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Statement of Problem: Papillon Lefevre syndrome (PLS) is a rate autosomal recessive disorder, which is characterized by palmar- plantar hyperkeratosis and rapid periodontal destruction of primary and permanent dentitions. Purpose: The aim of the present study was to evaluate the peripheral blood neutrophil function including random locomotion, chemotaxis and oxidative mechanism of killing in a group of patients with PLS. Materials and Methods: Peripheral blood was obtained from 8 PLS patients and 92 healthy control subjects. PMN mobility was measured by a modification of the micromethod of Addison and Babbage. Latex-Stimulated NBT reduction test described by Park et al was followed. Data were analyzed by Mann Whitney U test. Results: The chemotactic activity in the PLS group was significantly lower than control group (89.5±21.6 vs 113±16 m, P0.05). Conclusion: The present study indicated an impaired neutrophil chemotaxis in PLS patients.

Background: Cellular transplantation is a promising treatment strategy for neurological diseases. Objective: To report the results of intrathecal hematopoietic stem cell therapy in different neurological diseases in the past 6 years in a single center. Methods: From October 2011 to September 2018, 220 patients with various neurological diseases were transplanted intrathecally by their bone marrow stem cells. To have a longer follow up, we only reported the first 80 patients, transplanted up to July 2015--10 patients had spinal cord injuries and paralysis, 12 had advanced Parkinson's disease, 28 had cerebral palsy, 7 had hypoxic brain damage, 2 had autism, 4 had multiple sclerosis, 5 had progressive cerebellar atrophy, and 12 had other neurological diseases. The patients were admitted to the Bone Marrow Transplant Unit. On the first day, 50-200 (median 100) mL bone marrow was aspirated from the patients' posterior iliac crests, mixed with 120 mL culture media (RPMI), and 12 mL heparin. The samples were then transferred to immunology lab in cold box. Mononuclear cells (MNCs) were separated by a Ficoll-Hypaque gradient, washed, and suspended in ringers. Cell viability was assessed with trypan blue viability test. Transplantation was performed 3-4 hours after bone marrow collection. 5-10 mL of the cerebrospinal fluids were aspirated and about 20 mL MNCs (containing stem cells) in ringers were injected intrathecally (IT). The patients were laid down on their back for 4-5 hours. The median number of MNCs was 4 x 107 (range 1-450 x 107). The median viability of the cells was 90% (range 60%-98%). The patients received intravenous ceftriaxone every 12 hours and were discharged from the hospital few days after autologous stem cell therapy. Results: We noted clinical improvements in 9 of 12 patients with Parkinson's disease, 20 of 28 patients with cerebral palsy, 6 of 7 patients with hypoxic brain damage, 2 of 4 patients with multiple sclerosis, and 4 of 5 patients with cerebellar atrophy. The improvements were noted after 2-4 weeks of cell therapy. There were no improvements in patients with spinal cord injury and complete paralysis and those with autism. There were variable improvements in other patients treated. Conclusion: Most patients with advanced Parkinson's disease, cerebral palsy, hypoxic brain damage, progressive cerebellar atrophy, and kernicterus neuropathy reported clinical effects of this safe intervention resulting in better functioning and an increased quality of life. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Graves’ disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls. Materials and methods In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves’s disease. The findings were compared with 40 healthy controls. Results The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001). Conclusion The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.

Medicinal plants have been widely investigated for their various effects. Dracocephalum kotschyi Boiss (Labiatae) is used in Iranian traditional medicine for the treatment of rheumatoid diseases. The inhibitory effect of D. kotschyi on the lectin-induced cellular immune response has been demonstrated previously. In this study, mitogen-treated lymphocytes were exposed to the extract of D. kotschyi and analysed for the induction of apoptosis using flow cytometry and gel electrophoresis. The data obtained indicated a dose-dependent increase of cells in the sub-G1 phase of cell cycle. Study of internucleosomal DNA fragmentation showed a typical DNA laddering in agarose gels. A bioactivity-guided fractionation assay to find the active components responsible for the inhibitory effect of D. kotschyi on mitogen-induced lymphocyte proliferation led to the isolation of calycopterin from the ethyl acetate extract of D. kotschyi. Its structure was identified by spectroscopic methods including( 1)H-NMR, (13)C-NMR, MS and UV spectra. Calycopterin inhibited lymphocyte proliferation in a dose-dependent manner with an IC(50) value of 1.7 microg/mL. In conclusion, the results of this study suggest that D. kotschyi extract has the capacity to induce apoptosis in the lymphocytes and that isolated calycopterin is responsible for the inhibitory effect of D. kotschyi on lymphocyte proliferation. [ABSTRACT FROM AUTHOR]

A total extract of Linum persicum Kotschy ex Boiss. was investigated for biological activity. The extract was not active against Gram-negative and Gram-positive bacteria. The extract exhibited significant activity against brine shrimp (Artemia salina). Cytotoxic activity of the extract was evaluated by the MTT assay on five different cell lines. The total extract showed the highest cytotoxicity against human chronic myeloid leukemia (K-562), T-cell lines (Jurkat), and lung carcinoma (A5). Three aryltetralin lignans, podophyllotoxin, 5-methoxypodophyllotoxin, and 5-methoxy podophyllotoxin acetate, were isolated from the methanol extract of the aerial parts of L. persicum, and the structures were confirmed by spectroscopic methods. [ABSTRACT FROM AUTHOR]

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto's thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT. [ABSTRACT FROM AUTHOR]

In this research work, two new palladium complexes [trans-Pd(C15H10NOCH3)2]Cl2 (1) and [cis- Pd(C15H10NOCH3)(PPh3)2Cl]Cl (2) were synthesized using an alkoxyme ligand named isophethalaldoxime. Then structure characterization has been done by FT-IR and different NMR ( 1 H, 13 C and 31 P) spectroscopy. Then, their interactions with biological macromolecules including deoxyribonucleic acid and bovine serum albumin were studied using various spectroscopic methods such as UV-Vis absorption, fluorescence emission spectroscopy and circular dichroism. The results showed the binding of the prepared complexes to the deoxyribonucleic acid via grooves and different binding sites of bovine serum albumin. Fluorescence emission data showed that the mechanism of extinction of albumin emission by these compounds is static. Competitive titration was performed on albumin with eosin-Y, ibuprofen and digoxin as site markers I, II and III. The antitumor activity and toxicity of these compounds were evaluated on cancer cell lines A549 (leukemia) and K562 by in-vitro cytotoxicity test. The IC50 values showed the good activity of these complexes in inhibiting cancer cells. In the last section, the release mechanism of synthesized complexes from albumin nanoparticles (BNPs) was investigated and theoretical calculations were performed that showed Korsmeyer-Peppas mechanism for complex (1) and Quadratic mechanism for complex (2)., 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 © 2023 Elsevier B.V. All rights reserved.)

Introduction: Vitiligo is thought to be an autoimmune disorder caused by melanocytes dysfunction and depigmentation. Among different executors of the immune system in developing the disease, the role of various cytokines has been defined., Objectives: We have focused on IL-38, the tenth member of IL-1 cytokine family with a proposed anti-inflammatory role, which has not hitherto been introduced as an anti-inflammatory factor in vitiligo., Methods: Sixty-nine generalized vitiligo patients and 72-year-old- and sex-matched healthy individuals were included in this study. IL-38 level was evaluated in sera of all participants using ELISA assay. The relation of IL-38 level to patients characteristics was evaluated., Results: IL-38 serum level in vitiligo patients (159.5±39.7 pg/ml) was lower than the healthy controls (166.7±34.8pg/ml) (P = 0.039). A weak negative correlation between the age of male patients and their IL-38 serum levels was identified (r = 0.38, P = 0.058). Evaluation of the IL-38 serum levels relationship with patients clinical characteristics showed no correlation with disease onset, stage of depigmentation, and disease activity status., Conclusions: The lower levels of IL-38 as an anti-inflammatory cytokine support the inflammatory nature of vitiligo. It indicates the difference of IL-38 in sera of vitiligo patients and healthy controls, as the first report of the lower level of this cytokine in the context of vitiligo. The reason of this difference remains to be clarified; as there are not sufficient study reports revealing the role of gender, ethnicity and inflammation on the cytokine network in the context of vitiligo.

In this study, a lactose fatty acid ester was enzymatically synthesised using immobilized Candida rugosa lipase (CRL). Its anticancer property against K562 leukemia and HeLa cancer cells was carefully investigated. In the first step, a de novo strategy was applied to encapsulate CRL into a microporous zeolite imidazolate framework called ZIF-8. Various characterization techniques including powder X-ray diffraction, Fourier transform infrared spectroscopy, N 2 adsorption-desorption, field-emission scanning electron microscopy and thermogravimetric analysis were used to prove the successful encapsulation of CRL molecules during the formation of ZIF-8 crystals with an enzyme loading of 98% of initial CRL. The effect of various factors such as pH and temperature, affecting the enzymatic activity and reusability of the CRL@ZIF-8 composite were assessed against the free enzyme. Additionally, enzyme catalysis parameters, such as K m and V max , were also assessed. The obtained biocatalyst showed excellent activity in a wide pH range of 2-9 and a temperature range of 30-60 °C. According to the experimental results, the CRL@ZIF-8 composite maintained about 63% of its initial activity after 6 cycles of use. In the next step, the synthesized catalyst was applied for the synthesis of lactose caprate via enzymatic esterification of lactose with capric acid. Further experiments were performed to obtain the cytotoxicity profile of the new derivative. The growth inhibitory effect of the produced lactose caprate on K562 leukemia and HeLa cancer cells determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed its potential anticancer effects against both cell lines (IC 50 , 49.6 and 57.2 μg mL -1 ). Our results indicate that lactose caprate might be a promising candidate for further studies on K562 leukemia and HeLa cancer cells owing to its possible therapeutic usefulness., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Behçet's Disease (BD) is a chronic autoimmune disease with unknown etiology. Adipokines due to their roles in the regulation of immune responses might be important in the induction and progression of BD., Subjects and Methods: This case-control study included 340 patients with BD and 310 healthy controls. Single nucleotide polymorphisms (SNPs) in adiponectin (rs266729 and rs1501299) and leptin (rs7799039 and rs2167270) genes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum levels of adipokines were measured using enzyme-linked immunosorbent assay (ELISA)., Results: A higher frequency of leptin rs7799039 GG, AG, and AG +GG genotypes and G allele was revealed in patients. Besides, patients had more leptin rs2167270 AG and AG +AA genotypes and A allele. Furthermore, rs2167270 AA genotype and A allele were more frequently seen in total and female patients who had genital aphthous. Patients had significantly more serum levels of adiponectin while those with genital aphthous had significantly more leptin levels. No significant association was observed between genotypes and alleles of adiponectin SNPs and BD., Conclusion: Our findings indicated that leptin gene polymorphisms might predispose Iranian individuals to BD. Besides, elevated serum levels of adiponectin might facilitate BD pathogenesis., 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 Elsevier Ltd. All rights reserved.)

Antigens derived from engulfed apoptotic bodies that are presented by dendritic cells can amplify Ag-specific T-cells. Accelerated co-cultured DC (acDC) strategy keeps lymphocytes in contact with differentiating DCs. Therefore, Ag-specific T-cell activation can occur during DC maturation. Our aim was to prepare DCs by acDC method and check the subsequent engulfment of the apoptotic body by acDC. We have proposed that this method could be feasible if we transfect the apoptotic bodies with the antigen. DCs were prepared using acDC method and their maturation markers were confirmed by flow cytometry. Ultraviolet was used for inducing apoptosis in the PBMCs and induction of apoptosis checked by propidium iodide and 7-aminoactinomycin D staining. Flow cytometry and immunohistochemistry were used for checking the uptake of apoptotic bodies by the DCs. The alloreactivity against apoptotic bodies was examined by enzyme-linked immunospot (ELISPOT) assay. Results showed that 40.4% of DCs could efficiently engulf the apoptotic bodies. The results indicated that acDC method is capable to isolate a high yield of DCs, and these cells could properly engulf the apoptotic bodies, more works should be performed to use this method for Ag discovery through delivering the Ag by apoptotic bodies into the DCs.

Background: FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases., Objectives: To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics., Methods: Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed., Results: The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity., Conclusions: FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neurological impairments. The etiology of MS is not clearly understood, but genetics and environmental factors can affect the susceptibility of individuals. Obesity or a body mass index of (BMI) > 30 kg/m2 is associated with serious health consequences such as lipid profile abnormalities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D, and a systemic lowgrade inflammatory state. The inflammatory milieu can negatively affect the CNS and promote MS pathogenesis due in part to the increased blood-brain barrier permeability by the actions of adipose tissue-derived cytokines or adipokines. By crossing the blood-brain barrier, the pro-inflammatory adipokines such as leptin, resistin, and visfatin activate the CNS-resident immune cells, and promote the inflammatory responses; subsequently, demyelinating lesions occur in the white matter of the brain and spinal cord. Therefore, better knowledge of the adipokines' role in the induction of obesity-related chronic inflammation and subsequent events leading to the dysfunctional blood-brain barrier is essential. In this review, recent evidence regarding the possible roles of obesity and its related systemic low-grade inflammation, and the roles of adipokines and their genetic variants in the modulation of immune responses and altered blood-brain barrier permeability in MS patients, has been elucidated. Besides, the results of the current studies regarding the potential use of adipokines in predicting MS disease severity and response to treatment have been explored., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Insulitis is defined by the presence of immune cells infiltrating in the pancreatic islets that might progress into the complete β-cell loss. The immunomodulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have attracted much attention. This study aimed to evaluate the possible immunomodulatory effects of rat BM-MSCs and MSCs-derived insulin-producing cells (IPCs) in a mouse model of pancreatic insulitis., Methods: Insulitis was induced in BALB/c mice using five consecutive doses of streptozotocin. MSCs or IPCs were directly injected into the pancreas of mice and their effects on the expression of Th subsets-related genes were evaluated., Results: Both BM-MSCs and IPCs significantly reduced the expression of pancreatic Th1-related IFN-γ (P < 0.001 and P < 0.05, respectively) and T-bet genes (both P < 0.001). Moreover, the expression of IL-10 gene was significantly increased in IPC-treated compared to BM-MSC- or PBS-treated mice (P < 0.001 both comparisons)., Conclusions: BM-MSCs and IPCs could successfully suppress pathologic Th1 immune responses in the mouse model of insulitis. However, the marked increase in IL-10 gene expression by IPCs compared to BM-MSCs suggests that their simultaneous use at the initial phase of autoimmune diabetes might be a better option to reduce inflammation but these results need to be verified by further experiments., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021. Published by Elsevier B.V.)

New palladium complexes with general formula trans-[Pd(L) 2 (OAc) 2 ] (1,2), (L = Benzhydrazide and 2-Furoic hydrazide) have been synthesized and characterized with various methods including elemental analysis, FT-IR, 1 HNMR and mass spectroscopy. Afterward their interactions with bovine serum albumin and calf thymus deoxyribonucleic acid have been investigated by UV-vis absorption, fluorescence emission and circular dichroism spectroscopy. Also, site-selective replacement experiments with site probes have been carried out. Analysis of fluorescence spectrum indicated static quenching mechanism. Spectroscopic measurements for DNA binding showed the groove binding to DNA for both complexes. Furthermore, cytotoxicity studies of complexes and cis-platin have been done against colon carcinoma (CT26) and breast cancer (4T1) cell lines. Evaluation of complexes (1) and (2) on induction of apoptosis in CT26 cells has been done. Finally, plasmid cleavage ability of (1) and (2) was investigated by gel electrophoresis that indicate the more activity of (1) than (2)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p < 0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p = 0.04) and rs2294021 CT genotype (p = 0.01) in female patients compared to controls. ACC (p = 0.04) and ATC haplotypes (p = 0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p < 0.0001), shorter EFS, increased death rate (p = 0.002) and shorter OS compared to C genotype (p = 0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p = 0.02) and those with rs2294021 CT had longer EFS and OS (p < 0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.

Objective: Interleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc)., Subjects and Methods: A total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA., Results: Levels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls., Conclusion: The higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases., (© 2020 The Author(s). Published by S. Karger AG, Basel.)

Background: Macrophages are the main players involved in inflammation. Intercellular adhesion molecule-1 (ICAM-1) facilitates macrophage polarization prior to extravasation into inflamed tissue. Piperine, a natural product derived from black pepper, possesses useful biological and pharmacological activities. In the current study, the possible anti-inflammatory effect of piperine on the expression of ICAM-1 on J774.1 murine macrophage cell line was investigated., Methods: Lipopolysaccharide (LPS)-stimulated J774.1 cells were cultured in the presence of different concentrations of piperine to examine the changes in ICAM-1 expression by real-time PCR and flow cytometry., Results: We found that piperine decreased ICAM-1 gene expression level from 2.4 ± 0.25 RFC (relative fold change) in LPS-only treated cells to 0.85 ± 0.525 RFC at 1µg/ml (p<0.05), 0.43 ± 0.27 RFC at 10µg/ml (p<0.01), and 0.26 ± 0.25 RFC at 20µg/ml (p<0.01). In flow cytometry, piperine at all concentrations significantly decreased ICAM-1 surface expressions (P<0.05). The geometric mean fluorescence intensity (g-MFI) in LPS-only treated cells (792 ± 57.3) decreased to 482±70 g-MFI at 20 μg/ml piperine., Conclusion: According to the results of this study, by decreasing the expression of ICAM-1, piperine has been suggested to reduce inflammation and have the potential to provide therapeutic benefits for immune-mediated diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Behcet's disease (BD) is a systemic vasculitis, characterized by recurrent oral aphthous, genital ulcers, ocular lesions, and other organ involvement. Interleukin (IL)-27 with its pro- and anti-inflammatory effects might be an important effective cytokine in this disease. The aim of this study was to investigate the association of IL-27 serum concentration and a single-nucleotide polymorphism (SNP) rs153109 (-964 A > G) with the risk and clinical features of the patients with BD. IL-27 Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the IL-27 serum levels were measured using enzyme-linked immunosorbent assay (ELISA). It is shown that AG, GG, and AG + GG genotypes, as well as G allele of rs153109, can significantly increase the risk of BD in total and in male individuals. Significantly higher frequencies of AG and GG genotypes and G allele were observed in total and male patients with an active form of BD. AG and GG genotypes were associated with joint (p = 0.046) and vascular (p = 0.02) involvement. The frequency of the G allele was higher in all patients, as well as in female patients with vascular involvement (p = 0.02). Serum cytokine analysis indicated an increased level of IL-27 in BD patients compared to healthy subjects (p = 0.038). Additionally, a higher level of IL-27 was detected in patients carrying the rs153109 GG genotype (p = 0.04) and those with renal (p = 0.009) and skin (p = 0.05) involvement. In conclusion, this study underscores the involvement of IL-27 rs153109 variants and increased serum level in BD susceptibility and pathogenesis.

A rational approach was adopted to design high-potential metal-based antitumor agents. A series of organometallic Pd(ii) complexes with a general formula of [Pd{κ2(C,C)-[(C6H4-2)PPh2]CH(CO)C6H4Ph-4}{κ2(N,O)}] (N,O = alanine (Pd-A), valine (Pd-V), leucine (Pd-L), l-isoleucine (Pd-I) and phenylalanine (Pd-F)) were prepared by cyclopalladation of the phosphorus ylide, bridge cleavage reaction and subsequent chelation of natural α-amino acids. The complexes were fully identified using IR and multinuclear 1H, 13C, 31P NMR spectroscopic methods. X-ray crystallography exhibited that the Pd(ii) atom is located in a slightly distorted square-planar environment surrounded by C,C-orthometallated phosphorus ylide as well as NO-pendant amino acid functionality. In vitro cytotoxicity evaluation of new cyclometallated Pd(ii) complexes toward a human leukemia (K562) cancer cell line indicated promising results. The highest cytotoxic activity was discovered in the case of phenylalanine (CH2C6H5). IC50 values of this complex on a panel of human tumor cell lines representative of liver (HepG2), breast (SKBR-3), and ovarian (A2780-Resistance/Sensitive) cancers also indicated promising antitumor effects in comparison with standard cisplatin. The binding interaction ability of the phenylalanine-containing orthopalladated complex, as the most efficient compound, with calf-thymus deoxyribonucleic acid (CT-DNA) and bovine serum albumin (BSA) was investigated. UV-Vis spectroscopy, competitive emission titration, and circular dichroism (CD) techniques demonstrated the intercalative binding of the Pd(ii) complex with DNA. Molecular docking studies also fully agreed with the experimental data. Examination of the reactivity towards the protein BSA revealed that the static quenching mechanism of BSA intrinsic fluorescence by the Pd(ii) complex with a binding constant (Kb) of ∼105 is indicative of the high affinity of the complex. The competitive binding experiment using site markers with definite binding sites demonstrated that the hydrophobic cavities of site I (subdomain IIA) are responsible for the bimolecular interaction between protein BSA and the complex. Molecular docking studies effectively confirmed the significance of hydrophobic interactions in Pd(ii)-BSA binding. The results of this study could greatly contribute to exploring new potent metal-based anticancer drugs.

Failure of apoptosis contributes to leukemia progression. We investigated extracts of a native Iranian plant, Satureja bachtiarica , for possible anti-leukemia activity by induction of apoptosis and changes to the cell cycle. Growth inhibition caused by aqueous, butanol, dichloromethane and hexane extracts of S. bachtiarica on K562 and Jurkat leukemia cells was assessed using a colorimetric assay. Extracts were analyzed for induction of apoptosis and cell cycle arrest using flow cytometry and measurement of caspase-3 activity. Dichloromethane and hexane extracts inhibited leukemia cell proliferation in a dose-dependent manner. The IC 50 values of these extracts were 22-33 µg/ml. Flow cytometric determination of annexinV/propidium iodide positive cells verified a significantly increased percentage of apoptotic cells compared to negative controls. Both 50 μg/ml dichloromethane and hexane extracts induced apoptosis in 89-97% of K562 and 94-97% of Jurkat cells 48 h after treatment. The effects of extracts on the cell cycle included significantly increased numbers of K562 and Jurkat cells in the subG1 phase and decreased numbers of cells in the G1, S and G2/M phases. After 24 h, we found increased levels of caspase-3 activation in cells treated with 25 μg/ml dichloromethane and hexane extracts compared to untreated cells. Our findings indicate the anti-leukemic effects of dichloromethane and hexane extracts of S. bachtiarica due to induction of apoptosis and inhibition of cell cycle progression.

Background: It has been well-documented that the Fc receptor-like (FCRL) molecule contributes to the pathogenesis of certain autoimmune disorders. FCRL molecules belong to the immunoglobulin superfamily produced by B cells. Also, these molecules induce activating or inhibitory signals of B cells. According to this information and also considering the critical role of immune reactions in organ transplantation, the following experiment was performed to analyze the gene expression level of FCRLs in peripheral blood mononuclear cells of kidney transplant recipients., Materials and Methods: Blood samples were obtained from 32 renal transplant patients on days 1, 3, and 7 post-transplantations. Patients were divided into two groups according to the presence or absence of rejection. Also, 24 age-matched healthy subjects were enrolled as control group. After total RNA extraction from peripheral blood mononuclear cells (PBMC) and cDNA synthesis, the gene expression levels of FCRL1 , FCRL2 , and FCRL4 in each group were measured by real-time polymerase chain reaction., Results: Our results showed that FCRL1 expression levels in kidney transplant patients were significantly less than healthy controls. The overall FCRL2 expression level was not significantly different between them. However, at days 1 and 7, following transplantation in the non-rejected group FCRL2 level was significantly higher than the control group. Comparing the FCRL4 gene expression levels of both groups with healthy controls showed a significant decrease in the third and seventh days post-transplantation., Conclusion: It can be concluded that mononuclear cells, mainly B cells, have an essential role to play in kidney transplantation., (Copyright© 2020, Galen Medical Journal.)

Plasmodium falciparum causes the most severe form of malaria disease and is the major cause of infection-related mortalities in the world. Due to increasing in P. falciparum resistance to the first-line antimalarial drugs, an effective vaccine for the control and elimination of malaria infection is urgent. Because the pathogenesis of malaria disease results from blood-stage infection, and all of the symptoms and clinical illness of malaria occur during this stage, there is a strong rationale to develop vaccine against this stage. In the present study, different structural-vaccinology and immuno informatics tools were applied to design an effective antibody-inducing multi-epitope vaccine against the blood-stage of P. falciparum. The designed multi-epitope vaccine was composed of three main parts including B cell epitopes, T helper (Th) cell epitopes, and two adjuvant motives (HP91 and RS09), which were linked to each other via proper linkers. B cell and T cell epitopes were derived from four protective antigens expressed on the surface of merozoites, which are critical to invade the erythrocytes. HP91 and RS09 adjuvants and Th cell epitopes were used to induce, enhance and direct the best form of humoral immune-response against P. falciparum surface merozoite antigens. The vaccine construct was modeled, and after model quality evaluation and refinement by different software, the high-quality 3D-structure model of the vaccine was achieved. Analysis of immunological and physicochemical features of the vaccine showed acceptable results. We believe that this multi-epitope vaccine can be effective for preventing malaria disease caused by P. falciparum., 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 © 2020 Elsevier Inc. All rights reserved.)

Though the exact etiology of rheumatoid arthritis (RA) is unknown, the contribution of immune cells in the disease process is completely acknowledged. T helper (Th) 1 and Th17-related cytokines are required for the disease development and progression, while Th2 and regulatory T cells (Tregs)-derived cytokines are protective. Studies have shown that sodium benzoate (NaB) can switch the balance of Th cell subsets toward Th2 and Tregs. The present study aimed to evaluate the possible effects of NaB on the expression of CD4+T cells-related cytokines and transcription factors in splenocytes derived from an animal model of RA, adjuvant-induced arthritis (AIA). AIA was induced in rats by injection of Freund's adjuvant containing mycobacterial antigens (Mtb). Splenocytes were isolated from AIA rats and restimulated ex vivo with Mtb in the presence or absence of NaB for 24 h. To determine the effects of NaB on the expression of T cells-related cytokine and transcription factor genes, real-time PCR was performed. NaB treatment of Mtb-stimulated splenocytes derived from arthritic rats resulted in significant increases in the gene expressions of Tregs-related cytokines (IL-10 and TGF-β) and Foxp3 transcription factor, and significant decreases in the expression of Th1-related cytokines (TNF-α and IFN-γ) and the T-bet transcription factor. The ratios of Th1/Th2 (IFN-γ/IL-4), Th1/Treg (IFN-γ/TGF-β and IFN-γ/IL-10) and Th17/Treg (IL-17/IL-10 and IL-17/IL-10+TGF-β)-related cytokines were also significantly decreased. In conclusion, NaB can potentially be considered as a useful therapeutic agent for the treatment of RA and other Th1 and Th17-mediated diseases.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. In this study, we investigated the serum levels of interleukin (IL)-35 and IL-18 in children with ALL to compare with healthy subjects and find their relationship with prognostic factors and response to therapy. IL-35 and IL-18 serum concentrations in 40 children diagnosed with ALL and 35 age-matched and sex-matched healthy children were measured using ELISA. The association between cytokine levels and patients' clinical and laboratory data were determined. A significant difference was found in IL-35 serum levels between the patients (3.6±1.5 ng/mL) and controls (2.5±1.8 ng/mL) (P=0.007). No significant difference in IL-18 serum levels between these groups was observed. A positive correlation between IL-35 and IL-18 levels was detected (P=0.001). The authors found that patients with lower platelet count had higher IL-35 concentration (P=0.003). By considering a cut-off value of 6.21 ng/mL (mean±2SD of controls) for IL-35, it was found that white blood cell (WBC) count was higher in patients with IL-35 >6.21 ng/mL (P=0.016), and the majority of these patients had T-ALL (P=0.01). Although the mean overall survival in patients with IL-35 >6.21 ng/mL was shorter (937±381 d) than in those with IL-35 ≤6.21 ng/mL (1567±103 d), but the result was not significant (P=0.1, log-rank test). The IL-18 level was associated with a lower hemoglobin level (P=0.027). These data suggested a role for IL-35 in ALL development. The significant relation of IL-35 to white blood cells and platelet counts may imply a possible influence of IL-35 on ALL prognosis.

The tri-dentate Schiff base ligand 3-(2-hydroxyethylimino)-1-phenylbut-1-en-1-ol (L) produced the tetra-nuclear Cu(II) distorted cubane complex which contain Cu 4 O 4 core, upon reaction with Cu(II)acetate.H 2 O. The complex was structurally characterized by X-ray crystallography and found that, in this tetrameric and tetra-nuclear distorted cubane structure, each two-fold deprotonated Schiff base ligand coordinated to a Cu(II) center with their alcoholic oxygens and imine nitrogens and formed six and five-membered chelate rings. At the same time, each ligand bridged to a neighboring Cu(II) atom by its alcoholic oxygen, thus the metal centers became penta-coordinated. The copper(II) complex with μ-ɳ 2 -hydroxo bridges and Cu….Cu distance about 3 Å was structurally similar to the active site of natural catechol oxidase enzyme and exhibited excellent catecholase activity in aerobic oxidation of 3,5-di-tert-butyl catechol to its o-quinone. The kinetics and mechanism of the oxidation of 3, 5-DTBCH 2 catalyzed by [CuL] 4 complex, were studied at four different temperatures from 283 to 313K by UV-Vis spectroscopy. Interaction of [CuL] 4 complex with FS-DNA was investigated by UV-Vis and fluorescence spectroscopy, viscosity measurements, cyclic voltammetry (CV), circular dichroism (CD) and agarose gel electrophoresis. The main mode of binding of the complexes with DNA was intercalation. The interaction between [CuL] 4 complex and bovine serum albumin (BSA) was studied by UV-Vis, fluorescence and synchronous fluorescence spectroscopic techniques. The results indicated a high binding affinity of the complex to BSA. In vitro anticancer activity of the complex was evaluated against A549, Jurkat and Ragi cell lines by MTT assay. The complex was remarkably active against the cell lines and can be a good candidate for an anticancer drug. Theoretical docking studies were performed to further investigate the DNA and BSA binding interactions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Natural resources such as plants are an upright curing option in treating cancers and reducing the side effects of current therapeutic modalities. Allium genus vegetables are of the most interesting herbs in restricting cancers that includes garlic, onions, leeks, chives, and shallots. These plants have been exploited in folk medicine because of their beneficial health effects in improving numerous diseases. The phytochemical analysis of various Allium genus members showed that, to date, 16 species have proved potential anticancer properties due to the accumulation of various sulfur and organic compounds like S-allyl mercaptocysteine, quercetin, flavonoids, and ajoene. These compounds with various mechanisms such as hindering cell cycle, inhibiting signaling pathways, inducing apoptosis, and antioxidant activity interfere with diverse stages of formation, growth, differentiation, and metastasis of cancer cells. Similar to garlic and onion, other species have exhibited anticancer activities, so that active natural molecules extracted from them might serve as possible anticancer agents. Therefore, evaluating the main ingredients and studying their anticancer mechanisms are of great importance. In this review, we aim to summarize the available data on anticancer mechanisms of 16 species of Allium genus and their major compounds to assist further researches on the treatment and prevention of cancers., (© 2019 John Wiley & Sons, Ltd.)

New dendritic silica/titania mesoporous nanoparticles (DSTNs) loaded with curcumin (CUR) were synthesized and coated with polyethylenimine-folic acid groups (PEI-FA) for an ultrasound (US)-triggered drug release and combined chemo-sonodynamic therapy. The PEI-FA groups play a gatekeeper role, strongly encapsulate the CUR molecules inside the nanocarrier, and prevent the unwanted premature release by blocking the mesoporous channels. The results showed that the specific cancer cell uptake is improved by FA groups on the surfaces of DSTNs via receptor-mediated endocytosis. The TiO 2 layer as a sonosensitizer agent coated on the mesoporous silica nanoparticles generates reactive oxygen species. Following the US irradiation, the PEI molecules were cut off by free radicals, including OH · and O 2 - , on the exterior surface of DSTNs, and the CUR loaded in the nanocarrier was then released into the cancer cell cytosol. The release profiles of the CUR@PEI-FA-DSTN system showed that the amount of CUR released from DSTNs is controlled by tuning the US radiation time. The results of the MTT cytotoxicity tests of free CUR, free PEI-FA-DSTN nanocarrier, and CUR@PEI-FA-DSTNs against A549 (human lung carcinoma cell lines) and HeLa (human cervical carcinoma cell lines ( showed that the toxicity of CUR@PEI-FA-DSTNs is higher than those of CUR and PEI-FA-DSTNs alone. In addition, the specific targeting ability, the cellular uptake, and the anticancer activity of the synthesized compounds for targeted cancer treatment were investigated using different staining methods and fluorescence microscopy. The results revealed that the new system, CUR@PEI-FA-DSTNs, can be considered as a potent drug delivery system for increasing effectiveness of the anticancer activity of curcumin in the combined chemo-sonodynamic therapy.

Behcet's disease (BD) is a chronic multisystem autoimmune disorder. Various cytokines take part in the pathogenesis of this disease. Interleukin (IL)-38, a new member of IL-1 cytokine family, has been reported to have anti-inflammatory properties; however, its role in BD has not been investigated yet. In this study, we aimed to examine the probable role of IL-38 in the clinical context of BD. A total of 81 patients with BD and 81 age- and sex-matched healthy subjects as controls were included in this study. The serum levels of IL-38 were measured in patients and controls sera using enzyme-linked immunosorbent assay. The relationship between the serum levels of IL-38 and clinical and laboratory characteristics of the patients were determined. IL-38 serum levels were significantly lower in patients in comparison with healthy controls at P = 0.003. We found significant differences between IL-38 levels in BD patients with positive and negative pathergy tests (P = 0.048) and patients with and without eye involvement (P = 0.046). Despite the absence of significant differences in serum levels between male and female patients, IL-38 levels were higher in female patients with a positive pathergy test (P = 0.048) and those patients with eye involvement (P = 0.046). As healthy controls showed higher IL-38 serum levels than patients, a protective anti-inflammatory role of IL-38 in BD is suggested. Together, these results suggest that the positive relationship between IL-38 serum levels and eye involvement that IL-38 may play a role in this clinical feature of the disease.

Background: Immunomodulatory materials from natural herbs and the characterization of their immune enhancement effects may have tremendous potential as cancer treatment. The aim of the present study was to investigate the apoptosis-inducing activities of Euphorbia hebecarpa Boiss and Euphorbia petiolata Banks & Sol. plant extracts and their effects on cytokine secretion by lymphocytes. Materials and Methods: We assessed the apoptosis-inducing effect of the plants’ hexane extracts on previously determined sensitive cell lines (HeLa for E. hebecarpa and K562 for E. petiolata) by flow cytometry and measurement of caspase 3 activation. The apoptosis-related gene expressions were examined by real-time PCR. The effects of the extracts on lymphocyte proliferation and cytokine secretion were examined. Results: Flow cytometry analysis showed that the inhibitory effect of the extracts on tumor cell growth was due to cell apoptosis. The plant extracts at the 100 μg/ml dose induced apoptosis in HeLa (98.5 ± 0.1%) and K562 (57.7 ± 1.9%) cells. The extracts increased caspase 3 activation (≈2-fold>control). Real-time PCR showed Fas and Bax gene upregulation and Bcl-2 downregulation, which resulted in an increased Bax/Bcl-2 expression ratio. The extracts increased lymphocyte proliferation and increased levels of IFN-γ production in the presence and absence of mitogen (p < 0.05). They significantly increased IL-4 and decreased IL-10 secretion by mitogen-stimulated lymphocytes. E. hebecarpa also increased IL-17 release. Conclusion: These results have shown that both extracts possess antitumor activity by inducing apoptosis, possibly through both intrinsic and extrinsic pathways. In addition, they induced secretion of different T helper subset related cytokines that are effective in the immune response against cancer.