L-tryptophan production by Escherichia coli in the presence of Iranian cane molasses

The essential amino acid L-tryptophan (Trp) has importance as a pharmaceutical agent, especially in neuro-medicine. It is also added to feed products as a food fortifier. Furthermore, application of Trp is widespread in biotechnology. Trp is produced by a condensation reaction between indole and L-serine, which is catalyzed by bacterial tryptophanase activity. In this study, we have investigated Trp production using microbial system in the presence and absence of its precursors and Iranian cane molasses. The results showed that the optimum concentration of the molasses for maximum bacterial growth is 10 g/lit. Furthermore, in order to assay the amount of tryptophan produced, thin layer chromatography was used. The results showed that Iranian cane molasses contains considerable amounts of serine and indole, enough for Trp production (0.48 mM) in culture medium. But additional indole has inhibitory effects on Trp production. The data are compatible with previous reports on inhibitory effect of indole not only on cell growth but also on tryptophanase formation and function

In silico data analyses of the hotspot mutations of CHM gene in choroideremia disease

This data article provides compelling computational analysis of the hotspot CHM gene mutations that contribute to the progressive causativeness and susceptibility of Choroideremia in patients. We performed structural and molecular dynamics (MD) simulation analysis on abnormal states of the CHM protein caused by deleterious and disease-causing hotspot mutant forms of CHM: S89C, E177K, and V529H. Within 40 ns, MD simulation time composed of the E177K mutant shows conformational alteration especially in several parts of the variant. Mathematically, we applied eigenvector analysis to determine the modes of flexibility and atomic positional fluctuations that contribute significantly to the overall motion of the CHM protein in terms of structural alteration, free energy landscapes (FEL), entropy, enthalpy, and principal component analysis (PCA).The data described here are related to the article entitled “Molecular Genetics Characterization and Homology Modeling of the CHM Gene Mutation: A study on Its Association with Choroideremia” (Imani et al., 2018) [1]. Keywords: In silico, Choroideremia, Rab escort protein 1, Molecular dynamic simulatio

Effects of Herbal Compound (IMOD) on Behavior and Expression of Alzheimer's Disease Related Genes in Streptozotocin-Rat Model of Sporadic Alzheimer’s Disease

Purpose: Sporadic Alzheimer’s disease (AD) accounts for over 95% of cases. Possible mechanisms of AD such as inflammation and oxidative stresses in the brain motivate researchers to follow many therapies which would be effective, especially in the early stages of the disease. IMOD, the herbal extract of R. Canina, T. Vulgare and U. Dioica plant species enriched with selenium, has anti-inflammatory, immunoregulatory and protective effects against oxidative stress. Methods: In this study three AD-related genes, DAXX, NFκβ and VEGF, were chosen as candidate to investigate the neuroprotective effect of the extract by comparing their expression levels in the hippocampus of rat model of sporadic AD, using qPCR in the herbal-treated and control groups. The therapeutic effects on learning and memory levels were evaluated by Morris Water Maze (MWM) test. Results: Gene expression results were indicative of significant up-regulation of Vegf in rat’s hippocampus after treatment with the herbal extract comparing to model group (P-value= 0.001). The MWM results showed significant changes in path length and time for finding the hidden platform in all groups during test and the same change in the treated comparing to the control group in memory level. Conclusion: It could be concluded that the herbal extract may have significant effect on gene expression but not on behavioral level

Effects of Ectoine on Behavior and Candidate Genes Expression in ICV-STZ Rat Model of Sporadic Alzheimer’s Disease

Purpose: Alzheimer’s disease (AD) is pathologically defined by the presence of amyloid plaques and tangles in the brain, therefore, any drug or compound with potential effect on lowering amyloid plaques, could be noticed for AD management especially in the primary phases of the disease. Ectoine constitutes a group of small molecule chaperones (SMCs). SMCs inhibit proteins and other changeable macromolecular structures misfolding from environmental stresses. Ectoine has been reported successfully prohibit insulin amyloid formation in vitro. Methods: We selected eight genes, DAXX, NFκβ, VEGF, PSEN1, MTAP2, SYP, MAPK3 and TNFα genes which had previously showed significant differential expression in Alzheimer human brain and STZ- rat model. We considered the neuroprotective efficacy by comparing the expression of candidate genes levels in the hippocampus of rat model of Sopradic Alzheimer’s disease (SAD), using qPCR in compound-treated and control groups as well as therapeutic effects at learning and memory levels by using Morris Water Maze (MWM) test. Results: Our results showed significant down-regulation of Syp, Mapk3 and Tnfα and up-regulation of Vegf in rat’s hippocampus after treatment with ectoine comparing to the STZ-induced group. In MWM, there was no significant change in swimming distance and time for finding the hidden platform in treated comparing to STZ-induced group. In addition, it wasn’t seen significant change in compound-treated comparing to STZ-induced and control groups in memory level. Conclusion: It seems this compound may have significant effect on expression level of some AD- related genes but not on clinical levels

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways.

To discover vulnerabilities associated with dermokine (DMKN) as a new trigger of the epithelial-mesenchymal transition (EMT) -driven melanoma, we undertook a genome-wide genetic screening using transgenic. Here, we showed that DMKN expression could be constitutively increased in human malignant melanoma (MM) and that this correlates with poor overall survival in melanoma patients, especially in BRAF-mutated MM samples. Furthermore, in vitro, knockdown of DMKN inhibited the cell proliferation, migration, invasion, and apoptosis of MM cancer cells by the activation of ERK/MAPK signaling pathways and regulator of STAT3 in downstream molecular. By interrogating the in vitro melanoma dataset and characterization of advanced melanoma samples, we found that DMKN downregulated the EMT-like transcriptional program by disrupting EMT cortical actin, increasing the expression of epithelial markers, and decreasing the expression of mesenchymal markers. In addition, whole exome sequencing was presented with p.E69D and p.V91A DMKN mutations as a novel somatic loss of function mutations in those patients. Moreover, our purposeful proof-of-principle modeled the interaction of ERK with p.E69D and p.V91A DMKN mutations in the ERK-MAPK kinas signaling that may be naturally associated with triggering the EMT during melanomagenesis. Altogether, these findings provide preclinical evidence for the role of DMKN in shaping the EMT-like melanoma phenotype and introduced DMKN as a new exceptional responder for personalized MM therapy

Novel splicing variant c. 208+2T>C in BBS5 segregates with Bardet-Biedl syndrome in an Iranian family by targeted exome sequencing.

Bardet-Biedl syndrome (BBS) is a rare genetically heterogeneous ciliopathy which accompanies retinitis pigmentosa (RP). However, the BBS5 mutation remains unclear in Iranians with BBS. The purpose of study is to evaluate genetic analyses of a BBS Iranian family using targetted exome sequencing (TES). A male 11-year-old proband and three related family members were recruited. Biochemical tests, electrocardiography and visual acuity testing, such as funduscopic, fundus photography (FP), optical coherence tomography (OCT), and standard electroretinography, were conducted. Molecular analysis and high-throughput DNA sequence analysis were performed. The proband was diagnosed with possible BBS based on the presence of three primary features and two secondary features. The TES analysis of the proband with BBS resulted in the identification of a novel, homozygous splicing variant c. 208+2T>C of the BBS5 gene (NM_152384.2) in this Iranian BBS family. This variant was confirmed and was completely co-segregated with the disease in this family by Sanger sequencing. Thus, we report a novel, homozygous splicing site variant c.208+2T>C in the BBS5 gene for the first time in the Iranian family

Identification of a novel RPGRIP1 mutation in an Iranian family with leber congenital amaurosis by exome sequencing.

Leber congenital amaurosis (LCA) is a heterogeneous, early-onset inherited retinal dystrophy, which is associated with severe visual impairment. We aimed to determine the disease-causing variants in Iranian LCA and evaluate the clinical implications. Clinically, a possible LCA disease was found through diagnostic imaging, such as fundus photography, autofluorescence and optical coherence tomography. All affected patients showed typical eye symptoms associated with LCA including narrow arterioles, blindness, pigmentary changes and nystagmus. Target exome sequencing was performed to analyse the proband DNA. A homozygous novel c. 2889delT  (p.P963 fs) mutation in the RPGRIP1 gene was identified, which was likely the deleterious and pathogenic mutation in the proband. Structurally, this mutation lost a retinitis pigmentosa GTPase regulator (RPGR)-interacting domain at the C-terminus which most likely impaired stability in the RPGRIP1 with the distribution of polarised proteins in the cilium connecting process. Sanger sequencing showed complete co-segregation  in this pedigree. This study provides compelling evidence that the c. 2889delT  (p.P963 fs) mutation in the RPGRIP1 gene works as a pathogenic mutation that contributes to the progression of LCA

DMKN knockdown inhibits proliferation and invasion in advanced melanoma cell lines.

The dmkn gene (A) and protein (B) levels in DMKN-shRNA-transduced cells (shDMKN) compare to that in lentivirus-scrambled control (NC). Analysis of cell invasion by using a modified Boyden Chamber assay. in lentivirus control and DMKN-shRNA-transfected in the C8161 and MUM-2B cell lines. Microscopic picture of invaded cells (C) represents Bar graph (D) and the number of cells invaded the matrigel. (E) Relative cell viability of shDMKN (red line) or NC (black line) cells. Cell proliferation values are presented as the mean SEM of three independent tests. Values are as mean ± SEM, n = 3, **p < 0.001 for NC. The grouping of western blot gel cropped from different parts of the same gel. During the invasion assay, the leftover supernatants on the upper chamber of the transwell insert were collected from all the treatments of both cells.</p

The common oncogenic variables in the study of patients.

The common oncogenic variables in the study of patients.</p

The relative contribution of somatically point mutation variants between DMKN-shRNA lentivirus (KD) and GFP lentivirus (NC) control in MUM-2B cell line.

The relative contribution of somatically point mutation variants between DMKN-shRNA lentivirus (KD) and GFP lentivirus (NC) control in MUM-2B cell line.</p