Danggui Buxue Decoction exerts its therapeutic effect on rheumatoid arthritis through the inhibition of Wnt/ß-catenin signaling pathway.

BACKGROUND: Danggui Buxue Decoction (DBD) is a traditional Chinese medicine prescription, which has the functions of benefiting Qi, generating blood and regulating the immune system. At present, various clinical reports suggest that DBD has some efficacy in Rheumatoid arthritis (RA), but its mechanism of action is still unclear. Thus, the present study explored mechanism of this preparation on RA. METHODS: The effect of DBD was evaluated by tumor necrosis factor (TNF)-α-induced Human fibroblast-like synoviocyte of rheumatoid arthritis (HFLS-RA) cell model and collagen-induced arthritis (CIA) rat model, respectively. Inflammatory factors including TNF-ɑ, IL-1ß, IL-6 and IL-10 in the culture supernatants or rat serum were measured using ELISA. The related indexes including fur luster, mental state and activity of rat and the symptoms including swelling and deformation of toes and ankles were also measured. RESULTS: In vitro results showed that DBD cannot only inhibit the proliferation of HFLS-RA cells but also reduce the levels of pro-inflammatory factors while increasing the level of anti-inflammatory factors. Similar results were obtained from in vivo experiments. Rats receiving DBD showed a decrease in the severity of rheumatoid arthritis in rat models. Moreover, the protein levels of c-myc and ß-catenin decreased significantly, while the protein level of SFRP4 increased, which indicated that DBD might inhibit the inflammatory reaction by regulating Wnt/ß-catenin signaling pathway, thus alleviating the symptoms of RA. CONCLUSION: Our findings not only provide insights for understanding the molecular mechanism of DBD in treating RA, but also provide the theoretical basis for further clinical prevention and treatment.

Identification of Immune-Related Prognostic Markers in Gastric Cancer.

Gastric cancer (GC) is a malignant tumor with a high fatality rate. Poor prognosis is the main cause of death caused by GC. In this study, the gene expression difference between GC and the control group was analyzed. Differentially expressed genes (DEGs) related to immunity were screened for enrichment analysis. The differences in immune cell infiltration and immune function between GC and normal were identified. Cox regression analysis and survival analysis were used to determine the prognostic genes of GC in TCGA and GSE62254. The potential prognostic role of genes was further evaluated by risk score. Difference genes in GC were analyzed in TCGA. Candidate genes in TCGA and GSE62254 are analyzed, and prognostic genes are determined. The potential prognostic role of genes was further evaluated by risk score. The immune-related prognostic markers in GC were determined. FABP4, LBP, LCN1, CMA1, INHBA, ANGPTL1, ACKR1, GHR, and OGN may be used as markers for monitoring the prognosis of GC in the future.

Rectosigmoid-Junction Squamous Cell Carcinoma With pMMR/MSS Achieved a Partial Response Following PD-1 Blockade Combined With Chemotherapy: A Case Report.

Colorectal squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. And the pMMR/MSS colorectal cancer is related to a limited response to programmed death ligand-1 (PD-1) blockade monotherapy. However, the clinical activity of PD-1 blockade monotherapy or combination therapy in colorectal SCC is unknown. One patient with rectosigmoid-junction SCC was treated with PD-1 blockade combined with chemotherapy. After 3 months of PD-1 blockade and chemotherapy, the computed tomography imaging showed that this patient achieved a partial response. The next generation sequencing and immunohistochemistry analysis showed that the patient had tumors with proficient mismatch repair (pMMR) and microsatellite stability (MSS), strong PD-L1 expression, and tumor mutational burden-high (TMB-High), respectively. This case suggests that PD-1 blockade combined with chemotherapy might be an effective therapy for colorectal SCC with pMMR/MSS status. Moreover, the PD-L1 expression and TMB might be the potential predictors of PD-1 blockade response for colorectal SCC patients.

Dynamic Response of Rock-like Materials Based on SHPB Pulse Waveform Characteristics.

Rock-like brittle materials under dynamic load will show more complex dynamic mechanical properties than those under static load. The relationship between pulse waveform characteristics and strain rate effect and inertia effect is rarely discussed in the split-Hopkinson pressure bar (SHPB) numerical simulation research. In response to this problem, this paper discusses the effects of different pulse types and pulse waveforms on the incident waveform and dynamic response characteristics of specimens based on particle flow code (PFC). The research identifies a critical interval of rock dynamic strength, where the dynamic strength of the specimen is independent of the strain rate but increases with the amplitude of the incident stress wave. When the critical interval is exceeded, the dynamic strength is determined by the strain rate and strain rate gradient. The strain rate of the specimen is only related to the slope of the incident stress wave and is independent of its amplitude. It is also determined that the inertia effect cannot be eliminated in the SHPB. The slope of the velocity pulse waveform determines the strain rate of the specimen, the slope of the force pulse waveform determines the strain rate gradient of the specimen, and the upper bottom time determines the strain rate of the specimen. It provides a reference for SHPB numerical simulation. A dynamic strength prediction model of rock-like materials is then proposed, which considers the effects of strain rate and strain rate gradient.

Investigation of miRNA- and lncRNA-mediated competing endogenous RNA network in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a biliary malignancy which is prone to lymphatic metastasis and has a high mortality rate. This disease lacks effective therapeutic targets and prognostic molecular biomarkers. The aim of the current study was to investigate differentially expressed genes and elucidate their association with CCA and the underlying mechanisms of action. mRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) obtained from 36 CCA samples and nine normal samples from The Cancer Genome Atlas were integrated. Subsequently, 1,095 differentially expressed (DE) mRNAs and 75 DE miRNAs were identified using a threshold of |log2 fold change|>2 and an adjusted P<0.01. Weighted gene co-expression network analysis was used to identify the DEmRNAs that could be key target genes in CCA. A total of 12 hub DEmRNAs were identified as targetable genes. Furthermore, the hub DEmRNAs-DElncRNAs pairs were identified using the miRTarBase and miRcode databases. Cytoscape software was used to construct and visualize the protein-protein interactions and the competing endogenous RNA network. Survival time analysis and correlation analysis were used to further evaluate the hub genes. The results obtained in the current study suggested that spalt like transcription factor 3 and OPCML intronic transcript 1 may serve an important role in the development and progression of CCA.

Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines.

Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.