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At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle. It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear. Aim of the study: To investigate P.V in treating CRC and clarify the underlying mechanism. This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology, and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot. The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF- α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment. P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment. [Display omitted] • Patrinia villosa has a certain therapeutic effect on the CRC. • Patrinia villosa could up-regulate in 41 kinds, including sn-glycero-3-Phosphocholine, 1-Acyl-sn-glycero-3-phosphocholine, Diacylglycerol, etc. And down-regulate in 9 kinds, including Phytosphingosine, etc. These changes are mainly related to glycerophospholipid metabolism, sphingolipid metabolism, cysteine and methionine metabolism, glycine, serine and threonine metabolism. • Patrinia villosa treat CRC though the PI3K target and PI3K/Akt signaling pathway. • Patrinia villosa reduced the protein expression of PI3K, Akt, VEGFA, P38, JNK, ERK1/2, TP53, IL-6, TNF- α , Caspase-3, and VEGFA and increased the protein expression of Caspase-9. [ABSTRACT FROM AUTHOR]

Pyroptosis is triggered by inflammasomes after its activation by various inflammatory stimulations, including lipopolysaccharide (LPS) and improper pH. This may result in programmed death of the affected cell. It is well known that NLRP1 and NLRP3 inflammasomes mediate the production of various cytokines in inflammatory disorders; however, it is still unknown whether NLRP1 and NLRP3 inflammasomes can influence the LPS‑induced pyroptosis in the progression of knee osteoarthritis (KOA). In the present study, the correlation between the NLRP inflammasomes and fibroblast‑like synoviocytes (FLSs) pyroptosis was investigated in vivo and in vitro. Human synovial samples were collected from KOA patients and the expression of NLRP1 and NLRP3 inflammasomes was analyzed. Human FLS were isolated in vitro and stimulated with LPS. To determine whether NLRP1 and NLRP3 inflammasomes are involved in FLS pyroptosis, NLRP1 and NLRP3 small interfering RNAs (siRNAs) were used. The results showed that the expression of NLRPs and inflammasome‑related proteins were upregulated and FLS stimulated with LPS+ATP resulted in cell pyroptosis. However, LPS+ATP‑induced pyroptosis was attenuated by NLRP1 and NLRP3 siRNAs. The results of the present study indicate that LPS‑induced FLS pyroptosis may be mediated by either NLRP1 or NLRP3 inflammsomes. Overall, based on the data obtained from patients and in vitro cells, the present finsings showed that NLRP1 and NLRP3 inflammasomes are highly involved in the FLS inflammation and pyroptosis. Furthermore, inhibition of NLRP1 and NLRP3 led to a remarkable reduction of pyroptosis‑related cytokines. Thus, NLRP1 and NLRP3 inflammasomes may be important in the pathogenesis of OA and may represent a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey-pig interspecies somatic cell nuclear transfer (iSCNT) embryos. Results: Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p < 0.05), but not of Sox2 compared with untreated embryos at the 2-4-cell stage. Expression of the anti-apoptotic gene, Bcl2, and the pro-apoptotic gene Bax was also affected at the 2-4-cell stage. RepSox treatment also increased the immunostaining intensity of Oct4 at the blastocyst stage (p < 0.05). Although the blastocyst developmental rate was higher in the group treated with 25 µM RepSox for 24 h than in the untreated control group (2.4 vs. 1.2%, p > 0.05), this was not significant. Conclusion: RepSox can improve the developmental potential of rhesus monkey-pig iSCNT embryos by regulating the expression of pluripotency-related genes. [ABSTRACT FROM AUTHOR]