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Using density functional theory, three noncovalent interactions and mechanism of covalent functionalization of drug artemisinin onto γ-Fe2O3 nanoparticles have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of drug artemisinin with γ-Fe2O3 nanoparticles is thermodynamically suitable. Hardness and the gap of energy between LUMO and HOMO of artemisinin drug are higher than those of noncovalent artemisinin-γ-Fe2O3 nanoparticle configurations, showing the reactivity of artemisinin increases in the presence of γ-Fe2O3 nanoparticles. Artemisinin can bond to γ-Fe2O3 nanoparticles through carbonyl group. The activation energies, the activation enthalpies and the activation Gibbs free energies of this reaction were calculated. The activation parameters and thermodynamic data indicate that this reaction is exothermic and spontaneous and can take place at room temperature. These results could be generalized to other similar drugs. [ABSTRACT FROM AUTHOR]

Herein, (E)-4-{[(2-amino-5-chlorophenyl)imino]methyl}-5-(hydroxymethyl)- 2-methylpyridin-3-ol [HL] Schiff base and its [Cu(L)Cl] complex were newly synthesized and characterized by several spectroscopic methods. In addition, density functional theory (DFT) methods were used for investigation of the tautomerization of the HL Schiff base, structural parameters of HL and [Cu(L)Cl] species, assignment of the IR vibrational bands and the NMR chemical shifts as well as natural bond orbital (NBO) analyses. The most stable tautomer of the HL Schiff base is the enol form of the meta isomer. The optimized geometry of the free HL Schiff base is not planar. The L- acts as a N2O tridentate ligand, which is bonded to Cu2+ via the deprotonated phenolic oxygen, and the amine and azomethine nitrogens. The [Cu(L)Cl] has a square planar geometry in which the chloro ligand occupies the fourth coordination position. The DFT-computed values are in good consistency with the corresponding experimental values, confirming the suitability of the optimized geometries for HL and [Cu(L)Cl] species. According to the high-energy gaps, these compounds are stable. The atoms in molecule (AIM) analysis was used to evaluate strength of the bonding interactions and electron densities in structure of the compounds.

In recent decades, extensive research has been done on substrates (i.e., titanium and carbon) with lead dioxide coating to design a cheap anode in electrochemical systems instead of a platinized (Pt) electrode. Various factors can affect the structure and catalytic activity of lead dioxide coating. The most important of them are the type of substrate, how to prepare the substrate for the coating process and the types of lead dioxide additives. In this work, the effective factors in the preparation of the substrate were first investigated. Subsequently, the effect of neodymium as an additive on the catalytic activity of the electrode was studied. We prepared these electrodes and they were first evaluated by scanning electron microscopy (SEM), X-ray diffraction (XRD) spectrometer, voltammetry and electrochemical impedance spectrometer (EIS). The results showed that the potential of water oxidation on the modified $Pb{O}_{2\,}$ electrodes by neodymium was 2 V. Here, we used an electrochemical method to prepare perchlorate. Since the anode potential for perchlorate oxidation is near that for water oxidation, conventional electrodes can’t be used in the perchlorate electrosynthesis. To achieve high production yield in the preparation of perchlorate from chlorate, various parameters including pH, time, and current density were optimized by the Box-Behnken design of the experiment method. The optimal values for this process were obtained at pH = 11, temperature 40 °C and current density of 0.5 mA cm ^−2 . The results at the optimal condition showed that the perchlorate production yield by modified $Pb{O}_{2\,}$ electrodes was 80% in the 300 min. This value was only 60% for the unmodified $Pb{O}_{2\,}$ electrode.

At least 25 types of degenerative diseases are thought to be caused by amyloid-beta, including Alzheimer's. However, the exact mechanism of Alzheimer's is still unknown. It has been shown that amphiphilic surfactants with varying tail lengths, PC20:0 and di-C7-PC, have differing effects on the structures of Aβ (1–40) and Aβ (1–42). This paper examines the interaction between these surfactants and peptides. The calculations were performed at concentrations lower than the critical micelle concentration. Four and 12 peptides of beta-amyloid isomers regimens were used for each simulation. Direct and indirect behavioral effects were extensively investigated. A number of critical analyses, including RMSD, ∆RMSF, Pi, and the hydration network, were performed to examine these peptides in the absence and presence of ligands. There can be a negative ∆RMSF for each sequence as a result of ligand or surfactant binding to that sequence; otherwise, the structure is partially or locally folded. Demonstrated that PC20:0 and di-C7-PC amphiphilic surfactants affect the aggregation of Aβ1–40 and Aβ1–42. The results of our simulations showed that the negative values of ΔRMSF match with some Pi > 1 values for both the hydrophobic and hydrophilic sides of ligands. Therefore, potential interactions between residual peptides and ligands were identified. A negative ΔRMSF did not match the Pi > 1 value, indicating the folding behavior of peptide residues. [ABSTRACT FROM AUTHOR]

Background and aims: In nanofibrous filters, morphological properties, diameter of fibers and porosity percent of media are the most filtration characteristics. Therefore, the present study aimed to optimize the electrospinning parameters for reaching to the desired values of the mentioned filter characteristics. Method: For this purpose, a study design was prepared using response surface methodology (RSM), in which electrospinning factors such as solution concentration, applied voltage and electrospinning distance were considered input variables and the fiber diameter, porosity, bead number and average bead diameter to average fiber diameter (ABD/AFD) ratio were considered the output variables. Morphological features of fibers and porosity of media were done through image processing approach of Scanning Emission Microscopy (SEM) images. Results: Maximum concentration in assessed range can provide the best morphology and also the maximum diameter. The highest correlation coefficient has been seen between fiber diameter and solution concentration (p 0.05, r=0.39). There was the significant relationship between both concentration and electrospinning distance and bead size (r=-1.6, r=0.56, respectively). Bead number was decreased specially with increase in concentration. Conclusion: Totally, RSM could well determine the relationship between input and response variables. High regression coefficient in mathematical models indicated the importance of the experimental values. The validation test shown the experimental data are in good agreement with the predicted ones.

Electrospun nanofibrous filter media have attracted considerable attention in the last decade. The present study aimed to develop the electrospun PAN (polyacrylonitrile) filter media through experimental investigations for application in high-performance air filters. For this purpose, an experimental design was proposed to assess the effect of electrospinning process conditions including solution concentration, electric voltage and nozzle-collector distance on the structural properties of filter media including the fiber diameter, percent of porosity and bead number. Optimization of electrospinning parameters was conducted through the Response Surface Methodology to obtain the desired values for fibrous media variables. The morphology of the mats (including bead number and fiber diameter) were studied using SEM images through, Microstructure Measurement image analyzer. The porosity was determined using image analysis algorithms by MATLAB. The findings indicated that the concentration is the most influencing factor on fiber diameter (r= 0.73, p0.05), so that the lower concentrations led to lower fiber diameter and more bead number. Among the electrospinning parameters, the highest correlation coefficient was achieved between porosity of PAN media and applied voltage (r=0.39, p>0.05). There was a negative relationship between fiber diameter and both percent of porosity (r=-23; p>0.05) and bead number(r=-0.53; p

Using density functional theory, the six noncovalent interactions and possible mechanisms of covalent functionalization of drug 6-thioguanine with COOH and COCl functionalized carbon nanotube (NTCOOH and NTCOCl) have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of drug 6-thioguanine with NTCOOH has more binding energy than NTCOCl and can act as a favorable system for 6-thioguanine drug delivery within biological and chemical systems (noncovalent). NTCOOH and NTCOCl can bond to the amino groups of 6-thioguanine through OH (COOH mechanism) and Cl (COCl mechanism) groups, respectively. The activation energies, the activation enthalpies and the activation Gibbs free energies of six pathways were calculated and compared with each other. The activation parameters related to COOH mechanism are higher than those related to COCl mechanism and therefore COCl mechanism is suitable for covalent functionalization. These results could be generalized to other similar drugs. [ABSTRACT FROM AUTHOR]

Introduction: In normal pregnancy the maternal immune system is directed towards tolerance or suppression in order to prevent the rejection of the semi allogenic fetus. Antigen presenting cells especially dendritic cells (DCs) are the key cells in initiation and regulation of immune responses. The presence of potent immunostimulatory dendritic cells in the decidual tissue of pregnancy has been demonstrated. The aim of this study was to determine how allostimulatory activity of DCs could be affected during pregnancy. Materials and Methods: DCs were isolated from spleen of pregnant or non-pregnant Balb/c mice and co-cultured with allogenic C57BL/6 T lymphocytes prepared by nylon wool method from brachial lymph nodes. Some cultures of non-pregnant female DCs were treated by 2.5% serum obtained from pregnant mice at early, middle or late gestational periods and were used in the same mixed lymphocyte reaction (MLR) settings. Cell proliferation was measured by ³H thymidin incorporation and cytokine production was measured in supernatants of MLR cultures using ELISA method. Effect of pregnant mouse serum on expression of DC surface markers was evaluated by flow cytometry. Results: No significant difference was found between stimulatory potential of splenic DCs from pregnant and non-pregnant mice in induction of allogenic T cell proliferative response. Moreover, serum of early or late pregnancy did not have any effect on DCs function in comparison with non-pregnant mouse serum, while mid-pregnancy serum significantly inhibited allostimulatory activity of DCs. IFNγ production in co-culture of DCs treated with pregnant mouse serum was significantly lower than that of control group, however, no significant difference in IL-10 production was observed. Treatment of DCs with pregnant mouse serum did not influence the percentage of cells expressing MHCII, CD86, CD8α or CD11b. However a marked reduction of the mean fluorescence intensity of MHC-II was observed. Conclusion: Our results concerning the diminished capacity of DCs to induce production of TH1 cytokines and allogenic T cell proliferation after treatment with pregnant mouse serum reveals a new way of immunologic tolerance against semi-allogenic fetus. [ABSTRACT FROM AUTHOR]

Background: The reconstitution of different T-cell subsets following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critical for efficient pathogen protection and the prevention of graft-versus-host disease (GvHD). In particular, studies have highlighted the importance of balanced ratios of regulatory T-cells (Tregs) and distinct functionally T-cells in preventing acute and chronic GvHD., Methods: We evaluated the regeneration of CD4 and CD8 T-cell subpopulations in nine pediatric patients with non-malignant disorders following allo-HSCT from a fully HLA-identical donor., Results: CD4 and CD8 T-cells were higher 12 months after the transplant but still lower than in healthy controls and pre-transplant. However, we found after allo-HSCT, central memory and effector memory cell subsets were the predominant phenotypes in the CD4 and CD8 T-cell populations, respectively. In patients who had developed acute GvHD, there was an increase in the frequency of TEMRA (effector memory T cells that re-express CD45RA) cells within the CD4 T-cell population. Meanwhile, in patients with chronic GvHD, we observed a decrease in Th1 cells in CD4 T-cells and effector memory cells within the CD8 T-cell population. In addition, we found decreased TEMRA cell subsets in CD4 and CD8 T-cell populations in chronic GvHD., Conclusion: Our findings suggest a possible relationship between the influence of acute GvHD and its prevention on delayed CD4 T-cell reconstitution and, reciprocally, unbalanced regeneration of CD4 and CD8 T-cell subsets in the development of chronic GvHD., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Cancer stem cells (CSCs), a rare sub-fraction of tumor cells, with the capability of self-renewal and strong oncogenicity are tightly responsible for chemo and radio resistance and tumor metastasis in colorectal cancer. Hence, CSCs targeting would improve the efficacy of therapeutic strategies and clinical outcomes., Methods: Here, using three-dimensional CSC spheroids and syngeneic mice model, we evaluated the cancer preventive impact of CSCs-based vaccination. CSCs enrichment was performed via colonosphere formation from CT-26 cell line and CT-26-derived tumor biopsy and characterized by confirming high expression of key stemness genes (OCT4, SOX2, and NANOG) and CSC-related surface biomarkers (CD166, DCLK1, and CD133) via real-time PCR and flow cytometry, respectively. Then, the stemness phenotype and self-renewal in CSC-enriched spheroids were further confirmed by showing serial sphere formation capacity, clonogenicity potential, and enhanced in vivo tumorigenic capacity compared to their parental counterparts. CSCs lysates were used as vaccines in prophylactic settings compared to the parental cell lysate and PBS groups., Result: Immunization of syngeneic mice with CSCs lysates was effective in the prevention of tumor establishment and significantly decreased tumor growth rate accompanied by an improvement in survival rate in tumor-bearing mice compared to groups subjected to parental cells lysate and PBS. These results, for the first time, showed that mice immunized with cell lysate from tumor biopsy-derived spheroids are resistant to tumor induction. Immunofluorescence staining indicated that only the serum antibodies from CSC-vaccinated mice reacted with colonospheres., Conclusions: These findings represent CSCs lysate-based vaccination as a potential approach to hampering immunotherapy failure of colorectal cancer which along with other traditional therapies may effectively apply to prevent the establishment of aggressive tumors harboring stemness features., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for hereditary hemoglobin disorders, such as beta-thalassemia; However, this procedure is not without constraints, mainly engendering complications such as acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), and susceptibility to infections. The clinical outcomes of allo-HSCT are highly dependant on the quality and quantity of T-cell subsets reconstitution. Following the allo-HSCT of six pediatric patients afflicted with beta-thalassemia, their mononuclear cells were isolated, and then cultured with a combination of phorbol myristate acetate (PMA)/ionomycin and Brefeldin A. The content of CD4 T-cell subsets, including T helper 17 (Th17) cells and regulatory T cells (Tregs), were determined by specific conjugated-monoclonal antibodies three and six months post-HSCT. An increased frequency of total CD4 T-cells, Tregs and Th17 cells was observed at day 90 and 180 after allo-HSCT, albeit the numbers were still lower than that of our healthy controls. In patients who developed cGvHD, a lower Th17/Treg ratio was observed, owing it to a decreased proportion of Th17 cells. In conclusion, creating balance between Th17 and Treg subsets may prevent acute and chronic GvHD in patients after allo-HSCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Beta-thalassemia major is an autosomal recessive disorder in hemoglobin synthesis. Ineffective erythropoiesis is the main characteristic of the disease, which results in anemia following the extensive destruction of red blood cells. Chronic antigenic stimulation following frequent blood transfusions lead to immune abnormalities, especially regarding T cells, which is one of the reasons for the high susceptibility to infection in beta-thalassemia., Methods: Six pediatric patients and six age- and sex-matched healthy children were selected. Immunophenotyping of functional T-cells was performed using flow cytometry with staining for surface and intracellular markers. The proliferative response of T lymphocytes was also investigated after labeling with CFSE and following stimulation with anti-CD3 and anti-CD28., Results: Examination of T lymphocyte subpopulations showed a significant increase in regulatory T cells (Tregs) in beta-thalassemia patients. Hence, the Treg:Tcons (conventional T cells) and Treg:CD8 ratios were significantly increased. In addition, a significant increase in CD8 T cell proliferation activity was observed. Multivariate analysis showed a significant association of central memory cells with serum ferritin levels and the duration of transfusion. In particular, patients with cytomegalovirus (CMV) infection exhibited a significant increase in CD4 central memory cells., Conclusion: Patients with beta-thalassemia have functionally distinct CD4 and CD8 T cell subsets imbalances, and this may contribute to their high susceptibility to infections and immune dysregulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Introduction: The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID-19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID-19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA-DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID-19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA-DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8-HLA-DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA-DR+ T, CD8- HLA-DR+ T, and CD8+ HLA-DR+ T cells was associated with mortality in COVID-19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA-DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA-DR+ T cells in COVID-19 patients may be helpful to identify high-risk patients. However, further studies with larger sample size are needed., (© 2022 Wiley Periodicals LLC.)

Placental extract (PE) and exosomes from pregnant mice appear to have immunomodulatory and neuroprotective effects. In this study, we assessed the potential therapeutic effects of PE and exosomes obtained from pregnant mice in experimental autoimmune encephalomyelitis (EAE) mouse models. C57BL/6 mice, 8 to 12 weeks of age, were prepared and administered PE, exosomes, and glatiramer acetate (GA), as an FDA-approved treatment for multiple sclerosis (MS), after EAE induction. Thereafter, the therapeutic effects of treatment were evaluated by measuring the clinical courses of the mice as well as determining the number of regulatory T (Treg) cells using flow cytometry, cytokine levels, and microRNA-326 expression via real-time PCR. GA, PE, and exosomes reduced clinical severity, the extent of spinal cord demyelination, and the infiltration of inflammatory cells into the spinal cord. The frequency of CD4+CD25+FoxP3+ Treg cells increased after treatment of EAE mice with GA, PE, and exosomes. The mRNA expression of the inflammatory cytokines (interleukin-17  and interferon-gamma), as well as miR-326 expression, decreased significantly in the EAE mice after treatment with GA and exosomes. PE and exosomes from pregnant mice are involved in the modulation of Treg/Th17 balance and provide a therapeutic approach for MS. Further clinical studies will hopefully confirm the safety and efficacy of such treatments in MS patients.