Dysregulation of miR-223, miR-146a, and miR-193a Expression Profile in Acute and Chronic Phases of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice.

Multiple sclerosis (MS) is a chronic autoimmune disease with an unknown etiology. The purpose of this research was to assess miR-223, miR-146a, and miR-193a in acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) mice to consider the possible role of these genes in the pathogenesis of MS. EAE induction was given by myelin oligodendrocyte glycoprotein peptide on female C57BL/6 mice. Clinical scores and other criteria were followed daily until day 21 for the acute group and day 77 for the chronic group. At the end of the course, inflammation and demyelination of the central nervous system (CNS) were assessed by histological analysis. MicroRNA expression levels were assessed by real-time PCR. EAE development attenuated in the chronic group, and histological analysis showed less infiltration and demyelination in the chronic group compared to the acute group. The upper expression of miR-223 is demonstrated in the acute phase of EAE. Moreover, the expression levels of miR-146a and miR-193a decreased in the chronic phase of EAE. MiR-223 showed a highly coordinated elevation in the acute phase both in vivo and in vitro. MiR-146a shares a pathway with miR-223 through effecting IL-6 expression. Further studies are needed to reveal their impact on EAE and possible applications as drug targets and biomarkers.

Reprogramming tumor-associated macrophages using exosomes from M1 macrophages.

Macrophages, abundant in tumors, are classified as M1 or M2 types with M2 dominating the tumor microenvironment. Shifting macrophages from M2 to M1 using exosomes is a promising intervention. The properties of exosomes depend on their source cells. M1-exosomes are expected to polarize macrophages towards M1 phenotype. We compared M1-exosomes and M0-exosomes' effects on M2 macrophage polarization. The RAW264.7 cells were cultured and one group of them was exposed to LPS. The serum-free medium was collected and exosomes were extracted. Exosomes were analyzed by scanning and transmission electron microscopy, dynamic light scattering and Western blot. Subsequently, M1 or M0 exosomes were applied to M2 macrophages induced by IL4. The macrophages polarization, including M1 and M2 genes and surface markers expression, cytokines secretion, and phagocytosis ability were evaluated. It was demonstrated that M1-exosomes induced macrophage polarization toward the M1 phenotype, characterized by an upregulation of M1-specific markers and a downregulation of M2 markers. Furthermore, the secretion of TNF-α was increased, while the secretion of IL-10 was decreased. The phagocytosis ability of M1-exosome-treated macrophages was also augmented. This research suggested that M1-exosomes might be promising candidates for modulating immune response in situations marked by an overabundance of M2 polarization, like in cancer.

Terahertz electromagnetically induced optical limiter in asymmetric coupled quantum wells.

This paper explores the optical limiting (OL) characteristics of an input probe field within a closed-loop asymmetric coupled quantum well (ACQW) system. Our research reveals that the application of Terahertz (THz) coupling laser fields can induce the OL behavior within the THz domain in the ACQW. The study demonstrates that revers saturable absorption arises through cross-Kerr nonlinearity, contributing to the emergence of OL behavior. Additionally, it is shown that the self-defocusing is induced concurrently within the system, further enhancing nonlinear refractive OL effects. Furthermore, it is revealed that the properties of induced OL can be manipulated by adjusting the characteristics of the applied fields. The discovered outcomes hold potential utility in safeguarding sensors and detectors operating within the THz band.

Current status of intestinal parasitic infections and associated risk factors in rural population of Guilan province, northern Iran: trichostrongyliasis is the most prevalent helminthic infection.

Aim: This study aimed to determine the distribution of enteric parasitic infections and related risk factors among rural communities of Guilan province, Northern Iran, and to compare the results with the situation in the past. Background: Intestinal parasitic infections are still considered as a major public health concern, particularly in human communities with poor economy and sanitation. Methods: This cross-sectional study was performed in rural areas of Masal and Shanderman district from February to December 2020. A total of 917 stool samples were collected and examined for presence of intestinal helminthes and protozoa using direct, formalin-ether and Kato-Katz techniques. Results: A total of 156 (17%) out of 917 examined individuals were infected with intestinal parasites. The overall prevalence of protozoa, helminths and mixed infections were 11.8% (108/917), 4.5% (41/917) and 0.8% (7/917), respectively. Blastocystis was the most prevalent intestinal protozoa (9.6%) followed by Giardia lamblia (1.9%), Endolimax nana (1.1%), E. coli (0.8%) and Entamoeba hartmani (0.1%). The highest prevalence of intestinal helminths belonged to Trichostongylus spp. (3.5%) and Strongyloides stercoralis (1.3%). Statistical analysis showed significant association between giardiasis and sex (P<0.03). On the other hand, prevalence of enteric helminths was influenced by close contact with livestock, keeping herbivorous animals at home, job, education, and consumption of uncooked vegetables (P<0.05). Conclusion: The findings indicate a decreasing trend in the prevalence of intestinal parasitic infections in Guilan province in comparison to the past few decades. Hookworm infections, which was very prevalent in the area, are now rare, while trichostrongylosis showed a high prevalence in rural residents of the study area.

Corrigendum to "Molecular detection of Toxoplasma gondii in chicken hearts from markets and retail stores in Northern Iran" [Food and Waterborne Parasitology 27 (2022) e00166].

[This corrects the article DOI: 10.1016/j.fawpar.2022.e00166.].

Voltage-controlled two-dimensional Fresnel diffraction pattern in quantum dot molecules.

This study explores the influence of inter-dot tunneling effects within a quantum dot molecule on the Fresnel diffraction phenomenon. Our findings indicate that the Fresnel diffraction of the output probe Gaussian field can be manipulated by adjusting the inter-dot tunneling parameter's strength and the characteristics of the coupling field. The inter-dot tunneling effect establishes a closed-loop system, setting conditions for the interference of the applied fields. We specifically examine a Laguerre-Gaussian (LG) coupling field, investigating how its properties-such as strength, value, and sign of the orbital angular momentum (OAM)-impact the Fresnel diffraction of the output probe field. Increasing the inter-dot tunneling parameter and the coupling LG field's strength allows for control over the spatial distribution of the Fresnel diffraction pattern. Notably, the inter-dot tunneling parameter can disturb the symmetry of the diffraction patterns. Additionally, considering a negative OAM for the coupling LG field transforms the diffraction pattern into its inverse shape. This suggests that, in the presence of the inter-dot tunneling effect, the Fresnel diffraction pattern is contingent on the direction of rotation of the helical phase front of the coupling LG field. Our results offer insights into quantum control of Fresnel diffraction patterns and the identification of OAM in LG beams, presenting potential applications in quantum technologies.

Microwave optical limiting via an acoustic field in a diamond mechanical resonator.

We investigate the generation and control of the reverse saturable absorption (RSA) and optical limiting (OL) at microwave (mw) range in high-Q single-crystal diamond mechanical resonator (DMR) embedded with many nitrogen-vacancy (NV) centers. The strain-induced acoustic modes enable mechanical manipulation of NV centers. On the basis of strain-coupling mechanism, it is shown that the saturable absorption (SA) switches to the RSA by applying the acoustic field, leading to induce the OL in the diamond through the cross-Kerr effect. We demonstrate that the OL characteristics such as, threshold, efficiency, and dynamic range can be controlled by changing either the intensity or frequency of the acoustic field. Moreover, we show that this optical limiter can amplify noiselessly the low intensity of the mw field input to the sensors and also attenuate any gain-induced noise and increase in the intensity of the mw field if it exceeds the intensity threshold. In addition, it is shown that by increasing either the number of NV centers or length of the diamond, the optical limiter can be more efficient. The physical mechanism of the OL establishment is explained using the analytical expressions, which are in good agreement with the numerical results. Our proposed acoustic-induced optical limiter can be a scheme for protecting different optical and electronic devices in mw range, remote sensing, navigation, communications, microwave heating and thermo/laser therapy.

Latent toxoplasmosis in COVID-19 patients and link with higher mortality in COVID-19 male patients.

BACKGROUND: Immunocompromised patients may be at risk for reactivating the toxoplasmosis infection; therefore, early diagnosis would be highly desirable in these individuals. This study evaluated the possible association between coronavirus disease 2019 (COVID-19) and latent Toxoplasma gondii infection in Guilan province, Iran. MATERIALS AND METHODS: The study was performed among 210 COVID-19 patients referred to Guilan University of Medical Sciences hospitals in 2022. Peripheral blood samples were taken for serum separation, collected into tubes, and kept at - 20 °C until use. Blood samples were obtained from COVID-19 patients. IgG antibody to Toxoplasma gondii was detected by a commercial ELISA kit. Accordingly, IgG absorbance levels <9 were considered harmful, 9-11 was considered borderline, and >11 was positive. RESULTS: Toxoplasma IgG antibodies were found in 73.9 % of patients with COVID-19 in male patients. The seroprevalence of Toxoplasma in dead and lived COVID-19 male patients was 83.3 % and 66.7 %, respectively, and this difference was significant. A present study found a significant correlation between the rising titer of Toxoplasma IgG and the severity of COVID-19. There was no significant difference between the hospitalization duration factor and the seropositivity rate. CONCLUSION: Regarding the significant association between the rising titer of Toxoplasma IgG and the severity of COVID-19. The findings demonstrated an association between the severity and mortality rate of COVID-19 with higher titer Anti-Toxoplasma IgG antibodies. Toxoplasmosis is currently considered a risk factor for COVID-19.

Natural killer cells and their exosomes in viral infections and related therapeutic approaches: where are we?

Innate immunity is the first line of the host immune system to fight against infections. Natural killer cells are the innate immunity lymphocytes responsible for fighting against virus-infected and cancerous cells. They have various mechanisms to suppress viral infections. On the other hand, viruses have evolved to utilize different ways to evade NK cell-mediated responses. Viruses can balance the response by regulating the cytokine release pattern and changing the proportion of activating and inhibitory receptors on the surface of NK cells. Exosomes are a subtype of extracellular vesicles that are involved in intercellular communication. Most cell populations can release these nano-sized vesicles, and it was shown that these vesicles produce identical outcomes to the originating cell from which they are released. In recent years, the role of NK cell-derived exosomes in various diseases including viral infections has been highlighted, drawing attention to utilizing the therapeutic potential of these nanoparticles. In this article, the role of NK cells in various viral infections and the mechanisms used by viruses to evade these important immune system cells are initially examined. Subsequently, the role of NK cell exosomes in controlling various viral infections is discussed. Finally, the current position of these cells in the treatment of viral infections and the therapeutic potential of their exosomes are reviewed. Video Abstract.

Bleeding disorder of unknown cause: Results from Iranian study.

BACKGROUND: Definite diagnosis of patients with mild to moderate bleeding is challenging. Some studies reported that even more than 50% of their patients remained undiagnosed which is classified as a Bleeding disorder of unknown cause (BDUC). This study aims to document the clinical characteristics and proportion of patients with BDUC in the Iranian Comprehensive Hemophilia Care Center (ICHCC) one of the referral centers for diagnosis of congenital bleeding disorder in Iran. METHODS: This study was conducted on 397 patients who were referred with a bleeding manifestation to ICHCC from 2019 to 2022. Demographic and laboratory data were documented for all patients. Bleeding questionnaires including ISTH-Bleeding Assessment tool (ISTH-BAT) and the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 (MCMDM-1 (ISTH-BAT, MCMDM-1, and the Pictorial Bleeding Assessment Chart (PBLAC) were filled out for all patients. The data were analyzed by the statistical package for social science (SPSS version 22, SPSS, Chicago, Illinois, USA). RESULTS: BDUC was diagnosed in 200 patients and 197 patients reached the final diagnosis. Hemophilia, von Willebrand disease (VWD), factor (F) VII deficiency, and platelet functional disorders (PFDs) were confirmed in 54, 49, 34, and 15 of the patients, respectively. No significant difference was found in bleeding scores between patients with BDUC and those with confirmed disease. In contrast, after setting cut-off (ISTH-BAT for males ≥ 4 and females ≥ 6 and MCMDM-1 for males ≥ 3 and females ≥ 5) clinically significant difference was found. There was no association between having a positive consanguineous marriage and setting a diagnosis; however, significant associations were seen for having a positive family history of bleeding. Age (OR =0.977, 95% CI.965-0.989), gender (BDUC female, 151/200; final diagnosis female, 95/197) (OR=3.3, 95% CI 2.16-5.06), family history (OR = 3.19, 95% CI 1.99-5.11), and consanguineous marriage (OR=1.59, 95% CI 1.03-2.45) were considered as a risk factor for categorizing the patients with BDUC or final diagnosis. CONCLUSION: The findings are mainly in line with previous studies about BDUC patients. The large number of patients with BDUC underlines the incompleteness of available routine laboratory tests and shows the necessity of progress in the development of reliable diagnostic tools to identify underlying bleeding disorders.

Natural killer cells in COVID-19: from infection, to vaccination and therapy.

Natural killer (NK) cells are among the most important innate immunity members, which are the first cells that fight against infected cells. The function of these cells is impaired in patients with COVID-19 and they are not able to prevent the spread of the disease or destroy the infected cells. Few studies have evaluated the effects of COVID-19 vaccines on NK cells, though it has been demonstrated that DNA vaccines and BNT162b2 can affect NK cell response. In the present paper, the effects of SARS-CoV-2 on the NK cells during infection, the effect of vaccination on NK cells, and the NK cell-based therapies were reviewed.

Optical limiting via spontaneously generated coherence.

We investigate the reverse saturable absorption (RSA) and optical limiting (OL) in a three-level V-type quantum system considering the effect of the spontaneously generated coherence (SGC). It is shown that in the absence of the SGC effect, the saturable absorption (SA) is dominant in the system. By taking into account the SGC effect, we prove that the SA dramatically switches to the RSA. Moreover, it is demonstrated that the OL threshold and OL efficiency can be controlled by the SGC effect. In addition, we show that the applied field properties such as detuning can modify the SGC-induced optical limiter efficiency. It is also shown an increase in the atomic density and length of the medium makes the optical limiter more efficient. The analytical calculation shows that the Kerr nonlinearity caused by the SGC effect is the main mechanism of the system evolution. Finally, the theoretical Z-scan experiment is presented to confirm the obtained results. Our proposed scheme can be useful to design controllable atomic optical limiters for optical devices with different sensitivities.

Validity and reliability of the Persian version of the Cornell Scale for Depression in Dementia.

The current study aimed to evaluate the validity and reliability of the Persian version of the Cornell Scale for Depression in Dementia (CSDD) in 100 patients aged ≥60 with dementia in Tehran, Iran. Test-retest reliability and internal consistency were analyzed through intraclass correlation coefficient and Cronbach's alpha tests, respectively. The validity was assessed in the areas of face, content and structural validity. The Geriatric Depression Scale (GDS) and The Montgomery-Åsberg Depression Rating Scale (MADRS) were also used to determine the convergent validity. The intraclass correlation coefficient (ICC) was equal to or more than 0.8 between the results of determining depression twice via the CSDD. The internal consistency (Cronbach's α = 0.90) was excellent. The factor analysis, identified five main factors (mood-related signs, behavioral disturbance, physical signs, cyclic functions and ideational disturbance), aside from depression, demonstrated the variance to be 37.88%. Evaluating convergent validity showed satisfactory results (p < 0001). Using the MADRS as standard. the best cut-points for the CSDD via the use of the Youden index were scores of 5.5, 10.5 and 16.5 for mild, moderate and severe depression, respectively. The Persian version of the CSDD is sufficient in terms of validity and reliability for screening depression in the elderly with dementia in Iran.

The Role of NK Cells and Their Exosomes in Graft Versus Host Disease and Graft Versus Leukemia.

Natural killer (NK) cells are one of the innate immune cells that play an important role in preventing and controlling tumors and viral diseases, but their role in hematopoietic stem cell transplantation (HCT) is not yet fully understood. However, according to some research, these cells can prevent infections and tumor relapse without causing graft versus host disease (GVHD). In addition to NK cells, several studies are about the anti-leukemia effects of NK cell-derived exosomes that can highlight their roles in graft-versus-leukemia (GVL). In this paper, we intend to investigate the results of various articles on the role of NK cells in allogeneic hematopoietic cell transplantation and also their exosomes in GVL. Also, we have discussed the antiviral effects of these cells in post-HCT cytomegalovirus infection.

Seroepidemiological Study of Visceral Leishmaniasis (Kala-Azar) in Children under 12 Years Old in North of Iran: An Observational Study in 2019-2020.

Background: Visceral leishmaniasis (VL) caused by the Leishmania donovani complex that is transmitted by the bites of female sandflies. Mediterranean type of VL caused by L. infantum. While, Roudbar County of Guilan Province has been introduced as a suspected cutaneous leishmaniasis focus; there are no published data on the seroprevalence of VL in Guilan Province. We aimed to investigate the sero-prevalence of this disease in Roudbar County. Methods: This descriptive cross-sectional study was carried out in 2019-2020 among children less than 12 years of age to determine the seroprevalence of VL by direct agglutination test (DAT). Blood samples were randomly collected from 918 children under 12 years of age refers to the public health center in the clusters. Results: Out of 918 children, 14 (1.52%) showed anti-Leishmania antibodies, with 4 (0.43%), 2 (0.21%), 8 (0.87%) anti-L. infantum antibodies at titers 1:800, 1:1600 and ≥1: 3200 respectively. All children with anti-Leishmania antibody titers of ≥1:800 were evaluated by a physician. Clinical manifestation of VL including fever, anemia and hepatosplenomegaly observed in a 6-year-old boy from Defraz village with anti-Leishmania antibody of titers ≥102400.This patient was admitted to the pediatric hospital in Rasht, capital of Guilan province, Iran and was successfully treated. Conclusion: VL is being circulated with low prevalence in children up to 12 years old in Roudbar, northern part of Iran. Accordingly, it is critical to improve the awareness of physicians and public health supervisors about the importance of this fatal disease in Guilan province and especially in Roudbar area.

Kinetic studies of dexamethasone degradation in aqueous solution via a photocatalytic UV/H2O2/MgO process.

Wastewaters discharged from different industries and hospitals may contain pharmaceuticals, especially dexamethasone (DEX). Thus, we applied the UV/H2O2 photocatalytic method in the presence of the MgO nanoparticles to remove dexamethasone from synthetic wastewater. Moreover, the effects of parameters such as pH (3-11), hydrogen peroxide concentration (1-8 mM), initial DEX concentration (5-30 mg/L), and catalyst dosage (0.01-0.2 g/L) during the reaction times (0-30 min) were investigated. Furthermore, the efficiency of UV/H2O2 in the presence and absence of catalysts was investigated. The photocatalyst is characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), and Fourier-transform infrared spectroscopy (FTIR) techniques. It was found that the removal rate was enhanced by decreasing pH and the initial dexamethasone concentration. The removal rate was enhanced somewhat with concentrations of hydrogen peroxide and MgO. In the case of UV/H2O2/MgO, 87% removal efficiency was achieved, under the optimal conditions: pH 3, contact time of 30 min, dexamethasone concentration of 20 mg/L, H2O2 of 0.5 mM, and UV radiation of 55 watts. The kinetic data indicated that the reaction followed the second-order kinetic model. The results showed that the UV/H2O2 photochemical process can efficiently remove dexamethasone from aqueous in the presence of a MgO catalyst, and the mineralization efficiency was reached at about 98%.

Determining Effective Environmental Factors in the Distribution of Endangered Endemic Medicinal Plant Species Using the BMLR Model: The Example of Wild Celery (Kelussia odoratissima Mozaff., Apiaceae) in Zagros (Iran).

Kelussia odoratissima Mozaff. is a medicinal species native to Iran. The goal of this research was to determine the environmental factors important for the distribution of K. doratissima in Iran using BMLR modeling. Six random transects were established throughout the species' habitat, and 220 quadrats with an area of 4 m2 were plotted. The canopy cover percentages of K. doratissima were estimated in each quadrat. Topographic factors, including elevation, slope, and aspect maps, were generated by creating DEM images. Land use, land evaluation, evaporation, temperature, and precipitation maps of the area were created accordingly. The data collected from the experiments were analyzed using the Minitab and R statistical packages. To determine the effect of the studied factors in the distribution of K. doratissima, we ran a set of backward multiple linear regressions. The results showed that the effects of evaporation, elevation, and slope were significant in the species' distribution, with elevation having a positive effect and evaporation and slope showing negative effects. Further, elevation had the highest effect on distribution (greatest absolute value of beta at 9.660). The next most significant factors in the plant's distribution were evaporation (beta = 8.282) and slope (beta = 0.807), respectively.

Molecular detection of Toxoplasma gondii in chicken hearts from markets and retail stores in Northern Iran.

Detection of Toxoplasma gondii in chicken products indicates risk of transmission to consumers. The objective of the current study was to investigate the molecular prevalence of T. gondii in free-ranging and industrial chickens in Guilan province, Northern Iran. A total of 150 chicken heart samples including 75 free-range and 75 industrial chickens were collected from farmers' markets and chicken retailers in Guilan, Northern Iran, between October 2017 and August 2018. Genomic DNA were extracted from samples and examined for evidence of T. gondii using polymerase chain reaction (PCR) targeting the B1 gene. The B1-positive samples were further analyzed by nested-PCR for SAG1 gene. Of the 150 samples, T. gondii DNA fragments were detected in 59 (39.3%), including 30 (40%) free-range and 29 (38.7%) industrial chicken. No significant differences of T. gondii DNA detection was observed between the free-range and industrial chicken samples (p = 0.73). Four selected positive samples were used for amplifying and sequencing of the SAG1 gene. The results revealed that all four sequences of SAG1 had 100% similarity with T. gondii sequences previously isolated from an AIDS/HIV patient in Mazandaran province, Northern Iran. Furthermore, the phylogenetic analysis demonstrated that all four sequences were closely related to Type I of T. gondii. However, our Type I identification is preliminary and needs to be confirmed by further multilocus sequence typing (MLST) analysis. The findings of the present study provide new data about the presence of T. gondii DNA in chicken hearts in the study area. These results confirm that chicken can be used as sentinels for environment contamination; however, further studies are needed to determine the viability of T. gondii in chicken hearts from Iran for risk assessment.

Immune cells-derived exosomes function as a double-edged sword: role in disease progression and their therapeutic applications.

Exosomes, ranging in size from 30 to 150 nm as identified initially via electron microscopy in 1946, are one of the extracellular vesicles (EVs) produced by many cells and have been the subject of many studies; initially, they were considered as cell wastes with the belief that cells produced exosomes to maintain homeostasis. Nowadays, it has been found that EVs secreted by different cells play a vital role in cellular communication and are usually secreted in both physiological and pathological conditions. Due to the presence of different markers and ligands on the surface of exosomes, they have paracrine, endocrine and autocrine effects in some cases. Immune cells, like other cells, can secrete exosomes that interact with surrounding cells via these vesicles. Immune system cells-derived exosomes (IEXs) induce different responses, such as increasing and decreasing the transcription of various genes and regulating cytokine production. This review deliberate the function of innate and acquired immune cells derived exosomes, their role in the pathogenesis of immune diseases, and their therapeutic appliances.