A Study of Autoantibodies against Some Central Nervous System Antigens and the IL-35 Serum Level in Schizophrenia.

Schizophrenia (SCZ) is a debilitating mental disorder with various causes involving complex interactions between genetic factors and environmental agents. The immune system plays a vital role in the pathology and function of the nervous system. Interleukin 35 (IL-35) is a regulatory and anti-inflammatory cytokine that can prevent autoimmune and inflammatory diseases. This study aimed to investigate the role of autoantibodies against some central nervous system (CNS) antigens and IL-35 serum levels in patients with Schizophrenia. This case-control study involved 80 participants. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the autoantibodies in the CNS by indirect immunofluorescence assay (IFA). The serum levels of IL-35 were decreased in patient groups compared to healthy subjects. Autoantibodies against N-methyl-D-aspartate receptor (NMDAR) and myelin-associated glycoprotein (MAG) were positive in 15% (6/40) and 7.5% (3/40), respectively; however, no antibodies against myelin, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), voltage-gated potassium channel (VGKC), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), γ-butyric acid receptor type B1 γ-butyric acid receptor type B1 (GABABR), antidipeptidyl peptidase-like protein-6 (DPPX), immunoglobulin-like cell adhesion molecule 5 (IgLON5), Glycine receptor (R) and acetylcholine receptor (Ach R) were detected (No statistics were computed).  We found that decreased serum IL-35 levels and the existence autoantibodies against NMDAR antigen may contribute to the pathogenesis of SCZ.

Autoantibodies against Central Nervous System Antigens and the Serum Levels of IL-32 in Patients with Schizophrenia.

BACKGROUND: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. Interleukin-32 (IL-32) is a proinflammatory cytokine that is essential in activating innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. MATERIAL AND METHODS: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, amphiphysin, SOX1, Zic4, ITPR1, CARP, glutamic acid decarboxylase GAD, recoverin, titin, and ganglioside antigens was measured by the indirect immunofluorescence method. RESULTS: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. The frequency of autoantibodies against GAD and RI antigens in patients with schizophrenia was significantly higher than in the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for RI antigen. Autoantibodies were also positive in 2 patients for CV2, 1 patient for Hu, and 1 patient for CARP. Negative results were reported for other antigens. CONCLUSION: Our findings suggest that elevated the serum IL-32 level and autoantibodies against GAD and RI antigens may be a reflection of immune system dysregulation in patients with schizophrenia.

Immunological Properties of Exotoxin A Toxoid - Detoxified Lipopolysaccharide - Gold Nanoparticles Conjugate Against Pseudomonas aeruginosa Infection.

BACKGROUND: Pseudomonas aeruginosa is an important opportunistic pathogen, especially in patients with compromised host defense. OBJECTIVE: To prepare the conjugate of detoxified lipopolysaccharide (D-LPS) and exotoxin A toxoid (T-ETA) from P. aeruginosa in gold nanoparticles (Au NPs) in a mice model. METHODS: LPS and ETA were purified from P. aeruginosa PAO1. D-LPS was conjugated withT-ETA via the amidation method. Au NPs were bound to D-LPS-T-ETA conjugate via electrostatic interaction. Mice were immunized with D-LPS, D-LPS-Au NPs, T-ETA, T-ETA-Au NPs, D-LPS-T-ETA, D-LPS-T-ETA-Au NPs, D-LPS-Au NPs+T-ETA-Au NPs, Au NPs, and phosphate-buffered saline (PBS), and specific IgG titers were determined by the ELISA and the whole-cell ELISA methods. Mice in the vaccinated and control groups were exposed to a 2×LD50 of P. aeruginosa and mortality rates were recorded for one week. RESULTS: The results showed that vaccination by D-LPS, D-LPS-Au NPs, T-ETA, T-ETA-Au NPs, D-LPS-T-ETA, D-LPS-T-ETA-Au NPs and D-LPS-Au NPs+T-ETA-Au NPs induced specific IgG. Mice received the D-LPS-T-ETA-Au NPs conjugate showed significant protection against bacterial challenge. CONCLUSION: These data indicate that D-LPS-T-ETA-Au NPs conjugate has a significant immunogenicity potential to be applied as a new vaccine against Pseudomonas infections.

siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468).

CD44, as a superficial cellular glycoprotein, is an essential factor in cell-cell and cell-matrix interaction. The CD44 expression level has been substantially up-regulated in breast cancer, and this upregulation facilitates tumor proliferation and angiogenesis. This study aims to evaluate the combination therapy of Jet Pei/CD44-specific-siRNA/doxorubicin in breast cancer MDA-MB468 cell line. The MTT assay, wound healing test, colony formation assay, DAPI staining, and flow cytometry were performed to investigate the tumoral cell viability, migration, clonogenesis, and apoptosis progression. The quantitative real-time PCR (qRT-PCR) was performed to demonstrate the CD44 expression level. Finally, the effect of CD44 silencing on the expression of VEGF, CXCR4, MMP9, and MiR-142-3p was measured. The combination of CD44-specific-siRNA with doxorubicin decreased tumoral metastasis, proliferation, invasion, and migration, and increased apoptosis in MDA-MB468 cells. In conclusions, CD44 can serve as a therapeutic target in breast cancer. Moreover, the combination therapy of CD44-specific-siRNA with doxorubicin can be a promising treatment for patients with breast cancer.

Corneal epithelium tissue engineering: recent advances in regeneration and replacement of corneal surface.

Currently, many corneal diseases are treated by corneal transplantation, artificial corneal implantation or, in severe cases, keratoprosthesis. Owing to the shortage of cornea donors and the risks involved with artificial corneal implants, such as infection transmission, researchers continually seek new approaches for corneal regeneration. Corneal tissue engineering is a promising approach that has attracted much attention from researchers and is focused on regenerative strategies using various biomaterials in combination with different cell types. These constructs should have the ability to mimic the native tissue microenvironment and present suitable optical, mechanical and biological properties. In this article, we review studies that have focused on the current clinical techniques for corneal replacement. We also describe tissue-engineering and cell-based approaches for corneal regeneration.

Tumor-Associated Macrophages: Protumoral Macrophages in Inflammatory Tumor Microenvironment.

Tumor microenvironment consists of malignant and non-malignant cells. The interaction of these dynamic and different cells is responsible for tumor progression at different levels. The non-malignant cells in TME contain cells such as tumor-associated macrophages (TAMs), cancer associated fibroblasts, pericytes, adipocytes, T cells, B cells, myeloid-derived suppressor cells (MDSCs), tumor-associated neutrophils (TANs), dendritic cells (DCs) and Vascular endothelial cells. TAMs are abundant in most human and murine cancers and their presence are associated with poor prognosis. The major event in tumor microenvironment is macrophage polarization into tumor-suppressive M1 or tumor-promoting M2 types. Although much evidence suggests that TAMS are primarily M2-like macrophages, the mechanism responsible for polarization into M1 and M2 macrophages remain unclear. TAM contributes cancer cell motility, invasion, metastases and angiogenesis. The relationship between TAM and tumor cells lead to used them as a diagnostic marker, therapeutic target and prognosis of cancer. This review presents the origin, polarization, role of TAMs in inflammation, metastasis, immune evasion and angiogenesis as well as they can be used as therapeutic target in variety of cancer cells. It is obvious that additional substantial and preclinical research is needed to support the effectiveness and applicability of this new and promising strategy for cancer treatment.

Prostate cancer cells modulate the differentiation of THP-1 cells in response to etoposide and TLR agonists treatments.

The aim of this study was to determine the polarization of macrophages in the tumor microenvironment, as well as the effect of soluble factors secreted from these polarized macrophages on etoposide-induced cancer cell apoptosis. We investigated the effect of soluble factors secreted from the supernatant of PC3 cells treated with TLR4 and TLR8 agonists, and etoposide on macrophage polarization at the protein level through flow cytometry and enzyme-linked immunosorbent assay. We further explored the cell cycle distribution and phagocytic activity of THP-1 cells by flow cytometry. To imitate the relationship between cancer cells and tumor-associated macrophages (TAMs), we cocultured macrophages with etoposide-treated PC3 cells. After the incubation, the apoptosis in cancer cells was assessed through FACS analysis and by annexin V and PI staining. Our results demonstrate that protein expression of M1 and M2 markers confirmed the upregulation of M1 markers upon etoposide treatment, and mixed M1/M2 phenotype upon treatment with TLR agonists-treated PC3 supernatant. In coculture methods, our results demonstrate that the apoptosis of etoposide-treated cancer cells increases in the presence of M0 macrophages and THP-1 cells incubated with the supernatant of TLR4 agonists-treated PC3 cells. These results indicate clear protective effects of M0 macrophages and THP-1 cells incubated with the supernatant of PC3 cells treated with TLR4 agonists (THP-1 + SUP + TLR4a) on etoposide-induced cancer cell apoptosis.

Production and purification of polyclonal antibody against attenuated and wild type Leishmania infantum in dogs.

Antibodies are still widely used in several programs including early research, imaging, Targeting drug delivery system, Affinity chromatography, flowcytometry technic, diagnosis and treatment. Purification of antibody is a standard approach for detection of infection agent in different species. The reservoir hosts for Leishmania infantum are Dogs and they have active role in the transmission of leishmania to humans by the bite of a sand fly belonging to genus Phlebotomus and Lutzomiya. Consequently, elimination of dogs in endemic areas and vaccination of dogs contributes to reduction of the human and canine VL cases. Serological antibody tests such as IFAT (Indirect Fluorescent Antbody Test), DFAT (Direct Fluorescent Antbody Test), ELISA (Enzyme-Linked Immunosorbent Assay), PCR (Polymerase chain Reaction Assay) have been extensively used to investigate canine infection with L. infantum. In this study we produced and purified polyclonal antibody against attenuated and wild type leishmania infantum in dogs. Anti-leishmania in dog serums precipitated with ammonium sulphate. The IgG recovered from ammonium sulphate precipitation was subject to ion exchange chromatography (IEC) and the purity of IgG was confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reduced condition. The purity of proteins were above 95% and then purified IgG was conjugated with FITC. We determined optimum titer of dog IgG by observation parasites under fluorescent microscope. The optimum dilution of prepared FITC conjugated dog IgG was 1: 400. This polyclonal antibody can be used for other applications in research, diagnosis and clinic.

Development and characterization of polyclonal antibody against human kappa light chain in rabbit.

Polyclonal antibodies against kappa light chain are used to diagnose diseases producing free light chain. The kappa and lambda light chains are products of immunoglobulin synthesis and released into the circulation in minor amounts such as serum, cerebrospinal fluid, urine and synovial fluid in normal condition. The purpose of this study was the production and purification of polyclonal immunoglobulin G (IgG) against human kappa light chains. In this study, early human IgG was purified by ion-exchange chromatography, reduced with Dithiothreitol and heavy and light chains were separated with size-exclusion chromatography. Afterward, affinity chromatography with protein L Sepharose at pH 2.00 was displayed to be a dominant condition for the separation and purification of the kappa light chain of immunoglobulins from human serum. Eventually, the rabbit was immunized by human kappa light chains. The rabbit IgG was purified and labeled with horseradish peroxidase (HRP). Direct enzyme-linked immunosorbent assay was planned to determine the titer of HRP conjugated rabbit IgG against the human kappa light chain. The optimum titer of anti-kappa IgG was 1:16000. At the result, purified polyclonal anti-kappa is useful tool in biomedical and biochemical researches and diagnostic kits.

The effect of combined miR-200c replacement and cisplatin on apoptosis induction and inhibition of gastric cancer cell line migration.

One of the major obstacles in the treatment of cancer is resistance to standard chemotherapeutic drugs. According to the numerous reports, miR-200c is involved in many cancers, especially gastric cancer, and also miR-200c has been known as an effective factor in the elimination of chemotherapy resistance. The purpose of this study was to explore the potential function and mechanism of miR-200c and cisplatin in the inhibition of migration and induction of apoptosis in gastric cancer cells. In this study, first, miR-200c mimics and LNA-anti-miR-200c were transfected into KATOIII cells. Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay results revealed that increased miR-200c expression and cisplatin can more inhibited the proliferation of KATOIII cells. MiR-200c overexpression inhibited the movement of KATOIII cells in wound healing assay. Subsequently, miR-200c/cisplatin could suppress colony formation in KATOIII cells. To identify a potential miR-200c target, we investigated the effect of miR-200c modulation on RhoE, PTEN, VEGFR, and MMP9 expression levels. Increased miR-200c expression caused a reduction in VEGFR and MMP9 mRNA and protein, suggesting that VEGFR and MMP9 are targets of miR-200c. In addition, reverse-transcription polymerase chain reaction assays showed that RhoE is target gene of miR-200c and LNA-anti-miR-200c suppressed the expression of PTEN. Flow cytometry and 4',6-diamidino-2-phenylindole staining analysis indicated that miR-200c increased the cisplatin-induced apoptosis which may be associated with suppression of RhoE expression in KATOIII cells, also cell-cycle analysis showed the arrest of cell-cycle progression at the G2 phase. These data demonstrated that miR-200c functioned as a suppressor gene in KATOIII cells. Also, miR-200c can be a potential therapeutic approach to overcome chemoresistance during cisplatin chemotherapy.

The Study of HLA-G Gene and Protein Expression in Patients with Recurrent Miscarriage.

Purpose: Although it has been frequently confirmed that HLA-G plays an important role in the reproduction and pregnancy, the pattern of HLA-G gene and its protein expression are rarely addressed in studies. Therefore we conducted this study in regard to evaluate the HLA-G gene and its protein expression in the women's placenta with recurrent miscarriage. Methods: Placental samples were obtained from the women who were admitted for delivery or abortion in Al Zahra and Taleghani hospitals, Tabriz, Iran. HLA-G gene expression was determined by real-time polymerase chain reaction (PCR) and HLA-G protein expression was assessed by western blotting and immunofluorescence staining in the tissue samples. Results: The results showed a significant decrease in the expression of gene and proteins of HLA-G in the women with recurrent miscarriage compared to the control placental tissues. Conclusion: According to the obtained results, it was concluded that the decrement of HLA-G gene and protein expressions are associated with recurrent miscarriage. Since there are conflicting results from other studies, it is suggested to conduct a more comprehensive similar study with greater sample size.

Comparing the Levels of Gingival Crevicular Fluid Prostaglandin E2 in Generalized Chronic Periodontitis Between Healthy and Type 2 Diabetes Patients: A Case-Control Study

Objective: To compare the prostaglandin E2 (PGE2) levels of gingival crevicular fluid in generalized chronic periodontitis between healthy and type 2 diabetic patients. Material and Methods: 56 diabetic and non-diabetic participants with generalized chronic periodontitis were selected randomly. They were divided into two groups (G1: generalized chronic periodontitis patients with normal blood sugar; and G2: generalized chronic periodontitis patients with diabetes). Gingival crevicular fluid samples were obtained from both groups. The average of 2 samples per day were centrifuged in a laboratory at 2500 rpm and temperature of 4°C for 5 minutes and placed in a refrigerator at -20°C. The level of PGE2 was measured using ELISA and Abcam kit. Data were analyzed by Kolmogorov-Smirnov, Mann-Whitney U Test, Pearson and independent T tests. The significant amount was considered 0.05 in this test (α<0.05). Results: The mean level of PGE2 was significantly different in the two groups and the mean level of PGE2 in the control group was lower than the case group. There was no statistically significant relationship between PGE2 with pocket depth, fasting blood sugar (FBS) and HBA1C (p>0.05). Conclusion: PGE2 level of diabetic patient group with chronic generalized periodontitis was significantly more than non-diabetic group with generalized chronic periodontitis.

Anti-Mucin1 Aptamer-Conjugated Chitosan Nanoparticles for Targeted Co-Delivery of Docetaxel and IGF-1R siRNA to SKBR3 Metastatic Breast Cancer Cells

Background: Targeted co-delivery of siRNA and a chemotherapeutic drug is an attractive approach to cancer drug design and treatment. This study was carried out to design an anti-Mucin1 aptamer (Apt)-conjugated chitosan nanoparticle (NP) for targeted co-delivery of insulin-like growth factor receptor 1 (IGF-1R) Silencer siRNA and docetaxel (DTX) to SKBR3 cells. Methods: Characterization of nano-drugs, cellular uptake of NPs, cell viability, and gene expression studies were evaluated based on metastatic breast cancer cells. Results: The results of this study showed that NPs had spherical and smooth morphology with 110-118 nm in size and had positive zeta potential (12-14 mV). siRNA and DTX were considerably loaded into NPs. The appropriate conjugation of the Apt to the NPs was affirmed by gel electrophoresis. The Apt-conjugated NPs were observed to enhance the cellular uptake of NPs into the SKBR3 cells. Although the combination treatment significantly decreased the cell viability of SKBR3 cells, the augmentative effect was observed when Apt was conjugated to NPs. Furthermore, Apt-conjugated NPs dramatically reduced the genetic expression of IGF-1R, signal transducers and activators of transcription 3 (STAT3), matrix metalloproteinases (MMP9), and vascular growth factor (VEGF). Conclusion: The targeted NPs may augment the targeting of pathways involved in tumorigenesis and metastasis of breast cancer. Therefore, more animal model experiments are needed to further clarify the efficacy and safety of this functionalized nanodrug.

Evaluation of ERAP1 Gene Single Nucleotide Polymorphism in Impressing the Inflammatory Cytokine Profile of Ankylosing Spondylitis Patients.

Ankylosing spondylitis (AS), an autoinflammatory disease, has been associated with impaired Endoplasmic reticulum aminopeptidase (ERAP) 1 activity, which is involved in priming antigenic peptides. The purpose of this study was to evaluate if the genetic variant of ERAP1 gene could impress the inflammation status of the AS patients. For genotyping, 140 AS cases and 140 healthy controls were enrolled. After isolation of peripheral blood mononuclear cells (PBMCs) and DNA extraction, all the subjects were genotyped for rs27044 polymorphism using SSP-PCR assay. Total RNA of PBMCs was isolated, cDNA was synthesized, and quantitative analyses of mRNA expression of cytokines were performed via Real-time PCR using the SYBR Green Gene Expression MasterMix. To measure the concentration of cytokines in serum of subjects, Enzyme-linked immunosorbent assay (ELISA) was used. It was observed that the G allele of rs27044 polymorphism was significantly prevalent in AS patients. Moreover, the GG genotype and the GG+GC dominant model had significantly different distribution between study groups. There was a significant overexpression of mRNAs of IL-17A, IL-6, IL-33, TNF-α, and IFN-γ, while IL-10 was significantly downregulated in AS patients. The ELISA results were in line with that of the gene expression analysis. No significant differences in mRNA expression and concentration of cytokine were identified among AS patients with three genotypes for rs27044 SNP. This study replicated the association of polymorphisms in ERAP1 gene with the risk of AS in a population from Iranian. However, it did not directly determine the inflammatory profile of the AS patients.

Targeted Co-Delivery of Docetaxel and cMET siRNA for Treatment of Mucin1 Overexpressing Breast Cancer Cells.

Purpose: Targeted treatment of breast cancer through combination of chemotherapeutic agents and siRNA had been drawing much attention in recent researches. This study was carried out to evaluate mucin1 aptamer-conjugated chitosan nanoparticles containing docetaxel and cMET siRNA on SKBR3 cells. Methods: Nano-drugs were characterized by transmission electron microscope, Zetasizer and loading efficiency calculation. siRNA entrapment onto nanoparticles, stability of siRNA-loaded nanoparticles and conjugation of mucin1 aptamer to nanoparticles were evaluated via separate electrophoresis. Cellular uptake of the targeted nanoparticles was evaluated through GFP-plasmid expression in mucin1+ SKBR3 vs. mucin1- CHO cells. Protein expression, cell viability and gene expression were assessed by Western Blotting, MTT assay, and Quantitative Real Time-PCR, respectively. Results: Characterization of nano-drugs represented the ideal size (110.5± 3.9 nm), zeta potential (11.6± 0.8 mV), and loading efficiency of 90.7% and 88.3% for siRNA and docetaxel, respectively. Different gel electrophoresis affirmed the conjugation of aptamers to nanoparticles and entrapment of siRNA onto nanoparticles. Increased cellular uptake of aptamer-conjugated nanoparticles was confirmed by GFP expression. cMET gene silencing was confirmed by Western Blotting. The significant (p ≤0.0001) impact of combination targeted therapy vs. control on cell viability was shown. Results of Quantitative Real Time-PCR represented a remarkably decreased (p ≤0.0001) expression of the studied genes involving in tumorigenicity, metastasis, invasion, and angiogenesis (STAT3, IL8, MMP2, MMP9, and VEGF) by targeted combination treatment vs. control. Conclusion: The mucin1 aptamer-conjugated chitosan nanoparticles, containing docetaxel and cMET siRNA, is suggested for treatment of mucin1+ metastatic breast cancer cells. However, further studies should be conducted on animal models.

A methodological approach for production and purification of polyclonal antibody against dog IgG.

Antibodies are a class of biomolecules that has an important role in the immune system and lots of applications in biotechnological methods and in pharmaceutics. Production and purification of antibodies in laboratory animals is one of the first ways to manufacture of these prominent tools. The obtained antibodies from these process could be used in various types of bioassay techniques such as enzyme linked immunosorbent assay (ELISA), radioimmunoassay, etc. Also, antibodies employed in diagnostics applications in humans and other animals in order to detect specific antigens. In this study, we aimed to produce and purify anti-dog IgG via immunizing rabbits with dog IgG in combination with Freund's adjuvant. Polyclonal IgG were purified by ion exchange chromatography and then the purified antibody was labeled with horse radish peroxidase (HPR). Direct ELISA was used to determine the optimum titer and cross-reactivity of HRP conjugated IgG. The purity of various IgG preparations and the optimum dilution of prepared HRP conjugated IgG, respectively, was about 95.00% and 1:8000. This study showed that efficiency ion-exchange chromatography could be an appropriate method for purification of IgG antibodies. This antibody could be a useful tool for future dog immune diagnosis tests. This product characterization shown here sets the foundations for future work on dog IgGs.

Production and characterization of anti-human IgG F(ab')2 antibody fragment.

In present study an optimized protocol for the separation of antibodies into antigen-binding fragments F(ab')2 using pepsin digestion was investigated. The production of these fragments is a consequential step in the development of medical research, treatment and diagnosis. For production of polyclonal antibody rabbit received antigen in four steps. The rabbit serum at 1/128000 dilution showed high absorbance in reaction with human IgG at the designed ELISA method. Rabbit IgG was purified by Ion-Exchange Chromatography (IEC) method. Purity was assessed by SDS-PAGE method. In non-reduced condition only one band was seen in about 150 kDa MW position and in reduced form, two bands were seen in 50 and 25 kDa MW positions. Rabbit IgG was digested by pepsin enzyme. The antibody fragments solution was applied to Gel filtration column to isolate the F(ab')2. Non-reduced SDS-PAGE for determining the purity of F(ab')2 fragment resulted in one band in 100 kDa corresponds to F(ab')2 fragment and a band in 150 kDa MW position corresponds to undigested IgG antibodies. The activities of FITC conjugated F(ab')2 fragment and commercial ones were compared using flowcytometry method. The activity results implied that the FITC conjugated- anti human F(ab')2 fragment worked as efficiently as the commercial one.

MicroRNA implications in the etiopathogenesis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease that affects both axial and peripheral skeletons as well as soft tissues. Recent investigations offer that disease pathogenesis is ascribed to a complex interplay of genetic, environmental, and immunological factors. Until now, there is no appropriate method for early diagnosis of AS and the successful available therapy for AS patients stay largely undefined. MicroRNAs (miRNAs), endogenous small noncoding RNAs controlling the functions of target mRNAs and cellular processes, are present in human plasma in a stable form and have appeared as possible biomarkers for activity, pathogenesis, and prognosis of the disease. In the present review, we have tried to summarize the recent findings related to miRNAs in AS development and discuss the possible utilization of these molecules as prognostic biomarkers or important therapeutic strategies for AS. Further examinations are needed to determine the unique miRNAs signatures in AS and characterize the mechanisms mediated by miRNAs in the pathology of this disease.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR).