The involvement of Nrf2/HO-1/cytoglobin and Ang-II/NF-κB signals in the cardioprotective mechanism of lansoprazole against cisplatin-induced heart injury.

Cardiac toxicity is a serious adverse effect of cisplatin (CIS). Lansoprazole (LPZ) is a proton pump inhibitor with promising cardioprotective effects. Our study planned to examine the cardioprotective effect of LPZ against CIS-induced cardiac injury. To achieve this goal, 32 male rats were randomly allocated into four groups. CIS, 7 mg/kg, was injected i.p. on the fifth day of the experiment. LPZ was administered via oral gavage at a dose of 50 mg/kg. The present study revealed that CIS injection induced a remarkable cardiac injury evidenced by an increase in serum ALP, AST, CK-MB, LDH, and troponin-I levels. The cardiac oxidative damage was also observed after CIS injection and mediated by downregulation of GSH, SOD, GST, Nrf2, HO-1, PPAR-γ, and cytoglobin levels associated with the upregulation of MDA content. Besides, CIS injection caused a significant inflammatory reaction mediated by alteration of cardiac NF-κB, STAT-3, p-STAT-3, and IκB expressions. Additionally, cardiac Ang-II expression was significantly increased in CIS control rats, while Ang 1-7 expression was significantly reduced relative to normal rats. In contrast, LPZ administration remarkably ameliorated these changes in the heart of CIS-intoxicated rats. Collectively, LPZ potently attenuated cardiac toxicity induced by CIS via regulation of Nrf2/HO-1, PPAR-γ, cytoglobin, IκB/NF-κB/STAT-3, and Ang-II/Ang 1-7 signals.

Role of ultrasound biomicroscopy in the planning for secondary implantation of intra ocular lens in aphakia.

Purpose This is a prospective investigational study that was performed at Tanta University Eye Hospital, Tanta, Egypt to evaluate the role of ultrasound biomicroscopy (UBM) in planning secondary implantation of intra ocular lens (IOL) in aphakia. Methods Preoperative UBM was performed for the assessment of anterior segment of 30 aphakic eyes admitted for secondary IOL implantation with special attention to central corneal thickness (CCT), anterior chamber depth (ACD), ciliary sulcus (CS), anatomical changes, and posterior capsular (PC) integrity which had been assessed by measuring the remnants of PC with special attention to the 12, 3, 5, 6, 7, and 9 o'clock meridians. Results This study involved 30 eyes in 27 patients; 16 males and 11 females. The mean age was 8.39 ± 2.36 years. The causes of aphakia were: congenital cataract extraction in14 eyes (46.7 %); trauma in 14 eyes (46.7 %); and after extracapsular cataract extraction in 2 eyes (6.6 %). The mean CCT was 0.61 + 0.35 mm and the mean ACD was 3.03 + 0.41 mm. The ciliary sulcus was patent in 28 eyes (93.4 %). Posterior synechia was observed in 8 eyes (26.7 %), lens remnants in 11 eyes (36.7 %), corneal scars in 11 eyes (36.7 %), and vitreous in anterior chamber in 1 eye (3.3 %). The integrity of PC was illustrated with a diagram. Conclusions UBM is a useful device to evaluate aphakic eyes before secondary IOL implantation through good evaluation of the anterior segment with special attention to the posterior capsular integrity, ciliary sulcus, anterior chamber depth, corneal thickness, and detection of any structural changes in the anterior segment resulting from the remote cause of aphakia.

Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3ß) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.

Parkinson's disease (PD) is a progressive neurodegenerative disease of the brain due to degeneration of dopaminergic neurons in the substantia nigra (SN). Glycogen synthase kinase 3 beta (GSK-3ß) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3ß in PD neuropathology, and how GSK-3ß inhibitors affect PD neuropathology. GSK-3 is a conserved threonine/serine kinase protein that is intricate in the regulation of cellular anabolic and catabolic pathways by modulating glycogen synthase. Over-expression of GSK-3ß is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3ß in PD neuropathology is not fully clarified. Over-expression of GSK-3ß induces the development of PD by triggering mitochondrial dysfunction and oxidative stress in the dopaminergic neurons of the SN. NF-κB and NLRP3 inflammasome are activated in response to dysregulated GSK-3ß in PD leading to progressive neuronal injury. Higher expression of GSK-3ß in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3ß inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.

The therapeutic value of Myrtus communis L.: an updated review.

Myrtus communis L. (Family: Myrtaceae) is naturally found in the western part of Asia, Southern Europe, and North Africa. It has been reportedly applied in pharmaceutical industry, traditional medicine, cosmetics, spices, and food. Pubmed, Google scholar, Web of Science, and Scopus were utilized to seek out relevant content concerning the therapeutic potential of M. communis. Subsequently, we conducted a review to identity noteworthy updates pertaining to M. communis. Myrtle berries, leaves, seeds, and essential oils are natural sources of several nutrients and bioactive compounds with marked health effects. The chemical analysis showed that M. communis contained oils, alkaloids, flavonoids, phenolics, coumarins, saponosides, tannins, quinines, and anthraquinones. A pharmacological investigation revealed that M. communis possessed anti-inflammatory, analgesic, antimicrobial, antiparasitic, antioxidant, antidiabetic, anticancer, antimutagenic, immunomodulatory, dermatological, cardiovascular, central nervous system, and gastrointestinal protective effects, among numerous other biological effects. This current review focused on the biochemical, pharmacological, therapeutic effects, and various biological activities of different parts of M. communis. It signifies that M. communis is a therapeutic plant with numerous applications in medicine and could be used as a drug isolate based on its safety and effectiveness.

Prognostic value of myocardial scar in ischaemic and non-ischaemic cardiomyopathy using cardiac magnetic resonance imaging.

AIM: The aim of this research was to evaluate the prognostic value of myocardial scar using cardiac magnetic resonance (CMR) imaging in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM). METHODS: One hundred and fifty-four patients with either ICM or NICM underwent CMR with late gadolinium enhancement sequences for assessment of left ventricular ejection fraction (LVEF), and detection and quantification of any myocardial scar using three methods: manual, number of segments involved, and percentage of scarred myocardium. Patients were followed up for at least six months for clinical cardiac events. RESULTS: Patients were divided into two groups: group I, patients with ICM (58%) and group II, those with NICM (42%). Clinical presentation ranged from eventless lpar;10%) to chest pain (18%), heart failure (15%), hospitalisation (35%), syncope (1%), ventricular tachycardia (< 1%) and cardiac arrest (< 1%). The scar mass was larger in size in group I (17 ± 15%) than in group II (8 ± 13%). A direct relationship was observed between scar size and event severity (p < 0.001). An inverse relationship between LVEF and event severity was found in group I (p < 0.001) but not in group II (p = 0.128). CONCLUSIONS: Myocardial scar size was a strong predictor of clinical outcome in both the ICM and NICM patients. LVEF was less reliable in predicting morbidity in cardiomyopathy patients.

An electron microscopic and biochemical study of the potential protective effect of ginger against Cadmium-induced testicular pathology in rats.

Background: Cadmium (Cd) is a toxic heavy metal used in many industries. Since the second half of the 20th century, legislation on Cd use was put to limit the exponential rise in its environmental levels. This study aimed to investigate Cd's functional and ultrastructural changes on rats' reproductive systems and the role of Zingiber officinale (Ginger) in protecting against Cd-induced toxicity. Methods: Thirty adult male albino rats were randomly assigned into three equal groups (n = 10); control, Cd-exposed/untreated, and Cd-exposed/Gin-treated. Rat testes were weighed, and testicular tissue sections were examined under the electron microscope. Semen analysis, morphological examination of spermatozoa, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. In addition, testicular tissue homogenates were analyzed for malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) levels. Results: Cd-induced significant reduction in the mean testicular weight and GSH levels and plasma testosterone, LH and FSH levels with a concomitant increase in testicular MDA and NO levels. There was also a deterioration in semen analysis parameters and spermatozoa morphology, with testicular structural damage in the form of architecture distortion and necrosis of seminiferous tubules and testicular interstitial cells. Daily administration of ginger for 4 weeks protected against CD-induced toxicity, preserving tissue architecture, improved plasma levels of testosterone, LH and FSH and testicular levels of GSH, and reduced testicular levels of MDA, NO. Conclusion: Ginger has a protective effect on Cd-induced deterioration of testicular tissue's structural and functional integrity by improving testicular tissue antioxidant capacity and steroid production, which ameliorates sex hormone levels in the blood.

Therapeutic Potential of Mesenchymal Stem Cells versus Omega n - 3 Polyunsaturated Fatty Acids on Gentamicin-Induced Cardiac Degeneration.

This study compared the cardioprotective action of mesenchymal stem cells (MSCs) and PUFAs in a rat model of gentamicin (GM)-induced cardiac degeneration. Male Wistar albino rats were randomized into four groups of eight rats each: group I (control group), group II (gentamicin-treated rats receiving gentamicin intraperitoneally (IP) at dose of 100 mg/kg/day for 10 consecutive days), group III (gentamicin and PUFA group receiving gentamicin IP at dose of 100 mg/kg/day for 10 consecutive days followed by PUFAs at a dose of 100 mg/kg/day for 4 weeks), and group IV (gentamicin and MSC group receiving gentamicin IP at dose of 100 mg/kg/day followed by a single dose of MSCs (1 × 106)/rat IP). Cardiac histopathology was evaluated via light and electron microscopy. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), caspase-3 (apoptosis), Bcl2, and Bax expression was performed. Moreover, cardiac malonaldehyde (MDA) content, catalase activity, and oxidative stress parameters were biochemically evaluated. Light and electron microscopy showed that both MSCs and PUFAs had ameliorative effects. Their actions were mediated by upregulating PCNA expression, downregulating caspase-3 expression, mitigating cardiac MDA content, catalase activity, and oxidative stress parameters. MSCs and PUFAs had ameliorative effects against gentamicin-induced cardiac degeneration, with MSCs showing higher efficacy compared to PUFAs.

CT tractography in anterior abdominal stab wounds: a proposed algorithm.

PURPOSE: This study evaluates the accuracy of IV contrast-enhanced computed tomography (CT) tractography in the detection of peritoneal violation in anterior abdominal stab wounds (AASW) and its impact on the management algorithm. METHODS: This prospective study included 61 patients who presented to Kasr Alainy Hospital with AASW. According to the IV contrast-enhanced CT tractography, they were classified into penetrating, equivocal and non-penetrating injuries. The former two were subjected to diagnostic laparoscopy (DL), while the non-penetrating group was subjected to serial abdominal examination (SAE). The accuracy of CT tractography to detect peritoneal violation was assessed by correlating its findings with management outcome. RESULTS: CT tractography stratified the injuries into non penetrating (54.1%), equivocal (14.8%) and penetrating (31.1%). All non-penetrating stabs were managed successfully by SAE. DL proved negative for peritoneal violation in all equivocal injuries and positive in all injuries designated as penetrating. Consequently, sensitivity, specificity, positive and negative predictive values and accuracy of CT tractography in detecting peritoneal violation was 100%. No missed injuries were encountered in this study. CONCLUSION: IV contrast-enhanced CT tractography is an effective tool in the evaluation of patients with AASW. Patients with negative tractography can be safely managed by SAE. Positive tractography accurately indicates peritoneal violation which warrants further management. Patients with equivocal findings were all negative for peritoneal violation by laparoscopy, therefore, they might be reallocated for frequent SAE to reduce the rate of non-therapeutic interventions.

Regulation of IL-6/STAT-3/Wnt axis by nifuroxazide dampens colon ulcer in acetic acid-induced ulcerative colitis model: Novel mechanistic insight.

AIM: Ulcerative colitis (UC) is a common intestinal problem characterized by the diffusion of colon inflammation and immunity dysregulation. Nifuroxazide, a potent STAT-3 inhibitor, exhibits diverse pharmacological properties. The present study aimed to elucidate a novel anti-colitis mechanism of nifuroxazide against the acetic acid-induced UC model. METHODS: Rats were grouped into control (received vehicle), UC (2 ml of 5% acetic acid by intrarectal infusion), UC plus sulfasalazine (100 mg/kg/day, P.O.), UC plus nifuroxazide (25 mg/kg/day, P.O.), and UC plus nifuroxazide (50 mg/kg/day, P.O.) and lasted for 6 days. RESULTS: The present study revealed that nifuroxazide significantly reduced UC measures, hematological changes, and histological alteration. In addition, treatment with nifuroxazide significantly down-regulated serum CRP as well as the colonic expressions of MPO, IL-6, TNF-α, TLR-4, NF-κB-p65, JAK1, STAT-3, DKK1 in a dose-dependent manner. Besides, our results showed that the colonic Wnt expression was up-regulated with nifuroxazide treatment. In a dose-dependent manner, nifuroxazide markedly alleviated acetic acid-induced cellular infiltration and improved ulcer healing by increasing intestinal epithelial cell regeneration. SIGNIFICANCE: Our results collectively indicate that nifuroxazide is an effective anti-colitis agent through regulation of colon inflammation and proliferation via modulation IL-6/STAT-3/Wnt signaling pathway.

Umbelliferone alleviates hepatic ischemia/reperfusion-induced oxidative stress injury via targeting Keap-1/Nrf-2/ARE and TLR4/NF-κB-p65 signaling pathway.

Umbelliferone (UMB; 7-hydroxycoumarin) is a natural compound that exhibited a diversity of pharmacological activities. Its protective effects against various ischemia/reperfusion (IR) injuries, including heart, kidney, and testis, have been observed. However, their effect on hepatic IR is still not investigated yet. Here, this study was conducted to examine the potential protective role of UMB during the early phase of hepatic IR injury via targeting Keap-1/Nrf-2/ARE and its closely related signaling pathway, TLR4/NF-κB-p65. Experimentally, forty Wistar albino rats were randomly divided into 4 groups: Sham control group (received 1% carboxymethyl cellulose as a vehicle), UMB group (30 mg/kg/day, P.O.), IR group (subjected to complete hepatic IR injury), and IR + UMB group. Our results revealed that oral UMB effectively reduced the serum levels of ALT, AST, ALP, and LDH along with the restoration of oxidant/antioxidant status. At the molecular level, UMB markedly activated Nrf-2 expression and its down-streaming targets: HO-1, NQO1, GCLC, SOD3, and TNXRD1, along with Keap-1 down-regulation. Besides, UMB significantly down-regulated NF-κB-p65 and TLR4 expressions with subsequent decreased TNF-α and IL-1ß levels coupled with the up-regulation of the IL-10 level. Finally, biochemical findings were confirmed by attenuation of histopathological changes in liver tissues. Together, UMB is a promising agent for the amelioration of liver tissues against IR-induced oxidative injury through activation of the Keap-1/Nrf-2/ARE signaling pathway along with suppression of its closely related signaling pathways: TLR4/NF-κB-p65. Illustrated diagram explored the prospective underlying protective mechanism of UMB against IR-induced hepatic damage.

Arg753Gln Polymorphisms in the Toll-Like Receptor 2 Gene are Associated with Cytomegalovirus Infection in Egyptian Bone Marrow Recipients.

BACKGROUND: Previous studies have shown that cytomegalovirus (CMV) induced innate immune response via activation of Toll-like receptor 2 (TLR2). The association between CMV among specific single-nucleotide polymorphisms (SNPs) in the TLR2 gene was also investigated. OBJECTIVE: This study investigated the relationship between specific SNPs in the TLR2 gene (G>A), TLR2-Arg753Gln (rs5743708), and CMV replication after bone marrow transplantation. METHODS: The TLR2-Arg753Gln SNP was genotyped in 181 patients after bone marrow transplantation: 83 and 98 patients with and without CMV infection, respectively. CMV load was determined in serially collected blood samples using real-time PCR. Genotyping was performed using specific sequence primer PCR (SSP-PCR), and the results were confirmed by restriction fragment length polymorphism (RFLP) analysis of the PCR-amplified fragments for GG (wild type), GA and AA identification. RESULTS: Roughly, 85% of the patients screened for the presence of the TLR2-Arg753Gln were GG homozygous, and 15% were GA heterozygous; no patients were homozygous for the mutant allele (A). The GA heterozygous allele was more frequent in the CMV-infected group after bone marrow transplantation. CONCLUSION: To our knowledge, this is a novel observation that supports the notion that the functional missense mutation (TLR2-Arg753Gln polymorphism) is possibly associated with CMV replication after bone marrow transplantation. This suggests a role for TLR2 in the innate immune response of human CMV infection in Egyptian bone marrow recipients.

Coffea arabica Bean Extracts and Vitamin C: A Novel Combination Unleashes MCF-7 Cell Death.

BACKGROUND: Vitamin C (VC) is believed to enhance immunity and is regularly integrated as a supplementary agent during several treatments. OBJECTIVE: The green (GC) and roasted (RC) coffee (Coffea arabica) aqueous extracts (0, 125, 250 and 500 µg/ml) combined with VC (50 µg/ml) were examined on the cancerous MCF-7 cell line and normal human lymphocytes. METHODS: Neutral red uptake assay, comet assay, immunocytochemical reactivity for protein expression and mRNA expression of apoptosis-related genes were performed. RESULTS: A significant (P< 0.05) concentration-dependent increase of apoptotic features, such as morphological changes, and abundant nuclear condensation, altered the expression of p53 and caspase-3 mRNA, down-regulation of Bcl-2 protein as well as the acidic autophagosomal vacuolization in treated cells. The oxidative stress and DNA single-strand breaks were noticed too. CONCLUSION: These results suggest that coffee in combination with VC undergoes apoptotic anticancer pathway. This supports the integration of coffee and VC as a valuable candidate for anticancer research and treatments.

Gastric tube esophagoplasty for pediatric esophageal replacement.

BACKGROUND: Esophageal replacement in children is indicated in cases of esophageal atresia with or without fistula, in case of long gap esophageal atresia or failed primary repair. Intractable post corrosive esophageal stricture is considered also a major indication for replacement. METHODS: This is a cohort retrospective study of esophageal replacement cases by gastric tube carried out at the pediatric surgery department at Cairo University between 2011 and 2015. We reported 50 patients (30 boys and 20 girls); the ages ranged from 7months to 9years. Esophageal atresia cases were 27 while caustic esophageal stricture cases were 23. Isoperistaltic gastric tube technique was done in 45 patients while antiperistaltic (reversed) gastric tube technique was done in 5 cases. Retrosternal route was chosen in 38 patients while transhiatal route was chosen in 12 patients. RESULTS: Leakage and stricture were the most common complications. We had 5 cases of mortality, which were caused mainly by chest related complications. We had excellent to good results during long term follow up in terms of weight gain, swallowing pattern, quality of life, and overall satisfaction CONCLUSION: Gastric tube is a satisfactory surgical method for esophageal replacement in children. LEVEL OF EVIDENCE: III.