[Systematic review and Meta-analysis of efficacy and safety of Huachansu in treating cancer-related pain].

To evaluate the effectiveness and safety of Huachansu in the treatment of cancer-related pain,four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,PubMed) were systematically and comprehensively retrieved since the establishment of each database to October 2018. Randomized controlled trials( RCTs) for the treatment of cancer-related pain with Huachansu were screened out according to pre-established inclusion criteria and exclusion criteria. Rev Man5. 3 software was used for Meta-analysis. A total of 241 articles were retrieved,and finally 10 studies were included. The total sample size was 1 293,including 648 in the experimental group and 645 in the control group. The overall quality of the included studies was generally low. The results of Meta-analysis showed that Huachansu combined with Western medicine acesodynes was superior to the single use of Western medicine acesodynes in the treatment of short-term pain relief,improvement of quality of life and reduction of constipation,nausea and vomiting,dizziness,drowsiness,anorexia and other adverse reactions. And it also has the advantage of a shorter onset time and longer duration time of analgesia,but cannot reduce the incidence of dysuria. Based on the findings,Huachansu had a certain effect in the treatment of cancer-related pain,and a significant positive effect on the improvement of quality of life and the reduction of adverse reactions. No serious adverse reactions occurred. However,due to the small number of studies included,the low quality of the included studies,published biases and other restrictions,the evidence in this study has a low quality,and the conclusion shall be adopted with caution. The effectiveness and safety of Huachansu in the treatment of cancer-related pain remained to be further confirmed in the future with a well-designed,rigorous,and standardized report,with a large sample size,multiple centers,and sufficient follow-up time for randomized controlled trials.

Cimigenol depresses acute myeloid leukemia cells protected by breaking bone marrow stromal cells via CXCR4/SDF­1α.

The purpose of the present study was to evaluate cimigenol (Cim) treatment effects to cell proliferation by breaking bone marrow stromal cells (BMSCs) through C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor-1α (SDF-1α) pathway. MV-4-11 and U937 cell lines were used. The present study was divided into two parts. First, the cell lines were divided into normal control (NC), BMSC (cells co-cultured with BMSCs), BMSC + DMSO, BMSC + Low (treated with 5 mg/ml Cim), BMSC + Middle (treated with 10 mg/ml Cim), BMSC + High (treated with 20 mg/ml Cim). In the second step, the cell lines were divided into NC, BMSC, BMSC + BL8040 (treated with BL8040 which inhibits CXCR4), BMSC + Cim and BMSC + Cim + BL8040. EdU positive cell numbers were measured by EdU assay and apoptosis rate by flow cytometry and TUNEL assay. Relative gene and protein expression was measured by reverse transcription-quantitative PCR and western blotting assay. BMSCs were able to protect proliferation of cancer cells and decreased cell apoptosis compared with the NC group (P<0.001, respectively). With Cim supplement, the cell proliferation was decreased with cell apoptosis increasing compared with NC group (P<0.001 respectively). However, the anti-tumor effects of Cim were not significantly different from the BL8040 treated groups (P<0.001, respectively). In conclusion Cim decreased acute myeloid leukemia cells protected by BMSCs through the CXCR4/SDF-1α pathway.

Aqueous Extract of Cimicifuga dahurica Reprogramming Macrophage Polarization by Activating TLR4-NF-κB Signaling Pathway.

PURPOSE: Cimicifuga dahurica (C. dahurica), which has been used in traditional oriental medicine for a long period, was reported to exert extensive antitumor activity, but the effect and molecular biological mechanism of C. dahurica on multiple myeloma (MM) has not been elaborated. Tumor-associated macrophages (TAMs) exhibit a sustained polarization between tumor killing M1 subtype and tumor supporting M2 subtype. And a lower ratio of M1/M2 is associated with tumor angiogenesis, proliferation and invasion. We explored the inhibitory effect of the aqueous extract of the root of C. dahurica (CRAE) on tumor growth by reprogramming macrophage polarization in the tumor microenvironment. METHODS: Mice bearing SP2/0 multiple myeloma were treated with CRAE. Western blotting (WB), immunohistochemistry (IHC) and immunofluorescence staining were utilized to assess tumor growth and TAM populations. Macrophages were depleted by injection of clodronate liposomes to determine and measure the role of CRAE as an anti-tumor agent by targeting macrophages. To simulate tumor microenvironment, MM cells H929 and TAMs were co-cultured using the transwell co-culture system. By using CRAE as an immunoregulator in M2-like macrophages, we analyzed CRAE-treated macrophage-associated surface markers and cytokines by flow cytometry and WB. RESULTS: The results indicated that CRAE treatment could reduce tumor burden of MM mice and a high degree of M1-like macrophages infiltration was detected in tumor tissues. In vitro co-culture system, CRAE significantly promoted the polarization of M2 to M1 phenotype, which led to the increase in apoptosis of myeloma cells. It was found that the M1 polarization induced by CRAE depended on the TLR4-MyD88-TAK1-NF-κB signal transduction. CONCLUSION: This study elucidated the anticancer mechanism of the aqueous extract of C. dahurica (CRAE) through reprogramming macrophage polarization and highlighted that CRAE could act as a potential novel option for cancer immunotherapy.

Chinese Herbal Medicine Suyin Detoxification Granule Inhibits Pyroptosis and Epithelial-Mesenchymal Transition by Downregulating MAVS/NLRP3 to Alleviate Renal Injury.

PURPOSE: Proteinuria is an independent risk factor of chronic kidney disease (CKD). Albumin-induced tubulointerstitial inflammation and epithelial-mesenchymal transition (EMT) via the activation of NLRP3 inflammasome is a potential therapeutic target for CKD. Suyin Detoxification Granule (SDG) improves proteinuria and postpones renal failure. However, the underlying mechanism is still unknown. METHODS: Firstly, the rat model of renal failure was established using intragastric administration of adenine. Renal function, proteinuria, inflammatory indicators in serum, and renal pathology were assessed, and renal immunohistochemical staining of NLRP3 inflammasomes was performed after intervention with low and high concentrations of SDG. Secondly, the model of renal tubular epithelial HK-2 cells was established using albumin in vitro, and the cell viability, EMT phenotype, and the expression of proteins in the NLRP3 inflammasome signaling pathway were measured after the freeze-dried powder of Suyin Detoxification Prescription (SDP) and CY-09, which is a selective and direct NLRP3 inhibitor, were co-incubated with albumin. ATP, SOD, mitochondrial membrane potential, and ROS were further measured in vitro, and changes in the mitochondrial function after SDP intervention were observed. The mitochondrial antiviral signaling protein (MAVS) was knocked down using siRNA, and the interaction between MAVS and NLRP3 was verified using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. RESULTS: SDG improved renal function and proteinuria, alleviated renal fibrosis, and reduced serum inflammation and the expression of the components of the NLRP3 inflammasome in the kidney. In vitro, SDP and CY-09 enhanced cell viability after injury with albumin and inhibited pyroptosis induced by the NLRP3 inflammatory signaling pathway and expression of proteins involved in EMT. It was further found that SDP alleviated the mitochondrial dysfunction caused by albumin. The knockdown of MAVS reduced the expression of NLRP3 pathway proteins and their mRNA levels and also weakened the co-localization of NLRP3, thus, reducing cell pyroptosis. CONCLUSION: SDP protected renal tubular epithelial cells from cell pyroptosis and EMT by regulating the albumin-induced mitochondrial dysfunction/ MAVS/ NLRP3-ASC-caspase-1 inflammasome signaling pathway.

Shengma Biejia Decoction Inhibits Cell Growth in Multiple Myeloma by Inducing Autophagy-Mediated Apoptosis Through the ERK/mTOR Pathway.

Shengma Biejia decoction (SMBJD), a traditional Chinese formula recorded in the Golden Chamber, has been widely used for the treatment of malignant tumors. However, its underlying molecular targets and mechanisms are still unclear. This study showed that SMBJD inhibited tumor growth and stimulated hemogram recovery significantly in a multiple myeloma xenograft model. Western blot and immunohistochemistry assays of tumor tissues showed that SMBJD reduced the ratio of autophagy-related proteins LC3-II/LC3-I, while P62 and apoptosis-related proteins cleaved caspase-3/caspase-3 and Bax/Bcl-2 were upregulated. In vitro experiments demonstrated the time-dependent and dose-dependent cytotoxicity of SMBJD on multiple myeloma cell lines H929 and U266 through MTT assays. The LC3-II/LC3-I ratio and number of GFP-LC3 puncta showed that SMBJD inhibited the autophagy process of H929 and U266 cells. Moreover, both SMBJD and 3-methyladenine (3-MA) caused a decrease in LC3-II/LC3-I, and SMBJD could not reverse the upregulation of LC3-II/LC3-I caused by bafilomycin A1 (Baf-A1). Furthermore, the results of annexin V-FITC and propidium iodide double staining demonstrated that SMBJD treatment induced the apoptosis of H929 and U266 cells. These data prove that SMBJD inhibits autophagy and promotes apoptosis in H929 and U266 cells. The results also show that rapamycin could reduce the rate of SMBJD-induced apoptosis in H929 and U266 cells, at a concentration which had no effect on apoptosis but activated autophagy. In addition, analysis of the mechanism indicated that levels of phosphorylated ERK and phosphorylated mTOR were increased by treatment with SMBJD in vivo and in vitro. These results indicate that SMBJD, an old and effective herbal compound, could inhibit the viability of H929 and U266 cells and induce autophagy-mediated apoptosis through the ERK/mTOR pathway. Thus, it represents a potential therapy strategy for multiple myeloma.

Is sCD163 a Clinical Significant Prognostic Value in Cancers? A Systematic Review and Meta-Analysis.

BACKGROUND: Tumor associated macrophages (TAMs), a kind of inflammatory cells in the tumor microenvironment, are crucial for the occurrence and development of various tumors which increased the expression of CD163. Nevertheless, not much has been established regarding soluble CD163 and its connection to tumor diagnosis. In this case, a meta-analysis was conducted to determine the tumor diagnostic importance of serum sCD163. METHODS: In order to assess the correlation between sCD163 and the overall survival (OS) or progression-free survival (PFS) among tumor patients, a systematic perusal of literature published until June 2020 was conducted. Relevant data were primarily obtained from papers that have the following qualifications: 1) a confidence interval (CI) of 95%; 2) a report of the hazard ratios; and, 3) pooled by means of the Mantel-Haenszel random-effect representation. RESULTS: For the final meta-analysis, eight papers comprised of 1,236 cases were involved. Through pooled investigation, it was determined that a correlation exists between elevated serum sCD163 and worse OS (HR = 2.24, 95% CI: 1.50-3.35, P < 0.001) and PFS (HR = 3.90, 95% CI: 2.33-6.52, P < 0.001) among tumor cases. Subgroup analysis stratified by medium age at diagnosis demonstrated that patients over 60 years old with high sCD163 had worse OS (HR 2.28, 95% CI: 1.58-3.29, P < 0.001) than under 60 (HR 1.43, 95% CI: 1.15-1.77, P = 0.001). Subgroup analysis revealed that analysis method and medium age at diagnosis were the potential source of heterogeneity. CONCLUSIONS: Overall, diagnosis of tumor cases can be adversely determined through substantial sCD163 levels. Consequently, it is encouraged that extensive researches regarding the rates of cancer survival be accomplished.

Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis.

Solasonine, the main active ingredient of Solanum nigrum L., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) in vitro. Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia in vitro and in vivo and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.