Network pharmacology and bioinformatics analysis identify potential therapeutic effects of berberine on colon cancer complicated with radiation enteritis

Objective:Patients with colon adenocarcinoma(COAD)who undergo radiation therapy develop radiation enteritis(RE).The predictive value of RE in COAD is yet to be established.Berberine,an active compound derived from the traditional Chinese medicinal plant,Coptis chinensis,has notable anti-inflammatory properties and offers protection to the intestinal mucosa.This study aimed to evaluate the possible therapeutic effect and mechanism of berberine as a treatment for COAD complicated with RE(COAD&RE).Methods:Relevant genetic features of diverse COAD&RE populations were analyzed using bioinformatics and the Cox proportional hazards regression model.The therapeutic targets of berberine were predicted using network pharmacology and molecular docking.In vivo and in vitro experiments were conducted to validate the core genes identified using molecular docking.Results:RE has a certain impact on the prognosis of COAD and berberine may play an important role in the treatment of COAD&RE.In addition,we identified five core therapeutic targets of berberine by network pharmacology and molecular docking:CCND1,MYC,AR,LEP,and CYP19A1.In vivo experiments showed that berberine increased short-term survival rate,body weight,and intestinal epithelial cell recovery in mice after radiation.In an in vitro study,berberine promoted the proliferation of human intestinal epithelial cells and enhanced the radiosensitivity of HT29 cells after radiation,and the relative mRNA expression levels of CCND1 and MYC closely correlated with these effects.Conclusions:This study predicted the potential therapeutic effects of berberine on COAD&RE and verified the relevant mechanisms,which may provide insights and suggestions for the clinical treatment of COAD&RE.

Curcumin modulates oxidative stress to inhibit pyroptosis and improve the inflammatory microenvironment to treat endometriosis

Endometriosis(EM)is a common disease that affects approximately 10%-15%of women of childbearing age.The pathogenesis of EM is unclear,but studies have shown a strong association between EM and inflammation,as well as oxidative stress.^(1) Pyroptosis is also called inflammatory cell death.When pyroptosis occurs,it activates a strong inflammatory response.Pyroptosis is associated with oxidative stress,and Ros act as intermediate triggers to activate pyroptosi.

Calcium silicate bioactive ceramics induce osteogenesis through oncostatin M

Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation.Macrophages,the most vital factor in the immune response affecting implants,are critical in bone formation,as well as bone biomaterial-mediated bone repair.Therefore,it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization.Our previous study showed that calcium silicate(CS)bioceramics could significantly promote osteogenesis.Herein,we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis.Under CS extract stimulation,the macrophage phenotype was converted to the M2 extreme.Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs),indicating the important role of macrophage polarization in biomaterial-induced osteogenesis.Mechanistically,oncostatin M(OSM)in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways.This in vivo study further demonstrated that CS bioceramics could stimulate osteogenesis better thanβ-TCP implants by accelerating new bone formation at defective sites in the femur.These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the in vitro osteogenesis capability of bone substitute materials.