Diagnostic,prognostic, and therapeutic potency of microRNA 21 in the pathogenesis of colon cancer,current status and prospective

Aberrant microRNA (miR) expression is implicated in multiple human malignancies. miR-21, acting as a proto-oncogene, is involved in a variety of cellular processes and tumorigenesis and is frequently overexpressed in some cancer types. Several tumor suppressors, metastatic, and apoptotic genes have been identified as miR-21 targets, including Ras homolog gene family member B, PTEN, Sprouty2, programmed cell death 4, Integrin-β4, and E-cadherin thereby regulating tumor growth, invasion, and metastasis. There is a growing evidence that miR-21 expression is associated with clinical outcomes in patients with colorectal cancer (CRC). In this review, we summarize the potential diagnostic, prognostic, and therapeutic values of miR-21 in CRC progression for a better understanding and hence a better management of this disease.     

A Compact Nanoplasmonics Filter and Intersection Structure Based on Utilizing a Slot Cavity and a Fabry–Perot Resonator

By combining a Fabry–Perot (FP) cavity with a slot cavity, a compact filter structure is proposed. The peak resonance wavelength is determined by applying the FP resonance condition of the FP cavity. The relationship between filtering wavelength and cavity parameters is investigated. The results show that the filtering wavelength can be manipulated by changing the nanocavities' parameters. By using the finite difference time domain method, the theoretical predictions are confirmed. An intersection structure for nanoplasmonic waveguides is proposed and designed by utilizing two perpendicular filters. In addition to having compact dimensions, the proposed arrangement provides higher throughput and low cross talk. The proposed structure can be useful for designing compact integrated nanoplasmonic circuits.     

Mitochondria,spermatogenesis and male infertility

Mitochondria and its role in male reproduction has remained an enigma since long. Similarly, etiology of male infertility in a large percentage of individuals, mainly primary infertility, has evaded concrete conclusions. Oxidative metabolism, energy production and free radical generation are the principal biological reactions occurring inside mitochondria. In addition to the above, mitochondria participates in an important process of apoptosis. Mitochondrial causes of infertility have triggered interest because of its presence in the tail of sperm and immense need of energy for sperm motility. Several studies on mitochondria have strongly suggested its role in fertility, some of which support mitochondrial role presenting numerous hypotheses, whereas others deny its very existence as a causative factor. We have, in the present review of existing literature, covered the role of mitochondria right from spermatogenesis to male infertility.     

Enhancement of human granulocyte-colony stimulating factor production in recombinant E. coli using batch cultivation

Development of inexpensive and simple culture media is always favorable for recombinant protein over-expression in E. coli. The effects of medium composition on the production of recombinant human granulocyte-colony stimulating factor (rh-GCSF) were investigated in batch culture of E. coli BL21 (DE3) [pET23a-hgcsf]. First, the optimum medium for production of rh-GCSF was determined; and, then it was shown that mixture of amino acid addition at induction time, which was determined on the basis of amino acids frequency in the recombinant protein, increases recombinant protein expression level significantly. Furthermore, the effect of glucose concentration on productivity of rh-GCSF was investigated; 20 g/l of glucose will result in maximum attainable biomass and rh-GCSF in this process. At optimum conditions, a cell dry weight of 10.5 g/l, an expression level of about 35% of total cellular protein, rh-GCSF concentration of 1.75 ± 0.1 g/l, and overall rh-GCSF yield of 165 ± 5 mg/g were obtained.     

Establishment of a Mouse Model with Misregulated Chromosome Condensation due to Defective Mcph1 Function

Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1^gt/gt mice, the overall survival rates of the Mcph1^gt/gt animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.     

Theoretical investigations on the hydrolysis pathway of tin verdoheme complexes: elucidation of tin’s ring opening inhibition role

In order to obtain a better molecular understanding of inhibitory role of tin metal in the verdoheme ring opening process, hydrolysis of three possibly six, five, and four coordinate verdoheme complexes of tin(IV) and (II) have been studied using DFT method. The results of calculations indicate that, in excellent accord with experimental reports, hydrolysis of different possibly coordinated tin(IV) and (II) verdohemes does not lead to the opening of the macrocycle. Contrary to iron and zinc verdohemes, in five and four coordinate verdoheme complexes of tin(IV) and (II), formation of open ring helical complexes of tin are unfavorable both thermodynamically and kinetically. In these pathways, coordination of hydroxide nucleophile to tin metal due to the highly charged, exclusive oxophilicity nature of the Sn center, and high affinity of Sn to increase coordination state are proposed responsible as inhibiting roles of tin via the ring opening. While, in saturated six coordinate tin(IV) and (II) verdoheme complexes the ring opening of tin verdohemes is possible thermodynamically, but it is not predicted to occur from a kinetics point of view. In the six coordinate pathway, tin plays no coordination role and direct addition of hydroxide nucleophile to the positive oxo-carbon centers and formation of closed ring hydroxy compounds is proposed for preventing the verdoheme ring opening. These key points and findings have been corroborated by the results obtained from atomic charge analysis, geometrical parameters, and molecular orbital calculations. In addition, the results of inhibiting ring opening reaction of tin verdoheme complexes could support the great interest of tin porphyrin analogues as pharmacologic means of chemoprevention of neonatal jaundice by the competitive inhibitory action of tin porphyrins on heme oxygenase.     

Association of Genetic polymorphism of PPARγ-2, ACE,MTHFR, FABP-2 and FTO genes in risk prediction of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a non-autoimmune, complex, heterogeneous and polygenic metabolic disease condition characterized by persistent elevated blood glucose levels (hyperglycemia). India as said to be the diabetic capital of the world is likely to experience the largest increase in T2DM and a greater number of diabetic individuals in the world by the year 2030. Identification of specific genetic variations in a particular ethnic group has a critical role in understanding the risk of developing T2DM in a much efficient way in future. These genetic variations include numerous types of polymorphisms among which single nucleotide polymorphisms (SNPs) is the most frequent. SNPs are basically located within the regulatory elements of several gene sequences. There are scores of genes interacting with various environmental factors affecting various pathways and sometimes even the whole signalling network that cause diseases like T2DM. This review discusses the biomarkers for early risk prediction of T2DM. Such predictions could be used in order to understand the pathogenesis of T2DM and to better diagnostics, treatment, and eventually prevention.     

Strong binding active constituents of phytochemical to BMPR1A promote bone regeneration: In vitro,in silico docking,and in vivo studies

Two of the most problematic orthopedic and neurosurgeon visits are associated with spine and craniofacial fractures. Therefore, more attention needs to be paid to finding a medicine to repair these fractures. Amongst the most mysterious herbs, Aloe vera stands out. In the present study, the ameliorating function of A. vera on osteogenesis was studied in vitro and in vivo. Osteoblast-like cells were exposed to A. vera, followed by analysis of cell viability, lactate dehydrogenase release, and intracellular reactive oxygen species (ROS) production. The results showed an enhanced cell biocompatibility in a dose-dependent manner due to attenuated intracellular ROS production. Furthermore, a docking study indicated that the strong affinity of A. vera constituents to type I bone morphogenic protein receptor (BMPR1A) without the involvement of the BMPR1A chain B. The induction of osteogenesis prompts extracellular calcium deposition by osteoblasts, which affirms successful in vitro bone regeneration. However, injection of A. vera in rats with critical size calvarial defects induced Runx2, alkaline phosphatase (ALP), OCN, and BMP2 genes overexpression, which led to the formation of victorious bone with enhanced bone density and ALP activity. It is worthy to note that Aloin has the highest affinity to BMPR1A, whereas there are no reports regarding the impact of Aloenin, Aloesin, and γ-sitosterol on osteogenesis. Furthermore, some of them have antitumor potency, and it might be proposed that they are considered as a bone substitute in the osteotomy site of osteosarcoma with the aim of bone recovery and suppression of osteosarcoma. The whole consequences of this investigation manifests the plausibility of using A. vera as an antioxidant and osteoconductive substitute.     

Electrospun triple-layered PLLA/gelatin. PRGF/PLLA scaffold induces fibroblast migration

The function of fibroblast cells in wounded areas results in reconstruction of the extra cellular matrix and consequently resolution of granulation tissue. It is suggested that the use of platelet-rich plasma can accelerate the healing process in nonhealing or slow-healing wounds. In this study, a simple and novel method has been used to fabricate an electrospun three-layered scaffold containing plasma rich in growth factor with the aim of increasing the proliferation and migration of fibroblast cells in vitro. First, plasma rich in growth factor was derived from platelet rich plasma, and then a three-layered scaffold was fabricated using PLLA nanofibers as the outer layers and plasma rich in growth factor-containing gelatin fibers as the internal layer. The growth morphology of cells seeded on this scaffold was compared to those seeded on one layered PLLA scaffold. The study of the cell growth rate on different substrates and the migration of cells in response to the drug release of multilayered scaffold was investigated by the cell quantification assay and a modified under agarose assay. Scanning electron microscopy and fluorescence images showed that cells seeded on multilayered scaffold were completely oriented 72 hours after seeding compared to those seeded on PLLA scaffold. The cell quantification assay also indicated significant increase in proliferation rate of cells seeded on three-layered scaffold compared to those seeded on PLLA scaffold and finally, monitoring cell migration proved that cells migrate significantly toward the three-layered scaffold up to 48 to 72 hours and afterwards start to show a diminished migration rate toward this scaffold.