Полиморфизм вставки/делеции гена АПФ связан с глиобластомой у населения Ирана: исследование случай-контроль

Background. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has recently been reported to be associated with the pathogenesis and development of human cancers.This study aimed to assess the potential association between ACE (I/D) polymorphism and glioblastoma in an Iranian population.Material and Methods. This case-control study was conducted on 80 patients with glioblastoma and 80 healthy blood donors as controls. Gap-polymerase chain reaction (Gap-PCR) was used to determine the ACE (I/D) genotypes. PCR products were separated and measured by electrophoresis on a 2 % agarose gel.Results. Analysis of demographic data showed a significant difference in the family history of cancer between the case and control groups (p=0.03). The distribution of ACE gene variants including II, ID, and DD genotypes was also calculated, and significant differences were seen in the DD genotype (p=0.03) and D allele (p=0.04) between the glioblastoma cases and controls.Conclusion. ACE gene polymorphism was associated with glioblastoma in the study population. Further studies are needed to approve this finding.Актуальность. Недавно сообщалось, что инсерционно-делеционный (I/D) полиморфизм гена ангиотензин-превращающего фермента (АПФ) связан с патогенезом и развитием рака человека.Целью исследования была оценка потенциальной связи между I/D полиморфизмом гена АПФ и глиобластомой у населения Ирана.Материал и методы. В исследовании случай-контроль участвовали 80 пациентов с глиобластомой и 80 здоровых доноров в качестве группы контроля. Полимеразная цепная реакция (Gap-PCR) использовалась для определения генотипов I/D полиморфизма гена AПФ. ПЦР-продукты разделяли и измеряли электрофорезом в 2 % агарозном геле.Результаты. Анализ демографических данных показал значительную разницу в семейной истории рака между основной и контрольной группами (p=0,03). Было рассчитано распределение вариантов гена АПФ, включая генотипы II, ID и DD, и были обнаружены значительные различия в генотипе DD (p=0,03) и аллеле D (p=0,04) между группой больных с глиобластомой и контрольной группой.Заключение. Полиморфизм гена AПФ был связан с глиобластомой в исследуемой популяции. Необходимы дальнейшие исследования, чтобы подтвердить эти данные

Resveratrol supplementation and acute pancreatitis: A comprehensive review

Resveratrol, a natural polyphenolic ingredient extracted from herbs, suppresses oxidative stress and inflammation. We performed a comprehensive review to find any evidence about the effects of Resveratrol on acute pancreatitis (AP). Resveratrol has been found to directly impact cytokine generation. As these factors play a crucial role in the pathophysiology of AP, resveratrol might attenuate AP and its complications. Mechanistically, resveratrol exerts its pharmacological effects through anti-inflammatory and antioxidant mechanisms via interaction with different signaling molecules and transcription factors. Indeed, resveratrol might prove to be an effective therapeutic component for AP treatment in the future. In this review, we shed light on potential most recent pathways through which resveratrol might impact the management and control of AP. © 202

The role of MicroRNA signature as diagnostic biomarkers in different clinical stages of colorectal cancer

Objective: Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related death worldwide. The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MicroRNAs (miRNAs) have provided new insight into CRC development and have been suggested as reliable and stable biomarkers for diagnosis and prognosis. The aim of this study was to analyze the differential expression of miRNAs at different stages of CRC searching for possible correlation with clinicopathological features to examine their potential value as diagnostic biomarkers. Materials and Methods: In this case-control study, plasma and matched tissue samples were collected from 74 CRC patients at stage II-IV as well as blood samples from 32 healthy controls. After exhaustive study of the current literature, eight miRNAs including miR-200c, 20a, 21, 31,135b, 133b,145 and let-7g were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Statistical analysis, including t test , Mann-Whitney U, Kruskall-Wallis tests and receiver operating characteristic (ROC) curve was applied, where needed. Results: Significantly elevated levels of miR-21, miR-31, miR-20a, miR-135b, and decreased levels of miR-200c, miR-145 and let-7 g were detected in both plasma and matched tissue samples compared to the healthy group (P0.05). ROC for tissue miRNAs showed an area under the ROC curve (AUC) of 0.98 and P<0.001 for miR-21, 0.91 and P<0.001 for miR-135b, 0.91 and P<0.001 for miR-31, and 0.92 and P<0.001 for miR-20a. Conclusion: Our results indicate that the expression levels of microRNAs are systematically altered in CRC tissue and plasma. In conclusion, detection of miR-21, miR-135b, miR-31 and miR-20a levels in the tissue might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and serve as tumor-associated biomarkers for diagnosis. © 2018 Royan Institute (ACECR). All Rights Reserved

CANDIDIA AND HIV CO-INFECTIONS AMONG WOMEN ATTENDING HIV CLINIC AT GENERAL HOSPITAL EZZANGBO, NIGERIA

Candidiasis has been identified as a ubiquitous fungal infection commonly affecting people living with HIV/AIDS. This research ascertained the prevalence and risk factors forral and vaginal candidiasis among 180 HIV out-patients at Ebonyi State General Hospital, Ezzangbo. Oral and vaginal swabs were aseptically collected from the participants in duplicate. One of the swabs was streaked on Sabouraud's Dextrose Agar (SDA) and isolates were identified using macroscopic characteristics while the second swab was used for microscopic examination. Structured questionnaires were administered to participants to obtain risk factors associated with the infections. The antifungal susceptibility testing of the Candida isolates was performed using disc diffusion method. Data obtained was statistically analysed using Statistical Package for Social Scientist (SPSS). Results obtained from the study indicated 120(66.7%) were positive for Candidiasis; 31.7% was positive for only vaginal Candidiasis, 22.2% were positive for only oral Candidiasis while 12.8% had both. Candida albicans (CA) was dominant with 71% while none albicans Candida (NAC) was 29%. Isolates were most sensitive to Itraconazole and Griseofluvin and less sensitive to Ketoconazole, Nystatin and Fluconazole. The results of this study underlined essentials of good hygiene practices and importance of regularly assessing HIV patients for candidiasis

The role of thrombospondins in wound healing, ischemia, and the foreign body reaction

Thrombospondin (TSP) 1 and TSP2 have been implicated in the regulation of several processes during tissue repair. Due to their matricellular nature, these proteins are thought to modulate cell-matrix interactions through a variety of mechanisms specific to the spatio-temporal context of their expression. Most notably, TSP1 and TSP2 appear to play distinct, non-overlapping roles in the healing of skin wounds. In contrast, both proteins have been implicated as regulators of ischemia-induced angiogenesis. Moreover, TSP2 has been shown to be a critical regulator of angiogenesis in the foreign body response (FBR). In this review, we discuss the role of TSPs in tissue repair and examine the mechanistic data regarding the ability of the thrombospondins to modulate cell-matrix interactions in this context

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease

Targeted Expression of Cre Recombinase Provokes Placental-Specific DNA Recombination in Transgenic Mice

Background: Inadequate placental development is associated with a high incidence of early embryonic lethality and serious pregnancy disorders in both humans and mice. However, the lack of well-defined trophoblast-specific gene regulatory elements has hampered investigations regarding the role of specific genes in placental development and fetal growth. Principal Findings: By random assembly of placental enhancers from two previously characterized genes, trophoblast specific protein a (Tpbpa) and adenosine deaminase (Ada), we identified a chimeric Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the highest luciferase activity in cultured human trophoblast cells, in comparison with non-trophoblast cell lines. We used this chimeric enhancer arrangement to drive the expression of a Cre recombinase transgene in the placentas of transgenic mice. Cre transgene expression occurred throughout the placenta but not in maternal organs examined or in the fetus. Significance: In conclusion, we have provided both in vitro and in vivo evidence for a novel genetic system to achieve placental transgene expression by the use of a chimeric Tpbpa/Ada enhancer driven transgene. The availability of thi

Enhanced Proliferation of Monolayer Cultures of Embryonic Stem (ES) Cell-Derived Cardiomyocytes Following Acute Loss of Retinoblastoma

Background: Cardiomyocyte (CM) cell cycle analysis has been impeded because of a reliance on primary neonatal cultures of poorly proliferating cells or chronic transgenic animal models with innate compensatory mechanisms. Methodology/Principal Findings: We describe an in vitro model consisting of monolayer cultures of highly proliferative embryonic stem (ES) cell-derived CM. Following induction with ascorbate and selection with puromycin, early CM cultures are.98 % pure, and at least 85 % of the cells actively proliferate. During the proliferative stage, cells express high levels of E2F3a, B-Myb and phosphorylated forms of retinoblastoma (Rb), but with continued cultivation, cells stop dividing and mature functionally. This developmental transition is characterized by a switch from slow skeletal to cardiac TnI, an increase in binucleation, cardiac calsequestrin and hypophosphorylated Rb, a decrease in E2F3, B-Myb and atrial natriuretic factor, and the establishment of a more negative resting membrane potential. Although previous publications suggested that Rb was not necessary for cell cycle control in heart, we find following acute knockdown of Rb that this factor actively regulates progression through the G1 checkpoint and that its loss promotes proliferation at the expense of CM maturation. Conclusions/Significance: We have established a unique model system for studying cardiac cell cycle progression, and show in contrast to previous reports that Rb actively regulates both cell cycle progression through the G1 checkpoint an

BRCA1 is an essential regulator of heart function and survival following myocardial infarction

The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer but its role in protecting other tissues from DNA damage has not been explored. Here we show a new role for BRCA1 as a gatekeeper of cardiac function and survival. In mice, loss of BRCA1 in cardiomyocytes results in adverse cardiac remodelling, poor ventricular function and higher mortality in response to ischaemic or genotoxic stress. Mechanistically, loss of cardiomyocyte BRCA1 results in impaired DNA double-strand break repair and activated p53-mediated pro-apoptotic signalling culminating in increased cardiomyocyte apoptosis, whereas deletion of the p53 gene rescues BRCA1-deficient mice from cardiac failure. In human adult and fetal cardiac tissues, ischaemia induces double-strand breaks and upregulates BRCA1 expression. These data reveal BRCA1 as a novel and essential adaptive response molecule shielding cardiomyocytes from DNA damage, apoptosis and heart dysfunction. BRCA1 mutation carriers, in addition to risk of breast and ovarian cancer, may be at a previously unrecognized risk of cardiac failure

Laser-induced modification of the patellar ligament tissue: comparative study of structural and optical changes

The effects of non-ablative infrared (IR) laser treatment of collagenous tissue have been commonly interpreted in terms of collagen denaturation spread over the laser-heated tissue area. In this work, the existing model is refined to account for the recently reported laser-treated tissue heterogeneity and complex collagen degradation pattern using comprehensive optical imaging and calorimetry toolkits. Patella ligament (PL) provided a simple model of type I collagen tissue containing its full structural content from triple-helix molecules to gross architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6 mm) of equal dose, where the tissue temperature reached the collagen denaturation temperature of 60 ± 2°C at the laser spot epicenterin the first regime, and was limited to 67 ± 2°C in the second regime. The collagen network was analyzed versus distance from the epicenter. Experimental characterization of the collagenous tissue at all structural levels included cross-polarization optical coherence tomography, nonlinear optical microscopy, light microscopy/histology, and differential scanning calorimetry. Regressive rearrangement of the PL collagen network was found to spread well outside the laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical reorganization of collagen. Four zones of distinct optical and morphological properties were identified, all elliptical in shape, and elongated in the direction perpendicular to the PL long axis. Although the collagen transformation into a random-coil molecular structure was occasionally observed, it was mechanical integrity of the supramolecular structures that was primarily compromised. We found that the structural rearrangement of the collagen network related primarily to the heat-induced thermo-mechanical effects rather than molecular unfolding. The current body of evidence supports the notion that the supramolecular collagen structure suffered degradation of various degrees, which gave rise to the observed zonal character of the laser-treated lesion