Elevated HSP70 and HSP90 as Predictive Markers of Immune Activation and Lung Injury in SARS-COV-2 Disease

Background: Heat shock proteins (HSPs) are involved in innate and adaptive immune responses, especially inflammatory responses due to immune cell activation. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was one of the most important causes of death in the recent pandemic. Increased cellular stress and excessive inflammation are common in coronavirus disease-19 (COVID-19), although the underlying mechanisms are still poorlyunderstood.Objective: To evaluate the relationship between HSP and the pathological effects of COVID-19.Methods: A group of 107 patients was categorized to two populations (mild and severe) based on their chest high-resolution computed tomography (HRCT) results. The HSP70, HSP90 alpha, and serum levels of C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured by the automated analyzer.Results: Our data showed increased levels of HSP70 and HSP90 in patients with COVID-19. The HSPs levels were elevated in the severe group compared to the mild group. This study demonstrated a positive correlation between both elevated levels of HSP70, HSP90, and HRCT grade and also a positive correlation with CRP and CPK in the severe group.Conclusion: HSP90 and HSP70 contribute to excessive immune responses and cytokine storms. They may serve as prognostic serum markers for COVID-19 lung injury. Additionally, they arecandidates for anti-inflammatory therapy

Induced overexpression of MARCH-1 in human macrophages altered to M2 phenotype for suppressing inflammation process

Objective(s): The M1 macrophage is characterized by enhanced pro-inflammatory cytokines production, whereas macrophage (M2) has anti-inflammatory features. Macrophage polarization as a therapeutic target for controlling immune responses could be performed by gene transduction to control the regulation of exaggerated innate/adaptive immune responses. Materials and Methods: Macrophages were prepared from THP-1 cell line and human monocytes that were transduced with (Membrane-Associated RING-CH-type finger) MARCH-1 viral lentivector produced in HEK-293T cells. RT-PCR and Western blotting confirmed MARCH-1 gene transduction. Cytokine production, CD markers assay, macrophage phagocytosis potential activity and mixed leukocyte reaction (MLR) with CFSE were performed for M1/M2 plasticity. Results: The mean fluorescent intensity of HLA-DR and CD64 expression reduced in MARCH-1+ transduced macrophage population. However, CD206 and CD163 expression increased in these macrophages. The concentrations of IL-6, TNF-α and iNOS were decreased in MARCH-1 transduced cells, and TGF-β production showed an augmentation in concentration. Western blotting and real-time PCR measurement confirmed that the expression levels of MARCH-1 protein and arginase-1 enzyme were increased in transduced macrophages. Conclusion: The anti-inflammatory features of MARCH-1 revealed the reduced levels of pro-inflammatory factors and maintained M2 phenotype characterized by high levels of scavenger receptors. Therefore, targeting MARCH-1 in monocytes/macrophages could represent a new autologous cell-based therapies strategy for inflammatory conditions

Phylogenetic Groups of Escherichia coli Strains from Patients with Urinary Tract Infection in Iran Based on the New Clermont Phylotyping Method

Objectives.In2013,ClermontclassifiedE.colistrainsintoeightphylogeneticgroupsusinganewquadruplexPCRmethod.Theaims ofthisstudyweretoidentifythephylogeneticgroupsofE.colibasedonthismethodandtoassesstheirantibioticresistancepatterns inBushehr,Iran.Methods.Inthiscross-sectionalstudy,140E.coliisolatesweresubjectedtophylogenetictypingbyaquadruplex PCR method. Antimicrobial susceptibility testing was performed by disk diffusion method. Results. Phylogenetic group B2 was mostpredominant(39.3%),followedbyunknown(27.1%),E(9.3%),CandcladeI(each6.4%),B1(5%),FandD(each2.9%),and A(0.7%).Themostcommonantibioticresistancewasrelatedtoamoxicillin(82.1%)andtheleasttomeropenem(0.7%).82.14%of isolatesweremultipledrugresistant(MDR).AntibioticresistancewasmainlydetectedingroupB2(50%).Conclusions.Ourfindings showedthehighprevalenceofMDRE.coliisolateswithdominanceofgroupB2.About25%ofE.coliisolatesbelongtothenewly describedphylogroupsC,E,F,andcladeI.Suchstudiesneedtobedonealsoinotherregionstoprovidegreaterunderstandingof theantibioticresistancepatternandtheprevalencesofdifferentphylogeneticgroups

Mechanisms of tumor cell resistance to the current targeted-therapy agents

Abstract Resistance to chemotherapy agents is a major challenge infront of cancer patient treatment and researchers. It is known that several factors, such as multidrug resistance proteins and ATP-binding cassette families, are cell membrane transporters that can efflux several substrates such as chemotherapy agents from the cell cytoplasm. To reduce the adverse effects of chemotherapy agents, various targeted-based cancer therapy (TBCT) agents have been developed. TBCT has revolutionized cancer treatment, and several agents have shown more specific effects on tumor cells than chemotherapies. Small molecule inhibitors and monoclonal antibodies are specific agents that mostly target tumor cells but have low side effects on normal cells. Although these agents have been very useful for cancer treatment, however, the presence of natural and acquired resistance has blunted the advantages of targeted therapies. Therefore, development of new options might be necessary. A better understanding of tumor cell resistance mechanisms to current treatment agents may provide an appropriate platform for developing and improving new treatment modalities. Therefore, in this review, different mechanisms of tumor cell resistance to chemotherapy drugs and current targeted therapies have been described

Knockdown of microRNA-29a Changes the Expression of Heat Shock Proteins in Breast Carcinoma MCF-7 Cells

Breast cancer is the most commonly occurring cancer among women. MicroRNAs as noncoding small RNA molecules play pivotal roles in cancer-related biological processes. Increased levels of microRNA-29a in the serum of breast cancer patients have been reported. Since heat shock proteins (HSPs) play important roles in cell events, the quantitative fluctuations in their cellular levels could be deemed as key indicators of how the exerted treatment alters cell behavior. In this regard, using an antisense small RNA, we attempted to investigate the effects of miR-29a knockdown on the expression of HSPs genes in the MCF-7 breast cancer cell line. MCF-7 cells were cultured in high-glucose Dulbecco’s modified Eagle’s medium with 10% FBS. Studied cells were subdivided into five groups: treated with scramble, anti-miR-29a, anti-miR-29a + Taxol, Taxol, and control. Taxol was added 24 h post-anti-miR transfection and RNA extraction, and cDNA synthesis was done 48 h later. The changes in expression of HSP27, HSP40, HSP60, HSP70, and HSP90 were evaluated by real-time PCR. Our results revealed that inhibitors of microRNA-29a promote apoptosis through upregulation of HSP60 level and downregulation of HSP27, HSP40, HSP70, and HSP90 levels and could be contemplated as a compelling alternative for Taxol employment with similar effects and/or to sensitize cancer cells to chemotherapy with fewer side effects

Clinical Manifestations of β-Thalassemia Major in Two Different Altitudes; Bushehr and Shahrekord

Background: Patients with β-thalassemia major (TM) develop iron overload through increased iron absorption and transfusional therapy and it’s the most important complication of TM. Thalassemia is common in coastal regions and lands with low altitudes. The aim of this study is to determine the effect of high and low altitude on serum ferritin and treatment requirement in two groups of β-thalassemia major (TM) patients. Subjects and Methods: Patients were divided into two groups, the first group (No: 50) living at sea level (in the port of Bushehr, Iran) and the second group (No: 40) living at the altitude of 2061 m (in the city of Shahrekord, Iran). All patient’s clinical history, blood transfusion and laboratory tests including complete blood count and hemoglobin electrophoresis were reviewed. Results: There were no significant difference in ferritin levels, transfusion period and diabetes incidence of the two cities patients (P>0.05). Patient’s cardiac function and liver condition were significantly better in patients of Bushehr (P<0.05). Patients under 20 years in Bushehr were less splenectomized in comparison with Shahrekord (P<0.05). Conclusion: Our result showed that some of clinical manifestations of patients in low altitude such as cardiac and liver condition were better. But it did not affect ferritin level probably due to transfusion and chelating therapy. Totally patients of Bushehr had better conditions and had longer survivals. Keywords: β-thalassemia major, Ferritin level, Cardiac function, Altitud

The Evaluation of Nerve Growth Factor Over Expression on Neural Lineage Specific Genes in Human Mesenchymal Stem Cells

Objective Treatment and repair of neurodegenerative diseases such as brain tumors, spinal cord injuries, and functional disorders, including Alzheimer’s disease, are challenging problems. A common treatment approach for such disorders involves the use of mesenchymal stem cells (MSCs) as an alternative cell source to replace injured cells. However, use of these cells in hosts may potentially cause adverse outcomes such as tumorigenesis and uncontrolled differentiation. In attempt to generate mesenchymal derived neural cells, we have infected MSCs with recombinant lentiviruses that expressed nerve growth factor (NGF) and assessed their neural lineage genes. Materials and Methods In this experimental study, we cloned the NGF gene sequence into a helper dependent lentiviral vector that contained the green fluorescent protein (GFP) gene. The recombinant vector was amplified in DH5 bacterial cells. Recombinant viruses were generated in the human embryonic kidney 293 (HEK-293) packaging cell line with the helper vectors and analyzed under fluorescent microscopy. Bone marrow mesenchymal cells were infected by recombinant viruses for three days followed by assessment of neural differentiation. We evaluated expression of NGF through measurement of the NGF protein in culture medium by ELISA; neural specific genes were quantified by real-time polymerase chain reaction (PCR). Results We observed neural morphological changes after three days. Quantitative PCR showed that expressions of NESTIN, glial derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP) and Microtubule-associated protein 2 (MAP2) genes increased following induction of NGF overexpression, whereas expressions of endogenous NGF and brain derived neural growth factor (BDNF) genes reduced. Conclusion Ectopic expression of NGF can induce neurogenesis in MSCs. Direct injection of MSCs may cause tumorigenesis and an undesirable outcome. Therefore an alternative choice to overcome this obstacle may be the utilization of differentiated neural stem cells

Blood ordering and utilization in hospitals of Bushehr province

Cross over ordering of blood much in excess of actual or anticipated needs led to rising costs and transfusion associated morbidity. In order to reveal blood utilization, we evaluated blood ordering and transfusion practices in 437 cases in general surgery, obstetrics & gynecology , orthopedics, neurology and urology wards of different hospitals in Bushehr province using cross-match to transfusion ratio ( C/T ratio) and transfusion index ( TI ). The maximum (8.9) and minimum (1.2) ratios for C/T index were in obstetrics and gynecology and orthopedics wards, respectively. The maximum (1.85) and minimum (0.70) TI index were in orthopedics and obstetrics & gynecology wards, respectively. TI indices for general surgery and urology wards were 0.59 and 0.70, respectively. Therefore, blood ordering and transfusion practices in some wards of Bushehr hospitals, especially obstetrics and gynecology ward, should be reevaluated

Serum MicroRNAs: -28-3p, -31-5p, -378a-3p, and -382-5p as novel potential biomarkers in acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and accounts for 20% of acute leukemia in adults. Recently, microRNAs (miRNAs) have been described as important molecules in hematologic malignancies. This study aimed to evaluate the expression levels of miR-28-3p, miR-31-5p, miR-378a-3p, miR-382-5p in patients with ALL. Materials and methods In this study, 21 patients with ALL (before and after treatment) and 21 healthy people were evaluated. After directly synthesizing cDNA from serum, miR-28-3p, miR-31-5p, miR-378a-3p, miR-382-5p expression were measured using the qRT-PCR method. Data were analyzed using SPSS 20, Genex 6.1, and GraphPad Prism8 software. Results The expression levels of miR-378a-3p and miR-31-5p in patients with newly diagnosed ALL were significantly higher than in healthy individuals (P = 0.001, P = 0.004), and decreased significantly after treatment. (P = 0.04, P = 0.03). The expression of miR-28-3p and miR-382-5p in patients with newly diagnosed ALL were significantly lower than healthy individuals (P = 0.09, P = 0.01) and were increased significantly after treatment (P = 0.001, P = 0.006). Conclusion Our results indicated that miR-28-3p, miR-31-5p, miR-378a-3p, miR-382-5p may have a potential role in the pathogenesis of the disease; and also could be considered as a diagnostic marker and therapeutic target in ALL in future studies

Genetic damages in radiation workers of radiology centers in Bushehr port

Unstable genetic aberrations might provide a good marker for assessing genetic damage in populations exposed to low levels of ionizing radiation.The frequency of these aberrations was estimated in peripheral lymphocytes from hospital workers in Bushehr Port, occupationally exposed to low levels of ionizing radiation (54 subjects) and age and sex matched controls. A total of 34 (23 males & 11 females) subjects had unstable genetic aberrations (50 chromosomal-type & 31 chromatid type) but only 7 subjects in control group had unstable genetic aberrations. When compared with controls, exposed workers showed a significant increase in structural chromosomal-type aberrations (p<0.001 OR=11) chromosomal exchange being the most frequent alteration. Chromatid deletion (18 cases ) and ring chromosome (4 cases) were seen only in exposed group. There was no association between smoking status, sex, age, level of education or working years. The increased frequencies of chromosomal damage in radiation workers, indicate conducting cytogenetic analysis in parallel to physical dosimetry in the working place