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Abstract: Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neu-rological impairments. The etiology of MS is not clearly understood, but genetics and environ-mental 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 abnormal-ities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D, and a systemic low-grade 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-in-flammatory 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 dys-functional 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 per-meability 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.

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.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.Both BM-MSCs and IPCs significantly reduced the expression of pancreatic Th1-related IFN-γ (P0.001 and P0.05, respectively) and T-bet genes (both P0.001). Moreover, the expression of IL-10 gene was significantly increased in IPC-treated compared to BM-MSC- or PBS-treated mice (P0.001 both comparisons).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.

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 possess useful biological and pharmacological activities. In 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 Conclusion: According to the results of this study, by decreasing the expression of ICAM-1, piperine is suggested as a candidate to reduce inflammation and has the potential for therapeutic benefits for immune-mediated diseases.

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 adiponectin SNPs and the frequency of BD.Conclusion: Our findings indicated that leptin gene polymorphisms might predispose individuals to BD. Besides, elevated serum levels of adiponectin might promote the pathogenesis of BD.

A novel collection of tripodal β-lactam derivatives with 1,3,5-triazine as the central core is presented for the first time. The diastereoselective synthesis of tris-β-lactams was achieved via a [2 + 2] cycloaddition reaction between s-triazine-based tris-imines and activated aryloxyacetic acid derivatives. All the s-triazine hybrids were identified by FT-IR, 1H NMR, 13C NMR spectroscopies and elemental analysis, and found to have all-cis relative stereochemistry of the three β-lactams rings. The intermediate imines displayed moderate in vitro inhibitory activity against MCF-7 and HeLa cancer cell lines. The tris-β-lactams were tested against four kinds of bacteria including Gram-negative bacteria, E. coli and P. aeruginosa, a Gram-positive S. aureus and one capsulated Gram-negative K. pneumonia by the Kirby–Bauer disc diffusion method. Two compounds have shown moderate antibacterial activity against S. aureus, but not against the other bacteria, or fungal isolates C. albicans and A. fumigatus. The tris-β-lactams displayed good inhibitory behavior against the K562 human leukemia cell line, and antioxidant properties as radical scavengers.

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...

A new oxime ligand named isophthalaldoxime (1) was synthesized by the addition of hydroxylamine hydrochloride to isophthalaldehyde. Then, a four nuclear palladacycle complex {Pd4[(N,C)(NOHCHC6H2CHNOH)(μ-Cl)2]2} (2) was prepared and fully characterized using elemental analysis, FT-IR, and NMR spectroscopy. A desolvation method was employed for the synthesis of protein nanoparticles using bovine serum albumin (BSA). Then, complex (2) was loaded on the prepared nanoparticles with an optimized entrapment efficiency (EE) of 97.78% and loading capacity (LC) of 22.68%. FT-IR spectroscopy and circular dichroism (CD) were used for spectral studies. Field emission scanning electron microscopy (FESEM) and dynamic light scattering (DLS) measurement was applied for structural studies on the morphology, size, and zeta potential of BSA nanoparticles (BSA-NPs) and complex-loaded nanoparticles ((2)@BSA-NPs). The results showed the stability and acceptable size of nanoparticles prepared for the in vitro drug release experiment. Therefore, the in vitro release of (2) from BSA-NPs was studied using the dialysis bag method. In addition, the release mechanism was investigated by mathematical methods and the results showed that phase I and II of the release process followed Korsmeyer–Peppas and Higuchi models, respectively. Finally, the in vitro cytotoxicities of the synthesized nanoparticles, palladium complex, and complex-loaded nanoparticles were carried out against A549 human lung carcinoma and K562 human leukemia cell lines using MTT colorimetric assays.

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.

Several plants of Satureja genus have shown anti-tumor activity. We investigated the antileukemia effects of different fractions of Satureja hortensis (Summer savory). The growth inhibitory effect of S. hortensis fractions on K562 and Jurkat leukemia cells were determined by MTT assay. The most effective fractions were analyzed by flow cytometry and colorimetric assay for apoptosis induction and cell cycle changes. Various fractions from S. hortensis showed growth inhibitory effects on leukemia cells, among them two hexane and dichloromethane fractions with IC50 values of 32.1-47.8 μg/ml (K562) and 44.3-45.7 μg/ml (Jurkat) were the most effective. According to annexin V staining, both of these fractions significantly induced apoptosis at 50μg/ml in K562 (hexane; 73.06 ± 5.11% and dichloromethane; 96.14 ± 2.33%) and Jurkat cells (hexane; 78.85 ± 11.9% and dichloromethane; 94.05 ± 2.47%) 48 h after treatment. They increased cell accumulation in sub-G1 phase (>50%, p < .001) and decreased number of cells in G0-G1, S and G2M phases. The fractions significantly increased the caspase-3 activity in both cell lines (≈2.5-3.5 fold of untreated cells). Hexane and dichloromethane fractions of S. hortensis had the capacity to induce death and change the cell cycle distribution in leukemia cells; therefore they might be good candidates for more studies in regard to their possible therapeutic usefulness in leukemia.

Aim of the study In this study we investigated Fas, FasL and Foxp3 expression in relation to liver graft rejection and its severity in autoimmune hepatitis (AIH) patients. Material and methods Twenty-three AIH patients including five post-transplant patients with acute rejection (AR) and 18 patients without AR (non-AR) were studied for Fas, FasL and Foxp3 gene expression in peripheral blood mononuclear cells on days 1, 3 and 7 after transplantation by real-time PCR. The relationships between gene expression and clinical features were determined. Results Real-time PCR showed various Fas gene expression levels with no significant difference between the days in AR patients (p = 0.52). In non-AR patients, Fas level increased from 0.98 ±0.24 fold on the first day to 1.89 ±0.42 fold on day 3 after transplantation (p < 0.01). In this group of patients, we also found a significant increase in FasL expression on day 7 (29.91 ±6.89 fold) compared to day 1 (13.50 ±7.44 fold, p < 0.05). Foxp3 gene expression in both groups showed decreased levels during the first week after transplantation. The decreased Foxp3 expression in AR patients was correlated with rejection activity index (r = 0.86, p < 0.0001). Conclusions Increased Fas and FasL gene expression levels in non-AR patients and decreased Foxp3 gene expression in both groups suggested the important role of these molecules in the alloreactive response after liver transplantation in AIH patients. Foxp3 expression might be useful for monitoring rejection severity.

Context: Mentha longifolia (L.) Huds., has shown anti-inflammatory effects.Objective: To evaluate the immunomodulatory effects of menthol, the major constituent of Mentha longifolia on T cells as t...

Introduction: There are limited studies on the anti-cancer and immunomodulatory effects of the fig fruit latex. In this study, we aimed to investigate the effect of fig fruit latex on several cancer cell lines as well as its effect on lymphocytes proliferation and cytokines secretion. Methods: After preparing a methanolic extract from fig latex, its effect on various cancer cell lines including Fen (bladder cancer), K562 (myeloid leukemia), Hela (cervix carcinoma), Jurkat (lymphoid leukemia) and Raji (lymphoma) was examined by MTT colorimetric assay. For evaluating the effects of extract on lymphocyte proliferation and viability, BrdU assay and flow cytometry staining were used. Cytokine secretion was measured by ELISA assay. Results: The extract showed the strongest activity against K562 cell line (IC50, 234 µg/ml) and the least activity against Hela cells (IC50 >1000 µg/ml). On evaluation of the immunomodulatory effect of fig by BrdU assay, a reduction in lymphocytes proliferation by increasing the concentration of the extract was observed; proliferation index from 1.2±0.06 at 0.1 µg/ml of the extract reached to 0.13±0.2 at 800 µg/ml. In flow cytometry analysis, a significant cytotoxic effect at concentrations ≥400 µg/ml was observed. The extract at 100 and 200µg/ml had the ability to reduce secretion of interferon (IFN)-γ and interleukin (IL)-4 cytokines. Conclusion: Fig latex extract showed cytotoxicity on different cells particularly K562 leukemia cells which implied its anticancer activity. This extract at lower concentrations reduced lymphocytes proliferation and cytokine production which showed its immunoinhibitory effects and suggested its possible beneficial in treatment of immune-mediated diseases.

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 TiO2 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 O2-, 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.

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.

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.

Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of new data regarding the molecular heterogeneity of invasive cancers is quickly emerging; far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in heterogeneity feature of the BC. In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues (ANCTs). And finally, bioinformatic evaluation has been done.The qPCR results showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P= 0.0085 and P= 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P= 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with age at menarche

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

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

Failure of apoptosis contributes to leukemia progression. We investigated extracts of a native Iranian plant

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 Cancer is a major cause of mortality. The present study evaluates the antitumor effects of Ferula hezarlalehzarica Y. Ajani fractions on various cancer cell lines, including the Raji Burkitt’s lymphoma cells. Methods We evaluated the cytotoxic activity of various fractions of F. hezarlalehzarica against tumor cell lines by the MTT assay. Annexin V-PE/7-AAD and cell cycle analysis were assessed by flow cytometry. Expressions of genes associated with cell death and proliferation (Bax, Bcl-2, Fas, and c-Myc) were determined using real-time PCR. Alteration in mitochondrial membrane potential (MMP) was examined by JC-1 dye staining. Results The hexane fraction of F. hezarlalehzarica showed the highest degree of cytotoxicity against Raji cells (IC50 = 31.6 μg/ml). Flow cytometry analysis showed that 200 μg/ml of the fraction induced apoptosis in >96% of Raji cells after 24 h. In cell cycle analysis, at the same concentration, the percentage of apoptotic cells in the sub G1phase increased to 95.25 ± 1.76% at 48 h of treatment. The fraction induced cell cycle arrestat the G0/G1phase. Exposure to 100 μg/ml of the fraction after 48 h increased the percentage of G0/G1 cells (76.3 ± 6.08%) compared to the negative control (

The purpose of this study is to develop a targeted drug delivery system containing folic acid-conjugated dendritic amino mesoporous silica nanoparticles (DFMSNs) loaded with a cyclometallated gold(III) complex, [Au(bzpy)Cl2] (bzpy = 2-benzylpyridine), as a cytotoxic agent (Au(drug)@DFMSNs). The products, including the Au(III) complex, DFMSNs, and Au(drug)@DFMSNs, were characterized by transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), UV–Vis, 1H NMR, Fourier transformation infrared (FT-IR), Brunauer-Emmett-Teller (BET) surface area analysis, inductively coupled plasma-atomic emission spectroscopy (ICP-AES), zeta potential measurements, and dynamic light scattering (DLS). The in vitro release study in different pH conditions show that the release of the Au(III) complex from the folic acid functionalized amino mesoporous silica nanoparticles is sustained and pH dependent. The in vitro cytotoxicity test of the free Au(drug), free nanocarrier (DFMSNs), Au(drug) loaded folate-conjugated nanocarrier (Au(drug)@DFMSNs), and Au(drug) loaded nanocarrier without folate-conjugation (Au(drug)@DAMSNs) against two human cancer cell lines, including MCF-7 (human breast carcinoma cell lines) and A549 (human lung carcinoma cell lines) showed that the therapeutic efficacy of Au(drug)@DFMSNs is significantly greater than those in other compounds because the cancerous cells can uptake the folate-conjugated drug nanocarrier via folate receptors-mediated endocytosis. In addition, the different staining methods and fluorescence microscopic images were used to visualize the specific targeting ability, cellular uptake, and the anticancer activity of Au(drug)@DFMSNs and Au(drug)@DAMSNs toward the MCF-7 and A549 cancer cells. The results proved that the proposed system, Au(drug)@DFMSNs, can be used as a potent anticancer agent in targeted cancer therapies for breast cancer.

A water-soluble tetranuclear copper (II) Schiff base complex bridged by 2,6-bis-[(2-hydroxyethylimino)methyl]-4-methylphenol, namely [Cu4(L1)2(O)(OAc)4].2H2O was synthesized. The complex was characterized by 1HNMR, FT-IR, elemental analyses and single-crystal X-ray diffraction. The crystal structure analyses revealed that four Cu atoms were located around a central O atom in a distorted tetrahedral geometry. Beside the two ligands, four acetates also bridged the four Cu atoms. The interaction of the complex with Bovine serum albumin (BSA) was explored by absorption and emission titration methods the calculated binding constants revealed high affinity of the complex to BSA. The antitumor activity of the complex against Jurkat, Raji and A549 cell lines was assessed by the MTT colorimetric method. A strong activity against the cultured tumor cells was observed which makes the complex a possible candidate as an anticancer agent. Further investigation of the BSA-complex interactions was done by docking studies.

A stable colloidal solution of gold nanoparticle–3,4-dihydroxyphenylalanine (DOPA) zwitterion conjugates (Au NP–z-DOPA) was prepared using nanosecond-laser ablation of a gold target in an aqueous solution of zwitterionic DOPA (z-DOPA). Spectroscopic data revealed that Au NPs strongly interact with z-DOPA, which lead to a significant change in the electronic structure of z-DOPA. The adsorbed z-DOPA is highly stable against oxidation in aqueous solution, indicating a significant stabilizing effect of the Au NPs surface on this zwitterion. The electronic structures and geometries of z-DOPA and the other forms of DOPA (including uncharged, cationic, and anionic forms) adsorbed on the Au(111) nanosurface were determined by ONIOM calculations. The geometry and electronic structure of each DOPA form are significantly affected by the surface upon adsorption. The analysis of the frontier orbitals confirmed the significant stabilizing effect of the Au NPs on z-DOPA. The calculations are consistent with the variatio...

A new mononuclear of copper (II), [Cu(theophylline)2(H2O)3]·2H2O, has been synthesized by reaction of theophylline (1,3-dimethyl-7H-purine-2,6-dione) with copper (II) nitrate in water. Further, its nanocomplex has been prepared through the three different methods including sonication, grinding, and a combination thereof, sonication-grinding. The prepared nanocomplex was characterized using different techniques including FT-IR, UV–Vis, X-ray diffraction (XRD) analysis, and field-emission scanning electron microscopy (FE-SEM). Moreover, the anticancer activity of the precursor complex, nanocomplex, free theophylline ligand, and the starting copper salt (Cu(NO3)2·3H2O) was investigated against the K562 cell line. The results show that the nanocomplex is an effective nano metal–based anticancer agent with IC50 = 11.7 μM.

A new palladacyclic dimer [Pd2((C,N)L)2(μ-Sac)2] (1), in which L: C14H11NBr and sac: the saccharinate ligand, has been synthesized and completely characterized. X-ray crystallography has been used to determine the single crystal structure of this Pd(II) complex. In this dimer, two palladium(II) centers are bridged by a saccharinate anion, which is coordinated to the cyclopalladated units as a bidentate (N- and carbonyl O-atoms) ligand. According to DNA binding studies (UV-Vis spectroscopy, emission titration and viscosity measurements), the Pd(II) complex interacts with calf-thymus DNA (CT-DNA) through a groove binding mode with a binding affinity on the order of 105. Furthermore, UV-Vis and fluorescence emission spectroscopy have been used to monitor the binding of the complex to bovine serum albumin (BSA). The complex is mainly located in site I of the protein, based on the competitive experiments using Warfarin, Ibuprofen and Digoxin as site markers. The results of molecular docking confirmed the experimental data. Finally, the in vitro cytotoxicity of sodium saccharin, ligand LH (C14H12NBr), complex 1 and cisplatin against cervical cancer (HeLa), lung cancer (A549) and breast cancer (MCF-7) cell lines has been studied. The complexation process has significantly improved the anticancer activity, as the IC50 values show. Furthermore, complex 1 has been tested against NIH normal fibroblast cells. Therefore, based on the SI definition, 1 can be assigned as a selective compound against cancer cells.

A metformin containing palladium complex, [Pd(Met) 2 ](OAc) 2 ( 1 ), and several cyclopalladated complexes of the general formula [Pd(benzylamine)(Met)](NO 3 ), in which Met is metformin drug and benzylamine is dl -α-methylbenzylamine ( 2 ), N , N -dimethylbenzylamine ( 3 ), N -ethylbenzylamine ( 4 ) and N - t -buthylbenzylamine ( 5 ), have been synthesized and characterized using elemental analysis, FT-IR and NMR spectroscopy. Spectroscopic titrations, displacement experiments, DNA melting and circular dichroism (CD) spectroscopy have been applied in the investigation of complexes ( 1 ), ( 2 ) and free metformin, DNA binding properties. The complexes and free metformin bind to CT-DNA (Calf thymus DNA) efficiently through groove binding and intercalation modes, respectively, according to the results obtained. The corresponding intrinsic binding constants, K b , of the complexes and free metformin are as follows: metformin > complex ( 2 ) > complex ( 1 ). Strong association of complexes ( 1 ), ( 2 ) and free metformin with BSA via a static mechanism with intrinsic binding constants (K b ) in 1.18 × 10 4 –4.81 × 10 4 M −1 concentration range is indicated by absorption and emission measurements. The binding sites of complexes and free metformin on BSA were located at sites I and II of BSA, respectively, as demonstrated by competitive experiments. The in vitro cytotoxic activities of complexes ( 1 ), ( 2 ) and free metformin were evaluated against Hela (cervical cancer), MCF7 (breast cancer) and A549 (lung cancer) cellular lines.

Interleukin (IL)-27 is a cytokine with important anti-cancer activity. This study has evaluated the effects of IL-27 rs153109 and rs17855750 single nucleotide polymorphisms (SNPs) on risk of acute lymphoblastic leukemia (ALL) development, as well as their impact on prognosis and patient survival. A total of 200 patients and 210 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. We observed a higher frequency of rs153109 AG and rs17855750 TG genotypes and allele G in patients compared to controls (p

A novel water-soluble glycine bridged zinc(II) Schiff base coordination polymer was synthesized by the condensation of 2,6-diformyl-4-methylphenol, glycine, and zinc(II) chloride. The complex was characterized by 1HNMR, FT-IR, elemental analyses and X-ray crystallography. The polymeric complex was built up of two glycine-bridged Zn/L moieties, where L denotes the Schiff base containing 2,6-diformyl-4-methylphenol and glycine in 1:1 M ratio. The carboxylic group of L was coordinated to the Zn atoms of the neighboring moieties; thus each Zn center was five-coordinated. The interaction between polymeric Zn(II) complex and bovine serum albumin (BSA) was studied by UV–Vis, fluorescence, and synchronous fluorescence spectroscopic techniques. By considering the sign and values of the thermodynamic parameters (ΔH and ΔS), it is clear that the binding between BSA and complex was exothermic and entropy-driven and electrostatic interactions between the complex and BSA was supposed. Site-selective binding studies revealed that the complex were mainly located in the region of site II (subdomain IIIA) in BSA. From the synchronous fluorescence spectroscopic studies, it is concluded that complex could bind to tyrosine and tryptophan residues simultaneously. The Kb values indicated a high binding affinity of the complex to BSA. In vitro anticancer activity of the polymeric Zn(II) complex was evaluated against A549, Jurkat, and Raji cell lines by MTT assay. The complex was remarkably active against the cell lines and can be a good candidate for an anticancer therapy. Theoretical docking studies were performed to further investigate the BSA binding interactions.

A mononuclear ruthenium(II) complex, trans-[Ru(Hmel)2(dmso)2], was synthesized and characterized. The DNA- and BSA-binding properties of the mono-anionic meloxicam (Hmel−) ligand and its Ru(II) complex were investigated under physiological conditions. The interaction of the Hmel− ligand and the Ru(II) complex with fish sperm DNA were explored through UV–Vis spectroscopy, emission titration, and viscosity measurement. The results reveal that the mono-anionic Hmel− ligand binds to DNA through intercalation between the base pairs of double-stranded DNA, while the complex interacts with DNA through electrostatic or/and groove (major and minor) binding modes. The values of Kb for the DNA–Hmel− and DNA-complex systems indicate that the complex has stronger tendency to bind with DNA than the free Hmel− ligand. Both compounds interact with BSA and change its microenvironment during interaction. The values of quenching constants (Ksv) and binding constants (Kb) of both compounds with BSA show that the Ru(II) complex has more affinity for BSA. The in vitro cytotoxicity testes of Hmel− and trans-[Ru(Hmel)2(dmso)2] against the Jurkat, NB4, and CT-26 human cell lines demonstrated reasonable cytotoxicities. Furthermore, the binding of both compounds to DNA and BSA was modeled by molecular docking method.

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.