Liver fibrosis improvement in chronic hepatitis C after direct acting-antivirals is accompanied by reduced profibrogenic biomarkers-a role for MMP-9/TIMP-1.

BACKGROUND AND AIMS: Disturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy. METHODS: Clinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays. RESULTS: Cohort included 33 patients (59.5 ±â€¯9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ±â€¯15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators. CONCLUSION: Our data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.

Omentum acts as a regulatory organ controlling skeletal muscle repair of mdx mice diaphragm.

Duchenne muscular dystrophy is a lethal X-linked muscle wasting disease due to mutations of the dystrophin gene leading to distinct susceptibility to degeneration and fibrosis among skeletal muscles. This study aims at verifying whether intense mdx diaphragm remodeling could be attributed to influences from the omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. Mdx omentum produces growth factors HGF and FGF and increased amounts of VEGF with pleiotropic actions upon muscular progenitors and myoblast differentiation. Histology revealed that the absence of the omentum reduced inflammation and collagen deposition in the diaphragm. The diaphragm from omentectomized mdx mice presents impaired repair with a predominance of collagen type I deposition, decreased muscle regeneration and a reduction in collagen type IV and indication of altered basal lamina integrity in the diaphragm. Omentectomy further reduced inflammatory infiltration and NFκ-B activation but a change in the pattern of muscle inflammation with low numbers of the F4/80+CD206+ M-2 macrophage subset. Although omentectomized mice had high levels of Pax7, myogenin and TNF-α, the percentage of myofibers undergoing regeneration was low thus suggesting that a lack of the omentum halts the muscle differentiation program. Such results support that omentum exerts a regulatory function inducing an inflammatory process that favors regeneration and inhibits fibrosis selectively in the diaphragm muscle thus being a potential site for therapeutic interventions in DMD.

Perillyl alcohol, a pleiotropic natural compound suitable for brain tumor therapy, targets free radicals.

Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis. When cells are subjected to oxidative stress conditions, there is an accumulation of ROS that can lead to irreversible cell injury caused primarily by lipid peroxidation, protein aggregation and/or DNA damage. Malignant tumors, such as glioblastoma multiforme, display elevated rates of oxygen consumption, necrosis and abnormal structural microvasculature. Alterations in the tumor microenvironment are tightly linked to tumor progression and occur as a result of activation of complex signaling networks involving inter-clonal cooperation, cell-matrix interactions and an ongoing inflammatory response leading to genetic and epigenetic alterations. This review will focus on the pro- and anti-oxidant activities of POH, which are greatly dependent on the respective ROS levels within the tumor microenvironment and involve the ER stress response system. As well, some critical aspects of tumor-associated metabolic changes and the consequences of endogenous ROS production for tumor progression will be discussed.

Influence of Endodontic Treatment and Coronal Restoration on Status of Periapical Tissues: A Cone-beam Computed Tomographic Study.

INTRODUCTION: This cross-sectional study determined the prevalence of apical radiolucency in 1290 root canal-treated teeth and the correlation between endodontic treatment quality and the presence of coronal restorations with apical radiolucency using cone-beam computed tomographic imaging. METHODS: Cone-beam computed tomographic scans were analyzed, and teeth were classified as healthy or diseased according to the periapical status. Other factors were also evaluated for their association with the apical diagnosis including sex, quality of endodontic treatment, presence of coronal restorations and posts, and apical level of filling. RESULTS: Of the treated teeth, 48.83% were classified as healthy. Only 55.11% of the teeth had endodontic treatment rated as adequate. The quality of endodontic treatment and the presence of coronal restoration were statistically correlated with the presence or absence of an apical radiolucency (P < .0001). Combined data revealed that teeth with both adequate endodontic treatment and the presence of coronal restoration showed significantly better apical status than the other combinations (P < .001). Canals filled up to 0-2 mm short of the apex had a significantly higher number of teeth rated as healthy compared with overfilled or underfilled cases (P = .001). The presence of a post was not found to be a statistical significant factor (P = .81). CONCLUSIONS: Data showed a relatively high prevalence of apical radiolucencies in root canal-treated teeth. The quality of the endodontic treatment, the presence of coronal restoration, and apical extent of the root canal filling were significantly associated with healthy apical tissues.

Nuts and legume seeds for cardiovascular risk reduction: scientific evidence and mechanisms of action.

Consumption of tree nuts and legume seeds is associated with a reduction in cardiovascular risk. The reduction in blood lipids and in inflammatory and oxidative processes exhibited by bioactive compounds such as monounsaturated and polyunsaturated fatty acids, fibers, phenolic compounds, tocopherols, phospholipids, carotenoids, some minerals, and arginine, has stimulated research on the mechanisms of action of these substances through distinct experimental approaches. It is, therefore, important to know the metabolic effect of each nut and legume seed or the mixture of them to choose the most suitable nutritional interventions in clinical practice. The aim of this narrative bibliographic review was to investigate the effects of tree nuts and legume seeds on biomarkers of cardiovascular risk, as well as their mechanisms of action with regard to lipid profiles, insulin resistance, arterial pressure, oxidative stress, and inflammation. The findings indicate that a mixture of nuts and legume seeds optimizes the protective effect against cardiovascular risk.

Resection of the epileptogenic lesion abolishes seizures and reduces inflammatory cytokines of patients with temporal lobe epilepsy.

Persistent neuroinflammation is implicated in the pathogenesis of seizures and neuronal degeneration of temporal lobe epilepsy (TLE). Circulating level of inflammatory cytokines was determined during inter-ictal period of 25 non-operated and 10 patients (OP) submitted to anterior temporal lobectomy. OP patients showed marked reduction of IL-1ß, TNFα, MIP-1α, but not IL-6 and TGF-ß1. Paired analysis done before and after lobectomy showed reduction of inflammatory cytokines but increased TGF-ß1 levels, and lack of seizures for more than 6 months. Maintenance of high TGF-ß1 and IL-6 cytokines in both groups suggests a role in down-regulation of neuroinflammation and promotion of brain tissue remodeling for neuronal reorganization.