Resveratrol Inhibition of the WNT/β-Catenin Pathway following Discogenic Low Back Pain

Low back pain (LBP) management is an important clinical issue. Inadequate LBP control has consequences on the mental and physical health of patients. Thus, acquiring new information on LBP mechanism would increase the available therapeutic tools. Resveratrol is a natural compound with many beneficial effects. In this study, we investigated the role of resveratrol on behavioral changes, inflammation and oxidative stress induced by LBP. Ten microliters of Complete Freund’s adjuvant (CFA) was injected in the lumbar intervertebral disk of Sprague Dawley rats to induce degeneration, and resveratrol was administered daily. Behavioral analyses were performed on day zero, three, five and seven, and the animals were sacrificed to evaluate the molecular pathways involved. Resveratrol administration alleviated hyperalgesia, motor disfunction and allodynia. Resveratrol administration significantly reduced the loss of notochordal cells and degenerative changes in the intervertebral disk. From the molecular point of view, resveratrol reduced the 5th/6th lumbar (L5–6) spinal activation of the WNT pathway, reducing the expression of WNT3a and cysteine-rich domain frizzled (FZ)8 and the accumulation of cytosolic and nuclear β-catenin. Moreover, resveratrol reduced the levels of TNF-α and IL-18 that are target genes strictly downstream of the WNT/β-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NFkB pathway, the expression of iNOS and COX-2, and the levels of PGE2 in the lumbar spinal cord. Moreover, resveratrol reduced the oxidative stress associated with inflammation and pain, as shown by the observed reduced lipid peroxidation and increased GSH, SOD, and CAT activities. Therefore, resveratrol administration controlled the WNT/β-catenin pathway and the related inflammatory and oxidative alterations, thus alleviating the behavioral changes induced by LBP.     

S-Acetyl-Glutathione Attenuates Carbon Tetrachloride-Induced Liver Injury by Modulating Oxidative Imbalance and Inflammation

Liver fibrosis, depending on the stage of the disease, could lead to organ dysfunction and cirrhosis, and no effective treatment is actually available. Emergent proof supports a link between oxidative stress, liver fibrogenesis and mitochondrial dysfunction as molecular bases of the pathology. A valid approach to protect against the disease would be to replenish the endogenous antioxidants; thus, we investigated the protective mechanisms of the S-acetyl-glutathione (SAG), a glutathione (GSH) prodrug. Preliminary in vitro analyses were conducted on primary hepatic cells. SAG pre-treatment significantly protected against cytotoxicity induced by CCl4. Additionally, CCl4 induced a marked increase in AST and ALT levels, whereas SAG significantly reduced these levels, reaching values found in the control group. For the in vivo analyses, mice were administered twice a week with eight consecutive intraperitoneal injections of 1 mL/kg CCl4 (diluted at 1:10 in olive oil) to induce oxidative imbalance and liver inflammation. SAG (30 mg/kg) was administered orally for 8 weeks. SAG significantly restored SOD activity, GSH levels and GPx activity, while it strongly reduced GSSG levels, lipid peroxidation and H₂O₂ and ROS levels in the liver. Additionally, CCl4 induced a decrease in anti-oxidants, including Nrf2, HO-1 and NQO-1, which were restored by treatment with SAG. The increased oxidative stress characteristic on liver disfunction causes the impairment of mitophagy and accumulation of dysfunctional and damaged mitochondria. Our results showed the protective effect of SAG administration in restoring mitophagy, as shown by the increased PINK1 and Parkin expressions in livers exposed to CCl4 intoxication. Thus, the SAG administration showed anti-inflammatory effects decreasing pro-inflammatory cytokines TNF-α, IL-6, MCP-1 and IL-1β in both serum and liver, and suppressing the TLR4/NFkB pathway. SAG attenuated reduced fibrosis, collagen deposition, hepatocellular damage and organ dysfunction. In conclusion, our results suggest that SAG administration protects the liver from CCl4 intoxication by restoring the oxidative balance, ameliorating the impairment of mitophagy and leading to reduced inflammation.     

Spectroscopic and structural characterisation of a VOx (x≈1) ultrathin epitaxial film on Pt (111)

VO_x ultrathin epitaxial films (0.8≤x≤1.3), grown on Pt(111) by evaporating vanadium in a controlled water background (1×10⁻⁷ Pa), have been chemically characterised by X-ray photoelectron spectroscopy (XPS) and X-ray-excited Auger electron spectroscopy (AES), which confirm the presence of V(II). The VO film shows a NaCl-type structure exposing the (111) plane, as proven by XPD. Multiple scattering calculations are compatible with an O-terminated surface and a surface relaxation of the outermost atomic layers, which leads to a V---O bond length contraction amounting to 7%.     

Comparison of immediate-onset and delayed-onset posttraumatic stress disorder in military veterans.

Differences in symptoms, trauma exposure, dissociative and emotional reactions to trauma, and subsequent life stress in war veterans reporting immediate-onset or delayed-onset posttraumatic stress disorder (PTSD) or no PTSD were investigated. The role of life stress in delayed-onset PTSD was also studied. Retrospective interviews were conducted with 142 United Kingdom veterans receiving a war pension for PTSD or physical disability. Immediate-onset and delayed-onset PTSD were similar in the number and type of symptoms reported at onset, but the delayed-onset group differed in showing a gradual accumulation of symptoms that began earlier and continued throughout their military career. They were more likely to report major depressive disorder and alcohol abuse prior to PTSD onset. Both groups described similar amounts of trauma exposure, but those in the delayed-onset group reported significantly less peritraumatic dissociation, anger, and shame. Veterans with delayed onsets were more likely than veterans with no PTSD to report the presence of a severe life stressor in the year before onset. In conclusion, the results suggest that delayed onsets involve a more general stress sensitivity and a progressive failure to adapt to continued stress exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autophagy and Mitophagy Promotion in a Rat Model of Endometriosis

Endometriosis is a gynecological condition affecting patients in reproductive age. The aim of this paper was to assess the effects of the autophagy and mitophagy induction in a rat model of endometriosis. Endometriosis was induced by the injection of uterine fragments, and rapamycin (0. 5 mg/kg) was administered once per week. One week from the induction, rats were sacrificed, and laparotomy was performed to collect the endometriotic implants and to further process them for molecular analysis. Western blot analysis was conducted on explanted lesions to evaluate the autophagy pathway during the pathology. Elevated phospho-serine/threonine kinase (p-AKT) and mammalian target of rapamycin (mTOR) expressions were detected in vehicle-treated rats, while Beclin and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) expressions were low. Additionally, samples collected from vehicle groups indicated low Bnip3, Ambra1, and Parkin expressions, demonstrating impaired autophagy and mitophagy. Rapamycin administration reduced p-AKT and mTOR expressions and increased Beclin and LC3II, Bnip3, Ambra1, and Parkin expressions, activating both mechanisms. We also evaluated the impact of the impaired autophagy and mitophagy pathways on apoptosis and angiogenesis. Rapamycin was administered by activating autophagy and mitophagy, which increased apoptosis (assessed by Western blot analysis of Bcl-2, Bax, and Cleaved-caspase 3) and reduced angiogenesis (assessed by immunohistochemical analysis of vascular endothelial grow factor (VEGF) and CD34) in the lesions. All of these mechanisms activated by the induction of the autophagy and mitophagy pathways led to the reduction in the lesions’ volume, area and diameter.     

Stress‐Enhanced Swelling of Silica: Effect on Strength

From the work of Le Chatelier [1884], it is well known that chemical reactions that exhibit a change in volume are sensitive to the ambient pressure of the reaction. Increasing the pressure will alter the ratio of reaction products to reactants. If the change in volume is constrained to occur at a surface, then such reactions can result in residual stresses that affect the strength of the solid. These effects are applicable to silica glass, which increases in volume when reacting with water. In this paper, we discuss the possibility of using this effect to strengthen silica glass. Using a modification of Le Chatelier's theory to handle applied stresses, we show that water penetration into the surface of silica glass can yield sufficient residual stress to increase the strength of silica glass into the GPa range. Applying these ideas to recent data published by Lezzi et al., we are able to attribute the strengthening they observe to a water/silica reaction under an applied tensile stress.     

The effect of lighting changes on simultaneous colour contrast: a new aspect of colour rendition

Among the many metrics used to compute the colour rendition of a light source which have been investigated in recent years, most consider only the spectral power distribution of the light source being tested. To highlight aspects not usually considered in the development of colour rendition metrics, and to propose future directions for alternative approaches consistent with human visual perception, an experiment was conducted to examine colour appearance variations on certain spatial visual content configurations, in other words the effects of illusions under different light sources. Results indicate that stronger simultaneous contrast configurations have a more unpredictable variation in appearance. Therefore, it is proposed that colour spatial distribution should be considered for the future generation of rendering metrics.     

Caulerpin Mitigates Helicobacter pylori-Induced Inflammation via Formyl Peptide Receptors

The identification of novel strategies to control Helicobacter pylori (Hp)-associated chronic inflammation is, at present, a considerable challenge. Here, we attempt to combat this issue by modulating the innate immune response, targeting formyl peptide receptors (FPRs), G-protein coupled receptors that play key roles in both the regulation and the resolution of the innate inflammatory response. Specifically, we investigated, in vitro, whether Caulerpin—a bis-indole alkaloid isolated from algae of the genus Caulerpa—could act as a molecular antagonist scaffold of FPRs. We showed that Caulerpin significantly reduces the immune response against Hp culture filtrate, by reverting the FPR2-related signaling cascade and thus counteracting the inflammatory reaction triggered by Hp peptide Hp(2–20). Our study suggests Caulerpin to be a promising therapeutic or adjuvant agent for the attenuation of inflammation triggered by Hp infection, as well as its related adverse clinical outcomes.