Bacteriorhodopsin and its Mutants allude a breakthrough impending to artificial retina construction and strategies for curing blindness

       Bacteriorhodopsin, a model system in nanobiotechnology, is a light-sensitive protein found in the archaean Halobacterium salinarum and a very identical protein to visual Rhodopsin. The modification of biological function of BR and its versatile properties is valuable for technical applications including the artificial retina. These photoactive elements of native and particular mutants of bacteriorhodopsin make protein films, used in artificial retinal implants, to treat some retinal diseases and disorders. The two major reasons of retinal photoreceptor cell deterioration are Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP). As in vitro culture of Halobacterium is very difficult, and isolation procedure is much time consuming and usually inefficient, so genetic construction of protein is essential. Here, we have produced two types of bacteriorhodopsin, a native and a mutant BR (D85E) and studied their opto-electric responses with respect to wavelength and absorption properties. They are prerequisite for designing artificial retina (sensors) based on biomolecules. Therefore, the new promising technology soon will conceivably eradicate the blindness

A Mutational Hotspot in The LAMP2 Gene: Unravelling Intrafamilial Phenotypic Variation and Global Distribution of The c.877C>T Variant: A Descriptive Study

Objective: Danon disease is defined by a clinical trio of cardiomyopathy, skeletal myopathy, and cognitive impairment.It results from the lysosomal-associated membrane protein-2 (LAMP2) gene variants. The aim of study is determinationof genotype and phenotype of a newly diagnosed Iranian family with a unique phenotype due to a pathogenic variantof the LAMP2 gene along with a phenotypic comparison of all reported patients.Materials and Methods: In this descriptive study, we evaluated the demographic data, clinical features, managementprocedures, as well as genetic analysis of both patients in this newly diagnosed family. Whole genome sequencing(WGS) and in silico structural and functional predictions were applied. A comprehensive search of the c.877C>T variantin LAMP2 was conducted using the PubMed, Google Scholar, VarSome, ClinVar, Human Gene Mutation Database(HGMD), and Franklin databases to identify any genotype-phenotype correlations.Results: Nine patients were carriers of the c.877C>T variant. All patients were male, and displayed variable degreesof left ventricular hypertrophy (LVH) that ranged from mild to severe. All patients exhibited typical cardiac conductionabnormalities consistent with Danon disease. Four underwent heart transplants and survived. Skeletal muscleinvolvement and cognitive impairment were observed in four patients each. The mean age of onset was 14 years. Theproband in this study exhibited an earlier onset of cardiac symptoms.Conclusion: Genetic analysis is the preferred diagnosis approach for Danon disease and can assist families inmanaging affected patients, identify carriers, and assist with future family planning. This study highlights the intrafamilialphenotypic variability of Danon disease. It is possible that variants of this gene may be frequent in Iran

Antisense PNA accumulates in Escherichia coli and mediates a long post-antibiotic effect

Antisense agents that target growth-essential genes display surprisingly potent bactericidal properties. In particular, peptide nucleic acid (PNA) and phosphorodiamidate morpholino oligomers linked to cationic carrier peptides are effective in time kill assays and as inhibitors of bacterial peritonitis in mice. It is unclear how these relatively large antimicrobials overcome stringent bacterial barriers and mediate killing. Here we determined the transit kinetics of peptide-PNAs and observed an accumulation of cell-associated PNA in Escherichia coli and slow efflux. An inhibitor of drug efflux pumps did not alter peptide-PNA potency, indicating a lack of active efflux from cells. Consistent with cell retention, the post-antibiotic effect (PAE) of the anti-acyl carrier protein (acpP) peptide-PNA was greater than 11 hours. Bacterial cell accumulation and a long PAE are properties of significant interest for antimicrobial development.Peer reviewe

Orphan GPR26 Counteracts Early Phases of Hyperglycemia-Mediated Monocyte Activation and Is Suppressed in Diabetic Patients

Diabetes is the ninth leading cause of death, with an estimated 1.5 million deaths worldwide. Type 2 diabetes (T2D) results from the body's ineffective use of insulin and is largely the result of excess body weight and physical inactivity. T2D increases the risk of cardiovascular diseases, retinopathy, and kidney failure by two-to three-fold. Hyperglycemia, as a hallmark of diabetes, acts as a potent stimulator of inflammatory condition by activating endothelial cells and by dysregulating monocyte activation. G-protein couple receptors (GPCRs) can both exacerbate and promote inflammatory resolution. Genome-wide association studies (GWAS) indicate that GPCRs are differentially regulated in inflammatory and vessel cells from diabetic patients. However, most of these GPCRs are orphan receptors, for which the mechanism of action in diabetes is unknown. Our data indicated that orphan GPCR26 is downregulated in the PBMC isolated from T2D patients. In contrast, GPR26 was initially upregulated in human monocytes and PBMC treated with high glucose (HG) levels and then decreased upon chronic and prolonged HG exposure. GPR26 levels were decreased in T2D patients treated with insulin compared to non-insulin treated patients. Moreover, GPR26 inversely correlated with the BMI and the HbA1c of diabetic compared to non-diabetic patients. Knockdown of GPR26 enhanced monocyte ROS production, MAPK signaling, pro-inflammatory activation, monocyte adhesion to ECs, and enhanced the activity of Caspase 3, a pro-apoptotic molecule. The same mechanisms were activated by HG and exacerbated when GPR26 was knocked down. Hence, our data indicated that GPR26 is initially activated to protect monocytes from HG and is inhibited under chronic hyperglycemic conditions

In Vitro Comparative Study on Antineoplastic Effects of Pinoresinol and Lariciresinol on Healthy Cells and Breast Cancer-Derived Human Cells

Background: Herbal medicines are the preferred anticancer agents due to their lower cytotoxic effects on healthy cells. Plant lignans play an important role in treating various diseases, especially cancer. The present study aimed to evaluate the effect of podophyllotoxin, pinoresinol, and lariciresinol on cellular toxicity and inducing apoptosis in fibroblasts, HEK-293, and SkBr3 cell lines.Methods: An in vitro study was conducted from 2017 to 2019 at the Faculty of Biological Sciences, Tarbiat Modares University (Tehran, Iran). The cell lines were treated for 24 and 48 hours with different concentrations of lignans. Cell viability and apoptosis were examined using MTT and flow cytometry, respectively. Expression levels of cell cycle and apoptosis regulator genes were determined using quantitative real-time polymerase chain reaction. Data were analyzed using a two-way analysis of variance followed by Tukey’s HSD test. P<0.05 was considered statistically significant.Results: Podophyllotoxin significantly increased apoptosis in fibroblast cells compared to pinoresinol and lariciresinol (P<0.001). The percentage of cell viability of fibroblast cells treated for 48 hours with pinoresinol, lariciresinol, and podophyllotoxin was reduced by 49%, 47%, and 36%, respectively. Treatment with pinoresinol and lariciresinol significantly overexpressed pro-apoptotic genes and underexpressed anti-apoptotic genes in SkBr3 cells (P<0.001). SkBr3 cells treated with lariciresinol significantly reduced gene expression (P<0.001). Conclusion: Pinoresinol and lariciresinol can potentially be used as new therapeutic agents for the treatment of breast cancer

Detection of Intracellular Adhesion (ica) Gene and Biofilm Formation Staphylococcus aureus Isolates from Clinical Blood Cultures

Background: In fact the biofilms are composed of bacterial cells living inmulticellular structures such as tissues and organs embedded within a self-produced matrix of extracellular polymeric substance (EPS). Ability to attach and biofilm formation are the most important virulence factors Staphylococcus aureus isolates. The aims of this study were to detect intracellular adhesion (ica) locus and its relation to the biofilm formation phenotype in clinical isolates of S. aureus isolated from bloodcultures. Methods: A total of 31 clinical S. aureus isolates were collected from Loghman Hospital of Tehran, Iran. In vitro biofilm formation ability was determined by microliter tissue culture plates. All clinical isolates were examined for determination the ica locus by using PCR method. Results: Twelve (38.7%) of the isolates were strong biofilm producers. The results showed that 18(80.6%) of the isolates carried icaD gene, whereas the prevalence of icaA, icaB and icaC were 51.6%, 45.1% and 77.4% respectively. Conclusions: S. aureus clinical isolates have different ability to form biofilm. This may be caused by the differences in the expression of biofilm related genes, genetic make-up and physiological conditions

NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals

Mammalian inosine triphosphatase encoded by ITPA gene hydrolyzes ITP and dITP to monophosphates, avoiding their deleterious effects. Itpa− mice exhibited perinatal lethality, and significantly higher levels of inosine in cellular RNA and deoxyinosine in nuclear DNA were detected in Itpa− embryos than in wild-type embryos. Therefore, we examined the effects of ITPA deficiency on mouse embryonic fibroblasts (MEFs). Itpa− primary MEFs lacking ITP-hydrolyzing activity exhibited a prolonged doubling time, increased chromosome abnormalities and accumulation of single-strand breaks in nuclear DNA, compared with primary MEFs prepared from wild-type embryos. However, immortalized Itpa− MEFs had neither of these phenotypes and had a significantly higher ITP/IDP-hydrolyzing activity than Itpa− embryos or primary MEFs. Mammalian NUDT16 proteins exhibit strong dIDP/IDP-hydrolyzing activity and similarly low levels of Nudt16 mRNA and protein were detected in primary MEFs derived from both wild-type and Itpa− embryos. However, immortalized Itpa− MEFs expressed significantly higher levels of Nudt16 than the wild type. Moreover, introduction of silencing RNAs against Nudt16 into immortalized Itpa− MEFs reproduced ITPA-deficient phenotypes. We thus conclude that NUDT16 and ITPA play a dual protective role for eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals

The urgent need for integrated science to fight COVID-19 pandemic and beyond

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑ tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics