Exosomes from SHED-MSC regulate polarization and stress oxidative indexes in THP-1 derived M1 macrophages.

OBJECTIVE: The inhibition of M1 macrophages may be interesting for targeted therapy with mesenchymal stem cell-derived Exosomes (MSC-EXOs). This study aimed to investigate the stem cells of human exfoliated deciduous teeth-derived EXOs (SHED-MSC-EXOs) effect on regulating the pro- and anti-oxidant indexes and inhibiting M1 macrophage polarization. Besides, an in-silico analysis of SHED-MSC-EXO miRNAs as the highest frequency of small RNAs in the exosomes was performed to discover the possible mechanism. METHODS: The flow cytometry analysis of CD80 and CD86 as M1-specific markers confirmed the polarization of macrophages derived from THP-1 cells. After exosome isolation, characterization, and internalization, THP-1-derived M1 macrophages were treated with SHED-MSC-EXOs. M1-specific markers and pro- and anti-oxidant indexes were evaluated. For in-silico analysis of SHED-MSC-EXOs miRNAs, initial miRNA array data of SHED-EXOs is collected from GEO, and the interaction of the miRNAs in M1 macrophage polarization (M1P), mitochondrial oxidative stress (MOS) and LPS-induced oxidative stress (LOS) were analyzed by miRWalk 3.0 server. Outcomes were filtered by 75th percentile signal intensity, score cut-off ≥0.95, minimum free energy (MEF)≤ -20 kcal/mol, and seed = 1. RESULTS: It shows a decrease in the expression of CD80 and CD81, a reduction in pro-oxidant indicators, and an increase in the anti-oxidant indexes (P < 0.05). Computational analysis showed that eight microRNAs of SHED-MSC-EXO miRNAs can bind to and interfere with the expression of candidate genes in the M1P, MOS, and LOS pathways simultaneously. CONCLUSION: SHED-MSCs-EXOs can be utilized to treat conditions related to M1 macrophage-induced diseases (M1IDs) due to their unique physical properties and ability to penetrate target cells easily.

Electrochemical Wearable Biosensors and Bioelectronic Devices Based on Hydrogels: Mechanical Properties and Electrochemical Behavior.

Hydrogel-based wearable electrochemical biosensors (HWEBs) are emerging biomedical devices that have recently received immense interest. The exceptional properties of HWEBs include excellent biocompatibility with hydrophilic nature, high porosity, tailorable permeability, the capability of reliable and accurate detection of disease biomarkers, suitable device-human interface, facile adjustability, and stimuli responsive to the nanofiller materials. Although the biomimetic three-dimensional hydrogels can immobilize bioreceptors, such as enzymes and aptamers, without any loss in their activities. However, most HWEBs suffer from low mechanical strength and electrical conductivity. Many studies have been performed on emerging electroactive nanofillers, including biomacromolecules, carbon-based materials, and inorganic and organic nanomaterials, to tackle these issues. Non-conductive hydrogels and even conductive hydrogels may be modified by nanofillers, as well as redox species. All these modifications have led to the design and development of efficient nanocomposites as electrochemical biosensors. In this review, both conductive-based and non-conductive-based hydrogels derived from natural and synthetic polymers are systematically reviewed. The main synthesis methods and characterization techniques are addressed. The mechanical properties and electrochemical behavior of HWEBs are discussed in detail. Finally, the prospects and potential applications of HWEBs in biosensing, healthcare monitoring, and clinical diagnostics are highlighted.

Interaction of iron and zinc fortification and late-season water deficit on yield and fatty acid composition of Dragon's Head (Lallemantia iberica L.).

Dragon's head (Lallemantia iberica) is a rich source of alpha-linolenic acid, linoleic acid, essential oil, protein, and mucilage. Therefore, the aim of this study was to evaluate the effects of foliar application of three different concentrations of Fe and Zn (control, 4, and 8 g lit-1) at two different developmental stages (vegetative stage (VS) and reproductive stage (RS)) on the quantity and quality of dragon's head seed yield and fatty acid composition in two crop seasons (2018 and 2019) under two environments (normal irrigation as control (NI) and post-anthesis water deficit (WD). In NI, average yields of seed, oil, and protein were 1155, 340, and 183 kg ha-1, respectively, and in the WD, they were 879, 283, and 148 kg ha-1, respectively. By applying Zn and Fe, the mean values of seed, oil, and protein yields in the NI were 1425, 478, and 264 kg ha-1, while in the WD, they were 1011, 354, and 200 kg ha-1, respectively. Furthermore, the application of WD resulted in a significant increase in zinc concentration, protein percentage, and saturated fatty acid percentage in seeds. Unlike WD, iron and zinc treatments decreased the percentage of saturated fatty acids and increased the percentage of unsaturated fatty acids. The number of capsules per plant had the most positive indirect effect on grain yield. The results showed that foliar spraying of Fe and Zn could effectively mitigate the adverse effects of WD on the quality and quantity of seed and oil yield dragon's head.

Salivary anti-cyclic citrullinated peptide as a screening tool for rheumatoid arthritis.

Objectives: This study aims to evaluate the sensitivity and specificity of salivary anti-cyclic citrullinated peptide 3 (anti-CCP3) for the early diagnosis of rheumatoid arthritis. Patients and methods: Between June 2017 and April 2019, a total of 63 patients with rheumatoid arthritis (10 males, 53 females; mean age: 50.4±9.5 years; range, 27 to 74 years) and 49 healthy controls (8 males, 41 females; mean age: 49.3±9.3 years; range 27 to 67 years) were included. Salivary samples were collected by passive drooling. Anti-cyclic citrullinated peptide analyses of salivary and serum samples were performed. Results: The mean polyclonal immunoglobulin (Ig)G-IgA anti-CCP3 salivary levels were significantly different in patients (149.2±134.2) compared to healthy controls (28.5±23.9). The mean polyclonal IgG-IgA anti-CCP3 serum levels were measured as 254.0±169.5 in patients and 3.8±3.6 in healthy individuals. The diagnostic accuracy analysis of salivary IgG-IgA anti-CCP3 results in an area under the curve (AUC) of 0.818, as well as 91.84% specificity and 61.90% sensitivity. Conclusion: Salivary anti-CCP3 may be considered as an additional screening test for rheumatoid arthritis.

B cells and T cells abnormalities in patients with selective IgA deficiency.

BACKGROUND: Selective IgA deficiency (SIgAD) is the most prevalent inborn errors of immunity with almost unknown etiology. This study aimed to investigate the clinical diagnostic and prognostic values of lymphocyte subsets and function in symptomatic SIgAD patients. METHODS: A total of 30 available SIgAD patients from the Iranian registry and 30 age-sex-matched healthy controls were included in the present study. We analyzed B and T cell peripheral subsets and T cell proliferation assay by flow cytometry in SIgAD patients with mild and severe clinical phenotypes. RESULTS: Our results indicated a significant increase in naïve and transitional B cells and a strong decrease in marginal zone-like and switched memory B-cells in SIgAD patients. We found that naïve and central memory CD4+ T cell subsets, as well as Th1, Th2 and regulatory T cells, have significantly decreased. On the other hand, there was a significant reduction in central and effector memory CD8+ T cell subsets, whereas proportions of both (CD4+ and CD8+) terminally differentiated effector memory T cells (TEMRA) were significantly elevated in our patients. Although some T cell subsets in severe SIgAD were similar, a decrease in marginal-zone and switched memory B cells and an increase in CD21low B cell of severe SIgAD patients were slightly prominent. Moreover, the proliferation activity of CD4+ T cells was strongly impaired in SIgAD patients with a severe phenotype. CONCLUSION: SIgAD patients have varied cellular and humoral deficiencies. Therefore, T cell and B cell assessment might help in better understanding the heterogeneous pathogenesis and prognosis estimation of the disease.

Reinforcement of Calcium Phosphate Cement with Hybrid Silk Fibroin/Kappa-Carrageenan Nanofibers.

Calcium phosphate cements (CPCs) offer a promising solution for treating bone defects due to their osteoconductive, injectable, biocompatible, and bone replacement properties. However, their brittle nature restricts their utilization to non-load-bearing applications. In this study, the impact of hybrid silk fibroin (SF) and kappa-carrageenan (k-CG) nanofibers as reinforcements in CPC was investigated. The CPC composite was fabricated by incorporating electrospun nanofibers in 1, 3, and 5% volume fractions. The morphology, mineralization, mechanical properties, setting time, injectability, cell adhesion, and mineralization of the CPC composites were analyzed. The results demonstrated that the addition of the nanofibers improved the CPC mixture, leading to an increase in compressive strength (14.8 ± 0.3 MPa compared to 8.1 ± 0.4 MPa of the unreinforced CPC). Similar improvements were seen in the bending strength and work fracture (WOF). The MC3T3-E1 cell culture experiments indicated that cells attached well to the surfaces of all cement samples and tended to join their adjacent cells. Additionally, the CPC composites showed higher cell mineralization after a culture period of 14 days, indicating that the SF/k-CG combination has potential for applications as a CPC reinforcement and bone cell regeneration promoter.

Anticancer potential of fermented milk with autochthonous lactic acid bacteria.

AIMS: The purpose of this study was to investigate the effect of fermented milk supernatants of autochthonous lactic acid bacteria, including Lactobacillus helveticus KMCH1 (ON561781), Lactococcus lactis KMCM3 (ON561782), and Lactiplantibacillus plantarum KMJC4 (ON615217), on human colon cancer (HT-29) and normal mouse fibroblast (L929) cells in vitro. METHODS AND RESULTS: Proteolytic activity, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test, evaluation of apoptosis induction, and cell cycle arrest by flow cytometry were the assays performed in this study. The measurement of proteolytic activity of three types of fermented milk supernatant using an orthophthalaldehyde reagent showed that the fermented milk supernatant of L. helveticus KMCH1 included the highest proteolysis. Three types of fermented milk supernatant showed anticancer effects on HT-29 cell in a time- and concentration-based manner (at a concentration of 16 mg ml-1 for 72 h of incubation), while the effect of three types of supernatant on inhibition of L929 cell was 3%-10%. Besides, three types of supernatant inhibited HT-29 cell proliferation by inducing apoptosis and cell cycle arrest in the S phase. CONCLUSIONS: Autochthonous lactic acid bacteria strains were able to produce bioactive peptides with anticancer effects in fermented milk. Inhibition of HT-29 cell proliferation was dependent on peptide concentration.

Comparison of a Suggested Model of Fibrosis in Human Dermal Fibroblasts by Serum from Systemic Sclerosis Patients with Transforming Growth Factor ß Induced in vitro Model.

Systemic sclerosis (SSc) is a chronic autoimmune disease, featuring fibrosis in multiple organs. The serum from SSc patients contain inflammatory mediators, contributing to SSc pathogenesis and could be used to develop cell culture models. Here, we compared the fibrotic effects of serum samples from SSc patients with TGFß1 on human dermal fibroblasts (HDFs). HDF cells were cultured in four different culture media supplementations; 10% SSc serum, 10% healthy human serum, 10% fetal bovine serum or 10% FBS supplemented with 10 ng/Ml human TGFß. The collagen content in cell layers was measured by spectrophotometric Picro-Sirius red staining. The mRNA expression of α-SMA, COL I and III, TGFß1, arginase and E-Cadherin genes were determined by real time RT-PCR. TGF-ß1 levels in cell culture supernatants were measured using ELISA. Cell layer collagen content was significantly increased following TGF-ß1 treatment, compared with FBS group and SSc serum treatment in comparison with healthy controls. Although not statistically significant, the mRNA expression of α-SMA, COLI and III, TGFß1, and arginase increased upon TGF-ß1 treatment in comparison with FBS group, and in SSc serum treatment group in comparison with healthy controls. E-Cadherin decreased following TGF-ß1 treatment and SSc serum treatment in comparison with their counterparts. TGF-ß1 levels increased in cell culture supernatants of HDF cells exposed to TGF-ß1 and SSc serum. An in vitro model of SSc serum-induced fibrosis using human HDF cells was evaluated in comparison to the TGF-ß1 fibrosis induced model and data suggested that it may be used in documenting the role of pro-fibrotic factors in serum or plasma from SSc patients.

Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency

Background: Selective IgA deficiency is the most prevalent form of primary immunodeficiencies. The pathogenesis of the disease is still unknown. Several studies have suggested a defect in B cell responses to IL-10; however, the main reason for this defect has not been reported. Elucidating IL-10 signaling defects and their correlation with clinical manifestations could be helpful for better understanding and treatment of the disease. Methods: In this study, 15 SIgAD patients and 15 age- and sex-matched healthy controls were included. Surface expression of transforming growth factor ß receptor II (TGF-ß RII), IL-10R and IgA was assessed by flow cytometry in human purified B cells before and after stimulation by IL-10. Protein expression of STAT3, p-STAT3 and SOCS3 was measured by Western blotting analysis. TGF-ß and IgA secretion was evaluated by ELISA. Finally, the measurement of B cell apoptosis was performed by flow cytometry. Results: The TGF-ßRII expression level was decreased after stimulation with IL-10 in patients compared with controls. Notably, the TGF-ß level were higher after stimulation with mCD40L and IL-10 in the control group as compared to stimulation with mCD40L alone. The IgA+ B cell percentage and IgA secretion levels were significantly increased in controls as compared with SIgAD patients. The relative concentration of the total STAT3 was decreased as compared with controls. Conclusion: The defect in IgA production in SIgAD patients could be due to inadequate B cell responses to IL-10 stimulation that probably originate from defective regulation of IL-10-mediated TGF-b 'symbol' production TGF-ß response by IL-10. Furthermore, it is suggested that the absence of STAT3 protein baseline expression could impair cytokine-mediated signaling such as thatinduced by IL-!0 and IL-21.

Multilayered Mesoporous Composite Nanostructures for Highly Sensitive Label-Free Quantification of Cardiac Troponin-I.

Cardiac troponin-I (cTnI) is a well-known biomarker for the diagnosis and control of acute myocardial infarction in clinical practice. To improve the accuracy and reliability of cTnI electrochemical immunosensors, we propose a multilayer nanostructure consisting of Fe3O4-COOH labeled anti-cTnI monoclonal antibody (Fe3O4-COOH-Ab1) and anti-cTnI polyclonal antibody (Ab2) conjugated on Au-Ag nanoparticles (NPs) decorated on a metal-organic framework (Au-Ag@ZIF-67-Ab2). In this design, Fe3O4-COOH was used for separation of cTnI in specimens and signal amplification, hierarchical porous ZIF-67 extremely enhanced the specific surface area, and Au-Ag NPs synergically promoted the conductivity and sensitivity. They were additionally employed as an immobilization platform to enhance antibody loading. Electron microscopy images indicated that Ag-Au NPs with an average diameter of 1.9 ± 0.5 nm were uniformly decorated on plate-like ZIF-67 particles (with average size of 690 nm) without any agglomeration. Several electrochemical assays were implemented to precisely evaluate the immunosensor performance. The square wave voltammetry technique exhibited the best performance with a sensitivity of 0.98 mA mL cm-2 ng-1 and a detection limit of 0.047 pg mL-1 in the linear range of 0.04 to 8 ng mL-1.

The antifibrotic effects of naringin in a hypochlorous acid (HOCl)-induced mouse model of skin fibrosis.

OBJECTIVES: Fibrosis is a chronic inflammation caused by the loss of innate compensational mechanisms. Naringin (NR) is a flavonoid with antineoplastic and anti-inflammatory effects. Here, we aimed to investigate the antifibrotic effects of NR and underlying mechanisms in a Hypochlorous acid (HOCl)-induced mouse model of skin fibrosis. MATERIALS AND METHODS: A total of 24 six-week-old female BALB/c mice were randomly allocated into five groups: HOCl, Sham, PBS, HOCl + NR and DMSO and selected skin regions were treated for 6 weeks, until sacrifice. The histopathologic and collagenesis of skin resections were analyzed using H&E and PR staining. The mRNA levels of COL1, COL3 and αSMA genes were quantified. Serum samples were also used to evaluate TGF-ß levels and LDH activity. RESULTS: HOCl could increase the relative collagen content, while NR administration on HOCl-treated biopsies decreased collagenesis. COL1, COL3 and αSMA mRNA levels were significantly increased among HOCl-treated skin samples, while NR treatment could decrease these mRNA levels of genes to the extent equal to the levels in the Sham group. Similarly, Naringin-treated samples could decrease TGF-ß levels. CONCLUSIONS: We demonstrated that Naringin could exert protective effects against fibrotic complications of HOCL in skin tissue in vivo, by reducing the collagenesis and decreasing the levels of fibrosis-associated genes.

Age- and Gender-Related Serum Level of Interleukin 18 in Iranian Fars Ethnic Group with Metabolic Syndrome.

Background: The purpose of the present study was to investigate the age- and gender-related serum level of interleukin 18 (IL18) in male and female Iranian Fars ethnic group with metabolic syndrome components. Methods: The study included 226 native Iranian Fars ethnic groups. One hundred sixteen females and 110 men were selected. There were 60 females and 50 males with metabolic syndrome and 56 females and 60 males without metabolic syndrome. The serum fasting blood glucose (FBS), lipid profiles, and IL18 were measured. The National Cholesterol Education Program Adult treatment Panel III criteria were used to determine metabolic syndrome components. Results: There were significant differences between the males and females [except high-density lipoprotein (HDL)] with and without metabolic syndrome for the mean body mass index, FBS, HDL-cholesterol, waist circumference (WC), triglyceride (TG), and IL18 levels in all age groups. Serum IL18 was the highest in males and females in age groups 61-70 and 41-50 years with metabolic syndrome, respectively. Serum IL18 levels significantly correlated with TG and waist WC in males (and also correlated with HDL) and females with the metabolic syndrome. There were significant correlations between IL18 and TG and WC in males (and also correlated with HDL) in ages 61-70 years and females in ages 41-50 years with the metabolic syndrome. Conclusions: The increased IL18 level in both gender and different ages may have an important role in the alteration of some metabolic syndrome components. These alterations may be made to happen in different related metabolic diseases. IL18 seems to be a useful biomarker for the management of metabolic syndrome components and the risk factors of cardiovascular disease.

Genetic polymorphisms -137 (G > C) (rs187238) and -607 (C > A) (rs1946518) and serum level of interleukin 18 in Fars ethnic groups with metabolic syndrome in Northern Iran.

INTRODUCTION: We aimed to determine the genetic polymorphisms and serum level of interleukin 18 in Fars ethnic groups. MATERIAL AND METHODS: 226 Fars ethnic groups were participated. The ATP III criteria were used to assess MS components. The SNPs of the IL-18 gene were determined with ARMS-PCR. RESULTS: The GG, GC, and CC genotypes of -137 were 50%, 40%, and 10%. The CC, CA, and AA genotypes of -607 were 45%, 37%, and 18%. The GG, GC, and CC genotypes of -137 were 44.20%, 43.40%, and 12.40%, and were 55.75%, 36.28%, and 7.97% in subjects with and without MS, respectively. The CC, CA, and AA genotypes of -607 were 48.70%, 37.20%, and 14.20% and were 41.60%, 37.20%, and 21.20% in both groups, respectively. CONCLUSION: IL-18 gene may different in specific populations, different ethnic groups and geographic regions. The IL-18 polymorphisms might not be used as a marker of metabolic syndrome.

Using Anti-SARS-CoV-2 IgG and IgM Antibodies to Detect Outpatient Cases with Olfactory and Taste Disorders Suspected as Mild Form of COVID-19: a Retrospective Survey.

Many patients with olfactory disorders were referred during the COVID-19 pandemic in 2020. The aim of this study was to detect outpatient cases with olfactory and taste disorders suspected to mild form of COVID-19 disease in Gorgan city in the north of Iran retrospectively. This study was performed on patients who had the complaints of olfactory disorders during 03/01/2020 to 04/01/2020. They also had the mild symptoms of upper respiratory tract infection. The control group included patients who had similar symptoms during this period but did not report olfactory or taste disturbances. Due to the limitations of serologic kits, this study was performed 2-3 months after the onset of symptoms. The number of patients and controls was 72 and 36 respectively. The range and the mean ± SD of patient's age were 21-63 and 39.82 ± 9.82 years. In both groups, 44.44% were male and 55.56% were female. The time interval between the onset of symptoms and the serologic tests in both groups was 91.11 ± 16.20 days. In the cases and controls, the IgG titer was positive in 44.4% and 22.2% and the IgM titer was positive in 5.6% and 8.3% respectively. IgG antibody titers were higher in cases than in the control group (P = 0.024). There was no correlation among antibody titers and the severity of olfactory disturbances, the gender, and the age. The high COVID-19 IgG antibody titer in patients with olfactory disorder during the pandemic can probably be considered as a warning complaint of COVID-19 and may be used for isolation plans.

Immune responses modulation by curcumin and allergen encapsulated into PLGA nanoparticles in mice model of rhinitis allergic through sublingual immunotherapy.

The purpose of this study was the combination of curcumin and ovalbumin in free form or encapsulated into PLGA NPs (polylactic co-glycolic acid nanoparticles) to enhance their sublingual immunotherapy (SLIT) efficiency in mouse model of rhinitis allergic. PLGA NPs containing curcumin (CUR), ovalbumin (OVA) or both were prepared by emulsion-solvent evaporation method and characterized. After sensitization of BALB/C mice with ovalbumin, SLIT with free or encapsulated formulations was carried out and immunological profiles were evaluated. SLIT treatment with all synthesized PLGA formulations lead to significantly decreased total IgE. The combination immunotherapy in the present of free form of curcumin or ovalbumin with encapsulated forms of the another substance (P.OVA-CUR 10 and P.CUR 5-OVA), showed the highest level of IFN-γ:IL-4 compared to other target groups. On the other hands, a significant increasment was observed in this ratio between these optimal groups and treated group with subcutaneous administration of OVA as the most commonly used method for immunotherapy. The study of nasal lavage fluid (NALF) showed significant decreased levels of total and eosinophil cell count in the traeted nano-formulation groups. The histopathological results of NAL were also like normal with no cellular infiltration and no inflammation in the optimal formulations. Therefore, using curcumin and nanoparticles with allergen can be considerd as potential immune modulatory agents.

Human chorionic gonadotropin attenuates amyloid-ß plaques induced by streptozotocin in the rat brain by affecting cytochrome c-ir neuron density.

OBJECTIVES: Amyloid ß plaques, in Alzheimer's disease, are deposits in different areas of the brain such as prefrontal cortex, molecular layer of the cerebellum, and the hippocampal formation. Amyloid ß aggregates lead to the release of cytochrome c and finally neuronal cell death in brain tissue. hCG has critical roles in brain development, neuron differentiation, and function. Therefore, we investigated the effect of hCG on the density of the congophilic Aß plaque and cytochrome c-ir neurons in the hippocampus, prefrontal cortex, and cerebellum of Streptozotocin (STZ)-treated rats. MATERIALS AND METHODS: Alzheimer model in rats (except the control group) was induced by streptozotocin (3 mg/kg, Intracerebroventricularly (ICV)). Experimental group rats received streptozotocin and then different doses of hCG (50, 100, and 200 IU, intraperitoneally) for 3 days. 48 hr after last drug injection and after histological processing, the brain sections were stained by congo red for congophilic amyloid ß plaques and cytochrome c in the hippocampus, prefrontal cortex, and cerebellum were immunohistochemically stained. RESULTS: Density of congophilic Aß plaques and cytochrome c-immunoreactive neurons was significantly higher in ICV STZ treated rats than controls. Treatment with three doses of hCG significantly decreased the density of congophilic Aß plaques and cytochrome c-immunoreactive neurons in the rat hippocampus, prefrontal cortex, and cerebellum in ICV STZ-treated rats (P<0.05). CONCLUSION: hCG can be useful in AD patients to prevent the congophilic Aß plaque formation and decrease cytochrome c-immunoreactive neuron density in the brain.

Analysis of poliovirus receptor, CD155 expression in different human colorectal cancer cell lines: Implications for poliovirus virotherapy.

CONTEXT: Poliovirus (PV) receptor (CD155) is expressed on several kinds of cells and exerts diverse functions. Various investigations have confirmed that changes in CD155 expression in cancer cell lines affect metastasis, proliferation, and migration. AIMS: The purpose of the present study was to investigate the CD155 transcript and protein expression in human colon adenocarcinoma cell lines in comparison to normal fetal human colon (FHC) cells. MATERIALS AND METHODS: The CD155 expression level in four human adenocarcinoma cell lines and normal colon cell line were assessed using the SYBR green quantitative real-time polymerase chain reaction (PCR) and flowcytometry. RESULTS: The results of real-time PCR indicated that CD155 was significantly overexpressed in all human adenocarcinoma cell lines (P = 0.000). The highest and the lowest expression level of CD155 messenger RNA was observed in SW480 and HT29 cell lines by 491.14, and 12.04 fold changes, respectively, in comparison with the human normal cell line (FHC). Results of flowcytometry indicate that protein was strongly expressed in cancer cell lines. SW480 cells showed the highest CD155 protein expression level of 98.1%, whereas this protein expression was 1.3% in human normal colon cell line (FHC). Totally, these data indicate that CD155 expression is significantly elevated in cancer cell lines. CONCLUSIONS: The preferential expression of CD155 on cancer cell lines rather than on normal cell line suggests that CD155 could be targeted for future PV virotherapy.

Non-replicating Newcastle Disease Virus as an adjuvant for DNA vaccine enhances antitumor efficacy through the induction of TRAIL and granzyme B expression.

The potential of non-replicating Newcastle Disease Virus (NDV) as an adjuvant for DNA vaccination remains to be elucidated. To assess the therapeutic effects of DNA vaccine (HPV-16 E7 gene) adjuvanted with NDV, female C57/BL6 mice were inoculated with murine TC-1 cells of human papillomavirus (HPV)-related carcinoma, expressing human papillomavirus 16 (HPV-16) E6/E7 antigens, and immunized with DNA vaccine alone or pretreated with NDV. One week after third immunization, Cytotoxic T lymphocytes (CTLs), splenocyte proliferation, cytokine balance (IFN-γ, IL-4 and IL-12 secretions) and intratumoral expression of cytotoxicity related proteins in tumor lysates were investigated. The results showed that treatment with non-replicating NDV prior to DNA vaccine induced tumor-specific cytolytic and splenocyte proliferation responses. The levels of cytokines IL-12, IL-4 and IFN-γ after treating with combined E7-DNA -non-replicating NDV (NDV-DNA Vaccine) were significantly higher than those of control groups. The intratumoral granzyme B and Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL)-mediated apoptosis was also significantly increased. Tumor therapeutic experiments showed that the NDV pretreatment could reduce the tumor progression of established E7-expressing TC-tumors. Taken together these data suggest that the significant antitumor responses evidenced during treatment with non-replicating NDV prior to DNA vaccine are due, in part, to strong E7-induced cellular immunity and enhanced expression of cytotoxicity related proteins in the tumor microenvironment. These observations indicated the potential of non-replicating NDV as an adjuvant for enhancing therapeutic DNA vaccines -induced immunity and antitumor responses.

The SAFE pathway is involved in the postconditioning mechanism of oxytocin in isolated rat heart.

Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model. Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion. Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT. Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase.