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In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-β [TGF-β], and IL-10), and cytokine secretion levels (TGF-β and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients., (© 2020 Wiley Periodicals LLC.)

Dietary therapy has an important role in the therapeutic process in children suffering refractory epilepsy. There are two kinds of dietary therapy which are the most common in children with refractory epilepsy: The classic ketogenic diet (KD) and the modified Atkins diet (MAD). The purpose of the present study was to compare the efficacy, tolerability, and compliance of these two dietary therapies in the children who have refractory epilepsy during 6 months of treatment. From March 2017 to November 2018, 45 children aged 2-15 years who had refractory epilepsy were randomly allocated in KD or MAD group. The intervention period was 6 months in both groups. The frequencies of seizures were determined from parental reports and were compared between the groups. The patients with upper than 50% reduction in seizure frequency were deemed as responders to the diets. Twenty-four patients were assigned to the KD and 11 patients to the MAD. Overall, 45.8% of children treated with the KD and 45.5% of children treated with MAD had over than 50% response to the diet therapies. The difference was not statistically significant (P = 0.437). The MAD was more advantageous regarding better tolerability and fewer side effects. There is not much difference regarding the efficacy between the MAD and classic KD. The MAD with fewer side effects may be more suitable as the first line of dietary therapy in children with refractory epilepsy.

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.

In 2015, Lad, Sanfilippo and Agrò proposed an alternative measure of uncertainty dual to the entropy known as extropy. This paper provides some results on a dispersion measure of extropy of random variables which is called varextropy and studies several properties of this concept. Especially, the varextropy measure of residual and past lifetimes, order statistics, record values and proportional hazard rate models are discussed. Moreover, the conditional varextropy is considered and some properties of this measure are studied. Finally, a new stochastic comparison method, named varextropy ordering, is introduced and some of its properties are presented.

As the Coronavirus disease 2019 (COVID-19) epidemic begins to stabilize, different medical imaging facilities not directly involved in the COVID-19 epidemic face the dilemma of how to return to regular operation. We hereby discuss various fields of concern in resuming breast imaging services. We examine the concerns for resuming functions of breast imaging services in 2 broad categories, including safety aspects of operating a breast clinic and addressing potential modifications needed in managing common clinical scenarios in the COVID-19 aftermath. Using a stepwise approach in harmony with the relative states of the epidemic, health care system capacity, and the current state of performing breast surgeries (and in compliance with the recommended surgical guidelines) can ensure avoiding pointless procedures and ensure a smooth transition to a fully operational breast imaging facility., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal., Main Body: Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as "living drugs" presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion., Conclusion: Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.

In this paper, the amount of 19 elements in three species of algae and associated sediment in the northern margin of the Persian Gulf was investigated. A sampling of algae was performed on the coast with a length of 5 km in each station and surface sediment was sampled at the same time in low and middle intertidal zones. The values of elements in the samples were measured by using an inductively coupled plasma mass spectrometry (ICP-MS) device. Then, the amount of bioaccumulation factor in algae tissue relative to sediment (biota-sediment accumulation factor, BSAF) was determined. The value of BSAF was compared with the empirical cumulative entropy (ECE). ECE is based on comparing the element information in algae with those in sediments. The results showed that BSAF was very closely related to the ECE factor so that significant correlations were obtained for algae species of P. gymnospora (ECE = 0.477 BSAF, R 2 : 0.967), H. hamulosa (ECE = 0.542 BSAF, R 2 : 0.979), and C. membranacea (ECE = 0.356 BSAF, R 2 : 0.976). The ECE values > 0.4 were similar to those obtained for BSAF > 1, exhibiting that the element accumulation in algae was higher than in sediments. Based on ECE, to determine the vanadium accumulation in the environment, the C. membranacea algae are more appropriate than H. hamulosa. Overall, the data showed that ECE is a good alternative to BSAF in estimating marine pollution.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel zoonotic virus identified as the cause of coronavirus disease 2019 (COVID-19) that has crossed species and infected humans. In order to develop new insights on the immune-based treatments against this disease, it is vital to understand the immunopathology of the COVID-19, implications of the immune response to SARS-CoV-2, and immune dysfunction in response to SARS-CoV-2. There is no approved drug for the treatment of COVID-19. It is, thus, promising to design immune-based treatments that inhibit the infectious mechanism of the virus, improve the inadequate immune response, or regulate the hyperactivated immune response in severely ill patients. According to the antiviral immune response against the virus, antibody-based immunotherapies of COVID-19 include injection of convalescent plasma from recovered patients, high-dose intravenous immunoglobulins (IVIG), monoclonal antibodies, and polyclonal antibodies. Also, cell-based treatment, vaccine-based approaches, cytokine-based immunotherapy, immune checkpoint inhibitors, JAK inhibitors, decoy receptors, and immunosuppressive drugs are discussed in this chapter.

Background: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells, but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet. The aim of the present study is to investigate the effects of KW-2449 on EAE mouse model., Methods: In this study, C57BL/6 EAE mice were orally treated with (10 mg/kg/day) KW-2449 solution and compared with EAE and control mice. Following the treatment, histological analyses were performed on the brain and cerebellum to evaluate the pathological score. The gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) were measured using qRT-PCR. The serum levels of TNF-α, IL-6, CCL-2 and MMP-2 were determined by using quantitative enzyme-linked immunosorbent assay (ELISA)., Results: The results indicated that the clinical score, the infiltration of inflammatory cells and the demyelination in EAE mice treated with KW-2449 decreased significantly compared to control groups. KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice., Conclusion: The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma and reduces EAE pathogenesis manifestation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The most effective utilization of platinum (Pt) in fuel cells is achieved through the use of nanoparticles (NPs) that offer a large electrochemically active surface area. Because the stability of NPs decreases as they become smaller, their size and size distribution must be known in order to optimize the catalysts' durability, while offering high catalytic activity. Single particle inductively coupled plasma mass spectrometry (spICPMS) can quantify the mass of metallic NPs suspended in aqueous medium, which can then be converted into a size if the NPs' shape, density and composition are known. In this study, for the first time, spICPMS was compared to transmission electron microscopy (TEM) for the characterization of 10 nm Pt NPs. After verifying the accurate sizing of commercial Pt NPs with diameters of 30, 50 and 70 nm, spICPMS with solution calibration was applied to laboratory-synthesized 10 nm Pt NPs possessing a near spherical shape and 10 ± 2 nm diameter according to TEM. The same NPs were also analyzed by spICPMS with Pt size calibration using Pt NPs standards. Irrespectively of the calibration strategy, spICPMS measured the entire population of 659 Pt NPs (6-65 nm), while TEM analyzed the 500 Pt NPs that appeared isolated in the field of view (6-18 nm). Analysis of the size distribution histograms revealed that the modal and mean diameters were respectively 10 and 11 ± 2 nm using solution calibration, and 12 and 13 ± 2 nm using particle size calibration. Both of these mean diameters are in agreement with the TEM measurements according to a Student's t-test at the 95% confidence level, demonstrating that spICPMS, with a size detection limit of 6 nm, can accurately quantify 10-nm Pt NPs while at the same time analyzing the entire sample., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

At the end of December 2019, a novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) appeared as the third unheard of outbreak of human coronavirus infection in the 21st century. First, in Wuhan, China, the novel SARS-CoV2 was named by the World Health Organization (WHO), as 2019-nCOV (COVID-19), and spread extremely all over the world. SARS-CoV2 is transmitted to individuals by human-to-human transmission leading to severe viral pneumonia and respiratory system injury. SARS-CoV2 elicits infections from the common cold to severe conditions accompanied by lung injury, acute respiratory distress syndrome, and other organ destruction. There is a possibility of virus transmission from asymptomatic cases as active carriers, in addition to symptomatic ones, which is a crucial crisis of COVID-19 that should be considered. Hence, paying more attention to the accurate and immediate diagnosis of suspected and infected cases can be a great help in preventing the rapid spread of the virus, improving the disease prognosis, and controlling the pandemic. In this review, we provide a comprehensive and up-to-date overview of the different types of Clinical and Para-clinical diagnostic methods and their practical features, which can help understand better the applications and capacities of various diagnostic approaches for COVID-19 infected cases., (© 2020 Wiley Periodicals LLC.)

Background: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease with chronic inflammation. In the course of the disease, the increased levels of Th17 cell, and its relevant inflammatory factors, may cause disease inflammation and progression. Ozone therapy with anti-oxidant and anti-inflammatory functions is known as a beneficial therapeutic approach. The current non-controlled study aimed to evaluate the therapeutic implications of ozone autohemotherapy on Th17 responses in MS patients., Methods: 20 MS patients as the experimental group received ozone therapy (100 ml of O2/O3 compound (25 ugs/ml concentration) with 100 ml of autologous blood) twice per week for 6 months. The frequency of Th17 cells, gene expression of the relevant factors (RORɣt, IL-17, IL-23, miR-141, miR-155, and miR-200), as well as the secretion levels of IL-17 and IL-23 cytokines, were compared between the patient and control groups, as well as the group of patients before and after ozone therapy using the flow cytometry, Real-time PCR, and ELISA techniques, respectively., Results: Findings indicated the significant decrease in the frequency of Th17 cells (P = 0.0002), the expression levels of RORɣt and IL-17 (P = 0.0001 and P = 0.0004, respectively), as well as miR-141 and miR-155 (P<0.0001 and P<0.0001, respectively) in post-treatment condition with Ozone compared to pre-treatment condition. Also, the significant reduction in the secretion level of IL-17 (P = 0.043) was detected in treated patients., Discussion: Since increased levels and responses of Th17 cells may have critical roles in MS pathogenesis and inflammation, our findings revealed that ozone autohemotherapy could lower the Th17 responses in peripheral blood of MS patients and can be a beneficial approach in MS treatment., (Copyright © 2020. Published by Elsevier B.V.)

Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer (BC), and its diagnosis is associated with negative expression of hormone receptors and HER2/neu. It consists of 10-20% of all BCs diagnosed., Methods and Materials: This study focuses on three groups with different pathology: group one showed complete triple-negative HER2 expression with IHC of BC; groups two and three included patients with ER-, PR-, and HER21+, and ER-, PR-, and HER22+ with a negative FISH test. These three groups were compared from the point of prognosis, which consisted of tumor size, patients' age, lymphatic, vascular and perineural invasion, organ metastasis, number of lymph nodes involvement, and the survival rate., Results: A total of 459 TNBC patients were enrolled, of which 268 were placed in the HER20 group, 146 in the HER21+ group, and 45 in the HER22+ group. Distant metastasis and recurrence rate were more common in HER20 patients, but bone metastasis was more common in patients with low HER2 expression. All patients with HER20 had a smaller tumor size at the time of BC diagnosis in comparison to patients in the low HER2 expression group. Patients with HER22+ had less lymphatic and vascular invasion as well as axillary lymph nodes involvement, but larger tumor size at presentation, resulting in a lower rate of recurrence and higher overall survival., Conclusion: The findings revealed that patients with HER22+ had better outcome in comparison to the patients with HER20 and HER21+. Furthermore, the results showed that many patients with HER22+ expression were not basal-like and had good prognosis amongst TNBC patients.

Translational control in mammalian cells plays a critical role in regulating differentiation, cell growth, cell cycle and response to diverse stresses. Macrophages are one of the most versatile cell types in the body. They are professional phagocytic cells that can be found in almost all tissues and adapt tissue-specific functions. Recent studies highlight the importance of translational control in macrophages during invasion of pathogens, exposure to cytokines and in the context of tissue specific functions. In this review, we summarize the current knowledge regarding the role of mRNA translational control in regulation of macrophages., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Published by Elsevier Inc.)

β-Thalassemia (β-thal) is one of the most common diseases in Iran. Here, we report the spectrum of HBB gene mutations in 176 Kurdish β-thal carriers from the northern part of Ilam Province, Iran. The amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used to identify common β-globin gene mutations observed in Iran. Samples negative on ARMS-PCR were analyzed by direct sequencing of the β-globin gene. In total, 12 different mutations were identified on the β-globin gene. The mutations of IVS-II-1 (G>A) ( HBB : c.315+1G>A), codons 8/9 (+G) ( HBB : c.27&#95;28insG), codons 36/37 (-T) ( HBB : c.112delT) and IVS-I-110 (G>A) ( HBB : c.93-21G>A), were the most prevalent mutations in our samples, with frequencies of 59.09, 10.80, 7.95 and 7.39%, respectively. In general, the mutation spectrum of the β-globin gene in the northern part of Ilam Province is most similar to that in other western provinces of Iran. On the other hand, due to the high prevalence of carriers and β-thal major (β-TM) patients in this province, our results can be helpful in identifying carriers as well as at-risk fetuses through the prenatal diagnosis program.

Due to reliability and performance considerations, employing multiple software-defined networking (SDN) controllers is known as a promising technique in Wireless Sensor Networks (WSNs). Nevertheless, employing multiple controllers increases the inter-controller synchronization overhead. Therefore, optimal placement of SDN controllers to optimize the performance of a WSN, subject to the maximum number of controllers, determined based on the synchronization overhead, is a challenging research problem. In this paper, we first formulate this research problem as an optimization problem, then to address the optimization problem, we propose the Cuckoo Placement of Controllers (Cuckoo-PC) algorithm. Cuckoo-PC works based on the Cuckoo optimization algorithm which is a meta-heuristic algorithm inspired by nature. This algorithm seeks to find the global optimum by imitating brood parasitism of some cuckoo species. To evaluate the performance of Cuckoo-PC, we compare it against a couple of state-of-the-art methods, namely Simulated Annealing (SA) and Quantum Annealing (QA). The experiments demonstrate that Cuckoo-PC outperforms both SA and QA in terms of the network performance by lowering the average distance between sensors and controllers up to 13% and 9%, respectively. Comparing our method against Integer Linear Programming (ILP) reveals that Cuckoo-PC achieves approximately similar results (less than 1% deviation) in a noticeably shorter time.

Background: Intraoperative radiation therapy (IORT) is the delivery of radiation at the time of surgery. Whereas the dose delivered by external beam radiation therapy (EBRT) is limited by the tolerance of the surrounding normal tissues, IORT allows exclusion of a part or all of the dose-limiting sensitive structures by operative mobilization and/or direct shielding of these structures. The aim of the present study was to report the non-breast cancer patients' outcomes after receiving IORT in Shiraz, Iran. Methods: In this retrospective study, all cases who had received IORT and had non-breast malignancies were selected. Diagnosis was confirmed by biopsy. Additional imaging was done by sonography, magnetic resonance imaging (MRI) and computed tomography (CT). IORT was applied by self-shielded, LIAC 6-12 MeV Sordina mobile linear accelerator. Typically, a single dose of 10-21 Gy was given for maximally resected tumors. The statistical analyses were carried out using SPSS (version 21). Results: Twenty-six patients were treated with IORT alone or combined with EBRT. Different tumors were treated, including colorectal adenocarcinoma (10 cases, 38.4 %), Soft Tissue Sarcomas (STS, 11 cases, 42.3 %), head and neck cancers (3 cases, 11.5 %), one cervix malignancy case and one paravertebral fibromatosis case. Mean ± SD overall survival was 15±14.89 (0-38) and 34.3±15.72 (14-53) months for colorectal cancer and STS, respectively. Conclusion: IORT is mostly useful for pelvic and abdominal malignancies where normal bowel limits the dose that can be delivered with EBRT. However, the dose delivered in a single fraction with IORT is rarely sufficient for tumor control; therefore, IORT is usually preceded or followed by additional EBRT which should be further evaluated preferably in prospective randomized trials., (© 2020 Iran University of Medical Sciences.)

A cochlear implant (CI) is a surgically implanted electronic device that partially restores hearing to people suffering from profound hearing loss. Although CI users, in general, obtain a very good reception of continuous speech in the absence of background noise, they face severe limitations in the context of music perception and appreciation. The main reasons for these limitations are related to channel interactions created by the broad spread of electrical fields in the cochlea and to the low number of electrodes that stimulate it. Moreover, CIs have severe limitations when it comes to transmitting the temporal fine structure of acoustic signals, and hence, these devices elicit poor pitch and timber perception. For these reasons, several signal processing algorithms have been proposed to make music more accessible for CI users, trying to reduce the complexity of music signals or remixing them to enhance certain components, such as the lead singing voice. In this work, a deep neural network that performs real-time audio source separation to remix music for CI users is presented. The implementation is based on multi-layer perception (MLP) and has been evaluated using objective instrumental measurements to ensure clean source estimation. Furthermore, experiments in 10 normal hearing (NH) and 13 CI users to investigate how the vocals to instruments ratio (VIR) set by the tested listeners were affected in realistic environments with and without visual information. The objective instrumental results fulfill the benchmark reported in previous studies by introducing distortions that are shown to not be perceived by CI users. Moreover, the implemented model was optimized to perform real-time source separation. The experimental results show that CI users prefer vocals 8 dB enhanced with the respect to the instruments independent of acoustic sound scenarios and visual information. In contrast, NH listeners did not prefer a VIR different than zero dB., (Copyright © 2020 Tahmasebi, Gajȩcki and Nogueira.)

In order to identify the α-thalassemia (α-thal) mutation spectrum in Kurdistan Province, West Iran, a total of 217 individuals, including 154 α-thal carriers and 63 normal subjects were investigated in this study. Molecular analysis of α1- and α2-globin genes using multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR or direct DNA sequencing, showed 11 different α-globin variants. The -α 3.7 (rightward) deletion (NG&#95;000006.1: g.34164&#95;37967del3804) (70.32%), polyadenylation signal (polyA2) site (AAT A AA>AAT G AA) (α polyA2 α) ( HBA2 : c.*92A>G) (7.74%), -α 4.2 (leftward) deletion (6.45%) and codon 59 (or Hb Adana) (G>A) (αα codon 59 ) ( HBA1 : c.179G>A) (4.52%) were the most frequent mutations in the present study. In conclusion, the spectrum of α-thal mutations in Kurdistan Province is closest to that in western provinces of Iran (Kurdish and Laki populations). In addition, it was revealed that the codon 59 mutation is common in the Kurdish population. On the other hand, despite the same ethnic background of Kurds in Iran and Iraq, the - - MED I double gene deletion and polyA2 point mutation have different distributions in these two populations. Therefore, further studies are needed to identify the cause of these differences.

Deregulation of mRNA translation engenders many human disorders, including obesity, neurodegenerative diseases, and cancer, and is associated with pathogen infections. The role of eIF4E-dependent translational control in macrophage inflammatory responses in vivo is largely unexplored. In this study, we investigated the involvement of the translation inhibitors eIF4E-binding proteins (4E-BPs) in the regulation of macrophage inflammatory responses in vitro and in vivo. We show that the lack of 4E-BPs exacerbates inflammatory polarization of bone marrow-derived macrophages and that 4E-BP-null adipose tissue macrophages display enhanced inflammatory gene expression following exposure to a high-fat diet (HFD). The exaggerated inflammatory response in HFD-fed 4E-BP-null mice coincides with significantly higher weight gain, higher Irf8 mRNA translation, and increased expression of IRF8 in adipose tissue compared with wild-type mice. Thus, 4E-BP-dependent translational control limits, in part, the proinflammatory response during HFD. These data underscore the activity of the 4E-BP-IRF8 axis as a paramount regulatory mechanism of proinflammatory responses in adipose tissue macrophages., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Background: Recent studies have reported observing antioxidant, anti-inflammatory, and anti-aging properties of α-L-Guluronic acid (G2013) in animal and human studies. It has been theorized that the antioxidant and anti-inflammatory properties of G2013 might be beneficial in epilepsy treatment. Objective: We sought to determine G2013's effects on epileptic activity in a kindling-induced animal model. Methods: Thirty rats were randomly divided evenly into three groups (10 rats in each group): 1) the G2013 group, which was treated with daily injections of G2013 for five days prior to the start of the study; during the 14-day study period, the G2013 rats were given single, daily injections of G2013 that preceded single daily injections of pentylenetetrazole (PTZ), a compound used to induce seizures; 2) the Normal group, which only received injections of saline during the 14-day study, with no seizure induction; and 3) the Control group, which received PTZ injections alone (for seizure induction) for the 14-day study period. The latency between seizure stages and duration of seizures in the G2013 and Control groups were measured using a 5-stage seizure severity scale. Brain samples were taken from all three groups and analyzed histopathologically for parenchymal and meningeal inflammatory cell infiltration. Additionally, the brain samples were analyzed to determine gene expression levels of interleukin-1-beta (IL-1β), IL-6, IL-10), tumor necrosis factor (TNF), chemokine (C-C motif) ligand-2 (CCL2), cyclooxygenase-2 (COX-2), and interferon-gamma (IFN-γ). Results: The G2013 group demonstrated lower latency between Stages 2 and 5 seizures, with significantly longer mean duration of Stage 5 seizures, compared to the Control group. No significant differences were observed between the three groups histopathologically nor were there any observed differences in gene expression levels. Conclusion: Our results demonstrated a greater predisposition to PTZ-induced seizures in the rats who received G2013 and PTZ compared to rats who received PTZ alone, suggesting that G2013's epileptogenic property overshadows its anti-inflammatory effects when applied to a kindled animal model of study., Competing Interests: FUNDING:This study was funded by vice chancellor for research, Alborz University of Medical Sciences, under Grant No. 1397-03-00-1829. DISCLOSURES:The author has no conflicts of interest relevant to the content of this article., (Copyright © 2020. Matrix Medical Communications. All rights reserved.)

Objective: To investigate the effect of intravenous regional anesthesia with single-cuff forearm tourniquet and hematoma block on intraoperative and postoperative pain intensity of patients with distal radial bone fracture., Methods: In this randomized clinical trial, a total number of 52 patients with distal radius fractures were randomly assigned to receive either a traditional Bier block with 3 mg.kg -1 lidocaine (D group) or a single-cuff forearm tourniquet intravenous regional anesthesia with 1.5 mg.kg -1 lidocaine and a hematoma block with 10 mL 0.5% bupivacaine (S group). Pain intensity score of numerical rating scale (NRS) was measured hourly for 6 hours, then every two hours till 12 th hour and every 4 hours until 24 th postoperative hour. Total morphine consumption in the first 24 hours after surgery, its side effects and the patients' global satisfaction were assessed in each group., Results: Mean total morphine consumption during the first 24 hours after surgery was 11.68±7.88 mg in group D and 7.12±4.42 mg in group S ( p =0.13). Pain intensity score of NRS both during recovery room and surgical ward stay was less in S group compared to D group (0.016 and 0.02, respectively)., Conclusion: Intravenous regional anesthesia with single cuff forearm tourniquet and hematoma block compared to the traditional Bier block reduced intraoperative and postoperative pain intensity more effectively in patients with distal fracture of the radius bone and also reduced morphine consumption during the first 24 hours after surgery., (© 2020 Trauma Research Center, Shiraz University of Medical Sciences.)

Despite the current advancements, cancer treatment approaches have limitations restricting their cure rate. Immunotherapy techniques are among novel and promising cancer therapeutic approaches. Therapeutic antibodies and adoptive cell therapy (ACT) are the main branches of immunotherapy. T lymphocytes and genetically engineered cells are among important cells which can be used in ACT. This review has focused on recent advances in engineered cell-based immunotherapy based on T lymphocytes with chimeric antigen receptors (CARs). CARs are recombinant receptors expressing T cell signaling domains with or without co-stimulatory molecules. CAR-T cells are expanded ex vivo and re-infused to patients in order to improve their therapeutic efficacy. Nowadays, the beneficial function of CAR-T cell therapy has been indicated in various diseases including hematological malignancies, solid tumors, autoimmune diseases, and allergic diseases such as asthma. Furthermore, antigen-specific T regulatory cells (T regs ) and gene-edited T cells seem to be beneficial in controlling inflammation in allergic asthma. In fact, dysregulated function of T regs is responsible for dominance of T helper 2 immune response and progression of allergic asthma. CAR-T reg cells can also be designed and reproduced using iT reg population to manage asthma. In addition, universal CAR-T cells can be modified to selectively target multiple antigens. The fourth generation CAR-T cells (i.e. TRUCK cells) represent novel strategies to cure asthma and allergic diseases as well. Despite the advantages of CAR-T cells, their applications can be associated with some unwanted reactions such as cytokine storm, anaphylaxis, neurotoxicity, etc. For clinical application, there is a need to prevent and manage these complications by optimizing ACT protocols., Competing Interests: Declaration of Competing Interest The authors declare that the current research was conducted in the absence of any commercial or financial relationships which could be construed as a potential conflict of interest., (Copyright © 2019 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Biomass yield is an important trait for wheat breeding programs. Enhancing the yield of the aerial components of wheat cultivars will be an integral part of future wheat improvement. Aluminum (Al) toxicity is one of the main factors limiting wheat growth and production in acid soils, which occur on up to 50% of the arable lands of the world especially in tropical and subtropical regions., Objective: Our objective was to identify quantitative trait loci (QTL) of plant growth characteristics and yield in wheat., Methods: A recombinant inbred line (RIL) population consisting of 167 lines, derived from a cross between SeriM82 and Babax were evaluated under two Al treatments (+ Al, 800 µM of Al; -Al, 0 µM of Al) in the field based on an alpha lattice design with two replications for two consecutive crop seasons., Results: A total of 40 QTLs including nine putative and 31 suggestive QTLs were found for all traits using the composite interval mapping (CIM) method. By mixed model-based composite interval mapping (MCIM) method, 42 additive QTLs and nine pairs of epistatic effects were detected for studied traits, of which 20 additive and six pairs of epistatic QTLs showed significant QTL × environment interactions. Most of the detected QTLs across environments were stable, and the highest number of stable QTLs was related to A genome. Co-localization of QTL was found on linkage groups (LGs) 2B, 4B, 6A-a, and 7A (CIM method) and 2A-d, and 6A-a (MCIM method)., Conclusion: These results have implications for selection strategies in biomass yield and for increasing the yield of the aerial part of wheat following further evaluations in various genetic backgrounds and environments.

Introduction: Epilepsy is a most common neurological disorder that has negative effects on cognition. In the present study, we investigated the protective effect of Nigella sativa (NS) and probiotics on seizure activity, cognitive performance, and synaptic plasticity in pentylenetetrazole (PTZ) kindling model of epilepsy., Methods: One hundred and forty-four rats were divided into 2 experiments: In experiment 1, animals were grouped and treated as follows: 1) control (PTZ + saline), 2) NS treatment, 3) probiotic treatment, and 4) NS and probiotic treatment. Six weeks after the treatment, PTZ kindling were performed, and 48 h after kindling, spatial learning and memory were measured in Morris water maze (MWM) test. Animals in experiment 2 received the same treatment as experiment 1: in control nonkindled groups, control animals were treated with probiotics, NS, and probiotics + NS. Six weeks after the treatment, PTZ kindling were performed, and 48 h after kindling, field potentials were recorded from the dentate gyrus area of the hippocampus; synaptic transmission and long-term potentiation (LTP) was measured., Results: The results showed that the probiotic and NS supplementation significantly reduces kindling development so that animals in PTZ + NS + probiotic did not show full kindling. In MWM test, the escape latency and traveled path in the kindled group were significantly higher than the control group. In PTZ + NS + probiotics, these parameters were significantly lower than those in the PTZ + saline group. Adding probiotic and NS supplementation significantly reduced population spike (PS)-LTP as compared with the PTZ + saline group., Conclusion: Probiotic and NS supplementation have some protection against seizure, seizure-induced cognitive impairment, and hippocampal LTP in kindled rats., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We describe a novel compound heterozygous genotype which consists of two point mutations named Hb Adana ( HBA1 : c.179G>A) and codon 127 ( HBA2 : c.382A>T) in a Kurdish family with two girls affected with severe α-thalassemia (α-thal). Both patients (the proband and her sister) had a history of splenectomy during childhood. Although the proband had no blood transfusion history, her affected sister has had two blood transfusions so far. In conclusion, diagnosing and reporting new genotypes on the α-globin genes will improve our knowledge about complicated genotype-phenotype correlations in α-thal disorder.

Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are well known for their capacity to drive necroptosis via mixed-lineage kinase-like domain (MLKL). Recently, RIPK1/3 kinase activity has been shown to drive inflammation via activation of MAPK signaling. However, the regulatory mechanisms underlying this kinase-dependent cytokine production remain poorly understood. In the present study, we establish that the kinase activity of RIPK1/3 regulates cytokine translation in mouse and human macrophages. Furthermore, we show that this inflammatory response is downregulated by type I interferon (IFN) signaling, independent of type I IFN-promoted cell death. Specifically, low-level constitutive IFN signaling attenuates RIPK-driven activation of cap-dependent translation initiation pathway components AKT, mTORC1, 4E-BP and eIF4E, while promoting RIPK-dependent cell death. Altogether, these data characterize constitutive IFN signaling as a regulator of RIPK-dependent inflammation and establish cap-dependent translation as a crucial checkpoint in the regulation of cytokine production., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To identify the human factors contributing to traffic accidents with a special focus on psychosocial factors amongst young girls of Tehran, Iran., Methods: In a descriptive study conducted in Tehran, Iran in 2013, 108 girls aged 18-24 were enrolled by using a stratified cluster sampling method. Participants filled a wide range of validated questionnaires about traffic psychology., Results: The developed psychological model about behaviors of drivers' factors as well as agreeable and aggressive personality trait with B coefficient of 0.25% and 0.37% were able to predict violation, driving style, perception of police laws, and off hook scheme and the mistrust with B coefficient of 0.33%, 0.23% and 0.28% in the level of 0.1 were able to predict violations and lapses of sample group, respectively. Extroversion with B coefficient of 0.27% also predicted unintentional violations of girls. B coefficient for perception of police laws was 0.22%. This was 0.25% for openness to experiences. Concerning driving accidents, the perception of police rules has the highest predictability., Conclusion: According to the results of the current research amongst girls in Tehran, a gender-sensitive interventional model can be designed for reduction of traffic accidents for this population group.

Background and Objective: We evaluated clinicopathological changes of breast cancer (BC) during a 22-year time period among the Iranian population., Methods: This study is part of the largest BC registry in Iran. Patients were categorized as those diagnosed with BC during 1993-2005, 2006-2011, and 2012-2017 and compared regarding baseline characteristics and socioeconomical determinants, and obstetrical/gynecological and BC characteristics., Results: Overall, 688, 1871, and 3020 patients entered the 1993-2005, 2006-2012, and 2012-2017 year groups, respectively. Mean (SD) age at first presentation of BC increased throughout the year groups (47.40 ± 10.34, 49.12 ± 11.70, and 49.43 ± 12.07 years, respectively; p < 0.001). Mean (SD) tumor size increased from 1993-2005 to 2006-2011 and decreased onto 2012-2017 (2.82 ± 1.69, 2.91 ± 1.49, and 2.66 ± 1.52 cm, respectively; p < 0.001). Number of individuals with stage 4 and grade 3 BC also showed an increasing pattern (p < 0.001). Tumor necrosis rates showed an increase onto 2011-2017 (43%, 47.3%, and 56%, respectively; p < 0.001). ER positive (62.4%, 73.4%, and 77.1%, respectively; p < 0.001) and PR positive individuals (59.5%, 64.3%, 72.6%, respectively; p < 0.001) showed an increasing trend. HER2 positive expression rates increased from 1993-2005 to 2005-2011 (24.5% and 31.5%, respectively) and decreased onto 2012-2017 (31.5% and 26.8%, respectively, p < 0.001). Number of involved lymph nodes increased (5.70 ± 6.56, 5.65 ± 6.00, and 5.95 ± 6.99, respectively; p < 0.001). Pattern of BC invasion and recurrence showed significant change (p < 0.001)., Conclusion: Clinical and pathological characteristics may be showing a changing pattern among the Iranian population.

Objective: Cancer is a stressful event in life, and the dreadful impact and problems created for patients and families, by cancer negatively affect their quality of life. Therefore, regarding the increasing number of cancer patients and the, nature of this disease, the need to recognize and understand the priorities and problems of patients after the diagnosis of, cancer is of high importance. This study was designed and implemented with the aim of identifying the perceived, priorities of women with breast cancer., Methods: This study is a qualitative research of content analysis type. To collect, data, purposeful sampling and deep semi-structured individual interviews were used. The subjects were women with, breast cancer who visited the Breast Disease Research Center of Shahid Motahari Clinic in Shiraz, and the data were, saturated after 15 interviews. The four criteria presented by Lincken and Guba were used to evaluate the validity and, reliability. To analyze the qualitative data, conventional qualitative data analysis and MAXQDA10 software were used., Two themes were obtained in the assessment of interviews and analysis of data: 1) Supportive relief; 2) Therapeutic, support., Results: Some of the participants highlighted the role of social and family support in coping with the disease,, and considered social communication and continued support in the form of empathic relationship as a turning point, in their lives. The absence of a fertility specialist in the cancer treatment system was the main complaint of most, participants. The results showed that receiving support from family and the healthcare system is the most important, perceived priorities in breast cancer patients., Conclusion: The results of this study show the importance of social support, as a perceived priority in breast cancer patients to improve their quality of life. Development and reinforcement of the, supportive network seem to be essential to provide the best possible help to these patients.

We study the impairment of locomotion and rearing behavior in rats with a common bile duct ligation (BDL), and the possible involvement of the PKCγ and CamKIIα gene expression in the brain. Male Wistar rats undergo either sham operation or BDL to induce a rat model of cirrhotic hepatic encephalopathy (HE). Six groups of the animals were divided into three sets of sham-operated and BDL groups. In the first set, locomotion and rearing behavior were assessed on days 1, 7, 14, 21 and 28 of BDL. On day 28 of BDL, blood samples were collected from the second set of the animals for biochemical analysis, and the rats in the third set were used to extract the PFC, the hippocampus, and the cerebellar cortex for examining the Pkcγ and CamKIIα gene expression. The results showed that locomotion and rearing were decreased during 28 days of BDL with the most significant change on the 28th day. Biochemical analysis of the blood revealed hyperammonemia, increases in liver enzymes, and a decrease in albumin indicating liver damage and induction of cirrhotic HE. The results also showed that both of the Pkcγ and CamKIIα gene expressions were increased in the PFC but decreased in the hippocampus. However, the Pkcγ gene expression was decreased but the CamKIIα gene expression was increased in the cerebellar cortex. It can be concluded that the Ca 2+ -dependent kinases in different brain areas have a site-specific association with the impairment of locomotion and rearing behavior in the cirrhotic HE model rats., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Adoptive cell therapy using CAR T cells has emerged as a novel treatment strategy with promising results against B cell malignancies; however, CAR T cells have not shown much success against solid malignancies. There are several obstacles which diminish the efficacy of CAR T cells, but the immunosuppressive tumor microenvironment (TME) of the tumor stands out as the most important factor. TME includes Tumor-Associated Stroma, Immunosuppressive cells and cytokines, tumor hypoxia and metabolism, and Immune Inhibitory Checkpoints which affect the CAR T cell efficacy and activity in solid tumors. A precise understanding of the TME could pave the way to engineer novel modifications of CAR T cells which can overcome the immunosuppressive TME. In this review, we will describe different sections of the TME and introduce novel approaches to improve the CAR T cells potential against solid tumors based on recent clinical and preclinical data. Also, we will provide new suggestions on how to modify CARs to augment of CAR T cells efficacy. Since there are also some challenges beyond the TME that are important for CAR function, we will also discuss and provide data about the improvement of CAR T cells trafficking and delivery to the tumor site and how to solve the problem of tumor antigen heterogeneity.

Purpose: This pilot study aimed to evaluate the effect of an 8-weeks-yoga intervention on quality of life and upper extremity edema volume in women with breast cancer related lymphedema., Methods: This was a controlled trial with pre-post design. A total of 40 women with breast cancer related lymphedema were randomly assigned into an intervention or control groups. The intervention group participated in a yoga exercise class for 8 weeks, in a twice a week instructor-led practice and once a week home practice. Outcomes were EORTC QLQ&#95;C30 to measure quality of life, and water displacement volume-meter to measure upper extremity edema volume. The outcomes were evaluated at baseline, 4th and 8th week. Data were analyzed using SPSS., Results: Four weeks after the intervention, a significant difference was observed between the groups with respect to role functioning of quality of life (P = 0.03). Eight weeks after the intervention, a significant difference was observed between groups concerning physical and emotional functioning of quality of life (P < 0.05). The changing trend in physical, role, emotional, and cognitive functioning had increased, and in some scales such as fatigue, pain, insomnia, and financial difficulties the scores were reduced in the intervention group. Regarding edema volume, no significant difference was found between both groups on the 4th and 8th week after the intervention (P > 0.05)., Conclusion: As yoga exercise might improve physical, role, and emotional functioning of quality of life as well as reduce fatigue, pain, and insomnia, using this intervention can be suggested amongst women with breast cancer related lymphedema., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Protein synthesis and its regulation are central to all known forms of life and impinge on biological arenas as varied as agriculture, biotechnology, and medicine. Otherwise known as translation and translational control, these processes have been investigated with increasing intensity since the middle of the 20th century, and in increasing depth with advances in molecular and cell biology. We review the origins of the field, focusing on the underlying concepts and early studies of the cellular machinery and mechanisms involved. We highlight key discoveries and events on a timeline, consider areas where current research has engendered new ideas, and conclude with some speculation on future directions for the field., (Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.)

Genetic improvement of aluminum (Al) tolerance is one of the cost-effective solutions to improve plant productivity in acidic soils around the world. This study was performed to progress our understanding of the genetic mechanisms of aluminum tolerance underlying wheat ( Triticum aestivum L.) flag leaf morphological and physiological traits. A recombinant inbred line population derived from SeriM82 and Babax was used for mapping quantitative trait loci (QTL) in wheat for tolerance to Al toxicity through 477 DNA markers. Based on a single-locus analysis, 48 QTLs including 16 putative and 32 suggestive QTLs were identified for all studied traits. Individual QTL explained 4.57-11.29% of the phenotypic variance in different environments during both the crop seasons. These QTLs located unevenly throughout the wheat genome. Among them, 52.08%, 29.17%, and 18.75% were in the A, B, and D genomes, respectively. Based on two-locus analysis, 54 additive QTLs and 6 pairs of epistatic effects were detected, among which 29 additive and 5 pairs of epistatic QTLs showed significant QTL × environment interactions. The highest number of stable QTLs was identified on genome A. Determining a number of QTL clusters indicated tight linkage or pleiotropy in the inheritance of different traits. The stable and major QTLs controlling traits in this research can be applied for verification in different environments and genetic backgrounds and identifying superior allelic variations in wheat to increase the performance of selection of high yielding lines adapted to Al stress in breeding programs., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

Purpose: In recent years, the prognostic/predictive significance of tumor infiltrating lymphocytes (TILs) has become a topic of interest. Here, we aimed to evaluate the prognostic significance of CD3+, CD8+, CD45RO+ and Foxp3+ TILs in breast cancer, as well as the relation of these markers to other clinicopathological features of this disease., Methods: FFPE tumor samples from 94 females with invasive ductal carcinoma of the breast were retrospectively selected and immunohistochemically assessed for CD3, CD8, CD45RO and Foxp3 expression. Digital photos were acquired from the center (CT) and invasive margins (IM) of the tumors, after which positive cells were counted using ImageJ software., Results: We found that greater infiltrations of target lymphocyte subpopulations were associated with TNM stage III, lymph node metastasis, high histological grade, ER negativity and HER2 positivity. The ratios of CD8+ cytotoxic T cells to CD3+, CD45RO+ and Foxp3+ TILs were found to be relatively higher in tumors exhibiting the aforementioned characteristics. In univariate survival analyses, CD8+ TILs in the IM and total CD45RO+ TILs were found to be significantly associated with overall survival (OS). Infiltration of CD45RO+ TILs in the CT and lymph node status were variables that significantly correlated with disease-free survival (DFS). Multiple Cox regression analyses revealed independent significant prognostic effects of total CD45RO+ TILs and lymph node status (HR of 3.24 and 3.19, respectively) in predicting OS. Infiltration of CD45RO+ TILs in the CT (HR 3.12) and lymph node status (HR 3.15) also exhibited significant prognostic effects on DFS., Conclusion: From our data we conclude that CD45RO+ TILs serve as prognostic factors for predicting OS and DFS of breast cancer patients.

Purpose: Vaginal atrophy is one of the most common side effects of using tamoxifen in women with breast cancer. Hormone therapy for vaginal atrophy is prohibited in these women. The present study was conducted to investigate the effect of vitamin D and E vaginal suppositories on vaginal atrophy in women with breast cancer receiving tamoxifen., Methods: Women under breast cancer management receiving tamoxifen and showing symptoms of vaginal atrophy were randomized triple-blind to an 8-week trial on vaginal suppository vitamin E or vitamin D or placebo administered every night before bedtime. The genitourinary atrophy self-assessment tool was administered, and pH was measured in all three groups before the intervention and at the end of weeks 2, 4, and 8 of the intervention. The Vaginal Maturation Index (VMI) was also measured before the intervention and at the end of the eighth week. Data were analyzed with paired t tests, repeated measures analysis of variance, and chi-square test., Results: Thirty-two patients were randomized in each group. The results obtained showed an increase in the VMI by the end of the eighth week of the intervention in the groups receiving the vitamin D and E vaginal suppositories compared with the placebo group (P < 0.001). The vaginal pH also reduced in both groups compared with that in the placebo group (P < 0.001). The symptoms of self-reported genitourinary atrophy also improved in the two intervention groups compared with those in the placebo group by the end of the eighth week (P < 0.001)., Conclusion: These data support that vitamin D and E vaginal suppositories were beneficial in improving vaginal atrophy in women with breast cancer receiving tamoxifen. Given the prohibition on hormone therapy in these women, the suppositories can be used as an alternative therapy to improve these symptoms.

The relationship between diabetes and endothelial dysfunction remains unclear, particularly the association with pathological activation of calpain, an intracellular cysteine protease. Here, we used human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) to investigate the effects of diabetes on vascular health. Our results indicate that iPSC-ECs exposed to hyperglycemia had impaired autophagy, increased mitochondria fragmentation, and was associated with increased calpain activity. In addition, hyperglycemic iPSC-ECs had increased susceptibility to cell death when subjected to a secondary insult-simulated ischemia-reperfusion injury (sIRI). Importantly, calpain inhibition restored autophagy and reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, normalized reactive oxygen species levels and reduced susceptibility to sIRI. Using a human iPSC model of diabetic endotheliopathy, we demonstrated that restoration of autophagy and prevention of mitochondrial fragmentation via calpain inhibition improves vascular integrity. Our human iPSC-EC model thus represents a valuable platform to explore biological mechanisms and new treatments for diabetes-induced endothelial dysfunction., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

α-Thalassemia (α-thal) is one of the most common genetic disorders worldwide. The aim of this study was to investigate for the first time the α-thal mutation spectrum in the Lak population living in Lorestan Province, Iran. One hundred and seventy-six α-thal carriers participated in the study. Multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing were used for the detection of different mutations on the α-globin ( HBA1 and HBA2 ) genes. A total of 11 different mutations was identified. The -α 3.7 (rightward; NG&#95;000006.1: g.34164&#95;37967del3804) deletion was observed most frequently (56.35%), followed by α -5 nt α ( HBA2 : c.95+2&#95;95+6delTGAGG), α polyA2 α ( HBA2 : c.*92A>G) and - - MED I (NG&#95;000006.1: g.24664&#95;41064del16401), with frequencies of 15.47, 9.39, and 6.08%, respectively. These four mutations accounted for more than 87.0% of the total mutated alleles. Moreover, 19 different genotypes were identified. The types and distribution pattern of the mutations identified in this study, in comparison with other studies conducted in Iran, was most similar to the Kurdish population of Kermanshah Province, Iran. Due to the lack of information on α-thal in Lorestan Province, it was not possible to compare the mutation spectrum in the Lur and Lak populations. In conclusion, our results may help in setting up a strategy for an α-thal screening program and genetic counseling in the Lak people.

Simultaneous measurements of mRNA and protein abundance and turnover in mammalian cells, have revealed that a significant portion of the cellular proteome is controlled by mRNA translation. Recent studies have demonstrated that both embryonic and somatic stem cells are dependent on low translation rates to maintain an undifferentiated state. Conversely, differentiation requires increased protein synthesis and failure to do so prevents differentiation. Notably, the low translation in stem cell populations is independent of the cell cycle, indicating that stem cells use unique strategies to decouple these fundamental cellular processes. In this chapter, we discuss different mechanisms used by stem cells to control translation, as well as the developmental consequences of translational deregulation.

Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice., Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits., Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice., Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Among all diagnostic techniques for breast lesions, fine-needle aspiration (FNA) is the simplest, most reliable and cheapest one., Aim: To compare liquid-based and conventional cytology in diagnosis of breast mass., Materials and Methods: About 101 patients with breast mass were enrolled. The aspirated materials were divided into two parts. One was poured into a liquid medium and the other part was directly spread on clean glass slides. Conventional and liquid-based preparations were compared using several criteria including adequacy (presence of the epithelial cluster or myoepithelial cells), overall cellularity, presence of single epithelial cells, presence of myoepithelial cells, epithelial architecture, nuclear detail, nuclear atypia and inflammatory/proteinaceous background and final diagnosis., Results: Among 101 cases, 85 (84.1%) were malignant and 16 (15.9%) were benign. Conventional and liquid-based cytology were similar according to adequacy ( P = 0.65), cellularity ( P = 0.13), epithelial architecture ( P = 0.15), presence of myoepithelial cells ( P = 0.61), nuclear detail ( P = 0.57) and nuclear atypia ( P = 0.44), while there were a significant difference between the two methods according to the presence of single epithelial cells ( P < 0.001) and background ( P < 0.001)., Conclusion: Liquid-based cytology of breast specimens is an accurate diagnostic tool with high diagnostic yield in benign and malignant lesions., Competing Interests: There are no conflicts of interest.

Background and Aim: The prevalence of cancer in women under 50 years of age has been increased in recent years. Cancer treatment methods can lead to infertility in women with cancer. Fertility and childbearing, as the most important conflicts in the life of women with breast cancer, significantly affect their quality of life., Materials and Methods: This research is a qualitative study of content analysis type. Purposeful sampling and semi-structured individual interviews were performed for data collection. The participants were women with breast cancer referred to the Breast Disease Research Center of Shahid Motahari Clinic in Shiraz. The data were saturated after 15 interviews. To assess the validity and reliability, we used the four criteria provided by Lincoln and Guba. The conventional qualitative data analysis and MAXQDA10 software were used to analyze the qualitative data., Results: Explaining the conflicts which women with breast cancer are faced has led to the extraction of four main categories: (1) paradox of decision-making to childbearing, (2) fear, (3) sinister emotions, and (4) challenges. The results showed that the paradox of decision-making on childbearing is the most important challenge with which the patients with breast cancer are faced, causing a state of fear, anxiety, and the emergence of sinister emotions in them., Conclusion: It seems that paying more attention to preserving reproductive capacity before starting the treatment plays an important role in solving the biggest conflict in the life of breast cancer patients., Competing Interests: There are no conflicts of interest.

β-Thalassemia (β-thal) is the most frequently observed hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Detecting thalassemia mutations are necessary for prenatal diagnosis (PND) programs leading a better quality of life for the patients, as well as a reduction in the cost of their medical care. There are more than 900 different genomic mutations of the β-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we identified a mid-intronic mutation at IVS-II-821 (A>C) ( HBB : c.316-30A>C) position in the HBB gene of an Iranian proband and two of her siblings that was associated with β-thal clinical features. Direct DNA sequence analysis was performed by mutation scanning of the β-globin gene. Based on the observed β-thal phenotype and bioinformatics analysis results, we concluded that this β-globin gene mutation was associated with a mild phenotype of β-thal through activating potential splice sites by creating exonic splicing enhancers (ESEs), exon-identity element (EIE) and exonic splicing regulatory sequences (ESRs) sites.

Objective: Poor bone health with related morbidity is a major problem with Duchene Muscular Dystrophy (DMD). Decreased mobility and long-term corticosteroid therapy are involved in poor bone health in DMD. We investigated bone mineral density and bone metabolism in 30 steroid treated DMD patients and also compared mentioned factors between ambulated and non-ambulated patients., Materials & Methods: In this cross-sectional study, 30 boys (21 patients ambulate and 9 non-ambulate) with documented DMD, according to genetic analysis, were enrolled in 2015. Demographic characteristics, neurologic exam findings, muscle function score, corticosteroid dose and duration and food frequency questionnaire were recorded. Bone mineral density was measured with dual- energy X-ray absorptiometry (DEXA) on lumbar spine and left proximal femur. Serum 25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone (PTH) levels were measured., Results: Osteoporosis was found in 86.7% patients. Mean bone density in the lumbar spine was -1.5±0.24 and -1.4±0.27 in ambulates and non-ambulates respectively ( P =0.7). Mean bone density at proximal femur was -3.4±0.2 in ambulates and -3.4±0.3 in non-ambulates ( P =0.48). Intra-groups statistical analysis showed significant difference between bone mineral density at lumbar spine and proximal femur in both mentioned groups ( P <0.05). Vitamin D deficiency was detected in 13 patients (43.3%) and its serum level was significantly lower in non-ambulates compared with ambulates., Conclusion: Considering high prevalence of vitamin D deficiency and osteoporosis in DMD patients, it seems vitamin D supplementation can improve vitamin D status and osteoporosis in these patients, especially in non-ambulates.

Advances in sequencing and high-throughput techniques have provided an unprecedented opportunity to interrogate human diseases on a genome-wide scale. The list of disease-causing mutations is expanding rapidly, and mutations affecting mRNA translation are no exception. Translation (protein synthesis) is one of the most complex processes in the cell. The orchestrated action of ribosomes, tRNAs and numerous translation factors decodes the information contained in mRNA into a polypeptide chain. The intricate nature of this process renders it susceptible to deregulation at multiple levels. In this Review, we summarize current evidence of translation deregulation in human diseases other than cancer. We discuss translation-related diseases on the basis of the molecular aberration that underpins their pathogenesis (including tRNA dysfunction, ribosomopathies, deregulation of the integrated stress response and deregulation of the mTOR pathway) and describe how deregulation of translation generates the phenotypic variability observed in these disorders.

Aim: This is a description of the largest breast cancer (BC) registry in Iran, termed the Shiraz Breast Cancer Registry (SBCR)., Methods: Data on baseline and clinical characteristics, socioeconomic status, imaging, physical examination, histopathology, treatment and prognosis have been recorded for each individual., Results: Overall, 5937 were included in the report. Mean age of first presentation was 49.05 ± 11.69 years. Mean tumor size was 2.78 ± 1.76 cm. Most patients had stage 2 (46.9%) and 3 (25.5%) BCs, respectively. Most common type of BC was invasive ductal carcinoma (83.3%), followed by medullary carcinoma (3.8%). Overall, 12.9% were triple negative (HER2-, ER- and PR-)., Conclusion: The study provides an overview on the status of BC's in Iran and a wide opportunity for future studies.