Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism ...of its action remains to be further clarified.
To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation.
Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence.
Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations
Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.
Tumor-associated macrophages (TAMs) and how they are activated play critical roles in tumor progression and metastasis, and in hepatocellular carcinoma (HCC), they are associated with sorafenib ...resistance. Reprogramming of TAMs into M1-like macrophages has been proposed as an approach to stimulate tumor regression. Here we studied the collective effects of interferon-alpha (IFN-α) and sorafenib on HCC. We found that IFN-α delayed tumor growth and inhibited pulmonary metastasis in an orthotopic HCC implantation model. Via
studies, we found that IFN-α treatment could reprogram M2-like RAW264.7 and THP-1 macrophage cells toward M1-like cells. In addition, we also found that IFN-α combined with a low dose of sorafenib has a synergistic inhibitory effect on HCC tumor growth and pulmonary metastasis without obvious toxicity in an
mice model. Moreover, IFN-α increased sorafenib's therapeutic efficacy by shifting TAM polarization to an M1-like phenotype, increasing and activating intratumoral CD8
T cells in HCCs. In conclusion, a combination of IFN-α and sorafenib have synergistic inhibitory effects on HCC growth and metastasis resulting from a shift in TAM polarization rather than their depletion. Our study supports the future clinical use of a combination of IFN-α and sorafenib for the treatment of advanced HCC.
Here, we reported on a label-free cross-priming amplification (CPA) scheme that utilized endonuclease restriction for simultaneous detection of nucleic acids and elimination of carryover ...contamination. Reaction mixtures were detected in a nanoparticle-based lateral flow biosensor (LFB). The assay exhibited attractive traits in that it did not require the use of labeled primers or labeled probes, and thus, the technique could prevent undesired results arising from unwanted hybridization between labeled primers or between a probe and labeled primer. Isothermal amplification and endonuclease restriction digestion were conducted in a single pot, and the use of a closed-tube amplification removed false-positive results due to contaminants. To validate the assay's applicability, we employed the novel technique to detect the pathogen
in pure cultures and artificial blood samples. The assay could detect target bacterium in pure culture with a 100 fg.μL
detection limit, and in spiked blood samples with a 700 cfu.mL
detection limit. The whole process, including sample procedure (20-min), isothermal amplification (60-min), endonuclease digestion (10-min) and result reporting (within 2-min), could be finished within 95-min. As a poof-of-concept assay, the technique devised in the current report could be employed for detecting various other sequences if the specific CPA primers were available.
The current study reports on a cross-priming amplification (CPA) scheme that utilizes antarctic thermal sensitive uracilDNA-glycosylase (AUDG) for simultaneous detection of nucleic acids and ...prevention of carryover contamination. Amplification products were applied in a nanoparticle-based lateral flow biosensor (LFB). The method shows attractive features in that it only requires the use of a labeled primer, eliminating the use of labeled probes. Thus, it is able to remove false-positive results yielded by undesired hybridization between two labeled primers or between a probe and labeled primer. CPA amplification and AUDG cleavage are carried out in a single pot, and the use of a closed-vessel reaction eliminates unwanted results due to carryover contamination. Then, the assay devised in this report was applied to the detection of the hospital-acquired pathogen
in pure cultures and artificial sputum samples. This biosensor can detect
in pure cultures with a 100 fg ·
L
detection limit, and in artificial sputum samples with a 520 cfu · mL
detection limit. The whole procedure, including specimen processing (20-min), CPA amplification (60-min), AUDG digestion (5-min) and result indicating (within 2-min), can be completed within 1.5 h. As a proof-of-concept technique, this method can be used for detecting a wide variety of other targets if the specific CPA primer set is available.
The current report devised a novel isothermal diagnostic assay, termed as nanoparticle-based biosensor (NB)- and antarctic thermal sensitive uracil-DNA-glycosylase (ATSU)-supplemented polymerase ...spiral reaction (PSR; NB-ATSU-PSR). The technique merges enzymatic digestion of carryover contaminants and isothermal nucleic acid amplification technique (PSR) for simultaneous detection of nucleic acid sequences and elimination of carryover contamination. In particular, nucleic acid amplification and elimination of carryover contamination are conducted in a single pot and, thus, the use of a closed-tube reaction can remove undesired results due to carryover contamination. For demonstration purpose,
is employed as the model to demonstrate the usability of NB-ATSU-PSR assay. The assay's sensitivity, specificity, and practical feasibility were successfully evaluated using the pure cultures and sputum samples. The amplification products were detectable from as little as 100 fg of genomic DNAs and from ~550 colony-forming unit (CFU) in 1 ml of spiked sputum samples. All
strains examined were positive for NB-ATSU-PSR detection, and all non-
strains tested were negative for the NB-ATSU-PSR technique. The whole process, including rapid template preparation (20 min), PSR amplification (60 min), ATSU treatment (5 min), and result reporting (within 2 min), can be finished within 90 min. As a proof-of-concept methodology, NB-ATSU-PSR technique can be reconfigured to detect various target nucleic acid sequences by redesigning the PSR primer set.
Gastric cancer has high incidence and fatality rates, making chemoprevention agents necessary. There is an ongoing debate about aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) use can ...significant reduce the risk of GC. We conducted a meta-analysis of existing studies evaluating the association of anti-inflammatory drug and GC. We performed a systematic literature search of PubMed, Web of Science, Embase, OVID, Cochrane Library and Clincialtrials.gov up to August 31, 2015. Either a fixed-effects or a random-effects model using was based on the result of homogeneity analysis. Subgroup, sensitivity, meta-regression, and publication bias analyses were evaluated. Forty-seven studies were finally included in this meta-analysis. The overall GC risk reduction benefit associated with anti-inflammatory drug use represented an RR of 0.78 (95% CI 0.71 to 0.85) and an adjusted RR of 0.74 (95% CI 0.71 to 0.77). Besides, the prevention benefit of aspirin/NSAIDs ingestion appeared to be confined to those patients with regiment of short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day). Further, our data also suggest that COX-2 inhibitors use is a more effective approach in GC prevention (RR, 0.45; 95% CI, 0.29-0.70). In this meta-analysis, our finding support short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day) aspirin/NSAIDs intake is a well method for GC prevention and also confirm the inverse association between aspirin/NSAIDs use and GC risk. Additionally, selective COX-2 inhibitors use probably a more effective approach to reduce GC risk.
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