the therapeutic effects of cholesterol-lowering drugs on HCC are controversial, indicating that the relationship between cholesterol metabolism and HCC is more complex than anticipated. A positive feedback between cholesterol synthesis and the pentose phosphate pathway (PPP) rather than glycolysis was formed in tumors of c-Myc mice. Blocking the PPP prevented cholesterol synthesis and thereby HCC in c-Myc mice, while ablating glycolysis did not affect cholesterol synthesis and failed to prevent c-Myc-induced HCC. Unexpectedly, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) and G6PD (glucose-6-phosphate dehydrogenase), the rate-limiting enzymes of cholesterol synthesis and the PPP, were identified as direct targets of microRNA-206. By targeting Hmgcr and G6pd, microRNA-206 disrupted the positive feedback and fully prevented HCC in c-Myc mice, while 100% of control mice died of HCC. Disrupting the interaction of microRNA-206 with Hmgcr and G6pd restored cholesterol synthesis, the PPP and HCC growth that was inhibited by miR-206. This study identified a previously undescribed positive feedback loop between cholesterol synthesis and the PPP, which drives HCC, while microRNA-206 prevents HCC by disrupting this loop. Cholesterol synthesis as a process rather than cholesterol itself is the major contributor of HCC.

Synthesis, Biological Evaluation and Action Mechanism Study of New Mitochondria-Targeted Curcumin Derivative as Potential Antitumor Drugs.

Mitochondria have emerged as important targets in cancer therapy due to their key role in regulating energy supply, maintaining redox homeostasis, and intrinsic apoptosis. Curcumin (CUR) has shown promise in inhibiting the proliferation and metastasis of cancer cells by inducing apoptosis and arresting cell cycle. However, the clinical application of CUR has been limited by its low stability and poor tumor selectivity. To address these issues, the novel mitochondria-targeted curcumin derivatives were synthesized through the unilateral coupling (CUR-T) or bilateral coupling (CUR-2T) of curcumin's phenolic hydroxy groups with triphenyl phosphorus via ester bond. The aim was to achieve better stability, higher tumor selectivity, and stronger curative efficacy. The results of stability and biological experiments indicated that both stability and cytotoxicity were arranged in descending order of CUR-2T>CUR-T>CUR. In ovarian cancer cells (A2780 cells), CUR-2T showed well-defined preferential selectivity towards cancer cells and exhibited efficient anticancer efficacy due to its superior mitochondria accumulation ability. Subsequently, the mitochondrial redox balance was disrupted, accompanied by increased ROS levels, decreased ATP levels, dissipated MMP, and increased G0 /G1 phase arrest, leading to a higher apoptotic rate. In summary, the results of this study suggest that CUR-2T holds substantial promise for further development as a potential agent for the treatment of ovarian cancer.

Formulation and evaluation of a two-stage targeted liposome coated with hyaluronic acid for improving lung cancer chemotherapy and overcoming multidrug resistance.

Multidrug resistance (MDR) has emerged as a prominent challenge contributing to the ineffectiveness of chemotherapy in treating non-small cell lung cancer (NSCLC) patients. Currently, mitochondria of cancer cells are identified as a promising target for overcoming MDR due to their crucial role in intrinsic apoptosis pathway and energy supply centers. Here, a two-stage targeted liposome (HA/TT LP/PTX) was successfully developed via a two-step process: PTX-loaded cationic liposome (TT LP/PTX) were formulated by lipid film hydration & ultrasound technique, followed by further coating with natural anionic polysaccharide hyaluronic acid (HA). TT, an amphipathic polymer conjugate of triphenylphosphine (TPP)-tocopheryl polyethylene glycol succinate (TPGS), was used to modify the liposomes for mitochondrial targeting. The average particle size, zeta potential and encapsulation efficiency (EE%) of HA/TT LP/PTX were found to be 153 nm, -30.3 mV and 92.1% based on the optimal prescription of HA/TT LP/PTX. Compared to cationic liposome, HA-coated liposomes showed improved stability and safety, including biological stability in serum, cytocompatibility, and lower hemolysis percentage. In drug-resistant A549/T cells, HA was shown to improve the cellular uptake of PTX through CD44 receptor-mediated endocytosis and subsequent degradation by hyaluronidase (HAase) in endosomes. Following this, the exposure of TT polymer facilitated the accumulation of PTX within the mitochondria. As a result, the function of mitochondria in A549/T cells was disturbed, leading to an increased ROS level, decreased ATP level, dissipated MMP, and increased G2/M phase arrest. This resulted in a higher apoptotic rate and stronger anticancer efficacy.

Effects of Baduanjin exercise on the physical function of middle-aged and elderly people: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Chinese mind-body exercise-Baduanjin has received increasing attention for health promotion among middle-aged and older adults in China, but there is a lack of high-quality evidence on its effectiveness. This systematic review and meta-analysis was conducted to investigate the effects of Baduanjin on physical function in middle-aged and older adults. METHODS: Seven electronic databases were searched for articles published before 22 June 2021 with the keywords Baduanjin exercise combined with physical-function-related outcomes. Risk of bias was assessed in the included studies, and data were analyzed using Review Manager software V5.3. RESULTS: Fifteen articles, including 14 randomized controlled trials, were included in this study. The results of the meta-analysis showed that Baduanjin significantly improved muscle strength (grip strength: SMD = 0.63, 95% CI 0.22 to 1.04, p = 0.003), balance ability (timed up-and-go test score: MD = -2.21, 95% CI -3.91 to -0.51, p = 0.01; one-leg stand test score: MD = 3.75, 95% CI 1.96 to 5.55, p < 0.0001; Berg balance scale score: MD = 4.16, 95% CI 2.49 to 5.83, p < 0.00001; strengthening Romberg's test result: SMD = 1.02, 95% CI 0.17 to 1.86, p = 0.02); and cardiorespiratory fitness (diastolic blood pressure: MD = -3.62, 95% CI -3.95 to -3.30, p < 0.00001; resting heart rate: MD = -1.30, 95% CI -1.57 to -1.03, p < 0.00001; step test: MD = 4.25, 95% CI 0.76 to 7.74, p = 0.02). No adverse events were reported. CONCLUSIONS: Baduanjin exercise may be an effective intervention to improve physical function in the middle-aged and elderly population. However, more RCTs with larger sample sizes and more rigorous research designs are needed in the future to confirm the results.

Ellagitannins-Derived Intestinal Microbial Metabolite Urolithin A Ameliorates Fructose-Driven Hepatosteatosis by Suppressing Hepatic Lipid Metabolic Reprogramming and Inducing Lipophagy.

Excessive fructose consumption exacerbates the progression of nonalcoholic fatty liver disease (NAFLD) by disrupting hepatic lipid homeostasis. This study sought to evaluate the efficacy of urolithin A (UroA) in a fructose-induced NAFLD mouse model. UroA was administered in the high-fructose-fed mice to investigate the antisteatotic effects in vivo. Fructose-stimulated HepG2 cells and primary hepatocytes were established for in vitro mechanistic assessment. The results suggested that UroA ameliorated fructose-induced hepatic steatosis in mice. Mechanistically, UroA impaired lipogenesis and enhanced ß-oxidation in the livers of fructose-fed mice. Notably, UroA facilitated hepatic lipophagy through the AMPK/ULK1 pathway both in vivo and in vitro, degrading lipid droplets for fueling ß-oxidation. This study indicates that UroA alleviates excessive lipid accumulation and restores lipid homeostasis in the livers of fructose-fed mice by suppressing lipid metabolic reprogramming and triggering lipophagy. Therefore, dietary supplementation of UroA or ellagitannins-rich foods may be beneficial for NAFLD individuals with high fructose intake.

The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery.

In order to precisely deliver celastrol into mitochondria of tumor cells, improve antitumor efficacy of celastrol and overcome its troublesome problems in clinical application, a novel multistage-targeted celastrol delivery system (C-TL/HA) was developed via electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes composed of natural soybean phosphatidylcholine and cholesterol modified with mitochondrial targeting molecular TPP. Study results in this article showed that C-TL/HA successfully transported celastrol into mitochondria, effectively activated apoptosis of mitochondrial pathway, exerted higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. More importantly, HA coating not only enabled this delivery system to have good stability and safety in vivo, but also increased drug uptake and facilitated tumor targeting through recognizing CD44 receptors rich on the surface of tumor cells. Conclusively, this HA-coated mitochondrial targeting liposomes may provide a prospect for the clinical application of celastrol in tumor therapy.

Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway.

BACKGROUND: High levels of glycolysis supply large quantities of energy and biological macromolecular raw materials for cell proliferation. Triptolide (TP) is a kind of epoxy diterpene lactone extracted from the roots, flowers, leaves, or grains of the Celastraceae plant, Tripterygium wilfordii. TP has multiple biological activities, including anti-inflammatory, immunologic suppression, and anti-cancer effects. Nevertheless, it is little known regarding its anti-intrahepatic cholangiocarcinoma (ICC) growth, and the mechanism still require exploration. PURPOSE: This research explored the effect of TP on ICC growth and investigated whether TP inhibits glycolysis via the AKT/mTOR pathway. METHODS: Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8), clonogenic assay, and flow cytometry. The underlying molecular mechanism was identified by determining glucose consumption, ATP production, lactate production, hexokinase (HK) and pyruvate kinase (PK) activity, and Western blot analysis. A rapid ICC model of AKT/YapS127A oncogene coactivation in mice was used to clarify the effect of TP treatment on tumor growth and glycolysis. RESULTS: The results showed that TP treatment significantly inhibited ICC cell proliferation and glycolysis in a dose- and time-dependent manner(P < 0.05). Further analysis suggested that TP suppressed ICC cell glycolysis by targeting AKT/mTOR signaling. Additionally, we found that TP inhibits tumor growth and glycolysis in AKT/YapS127A mice(P < 0.05). CONCLUSION: Taken together, we revealed that TP suppressed ICC growth by suppressing glycolysis via the AKT/mTOR pathway and may provide a potential therapeutic target for ICC treatment.