Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis.

Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.

In-Vitro Anticancer and Antioxidant Activities of Eremina desertorum (Forsskal, 1775) Snail Mucin.

OBJECTIVES: The aim of the present research is to elucidate the anti-oxidant and anti-tumor activities of the mucin extracted from Ereminia desertorum snails´ mucus against two types of tumor cell lines; human colon adenocarcinoma (CACO-2) cells and human hepatoma (HepG-2) cells. METHODS: Both cell lines were treated with Ereminia desertorum snails´ mucin and the oxidative markers were measured in culture media and cells by biochemical and gene expression analysis using RT-PCR. The tumor suppressor gene expression was also evaluated using RT-PCR. RESULTS: The culture media of HepG-2 or CACO-2 cells treated with the extract have high significant increased levels of catalase, SOD, GSH and total antioxidants. Apart from SOD in CACO-2 cells that didn't differ from untreated cells. Also, Gene expression levels (2^-ddct) of the antioxidant markers in HepG-2 cells; GSTA-1, catalase, SOD, and GPx increased in mucin- treated cells. Also, these antioxidant genetic markers were up-regulated in CACO-2 cells by treatment with mucin extract. Gene expression levels (2^-ddct) of tumor suppression genes (p53, Rb, APC, and PTEN) in both HepG-2 and CaCO-2 cells were increased in mucin extract-treated cells. CONCLUSION: The present study highlighted the anti-oxidant and the anti-cancer activities of the mucin extracted from E. desertorum snails´ mucus that could attract attention to such natural product as a possible source of therapeutic compounds against liver and colon cancers.

Taurine Upregulates miRNA-122-5p Expression and Suppresses the Metabolizing Enzymes of Glycolytic Pathway in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a complicated disease with a poor prognosis and high mortality rates. The prevention, control, diagnosis, and treatment of liver cancer have become vital focuses in healthcare research. AIM: This study aimed to evaluate the in vitro effect of taurine (Tau) on the expression of miR-122-5p that targets some limiting glycolytic enzymes and affects the overall glycolytic pathway in HepG2 cells. METHOD: IC50 and the inhibitory effect of Tau on cell proliferation were measured after 48 h by MTT assay. Then, the mRNA expressions of some apoptosis-related genes P53, BAX, Caspase-3, and Bcl-2 were measured using quantitative real-time (qRT-PCR) and the protein levels were confirmed by enzyme-linked immunosorbent assay (ELISA). The activities of some antioxidant's biomarkers were assessed. The gene expression of miR-122-5p that targets some limiting glycolytic enzymes; Aldolase and Lactate dehydrogenase (LDH), were evaluated after treatment with Tau for 48 h. RESULTS: A Significant inhibition in the proliferation of HepG2 was encountered after treatment with Tau in a dose-dependent manner. Moreover, the expression of apoptotic genes p53, Bax, and Caspase-3 exhibited a significant upregulation, while Bcl-2 showed a significant downregulation. These alterations in the expression levels were also confirmed on the protein level. The antioxidant activities of GPx, CAT, and NO were significantly elevated versus untreated control. Also, a significant increase in the expression level of miR-122-5p was observed after treatment with Tau affecting the metabolic activity of HCC cells. Concomitantly, a significant inhibition in ALDOA protein and the hallmark of glycolytic enzymes LDH and Aldolase were observed. CONCLUSIONS: These observations showed that taurine inhibits HepG2 cell proliferation and restores the expression of miR-122-5p which inhibits the hallmark glycolytic enzymes and ultimately the metabolic activity of HCC cells. Tau is assumed to be a promising and effective antitumor therapy of HCC.