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Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

Due to the special nature of karst landforms, quantification of their vegetation dynamics and their underlying driving factors remains a formidable challenge. Based on the NDVI dataset, this study uses principal component analysis to extract comprehensive factors and utilizes an optimized parameter-based geographical detector and geographically weighted regression models to assess the explanatory capacity of comprehensive factors concerning the spatial differentiation of vegetation change. The results of this study revealed the following: (1) In terms of temporal and spatial vegetation changes, the Asian karst concentrated distribution area (AKC) displayed overall stability and an increasing trend between 2000 and 2020. Notably, the northern (Southwest China) karst region experienced the most substantial vegetation increase, with increased areas exceeding 70%, primarily concentrated in the provinces of Guizhou and Guangxi. In contrast, the southern (Indochina Peninsula) karst region, particularly in Cambodia, Laos, and Vietnam (CLV), exhibited a significant decreasing trend, with decreased areas exceeding 30%. (2) By analyzing the driving factors affecting vegetation change, vegetation changes exhibited distinct spatial differentiations, along with positive and negative effects. Human factors, including human activity intensity, urban economic development, and agricultural economic development (explanatory power and local R2 were both greater than 0.2), exerted a more significant impact on vegetation change in the AKC than natural factors such as thermal conditions, water conditions, and soil conditions. This impact was positive in Southwest China but inhibited in the Indochina Peninsula, particularly within the CLV karst area. Notably, the interaction between natural and human factors greatly enhanced their impacts on vegetation changes. These results provide valuable insights into vegetation changes and their driving mechanisms, which are crucial for preserving the stability of delicate karst ecosystems and facilitating vegetation recovery.

Guided bone regeneration (GBR) is a standard therapy for treating bone defects, with collagen-based barrier membranes widely used clinically. However, these membranes face challenges like poor mechanical properties, early bacterial invasion and immunomodulation deficiency, potentially risking GBR failure. Orchestrating macrophage activation and controlling their M1 or M2 polarization are effective strategies for bone repair. Here, we present a Janus collagen-based barrier membrane with immunomodulation. The porous layer promotes direct osteogenic differentiation and inward growth of osteoblasts. The dense layer prevents invasion of soft tissue into bone defects and protects bone defects from bacterial infection. The membrane also enhances rat bone marrow-derived mesenchymal stem cell infiltration, proliferation, and osteogenic differentiation by regulating the immune microenvironment, demonstrating superior bone regeneration compared to the commercial Bio-Gide® membrane. Overall, the Janus collagen-based membrane reduces tissue inflammation and fosters an osteoimmune environment conducive to new bone formation, offering effective material design for advanced GBR technology. Guided bone regeneration (GBR) membranes are used to treat bone defects, but face challenges in regulating the immune microenvironment. Here, Yang et al. report a Janus collagen-based barrier membrane that modulates the osteoimmune microenvironment to effectively promote bone regeneration.

Background We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). Methods In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). Results The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P < 0.001; SYNTAX score: 15.88 ± 16.36 vs. 7.28 ± 10.54, P = 0.003) were higher and FMD was lower (6.03 ± 2.08% vs. 6.94 ± 2.20%, P = 0.036) in diabetic patients with poor glycemic control (HbA1c ≥ 7.0%; n = 56) compared to those with good glycemic control (HbA1c < 7.0%; n = 46). Multivariate regression analysis revealed that tertile of FMD was an independent determinant of presence of significant coronary artery stenosis (OR = 0.227 95% CI 0.056–0.915, P = 0.037), Gensini score (β =  − 0.470, P < 0.001) and SYNTAX score (β =  − 0.349, P = 0.004) in diabetic patients with poor glycemic control but not for those with good glycemic control (P > 0.05). Conclusion Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.

Yinchenhao decoction (YCHD), comprising Yinchenhao ( Artemisiae Scopariae Herba), Zhizi ( Gardeniae Fructus ) and Dahuang ( Radix Rhei et Rhizoma ), is widely used for treating various diseases. We aimed to investigate the bile acid metabolic mechanism of YCHD in dimethylnitrosamine (DMN)-induced liver fibrosis model. Rats received DMN (10 mg/kg, intraperitoneally) for four successive weeks for liver fibrosis induction and were treated with YCHD for the last 2 weeks. Histopathological analysis showed that YCHD prevented DMN-induced histopathological changes in liver tissues. Serum liver function in YCHD group improved. Ultraperformance liquid chromatography-mass spectrometry analysis showed that YCHD significantly restored both free and conjugated bile acid levels increased by DMN, to normal levels. RT-qPCR results showed that YCHD treatment upregulated the expression of genes related to bile acid synthesis, reabsorption, and excretion. Western blotting analysis showed that YCHD downregulated α-SMA, TGF-β1, p-Smad3, and p-ERK1/2 expression in chenodeoxycholic acid (CDCA)-activated hepatic stellate cells (HSCs). The viability of CDCA-activated HSCs significantly increased after treatment with YCHD and PD98059 (an ERK inhibitor) compared to YCHD treatment alone. Our findings suggest that YCHD alleviated DMN-induced liver fibrosis by regulating enzymes responsible for bile acid metabolism. Additionally, it inhibits CDCA-induced HSC proliferation and activation via TGF-β1/Smad/ERK signalling pathway.

Background Diabetic kidney disease (DKD) is one of the most pervasive complications of diabetes worldwide. However, the pathogenesis of DKD remains poorly understood, due to limitations of the models. The hPSC-derived kidney organoids may offer a new possibility to solve the problem. Methods We generated human pluripotent stem cells (hPSCs) derived kidney organoids to model DKD injury by glucose intervention for 24 and 72 h, respectively. RT-qPCR was used to assess gene expression, while immunofluorescence was performed to evaluate protein expression. PAS staining was applied to examine organoid morphology, and Sirius Red staining was used to assess fibrosis. Results Firstly, qPCR results showed that glucose and lipid metabolism-related genes such as LDH , HK2 , SGLT2 , PLIN2 , PPARA , PGC1A , and HSL mRNA expression were upregulated after glucose intervention. Secondly, qPCR and immunofluorescence staining results revealed that the expression of pro-inflammatory cytokines IL6, IL1B, TNFA, VCAM1 and IL-10 were increased, which suggested kidney organoids possess inflammatory responses in high glucose environments. Thirdly, KIM1, a kidney injury maker was upregulated after glucose intervention, and increased apoptosis cells in kidney organoids were confirmed by TUNEL assay. Finally, qPCR and immunofluorescence staining results revealed that the expression of fibrosis-related molecules TGF-β1 and COL4 were increased. Conclusion In general, diabetic kidney disease organoid models provide a valuable model for studying the onset, progression, and injury of DKD. Clinical trial number Not applicable.

Fuzheng huayu formula (FZHY), an antifibrotic traditional Chinese medicine, is frequently used for the treatment of liver fibrosis. In this study, network analysis, transcriptomic analysis, assays of cell apoptosis, viability and protein expression were used for investigating the effects and mechanisms of compounds derived from FZHY on hepatic parenchymal cell (HPC) protection and hepatic stellate cell activation. Network pharmacology analysis found that 6 major compounds and 39 potential targets were important network nodes. Our analysis predicted that the active compounds of FZHY, including hederagenin, luteolin and tanshinone IIA inhibited cell apoptosis (p < 0.05), increased PI3K expression and reduced cleaved caspase 3 expression and the Bax/Bcl-w ratio (p < 0.05) in L02 cells that had apoptosis induced by TNF-α. Few significant changes caused by FZHY, hederagenin, luteolin and tanshinone IIA were observed in hepatic stellate Lx2 cells upon TGF-β1 induction. These data suggest that FZHY is active against liver fibrosis, protects hepatic parenchymal cells from apoptosis, and recovers liver function, possibly through the effects of its active compounds hederagenin, luteolin and tanshinone IIA and is involved in the inhibition of apoptosis in HPCs, possibly through regulating the PI3K, ERK, cleaved caspase 3 and Bax/Bcl-w levels.

There is a lack of effective therapeutic drugs in patients with postoperative colorectal cancer (PCRC). This study aimed to investigate the therapeutic effect and mechanisms of Bushen-Jianpi-Jiedu decoction (BSJPJDD) combined with chemotherapeutic drugs (oxaliplatin) on PCRC with liver and kidney yin deficiency and spleen deficiency syndrome (LKYD-SDS) through the therapeutic evaluation of clinical therapy and the integrative analysis of network pharmacology, RNA-seq and label-free data, and experiment verification in vitro . In clinical therapy, the median progression-free survival (PFS) and Karnofsky performance score (KPS) were increased in PCRC patients by the aqueous extract of BSJPJDD combined with oxaliplatin treatment for three months, compared to oxaliplatin alone ( p < 0.05). The integrative analysis showed that 559 differentially expressed genes (DEGs) and 11 differentially expressed proteins (DEPs) were regulated by BSJPJDD, among which seven bioactive compounds through 39 potential targets were involved in the regulation of multiple signaling pathways including MAPK, PI3K-Akt, and HIF-1, etc. In the experimental verification, an ELISA assay showed that plasma ZEB2, CAT, and KRT78 were decreased, and IL-1Α, CD5L, FBLN5, EGF, and KRT78 were increased in comparison to the above ( p < 0.05). Furthermore, the SW620 cell viability was inhibited and the expressions of MAPK and the p-ERK/ERK ratio were significantly downregulated by the aqueous extract of BSJPJDD combined with oxaliplatin treatment, compared with oxaliplatin treatment alone ( p < 0.05). These data suggested that BSJPJDD combined with oxaliplatin prolongs the survival and improves Karnofsky performance status of PCRC patients with LKYD-SDS, and may be associated with the regulation of multiple signaling pathways.

Objective To evaluate the therapeutic effect of Traditional Chinese Medicine (TCM), specifically Fuzheng Qingdu (FZQD) therapy, on the survival time of metastatic GC patients. Patients and Methods Databases of medical records of 6 hospitals showed that 432 patients with stage IV GC were enrolled from March 1, 2012 to October 31, 2020. Propensity score matching (PSM) was used to reduce the bias caused by confounding factors in the comparison between the TCM and the non-TCM users. We used a Cox multivariate regression model to compare the hazard ratio (HR) value for mortality risk, and Kaplan-Meier survival curve for the survival time of GC patients Results The same number of subjects from the non-TCM group were matched with 122 TCM-treated patients after PSM to evaluate their overall survival (OS) and progression-free survival (PFS). Median time of OS of TCM and non-TCM users were 16.53 and 9.10 months, respectively. TCM and non-TCM groups demonstrated a 1-year survival rate of 68.5% and 34.5%, 2-year survival rate of 28.6% and 3.5%, and 3-year survival rate of 17.8% and 0.0%, respectively. A statistical difference exists in OS between the 2 groups (χ2 = 33.39 and P < .0001). The PFS of TCM users was also longer than that of non-TCM users (χ2 = 4.95 and P = 0.026). Notably, Chinese herbal decoction, Shenmai and compound Kushen injections were commonly used for FZQD therapy. Conclusion This propensity-matched study showed that FZQD therapy could improve the survival of metastatic GC patients.

X80 pipeline steel is widely used in oil and gas pipelines because of its excellent strength, toughness, and corrosion resistance. It is welded via gas metal arc welding (GMAW), risking high cold crack sensitivities. There is a certain relationship between the joint hardness and cold crack sensitivity of welded joints; thus, predicting the joint hardness is necessary. Considering the inefficiency of welding experiments and the complexity of welding parameters, we designed a set of processes from temperature field analysis to microstructure prediction and finally hardness prediction. Firstly, we calculated the thermal cycle curve during welding through multi-layer welding numerical simulation using the finite element method (FEM). Afterwards, BP neural networks were used to predict the cooling rates in the temperature interval that ferrite nuclears and grows. Introducing the cooling rates to the Leblond function, the ferrite fraction of the joint was given. Based on the predicted ferrite fraction, mapping relationships between joint hardness and the joint ferrite fraction were built using BP neural networks. The results shows that the error during phase fraction prediction is less than 8%, and during joint hardness prediction, it is less than 5%.