Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling.

OBJECTIVE: Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD). METHODS: An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways. RESULTS: AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 µmol/L and 1 µg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells. CONCLUSION: AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity. Please cite this article as: Han LL, Zhang X, Zhang H, Li T, Zhao YC, Tian MH, Sun FL, Feng B. Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling. J Integr Med. 2024; 22(1): 83-92.

Dual-Site Förster Resonance Energy Transfer Route of Upconversion Nanoparticles-Based Brain-Targeted Nanotheranostic Boosts the Near-Infrared Phototherapy of Glioma.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor with low survival, primarily due to the blood-brain barrier (BBB) and high infiltration. Upconversion nanoparticles (UCNPs)-based near-infrared (NIR) phototherapy with deep penetration is a promising therapy method against glioma but faces low photoenergy utilization that is induced by spectral mismatch and single-site Förster resonance energy transfer (FRET). Herein, we designed a brain-targeting NIR theranostic system with a dual-site FRET route and superior spectral matching to maximize energy utilization for synergistic photodynamic and photothermal therapy of glioma. The system was fabricated by Tm-doped UCNPs, zinc tetraphenylporphyrin (ZnTPP), and copper sulfide (CuS) nanoparticles under multioptimized modulation. First, the Tm-doping ratio was precisely adjusted to improve the relative emission intensity at 475 nm of UCNPs (11.5-fold). Moreover, the J-aggregate of ZnTPP increased the absorption at 475 nm (163.5-fold) of monomer; both together optimize the FRET matching between UCNPs and porphyrin for effective NIR photodynamic therapy. Simultaneously, the emission at 800 nm was utilized to magnify the photothermal effect of CuS nanoparticles for photothermal therapy via the second FRET route. After being modified by a brain-targeted peptide, the system efficiently triggers the synergistic phototherapy ablation of glioma cells and significantly prolongs the survival of orthotopic glioma-bearing mice after traversing the BBB and targeting glioma. This success of advanced spectral modulation and dual-site FRET strategy may inspire more strategies to maximize the photoenergy utilization of UCNPs for brain diseases.

An overview of systematic reviews of acupuncture for diabetic gastroparesis.

Background: To date, several systematic reviews and/or meta-analyses (SRs/MAs) on the topic of acupuncture as a treatment for diabetic gastroparesis (DGP) have been published. However, whether acupuncture is an effective and safe treatment for DGP remains controversial. In this study, we aimed to determine whether the methodology and results of previously published SRs/MAs of acupuncture as a treatment for DGP were of sufficient quality to be considered reliable. Methods: We extensively searched seven databases, including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge, Wan Fang, and Chongqing VIP, for SRs/MAs published before or on September 16, 2022. The SRs/MAs that met the inclusion criteria were evaluated for the quality of the methodology and results using the Assessing the Methodological Quality of Systematic Reviews Two (AMSTAR-2) and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tools. A re-meta-analysis of primary outcome indicators was also performed. Results: Ten SRs/MAs that met the inclusion criteria were obtained. Using the AMSTAR-2, which is a methodological quality assessment tool, two MAs were rated as low quality, and eight SRs/MAs were rated as extremely low quality. Assessment with the GRADE tool revealed that, among 20 results, 4 were of moderate quality, 10 were of low quality, and 6 were of very low quality. Re-meta-analysis of primary outcome indicators revealed that, in terms of total efficiency, all types of acupuncture interventions, such as acupuncture, electroacupuncture, and acupoint injection, performed better than the controls, such as gastroprokinetic agents and sham acupuncture. Moreover, in the treatment of DGP, acupuncture exhibited fewer side effects compared to the controls. Conclusion: Acupuncture appears to improve the symptoms of patients with DGP, and the side effects of acupuncture as a treatment for DGP are inferior to those of the controls. However, owing to the low quality of the methodology and results of the SRs/MAs, these findings cannot be considered reliable and need to be validated by additional studies with rigorous standards of experimental design and protocols and larger sample sizes.

Mechanisms of the Jian Pi Tiao Gan Yin in the treatment of simple obesity revealed by network pharmacology.

Background: This study sought to examine the mechanism of the Jian Pi Tiao Gan Yin in the treatment of obesity by network pharmacology. Methods: The active components and corresponding targets of the Jian Pi Tiao Gan Yin were identified using the traditional Chinese medicine systems pharmacology database and analysis platform, and the obesity-related targets were acquired from the Online Mendelian Inheritance in Man database. The drug and disease targets were also identified. Cytoscape software was used to construct the "active component target" network diagram. The protein-protein interaction network was drawn using the Search Tool for the Retrieval of Interacting Genes/Proteins platform, and the Cytoscape MCODE plugin was used to find clusters for the protein cluster analysis. The gene annotation and analysis were performed with the Metascape database via functional databases, such as the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Autodock and PyMOL were used for the molecular docking. Results: The GO analysis identified 244 target genes of the Jian Pi Tiao Gan Yin, 1,378 targets of obesity, and 123 targets of drug and disease. Additionally, 208 biological process items, 38 molecular function items, and 33 cell component items were also identified. The KEGG pathway analysis identified the hypoxia-inducible factor, forkhead box O, cyclic adenosine monophosphate, and vascular endothelial growth factor signaling pathways. The results of the molecular docking showed that the main active components of the Jian Pi Tiao Gan Yin in the treatment of obesity were quercetin, kaempferol, stigmasterol, luteolin, isorhamnetin, ß-sitosterol, sapogenin, tanshinone, and formononetin, all of which have been proven to bind to core obesity-related proteins, such as AKT1, interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF), tumor protein 53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 1 (MAPK1), JUN, and epidermal growth factor (EGF). Thus, our study revealed the potential mechanism of the Jian Pi Tiao Gan Yin as a multi-component, multi-target, and multi-channel treatment for obesity. These findings lay the foundation for further studies on the mechanism of the Jian Pi Tiao Gan Yin in obesity treatment. Conclusions: The Jian Pi Tiao Gan Yin can be used as a multi-component, multi-target, and multi-channel treatment for obesity.

Noncovalent Self-Assembled Smart Gold(III) Porphyrin Nanodrug for Synergistic Chemo-Photothermal Therapy.

Self-assembly is a powerful means to fabricate multifunctional smart nanotheranostics. However, the complicated preparation, toxicity of responsive carriers, and low loading efficiency of drug cargo hinder the outcome. Herein, we developed a responsive carrier-free noncovalent self-assembly strategy of a metallized Au(III) tetra-(4-pyridyl) porphine (AuTPyP) anticancer drug for the preparation of a heat/acid dual-stimulated nanodrug, and it generated a better photothermal effect than monomers under irradiation. The photothermal effect promoted the protonation of the hydrophobic pyridyl group and the following release into tumorous acidic microenvironments. With cRGD modification, the released drug induced the aggravation of intracellular reactive oxygen species (ROS) via the activity inhibition of thioredoxin reductase (TrxR) for synergistic chemo-photothermal therapy of tumors.

The relationship between serum fibroblast growth factor 23, Klotho, and lumbar spine bone mineral density in northern Chinese postmenopausal women.

OBJECTIVES: Changes in serum protein levels of fibroblast growth factor 23 (FGF23) and Klotho resulting from bone metabolism are still controversial. The purpose of this study was to observe the relationship between FGF23 and Klotho serum proteins and lumbar spine bone mineral density (LBMD) in northern Chinese postmenopausal women. METHODS: This was a community-based cross-sectional study carried out in Shenyang, a northern Chinese city. The study included 355 postmenopausal women with an average age of 62.92 ±â€Š8.78 years. FGF23 and Klotho serum proteins were measured using a sandwich enzyme immunoassay. LBMD was examined using dual-energy X-ray absorptiometry. Pearson's correlation and regression analyses were performed to investigate the associations among them. RESULTS: The LgKlotho was positively correlated with LBMD (r = 0.105). There was a linear relationship between LgKlotho serum levels and LBMD (P = 0.007) after adjusting for BMI, and the relationship still existed after adjustments for many confounding variables (P = 0.045), including age, BMI, systolic blood pressure, diastolic blood pressure, total protein, total bilirubin, high-density lipoprotein cholesterol, fasting blood glucose, serum calcium, estimated glomerular filtration rate, serum uric acid, estradiol, cigarette smoking, alcohol consumption, milk intake, calcium and vitamin D supplements, physical exercise, and fracture history in postmenopausal women. FGF23 serum levels were, however, not significantly associated with LBMD. CONCLUSIONS: Klotho was positively correlated with LBMD, and there was a linear relationship between Klotho serum protein levels and LBMD; however, the levels of serum Klotho were not independently associated with reduced LBMD in northern Chinese postmenopausal women. Moreover, serum FGF23 levels were not significantly related to LBMD in this sample population.

Catechin supplemented in a FOS diet induces weight loss by altering cecal microbiota and gene expression of colonic epithelial cells.

Our previous study showed that catechin controlled rats' body weights and changed gut microbiota composition when supplemented into a high-fructo-oligosaccharide (FOS) diet. This experiment is devised to further confirm the relationship between specific bacteria in the colon and body weight gain, and to investigate how specific bacteria impact body weight by changing the expression of colonic epithelial cells. Forty obese rats were divided into four groups: three catechin-supplemented groups with a high-FOS diet (100, 400, and 700 mg kg-1 d-1 catechin, orally administered) and one group with a high-FOS diet only. Food consumption and body weights were recorded each week. After one month of treatment, rats' cecal content and colonic epithelial cells were individually collected and analyzed with MiSeq and gene expression profiling techniques, respectively. Results identified some specific bacteria at the genus level-including the increased Parabacteroides sp., Prevotella sp., Robinsoniella sp., [Ruminococcus], Phascolarctobacterium sp. and an unknown genus of YS2, and the decreased Lachnospira sp., Oscillospira sp., Ruminococcus sp., an unknown genus of Peptococcaceae and an unknown genus of Clostridiales in rats' cecum-and eight genes-including one downregulated Pla2g2a and seven upregulated genes: Apoa1, Apoa4, Aabr07073400.1, Fabp4, Pik3r5, Dgat2 and Ptgs2 of colonic epithelial cells-that were due to the consumption of catechin. Consequently, various biological functions in connection with energy metabolism in colonic epithelial cells were altered, including fat digestion and absorption and the regulation of lipolysis in adipocytes. In conclusion, catechin induces host weight loss by altering gut microbiota and gene expression and function in colonic epithelial cells.