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Introduction. The coronavirus pandemic can cause anxiety and stress among people, which can make them practice self-medication. This study aimed to investigate the relationship between fear of corona and self-medication and antibiotics use. Methods. In a convenience sampling method, 250 people referring to COVID-19 centers including 16-hour comprehensive health services in Kermanshah, Iran, who tested positive and were not hospitalized were extracted from the SIB system. Data collection tools include three questionnaires including corona fear questionnaire, self-medication questionnaire, and self-medication by antibiotic questionnaire and an information form including demographic characteristics. Data were analyzed by SPSS version 25. Results. The prevalence of self-medication was 59.6%. There was a significant correlation between self-medication and gender (P value <0.05) and education level (P value <0.05); the most common reason for self-medication was easy access to medicines through pharmacy drug stores. The mean score of fear of corona was higher in women and those who were not in a good financial position due to a lack of suitable economic status to see a doctor. Conclusion. There was a direct and significant relationship between self-medication and self-medication by antibiotics. 59.6% of the participants used medicines themselves, buying over-the-counter in pharmacies. Also, there was a statistically significant difference between the mean score of corona fear in terms of not having a suitable economic status to see a doctor. This indicates that the lack of proper economic status among people with the coronavirus positive test to see a doctor increases the fear of the disease. [ABSTRACT FROM AUTHOR]

In this paper we introduce the concept of (weak) fuzzy subsupermodules based on (thin) supermodules different from fuzzy subhypermodules. In this study, the concept of α-cuts play a main role for constructing of extended (weak) fuzzy subsupermodules. In final, we introduce a notation of residual quotients of (weak) fuzzy subsupermodules and obtain some conditions to be a (weak) fuzzy subsupermodule. Also obtained some applied results in residual quotients of (weak) fuzzy subsupermodules of superrings as specially subsupermodules. [ABSTRACT FROM AUTHOR]

Variable antigen-binding domain of camelid single chain antibodies (VHH, Nanobody) and its conjugates are considered among very promising candidates in tumor diagnosis and treatment because of its small size, stability, and favorable bio-distribution. CD22 is a receptor that is expressed on most B cells and modulates their function. Targeting CD22 in B cell malignancies and disorders by monoclonal antibodies has shown promising results in vitro and in clinical trials. In this study, we investigate the impact of an anti-human CD22 VHH binding to CD22 on B cells and its internalization following attachment. Our findings demonstrate the proliferation inhibiting of these cells with no effect on apoptosis, in addition to the rapid internalization of the VHH. [ABSTRACT FROM AUTHOR]

CD22 is a B‐cell‐specific trans‐membrane glycoprotein, which is found on the surface of the most B cells and modulates their function, survival, and apoptosis. Recently, targeting this cell surface biomarker in B‐cell malignancies and disorders has attracted a lot of attention. The variable domain of camelid single‐chain antibodies (VHH, nanobody) is a form of antibodies with novel properties including small size (15–17 kDa), thermal and chemical stability, high affinity and homology to human antibody sequences. In this study, a novel anti‐CD22‐specific VHH (Nb) has been developed and characterized by the screening of an immunized phage display library and its binding to CD22+ B cells is evaluated. Produced anti‐CD22 VHH had a single protein band about 17 kDa of molecular size in Western blotting and its binding affinity was approximately 9 × 10−9 M. Also, this product had high specificity and it was able to recognize the natural CD22 antigen in CD22+ cell lysate as well as on the cell surface (93%). This anti‐CD22 VHH with both high affinity and specificity recognizes CD22 antigen well and can be used in diagnosis and treatment of B cell disorders and malignancies. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa possesses various virulence factors which contribute to the bacterial invasion and toxicity. Moreover, children suffered from Cystic Fibrosis (CF) and burn wounds are at a high risk of various bacterial infections. The aim of this study was to determine the prevalence of virulent genes in P. aeruginosa isolated from children with CF and burn wounds and comparing their virulence genes to figure out the role of every virulent factor in the infections. P. aeruginosa were isolated from sputum, oropharyngeal swabs, and broncho-alveolar lavage (BAL) specimens from CF and burn wounds between June 2013 and June 2014 in Tehran's hospitals. Bacterial genomic DNAs were extracted and uniplex, duplex and multiplex PCR were performed for detection of toxA , algD and plcN , exoS, lasB, plcH genes, respectively. The prevalence rate of virulence genes in P. aeruginosa isolated from CF was; toxA (63.1%), algD (64.6%), plcH (87.7%), plcN (60%), lasB (95.4%) and exoS (70.8%) and virulence genes in P. aeruginosa from burn patients were: toxA (36.9%), algD (70.1%), plcH (79%), plcN (63.1%), lasB (82%) and exoS (21.1%). The prevalence of three virulent genes in P. aeruginosa was higher in CF comparing to burn wound infections. We found that the number of toxA , lasB and exoS were significantly higher in the bacteria which were isolated from children with CF. This finding shows that these virulence factors play an important role in CF infections by P. aeroginosa . [ABSTRACT FROM AUTHOR]

Objective(s): Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL- 23, IL-4 and IFN-γ were assessed in activated chromatin-induced mouse model for SLE. Materials and Methods: Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3 starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-γ were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits. Results: The results showed that IL-17, IL-23, and IFN-γ mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL- 23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer. Conclusion: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii (T. gondii) is a ubiquitous protozoan parasite on our planet that causes toxoplasmosis. This study evaluated the seroprevalence and related risk factors for T. gondii infection in a population referred to healthcare centers in Meshkin-Shahr, Northwest Iran. Methods: A total of 400 blood samples were randomly collected from the general population and assessed using the anti-Toxoplasma antibodies, Immunoglobulin G and M (IgG and IgM) Enzyme-linked immunosorbent assay (ELISA) Kits in two steps before and during the coronavirus disease 2019 (COVID-19) pandemic, 2019–2020. The results were analyzed through logistic regression via SPSS 26 software. Results: Before the COVID-19 pandemic, anti-toxoplasma antibodies were detected in 39% of individuals (IgG: 38%, IgM: 0.5%, and IgG-IgM: 0.5%). Among the eleven risk factors evaluated, contact with soil and people awareness were significantly associated with T. gondii infection (p < 0.05). However, factors such as females, 20–39 age groups, junior high schools, housewives, rural areas, raw meat or vegetable consumption, vegetable or fruits washed by water, not detergent, and cat owners did not show a significant relationship with seropositivity (p > 0.05). After the outbreak of the COVID-19 pandemic, the overall seroprevalence for anti-T. gondii antibody increased to 49.7% (IgG: 47.7%, IgM: 0.5%, and IgG and IgM: 1.5%). Among these patients, 26% were positive for COVID-19. Additionally, before the COVID-19 pandemic, 40 samples were negative for anti-T. gondii antibodies but later became positive. The crude and adjusted models suggested that toxoplasmosis may be a possible risk factor for increased susceptibility to COVID-19, with an odds ratio (OR) of 1.28 (95% confidence interval (CI), 0.82–1.99; P < 0.05). Conversely, a non-significant protective effect against latent toxoplasmosis was observed in COVID-19-positive individuals (OR = 0.99; 95% CI, 0.51–1.92; P > 0.05), and COVID-19 positivity did not increase the levels of anti-T. gondii IgG antibodies. Conclusions: The general population in this region had a moderate seroprevalence of T. gondii. The increased number of COVID-19-positive patients with latent toxoplasmosis highlights the need to pay attention to the early diagnosis and proper treatment of toxoplasmosis in these patients and implement preventive programs in these areas for future possible viral infections. [ABSTRACT FROM AUTHOR]

Background: Aquaporins are channel proteins, form pores in the membrane of biological cells to facilitate the transcellular and transepithelial water movement. The role of Aquaporins in carcinogenesis has become an area of interest. In this study, we aimed to investigate the effects of adipose-derived mesenchymal stem cells secreted exosomes on the expression of aquaporin 5 and EGFR genes in the HCT-116 tumor cell line. Methods and results: Surface antigenic profile of Ad-MSCs was evaluated using specific markers. Exosomes were purified from the Ad-MSc supernatant while the quality and the shape of isolated exosomes were assessed by western blot and transmission electron microscopy (TEM) respectively. HCT-116 cells were co-cultured with MSC-conditioned medium (MSC-CM) and/or with 100 μg/ml of MSC-derived exosomes for 48 h and. Real-time PCR was carried out to determine the expression of aquaporin5 and EGFR in HCT-116. Relative expression levels were calculated using the 2-ΔΔct method. Our result showed that AQP5 and EGFR mRNA levels were significantly reduced in CM and/or exosomes treated HCT116 compare to the control group (P-value < 0.05). Conclusion: The current study showed that MSC derived exosomes could inhibit expression of two important molecules involved in tumor progression. Hence it seems MSCs-derived exosomes may hold a hopeful future as drug delivery vehicles which need the furtherer investigation. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer, the most common reproductive system cancer being women, is the fourth leading cause of cancer-related deaths. The use of mesenchymal stem cells (MSCs) for treating various diseases is being studied, but their use in cervical cancer has not been well explored. In this study we study investigated the effect of adipose tissue-derived MSCs on the apoptosis and proliferation of peripheral blood mononuclear cells (PBMCs) in co-culture with the HeLa cell line. MSCs were isolated from adipose tissue and then co-cultured with PBMCs, and HeLa cells at different time points (24, 48, and 72 hours). Materials and Methods: The effect of MSC cells on proliferation, apoptosis, and gene expression of the cytokines tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), interleukin (IL)-4, IL-2, and interferon-γ in PBMCs cultured together with HeLa cells was investigated using flow cytometry and real-time polymerase chain reaction (PCR), respectively. Results: Flow cytometry showed that co-culture of PBMCs/MSCs/HeLa significantly increased the proliferation of PBMCs at different time points, with a p-value of 0.0022. In addition, MSCs significantly decreased apoptosis of PBMCs in co-culture with HeLa at 48 h. the p-value was 0.0022. Real-time PCR showed that the expression of TGF-β in PBMCs/MSCs/HeLa co-culture increased after 24 h, with a p-value of 0.006. Conclusion: These data showed that adipose-derived MSCs can stimulate the proliferation and survival of PBMCs and enhance the apoptosis of HeLa cells, indicating their potential as immunomodulatory therapy for cervical cancer cells. However, further research is required to fully understand the underlying mechanisms and optimize therapeutic approaches involving PBMCs and MSCs. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GvHD) is the most common complication after stem cell transplantation, and also it is one of the primary limiting factors for the use of hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic cancers. GvHD. a systemic inflammatory disease, is caused by donor T cells recognizing the recipient's foreign antigens. In addition, an immune dysrégulation, caused by autoreactive immune cells, complicates potent inflammatory process following HSCT. While there is no one approved treatment method for GvHD, corticosteroids are the most common first-line treatment. Exosomes are biological vesicles between 30 and 120 nm in diameter, which carry various biologically active molecules. They are known to play a key role in the paracrine effect of mesenchymal stem cells with therapeutic and tissue repair effects, including an immunosuppressive potential. Exosomes are unable to replicate themselves but because of their small size and fluidlike structure, they can pass through physiological barriers. Exosome are relatively easy to prepare and they can be quickly sterilized by a filtration process. Administration of exosomes, derived from mesenchymal stem cells, effectively reduced GvHD symptoms and significantly increased HSCT recipients' survival. Mesenchymal stem cell-derived exosome therapy reduced clinical symptoms of GvHD in patients after HSCT. Studies in patients with GvHD described that that mesenchymal stem cell-derived exosomes inhibited the release of IFN-y and TNF-« by activated natural killer (NK cells), thereby reducing the lethal function of NK cells and inflammatory responses. Current review provides a comprehensive overview about the use of mesenchymal stem cells and their derived exosomes for the treatment of GvHD. [ABSTRACT FROM AUTHOR]

Despite knowledge gaps in understanding the full spectrum of the hyperinflammatory phase caused by SARS-CoV-2, according to the World Health Organization (WHO), COVID-19 is still the leading cause of death worldwide. Susceptible people to severe COVID-19 are those with underlying medical conditions or those with dysregulated and senescence-associated immune responses. As the immune system undergoes aging in the elderly, such drastic changes predispose them to various diseases and affect their responsiveness to infections, as seen in COVID-19. At-risk groups experience poor prognosis in terms of disease recovery. Changes in the quantity and quality of immune cell function have been described in numerous literature sites. Impaired immune cell function along with age-related metabolic changes can lead to features such as hyperinflammatory response, immunosenescence, and inflammaging in COVID-19. Inflammaging is related to the increased activity of the most inflammatory factors and is the main cause of age-related diseases and tissue failure in the elderly. Since hyperinflammation is a common feature of most severe cases of COVID-19, this pathway, which is not fully understood, leads to immunosenescence and inflammaging in some individuals, especially in the elderly and those with comorbidities. In this review, we shed some light on the age-related abnormalities of innate and adaptive immune cells and how hyperinflammatory immune responses contribute to the inflammaging process, leading to clinical deterioration. Further, we provide insights into immunomodulation-based therapeutic approaches, which are potentially important considerations in vaccine design for elderly populations. [ABSTRACT FROM AUTHOR]

Immune response elicited by therapeutic proteins is an important safety and efficacy issue for regulatory agencies, drug manufacturers, clinicians, and patients. Administration of therapeutic proteins can potentially induce the production of anti-drug antibodies or cell-mediated immune responses. At first, it was speculated that the immunogenicity is related to the non-human origin of these proteins. Later on, it was confirmed that the human proteins may also show immunogenicity. In this review article, we will focus on a number of factors, which play crucial roles in the human protein immunogenicity. These factors are related to the patient's status (or intrinsic properties) and molecular characteristics of the therapeutic protein's (or extrinsic properties). Furthermore, we will discuss available in silico, in vitro, and in vivo methods for the prediction of sequences, which may generate an immune response following parenteral administration of these proteins. In summary, nowadays, it is possible for drug manufacturers to evaluate the risk of immunogenicity of therapeutic proteins and implement a management plan to overcome the problems prior to proceeding to human clinical trials. [ABSTRACT FROM AUTHOR]

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection. [ABSTRACT FROM AUTHOR]

Background and objectives Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines. Materials and methods PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively. Results In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs. Conclusions This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is the main manifestation of systemic Lupus Erythematosus (SLE). MicroRNAs (miRNAs) and autoantibodies could be suitable candidate biomarkers of LN. This study evaluates the expression of circulating miR-148a and miR-126 along with anti-dsDNA, anti-C1q, and anti-C3b autoantibodies in SLE patients with LN (SLE + LN). 30 women with SLE, 30 women with SLE + LN, and 25 women as healthy controls (HCs) were enrolled in this study. The plasma expression of selected miRNAs was evaluated by real-time PCR. The serum level of anti-dsDNA, C1q, and C3b antibodies was measured by the ELISA. The expression of miR-148a was significantly increased in SLE and SLE+LN groups compared with the control group. No significant difference was found in the expression of miR-126 among the groups. The frequency of autoantibodies was significantly higher in the SLE + LN group than SLE. The Higher levels of circulating miR-148a in the SLE samples compared with the HCs suggest that this miRNA could be a reliable biomarker for SLE patients (with or without LN). Also, autoantibodies against dsDNA, C1q, and, C3 could be used for the prediction of SLE nephritis, independently. However, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. The aim of this study was to determine the frequency of HLA-DRB1 alleles in Iranian patients with AIH and investigate the association between HLA alleles and the different types of the disease. Fifty-four AIH patients and 100 age- and sex-matched healthy controls were subjected to low resolution HLA-DRB typing performed by polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. The results revealed higher frequencies of HLA-DRB1 ∗ 03, and DRB1 ∗ 13 alleles in patients with AIH compared to controls. However, DRB1 ∗ 11 was less frequent in AIH patients. In type I AIH patients HLA-DRB1 ∗ 03, HLA-DRB1 ∗ 04, HLA-DRB1 ∗ 08, and HLA-DRB1 ∗ 13 were the most frequent alleles. While in type II, the most frequent alleles were HLA-DRB1 ∗ 07 and HLA-DRB1 ∗ 13. The seronegative patients showed more frequency of HLA-DRB1 ∗ 03 and HLA-DRB3. In contrary, the frequency of HLA-DRB1 ∗ 11, HLA-DRB1 ∗ 15 and HLA-DRB5 in type 1 was less than healthy individuals. These findings indicate the role of HLA-DRB haplotypes in AIH susceptibility and protection, in the Iranian population. [ABSTRACT FROM AUTHOR]

Immunotherapy has improved cancer treatment based on investigations of tumor immune escape. Manipulation of the immune system stimulates antitumor immune responses and blocks tumor immune escape routes. Genetically adoptive cell therapy, such as T cells, has yielded promising results for hematologic malignancies, but their application to solid tumors has been challenging. Macrophages have a wide broad of capabilities in regulating immune responses, homeostasis, and tissue development, as well as the ability to phagocyte, present antigens, and infiltrate the tumor microenvironment (TME). Given the importance of macrophages in cancer development, they could serve as novel tool for tumor treatment. Therefore, macrophages are used in different formats for direct and indirect targeting of tumor cells. This review summarized the available data on the various applications of macrophages in cancer immunotherapy. [Display omitted] • The application of CAR-T cell therapy to solid tumors remains challenging. • Macrophages can overcome these challenges. • Macrophages are used in different approaches for tumor treatment. • Promising results have been obtained in studies using macrophages • Macrophages are a promising alternative to CAR-T cells. [ABSTRACT FROM AUTHOR]

The purpose of this research was to investigate the gene expression levels of inflammatory cytokines interferon (IFN)γ, tumor necrosis factor (TNF)α, interleukin (IL)1β, IL2, IL6, IL8, and IL17, and anti-inflammatory cytokines IL4, IL10, IFNα, and IFNβ, as well as relevant key transcription factors (TFs), including GATA3, PU1, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), IRF3 (interferon regulatory factor 3), BCL6 (B cell lymphoma 6 protein), FOXP3 (forkhead box P3), RORγt, and T-bet (T-box expressed in T cell) in Iranian patients with moderate and severe coronavirus disease 2019 (COVID-19). Fifty-six patients with COVID-19, and 25 healthy controls (HCs) age and sex matched were investigated. Based on the interim guidance of COVID-19 from the World Health Organization, the patients were classified into 33 moderate and 23 severe patients with COVID-19. The gene expression levels of cytokines and relevant TFs were quantified in peripheral blood mononuclear cells by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression levels of TFs RoRγ (RAR-related orphan nuclear receptor γ), NF-κB, and T-bet were significantly higher in patients with COVID-19 compared with HCs. Furthermore, the gene expression levels of cytokines, including IL2, IFNγ, IL6, TNFα, IL1β, IL8, and IL17, were significantly higher in patients with COVID-19 than HCs. However, there was a significant increase for IL6, TNFα, and IL17 in severe compared with moderate patients with COVID-19. Finally, The Spearman correlation analysis revealed a significantly positive correlation for IL6 and TNFα, IL6 and IL2, IL6, IFNγ, and IL2 and IFNγ. These data suggest that expression of IL6, TNFα, and IL17 as well as the synergic effect of elevated values of IL2 and IFNγ should be considered in the treatment and management of patients with severe COVID-19. [ABSTRACT FROM AUTHOR]

Context: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention. Objective: In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model. Materials and methods: Female Balb/c mice were divided into four groups: Group one: injected with PBS and Freund's adjuvant; Group two: injected with non-activated chromatin; Group three: Lupus-like disease was induced with activated chromatin; Group four: Mice were initially treated for two weeks with 1,25-dihydroxyvitamin D3 and then lupus-like disease was induced. Group five: Four mice from group one were treated with 1,25-dihydroxyvitamin D3 for two weeks after disease establishment. Ten weeks after the last injection the mice were killed and spleens were studied for Treg percentages and expression of cytokine genes. Results: We found that treatment with 1,25-dihydroxyvitamin D3 reduces IL-6 and IL-10 mRNA expression and increases TGF-β and Foxp3 mRNA expression levels, and also enhances spleen Treg percentage. Conclusions: The remarkable reduction of IL-6 and IL-10 gene expressions, significant enhancement of TGF-β and Foxp3 gene expressions, along with an increase in Treg cell population after oral 1,25-dihydroxyvitamin D3 administration suggest a possible role for this vitamin as a prophylactic supplement in SLE. [ABSTRACT FROM AUTHOR]

In this blinded clinical trial, we attempted to compare the efficacy and safety of administering tranexamic acid, dexmedetomidine and nitroglycerin in preventing intraoperative bleeding and improving the quality of the surgical field during septorhinoplasty under general anesthesia. A total of 105 patients scheduled for septorhinoplasty were enrolled and randomly assigned into three groups based on the balanced-block randomization method. First group received 1 μg/kg intravenous injection dexmedetomidine, second group received 10 mg/kg intravenous injection tranexamic acid and third group received 0.5 μg/kg nitroglycerin, intravenously. The study sample was composed of 105 participants with the total mean age of 25.85 ± 6.52 years, and 59.05% of participants were female and the mean of body mass index was 24.34 ± 2.57 kg/m2. The results showed that there was no statistically significant difference in terms of arterial oxygen saturation, mean arterial pressure, heart rate, bleeding rate, duration of surgery, and surgeon satisfaction among the three groups; however, there was a significant difference in the extubation time, recovery time and the dose of administered propofol among the three groups. Dexmedetomidine reduced the dose of administered propofol while increasing the extubation time and recovery time. In the tranexamic acid group compared with the other two groups, the recovery time was shorter. However, all the three drugs could reduce intraoperative bleeding and lead to surgeon satisfaction. It can be concluded that all these three drugs can be utilized to control bleeding and improve the quality of the surgical field but the ultimate decision lies with the anesthesiologist's judgment and the conditions of the patient. The study protocol was registered in the Iranian Registry of Clinical Trials (registration No. IRCT20141209020258N121) on September 24, 2019 and it was ethically approved by the Ethical Committee of Arak University of Medical Sciences (approval No. IR.ARAKMU.REC.1397.355) on February 24, 2019. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) are common acute leukemia in adults and children, respectively. In these malignancies, chemotherapy is the main treatment strategy that fails in many cases and is usually associated with adverse effects on healthy cells. In this regard, the development of new therapies is essential. Monoclonal antibodies directed to the cell surface markers of leukemic blasts may have promising consequences with minimal toxic effects on normal cells. Since cluster of differentiation 45Ra (CD45Ra) and CD123 antigens, two considered surface markers of leukemic blasts in AML and ALL respectively, are overexpressed on AML and ALL blasts, CD34+ leukemic progenitors, and AML-LSCs in comparison with normal hematopoietic stem cells (HSCs), they were selected to be targeted; using specific monoclonal antibodies. In this project, CD45Ra+ cells and CD123+ cells were targeted by anti-CD45Ra and/or anti-CD123 monoclonal antibodies. Cytotoxicity effect and cell death induction was determined by 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Changes in the expression profile of MCL1, cMyc, Survivin, Id1, and PIM1 genes were assessed by real-time PCR. Statistical analysis of the results showed effective antibody-mediated cytotoxicity and induction of apoptosis in KG1a (CD45Ra+) and Nalm6 (CD123+) cell lines. Also, a significant change in the expression level of some of the apoptosis-related genes was observed. According to the results of this study, it can be concluded that an effective targeting of AML and ALL cancerous cell lines can be performed by anti-CD45Ra and anti-CD123 monoclonal antibodies through their effector functions and apoptosis induction. [ABSTRACT FROM AUTHOR]

Objectives: Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor. Materials and methods: In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays. Functional assessments included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays. Results: Based on the results, 3Nb3 specifically binds to DLL4 and internalizes into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of cells and also neovascularization in the CAM. Conclusions: These data demonstrated the potential of Nanobody for application in targeting DLL4. Our findings may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans. Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients. Patients and Methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-β, and IFN-γ were measured by the enzyme linked immunosorbent assay (ELISA). Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p =0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p< 0.0001). However, there were no significant differences in TGF-β and IFN-γ between both groups. In addition, IL-17/IFN-γ and IL-17/IL-27 ratios were higher in patients compared to the control group. Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in β cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to β cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of β cells and progression of the disease to the clinical end stages. [ABSTRACT FROM PUBLISHER]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is currently the major global health problem. Still, it continues to infect people globally and up to the end of February 2022, over 436 million confirmed cases of COVID-19, including 5.95 million deaths, were reported to the world health organization (WHO). No specific treatment is currently available for COVID-19, and the discovery of effective therapeutics requires understanding the effective immunologic and immunopathologic mechanisms behind this infection. Type-I interferons (IFN-Is), as the critical elements of the immediate immune response against viral infections, can inhibit the replication and spread of the viruses. However, the available evidence shows that the antiviral IFN-I response is impaired in patients with the severe form of COVID-19. Moreover, the administration of exogenous IFN-I in different phases of the disease can lead to various outcomes. Therefore, understanding the role of IFN-I molecules in COVID-19 development and its severity can provide valuable information for better management of this disease. This review summarizes the role of IFN-Is in the pathogenesis of COIVD-19 and discusses the importance of autoantibodies against this cytokine in the spreading of SARS-CoV-2 and control of the subsequent excessive inflammation. [Display omitted] • Antiviral IFN-I response is impaired in severe COVID-19 patients. • About 10% of COVID-19 patients have autoantibodies against IFN-I. • Administration of external IFN-Is is a strategy to replace the patient's nonfunctional or reduced endogenous IFN-I. • There are still many contradictions and questions regarding the administration of IFN-Is. • There is very limited available data regarding IFN-Is roles in COVID-19 Immunopathology, yet. [ABSTRACT FROM AUTHOR]