Abdelrahman Ibrahim Abushouk

An updated review of Zika virus

The current outbreak of Zika virus (ZIKV) in South America is one of the most serious public health emergencies since the Ebola outbreak of West Africa [2014]. ZIKV belongs to the flaviviridae family and has two lineages (Asian and African). The virus was first discovered in Uganda [1947] and the first human infection was identified in Nigeria [1952]. The current epidemic is the third of its type after that of Yap Island, Micronesia [2007] and French Polynesia [2013]. Phylogenetic studies revealed that the current strain shares about 99.7% of nucleotides and 99.9% of amino acids with the strain of French Polynesia epidemic [2013], suggesting that it has spread across the Pacific Ocean to invade South America. Aedes Aegypti mosquito is the main vector for ZIKV and there are some reports describing possible sexual and maternal to fetal transmission. ZIKV infection is known to be self-limited. However, recent reports suggested that it can be associated with neurological manifestations as Guillan-Barrè Syndrome and microcephaly in the newborn population. Currently, vector control seems to be the most effective available preventive measure against ZIKV spread. The development of broad spectrum antivirals and ZIKV vaccines should be a priority of future research.

Malignant transformation of oral lichen planus and oral lichenoid lesions: A meta-analysis of 20095 patient data.

OBJECTIVES For over a century, a heated debate existed over the possibility of malignant transformation of oral lichen planus (OLP). We performed this meta-analysis to evaluate the malignant potential of OLP and oral lichenoid lesions (OLL) and investigate the possible risk factors for OLP malignant transformation into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS We searched Medline, Scopus, and Web of Knowledge for relevant observational studies. Data on OLP malignant transformation were calculated as a pooled proportion (PP), using the Der-Simonian Liard method. We performed subgroup analyses by OLP diagnostic criteria, site, and clinical type, using Open Meta[Analyst] software. Data on possible risk factors for malignant transformation were pooled as odds ratios (ORs), using Comprehensive Meta-Analysis software. RESULTS Pooling data for OLP malignant transformation from 57 studies (19,676 patients) resulted in an overall PP of 1.1% [95% CI: 0.9%, 1.4%], while pooling data from 14 recent studies that used the World Health Organization-2003 diagnostic criteria resulted in an overall-PP of 0.9% [95% CI: 0.5%, 1.3%]. The risk of malignant transformation was higher (PP=2.5%, 95% CI [1%, 4%]) in OLL patients (419 patients). A significant increase of malignant transformation risk was noted among smokers (OR=2, 95% CI [1.25, 3.22]), alcoholics (OR=3.52, 95% CI [1.54, 8.03]), and HCV-infected patients (OR=5, 95% CI [1.56, 16.07]), compared to patients without these risk factors. CONCLUSION A small subset of OLP patients (1.1%) develop OSCC; therefore, regular follow-up for these patients is recommended. A higher incidence of malignant transformation was found among smokers, alcoholics, and HCV-infected patients; however, these associations should be further investigated.

Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity

Doxorubicin (DOX) is an anthracycline antibiotic, which is effectively used in the treatment of different malignancies, such as leukemias and lymphomas. Its most serious side effect is dose-dependent cardiotoxicity, which occurs through inducing oxidative stress apoptosis. Due to the myelosuppressive effect of dexrazoxane, a commonly-used drug to alleviate DOX-induced cardiotoxicity, researchers investigated the potential of phytochemicals for prophylaxis and treatment of this condition. Phytochemicals are plant chemicals that have protective or disease preventive properties. Preclinical trials have shown antioxidant properties for several plant extracts, such as those of Aerva lanata, Aronia melanocarpa, Astragalus polysaccharide, and Bombyx mori plants. Other plant extracts showed an ability to inhibit apoptosis, such as those of Astragalus polysaccharide, Azadirachta indica, Bombyx mori, and Allium stavium plants. Unlike synthetic agents, phytochemicals do not impair the clinical activity of DOX and they are particularly safe for long-term use. In this review, we summarized the results of preclinical trials that investigated the cardioprotective effects of phytochemicals against DOX-induced cardiotoxicity. Future human trials are required to translate these cardioprotective mechanisms into practical clinical implications.

Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP) and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM), insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: Future applications in Parkinson’s disease

Parkinsons disease (PD) is the second most common neurodegenerative disease after Alzheimers disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models. Multiple experimental studies showed the ability of several plant extracts to protect against MPTP induced neurotoxicity through activation of catalase, superoxide dismutase, and glutathione reductase enzymes, which reduce the cellular concentration of free radicals, preventing intracellular Ca++ release and subsequent apoptosis signaling. Other neuroprotective mechanisms of plant extracts include promoting autophagy of alpha-synuclein molecules and exerting an antiapoptotic activity via inhibition of proteolytic poly (ADP-ribose) polymerase and preventing caspase cleavage. The variety of neuroprotective mechanisms of natural plant extracts may allow researchers to target PD progression in different pathological stages and may be through multiple pathways. Further investigations are required to translate these neuroprotective mechanisms into safe and effective treatments for PD.

Parkinson’s disease and pesticides: A meta-analysis of disease connection and genetic alterations

Parkinsons disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant heterogeneity among included studies. Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no statistically significant association between exposure to pesticides and alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI [0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91, 2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta-analysis provides evidence that pesticide exposure is significantly associated with the risk of PD and alterations in genes involved in PD pathogenesis. However, the underlying mechanism of this association and the effect of the duration of exposure or the type of pesticides should be addressed by future research.

Curing neurophobia in medical schools: evidence-based strategies

Medical students often perceive neurology as the most difficult medical specialty. This perception is described as ‘neurophobia’ in the medical literature. Several studies have cited poor teaching, complex examination, and separation of basic and clinical sciences as major factors in the development of neurophobia. These negative perceptions can have serious implications, such as decreasing the students’ desire to consider neurology as a future career and increasing referrals from other specialists to avoid dealing with neurological conditions. Faced with increasing demands of healthcare systems and the global burden of neurological conditions, there is a rising need for further research and innovative strategies to improve students’ perceptions of clinical neurology. This review discusses evidence-based recommendations and educational interventions to cure neurophobia in medical education.

Effects of Antioxidant Supplements on the Survival and Differentiation of Stem Cells

Although physiological levels of reactive oxygen species (ROS) are required to maintain the self-renewal capacity of stem cells, elevated ROS levels can induce chromosomal aberrations, mitochondrial DNA damage, and defective stem cell differentiation. Over the past decade, several studies have shown that antioxidants can not only mitigate oxidative stress and improve stem cell survival but also affect the potency and differentiation of these cells. Further beneficial effects of antioxidants include increasing genomic stability, improving the adhesion of stem cells to culture media, and enabling researchers to manipulate stem cell proliferation by using different doses of antioxidants. These findings can have several clinical implications, such as improving neurogenesis in patients with stroke and neurodegenerative diseases, as well as improving the regeneration of infarcted myocardial tissue and the banking of spermatogonial stem cells. This article reviews the cellular and molecular effects of antioxidant supplementation to cultured or transplanted stem cells and draws up recommendations for further research in this area.

Peroxisome proliferator-activated receptors as therapeutic targets for heart failure

Heart failure (HF) is a common clinical syndrome that affects more than 23 million individuals worldwide. Despite the marked advances in its management, the mortality rates in HF patients have remained unacceptably high. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription regulators, involved in the regulation of fatty acid and glucose metabolism. PPAR agonists are currently used for the treatment of type II diabetes mellitus and hyperlipidemia; however, their role as therapeutic agents for HF remains under investigation. Preclinical studies have shown that pharmacological modulation of PPARs can upregulate the expression of fatty acid oxidation genes in cardiomyocytes. Moreover, PPAR agonists were proven able to improve ventricular contractility and reduce cardiac remodelling in animal models through their anti-inflammatory, anti-oxidant, anti-fibrotic, and anti-apoptotic activities. Whether these effects can be replicated in humans is yet to be proven. This article reviews the interactions of PPARs with the pathophysiological mechanisms of HF and how the pharmacological modulation of these receptors can be of benefit for HF patients.

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases.