Determining the Reference Range of Amino Acids in Healthy Neonatal Blood Samples in Northeast Iran Using LC-MS/MS.

Background: Amino acid analysis is an important tool for the diagnosis of metabolic disorders in newborns. Today, Liquid Chromatography tandem mass spectrometry (LC-MS/MS) has emerged as a powerful technique for amino acid analysis. We aimed to determine the local normal range of amino acids in dried blood spot (DBS) samples of neonates using LC-MS/MS.

Determination of Normal Range of Acylcarnitine in Neonatal Dried Blood Spots using LC-MS/MS.

Background: Acylcarnitine is one of the crucial markers of fatty acid metabolism, and examination of their level in infants can reveal several Inherited Metabolic Disorders (IDM) or Inborn errors of Metabolism (IEM). Because of the great importance of hereditary, metabolic, and other inherited disorders early diagnosis before the appearance of clinical symptoms, this study was carried out to establish a reference range for carnitine analytes and to identify acylcarnitine profiles in normal weight neonatal dried blood spots (DBS) specimens.

Methods: By using liquid chromatography tandem mass spectrometry (LC-MS/MS) for neonatal screening and eventually the examination and analysis of LC-MS/MS results, 34 acylcarnitine derivatives were identified.

Advances in the treatment of human T-cell lymphotropic virus type-I associated myelopathy.

Introduction: Nearly 2-3% of those 10 to 20 million individuals infected with the Human T-cell lymphotropic virus type-1 (HTLV-1); are predisposed to developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is a neuro-inflammatory disease; differentiated from multiple sclerosis based on the presence of typical neurologic symptoms, confirmation of HTLV-1 infection, and other molecular biomarkers.

Areas Covered: A brief review of the epidemiology, host immune responses, and molecular pathogenesis of HAM/TSP is followed by detailed discussions about the host-related risk factors for developing HAM/TSP and success/failure stories of the attempted management strategies.

Rigosertib is more potent than wortmannin and rapamycin against adult T-cell leukemia-lymphoma.

Human T lymphotropic virus type 1 (HTLV-1) infection can cause adult T-cell lymphoblastic leukemia (ATLL), an incurable, chemotherapy-resistant malignancy. In a quest for new therapeutic targets, our study sought to determine the levels of AKT, mTOR, and PI3K in ATLL MT-2 cells, HTLV-1 infected NIH/3T3 cells (Inf-3T3), and HTLV-1 infected patients (Carrier, HAM/TSP, and ATLL). Furthermore, the effects of rigosertib, wortmannin, and rapamycin on the PI3K/Akt/mTOR pathway to inhibit the proliferation of ATLL cells were examined.

Fenugreek Seed Extract Regulates Human Umbilical Vein Endothelial Cell Angiogenesis and Proliferation via the PI3K/Akt/Cyclin D1 Pathway.

The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs).

Development of Potential Inhibitors for Human T-lymphotropic Virus Type I Integrase Enzyme: A Molecular Modeling Approach.

Introduction: Integration of viral DNA into the host cell genome, carried out by the HTLV-1 integrase enzyme, is a crucial step in the Human T-lymphotropic Virus type I (HTLV-1) life cycle. Thus, HTLV-1 integrase is considered an attractive therapeutic target; however, no clinically effective inhibitors are available to treat HTLV-1 infection.

Objective: The main objective was to identify potential drug-like compounds capable of effectively inhibiting HTLV-1 integrase activity.

The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes.

Prostate cancer is one of the main global health threats for men which is in close association with chronic inflammation. Neuropeptide substance P (SP), acting through neurokinin receptor (NK-1R), induces various pro-inflammatory responses which are strongly involved in the pathogenesis of several diseases as well as cancer. Therefore, we aimed to investigate the pro-inflammatory functions of the SP/NK1R complex in prostate cancer and the therapeutic effects of its inhibition by NK-1R antagonist, aprepitant, in vitro.

Molecular insight into the study of adult T-cell leukemia/lymphoma (ATLL): Ten-year studies on HTLV-1 associated diseases in an endemic region.

The outcome of successful infection, including human T-cell leukemia virus type 1 (HTLV-1), is determined by the interactions between the host and the infectious agent. Ten years of work on HTLV-1-associated diseases in an endemic region of Iran have been critically compared in the present study. The outstanding findings of RNA-seq, system biology analysis, and gene expression measurements on adult T-cell leukemia/lymphoma (ATLL) and enzootic bovine leukosis(EBL) in our lab encouraged us to investigate the significant role of oncogenes in the ATLL malignancy.

Glutathione reductase system changes in HTLV-1 infected patients.

Unlabelled: During chronic HTLV-1 infections oxidative stress occurs and contributes in viral pathogenesis. Glutaredoxin (Grx) system is one of the most effective antioxidant components. The system maintains the cellular redox and scavenges reactive oxygen species through the function of glutathione reductase (GR) enzyme, NADPH and reduced glutathione (GSH).

Challenges of expressing recombinant human tissue factor as a secreted protein in .

Tissue factor (TF) is the core reagent in the prothrombin time (PT) assay. In this study, expression and α-factor mediated secretion of three forms of tissue factor (full-length TF (Full-TF), extracellular plus transmembrane domain (TED-TF), and only extracellular domain (ED-TF) were investigated in . The amino acid sequence of TF was obtained from the UniProt database, back-translated and codon-optimized for expression in .

Interleukin-6 as A Prognostic Biomarker in Perinatal Asphyxia.

Objective: Early diagnosis is has a crucial role in both prevention and treatment of asphyxia-related complications. The current study aimed to evaluate the prognostic value of interleukin-6 (IL-6) and hypoxic-ischemic encephalopathy grade in the prediction of mortality and the developmental status of neonates affected by prenatal asphyxia.

Materials & Methods: This cohort study was conducted on 38 term asphyxiated infants at Ghaem hospital, Mashhad, Iran, from 2013 to 2017.

The Level of Mesenchymal-Epithelial Transition Autophosphorylation is Correlated with Esophageal Squamous Cell Carcinoma Migration.

Background: The MET receptor is a critical member of cancer-associated receptor tyrosine kinases and plays an important role in different biological activities, including differentiation, migration, and cell proliferation.

Methods: In this study, novel MET inhibitors were introduced and applied on esophageal squamous carcinoma cell line KYSE-30, and the level of proliferation and migration, as well as the activated form of MET receptor protein were assessed in the examined cells. The human KYSE-30 cell line was cultured according to ATCC recommendations.

PD-1 and PD-L1 inhibitors foster the progression of adult T-cell Leukemia/Lymphoma.

Immunotherapy through immune checkpoints blockade and its subsequent clinical application has revolutionized the treatment of a spectrum of solid tumors. Blockade of Programmed cell death protein-1 and its ligand has shown promising results in clinical studies. The clinical trials that enrolled patients with different hematopoietic malignancies including non-Hodgkin lymphoma, Hodgkin lymphoma, and acute myeloid leukemia (AML) showed that anti-PD-1 agents could have potential therapeutic effects in the patients.

Protective effects of BiP inducer X (BIX) against diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DC) is associated with impaired endoplasmic reticulum (ER) function, development of ER stress, and induction of cardiac cell apoptosis. Preventive effects of BiP inducer X (BIX) were investigated against DC characteristic changes in a type 2 diabetes rat model. To establish diabetes, a high-fat diet and a single dose of streptozotocin were administered.

Application of Molecular Docking for the Development of Improved HIV-1 Reverse Transcriptase Inhibitors.

Introduction: Inhibition of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV) by low molecular weight inhibitors is still an active area of research. Here, protein-ligand interactions and possible binding modes of novel compounds with the HIV-1 RT binding pocket (the wild-type as well as Y181C and K103N mutants) were obtained and discussed.

Methods: A molecular fragment-based approach using FDA-approved drugs were followed to design novel chemical derivatives using delavirdine, efavirenz, etravirine and rilpivirine as the scaffolds.

Substance P accelerates the progression of human esophageal squamous cell carcinoma via MMP-2, MMP-9, VEGF-A, and VEGFR1 overexpression.

Tachykinins such as Substance P (SP) are a group of neuropeptides that are involved in cancer development. Neurokinin-1 receptor (NK-1R) is the main tachykinin receptor mediating the effects of SP, which is overexpressed in human esophageal squamous cell carcinoma (ESCC) and other malignant tissues. However, the effects of SP/NK-1R system on the migration of esophageal cancer cells and angiogenesis is not clear yet.

Construction of Epstein-Bar virus cocktail peptide fused with Fcγ of IgG: as a potential delivery system for vaccine development.

Epstein-Barr virus (EBV) associated with several diseases such as contagious mononucleosis chronic active EBV infection, and diverse sorts of malignant tumors. Therefore, using applicable vaccines could be advantageous for public health. Yet, the vaccine has been unavailable to protect from EBV so far.

Designing a multifunctional staphylokinase variant (SAK-2RGD-TTI) with appropriate thrombolytic activity in vitro.

Objective: Thrombin, platelets, and plasmin are three key factors involved in hemostasis and thrombolysis. Thrombolytic therapy with clinically approved drugs is often followed by recurrent thrombosis caused by thrombin-induced platelet aggregation from the clot debris. In order to minimize these problems, new constructs were designed for the expression of recombinant staphylokinase (rSAK) and also a fusion protein composed of staphylokinase, 20 amino acids containing 2 RGD followed by tsetse thrombin Inhibitor (SAK-2RGD-TTI) in Pichia pastoris.

Bacterial staphylokinase as a promising third-generation drug in the treatment for vascular occlusion.

Vascular occlusion is one of the major causes of mortality and morbidity. Blood vessel blockage can lead to thrombotic complications such as myocardial infarction, stroke, deep venous thrombosis, peripheral occlusive disease, and pulmonary embolism. Thrombolytic therapy currently aims to rectify this through the administration of recombinant tissue plasminogen activator.

Complete sequence of human T cell leukemia virus type 1 in ATLL patients from Northeast Iran, Mashhad revealed a prematurely terminated protease and an elongated pX open reading frame III.

To gain insight into the origin, evolution, dissemination and viral factors affecting HTLV-1-associated diseases, knowing the complete viral genome sequences is important. So far, no full-length HTLV-1 genome sequence has been reported from Iran. Here we report the complete nucleotide sequence of HTLV-1 viruses isolated from adult T cell leukemia/lymphoma (ATLL) patients from this region.

Comparison of expression optimization of new derivative of staphylokinase (SAK-2RGD-TTI) with the rSAK.

Staphylokinase (SAK) is a promising thrombolytic agent for the treatment of patients suffering from blood-clotting disorders. To increase the potency of SAK and to minimize vessel reocclusion, a new construct bearing SAK motif fused to tsetse thrombin inhibitor (TTI) via a 20-amino acid linker with 2 RGD (2 × arginine-glycine-aspartic acid inhibiting platelet aggregation via attachment to integrin receptors of platelet) was codon optimized and expressed comparatively in Pichia pastoris GS115 as a Mut strain and KM71H as a Mut strain. Fusion protein was optimized in terms of best expression condition and fibrinolytic activity and compared with the rSAK.

Production of Universal Group O Red Blood Cells by Alpha--Acetylgalactosaminidase Enzyme Expressed in .

Enzymatic removal of blood groups antigens A and B is an efficient method for production of universal red blood cells. In this research, an α--acetylgalactosaminidase (NAGA) enzyme was expressed in for digestion of the A blood antigen. DNA sequence of the gene NAGA, originally expressed in Elizabethkingia meningosepticum (NAGA-EM), was ordered for optimization and synthesis.

Molecular targeting for treatment of human T-lymphotropic virus type 1 infection.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15-20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies.