Huaier inhibits cholangiocarcinoma cells through the twist1/FBP1/Wnt/ß-catenin axis.

BACKGROUND: Although Huaier granules can be used as prospective anti-cholangiocarcinoma drugs, the mechanism of action of Huaier granules in cholangiocarcinoma is not clear. The anti-cholangiocarcinoma effect of Huaier granules was validated in cell line research. In vitro experiments were conducted to investigate the signalling pathways affected by Huaier in CCA cells. METHODS AND RESULTS: Real-time quantitative PCR (RT‒qPCR) and Western blot analysis were performed to analyse gene expression in CCA cells. MTT assays, scratch tests, and Transwell assays were used to explore the effects on the proliferation and metastasis of CCA cells. Chromatin immunoprecipitation assays were performed to reveal the potential underlying mechanisms involved. Twist1 was upregulated in human CCA tissues. In addition, its expression levels were negatively related to FBP1 expression levels. Mechanistically, Twist1 can bind to the region of the FBP1 promoter to reduce its expression. Huaier plays an indispensable role in suppressing Twist1 expression to inhibit the Twist1/FBP1/Wnt/ß-catenin axis. Then, we verified the effect of Huaier in vitro. CONCLUSIONS: These findings suggested that Huaier granules were capable of inhibiting CCA development through regulating the Twist1/FBP1/Wnt/ß-catenin signalling axis and provided a novel orientation for the development of novel anti-CCA drugs.

Establishment and validation of a nomogram model for preoperative prediction of the risk of cholangiocarcinoma with perineural invasion.

OBJECTIVE: To establish and validate a nomogram model for predicting the risk of cholangiocarcinoma with perineural invasion. METHODS: We retrospectively collected the clinical data of 356 patients with surgically confirmed cholangiocarcinoma, including 98 cases of extrahepatic cholangiocarcinoma (eCCA), 197 cases of intrahepatic cholangiocarcinoma (iCCA), and 61 cases of perihilar cholangiocarcinoma (pCCA). RESULTS: Based on these data, we determined the influencing factors of preoperative perineural invasion risk in patients with cholangiocarcinoma by forward multivariate regression analysis. Based on these variables, we established two nomogram models. The model variables for predicting perineural invasion of eCCA included prothrombin time, high-density lipoprotein and tumor size (all P<0.05). The consistency index (C-index) of internal and external validation was 0.845 and 0.806, respectively. In addition, the model variables for predicting perineural invasion of iCCA included carcinoembryonic antigen, carbohydrate antigen 19-9 and tumor size (all P<0.05). The internal and external validation of the C-index was 0.735 and 0.886, respectively. Both models have considerable results in terms of calibration accuracy and clinical decision-making. Kaplan-Meier survival analysis showed that the survival time of patients with perineural invasion was significantly reduced (P=0.033). CONCLUSIONS: We established a predictive model for preoperative perineural invasion in patients with iCCA and eCCA, and this model can provide good predictive value for clinicians. However, we have not obtained relevant predictive variables for predicting perineural invasion of pCCA, and the number of modeling cases was relatively small, so this study needs to be further explored.

Chelidonine reduces IL-1ß-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats.

Chondrocyte inflammation and catabolism are two major features in the progression of osteoarthritis (OA). Chelidonine, a principal alkaloid extracted from Chelidonium majus, is suggested to show anti-inflammation, anti-apoptosis, and anti-oxidation activities in various diseases. However, its potential effects on OA cartilage degeneration remains unclear. To evaluate the effect of chelidonine on OA and its underlying mechanism, we incubated chondrocytes with interleukin (IL)-1ß and chelidonine at varying concentrations. Then, we performed the CCK-8 assay, fluorescence immunostaining, reverse transcription PCR, ELISA, and western blotting to evaluate cell viability, catabolic/inflammatory factors, levels of extracellular matrix (ECM)-related proteins, and the involved pathways. H&E and Safranin-O staining and ELISA were performed to measure cartilage degradation and synovial inflammation. Chelidonine suppressed the IL-1ß-mediated catabolism and inflammation of chondrocytes. Chelidonine suppressed the NF-κB pathway activation. Similarly, our in vivo experiment showed that chelidonine partially attenuated cartilage degradation while inhibiting synovial inflammation. Chelidonine inhibited inflammation and catabolism through modulation of NF-κB pathways in vitro, thereby avoiding rat cartilage degeneration and synovial inflammation within OA.

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a type of liver cancer that originates from liver cells. It is one of the most common types of liver cancer and a leading cause of cancer-related death worldwide. Early detection and treatment can improve the HCC prognosis. Therefore, it is necessary to further improve HCC markers and risk stratification. PANoptosome is a cytoplasmic polymer protein complex that regulates a proinflammatory programmed cell death pathway called "PANoptosis". The role of PANoptosis in HCC remains unclear. In this study, the molecular changes of PANoptosis related genes (PAN-RGs) in HCC were systematically evaluated. We characterized the heterogeneity of HCC by using consensus clustering to identify two distinct subtypes. The two subtypes showed different survival rate, biological function, chemotherapy drug sensitivity and immune microenvironment. After identification of PAN-RG differential expression genes (DEGs), a prognostic model was established by Cox regression analysis using minimum absolute contraction and selection operator (LASSO), and its prognostic value was verified by Cox regression analysis, Kaplan-Meier curve and receiver operating characteristic (ROC) curve. Our own specimens were also used to further validate the prognostic significance and possible clinical value of the selected targets. Subsequently, we conducted a preliminary discussion on the reasons for the influence of the model on the prognosis through TME analysis, drug resistance analysis, TMB analysis and other studies. This study provides a new idea for individualized and precise treatment of HCC.

Chelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats

Chondrocyte inflammation and catabolism are two major features in the progression of osteoarthritis (OA). Chelidonine, a principal alkaloid extracted from Chelidonium majus, is suggested to show anti-inflammation, anti-apoptosis, and anti-oxidation activities in various diseases. However, its potential effects on OA cartilage degeneration remains unclear. To evaluate the effect of chelidonine on OA and its underlying mechanism, we incubated chondrocytes with interleukin (IL)-1β and chelidonine at varying concentrations. Then, we performed the CCK-8 assay, fluorescence immunostaining, reverse transcription PCR, ELISA, and western blotting to evaluate cell viability, catabolic/inflammatory factors, levels of extracellular matrix (ECM)-related proteins, and the involved pathways. H&E and Safranin-O staining and ELISA were performed to measure cartilage degradation and synovial inflammation. Chelidonine suppressed the IL-1β-mediated catabolism and inflammation of chondrocytes. Chelidonine suppressed the NF-κB pathway activation. Similarly, our in vivo experiment showed that chelidonine partially attenuated cartilage degradation while inhibiting synovial inflammation. Chelidonine inhibited inflammation and catabolism through modulation of NF-κB pathways in vitro, thereby avoiding rat cartilage degeneration and synovial inflammation within OA.

Thio-bisnaphthalimides as Heavy-Atom-Free Photosensitizers with Efficient Singlet Oxygen Generation and Large Stokes Shifts: Synthesis and Properties.

By structure transformation of benzo[k,l]thioxanthene-naphthalimide derivatives (ND-S), a novel series of nonplanar thio-heterocyclic bisnaphthalimide derivatives are designed and synthesized. They display high molar absorptivity and large Stokes shifts. They are also heavy-atom-free photosensitizers with high singlet oxygen quantum yields of 0.75 and 0.82. Thus, these new structures based on the naphthalimide skeleton have great potential for singlet oxygen applications.

Performance of a multilayered small-diameter vascular scaffold dual-loaded with VEGF and PDGF.

The urgent needs of functional arterial replacements for curing the vascular system diseases have been proposed for many years. However, an ideal small-diameter vascular scaffold, which is nonthrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of natural vessels, and supports neovascular tissue reconstruction, is still in progress. For this purpose, we previously attempted dual-delivery of VEGF and PDGF by double-layered electrospun membranes. Here, a multilayered vascular scaffold in 1.5-mm diameter with sufficient mechanical properties was developed by electrospinning from poly(ethylene glycol)-b-poly(L-lactide-co-ε-caprolactone) (PELCL), poly(L-lactide-co-glycolide) (PLGA), poly(ε-caprolactone) (PCL) and gelatin. Spatio-temporal releases of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGF) were specially controlled by the inner PELCL and middle PLGA layers, respectively, and the outer PCL layer contributed to the mechanical stability. Introduction of gelatin improved vascular endothelial cells adhesion at first, and loosen membrane after its degradation facilitated vascular smooth muscle cells (VSMCs) ingrowth. Cell activities indicated dual release of growth factors promoted endothelialization and inhibited VSMCs hyperproliferation. The small-diameter vascular scaffold dual-loading VEGF and PDGF could maintain patency in rabbit left common carotid artery for 8 weeks. It is concluded that the specially prepared fibrous scaffold in multilayer could benefit blood vessel reconstruction.

(2,2'-Bipyridine-κN,N')bis-(4-chloro-benzoato-κO)zinc.

In the title compound, [Zn(C(7)H(4)ClO(2))(2)(C(10)H(8)N(2))], the Zn(II) atom is coordinated by two O atoms from two 4-chloro-benzoate ligands and two N atoms from a chelating 2,2'-bipyridine (bpy) mol-ecule in a distorted N(2)O(2) tetra-hedral geometry. The Zn(II) atom is located on a twofold rotation axis, which also passes through the mid-point of the central C-C bond of the bpy ligand. In the crystal, weak C-H⋯O hydrogen bonds and π-π stacking inter-actions between the pyridine rings of the bpy ligands [centroid-centroid distance = 3.642 (3) Å] link the complex mol-ecules into a two-dimensional supra-molecular structure parallel to (100). An intra-molecular C-H⋯O hydrogen bond is also observed.

1-[(2,3,4,5,6-Penta-fluoro-phen-yl)ethyn-yl]ferrocene.

The mol-ecular structure of the title compound, [Fe(C(5)H(5))(C(13)H(4)F(5))], consists of a ferrocenyl group and a 2,3,4,5,6-penta-fluoro-benzene group linked through an ethyne spacer. The crystal packing is dominated by inter-molecular C-H⋯F hydrogen bonds, C-F⋯π inter-actions between the penta-fluoro-benzene groups [F⋯centroid distances = 3.882 (2) and 3.884 (2) Å] and π-π inter-actions between the penta-fluoro-benzene and cyclo-penta-dienyl rings [centroid-centroid distance = 3.741 (1) Å].