Potential neuroprotective role of astroglial exosomes against smoking-induced oxidative stress and HIV-1 replication in the central nervous system

Introduction: HIV-1-infected smokers are at risk of oxidative damage to neuronal cells in the central nervous system by both HIV-1 and cigarette smoke. Since neurons have a weak antioxidant defense system, they mostly depend on glial cells, particularly astrocytes, for protection against oxidative damage and neurotoxicity. Astrocytes augment the neuronal antioxidant system by supplying cysteine-containing products for glutathione synthesis, antioxidant enzymes such as SOD and catalase, glucose for antioxidant regeneration via the pentose-phosphate pathway, and by recycling of ascorbic acid.

Areas covered: The transport of antioxidants and energy substrates from astrocytes to neurons could possibly occur via extracellular nanovesicles called exosomes. This review highlights the neuroprotective potential of exosomes derived from astrocytes against smoking-induced oxidative stress, HIV-1 replication, and subsequent neurotoxicity observed in HIV-1-positive smokers.

Expert opinion: During stress conditions, the antioxidants released from astrocytes either via extracellular fluid or exosomes to neurons may not be sufficient to provide neuroprotection. Therefore, we put forward a novel strategy to combat oxidative stress in the central nervous system, using synthetically developed exosomes loaded with antioxidants such as glutathione and the anti-aging protein Klotho.     

Four-rooted maxillary first molar having C-shaped palatal root canal morphology evaluated using cone-beam computerized tomography: a case report

The aim of this article was to present an endodontically managed maxillary first molar with unusual C-shaped palatal root morphology confirmed by cone-beam computerized tomography (CBCT) images. CBCT axial images showed the presence of C-shaped palatal root canal anatomy with a palatal root bifurcation at the apical third. The evaluation of CBCT images can result in better understanding of root canal anatomy, which enables the clinician to investigate the root canal system and to clean, shape, and obturate it more effectively.     

Augmented visual feedback-aided interventions for motor rehabilitation in Parkinson’s disease: a systematic review

Purpose: A systematic review was performed to (1) evaluate the effectiveness of augmented visual feedback-based treatments for motor rehabilitation in Parkinson’s disease, and (2) examine treatment design factors associated with enhanced outcomes following these treatments.

Methods: Eight databases were searched from their start-date up to January 2017 using the key terms Parkinson’s Disease and augmented visual feedback. Two independent raters screened the abstracts and full articles for inclusion. Relevant data were extracted and summarized, and methodological quality of accepted articles was assessed.

Results: Eight single-group studies and 10 randomized control trials were included in the review. Augmented visual feedback-based treatments resulted in improved outcomes with small to large effect sizes post-treatment for the majority of impairment, activity, participation, and global motor function measures, and these improvements were often superior to traditional rehabilitation/education programs. Enhanced treatment outcomes were observed in studies that provided large amounts and high intensities of treatment; gamified feedback; and provided knowledge of performance feedback in real-time on 100% of practice trials.

Conclusion: Augmented visual feedback appears to be a useful motor rehabilitation tool in Parkinson’s disease; however, high-quality, rigorous studies remain limited. Future studies should consider factors that enhance rehabilitation outcomes when designing augmented visual feedback-based interventions.

• Implications for rehabilitation

• Augmented visual feedback is a useful tool for motor rehabilitation in Parkinson’s disease; augmented visual feedback-based treatments are often superior to traditional programs.

• These treatments are associated with improved outcomes in impairment, activity, participation, and global motor function domains.

• Rehabilitation professionals can optimize their use of augmented visual feedback-based treatments by providing large amounts and a high intensity of treatment, gamifying feedback, and providing knowledge of performance feedback in real-time and at a high frequency.

     

Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA

Hyperhomocysteinemia is an emerging risk factor for cardiovascular disease and stroke. The mechanisms underlying the pathophysiology of hyperhomocysteinemia are not completely defined, but endothelial dysfunction resulting from impaired bioavailability of nitric oxide is a consistent finding in experimental models. One potential mechanism for decreased nitric oxide bioavailability is inhibition of endothelial nitric oxide synthase by its endogenous inhibitor, asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA have been found in association with hyperhomocysteinemia and endothelial dysfunction in both animals and humans. Additional studies are required to determine the mechanisms by which ADMA accumulates in hyperhomocysteinemia and to define the importance of ADMA in the endothelial dysfunction of hyperhomocysteinemia in vivo.     

Safranal of Crocus sativus L. Inhibits Inducible Nitric Oxide Synthase and Attenuates Asthma in a Mouse Model of Asthma

The present study involves evaluation of antioxidant potential of Crocus sativus and its main constituents, safranal (SFN) and crocin (CRO), in bronchial epithelial cells, followed antiinflammatory potential of the active constituent safranal, in a murine model of asthma. To investigate the antioxidizing potential of Crocus sativus and its main constituents in bronchial epithelial cells, the stress was induced in these cells by a combination of different cytokines that resulted in an increase in nitric oxide production (NO), induced nitric oxide synthase (iNOS) levels, peroxynitrite ion generation, and cytochrome c release. Treatment with saffron and its constituents safranal and crocin resulted in a decrease of NO, iNOS levels, peroxynitrite ion generation, and prevented cytochrome c release. However, safranal significantly reduced oxidative stress in bronchial epithelial cells via iNOS reduction besides preventing apoptosis in these cells. In the murine model of asthma study, antiinflammatory role of safranal was characterized by increased airway hyper‐responsiveness, airway cellular infiltration, and epithelial cell injury. Safranal pretreatment to these allergically inflamed mice lead to a significant decrease in airway hyper‐responsiveness and airway cellular infiltration to the lungs. It also reduced iNOS production, bronchial epithelial cell apoptosis, and Th2 type cytokine production in the lungs. Copyright © 2015 John Wiley & Sons, Ltd.     

Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction

Levels of reactive oxygen species, including hydrogen peroxide(,) increase in blood vessels during hypertension and in response to angiotensin II (Ang II). Although glutathione peroxidases are known to metabolize hydrogen peroxide, the role of glutathione peroxidase during hypertension is poorly defined. We tested the hypothesis that glutathione peroxidase-1 protects against Ang II-induced endothelial dysfunction. Responses of carotid arteries from Gpx1-deficient (Gpx1(+/-) and Gpx1(-/-)) and Gpx1 transgenic mice, and their respective littermate controls, were examined in vitro after overnight incubation with either vehicle or Ang II. Under control conditions, relaxation to acetylcholine (ACh; an endothelium-dependent agonist) was similar in control, Gpx1(+/-), and Gpx1 transgenic mice, whereas in Gpx1(-/-) mice, responses to ACh were impaired. In control mice, ACh-induced vasorelaxation was not affected by 1 nmol/L of Ang II. In contrast, relaxation to ACh in arteries from Gpx1(+/-) mice was inhibited by approximately 60% after treatment with 1 nmol/L of Ang II, indicating that Gpx1 haploinsufficiency markedly enhances Ang II-induced endothelial dysfunction. A higher concentration of Ang II (10 nmol/L) selectively impaired relaxation to ACh in arteries from control mice, and this effect was prevented in arteries from Gpx1 transgenic mice or in arteries from control mice treated with polyethylene glycol-catalase (which degrades hydrogen peroxide). Thus, genetic and pharmacological evidence suggests a major role for glutathione peroxidase-1 and hydrogen peroxide in Ang II-induced effects on vascular function.