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Hossein Karami,1 Hadi Darvishi-Khezri,2 Mehrnoush Kosaryan,1 Rosetta Akbarzadeh,2 Mojdeh Dabirian3 1Department of Pediatrics, Thalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran; 2Student Research Committee, Thalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran; 3Department of Cardiology, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran Introduction: Pulmonary arterial hypertension (PAH) is relatively prevalent in patients with thalassemia. PAH treatment is necessary as the prevalence of Doppler-estimated PAH and the resultant mortality is high in such patients. Materials and methods: This study aimed at evaluating the effect of bosentan therapy on patients with thalassemia suspected of PAH. Based on pulsed Doppler echocardiography, all the cases were suspected of severe PAH. Consequently, bosentan was initiated at a dose of 62.5 mg twice a day for 4 weeks, which was increased to 62.5–125 mg twice a day, if no adverse side effects were observed. Results: The results of this study showed that pulmonary artery pressure (PAP) decreased after the administration of bosentan in three cases, from 160 to 120, 110 to 65, and 60 to 25 mmHg; in other words, the PAP reduced in the mentioned cases by 25%, 36.4%, and 58.4%, respectively. Conclusion: In this study, PAP improved after bosentan therapy in patients with β-thalassemia suspected of PAH; however, further studies are required to confirm the findings. Keywords: β-thalassemia major, pulmonary arterial hypertension, pulsed Doppler echocardiography, bosentan, tricuspid regurgitation jet velocity, right ventricular pressure

Critical-sized bone defects have, in many cases, posed challenges to the current gold standard treatments. Bioactive glasses are reported to be able to stimulate more bone regeneration than other bioactive ceramics; however, the difficulty in producing porous scaffolds made of bioactive glasses has limited their extensive use in bone regeneration. On the other hand, calcium phosphate ceramics such as synthetic hydroxyapatite and tricalcium phosphate are widely used in the clinic, but they stimulate less bone regeneration. This paper gives an overview of the recent developments in the field of bioactive nanoparticles, with a focus on nanohydroxyapatite and bioactive glasses for bone repair and regeneration. First, a brief overview of the chemical structure and common methods used to produce synthetic nanohydroxyapatite and bioactive glasses has been presented. The main body of the paper covers the physical and biological properties of these biomaterials, as well as their composites with biodegradable polymers used in bone regeneration. A summary of existing challenges and some recommendations for future directions have been brought in the concluding section of this paper.

Introduction: Combined factor V and VIII deficiency is a rare inherited autosomal recessive, which has been reported in a number of populations around the world. However, this disease appears to be most common in Mediterranean, and Middle East population. Recently the gene locus was mapped on the long arm of chromosome 18. Materials and Method: Five patients of a family with Combined deficiency of factor V and factor VIII were referred to Gh'm Hospital in Mashhad. Four affected children their and father were examined carefully. Diagnosis was made based on the clinical symptoms and Para clinic findings. Pedigree was drawn and after getting consent, peripheral blood samples from patients and parents were taken. Lymphocytes were cultured and cells were harvested. GTG bandings was performed and karyogram were analysed. Results: These patients were two girls (20 and 21 years old) and two boys (5 and 15 years old) alongside their father who was 44 years. Consanguinity was present in this family. Combined deficiency of factor V and factor VIII was diagnosed in all patients. They had mild bleeding manifestations, easy bruising, post-traumatic bleeding, and bleeding after tooth extractions. Clinical findings were confirmed as a prolonged prothrombin time and partial thromboplastin time; all members of this family had low levels of factor V and factor VIII. Cytogenetics study did not show any chromosomal abnormality. Conclusion: Since chromosomal abnormality was not revealed in all affected members of this family and consanguinity was present, so autosomal recessive and multifactorial condition could be mentioned. For further molecular genetics investigation, DNA samples from patients and healthy members in family were obtained. Identification of variation in this gene should provide new insight into the biology of Factor V and Factor VIII production. [ABSTRACT FROM AUTHOR]

Introduction: Wilson disease (WD) is caused by mutations in the ATP7B gene, a disorder in copper metabolism. It is characterized by neuropsychiatric symptoms with frequent extrapyramidal and intellectual presentations. Materials and Method: Clinical and laboratory findings of 30 patients who were referred to the Wilson's disease clinic in Ghaem Hospital, Mashhad, Iran were collected. Complete family history was obtained followed by a thorough physical examination and appropriate laboratory tests. Pedigrees were drawn and peripheral blood samples were taken. DNA was extracted based on the established methods. Results: Our finding showed that Initial symptoms occurred at a mean age of 12.3 years. The most common neurologic signs were dysarthria, tremor, writing difficulties, and ataxia followed by hyper salivation and headache. Somatic symptoms including abdominal pain, hepatomegaly, splenomegaly, cirrhosis of the liver, and thrombocytopenia were present in almost all patients. The diagnosis was confirmed by biochemical examinations, which found a low rate of copper in blood, a sinking rate of ceruloplasmin and a very high rate of urinary copper. The Kayser-Fleischer ring was presented in 28 patients (93%). Pedigrees analysis was showed 38% of patients had a history of Consanguinity. The most common psychiatric features were abnormal behavior and personality change. CT scan and MRI showed brain atrophy in 78% of the patients. Conclusion: The diagnosis of Wilson's disease still depends primarily on the evaluation of clinical and laboratory evidence of abnormal copper metabolism. Association of consanguinity and WD was confirmed in almost third of patients in this study, so a large number of patients in a population with first cousin marriages were suggested. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the effects of Aloe vera supplementation on serum inflammatory factors, blood sugar and lipid profiles in hemodialysis patients., Materials and Methods: Totally, 50 hemodialysis patients were allocated randomly to either Aloe vera or placebo groups. The Aloe vera group received 2 Aloe vera capsules daily for 8 weeks (500 mg/day). Serum C-reactive protein (hs- CRP), Fasting blood glucose (FBS), and lipid profiles levels were evaluated at the baseline and the end of the eighth week., Results: Aloe vera supplementation for 8 weeks was associated with a significant reduction of serum hs- CRP (p=0.004), total cholesterol (p=0.01), low density lipoprotein (LDL) (p=0.02) leves and increased high density lipoprotein (HDL) (p=0.002) concentration in the hemodialysis patients., Conclusion: Aloe vera supplementation is beneficial in improvement of cardiovascular risk factors in hemodialysis patients., Competing Interests: The authors have declared that there is no conflict of interest. We also declared no financial or other conflict with Barij Essence Kashan Company.

In this work, the interaction of NaCl aqueous solution with graphene (G), graphene oxide (GO), and graphite oxide (GTO) is studied using the ReaxFF module of Amsterdam Modeling Suite (AMS) software. We consider four models using the NaCl aqueous solution, containing a graphene sheet (G), a single sheet of GO with epoxide and hydroxyl groups on its surface, 4 layers of GO to model GTO, and a bulk NaCl solution as a reference. The structural and dynamical properties of G, GO, and GTO were quantified by analyzing the functional groups, radial distribution functions, density profiles and diffusivities of water and ions. Due to the reactive force field, the systems underwent spontaneous modification of surface functional groups during the first 750 ps after which the structure stabilizes (the energy stabilizes in less than 400 ps). Pristine graphene in contact with the NaCl solution formed hydroxyl groups on the edges, i.e. , converted to partially reduced graphene oxide. The epoxy groups (O e ) on the initial GO were rather unstable, leading to a reduction of their number, however, there was an increase in the number of hydroxyl groups (O h ), mainly at the edges. The interactions of NaCl with the carbon-based sheets are rather weak, including GO and GTO which are decorated with numerous functional groups. Diffusion coefficients of water agree with the available data, but discrepancies in Na + and Cl - diffusivity compared to other references underscore the need for further development in the dynamic parameters of the reactive force field used. In essence, our research provides specific data previously unreported, laying a foundation for advancing water desalination system design. The study's novelty lies in its realistic approach to graphene/graphene oxide modification, comprehensive characterization, and the application of the reactive force field to explore the graphene oxide-NaCl aqueous interface, contributing to the development of a practical membrane system for water desalination.

Monocytes play a significant role in the pathogenesis of most inflammatory diseases, including autoimmune diseases. Herein, different subpopulations of monocytes often play differential, partially antagonistic roles, in the regulation of tissue populations. Pemphigoid diseases constitute a group of autoimmune blistering skin diseases featuring a marked infiltration of the dermis with immune cells, including monocytes. The monocyte subsets infiltrating the skin, however, have largely remained elusive. Monocyte adhesion and recruitment into the inflamed tissues are regulated by chemokine receptors, most prominently by CCR2 and CX3CR1. To delineate the involvement of monocyte populations in autoimmune blistering skin diseases, we spatiotemporally monitored the dynamic spectrum of monocyte populations that infiltrate the inflamed skin using multiphoton intravital imaging and reporter mice for chemokine receptors. Experimental epidermolysis bullosa acquisita (EBA) was induced by injection of anti-murine type VII collagen (amCOLVII) IgG into the Csf1r EGFP -reporter mice, where circulating myeloid cells, such as monocytes and neutrophils, express an EGFP. EGFP + cells, including neutrophils and monocytes, were present in the skin, immediately after the deposition of the amCOLVII antibody at the dermal-epidermal junction. To investigate the recruitment and involvement of different monocyte-derived cell populations in the disease course further, EBA was induced in CCR2 RFP/+ -reporter and CX3CR1 GFP/+ -reporter mice. A comparable distribution of red fluorescent protein (RFP) + or green fluorescent protein (GFP) + was found in both diseased mice and their respective controls over time, indicating the similar recruitment of monocytes into the skin following the binding of autoantibodies. Experiments were extended to the CCR2 RFP/RFP -deficient and CX3CR1 GFP/GFP -deficient mice to determine whether monocyte recruitment and disease severity are compromised in the absence of the receptor. A comparable pattern was seen in the recruitment of monocytes into the skin in both reporter and deficient mice. However, in contrast to similar disease severity between CX3CR1-deficient and reporter mice, CCR2-deficient mice developed significantly less disease than CCR2-reporter mice, as indicated by the percentage of affected area of ears. Collectively, our observations indicate that while CCR2 and CX3CR1 receptors are not involved in the recruitment of monocytes into the skin, CCR2 deficiency is associated with improved disease outcomes in experimental EBA in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akbarzadeh, Czyz, Thomsen, Schilf, Murthy, Sadik and König.)

Detecting clinical keratoconus (KCN) poses a challenging and time-consuming task. During the diagnostic process, ophthalmologists are required to review demographic and clinical ophthalmic examinations in order to make an accurate diagnosis. This study aims to develop and evaluate the accuracy of deep convolutional neural network (CNN) models for the detection of keratoconus (KCN) using corneal topographic maps. We retrospectively collected 1758 corneal images (978 normal and 780 keratoconus) from 1010 subjects of the KCN group with clinically evident keratoconus and the normal group with regular astigmatism. To expand the dataset, we developed a model using Variational Auto Encoder (VAE) to generate and augment images, resulting in a dataset of 4000 samples. Four deep learning models were used to extract and identify deep corneal features of original and synthesized images. We demonstrated that the utilization of synthesized images during training process increased classification performance. The overall average accuracy of the deep learning models ranged from 99% for VGG16 to 95% for EfficientNet-B0. All CNN models exhibited sensitivity and specificity above 0.94, with the VGG16 model achieving an AUC of 0.99. The customized CNN model achieved satisfactory results with an accuracy and AUC of 0.97 at a much faster processing speed compared to other models. In conclusion, the DL models showed high accuracy in screening for keratoconus based on corneal topography images. This is a development toward the potential clinical implementation of a more enhanced computer-aided diagnosis (CAD) system for KCN detection, which would aid ophthalmologists in validating the clinical decision and carrying out prompt and precise KCN treatment., (© 2023. The Author(s).)

Introduction: Progressive loss of regulatory T cell (Treg)-mediated control over autoreactive effector T cells contributes to the development of systemic lupus erythematosus (SLE). Accordingly, we hypothesized that Treg may also have the capacity to suppress the activation of autoreactive CD4 + T cells that are considered to drive autoimmunity., Methods: To investigate whether Treg are involved in the control of autoreactive CD4 + T cells, we depleted CD25 + Treg cells either in vivo or in vitro , or combined both approaches before antigen-specific stimulation with the SLE-associated autoantigen SmD1(83-119) in the NZB/W F1 mouse model either after immunization against SmD1(83-119) or during spontaneous disease development. Frequencies of autoantigen-specific CD4 + T cells were determined by flow cytometry using the activation marker CD154., Results: Both in vitro and in vivo depletion of CD25 + Treg, respectively, increased the frequencies of detectable autoantigen-specific CD4 + T cells by approximately 50%. Notably, the combined in vivo and in vitro depletion of CD25 + Treg led almost to a doubling in their frequencies. Frequencies of autoantigen-specific CD4 + T cells were found to be lower in immunized haploidentical non-autoimmune strains and increased frequencies were detectable in unmanipulated NZB/W F1 mice with active disease. In vitro re-addition of CD25 + Treg after Treg depletion restored suppression of autoantigen-specific CD4 + T cell activation., Discussion: These results suggest that the activation and expansion of autoantigen-specific CD4 + T cells are partly controlled by Treg in murine lupus. Depletion of Treg therefore can be a useful approach to increase the detectability of autoantigen-specific CD4 + T cells allowing their detailed characterization including lineage determination and epitope mapping and their sufficient ex vivo isolation for cell culture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rosenberger, Undeutsch, Akbarzadeh, Ohmes, Enghard, Riemekasten and Humrich.)

Objectives: To compare changes in corneal biomechanical parameters one year after corneal cross-linking (CXL) in keratoconus (KCN) eyes of different severities., Methods: Seventy-five eyes with mild, moderate, and severe grades of KCN (n = 24, 31, and 20 eyes, respectively) that were treated with CXL, based upon the standard Dresden protocol, were included. The corneal biomechanical assessment was performed using Corvis ST and Ocular Response Analyzer (ORA). Changes in Corvis's dynamic corneal response (DCR) parameters and ORA's derived parameters (corneal hysteresis (CH), and corneal resistance factor (CRF)) were assessed whilst the corneal thickness and intraocular pressure were considered as covariates., Results: There was no statistically significant difference in the corneal biomechanical parameters obtained using both devices after surgery separately in different KCN grades, except for the deformation amplitude (DA) in the severe KCN group (P = 0.017). Changes in the classic parameters of the highest concavity phase of Corvis ST (peak distance, radius, and DA) were more positive and in the newer parameters (integrated inverse radius (IIR), deformation amplitude ratio (DAR)) more negative in the severe group compared to the other groups. Also, the mean change in CH (P = 0.710), and CRF (P = 0.565), showed a negative shift in higher grades of KCN; however, there was no significant difference in the mean changes of all parameters between different groups. (P > 0.05)., Conclusions: Similar changes in the Corvis ST and ORA parameters in mild, moderate, and severe KCN indicate biomechanical stability and the effective role of CXL in stopping the progressive nature of keratoconus in eyes of varying severities one year after CXL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Coronavirus 2019 (COVID-19) pandemic has incurred a health challenge. Patients suffer from many physical and mental disorders. To accurately identify the experience of patients with Covid-19 in the Iranian society., Materials and Methods: This qualitative research was conducted using the grounded theory. The data of this grounded theory study were collected using 32 semi-structured interviews with participants and field notes including the patients with Covid-19, nurses, physicians, and the patients' families. Data analysis was performed using Corbin and Strauss (2008) approach for concepts, context, process, and categories' integration., Results: Qualitative analysis of data led to the extraction of 54 sub-categories and 7 final categories. "Isolation, fear of death, and fear of infection of relatives and family members" were identified as the main issue. The context to this concern was the "unfamiliarity with the virus due to its ambiguous nature that was obtained with a wide range of symptoms." Facing this issue, the patients used the strategy of "adherence to health protocol in the coronavirus infection process" that was recognized as the central variable., Conclusion: The ambiguous and complex nature of the emerging virus, the appearance of different symptoms in different people, and the fear of infecting others, death and anxiety due to unknown complications of the disease make patients go through the most difficult experience of their lives. That requires ongoing training on up-to-date prevention and treatment protocols, along with the emergence of mutated viruses and new symptoms., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Education and Health Promotion.)

Systemic sclerosis (SSc) is a chronic, multisystem connective tissue, and autoimmune disease with the highest case-specific mortality and complications among rheumatic diseases. It is characterized by complex and variable features such as autoimmunity and inflammation, vasculopathy, and fibrosis, which pose challenges in understanding the pathogenesis of the disease. Among the large variety of autoantibodies (Abs) present in the sera of patients suffering from SSc, functionally active Abs against G protein-coupled receptors (GPCRs), the most abundant integral membrane proteins, have drawn much attention over the last decades. These Abs play an essential role in regulating the immune system, and their functions are dysregulated in diverse pathological conditions. Emerging evidence indicates that functional Abs targeting GPCRs, such as angiotensin II type 1 receptor (AT1R) and the endothelin-1 type A receptor (ETAR), are altered in SSc. These Abs are part of a network with several GPCR Abs, such as those directed to the chemokine receptors or coagulative thrombin receptors. In this review, we summarize the effects of Abs against GPCRs in SSc pathologies. Extending the knowledge on pathophysiological roles of Abs against GPCRs could provide insights into a better understanding of GPCR contribution to SSc pathogenesis and therefore help in developing potential therapeutic strategies that intervene with pathological functions of these receptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akbarzadeh, Müller, Humrich and Riemekasten.)

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus). Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases. Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions., (Copyright © 2023. Published by Elsevier B.V.)

Background: There is evidence that probiotics can increase the availability of iron. The aim of current study was to determine the effects of synbiotic supplementation on the haematological parameters and anaemia in haemodialysis patients., Methods: This study was a randomized, double-blind, placebo-controlled trial. Fifty patients were randomly selected from the haemodialysis section of Vaseii Hospital, Sabzevar, Iran. Subjects in the symbiotic and control groups received 2 capsules of synbiotic supplement or placebo, respectively, once a day for 8 weeks. Blood samples were divided into two test tubes in equal volumes. Blood haemoglobin, haematocrit, transferrin saturation, red blood cells (RBCs), and total iron binding capacity (TIBC) were measured with auto-analyser. Ferritin was determined using Sandwich enzyme-linked immunosorbent assay (ELISA)., Results: Twenty tree patients in each group completed the study. Significant results were recorded in synbiotic groups regarding the concentration of blood haemoglobin, haematocrit, transferrin saturation, the number of RBCs, and serum ferritin compare to placebo group (P < .05). At the end of week 8, TIBC significantly decreased in synbiotic than placebo group (P < .05)., Conclusion: Synbiotic supplementation could be a safe and promising candidate in improving anaemia in CKD patients., (© 2023 Asian Pacific Society of Nephrology.)

Purpose of Review: Low-dose interleukin-2 (IL-2) therapy is increasingly recognized as a promising novel therapeutic concept in inflammatory and autoimmune diseases, in particular in systemic lupus erythematosus (SLE). As IL-2 is indispensable for the growth and survival of regulatory T cells (Treg), deficiency of this regulatory cytokine plays a significant role in immune dysregulation and breach of tolerance in SLE. Recovery of Treg activity by low-dose IL-2 therapy directly interferes with the immune pathology in SLE and thus can be considered a targeted treatment approach with a unique and physiological mode of action., Recent Findings: In this review, the pathophysiological rationales behind the concept of low-dose IL-2 therapy in SLE will be explained and major advances in translational research and the clinical development of low-dose IL-2 therapy focusing on the results from two recent, randomized and placebo-controlled phase 2 trials will be highlighted., Summary: Several clinical studies including two recent randomized trials have proven the very good safety profile of low-dose IL-2 therapy and its capability to selectively recover and expand the Treg population in patients with active SLE. Given the emerging evidence for the clinical potential of low-dose IL-2 therapy in SLE, these studies strongly confirm the pathophysiological concept behind this targeted therapeutic approach in SLE and provide a robust basis for establishing further in-depth and confirmatory clinical trials testing the application of low-dose IL-2 in SLE and other autoimmune diseases., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Approximately 5% of the world-wide population is affected by autoimmune diseases. Overall, autoimmune diseases are still difficult to treat, impose a high burden on patients, and have a significant economic impact. Like other complex diseases, e.g., cancer, autoimmune diseases develop over several years. Decisive steps in the development of autoimmune diseases are (i) the development of autoantigen-specific lymphocytes and (often) autoantibodies and (ii) potentially clinical disease manifestation at a later stage. However, not all healthy individuals with autoantibodies develop disease manifestations. Identifying autoantibody-positive healthy individuals and monitoring and inhibiting their switch to inflammatory autoimmune disease conditions are currently in their infancy. The switch from harmless to inflammatory autoantigen-specific T and B-cell and autoantibody responses seems to be the hallmark for the decisive factor in inflammatory autoimmune disease conditions. Accordingly, biomarkers allowing us to predict this progression would have a significant impact. Several factors, such as genetics and the environment, especially diet, smoking, exposure to pollutants, infections, stress, and shift work, might influence the progression from harmless to inflammatory autoimmune conditions. To inspire research directed at defining and ultimately targeting autoimmune predisease, here, we review published evidence underlying the progression from health to autoimmune predisease and ultimately to clinically manifest inflammatory autoimmune disease, addressing the following 3 questions: (i) what is the current status, (ii) what is missing, (iii) and what are the future perspectives for defining and modulating autoimmune predisease., Competing Interests: Declaration of Competing Interest Christian M. Karsten has received honoraria for speaking from Alexion, and Vifor Pharma during the last 3 years. Peter Lamprecht has received honoraria for speaking or consulting or has obtained research grants from BMBF, BMS, DFG, DGRh, GSK, Janssen, Roche, UCB, and Vifor Pharma during the last 3 years. Gabriela Riemekasten has received honoraria for speaking or consulting or has obtained research grants from Abbvie, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Galapagos, Janssen Cilag, Novartis, Pfizer during the last 3 years. Enno Schmidt receives grant funding from Euroimmun, Incyte, Dompe, Admirx, Synthon/biondis, Bayer, Pharmix, Alpine Immune, AstraZeneca, Sanofi, ArgenX, UCB, Novartis, Biotest, Fresenius Medical Care, and is consulting for Roche, Imevax, Thermo Fisher, Janssen, Topas, Bristol-Myers Squibb, Almirall, and Chugai. Ralf J. Ludwig has received honoraria for speaking or consulting or has obtained research grants from Novartis, Lilly, Bayer, Dompe, Synthon, Argen-X, and Incyte during the last 3 years. All other authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the normal immune system, T cell activation is tightly regulated and controlled at several levels to ensure that activation occurs in the right context to prevent the development of pathologic conditions such as autoimmunity or other harmful immune responses. CD4 + FoxP3 + regulatory T cells (Treg) are crucial for the regulation of T cell responses in the peripheral lymphatic organs and thus for the prevention and control of autoimmunity. In systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease with complex etiology, a disbalance between Treg and pathogenic effector/memory CD4 + T cells develops during disease progression indicating that gradual loss of control over T cell activation is an important event in the immune pathogenesis. This progressive failure to adequately regulate the activation of autoreactive T cells facilitates chronic activation and effector/memory differentiation of pathogenic T cells, which are considered to contribute significantly to the induction and perpetuation of autoimmune processes and tissue inflammation in SLE. However, in particular in humans, little is known about the factors which drive the escape from immune regulation and the chronicity of pathogenic T cell responses in an early stage of autoimmune disease when clinical symptoms are still unapparent. Here we briefly summarize important findings and discuss current views and models on the mechanisms related to the dysregulation of T cell responses which promotes chronicity and pathogenic memory differentiation with a focus on the early stage of disease in lupus-prone individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ohmes, Comdühr, Akbarzadeh, Riemekasten and Humrich.)

The performance of a desalination membrane depends on a specific pore size suitable for both water permeability and salt rejection. To increase membrane permeability, the applied pressure should be increased, which creates the need to improve membrane stability. In this research article, a molecular dynamics (MD) simulation was performed using ReaxFF module from Amsterdam Modeling suite (AMS) software to simulate water desalination efficiency using a single and multi-layer graphene membrane. The graphene membrane with different pore sizes and a multi-layer graphene membrane with descending pore size in each layer were designed and studied under different pressures. The stability of the membrane was checked using Material Studio 2019 by studying the dynamics summary. The single-layer graphene membrane was evaluated under pressures ranging from 100 to 500 MPa, with the salt rejection ranging from 95% to 82% with a water permeability of 0.347 × 10 -9 to 2.94 × 10 -9 (mm.g.cm -2 s -1 .bar -1 ), respectively. Almost 100% salt rejection was achieved for the multi-layer graphene membrane. This study successfully demonstrated the design and optimization of graphene membrane performance without functionalization.

In this study, BiOCl based nanocomposites were used as photocatalytic membranes for a simulated study on water desalination in reverse osmosis membrane systems. Through molecular dynamic simulation, the molecular structure of BiOCl, BiOCl/Ag 2 S and BiOCl/Bi 2 O 3 heterojunctions were designed and their electronic properties, mechanical properties, and membrane performance for water desalination were evaluated for the first time. The molecular structure was created, and a geometry optimization task was used to optimize it. Material Studio 2019 CASTEP was used for simulation of the electronic and mechanical properties and water desalination was performed by ReaxFF software under pressures between 0 and 250 MPa. The novel BiOCl based nanocomposites showed improved electronic and mechanical properties and, most importantly, improvements in salt rejection and water permeability as compared to well-known materials such as graphene and MoS 2 . BiOCl and BiOCl/Ag 2 S had a bandgap around two, which is the ideal bandgap for semiconductor photocatalysts. A salt rejection of 98% was achieved under an applied pressure of 10 MPa. Salt rejection was higher for BiOCl/Bi 2 O 3 , while water permeability was higher for BiOCl/Ag 2 S. The monolayer BiOCl was unstable under pressures higher than 50 MPa, but the mechanical stability of BiOCl/Ag 2 S increased twofold and increased fourfold for BiOCl/Bi 2 O 3 , which is even higher than MoS 2 . However, between the three nanocomposites, BiOCl/Ag 2 S was found to be the most ideal photocatalytic nanocomposite membrane.

This study aimed to evaluate the ambient dose equivalent around a C-arm device during spinal surgeries and determine the optimum locations for the surgeon and staff to keep radiation exposure as low as reasonably achievable. Furthermore, cancer risk incidence was estimated using the excess relative risk (ERR) concept of the biologic effects of ionizing radiation VII report for operating room (OR) staff. A lateral projection of the C-arm setup was considered in the current study. The ambient dose equivalent rate was measured using an electronic dosimeter in 30° steps all around for 1, and 1.6-m heights as well as 1, and 2-m distances away from a water tank (scattering medium). By assuming a typical workload, the annual ambient dose and a maximum number of permissible operations were determined. For a worst-case scenario, the dose was used to estimate the ERR for various organs including prostate, ovary, breast, lung, thyroid, and colon for attained ages of 35, 40, and 50 years. The maximum ambient dose equivalent rate was seen at 330° and 30° (about 600 µSv/h at 1 m height and a distance of 1 m from the scattering medium). The corresponding permissible workload for an OR staff was about 30,660 operations. Based on the obtained results, 60° next to the image intensifier was the optimum position for the surgeon, while 30° next to the tube was the worst position because of backscattered radiation. The ERR results showed that the lung and colon have the highest cancer risk incidence among the considered organs for both males and females, respectively., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prostate cancer (PCa) and benign prostate hyperplasia (BPH) are highly prevalent heterogeneous disorders among men. Whereas PCa and BPH underline common pathological features, apoptotic-related genes might be differentially expressed in these diseases. This study was aimed at testing BCL-2 as well as BALR-2 and ZEB2-AS1 apoptosis-related long non-coding RNA (lncRNA) in patients with PCa and BPH. The expression levels of the BCL-2 gene and ZEB2-AS1 lncRNA were upregulated in tumoural tissues in comparison to adjacent non-cancerous tissues (ANCTs) and BPH tissues. In contrast, the expression level of BALR-2 lncRNA was significantly higher in BPH compared with tumoural tissues. Furthermore, while no association was noticed between the relative expression of ZEB2-AS1 and the tumour grade, the relative expression of BCL-2 and BALR-2 is strongly associated with a higher grade of the tumour in PCa samples compared with the ANCTs. The receiver operating characteristic (ROC) curve analysis indicated the highest specificity and diagnostic value in distinguishing PCa and ANCTs as well as PCa and BPH, respectively. In conclusion, altered expression of BCL-2 and BALR-2 was observed to be associated with tumoural progression and could be used as potential candidates for distinguishing PCa tissues from ANCTs or BPH samples., (© 2021 Wiley-VCH GmbH.)

Due to the rapid depletion of water resources, more interest is paid for the efficient desalination process in recent years. MoS 2 membrane aroused attention due to its high mechanical stability and electronic properties, which can sustain extra-large strains. In this study, the electronic properties and water desalination performance of TiO 2 /MoS 2 -hexagonal, and TiO 2 /MoS 2 -rhombohedral nanocomposites bilayer membranes were studied and simulated for the first time. The effect of TiO 2 in the performance of MoS 2 was observed in water desalination under the defined applied pressure ranging from 50 to 250 MPa with a 6.4 Å pore diameter. The membrane structure is created and optimized. The energy minimized for TiO 2 from - 19,596.4282 kcal/mol for the initial structure to - 19,605.1611 kcal/mol for the final structure. For TiO 2 /MoS 2 -hexagonal, the energy minimized from - 4955.54271 eV) to - 4955.62091 eV and TiO 2 /MoS 2 -rhombohedral from - 6042.26925 eV to - 6046.91835 eV. A molecular dynamic (MD) simulation was performed using Material Studio 2019 to study the electronic properties under 0-1 eV electric field using the CASTEP code. The results showed a better photocatalytic performance under the external electric field. The effect of external electric field significantly intensifies absorption in the visible range and achieved a high photocatalytic activity on TiO 2 /MoS 2 . TiO 2 , TiO 2 /MoS 2 -hexagonal and TiO 2 /MoS 2 -rhombohedral nanocomposites bilayer membranes are simulated and evaluated for the water desalination using ReaxFF software. Both MoS 2 phases with TiO 2 have achieved a high salt rejection up to 97% (P-value = 0.0036, R 2  = 0.958), while TiO 2 /MoS 2 -rhombohedral achieved the highest permeability (6.0*10 -8  mm g cm -2  s -1  bar -1 ) (P-value = 0.000296, R 2  = 0.972) under 250 MPa applied pressure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

DFT calculations using Material Studio (2019) were used to ascertain the changes in electronic properties of recycled expanded polystyrene (rEPS) after modification with nanoparticles of ZnS and ZnO. The nanocomposites were obtained using rEPS and suitable metal salt precursors via a solvothermal method. The XRD analysis was conducted to obtain the crystallography data of the new rEPS-based nanocomposites. Using Material Studio simulation software, the potential photocatalytic properties of the new prepared material was predicted and information on the electronic band structure was extracted. The calculated band gap values for rEPS and ZnS-ZnO-rEPS nanocomposite were 4.217 eV and 2.698 eV, respectively. Furthermore, our results showed that the nanocomposite is a p-type semiconductor. From the electronic structure and the band gap narrowing, these nanocomposites obtained from a waste material may have some potential in photocatalytic applications., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Monocyte chemoattractant protein-1 (MCP-1) is highly expressed by lymphocytes at skin sites affected by alopecia areata (AA). Variations in MCP-1 as well as in methylene-tetrahydrofolate reductase (MTHFR), a key enzyme related to many inflammatory pathologies, have been associated with several autoimmune disorders. This study was designed to test a possible association between MCP-1 and MTHFR variations and altered expression of their genes and the risk of AA., Methods: Blood samples of patients (60) suffering from AA as well as healthy subjects (60) were collected. Gene expression levels of MCP-1 and MTHFR were evaluated by real-time reverse-transcription polymerase chain reaction analysis. Moreover, MCP-1 rs1024611 (A-2518G) and MTHFR rs1801133 (C677T) polymorphisms were genotyped by using polymerase chain reaction-restriction fragment length polymorphism assays., Results: In contrast to MCP-1, the MTHFR gene expression was found to be significantly higher in patients than in controls. Further stratification of the patients revealed that polymorphic genotypes in MCP-1 (AG + GG) and MTHFR (CT + TT) could significantly alter gene expression levels. Elevation of MCP-1 expression was significantly associated with the total number of variant MCP-1 and MTHFR alleles. However, no statistically significant difference was noticed in the genotypic distribution of MCP-1 and MTHFR variations between patients and controls., Conclusion: In summary, despite MCP-1 rs1024611 and MTHFR rs1801133 variations are not associated with AA risk, they may implicate the disease pathogenesis by influencing MCP-1 activity., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: T-helper 2 (Th2)-associated cytokines are involved in the pathogenesis of bullous pemphigoid (BP), an autoimmune skin disease. Increased expression of Th2 cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13 have been observed in serum, skin biopsies and/or blister fluid. This study aimed to uncover a possible association between Th2 cytokine genetic variations and susceptibility to BP., Methods: In a cohort study, blood samples of BP patients and controls were obtained and variations in IL-4 (rs2243250 and rs2070874), IL-4R (rs1805010), IL-5 (rs2069812), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, and rs1800872), and IL-13 (rs1800925 and rs20541) were genotyped by PCR-RFLP assays. Furthermore, quantitative expression levels of IL-13 gene were evaluated by real-time RT-PCR analysis., Results: Among the studied variations, a significantly higher frequency of the C-allele was observed in IL-13 gene variation (rs1800925) in the healthy individuals than BP patients. This may indicate a protective effect of C-allele on predisposition to BP. Considering individuals carrying polymorphic genotypes compared to wild genotype, the minor G-allele of IL-4R rs1805010 and A-allele of IL-13 rs20541 had a promotive and protective effect, respectively, on predisposing to the development of BP. No significant difference in IL-13 mRNA expression was detected between BP patients and healthy individuals., Conclusions: Our results indicate that IL-13 rs1800925 variation may be a protective genetic marker for the development of BP. Given this preventive effect against BP, therapeutic strategies could potentially be developed interfering with the functions of IL-13 cytokine, which seems to be integral in the pathogenesis of eosinophilic inflammatory disorders, such as BP.

Background: Asthma is the most commonly occurring respiratory illness during pregnancy. Associations with complications of pregnancy and adverse perinatal outcome have been established. However, little is known about quality of life (QoL) in pregnant women with asthma and how it relates to asthma control particularly for Iran., Objective: To determine the relationship between asthma related QoL and asthma control and severity., Methods: We conducted a prospective study in pregnant women with asthma. We used the Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire (AQLQ) and the guidelines of the Global Initiative for Asthma for assessment of asthma severity., Results: Among 1603 pregnant women, 34 were diagnosed with asthma. Of these 13 had intermittent, 10 mild, 8 moderate and 3 severe persistent asthma. There was a significant decrease of QoL with poorer asthma control (p = 0.014). This decline could be due to limitations of activity in those with poorer asthma control, which is underlined by the significant decline of QoL with increasing asthma severity (p = 0.024)., Conclusion: Although the majority of pregnant women with asthma had a favorable score in AQLQ, reduced QoL was related to increased asthma severity and poor asthma control. This underlines the importance of controlling asthma during pregnancy not only for the prevention of adverse pregnancy outcomes but also for the preservation of QoL., (© 2021. The Author(s).)

Aim: Glioblastoma multiforme (GBM) is the most invasive type of glial tumors. MicroRNAs as the small, noncoding RNAs have been revealed that play an important role in tumorigenic processes. So, they may be used as potential biomarkers for detection and prognosis of cancers at the early stages. In addition, they can be applied as therapeutic targets. In the present study, the expression levels of hsa-miR-27a-3p and EGFR were investigated in GBM., Methods: Real-time RT-PCR was applied to evaluate hsa-miR-27a-3p and EGFR expressions in the formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 50 GBM and 50 normal people., Results: The expression level of hsa-miR-27a-3p and EGFR was significantly different between cases and controls. Positive association was found between gene expressions and immunohistochemistry markers, such as Ki67 and glial fibrillary acidic protein, except for IDH1 status., Conclusion: We showed the association of hsa-miR-27a-3p and EGFR with GBM and it can be concluded that they have a promising potential to use as primary cancer biomarkers., (© 2020 John Wiley & Sons Australia, Ltd.)

Purpose: Unpredictability in acquiring an adequate number of high-quality oocytes following ovarian stimulation is one of the major complications in controlled ovarian hyperstimulation (COH). Genetic predispositions of variations could alter the immunological profiles and consequently be implicated in the variability of ovarian response to the stimulation., Design: Uncovering the influence of variations in AMHR2, LHCGR, MTHFR, PGR, and SERPINE1 genes with ovarian response to gonadotrophin stimulation in COH of infertile women., Methods: Blood samples of the women with a good ovarian response (GOR) or with a poor ovarian response (POR) were collected. Genomic DNA was extracted, and gene variations were genotyped by TaqMan SNP Genotyping Assays using primer-probe sets or real-time PCR Kit., Results: Except for PGR (rs10895068), allele distributions demonstrate that the majority of POR patients carried minor alleles of AMHR2 (rs2002555, G-allele), LHCGR (rs2293275, G-allele), MTHFR (rs1801131, C-allele, and rs1801133, T-allele), and SERPINE1 (rs1799889, 4G allele) genes compared to the GOR. Similarly, genotypes with a minor allele in AMHR2, LHCGR, MTHFR, and SERPINE1 genes had a higher prevalence among POR patients with the polymorphic genotypes. However, further genotype stratification indicated that the minor alleles of these genes are not associated with poor response. Multivariate logistic analysis of clinical-demographic factors and polymorphic genotypes demonstrated a correlation between FSH levels and polymorphic genotypes of SERPINE1 in poor response status., Conclusions: Despite a higher prevalence of AMHR2, LHCGR, MTHFR, and SERPINE1 variations in the patients with poor ovarian response, it seems that these variations are not associated with the ovarian response., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent β-thalassemia (TDT), through a placebo-controlled, crossover study., Methods: Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL)., Results: Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively., Conclusion: Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results., (© 2021 John Wiley & Sons Ltd.)