Immunohistochemical Expression of Alpha-Methyl-Coa (AMACR) and ERG in Prostatic Adenocarcinoma and Prostatic Hyperplasia: A Comparative Study.

OBJECTIVE: This observational comparative study aimed at investigating the diagnostic accuracy of ERG in differentiating benign and malignant prostatic lesions and comparing it to the diagnostic accuracy of AMACR. We also aimed at comparing AMACR and ERG expression to Gleason grade of the carcinoma cases. METHODS: Seventy- two cases (22 prostatic hyperplasia and 50 prostatic carcinoma) were collected from the pathology department at Cairo university. The cases were immunostained by antibodies against AMACR and ERG. Immunohistochemical expressions of both markers were differentially examined in benign and malignant cases, compared to each other's, as well as, to the grade group of the malignant cases. RESULTS: AMACR showed 62% sensitivity and 86.4% specificity for the diagnosis of PC, with a statistically significant differential expression in benign and malignant lesions (P=0.001). Its expression also correlated significantly with the age (p=0.007), Gleason grade (P=0.006) and perineural invasion (P=0.011). Although ERG showed 100% specificity to PC with no expression in hyperplasia cases, it showed only 22% sensitivity for PC cases. ERG expression also showed statistically significant correlation with the Gleason grade. No association between ERG and AMACR expression was detected in our study (P=0.151). Regarding the diagnostic accuracy, although ERG accuracy was much lower than that of AMACR, combining both markers yielded a higher diagnostic accuracy. CONCLUSION: Although ERG proved no superior value than AMACR in diagnosing prostatic lesions, combining both markers may lead to higher diagnostic accuracy owing to higher ERG specificity for PC.

Combined tumor necrosis factor-α (-308 G/A) and tumor necrosis factor-ß (+ 252 A/G) nucleotide polymorphisms and chronicity in Egyptian children with immune thrombocytopenia.

BACKGROUND: Primary immune thrombocytopenia (ITP) is a common autoimmune disorder. Secretion of TNF-α, TNF-ß and IFN-γ plays a major role in the pathogenesis of ITP. OBJECTIVE: This cross-sectional study aimed to detect TNF-α (-308 G/A) and TNF-ß (+ 252 A/G) gene polymorphism in a cohort of Egyptian children with chronic ITP (cITP) to clarify their possible association with progression to chronic disease. METHODS: The study included 80 Egyptian cITP patients and 100 unrelated age- and sex-matched controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with TNF-α homozygous (A/A) genotype had significantly higher mean age, longer disease duration and lower platelet counts (p values 0.005, 0.024 and 0.008, respectively). TNF-α wild (G/G) genotype was significantly more frequent among responders (p = 0.049). Complete response was more frequent among wild (A/A) TNF-ß genotype patients (p = 0.011), and platelet count was significantly lower among homozygous (G/G) genotype (p = 0.018) patients. Combined polymorphisms were strongly associated with susceptibility to chronic ITP. CONCLUSION: Homozygosity in either gene might contribute to a worse course of disease, increased severity and poor response to therapy. Patients expressing combined polymorphisms are more prone to progression to chronic disease, severe thrombocytopenia and longer disease duration.

Umbelliferone attenuates diabetic cardiomyopathy by suppression of JAK/STAT signaling pathway through amelioration of oxidative stress and inflammation in rats.

Umbelliferone (UMB), 7-hydroxycoumarin, is a naturally occurring coumarin derivative that has a plethora of biological and therapeutic activities. The focus of this research was to elucidate the curative effects of two different doses of UMB on diabetic cardiomyopathy (DCM) in a type 2 diabetic rat model induced by 50 mg/kg body weight of streptozotocin (STZ). Diabetic rats orally received 10 or 30 mg/kg of UMB daily for 8 weeks. Compared to the nontreated diabetic group, both UMB treatment doses significantly decreased glucose levels, glycated hemoglobin (HbA1c), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), creatine kinase MB (CK-MB), cardiovascular risk indices, and oxidative stress by reducing malondialdehyde (MDA) and increasing the activity of the antioxidant enzymes. The hypercholesterolemia and hypertriglyceridemia also dramatically decreased in diabetic groups with UMB treatments accompanied by an improvement in insulin, and insulin sensitivity indices (HOMA-IR and QUICKI). Furthermore, the cardiac gene expressions and protein levels of Janus kinase2 (JAK2), signal transducer and activator of transcription3 (STAT3), and transforming growth factor beta1 (TGF-ß1) were also markedly downregulated in a dose-dependent manner by UMB treatments. Finally, the biochemical results were assured by the reduction of histological alterations in cardiac tissues. In conclusion, UMB is a propitious substance for the treatment of DCM by virtuousness of its antihyperglycemic, antihyperlipidemic, antioxidant, and anti-inflammatory properties through modulating the JAK/STAT signaling pathway that may be the underlying mechanism in UMB action.

Anti-vinculin antibodies as a novel biomarker in Egyptian patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder that causes vasculopathy and scarring, most commonly in the lungs and skin, but it can also affect other organs. Endothelial vinculin plays a critical role in angiogenesis regulation. Therefore, vinculin overexpression in SSc may give rise to anti-vinculin antibodies, which may contribute to the development of SSc vasculopathy. The current research aims to (1) determine whether anti-vinculin autoantibodies play a significant role in the diagnosis of SSc and (2) compare anti-vinculin serum levels between two scleroderma patient populations, namely, pulmonary artery hypertension (PAH)-predominant and interstitial pulmonary fibrosis (IPF)-predominant groups. METHODS: This research included 140 participants categorized into three groups: group I-patients with PAH-predominant; group II-patients with ILD-predominant; group III-the control group. Anti-vinculin antibodies were detected in serum samples collected from all participants using ELISA. All subjects underwent high-resolution computed tomography (CT), diffusing capacity for carbon monoxide, and pulmonary function tests. RESULTS: Patients in group I (PAH-predominant group, N = 35) were 41.3 [± 11.4] years old, with 80% being women. Patients in group II (ILD-predominant group, N = 35) were 41.0 [± 11.5] years old. The SSc group showed significantly higher anti-vinculin antibody levels than the control group (P < 0.001). The PAH-predominant group demonstrated significantly higher anti-vinculin antibody levels and anti-vinculin positivity than the ILD-predominant group. CONCLUSION: Anti-vinculin antibodies in the blood appear to be diagnostic biomarkers for scleroderma. Furthermore, they shed light on some novel perspectives on the pathophysiology of specific lung fibrotic changes. Key Points • This study included two groups of systemic sclerosis patients (PAH-predominant group, ILD-predominant group) as well as a control group to investigate the significance of anti-vinculin antibodies in such cases. • Our results have demonstrated that anti-vinculin antibodies can play a significant role in diagnosing and monitoring systemic sclerosis disease.

Interleukin-17A gene single nucleotide polymorphism and its relation to fungal growth in psoriatic patients: A preliminary study.

BACKGROUND: Although dysbiosis and the role of the microbiome in the pathogenesis of inflammatory skin diseases have been intensively investigated, fungal colonization or infection has received minimal attention. AIMS: To isolate and identify different fungal species namely Candida, Dermatophytes, Malassezia, and Aspergillus from plaque psoriasis patients, evaluate the association of IL-17A gene single nucleotide polymorphisms (SNPs) with psoriasis, and to reveal the relation between IL-17A gene SNPs and the fungal presence within the psoriatic plaques. PATIENTS/METHODS: Fifty plaque psoriasis patients and fifty healthy age and sex volunteers as controls were enrolled in this study. From psoriatic plaques, mycological isolation was done by direct microscopic examination (10% KOH mount), culture onto the three sets of media then species identification by phenotypic procedures. Genomic DNA extraction and genotyping for IL-17A (rs10484879) SNPs using polymerase chain reaction and restriction fragment length polymorphism were also done. RESULTS: Psoriasis cases showed higher frequency of fungal growth 86% vs. 14% in controls; (p < 0.001). The frequency of IL-17A GA, AA, and total polymorphism (GA+AA) genotypes in psoriasis cases was significantly higher than in controls. There was non-significant association between different IL-17A genotypes and fungal growth except Aspergillus flavus, which decreased gradually with GG, GA, and AA (37.5%, 20.8%, and 0%, respectively). CONCLUSIONS: Psoriasis cases are significantly associated with fungal growth, which may be a contributing factor in its pathogenesis. SNPs of IL-17A (rs10484879) G/A gene led to increased susceptibility toward pathogenesis of psoriasis. Fungal growth and IL-17A GA+AA genotypes are suggested to be independent predictors of psoriasis susceptibility.

Comparative Feasibility of Oxidative Stress and Immune-Inflammatory Response Induced in the Secondary Intermediate Host by Different Viability Status of the Hydatid Cysts.

BACKGROUND: Echinococcosis is a common health problem in the Mediterranean and the Middle East. Many hydatid cysts remain asymptomatic, even in advanced age due to the slow growth of the parasite. OBJECTIVE: The present study aimed to investigate the oxidative and inflammatory responses in rats' echinococcosis induced by three different viability statuses of the Echinococcus granulosus (G6) as diagnostic markers. METHODS: Forty-eight male albino rats were injected intraperitoneally with three different viability statuses of the hydatid cyst fluid of the camel strain. The groups included: the negative control group (1), the low viable protoscoleces (2), the high viable protoscoleces fluid (3) not viable and not completely transformed to the calcareous status of protoscoleces fluid (4). Serum was harvested at the end of each week from the 9th to the 12th week post-infection for measuring the oxidative stress by total antioxidant capacity (TAC), and lipid peroxide (Malondialdehyde) (Malondialdehyde or MDA). Splenic tissues from different groups were collected for histopathological examination. RESULTS: The results showed a histopathological change, a significant decrease in TAC levels, and an increase in malondialdehyde, the TNF-α, and IL-10 levels of the infected groups compared with the uninfected group (P<0.05). CONCLUSION: Our study concluded that echinococcosis induced severe oxidative stress and inflammatory responses including tissue necrosis and tissue degeneration are the factors that can be used in the early stages of infection, avoiding hazards of contamination.

Molecular effects of Moringa leaf extract on insulin resistance and reproductive function in hyperinsulinemic male rats.

BACKGROUND: Many studies have reported that insulin resistance impairs the antioxidant defense system and causes male infertility. Moringa oleifera is a medicinal plant that has been employed for the medicament of many disorders. It controls the levels of glucose and manages male sexual disorders. However, its extracts can reverse insulin resistance-linked metabolic alterations remains unknown. Therefore, the current study investigated the potential of the aqueous leaves extract from Moringa oleifera to reverse insulin resistance and testicular disorders in rats. METHODS: Rats were fed either a chow (as a control group) or a high fructose diet (HFD, to persuade a state of insulin resistance), in addition to a group of rats fed HFD and treated with Moringa (300 mg/kg) for 4 weeks. RESULTS: Moringa reversed hepatic insulin insensitivity and this was linked to up-regulation of genes involved in insulin receptors and glucose uptake in the liver. These results were associated with amended the insulin level in serum and standardization of insulin sensitivity. In addition, it improved the serum testosterone level and the gene expression of the testicular steridogenic acute regulatory protein (StAR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD). CONCLUSION: Taken together, our findings demonstrate that Moringa reversed HFD diet-induced insulin resistance and improved the testicular function.

Mesenchymal stem cells therapeutic potential alleviate lipopolysaccharide-induced acute lung injury in rat model.

Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. The current study examined the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) in lipopolysaccharide (LPS)-induced pulmonary congestion in rats as compared with dexamethasone (Dexa) and sodium bicarbonate (NaHCO3 ). LPS (20 µL of LPS of Escherichia coli in each nostril for two consecutive days) induced lung injury as marked by an elevation of number of inflammatory cells especially neutrophils, increased total protein levels, elevation of lipid peroxidation, and reduction of reduced glutathione in bronchoalveolar lavage along with the reduction of reduced glutathione. These deleterious effects were hampered after treatment with BM-MSCs (1 × 106 cells/rat) once before acute lung injury (ALI) induction with LPS to an even better extent than Dexa (2 mg/kg once, ip) and NaHCO3 (10-15 mL/day for two consecutive days). In summary, BM-MSCs have the ability to suppress the endotoxin-induced systemic inflammatory response and could prove to be a novel approach to therapy for ALI in rats.

Corruption drives the emergence of civil society.

Centralized sanctioning institutions have been shown to emerge naturally through social learning, displace all other forms of punishment and lead to stable cooperation. However, this result provokes a number of questions. If centralized sanctioning is so successful, then why do many highly authoritarian states suffer from low levels of cooperation? Why do states with high levels of public good provision tend to rely more on citizen-driven peer punishment? Here, we consider how corruption influences the evolution of cooperation and punishment. Our model shows that the effectiveness of centralized punishment in promoting cooperation breaks down when some actors in the model are allowed to bribe centralized authorities. Counterintuitively, a weaker centralized authority is actually more effective because it allows peer punishment to restore cooperation in the presence of corruption. Our results provide an evolutionary rationale for why public goods provision rarely flourishes in polities that rely only on strong centralized institutions. Instead, cooperation requires both decentralized and centralized enforcement. These results help to explain why citizen participation is a fundamental necessity for policing the commons.