Vitamin D levels in non-pregnant women with a history of recurrent pregnancy loss with and without autoantibodies.

Background: The objective of this study was to compare the levels of vitamin D in non-pregnant women with a history of recurrent pregnancy loss (RPL) who were seropositive or seronegative for autoantibodies (autoAbs). Methods: The study examined 58 RPL patients with autoAbs (ANA, anti-TPO, or APAs), 34 RPL patients without autoAbs, and 58 healthy women with prior successful pregnancies and without autoantibodies. The levels of 25 (OH) D were measured using the sandwich ELISA technique. Results: Our results showed insufficient serum 25(OH) D levels in study groups, with significantly lower levels observed in RPL patients with or without autoAbs compared to healthy women (P=0.0006). In addition, RPL patients with autoAbs had significantly lower 25(OH) D levels compared to RPL patients without autoAbs. We also found that serum levels of 25(OH) D in RPL patients with autoAbs were significantly lower than in RPL patients without autoAbs (20.51 ± 1.15 ng/ml Vs. 23.69 ± 0.74 ng/ml, P=0.0356). Further analysis indicated that RPL patients who were positive for ANA, and APAs, except anti-TPO, had significantly lower than 25(OH)D serum levels than RPL patients without autoAbs. Conclusion: These findings suggest that RPL patients, especially those with APAs or ANA, have lower vitamin D levels compared to healthy women. This may indicate a link between maternal immune dysregulation due to vitamin D deficiency and the presence of autoantibodies in RPL.

A comprehensive review on the role of T cell subsets and CAR-T cell therapy in Aspergillus fumigatus infection.

Understanding the immune response to Aspergillus fumigatus, a common cause of invasive fungal infections (IFIs) in immunocompromised individuals, is critical for developing effective treatments. Tcells play a critical role in the immune response to A. fumigatus, with different subsets having distinct functions. Th1 cells are important for controlling fungal growth, while Th2 cells can exacerbate infection. Th17 cells promote the clearance of fungi indirectly by stimulating the production of various antimicrobial peptides from epithelial cells and directly by recruiting and activating neutrophils. Regulatory T cells have varied functions in A.fumigatus infection. They expand after exposure to A. fumigatus conidia and prevent organ injury and fungal sepsis by downregulating inflammation and inhibiting neutrophils or suppressing Th17 cells. Regulatory T cells also block Th2 cells to stop aspergillosis allergies. Immunotherapy with CAR T cells is a promising treatment for fungal infections, including A. fumigatus infections, especially in immunocompromised individuals. However, further research is needed to fully understand the mechanisms underlying the immune response to A. fumigatus and to develop effective immunotherapies with CAR-T cells for this infection. This literature review explores the role of Tcell subsets in A.fumigatus infection, and the effects of CAR-T cell therapy on this fungal infection.

Intermittent fasting: A promising dietary intervention for autoimmune diseases.

Intermittent fasting, which includes periods of fasting and nutrition, has been considered a dietary approach for weight loss and metabolic health improvement. However, its potential benefits in autoimmune diseases have not been widely studied. This study aims to review the existing studies on the role and effects of intermittent fasting on autoimmune diseases. A comprehensive search was conducted on electronic databases such as PubMed, Scopus, Embase, and Web of Science, and relevant studies were included based on inclusion criteria. Studies show that intermittent fasting may have beneficial effects on various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, by reducing inflammatory markers, modulating the immune system, altering and improving gut microbiota, and enhancing cellular repair mechanisms through autophagy. However, evidence regarding the effects of intermittent fasting on other autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, thyroid diseases, and psoriasis is limited and inconclusive. Nevertheless, further research is needed to determine optimal intermittent fasting guidelines and its long-term effects on autoimmune diseases. Overall, this literature review proves intermittent fasting may be a promising dietary intervention for managing autoimmune diseases.

COVID-19 Death Rates in Iran and Iraq: Possible Relations Between Iraq's Pre-COVID-19 Mass Gatherings and Its Low Death Rate.

In recent years, COVD-19 has made millions of death worldwide. When reviewing the death rate, we encountered a very notable difference in death rate of Iran and Iraq, which are two neighboring countries. Investigating the COVID-19 risk factors, parameters, such as ethnicity and vaccination, do not appear not to be affecting our observation. We also could not find important differences in mortality rate being under-reported in the two countries. In this letter, we tried to discuss the possible effect of Iraq pre-COVID-19 mass gatherings on the death rate. The authors would like to highlight the effect of immune system on COVID-19.

Personality traits of patients with multiple sclerosis and their correlation with anxiety and depression levels: A cross-sectional case-control study.

OBJECTIVE: Multiple sclerosis is a chronic demyelinating disease of the central nervous system that can cause severe disability and impair the quality of life (QoL). METHODS: In the current cross-sectional, case-control study, we investigated personality traits, anxiety and depression levels, in 101 patients in the case group and 202 individuals as a control group. The personality traits of the participants were collected via the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) questionnaire. We evaluated the level of anxiety and depression based on the Hospital Anxiety and Depression Scale questionnaire. RESULTS: Our study showed in patients with disease duration above 1 year, the rates of agreement (29.78), anxiety (8.83), and depression level (6.39) were significantly higher than the control group (27.19, 6.47, and 4.97, respectively). Although patients with disease duration below 1 year showed a higher level of agreement and conscientiousness (29.65 and 34.35, respectively) than controls (26.6 and 30.86, respectively). The level of anxiety and depression in patients with a disability index above 4.5 was significantly higher than patients with a disability index below 1. Patients with a disability index below 1 showed a higher rate of extraversion and agreement and conscientiousness (31.47, 31.53, and 35.07, respectively) than controls (25.5, 26.23, and 3033, respectively). In addition, patients with a disability index above 4.5 showed a higher level of agreement (35.64), conscientiousness (35.5), anxiety (9.64), and depression (7.5) than controls (25.96, 30.71, 6.96, and 4.71, respectively). CONCLUSIONS: In conclusion, anxiety and depression levels were much higher among MS patients compared with controls and the severity of these conditions correlate with the score of the disability index. Therefore, a complete comprehension of these conditions by the neurologist could be vital in improving patients' QoL and increasing compliance and adherence to pharmacological therapy.

Evaluation of the relationship between serum levels of zinc, vitamin B12, vitamin D, and clinical outcomes in patients with COVID-19.

Due to the known anti-inflammatory and antiviral effects of zinc, 25(OH)D, and vitamin B12, in this study, we explored the association between serum levels of these micronutrients in coronavirus disease 2019 (COVID-19) patients at the time of admission and the clinical outcomes. This study was carried out on 293 patients with COVID-19, who were hospitalized at Imam Hassan hospital (Bojnourd, Iran). We collected demographic data, clinical characteristics, values of serum biochemical parameters in the first week of admission, and clinical outcomes from electronic medical records. We also measured serum levels of zinc, 25(OH)D, and vitamin B12 within 3 days of admission. Of the 293 hospitalized, the median age was 53 years, and 147 (50.17%) were female. Thirty-seven patients (12.62%) were admitted to the intensive care unit (ICU), and forty-two (14.32%) died. We found that the serum levels of zinc, vitamin B12, and 25(OH)D were lower in patients who died than those who were admitted to ICU or non-ICU and survived; however, these differences were not statistically significant for vitamin B12 and 25(OH)D (p > 0.05). The serum concentrations of zinc, vitamin B12, and 25(OH)D at the time of admission did not affect the length of hospital stay in patients with COVID-19. In general, it seems that serum levels of 25(OH)D, vitamin B12, and especially zinc at the time of admission can affect clinical outcomes in COVID-19 patients.

Enhanced antitumor immune response in melanoma tumor model by anti-PD-1 small interference RNA encapsulated in nanoliposomes.

Programmed cell death protein-1 (PD-1), as an immune checkpoint molecule, attenuates T-cell activity and induces T-cell exhaustion. Although siRNA has a great potential in cancer immunotherapy, its delivery to target cells is the main limitation of using siRNA. This study aimed to prepare a liposomal formulation as a siRNA carrier to silence PD-1 expression in T cells and investigate it's in vivo antitumor efficacy. The liposomal siRNA was prepared and characterized by size, zeta potential, and biodistribution. Following that, the uptake assay and mRNA silencing were evaluated in vitro at mRNA and protein levels. siRNA-PD-1 (siPD-1)-loaded liposome nanoparticles were injected into B16F0 tumor-bearing mice to evaluate tumor growth, tumor-infiltrating lymphocytes, and survival rate. Liposomal siPD-1 efficiently silenced PD-1 mRNA expression in T cells (P < 0.0001), and siPD-1-loaded liposomal nanoparticles enhanced the infiltration of T-helper 1 (Th 1) and cytotoxic T lymphocytes into the tumor tissue (P < 0.0001). Liposome-PD-1 siRNA monotherapy and PD-1 siRNA-Doxil (liposomal doxorubicin) combination therapy improved the survival significantly, compared to the control treatment (P < 0.001). Overall, these findings suggest that immunotherapy with siPD-1-loaded liposomes by enhancing T-cell-mediated antitumor immune responses could be considered as a promising strategy for the treatment of melanoma cancer.

Development of a PCR-RFLP method for detection of D614G mutation in SARS-CoV-2.

In late 2019, an outbreak of respiratory disease named COVID-19 started in the world. To date, thousands of cases of infection are reported worldwide. Most researchers focused on epidemiology and clinical features of COVID-19, and a small part of studies was performed to evaluate the genetic characteristics of this virus. Regarding the high price and low availability of sequencing techniques in developing countries, here we describe a rapid and inexpensive method for the detection of D614G mutation in SARS-CoV-2. Using bioinformatics databases and software, we designed the PCR-RFLP method for D614G mutation detection. We evaluated 144 SARS-CoV-2 positive samples isolated in six months in Northeastern Iran. Our results showed that the prevalent type is S-D in our isolates, and a small number of isolated belongs to the S-G type. Of 144 samples, 127 (88.2%) samples have belonged to type S-D, and 13 (9%) samples typed S-G. The first S-G type was detected on 2020 June 10. We have little information about the prevalence of D614G mutation, and it seems that the reason is the lack of cheap and fast methods. We hope that this method will provide more information on the prevalence and epidemiology of D614G mutations worldwide.

Cytokine profile and nitric oxide levels in peritoneal macrophages of BALB/c mice exposed to the fucose-mannose ligand of Leishmania infantum combined with glycyrrhizin.

BACKGROUND: The fucose-mannose ligand (FML) of Leishmania infantum is a complex glycoprotein which does not elicit adequate immunogenicity in humans. In recent years, adjuvant compounds derived from plants have been used for improving the immunogenicity of vaccines. Glycyrrhizin (GL) is a natural triterpenoid saponin that has known immunomodulatory activities. In the present study, we investigated the effects of co-treatment with FML and GL on the production of cytokines and nitric oxide (NO) by macrophages, in vitro. METHODS: Lipopolysaccharide (LPS) stimulated murine peritoneal macrophages were treated with FML (5 µg/ml) of L. infantum and various concentrations of GL (1 µg/ml, 10 µg/ml and 20 µg/ml). After 48 h of treatment, cell culture supernatants were recovered and the levels of TNF-α, IL-10, IL-12p70 and IP-10 were measured by sandwich ELISA and NO concentration by Griess reaction. RESULTS: Our results indicate that the treatment of activated macrophages with FML plus GL leads to enhanced production of NO, TNF-α and IL-12p70, and reduction of IL-10 levels in comparison with FML treatment alone. CONCLUSIONS: Therefore, we concluded that GL can improve the immunostimulatory effect of FML on macrophages and leads to their polarization towards an M1-like phenotype.

The protective effect of berberine against lipopolysaccharide-induced abortion by modulation of inflammatory/immune responses.

OBJECTIVE: Berberine is an isoquinoline derivative alkaloid with anti-inflammatory activity. In this study, we investigated the protective effects of berberine in prevention of LPS-induced abortion. MATERIALS AND METHODS: On the gestation day (GD) 9.5, the pregnant mice were injected with low, medium, and high doses of berberine or with PBS. After 4 h, berberine or PBS-pretreated mice were injected with LPS. On GD 11.5, blood samples and uterine tissues were collected from treated mice and percentage of abortion and serum levels of NO, TNF-α, IL-10, and IL12p70 were measured by macroscopic examination and sandwich ELISA, respectively. RESULTS: Our findings show that mice injected with berberine were resistant to LPS-induced abortion. We also found that this treatment prevents the reduction of IL-10 and the enhancement of NO, TNF-α, and IL-12p70 in LPS-treated pregnant mice. CONCLUSIONS: Taken together, our results suggest that berberine as an anti-inflammatory agent has protective effects on LPS-induced abortion by modulation of inflammatory/immune responses.

Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy.

OBJECTIVE: In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. METHODS: Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and 17ß-estradiol, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. RESULTS: We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and 17ß-estradiol levels, and a reduced frequency of macrophages and uNK cells. CONCLUSION: Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes.

The 14kDa protein molecule isolated from garlic suppresses indoleamine 2, 3-dioxygenase metabolites in mononuclear cells in vitro.

A wide range of biological activities of garlic in vitro and in vivo have been verified including its antioxidant, antitumor and anti-inflammatory effects. Indoleamine 2,3-dioxygenase (IDO) is an enzyme widely distributed in mammals and is inducible preferentially by IFN-gamma. IDO degrades the essential amino acid tryptophan to form N-formyl kynurenine. In the present in vitro study, the modulatory effect of 14kDa molecule isolated from garlic on IDO induction was tested. Cultures of mononuclear cells were exposed to 14kDa garlic fraction. Then, their proliferation responses and IDO metabolites were measured. A significant down-regulatory effect of garlic on IDO activity was found and also the proliferation responses of mononuclear cells increased. If these results are verified in vivo, an explanation will be provided on how garlic may interfere in IDO induction, which paves the way for elucidating its specific therapeutic effect in preventing tumor progress.