{"title":"Molecular Mechanisms of Angiotensin-converting Enzyme Inhibitory Peptide LAP Activity on Apoptosis of Vascular Smooth Muscle","authors":"Yi Shen, Hong Fang, A. O. Cavdar, Chi Liu","doi":"10.35248/2167-7956.19.8.178","DOIUrl":"https://doi.org/10.35248/2167-7956.19.8.178","url":null,"abstract":"We observe the expression levels of apoptotic cells, Bcl-2/Bax and caspase-9 on abdominal aorta of spontaneously hypertensive rats (SHRs) to investigate impact and mechanisms of angiotensin converting enzyme inhibitory peptide LAP in apoptosis of vascular smooth muscle cell. A total of 20 male SHRs were studied to detect apoptotic cells and the expression of apoptosis-related proteins (Bcl-2, Bax, caspase-9). The index of apoptotic cells in LAP group was significantly lower compared to the control group. The expression of Bcl-2 in the LAP group was significantly higher than the control group. However, the levels of Bax and caspase-9 expression in the LAP group were significantly lower compared to the control group. The apoptosis index was negatively correlated with Bcl-2 and positively correlated with Bax/caspase-9. Similarly, the inflammation markers in LAP group were significantly lower than those in the control group. The expression of Ang II was significantly decreased after treating with LAP in the abdominal arteries. Angiotensin- converting- enzyme inhibition peptide LAP inhibited apoptosis of vascular smooth muscle cells through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 in SHRs.","PeriodicalId":90579,"journal":{"name":"Journal of biomolecular research & therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69995024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reevaluation of Antioxidative Strategies for Birth Defect Prevention in Diabetic Pregnancies.","authors":"Zhiyong Zhao","doi":"10.4172/2167-7956.1000145","DOIUrl":"10.4172/2167-7956.1000145","url":null,"abstract":"<p><p>Diabetes mellitus in early pregnancy is the most severe maternal disease that is counted for 10% of newborn infants with structural defects. With the rapid increases in the number of diabetic women in childbearing age, the birth defect rate is projected to elevate dramatically. Thus, prevention of embryonic malformations becomes an urgent task. Animal studies have revealed an involvement of oxidative stress in diabetic embryopathy and treatment with antioxidants can reduce embryonic abnormalities. However, the failure of clinical trials using free radical-scavenging antioxidants to alleviate oxidative stress-related diseases prompts researchers to reevaluate the strategy in birth defect prevention. Hyperglycemia also disturbs other intracellular homeostasis, generating aberrant conditions. Perturbed folding of newly synthesized proteins causes accumulation of unfolded and misfolded proteins in the lumen of the endoplasmic reticulum (ER). The ER under the stress activates signaling cascades, known as unfolded protein response, to suppress cell mitosis and/or trigger apoptosis. ER stress can be ameliorated by chemical chaperones, which promote protein folding. Hyperglycemia also stimulates the expression of nitric oxide (NO) synthase 2 (NOS2) to produce high levels of NO and reactive nitrogen species and augment protein nitrosylation and nitration, resulting in nitrosative stress. Inhibition of NOS2 using inhibitors has been demonstrated to reduce embryonic malformations in diabetic animals. Therefore, targeting ER and nitrosative stress conditions using specific agents to prevent birth defects in diabetic pregnancies warrant further investigations. Simultaneously targeting multiple stress conditions using combined agents is a potentially effective and feasible approach.</p>","PeriodicalId":90579,"journal":{"name":"Journal of biomolecular research & therapeutics","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35428406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MicroRNA biomarkers for early detection of embryonic malformations in pregnancy.","authors":"Xuezheng Li, Zhiyong Zhao","doi":"10.4172/2167-7956.1000119","DOIUrl":"https://doi.org/10.4172/2167-7956.1000119","url":null,"abstract":"<p><p>Congenital birth defects, manifested in newborn infants, are formed during early embryogenesis. Targeted and individualized interventions to prevent birth defects require early detection of risk and signs of developmental abnormalities. Current diagnosis of structural anomalies largely relies on ultrasonography, which can only detect abnormities after their formation in fetuses. Biomolecules, mainly proteins, in maternal blood have been used as indicators of fetal anomalies; however, they lack adequate sensitivity for detecting embryonic malformations. Recently, cell-free microRNAs (miRNAs) have been found in blood and evaluated as biomarkers for diseases. Expression of certain miRNAs in maternal plasma has been shown to be correlated with birth defects in infants. Although their reliability and sensitivity remain to be validated, miRNAs, which can be amplified and sequenced, are potentially sensitive and specific biomarkers for early embryonic dysmorphogenesis.</p>","PeriodicalId":90579,"journal":{"name":"Journal of biomolecular research & therapeutics","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2167-7956.1000119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33203636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Delivery of Polymeric Nanoparticles to Target Vascular Diseases.","authors":"Edward Agyare, Karunyna Kandimalla","doi":"10.4172/2167-7956.s1-001","DOIUrl":"https://doi.org/10.4172/2167-7956.s1-001","url":null,"abstract":"<p><p>Current advances in nanotechnology have paved the way for the early detection, prevention and treatment of various diseases such as vascular disorders and cancer. These advances have provided novel approaches or modalities of incorporating or adsorbing therapeutic, biosensor and targeting agents into/on nanoparticles. With significant progress, nanomedicine for vascular therapy has shown significant advantages over traditional medicine because of its ability to selectively target the disease site and reduce adverse side effects. Targeted delivery of nanoparticles to vascular endothelial cells or the vascular wall provides an effective and more efficient way for early detection and/or treatment of vascular diseases such as atherosclerosis, thrombosis and Cerebrovascular Amyloid Angiopathy (CAA). Clinical applications of biocompatible and biodegradable polymers in areas such as vascular graft, implantable drug delivery, stent devices and tissue engineering scaffolds have advanced the candidature of polymers as potential nano-carriers for vascular-targeted delivery of diagnostic agents and drugs. This review focuses on the basic aspects of the vasculature and its associated diseases and relates them to polymeric nanoparticle-based strategies for targeting therapeutic agents to diseased vascular site.</p>","PeriodicalId":90579,"journal":{"name":"Journal of biomolecular research & therapeutics","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2167-7956.s1-001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33263836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Critical Role of Calpain in Cell Proliferation.","authors":"Laszlo Kovacs, Yunchao Su","doi":"10.4172/2167-7956.1000112","DOIUrl":"https://doi.org/10.4172/2167-7956.1000112","url":null,"abstract":"<p><p>Calpain is a conserved family of calcium-dependent, cytosolic, neutral cysteine proteases. The best characterized members of the family are the ubiquitously expressed calpain 1 and calpain 2. They perform controlled proteolysis of their target proteins. The regulation of these enzymes includes autolysis, calcium, phosphorylation as a posttranslational modification, and binding of calpastatin, phospholipids or activator proteins, respectively. Calpain are implicated in many physiological and pathological processes. They have significant role in the cell proliferation, differentiation and migration in a variety of mammalian cell types, contributing to the development of angiogenesis, vascular remodeling, and cancer. Therefore the knowledge of the precise mechanism of calpain signaling could provide therapeutic approaches in these processes.</p>","PeriodicalId":90579,"journal":{"name":"Journal of biomolecular research & therapeutics","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373195/pdf/nihms-1559748.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39328451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly Teske, Premchendar Nandhikonda, Jonathan W Bogart, Belaynesh Feleke, Preetpal Sidhu, Nina Yuan, Joshua Preston, Robin Goy, Leggy A Arnold
{"title":"Modulation of Transcription mediated by the Vitamin D Receptor and the Peroxisome Proliferator-Activated Receptor δ in the presence of GW0742 analogs.","authors":"Kelly Teske, Premchendar Nandhikonda, Jonathan W Bogart, Belaynesh Feleke, Preetpal Sidhu, Nina Yuan, Joshua Preston, Robin Goy, Leggy A Arnold","doi":"10.4172/2167-7956.1000111","DOIUrl":"https://doi.org/10.4172/2167-7956.1000111","url":null,"abstract":"<p><p>Herein we describe the evaluation of GW0742 analogs in respect to their ability to modulate transcription mediated by the vitamin D receptor (VDR) and the peroxisome proliferator activated receptor (PPAR) δ. The GW0742 analog bearing a carboxylic ester functionality in place of the carboxylic acid was partially activating both nuclear receptors at low concentration and inhibited transcription at higher compound concentrations. The GW0742 alcohol derivative was more active than the ester in respect to VDR but less active in regard to PPARδ. Importantly, the alcohol derivative was significantly more toxic than the corresponding acid and ester.</p>","PeriodicalId":90579,"journal":{"name":"Journal of biomolecular research & therapeutics","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255951/pdf/nihms597059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32888964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}