Search

The relation between microchimerism and allograft tolerance is still a mystery. In this study we determined the presence of peripheral blood microchimerism (PBMC) in female renal transplant recipients from living male donors with second round polymerase chain reaction (PCR). Second round PCR was used to find Y chromocome products. The degree of PBMC in renal transplant recipinents must be below the rate of 1.104 and second round PCR provides the deterction of PBMC at the rate of 1.106. we divided our patients into two groups according to allograft function. Group 1 (16 patients) and normal allograft function. Group 2 (6 patients) had chronic allograft dysfunction. First PCR didn’t show PBMC. Second round PCR with SRY primers of Y chromosome showed PBMC in 13.22 (59%) of patients. PMBC was positive in 10.016 (62%) of patients in-group 1 and 3.6 (50%) of patients in group 2. There was acute rejection in 4.13 (30.7%) and 2.9 (22.2%) of patients with positive and negative PBMC, respectively, in our study, there was no significant correlation between the presence of PBMC and allograft function and the frequency or severity of rejection episodes.

Adibrad M, Deyhimi P, Ganjalikhani Hakemi M, Behfarnia P, Shahabuei M, Rafiee L. Signs of the presence of Th17 cells in chronic periodontal disease. J Periodont Res 2012; 47: 525-531. © 2012 John Wiley & Sons A/S Background and Objective: The aim of this study was to identify the specific markers of T helper 17 (Th17) cells and their variations in people suffering from chronic periodontal disease in comparison with normal control subjects. Material and Methods: In 30 patients with periodontitis and 30 normal control subjects, the mRNA expressions of interleukin (IL)-17A and retinoic orphan receptor C2 (RORC2) were measured by quantitative RT-PCR. The protein levels of IL-17A and RORC2 were also evaluated by immunohistochemistry. The levels of these markers were compared between healthy and diseased periodontal tissues by the Mann-Whitney U-test. Results: In periodontal lesions, IL-17A and RORC2 were significantly overexpressed compared with normal tissues. According to our immunohistochemical analysis, the number of IL-17A-positive cells and RORC2-positive cells was significantly greater in periodontal lesions compared with control sites. Moreover, there was a positive correlation between the presence of IL-17A and RORC2 transcript and protein content levels in the gingiva of diseased patients. Conclusion: The results demonstrated a significant increase in the number of some specific markers of Th17 cells in patients suffering from periodontal disease in comparison with normal control subjects. [ABSTRACT FROM AUTHOR]

Introduction. Hepatitis C virus (HCV) infection is a hepatotropic virus causing a variety of extrahepatic immunological manifestations and is a risk factor of a variety of extrahepatic diseases, such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN), which is the most common glomerulonephritis. The aim of this study was to evaluate renal involvement in HCV-infected patients. Materials and Methods. A total of 300 randomly-selected HCV antibody-positive outpatients at the HCV clinic of Shariati hospital were enrolled. Serum creatinine was measured and glomerular filtration rate was estimated accordingly. Urine proteinuria was measured in 24-hour urine samples. Results. The patients were 249 men (83.2%) and 51 women (16.8%) with a mean age of 37.8 +/- 11.7 years (range, 18 to 70 years). Proteinuria was found in 12 HCV antibody-positive adults (4%), 1 of whom underwent biopsy. He was a 55- year-old man with a 4-month history of facial and lower extremities edema and 3-g proteinuria with a normal kidney function (glomerular filtration rate, 85 mL/min) and normocomplementemia. Kidney biopsy specimens showed MPGN. The frequency of low glomerular filtration rate was 0.7% (2 patients) in the HCV antibody-positive adults. There was no significant relationship between HCV seropositivity and low glomerular filtration rate. Conclusions. Our observations showed renal involvement in HCV antibody-positive patients. Among immune complex glomerular kidney diseases, MPGN without cryoglobulins is thought to be the most common in these patients. [ABSTRACT FROM AUTHOR]

Myeloid malignancies arise in bone marrow microenvironments and shape these microenvironments in favor of malignant development. Immune suppression is one of the most important stages in myeloid leukemia progression. Leukemic clone expansion and immune dysregulation occur simultaneously in bone marrow microenvironments. Complex interactions emerge between normal immune system elements and leukemic clones in the bone marrow. In recent years, researchers have identified several of these pathological interactions. For instance, recent works shows that the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), from bone marrow stromal cells contributes to immune dysregulation and the selective proliferation of JAK2V617F+ clones in myeloproliferative neoplasms. Moreover, inflammasome activation and sterile inflammation result in inflamed microenvironments and the development of myelodysplastic syndromes. Additional immune dysregulations, such as exhaustion of T and NK cells, an increase in regulatory T cells, and impairments in antigen presentation are common findings in myeloid malignancies. In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Cancer control and treatment remain a significant challenge in cancer therapy and recently immune checkpoints has considered as a novel treatment strategy to develop anti-cancer drugs. Many cancer types use the immune checkpoints and its ligand, PD-1/PD-L1 pathway, to evade detection and destruction by the immune system, which is associated with altered effector function of PD-1 and PD-L1 overexpression on cancer cells to deactivate T cells. In recent years, mAbs have been employed to block immune checkpoints, therefore normalization of the anti-tumor response has enabled the scientists to develop novel biopharmaceuticals. In vivo affinity maturation of antibodies in targeted therapy has sometimes failed, and current experimental methods cannot accommodate the accurate structural details of protein-protein interactions. Therefore, determining favorable binding sites on the protein surface for modulator design of these interactions is a major challenge. In this study, we used the in silico methods to identify favorable binding sites on the PD-1 and PD-L1 and to optimize mAb variants on a large scale. At first, all the binding areas on PD-1 and PD-L1 have been identified. Then, using the RosettaDesign protocol, thousands of antibodies have been generated for 11 different regions on PD-1 and PD-L1 and then the designs with higher stability, affinity, and shape complementarity were selected. Next, molecular dynamics simulations and MM-PBSA analysis were employed to understand the dynamic, structural features of the complexes and measure the binding affinity of the final designs. Our results suggest that binding sites 1, 3 and 6 on PD-1 and binding sites 9 and 11 on PD-L1 can be regarded as the most appropriate sites for the inhibition of PD-1-PD-L1 interaction by the designed antibodies. This study provides comprehensive information regarding the potential binding epitopes on PD-1 which could be considered as hotspots for designing potential biopharmaceuticals. We also showed that mutations in the CDRs regions will rearrange the interaction pattern between the designed antibodies and targets (PD-1 and PD-L1) with improved affinity to effectively inhibit protein-protein interaction and block the immune checkpoint., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdolmaleki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The development of a cancer vaccine has become an essential focus in the field of medical biotechnology and immunology. In our study, the NY-SAR-35 cancer/testis antigen was targeted to design a novel peptide vaccine using bioinformatics tools, and BALB/c mice were used to evaluate the vaccine's immunological function. This evaluation involved assessing peptide-specific IgG levels in the serum via ELISA and measuring the levels of IFN-γ, IL-4, and granzyme B in the supernatant of cultured splenocytes. The final vaccine construct consisted of two T lymphocyte epitopes linked by the AAY linker. This construct displayed high antigenicity, non-allergenicity, non-toxicity, stability, and ability to induce IFN-γ and IL-4. It showed stable dynamics with both human MHC-I and II molecules, as well as mouse MHC-II molecules, and revealed strong Van der Waals and electrostatic energies. Emulsifying our peptide vaccine in incomplete Freund's adjuvant resulted in a remarkable increase in the levels of IgG. The splenocytes of mice that received the combination of peptide and adjuvant displayed a noteworthy increase in IFN-γ, IL-4, and granzyme B secretion. Additionally, their lymphocytes exhibited higher proliferation rates compared to the control group. Our data demonstrated that our vaccine could stimulate a robust immune response, making it a promising candidate for cancer prevention. However, clinical trials are necessary to assess its efficacy in humans., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Samman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome ( NLRP3, ASC, and CASP1 ) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p =0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p =0.0001 for Caspase-1 and an AUC of 0.665 with p =0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested., Competing Interests: The authors do not have any conflicts of interest., (Copyright © 2024 Tehran University of Medical Sciences.)

Cancer is still considered a lethal disease worldwide and the patients' quality of life is affected by major side effects of the treatments including post-surgery complications, chemo-, and radiation therapy. Recently, new therapeutic approaches were considered globally for increasing conventional cancer therapy efficacy and decreasing the adverse effects. Bioactive peptides obtained from plant and animal sources have drawn increased attention because of their potential as complementary therapy. This review presents a contemporary examination of bioactive peptides derived from natural origins with demonstrated anticancer, ant invasion, and immunomodulation properties. For example, peptides derived from common beans, chickpeas, wheat germ, and mung beans exhibited antiproliferative and toxic effects on cancer cells, favoring cell cycle arrest and apoptosis. On the other hand, peptides from marine sources showed the potential for inhibiting tumor growth and metastasis. In this review we will discuss these data highlighting the potential befits of these approaches and the need of further investigations to fully characterize their potential in clinics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ghadiri, Javidan, Sheikhi, Taştan, Parodi, Liao, Tayybi Azar and Ganjalıkhani-Hakemi.)

Background: T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1., Methods: Cell lines were cultured in RPMI 1640 which supplemented with 10% FBS and 1% antibiotics. 24, 48, and 72 h after addition of recombinant Galectin-9 (Gal-9), RT-qPCR analysis, RP-HPLC and gas chromatography techniques were performed to evaluate the expression of glutaminase (GLS), glutamate dehydrogenase (GDH) enzymes, concentration of metabolites; Glutamate (Glu) and alpha-ketoglutarate (α-KG) in glutaminolysis pathway, respectively. Western blotting and MTT assay were used to detect expression of mammalian target of rapamycin complex (mTORC) as signaling factor, GLS protein and cell proliferation rate, respectively., Results: The most mRNA expression of GLS and GDH in HL-60 cells was seen at 72 h after Gal-9 treatment (p = 0.001, p = 0.0001) and in THP-1 cell line was observed at 24 h after Gal-9 addition (p = 0.001, p = 0.0001). The most mTORC and GLS protein expression in HL-60 and THP-1 cells was observed at 72 and 24 h after Gal-9 treatment (p = 0.0001), respectively. MTT assay revealed that Gal-9 could promote cell proliferation rate in both cell lines (p = 0.001). Glu concentration in HL-60 and α-KG concentration in both HL-60 (p = 0.03) and THP-1 (p = 0.0001) cell lines had a decreasing trend. But, Glu concentration had an increasing trend in THP-1 cell line (p = 0.0001)., Conclusion: Taken together, this study suggests TIM-3/Gal-9 interaction could promote glutamine metabolism in HL-60 and THP-1 cells and resulting in AML development., (© 2024. The Author(s).)

Introduction: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines., Methods: HL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography-mass spectrometry (GC-MS) to designate FFAs., Results: We observed the significant upregulated expression of GLUT-1 , HK-2 , PFKFB-3 , ACC-1 , CPT-1A , and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines ( p > 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p < 0.05)., Conclusion: TIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Rezaei, Ghanadian, Ghezelbash, Shokouhi, Bazhin, Zamyatnin and Ganjalikhani-Hakemi.)

Programmed death ligand‑1 (PD‑L1) is a pivotal inhibitory checkpoint ligand known to induce T-cell exhaustion via interaction with the programmed death‑1 (PD‑1) receptor. Beyond this, PD-L1's intrinsic signaling pathways within cancer cells warrant further exploration. This study aims to elucidate the effect of PD-L1 stimulation on the proliferation, survival, and apoptosis of acute myeloid leukemia (AML) cell lines. Two human AML cell lines, HL-60 and THP-1 were cultured and treated with phorbol 12-myristate 13-acetate (PMA) to induce PD-L1overexpression. Post-treatment PD-L1 expression was confirmed via flow cytometry. Subsequently, cell surface PD-L1 was stimulated using a recombinant PD-1, 24 hours post-PMA treatment. The expression alterations in pivotal genes including BCL2, MKI67, BAX, and CASP3 were monitored using quantitative real-time polymerase chain reaction 24 and 48 hours post-treatment. Additionally, annexin-V through flow cytometry. Findings reveal that PD-L1 stimulation augments AML cell proliferation and survival by enhancing MKI67 and BCL2 expressions while concurrently inhibiting cell apoptosis due to decreased BAX and CASP3 expression following PD-L1 stimulation. Notably, stimulated cells expressed exhibited reduced annexin-V compared to control cells. This study underscores that PD-L1 stimulation fosters AML cell proliferation and survival while impeding cell apoptosis. The results hold potential implications for targeting PD-L1 in AML treatment strategies.

One of the most critical issues concerning orthopedic implants is the risk of chronic inflammation, which poses a threat to the bone healing process. Osteo-immunomodulation plays a pivotal role in implant technology by influencing proinflammatory and anti-inflammatory responses, ultimately promoting bone healing. This study aims to investigate the morphology-dependent osteo-immunomodulatory properties of a hydroxyapatite (HA)/plasma electrolytic oxidation (PEO)-coated WE43 alloy. In this context, following the PEO process with various operational parameters (duty cycles of 50-40, 50-20, 70-40%, and frequencies of 0.5, 0.8, and 1 kHz), a layer of HA was applied as the top coating using a straightforward hot-dip process. The results revealed the formation of the PEO layer with distinct morphologies and pore sizes, depending on the operational parameters. Specifically, a uniform PEO coating with small pore sizes (5.2-5.3 μm) led to the creation of plate-like HA particles, while a random-like HA structure formed on nonuniform surfaces with large pores (7.0-11.1 μm) of PEO. Moreover, it was observed that the plate-like HA coating exhibited higher adhesion strength than the random one (classified as class 2 vs class 3 based on cross-cut standards). Furthermore, electrochemical impedance spectroscopy (EIS) and polarization studies confirmed a substantial increase in the polarization resistance (680 kΩ) and total impedance (48 559.6 Ω) for the plate-like HA/PEO as compared to the substrate (an increase of 1511-fold and 311-fold, respectively) and the random HA/PEO samples (an increase of 85-fold and 18-fold, respectively). In addition, compared to random HA coatings, there was a significant enhancement in the viability (150% control vs 96% control), proliferation, and differentiation of MG63 cells when exposed to plate-like HA coatings. Moreover, surface morphology and chemistry pronouncedly impacted macrophages' viability, morphology, and phenotype. Notably, plate-like HA coatings resulted in a higher upregulation of BMP-2 and TGF-β than proinflammatory cytokines (IL-6 and M-CSF), indicating a polarization of macrophage type 1 (M1) toward type 2 (M2). In summary, the bilayer HA/PEO coating exhibited remarkable osteo-immunomodulatory activity, making it highly appealing for use in bone implant applications.

Background: Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma . The current drugs for treating schistosomiasis are associated with some side effects., Objective: The aim of this systematic study was an overview of the treatment of diseases caused by Schistosoma based on nanoparticles., Methods: In the present systematic research with keywords " Schistosoma ", "parasitism", "anti- Schistosoma activity", "nanoparticles", "metal nanoparticles", "silver nanoparticles", "gold nanoparticles", "polymer nanoparticles", "PLGA nanoparticles", "nanoemulsions", " in vitro ", and " in vivo " from five English-language databases, including ScienceDirect, europePMC, PubMed, Scopus, Ovid, and Cochrane were searched from 2000 to 2022 by 2 researchers., Results: In the initial search, 250 studies were selected. Based on the inclusion and exclusion criteria, 27 articles were finally selected after removing duplicate, unrelated, and articles containing full text. In present article, the most nanoparticles used against Schistosoma were gold nanoparticles (22%)., Conclusions: The results indicate the high potential of various nanoparticles, including metal nanoparticles, against Schistosoma . Also, the remarkable anti-schistosomal activity of nanoparticles suggests their use in different fields to eliminate this pathogenic microorganism so that it can be used as an effective candidate in the preparation of anti-schistosomal compounds because these compounds have fewer side effects than chemical drugs. Ther Res Clin Exp . 2023; XX:XXX-XXX)., (© 2023 The Authors.)

Background: KIR/HLA mismatch in hematopoietic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia (AML), was related to decreased recurrence rates, improved engraftment, and a reduction in graft-versus-host disease, according to recent research (GVHD). Uncertainty exists about the impact of KIR/HLA mismatch on haploidentical-HSCTs treated with post-transplant cyclophosphamide (PTCy). We attempted to analyze the effects of KIR/HLA mismatch on clinical outcomes on transplant outcomes using the cohort of 54 AML patients who received a haplo-HSCT with PTCy., Results: In contrast to KIR/HLA match, our findings showed that donor KIR/HLA mismatch was substantially associated with superior OS (HR, 2.92; (P = 0.04)). Moreover, donor KIR/HLA mismatch (KIR2DS1 D /C2 + R and KIR2DS2 D /C1 + R mismatch versus KIR2DL1 D /C2 - R mm, KIR2DL2/3 D /C1 - R mm and KIR3DL1 D /Bw4 - mm) was correlated with the improvements in OS (HR, 0.74; P = 0.085) and activating. KIR/HLA mismatch versus KIR/HLA match was significantly correlated with improvements in OS (HR, .46; P = 0.03) and inhibitory. KIR/HLA mismatch versus KIR/HLA match was enhancement in the OS (HR, .93; P = 0.06). Despite a higher rate of aGvHD (grade I-IV) in the patients with KIR/HLA mismatch compared to KIR/HLA matched (57% vs. 33% (p = 0.04). However, the KIR/HLA mismatch group saw a decreased relapse rate (3.2% vs. 23%, p = 0.04)., Conclusion: This analysis shows the significance of KIR/HLA Incompatibility, other clinical variables like CMV, the relationship between donor/recipient and donor age, and the relationship between donor/recipient and donor age in the haplo-donor selection process. It also suggests that KIR and HLA mismatching between donor and recipient could be routinely performed for haplo-donor selection and may improve clinical outcomes after haplo-HSCTs with PTCy., (© 2023. The Author(s).)

Background: Leukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed Death Ligand -1 (CD-274) is one of the immune checkpoint ligands that do not only cause the immune escape of cancer cells, but also have some intracellular effects in these cells. PD-L1 is overexpressed on leukemic stem cells and relates with poor prognosis of AML. In this study, we investigated effects of PD-L1 stimulation on critical metabolic pathways of glucose and fatty acid metabolisms that have important roles in proliferation and survival of leukemic cells., Methods: After confirmation of PD-L1 expression by flow cytometry assay, we used recombinant protein PD-1 for stimulation of the PD-L1 on two AML cell lines, HL-60 and THP-1. Then we examined the effect of PD-L1 stimulation on glucose and fatty acid metabolism in cells at the genomic and metabolomic levels in a time dependent manner. We investigated expression changes of rate limiting enzymes of theses metabolic pathways (G6PD, HK-2, CPT1A, ATGL1 and ACC1) by qRT-PCR and also the relative abundance changes of free fatty acids of medium by GC., Results: We identified a correlation between PD-L1 stimulation and both fatty acid and glucose metabolism. The PD-L1 stimulated cells showed an influence in the pentose phosphate pathway and glycolysis by increasing expression of G6PD and HK-2 (P value = 0.0001). Furthermore, PD-L1 promoted fatty acid β-oxidation by increasing expression of CPT1A (P value = 0.0001), however, their fatty acid synthesis was decreased by reduction of ACC1 expression (P value = 0.0001)., Conclusion: We found that PD-L1 can promote proliferation and survival of AML stem cells probably through some metabolic changes in leukemic cells. Pentose phosphate pathway that has a critical role in cell proliferation and fatty acids β-oxidation that promote cell survival, both are increased by PD-L1 stimulation on AML cells., (© 2023. The Author(s).)

Mesenchymal stem/stromal cells (MSCs) are multipotent cells with immunomodulatory effects that have been attempted as a possible treatment for neurologic disorders. Since currently available drugs for neurologic disorders are limited, special attention has been paid to MSCs. With the ability to differentiate into neural cells, it has been shown that MSCs exert their effects in a paracrine manner by producing extracellular vesicles (EVs). Extracellular vesicles are small vesicles with a size of 30-1000 nm that are released by cells, such as MSCs, T cells, B cells, etc. EVs contain various molecules, including proteins, lipids, mRNAs, and microRNAs (miRNAs). In recent years, the administration of EVs in models of neurological disorders has been shown to improve neurological dysfunctions. miRNAs from MSC-EVs as one of the important mediators which regulate various genes and reduce neuropathological change have been identified in different neurological disorders. Here, we review the effects of EVs miRNAs from MSCs on different neurological disorders and their potential applications., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Natural killer (NK) cell behavior and function are controlled by a balance between negative or positive signals generated by an extensive array of activating and inhibiting receptors, including killer cell immunoglobulin-like receptor (KIR) proteins, main components of the innate immune system that contribute to initial responses against viral infected-transformed cells through generation of the release of cytokines and cytotoxicity. What is certain is that KIRs are genetically polymorphic and the extent of KIRs diversity within the individuals may have the potential outcomes for hematopoietic stem cell transplantation (HSCT). In this regard, recent studies suggest that KIR is as imperative as its ligand (HLA) in stem cell transplantation for malignant diseases. However, unlike HLA epitope mismatches, which are well-known causes of NK alloreactivity, a complete understanding of KIR genes' role in HSCT remains unclear. Because of genetic variability in KIR gene content, allelic polymorphism, and cell-surface expression among individuals, an appropriate selection of donors based on HLA and KIR profiles is crucial to improve outcomes of stem cell transplantation. In addition, the impact of the KIR/HLA interaction on HSCT outcomes needs to be investigated more comprehensively. The present work aimed to review the NK cell regeneration, KIR gene polymorphisms, and KIRligand binding on outcomes in hematologic malignancies following haploidentical stem cell transplantation. Comprehensive data gathered from the literature can provide new insight into the significance of KIR matching status in transplantations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acute myeloid leukemia (AML) is a type of leukemia with a poor prognosis and survival characterized by abnormal cell proliferation and differentiation. Despite advances in treatment, AML still has a low complete remission rate, particularly in elderly patients, and recurrences are frequently seen even after complete remissions. The major challenge in treating AML is the resistance of leukemia cells to chemotherapy drugs. Thus, to overcome this issue, it can be crucial to conduct new investigations to explore the mechanisms of chemo-resistance in AML and target them. In this review, the potential role of autophagy induced by FLT3-ITD and acid ceramidase in chemo-resistance in AML patients are analyzed. With regard to the high prevalence of FLT3-ITD mutation (about 25% of AML cases) and high level of acid ceramidase in these patients, we hypothesized that both of these factors could lead to chemo-resistance by inducing autophagy. Therefore, pharmacological targeting of autophagy, FLT3-ITD, and acid ceramidase production could be a promising therapeutic approach for such AML patients to overcome chemo-resistance. Video abstract., (© 2022. The Author(s).)

Multiple Sclerosis (MS) is the most common demyelinating disease with inflammatory demyelination in the central nerve system. Besides the defect in the myelin repair process, the balance change in inflammatory and anti- inflammatory cytokines is one of the most significant factors in MS pathogenesis. This study aimed at evaluating the effects of co-overexpressing beta interferon (IFN-β) and Leukemia inhibitory factor (LIF) in human adipose-derived stem cells (IFN-β/LIF-hADSCs) on the experimental autoimmune encephalomyelitis (EAE). 12 days after the induction of EAE on female mice C57Bl/6 with MOG35-55 and the emergence of primary clinical signs, the IFN-β/LIF-hADSCs were injected into the mice tail vein of the EAE mice. The mice were sacrificed after 32 days and the spinal cords of the experimental groups were dissected out for the histopathologic and real-time RT-PCR studies. Here, we showed that the clinical scores and infiltration of mononuclear cells of treated mice with IFN-β/LIF-hADSCs were decreased significantly. Demyelination and the number of Olig2 + and MBP + cells were significantly increased in the test (IFN-β/LIF-hADSCs) group. The findings revealed that the pattern of inflammatory and anti- inflammatory cytokines gene expression in the IFN-β/LIF-hADSCs group was reversed compared to the control group. Overexpression of LIF as a neurotrophic and IFN-β as an anti-inflammatory cytokine in hADSCs increases the immunomodulatory effect of hADSCs reduces the extent of demyelination, improves the number of Olig2 + cells, and also increases the amount of MBP protein which can increase the production of myelin in EAE model. This, besides hADSCs capacity for proliferation and differentiation, might enhance the treatment efficacy and provide a promising candidate for stem cell-based gene therapy of MS therapy in the future., (© 2022. The Author(s).)

Common variable immunodeficiency disorder (CVID) is a heterogeneous disorder and the most common symptomatic antibody deficiency disease characterized with hypogammaglobulinemia and a broad range of clinical manifestations. Multiple genetic, epigenetic, and immunological defects are involved in the pathogenesis of CVID. These immunological defects include abnormalities in the number and/or function of B lymphocytes, T lymphocytes, and other rare immune cells. Although some immune cells have a relatively lower proportion among total immune subsets in the human body, they could have important roles in the pathogenesis of immunological disorders like CVID. To the best of our knowledge, this is the first review that described the role of rare immune cells in the pathogenesis and clinical presentations of CVID., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The development of immune checkpoint inhibitors, the monoclonal antibodies that modulate the interaction between immune checkpoint molecules or their ligands on the immune cells or tumor tissue has revolutionized cancer treatment. While there are various studies proving their efficacy in hematological malignancies, there is also a body of accumulating evidence indicating that immune checkpoint inhibitors' clinical benefits are limited in such diseases. In addition, due to their regulatory nature that balances the immune responses, blockade of immune checkpoints may lead to toxic side effects and autoimmune responses, and even primary or acquired resistance mechanisms may restrict their success. Thus, the need for laboratory biomarkers to identify and monitor patient populations who are more likely respond to this type of therapy and the management of side effects seem critical. However, guidelines regarding the use of immune checkpoint inhibitors in hematological cancers and during follow-up are limited while there is no consensus on the laboratory parameters to be investigated for safety and efficacy of the treatment. This review aims to provide an insight into recent information on predictive and prognostic value of biomarkers and laboratory tests for the clinical follow up of hematological malignancies, with an emphasis on leukemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aru, Soltani, Pehlivanoglu, Gürlü, Ganjalikhani-Hakemi and Yanikkaya Demirel.)

The efficacy of the cancer vaccine is influenced by several factors, but one of the most important is the immunosuppressive tumor microenvironment, which can attenuate treatment effects. The combination of therapeutic cancer vaccines with other immunotherapies or conventional therapeutic approaches can promote vaccine efficacy by increasing immune surveillance and tumor immunogenicity and modulating immune escape in the tumor microenvironment. Inhibitory checkpoints have a significant role in the modulation of anticancer immune responses, and according to preclinical and clinical trials, administration of immune checkpoint inhibitors (ICIs) in combination with cancer vaccines can markedly improve their therapeutic effects, considering their low clinical efficacy. In addition, these combinatorial therapies have acceptable safety and minimal additional toxicity compared to single-agent cancer vaccines or ICIs. In this review, based on the results of previous studies, we introduce and discuss treatments that can be combined with therapeutic cancer vaccines to improve their potency. Our major focus is on checkpoint blockade therapies, which are the most well-known and applicable immunotherapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The idea of cancer immunotherapy is to stimulate the immune system to fight tumors without destroying normal cells. One of the anticancer therapy methods, among many, is based on the use of cancer vaccines that contain tumor antigens in order to induce immune responses against tumors. However, clinical trials have shown that the use of such vaccines as monotherapy is ineffective in many cases since they do not cause a strong immune response. Particular tumors are resistant to immunotherapy due to the absence or insufficient infiltration of tumors with CD8+ T cells, and hence, they are called cold or non-inflamed tumors. Cold tumors are characterized by a lack of CD8+ T cell infiltration, the presence of anti-inflammatory myeloid cells, tumor-associated M2 macrophages, and regulatory T cells. It is very important to determine the stage of the antitumor response that does not work properly in order to use the right strategy. Applying other therapeutic methods alongside cancer vaccines can be more rational for cold tumors, which do not provoke the immune system strongly. Herein, we indicate some combinational therapies that have been used or are in progress for cold tumor treatment alongside vaccines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Pollen is one of the most common allergens that cause respiratory allergies worldwide. Pollen grains from poplars have been reported as important sources of pollinosis in many countries., Objective: The aim of the present study was to determine the molecular and immunochemical characterization of Pop n 2, a novel allergen of Populus nigra (P nigra) pollen extract., Methods: In this study, the pollen extract of P nigra was analysed by SDS-PAGE, and the allergenic profile was determined by IgE immunoblotting and specific ELISA using the sera of twenty allergic patients. The coding sequence of Pop n 2 was cloned and expressed in the Escherichia coli BL21 (DE3) using plasmid the pET-21b (+). Finally, the expressed recombinant Pop n 2 was purified by affinity chromatography., Results: Pop n 2 belongs to the profilin family with a molecular weight of approximately 14 kDa. Pop n 2 is the most IgE-reactive protein (about 65%) in the P nigra pollen extract. The cDNA sequencing results indicated an open reading frame 396 bp that encodes 131 amino acid residues. The results of ELISA and Immunoblotting assays showed that recombinant Pop n 2 could react with the IgE antibody in patients' sera, like its natural counterpart., Conclusion: Our data revealed that Pop n 2 is a significant allergen in the P nigra pollen extract. Moreover, we observed that the recombinant Pop n 2 produced by the pET-21b (+) vector in the E colisystem acts as its natural counterpart., (© 2021 John Wiley & Sons Ltd.)