Helicobacter pylori-Toxoplasma gondii interplay with a possible role of IL-10.

Parasites are known for their modulatory effects on the immune response. The impact of toxoplasmosis on the immune response towards H. pylori is being studied in terms of IL-10 levels. This study included 110 patients suffering from persistent dyspepsia and 50 apparently healthy controls. Stool samples were collected and tested for H. pylori using colloidal gold one step test. Sera were examined for anti-Toxoplasma IgM and IgG using ELISA. IL-10 was also tested in the sera using ELISA. We found that Toxoplasma IgM and IgG tested positive in 1.8 % and 40 % of H. pylori positive patients, respectively. H. pylori-infected patients displayed higher IL-10 levels than the healthy controls (84 versus 0.59 pg/ml, respectively, P < 0.001). Classification of H. pylori positive patients according to Toxoplasma IgG titers yielded three groups: negative (58, 52.7 %), equivocal (8, 7.3 %), and positive (44, 40 %) groups, with the highest IL-10 levels detected in the double positive than the negative and the equivocal group (215 pg/ml versus 43 and 112.5 pg/ml, respectively, P < 0.001). There was strong positive correlation between Toxoplasma IgG titers and IL-10 levels (rs = 0.82, P < 0.001). Toxoplasma enhances IL-10 production in response to H. pylori infection. This could ameliorate the inflammatory response in the gastric mucosa, and subsequently more colonization with the H. pylori is achieved, resulting in persistent infection.

Innovative challenge for the inhibition of hepatocellular carcinoma progression by combined targeting of HSP90 and STAT3/HIF-1α signaling.

Hepatocellular carcinoma (HCC) is the third foremost cause of cancer-related deaths. HCC has a very bad prognosis because it is asymptomatic in the early stages, resulting in a late diagnosis, and it is highly resistant to conventional chemotherapy. Such chemotherapies have been proven disappointing because they provide extremely low survival benefits. This study discloses that the STAT3/HIF-1α is an auspicious therapeutic attack site for conceivable repression of HCC development. A site that can be targeted by simultaneous administration of a STAT3 inhibitor in the context of HSP90 inhibition. 17-DMAG binds to HSP90 and constrains its function, resulting in the degradation of HSP90 client proteins HIF-1α and STAT3. Hypoxia recruits STAT3/HIF-1α complex within the VEGF promoter. Additionally, it was acknowledged that STAT3 is an essential mediator of VEGF transcription by direct binding to its promoter. Furthermore, it induces HIF-1α stability and enhances its transcriptional activity. Herein, we revealed that the combination therapy using 17-DMAG and nifuroxazide, a STAT3 inhibitor, repressed the diethylnitrosamine-induced alterations in the structure of the liver. This effect was mediated via decreasing the levels of the HSP90 client proteins HIF-1α and pSTAT3 resulting in the suppression of the STAT3/HIF-1α complex transcriptional activity. To conclude, 17-DMAG/NFXZD combination therapy-induced disruption in the STAT3/HIF-1α loop led to a potential antiangiogenic activity and showed apoptotic potential by inhibiting autophagy and inducing ROS/apoptosis signaling. Additionally, this combination therapy exhibited promising survival prolongation in mice with HCC. Consequently, the use of 17-DMAG/NFXZD renders an inspirational perspective in managing HCC. However, further investigations are compulsory.