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Revealing the molecular mechanism of baohuoside I for the treatment of breast cancer based on network pharmacology and molecular docking.
Mu, J, Li, Y, Chen, Q, Xiao, Y, Hu, M, He, Z, Zeng, J, Ding, Y, Song, P, He, X, et al
Journal of ethnopharmacology. 2025;(Pt 3):118918
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In Traditional Chinese Medicine (TCM), there are many prescriptions for treating breast cancer (BC) that utilize the herb Epimedium brevicornum Maxim, which warms and replenishes kidney yang. Baohuoside I (BI) is a flavonoid compound found in Epimedium brevicornum Maxim. As a single glycoside, it is not easily hydrolyzed in the intestine and is typically absorbed as a precursor. As a natural product with potential anti-cancer properties, studies have shown that BI possesses anti-cancer activity and can inhibit the invasion and migration of BC cells. However, its underlying mechanisms remain unclear, thus further research is needed to validate its modern mechanisms for traditional uses. AIM OF THE STUDY This study aimed to explore the regulatory mechanism of BI in the signaling pathways of BC cells through network pharmacology (NP), molecular docking (MD) techniques and cellular experiments. METHODS Potential targets were predicted using public databases, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Key signaling pathways were validated through MD techniques, cellular experiments, RNA interference and Western blot (WB) analysis. RESULTS Treatment-associated targets included SRC, MAPK1, HSP90AA1, PIK3CA, TP53, AKT1, and EGFR. GO enrichment, KEGG enrichment analyses, and MD results indicated that BI exerts its anti-breast cancer effects by inhibiting the tyrosine kinase activity of EGFR, as well as through downstream MAPK signaling pathway and PI3K-Akt signaling pathway pathways. In vitro experiments confirmed that BI primarily induce cell apoptosis through the EGFR-mediated MAPK signaling pathway and PI3K-Akt signaling pathway. CONCLUSION BI can inhibit EGFR activation and promote BC cell apoptosis through the MAPK signaling pathway and PI3K-Akt signaling pathway, thereby exerting therapeutic effects on BC. This study not only provides experimental evidence for the accuracy of NP but also offers an effective approach for rational utilization of Baohuoside I-like flavonoid compounds as anti-breast cancer drugs.
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Small molecule-driven LKB1 deacetylation is responsible for the inhibition of hepatic lipid response in NAFLD.
Qin, W, Ding, Y, Zhang, W, Sun, L, Weng, J, Zheng, X, Luo, S
Journal of lipid research. 2025;:100740
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a progressive condition characterized by ectopic fat accumulation in the liver, for which no FAD-approved drugs currently exist. Emerging evidence highlights the role of liver kinase B1 (LKB1), a key metabolic regulator, has been proposed in NAFLD, particularly in response to excessive nutrient levels. However, few agents have been identified that can prevent the progression of nonalcoholic steatohepatitis (NASH) by targeting LKB1 deacetylation. Through comprehensive screening of our in-house chemical library, we identified tranilast, a small molecule with remarkable inhibitory efficacy against lipid deposition induced by palmitic acid/oleic acid (PO). In this study, we investigated the novel biological function and mechanism of tranilast in regulating hepatic lipid response in NAFLD, focusing on its role in LKB1 deacetylation within hepatocytes. Our findings demonstrate that tranilast effectively reduced hepatic steatosis, inflammation, and fibrosis in NASH models induced by high-fat and high-cholesterol (HFHC) and methionine choline-deficient (MCD) diets. Mechanistic analysis using RNA sequencing revealed that tranilast mitigated hepatic lipid response by promoting LKB1 deacetylation and activating AMPK. Notably, in vivo experiments showed that the beneficial effects of tranilast in MCD diet-induced NASH model were reversed by the compound C (C-C), a known AMPK inhibitor, confirming that tranilast's effects on hepatic lipid response are mediated through the AMPK pathway. In summary, tranilast inhibits hepatic lipid response in NAFLD through LKB1 deacetylation, providing robust experimental evidence for the role of LKB1 in NAFLD. These findings position tranilast as a promising therapeutic candidate for the pharmacological management of metabolic diseases.
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Effect of 5:2 Regimens: Energy-Restricted Diet or Low-Volume High-Intensity Interval Training Combined With Resistance Exercise on Glycemic Control and Cardiometabolic Health in Adults With Overweight/Obesity and Type 2 Diabetes: A Three-Arm Randomized Controlled Trial.
Li, M, Li, J, Xu, Y, Gao, J, Cao, Q, Ding, Y, Xin, Z, Lu, M, Li, X, Song, H, et al
Diabetes care. 2024;47(6):1074-1083
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Diet and physical activity are important lifestyle factors for the management of type 2 diabetes (T2DM). The aim of this 12-week randomised controlled trial, including 326 patients with T2DM and overweight/obesity, was to evaluate the effect of a 5:2 diet regime versus exercise versus standard education (control) on cardiometabolic parameters and glycaemic control. Participants in the 5:2 diet group received a formula containing 790 kcal on 2 days per week whilst eating their normal diet on the other 5 days; the participants in the exercise group engaged in a supervised high-intensity interval training combined with resistance training on 2 days per week. Participants were followed for a further 36 weeks following the 12-week intervention. Compared to control, the 5:2 diet group but not the exercise group had a significant improvement in HbA1c (glycaemic control). Other parameters of glycaemic control also improved in the diet but not the exercise group, relative to control. The diabetes went into remission in significantly more participants in the diet group (19.4%), compared to the control group (10.5%), whilst this was not significantly different between the exercise (11.8%) and the control group. Both the diet and the exercise group had significantly greater reductions in fat mass, fat-to-lean mass ratio and liver fat, compared to controls. Body mass and body mass index went down more in the diet than control group, whilst lean body mass only improved in the exercise group. 36 weeks after the interventions, there was no longer a difference between the groups in body weight or HbA1c. The authors conclude that a medically supervised 5:2 diet may be an alternative strategy for improving glycaemic control.
Abstract
OBJECTIVE We aimed to examine the effects of a 5:2 diet (2 days per week of energy restriction by formula diet) or an exercise (2 days per week of high-intensity interval training and resistance training) intervention compared with routine lifestyle education (control) on glycemic control and cardiometabolic health among adults with overweight/obesity and type 2 diabetes. RESEARCH DESIGN AND METHODS This two-center, open-label, three-arm, parallel-group, randomized controlled trial recruited 326 participants with overweight/obesity and type 2 diabetes and randomized them into 12 weeks of diet intervention (n = 109), exercise intervention (n = 108), or lifestyle education (control) (n = 109). The primary outcome was the change of glycemic control measured as glycated hemoglobin (HbA1c) between the diet or exercise intervention groups and the control group after the 12-week intervention. RESULTS The diet intervention significantly reduced HbA1c level (%) after the 12-week intervention (-0.72, 95% CI -0.95 to -0.48) compared with the control group (-0.37, 95% CI -0.60 to -0.15) (diet vs. control -0.34, 95% CI -0.58 to -0.11, P = 0.007). The reduction in HbA1c level in the exercise intervention group (-0.46, 95% CI -0.70 to -0.23) did not significantly differ from the control group (exercise vs. control -0.09, 95% CI -0.32 to 0.15, P = 0.47). The exercise intervention group was superior in maintaining lean body mass. Both diet and exercise interventions induced improvements in adiposity and hepatic steatosis. CONCLUSIONS These findings suggest that the medically supervised 5:2 energy-restricted diet could provide an alternative strategy for improving glycemic control and that the exercise regimen could improve body composition, although it inadequately improved glycemic control.
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COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.
Stoleriu, MG, Ansari, M, Strunz, M, Schamberger, A, Heydarian, M, Ding, Y, Voss, C, Schneider, JJ, Gerckens, M, Burgstaller, G, et al
Thorax. 2024;(6):524-537
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INTRODUCTION Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised. METHODS We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation. RESULTS COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC+) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub+), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5+ (P=0.018) and LAMB3+ (P=0.050) expression, as well as a significant activation of Wnt-specific (P=0.014) and Notch-specific (P=0.021) genes, especially in precursors of suprabasal and secretory cells. CONCLUSION We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.
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Biomaterial-assisted strategies to improve islet graft revascularization and transplant outcomes.
Qi, B, Ding, Y, Zhang, Y, Kou, L, Zhao, YZ, Yao, Q
Biomaterials science. 2024;(4):821-836
Abstract
Islet transplantation holds significant promise as a curative approach for type 1 diabetes (T1D). However, the transition of islet transplantation from the experimental phase to widespread clinical implementation has not occurred yet. One major hurdle in this field is the challenge of insufficient vascularization and subsequent early loss of transplanted islets, especially in non-intraportal transplantation sites. The establishment of a fully functional vascular system following transplantation is crucial for the survival and secretion function of islet grafts. This vascular network not only ensures the delivery of oxygen and nutrients, but also plays a critical role in insulin release and the timely removal of metabolic waste from the grafts. This review summarizes recent advances in effective strategies to improve graft revascularization and enhance islet survival. These advancements include the local release and regulation of angiogenic factors (e.g., vascular endothelial growth factor, VEGF), co-transplantation of vascular fragments, and pre-vascularization of the graft site. These innovative approaches pave the way for the development of effective islet transplantation therapies for individuals with T1D.
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Effects of a Multicomponent Intervention With Cognitive Training and Lifestyle Guidance for Older Adults at Risk of Dementia: A Randomized Controlled Trial.
Wang, P, Yang, T, Peng, W, Wang, M, Chen, X, Yang, Y, Huang, Y, Jiang, Y, Wang, F, Sun, S, et al
The Journal of clinical psychiatry. 2024;(2)
Abstract
Objective: This study examined the effects of a multicomponent intervention program on cognitive function in community-dwelling older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Methods: This was a 2-arm, randomized controlled trial in which a multicomponent intervention was applied. Participants were recruited from June 2020 to August 2020, randomization and intervention began in August 2020, and the entire program ended in January 2021. It included cognitive training (mnemonic strategy training) and lifestyle guidance (diet, sleep, and exercise guidance) for 7 weeks. A total of 123 Chinese community-dwelling older adults experiencing MCI or SCD were randomly divided into a multicomponent intervention group (n = 62) and a health education group (n = 61). The global cognitive function was measured using the Mini-Mental State Examination (MMSE). The cognitive domains outcomes included memory functions measured using the immediate and delayed tests of the Auditory Verbal Learning Test (AVLT) and Logical Memory Test (LMT), and executive function and attention measured using the Digital Symbol Substitution Test (DSST) and Digit Span Test (DST). Data were collected at baseline and postintervention. Results: For cognitive outcome, the results of linear mixed-effect model showed significant time × group effects in the MMSE (Cohen d =0.63 [95% CI, 0.27 to 1.00], F = 10.25, P = .002). This study found significant time × group effects in AVLT-immediate (Cohen d = 0.47 [95% CI, 0.11 to 0.83], F = 8.18, P = .005), AVLT delayed (Cohen d = 0.45 [95% CI, 0.10 to 0.81], F = 4.59, P = .034), LMT-delayed (Cohen d = 0.71 [95% CI, 0.34 to 1.07], F = 4.59, P = .034), DSST (Cohen d = 0.27 [95% CI, -0.08 to 0.63], F = 4.83, P = .030), and DST (Cohen d =0.69 [95% CI, 0.33 to 1.05], F = 8.58, P = .004). Conclusions and Implications: The results support the feasibility and effectiveness of the multicomponent intervention program in improving cognitive function in community dwelling older adults at risk of dementia. The high adherence of this program shows its potential for promotion in the community and supports a larger and longer trial. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061420).
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Chemical composition, health benefits, food processing effects and applications of Boletus: a review.
Liu, Q, Sun, L, Ding, Y, Zhuang, Y
Critical reviews in food science and nutrition. 2024;(29):10812-10834
Abstract
Boletus are wild edible mushrooms that are consumed worldwide for their appealing taste and abundant production. The aim of this review was to summarize and discuss the characteristics, effects of food processing and application of Boletus worldwide. A better understanding of Boletus nutritional profiles with high carbohydrate and protein, low fat and energy. Volatile (odor compounds) and nonvolatile (free amino acids, 5'-nucleotide and nucleoside, free sugars, organic acids and umami peptides) compounds together contribute to the flavor of Boletus. Varies bioactive substances such as phenols, flavonoids, polysaccharides, tocopherols, lectins and pigment, have also been identified in Boletus, showing wide spectrum biological activities, including antioxidant, antimicrobial, antitumor, immunomodulatory, hepatoprotective, antihyperglycemic and hypotensive activities. In addition, drying, storage and cooking influenced the physical, chemical, sensory properties and biological activities of Boletus. The application of Boletus was focused on food dietary supplement, enhancement of food nutrition and function, indicating Boletus can be further developed as a functional food for human health. Further research suggestions focus on the mechanism of bioactive substances, the novel umami peptides, and the digestion and absorption of Boletus.
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Diabetes in China part 1: epidemiology and risk factors.
Xu, Y, Lu, J, Li, M, Wang, T, Wang, K, Cao, Q, Ding, Y, Xiang, Y, Wang, S, Yang, Q, et al
The Lancet. Public health. 2024;(12):e1089-e1097
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Abstract
The prevalence of diabetes in China is rapidly increasing. China now has the largest number of people living with diabetes worldwide, accounting for approximately one-quarter of the global diabetes population. Since the late 1970s, China has experienced profound changes and rapid economic growth, leading to shifts in lifestyle. Changing dietary patterns, reduced physical activity, and stress have contributed to the growing prevalence of overweight and obesity, which are important determinants potentiating the link between insulin resistance and diabetes. Social and environmental factors, such as education, air pollution, and exposure to endocrine-disrupting chemicals, have also contributed to the growing diabetes epidemic in China. The country has one of the fastest ageing populations in the world, which forecasts continued increases in the prevalence of diabetes and its complications. This Review provides an overview of the ongoing diabetes epidemic and risk factors, providing evidence to support effective implementation of public health interventions to slow and prevent the diabetes epidemic in China.
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High Vasohibin-2 expression correlated with autophagy in proliferative diabetic retinopathy.
Ding, Y, Su, N, Luan, J, Xu, J, Qiu, S, Sun, Z
Experimental eye research. 2024;:109808
Abstract
Vasohibin-2 (VASH2) is confirmed to be associated with angiogenesis. To investigate the vitreous levels of VASH2 and how VASH2 induces angiogenesis in proliferative diabetic retinopathy (PDR), a total of 120 eyes were enrolled in this prospective and randomized controlled study and the vitreous level of VASH2 was quantified by Luminex liquid suspension chip. Vector systems were applied in human retinal microvascular endothelial cells (HRMECs) for VASH2 gene overexpression, along with interfering lentiviral vectors (VASH2-shRNA) for VASH2 gene silencing. Cell migration, autophagic flux, as well as the expression of α-tubulin, detyrosinated ⍺-tubulin, LC3 II/LC3 I, P62 were detected under normal, VASH2 overexpression, or interference conditions. The level of VASH2 in PDR patients was significantly higher (218.61 ± 30.14 pg/ml) than that in ERM/MH patients (80.78 ± 2.05 pg/ml) (P = 0.001). The migration ability of HRMECs was significantly increased in VASH2 overexpression group, while in the interfering group, the migration ability decreased. VASH2 increased the detyrosination of ⍺-tubulin. The high fluorescence intensity of autophagic flux showed an activation of autophagy in VASH2 overexpression group, which was also confirmed by the increase of LC3 II/LC3 I ratio and the decrease of P62. Collectively, the present study shows in PDR, vitreous level of VASH2 is higher. VASH2 promotes neovascularization by inducing autophagy, suggesting VASH2 could be a new anti-angiogenic drug target for PDR.
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Efficacy and safety of danshen class injections in the treatment of coronary heart disease: a network meta-analysis.
Dai, S, Ding, Y, Guo, J, Wang, X
Frontiers in pharmacology. 2024;:1487119
Abstract
BACKGROUND Danshen [Salvia miltiorrhiza Bunge (Lamiaceae; Salviae miltiorrhizae radix et rhizoma)] class injections (DSCIs) are widely used in the treatment of coronary heart disease (CHD). However, there are various types of DSCIs available on the market, and it remains uncertain which DSCI has the best clinical efficacy, as well as which one is most effective in regulating inflammatory markers and oxidative stress indicators. The aim of this network meta-analysis (NMA) is to compare the therapeutic effects of different DSCIs to identify the optimal DSCI for the treatment of CHD. METHODS The databases searched to identify randomized controlled trials (RCTs) of DSCIs for CHD included the China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library. The search period spanned from the inception of each database up to June 2024. NMA was conducted using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 106 studies including 14,979 patients, involving 10,931 patients, with 5,640 in the experimental group and 5,291 in the control group. And ten DSCIs were extracted, namely: Danhong injection (DH), Danshen injection (DS), Danshenchuanxiongqin injection (DSCXQ), Dansenduofensuanyan injection (DSDFSY), Danshenfen injection (DSFZ), Fufang Danshen injection (FFDS), Guanxinning injection (GXN), Sodium Tanshinone IIA Sulfonate injection (STS), Xiangdan injection (XD), Shenxiongputaotang injection (SXPTT). The results of NMA showed that, XD injection significantly enhances clinical efficacy; STS is more effective in reducing hs-CRP levels; DSDFSY shows better efficacy in decreasing IL-1 and increasing NO levels; DSCXQ has a greater advantage in reducing IL-6 levels; GXN is more effective in regulating SOD levels; and DH is better at reducing MDA levels. CONCLUSION The combined treatment of DSCIs and WM more significant efficacy in patients with CHD compared to WM treatment alone, including clinical efficacy evaluation, inflammatory markers, and oxidative stress markers. Overall, DSDFSY and DSCXQ show better performance in clinical efficacy evaluation and regulation of inflammatory markers, while DH exhibits a more stable effect in regulating oxidative stress. However, larger sample sizes and high-quality RCTs are still necessary to further compare the various DSCIs. SYSTEMATIC REVIEW REGISTRATION [PROSPERO], identifier [CRD42024548928].
