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There is a growing trend towards enhancing the post-harvest shelf life and maintaining the nutritional quality of horticultural products using eco-friendly methods. Raspberries are valued for their diverse array of phenolic compounds, which are key contributors to their health-promoting properties. However, raspberries are prone to a relatively short post-harvest lifespan. The present study aimed to investigate the effect of exogenous melatonin (MEL; 0, 0.001, 0.01, and 0.1 mM) on decay control and shelf-life extension. The results demonstrated that MEL treatment significantly reduced the fruit decay rate (P ≤ 0.01). Based on the findings, MEL treatment significantly increased titratable acidity (TA), total phenolics content (TPC), total flavonoid content (TFC), and total anthocyanin content (TAC). Furthermore, the MEL-treated samples showed increased levels of rutin and quercetin content, as well as antioxidant activity as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction activity potential (FRAP). Additionally, the samples exhibited higher levels of phenylalanine ammonia-lyase (PAL) and catalase (CAT) enzymes compared to the control samples. Moreover, the levels of pH, total soluble solids (TSS), and IC 50 were decreased in the MEL-treated samples (P ≤ 0.01). The highest amount of TA (0.619 g/100 ml juice), rutin (16.722 µg/ml juice) and quercetin (1.467 µg/ml juice), and PAL activity (225.696 nm/g FW/min) was observed at 0.001 mM treatment, while, the highest amount of TAC (227.235 mg Cy-g/100 ml juice) at a concentration of 0.01 mM and CAT (0.696 u/g FW) and TAL activities (9.553 nm/100 g FW) at a concentration of 0.1 mM were obtained. Considering the lack of significant differences in the effects of melatonin concentrations and the low dose of 0.001 mM, this concentration is recommended for further research. The hierarchical cluster analysis (HCA) and principal component analysis (PCA) divided the treatments into three groups based on their characteristics. Based on the Pearson correlation between TPC, TFC, TAC, and TAA, a positive correlation was observed with antioxidant (DPPH and FRAP) and enzyme (PAL and CAT) activities. The results of this study have identified melatonin as an eco-friendly compound that enhances the shelf life of raspberry fruits by improving phenolic compounds, as well as antioxidant and enzyme activities., (© 2024. The Author(s).)

Corn ( Zea mays L.) is an important annual grain that is cultivated as a food staple around the world. The current study examined the effect of wastewater and a combination of biological and organic fertilizers on the morphological and phytochemical traits of corn, using a factorial experiment based on a randomized complete block design with three replications. The first factor was biological and organic fertilizers at seven levels, including the control (no fertilization), bacterial biological fertilizers (NPK) along with iron and zinc Barvar biofertilizers, fungal biofertilizers made from Mycorrhiza and Trichoderma , biochar, a combination of bacterial and fungal biofertilizers, and a combination of bacterial and fungal biofertilizers with biochar. The second factor was irrigation at two levels (conventional irrigation and irrigation with wastewater). The traits studied included the morphological yield, phenols, flavonoids, polyphenols, glomalin, cadmium content in plant parts, and translocation factor (TF). The results disclosed that the best treatment in regard to the morphological traits was related to conventional water + biochar + mycorrhiza + Trichoderma + NPK. The highest phenol and flavonoid content were observed when biochar + mycorrhiza + Trichoderma + NPK treatments were used in both water treatments. Also, the wastewater + biochar + mycorrhiza + Trichoderma + NPK treatment demonstrated the highest total glomalin and phenylalanine ammonia-lyase (PAL) activity. The obtained results demonstrate that combined biological and organic fertilizer use on corn plants can effectively alleviate the deleterious effects of cadmium present in wastewater.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease and has adverse implications. The exact mechanism of its pathogenesis is not fully understood and remains to be elucidated. In the current study we aimed to identify key genes that can serve as potential biomarkers and therapeutic targets for MS and shed light on pathogenesis mechanisms involved in MS. We analyzed a gene expression dataset (GES21942) and found 266 differentially expressed genes (DEGs) including 183 upregulated and 83 downregulated genes in MS patients compared to controls. Then we conducted pathway enrichment on DEGs and selected the top enriched pathway i.e., B cell receptor signaling pathway, and 5 genes of this pathway (CR2, BLK, BLNK, RASGRP3, and KRAS) for further investigation in our clinical samples. We recruited 50 MS patients and 50 controls and assessed the expression of selected genes in the circulation of patients versus controls. Expression of CR2, BLK, BLNK, and RASGRP3 were significantly higher in MS cases compared with controls. There was no significant difference in expression of KRAS between patients and controls. All of the selected genes with differential expression had noticeable diagnostic power and CR2 was the most robust gene in differentiating MS cases from controls. Additionally, a combination of genes resulted in enhanced diagnostic power. Collectively our results suggest that the B cell receptor signaling pathway and the selected genes from this pathway may be implicated in the pathogenesis of MS and each of these genes can be considered as potential diagnostic biomarkers and therapeutic targets.

Protein aggregation and oxidative stress have gained significant research attention due to their association with a group of diseases known as amyloidosis. Among the strategies developed to prevent amyloidosis, utilization of polyphenols stands out as one of the most commonly employed approaches. Scutellaria baicalensis is renowned as one of the foremost herbal sources of polyphenols. In this study, we employed a direct oxidative pyrolysis method for polymerizing S. baicalensis's polyphenols (SBPPs) after their extraction, resulting in the formation of novel SBPPs nanoparticles. Upon polymerization, SBPPs nanoparticles showed remarkable properties including heightened water solubility, increased surface area, modified surface functional groups, and enhanced stability. As a result of these diverse factors, there was a considerable enhancement in the anti-amyloidogenic properties and antioxidant effects of SBPPs nanoparticles compared to its bulk form. The fibrillation kinetics, AFM images, and cytotoxicity assays strongly indicate that SBPPs nanoparticles are more effective than SBPPs at preventing amyloid fibril formation and associated cell toxicity. Additionally, SBPPs nanoparticles demonstrated more effective prevention of reactive oxygen species (ROS) production. In conclusion, the use of SBPPs in nanoparticle form presents a promising strategy to enhance anti-amyloidogenic properties, mitigate oxidative stress, and offer potential therapeutic benefits for amyloidosis-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Access to clean water for irrigation and drinking has long been a global concern. The need for fast, precise, and cost-effective methods to detect harmful bacteria like Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is high due to the potential for severe infectious diseases. Fortunately, recent research has led to developing and utilizing rapid bacterial detection methods. The creation of an aptamer-based biosensor (aptasensor) for the detection of E. coli O157:H7 using label-free aptamers and gold nanoparticles (AuNPs) is described in this study. The specific aptamers that can detect target bacteria are adsorbed on the surface of unmodified AuNPs to form the aptasensor. The detection is performed by target bacterium-induced aptasensor aggregation, which is associated with a red-to-purple color change under high-salt circumstances. We devised a quick and easy method for detecting bacteria using an anti-E. coli O157:H7 aptamer without the need for specialized equipment or pretreatment processes like cell lysis. The aptasensor could identify target bacteria with only as few as 250 colony-forming units (CFU)/ml in 15 min or less, and its specificity based on our test was 100%. This method not only provides a fast direct preparation process but also exhibits remarkable proficiency in promptly identifying the intended target with a heightened level of sensitivity and specificity. Therefore, it can serve as an intelligent tool for monitoring water reservoirs and preventing the transmission of infectious diseases associated with EHEC., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Major depressive disorder (MDD) is generally among the most prevalent psychiatric illnesses. Significant advances have occurred in comprehension of the MDD biology. However, it is still essential to recognize new biomarkers for potential targeted treatment of patients with MDD. The present work deals with in-depth comparative computational analyses to obtain new insights, such as gene ontology and pathway enrichment analyses and weighted gene co-expression network analysis (WGCNA) through gene expression dataset. The expression of selected hub-genes was validated in MDD patients using quantitative real-time PCR (RT-qPCR). We found that MDD progression includes the turquoise module genes (p-value = 1e-18, r = 0.97). According to gene enrichment analysis, the cytokine-mediated signaling pathway mostly involves genes in this module. By selection of four candidate hub-genes (IL6, NRG1, TNF, and BDNF), RT-qPCR validation was performed. A significant NRG1 downregulation was revealed by the RT-qPCR outcomes in MDD. In MDD patients, TNF and IL6 expression were considerably higher, and no considerable differences were found in the BDNF expression. Ultimately, based on ROC analyses, IL6, NRG1, and TNF had a higher MDD diagnostic performance. Therefore, our study presents information on the intricate association between MDD development and cytokine-mediated signaling, thus providing new rationales to develop new therapeutic approaches., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms., Materials and Methods: Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected., Results: Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R., Conclusion: These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway., (© 2023. The Author(s).)

Background: Bromodomain and extra-terminal (BET) proteins are recognized acetylated lysine of histone 4 and act as scaffolds to recruit many other proteins to promoters and enhancers of active genes, especially at the super-enhancers of key genes, driving the transcription process and have been identified as potential therapeutic targets in breast cancer. However, the efficacy of BET inhibitors such as JQ1 in breast cancer therapy is impeded by interleukin-6 (IL-6) through an as-yet-defined mechanism., Methods and Results: We investigated the interplay between IL-6 and JQ1 in MCF-7 and MDA-MB-231 human breast cancer cells. The results demonstrate that the efficacy of JQ1 on the inhibition of cell growth and apoptosis was stronger in MDA-MB-231 cells than in MCF-7 cells. Further, MCF-7 cells, but not MDA-MB-231 cells, exhibited increased expression of CXCR4 following IL-6 treatment. JQ1 significantly reduced CXCR4 surface expression in both cell lines and diminished the effects of IL-6 pre-treatment on MCF-7 cells. While IL-6 suppressed the extension of breast cancer stem cells in MCF-7 cells, JQ1 impeded its inhibitory effect. In MCF-7 cells JQ1 increased the number of senescent cells in a time-dependent manner., Conclusion: Analysis of gene expression indicated that JQ1 and IL-6 synergistically increase SNAIL expression and decrease c-MYC expression in MCF-7 cells. So, the BET proteins are promising, novel therapeutic targets in late-stage breast cancers. BET inhibitors similar to JQ1 show promise as therapeutic candidates for breast cancers, especially when triple-negative breast cancer cells are increased and/or tumor-promoting factors like IL-6 exist in the tumor microenvironment., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

We present an alternative to conventional Electron Paramagnetic Resonance (EPR) spectroscopy equipment. Avoiding the use of bulky magnets and magnetron equipment, we use the photoluminescence of an ensemble of Nitrogen-Vacancy centers at the surface of a diamond. Monitoring their relaxation time (or T1), we detected their cross-relaxation with a compound of interest. In addition, the EPR spectra are encoded through a localized magnetic field gradient. While recording previous data took 12 min per data point with individual NV centers, we were able to reconstruct a full spectrum at once in 3 s, over a range from 3 to 11 G. In terms of sensitivity, only 0.5 μL of a 1 μM hexaaquacopper(II) ion solution was necessary.

Diamond magnetometry makes use of fluorescent defects in diamonds to convert magnetic resonance signals into fluorescence. Because optical photons can be detected much more sensitively, this technique currently holds several sensitivity world records for room temperature magnetic measurements. It is orders of magnitude more sensitive than conventional magnetic resonance imaging (MRI) for detecting magnetic resonances. Here, the use of diamond magnetometry to detect free radical production in single living cells with nanometer resolution is experimentally demonstrated. This measuring system is first optimized and calibrated with chemicals at known concentrations. These measurements serve as benchmarks for future experiments. While conventional MRI typically has millimeter resolution, measurements are performed on individual cells to detect nitric oxide signaling at the nanoscale, within 10-20 nm from the internalized particles localized with a diffraction limited optical resolution. This level of detail is inaccessible to the state-of-the-art techniques. Nitric oxide is detected and the dynamics of its production and inhibition in the intra- and extracellular environment are followed., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Background: Vascular endothelial growth factor (VEGF) is one of the angiogenic mediators that can be secreted by leukemic cells and plays an important role in tumor invasion and metastasis. Another important agent contributing to the relapse of ALL is C-X-C chemokine receptor type-4 (CXCR-4), expression of this receptor in cancer cells has been related to metastasis. It has been identified that genistein-a soy-derived isoflavonoid-has anti-angiogenesis functions. We aimed to show the effects of this compound on VEGF and CXCR-4 in Acute lymphoblastic leukemia (ALL) cell models., Methods and Results: The cytotoxicity of Genistein was measured using the MTS colorimetric assay. After being treated with Genistein, the expression of VEGF in mRNA and protein levels was measured in MOLT-4 and Jurkat cells. We also used flow cytometry assay to determine the expression of CXCR-4 in cell surfaces. We found that Genistein decreased cell viability in two cell models while was more effective on MOLT-4 cells. After Genistein-treatment, surface expression levels of CXCR-4 were decreased, while VEGF secretion and mRNA expression levels were increased in MOLT-4 and Jurkat cells., Conclusions: The results suggest that Genistein may not be a reliable choice for the treatment of ALL; however, this different identified pattern can be useful for the recognition of VEGF and CXCR-4 modulators and thus for planning new treatments for leukemia and other VEGF related disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/TH2 balance in Allergic rhinitis (AR)., Objective: This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-β in nasal biopsies in AR patients and evaluate its correlation with the severity of AR., Material and Method: The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moderate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-β was evaluated by the quantitative real-time polymerase chain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured., Result: The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-β declined in the M/S PAR group rather than the AR- group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR- groups., Conclusion: We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation., (© 2022 Mirzaei Y et al.)

New strategies to increase the immune response to HIV-1 vaccine using immunological adjuvants such as Toll-like receptor agonists are needed. In this study, HIV-1 p24-Nef and conjugated form of the vaccine candidate to type-A flagellin (FLA) were injected in the BALB/c mice in different routes. Two weeks after the last immunization, lymphocyte proliferation was measured by the BrdU method. The IL-4 and IFN- γ levels, as well as the total IgG antibody and its isotypes titer, were evaluated by the enzyme-linked immunosorbent assay method. The IFN- γ ELISPOT was also performed. Our data showed that the HIV-1 p24-Nef alone and conjugated to type-A flagellin (FLA) significantly increased lymphocyte proliferation responses as well as higher levels of cytokines and IFN- γ producing lymphocytes and the level of humoral immune responses compared with the control groups. The cell-mediated immune responses through the subcutaneous route and humoral immune responses through the intramuscular route were significantly higher in the conjugated form than in the mere vaccine candidate. In conclusion, when the FLA as an adjuvant is constructed in the HIV-1 vaccine candidate, it could effectively improve both humoral and cellular immune responses. Furthermore, modification in the vaccine formulation could change the optimal route of vaccine inoculation.

Interleukin (IL)-35 and IL-37 are two anti-inflammatory cytokines. IL-35 inhibits the development of T-effector cells such as Th1, and Th17; while increasing regulatory T cells (Tregs). IL-37 causes the suppression of inflammatory cytokines. Regarding the positive impact of Helicobacter pylori (H. pylori) infection on inflammation and considering the anti-inflammatory effects of IL-35 and IL-37, this study aimed to evaluate the expression of these two cytokines in H. pylori-infected patients with gastrointestinal problems. The case group consisted of H. pylori-infected individuals with gastric ulcer and/or gastritis (n=50) and the control group consisted of cases with gastric ulcer and/or gastritis non-H. pylori-infected (n=50). Sampling and classification of patients were based on pathology findings. A real-time polymerase chain reaction was performed for evaluating the IL-35 and IL-37 expression levels. pylori-infected gastritis patients showed lower expression of IL-35 and IL-37 than the non-infected group. There was a significant difference between the expression levels of IL-35 and IL-37 in patients with gastric ulcers and/or gastritis who were infected and non-infected by H. pylori. There were no significant differences in the expression level of IL-35 and IL-37 in H. pylori-infected patients with gastric ulcer or gastritis. Interleukins 37 and 35 were less expressed in patients with H. pylori-infection. In differentiation between patients with gastrointestinal symptoms who have H. pylori infection or with similar symptoms who do not have H. pylori-infection, mentioned interleukins can be used as diagnostic markers.

Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3 + regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3 + Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non-tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3 + /CD4 + ) and Th17 (IL-17 + /CD4 + ), as well as AHR + cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3 + Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non-tumoural tissues. Also, the percentage of AHR + lymphocytes and AHR + cells was increased significantly in bladder tumour tissues rather than non-tumoural tissues. This study also found a relation between AHR and Foxp3 + /CD4 + T lymphocytes ratio cells in BC. The percentage of Foxp3 + Tregs and AHR + cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3 + Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3 + Treg in BC can lead to a potential cancer therapeutic possibility., (© 2021 Company of the International Journal of Experimental Pathology (CIJEP).)

PIWI-interacting RNAs (piRNAs) with the length of approximately 26-30 nucleotides are a distinct class of small non-coding RNAs that mainly expressed in the animal gonads. Other small RNAs originate from double stranded precursors but piRNAs derive from long single-stranded primary transcripts, which expressed from distinct genomic regions. piRNAs are involved in silencing of mobile elements named transposons and their main role is germline maintenance. Recent studies have opened new insights on biological and clinical significance of piRNAs in various diseases. Abnormal expression of piRNAs is a remarkable feature in many diseases especially human cancers, which emphasize on their important biological role in disease progression. Furthermore, they can be served as biomarkers and therapeutic targets for tumor diagnostics and treatment. In this review, we explained piRNAs characteristics, biogenesis process and functions, discuss new findings about involvement of these elements in various disease and their potential to be used as diagnostic biomarkers., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright © 2021 Shirzad. Published by Tehran University of Medical Sciences.)

Prostate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid-derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)-10 production. On the other hand, IL-17 + helper T cells (Th17) induce MDSCs and chronic inflammation in TME by producing IL-17. This study demonstrated that the frequency of CD33 + pSTAT3 + MDSC and IL-17 + lymphocyte as well as IL-10 messenger RNA (mRNA) expression were significantly higher in the PCa patients than in the benign prostatic hyperplasia (BPH) group. Moreover, there was no significant relationship between the frequency of CD33 + pSTAT3 + MDSC, and IL-17 + lymphocyte with Gleason scores in the PCa group. We suggested that the higher frequency of CD33 + pSTAT3 + MDSC and IL-17 + lymphocyte and the more frequent expression of IL-10 mRNA in PCa patients may play roles in tumor progression from BPH to PCa., (© 2021 International Federation for Cell Biology.)

Ethylene is the most important factor playing roles in senescence and deterioration of harvested crops including cut flowers. Brassinosteroids (BRs), as natural phytohormones, have been reported to differently modulate ethylene production and related senescence processes in different crops. This study was carried out to determine the effects of different levels of 24-epibrassinolide (EBL) on ACC oxidase enzyme activity, the final enzyme in ethylene biosynthesis pathway, vase life, and senescence rate in lisianthus cut flowers. Harvested flowers were treated with EBL (at 0, 3, 6, and 9 µmol/L) and kept at 25 °C for 15 days. The ACC oxidase activity, water absorption, malondialdehyde (MDA) production and vase solution absorption rates, chlorophyll and anthocyanin contents, and the vase life of the flowers were evaluated during and at the end of storage. EBL at 3 µmol/L significantly ( p ≤ 0.01) enhanced the flower vase life by decreasing the ACC oxidase activity, MDA production and senescence rates, and enhancing chlorophyll and anthocyanin biosynthesis and accumulation, relative water content, and vase solution absorption rates. By increasing the concentration, EBL negatively affected the flower vase life and postharvest quality probably via enhancing the ACC oxidase enzyme activity and subsequent ethylene production. EBL at 6 and 9 µmol/L and in a concentration dependent manner, enhanced the ACC oxidase activity and MDA production rate and decreased chlorophyll and anthocyanin accumulation and water absorption rate. The results indicate that the effects of brassinosteroids on ethylene production and physiology of lisianthus cut flowers is highly dose dependent.

Strawberry fruits are highly susceptible to cold burning, resulting in low storage periods at low temperatures. Plant extracts or essential oils (EOs) can potentially be used as preservatives in fruits throughout the refrigerated period. In the present study, the biochemicals, antioxidant characteristics, and shelf life of treated strawberries with Aloysia citrodora essential oil (ACEOs) were evaluated during keeping time. The treatments were produced as follows: T1, control; T2, 250 ppm ACEOs; T3, 500 ppm ACEOs; and T4, 750 ppm ACEOs. Total soluble solids (TSS), weight loss, titratable acidity (TA), antioxidant activity (DPPH assay), total phenolic (TPC), flavonoid and anthocyanin contents (TFC), and enzymes activity (peroxidase and ascorbate peroxidase) were evaluated during the refrigerated period (5 °C with relative humidity of 85-90% for 20 days). The results revealed that weight loss and TA were reduced in all treatments during storage, being that the rates were lower in samples treated with ACEOs. TPC, TFC, TSS, antioxidant, and enzymes activity were higher in treated fruits than control.

Background: Helicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors., Methods: In total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR., Results: CCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA + and babA2 + were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis., Conclusions: The increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Introduction and Purpose: Indoleamine 2, 3- dioxygenase (IDO) plays an importantrole in immunosuppressive pathway, as inhibits responsesof T cells and promotes immune tolerance. Host responsetoHelicobacter pylori (H. pylori) is involved in the infection persistenceand it is also associatedwith different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulator (Treg) cells., Materials and Methods: Antrum biopsy was obtained from H. pylori-negative patients (n = 48) and H. pylori-positive subjects (55 patients with gastritis and 47 patients with PUD), for performing H. pylori status and histopathological assessments. IDO protein expression was evaluated by Western blotting., Results: IDO protein expression was significantly higher in gastric biopsies from H. pylori-positive subjects compared to the H. pylori-negative subjects, and also in H. pylori-positive subjects with gastritis disease compared to H. pylori-positive subjects with PUD. Moreover, in H. pylori-positive subjects, a positive correlation was observed between IDO protein expression and the frequency of Treg cells. In addition, a negative correlation was observed between IDO protein expression and the number of Th1, Th17, and Th22., Conclusion: Increased IDO protein expression is able to change the number of Th1, Th17, Th22, and Treg cells and these changes are possibly associated with an increase in the risk of PUD development in H. pylori-infected patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

A DNA-silver nanocluster with two distinct emissions is devised, in which this unique modality has been exploited to develop a novel nanosensor for transgenic DNA detection. TEM and fluorescence analysis revealed the formation of Ag nanoclusters with a size of around 2 nm, which exhibit dual-emissions at 550 nm (green) and 630 nm (red). Moreover, in the presence of the target sequence (CaMV 35S promoter) from the transgenic plant, the nanoclusters showed an enhancement in the green emission and a reduction in the red emission. This property provided a ratiometric-sensing platform which lacks unavoidable noises. The ratio of green to red fluorescence emission (G/R) of the nanoclusters exhibited a linear relation with the target concentration in the range 10 to 1000 nM. However, the control DNA did not affect this ratio, which clearly confirmed the selective response of the designed nanosensor. This sensing platform had a detection limit of 1.5 nM and identified the DNA of transgenic soybeans within a short time. The mechanistic evaluation of the nanoclusters further revealed the role of protonated cytosine bases in the dual emission behavior. Finally, unique features of the designed nanosensor may improve the current approaches for the development and manufacturing of GMO detection tools.

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, in which proinflammatory cytokines play a critical role in the pathogenic formation of lesions. Caspase-1 is a cysteine protease that proteolytically cleaves precursors of interleukin (IL)-18 and IL-1β and turns them into their active forms. These inflammatory cytokines play an important role in the development of MS. The aim of the present study was the investigation of caspase-1 and its downstream products, IL-18 and IL-1β, in relapsing-remitting MS (RRMS) patients. In this study, we used an ELISA assay to measure serum and cellular caspase-1 and serum levels of IL-18 and IL-1β in RRMS patients in the relapse phase (n=23) and healthy age-and gender-matched controls (n=19). We observed that the caspase-1 level was significantly increased in the serum of MS patients compared to the healthy controls (p=0.03). Although caspase-1 concentration in the lysate of peripheral blood mononuclear cells (PBMCs) was higher than serum among patients and controls (p<0.001), no significant difference was found in cellular levels of caspase-1 between the two groups. There was no significant difference in serum levels of IL-18 and IL-1β between patients and controls. In this study, we found an elevation of extracellular caspase-1, as a reflection of its intracellular level, in the serum of RRMS patients during the relapse phase. Therefore, it suggests being a suitable peripheral biomarker of disease activity in multiple sclerosis.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1β and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1β was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1β in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1β protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1β and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1β mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1β and increasing IL-11 production.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Background: Tyrosinases are copper-containing enzymes that initiate the melanin synthesis. They catalyze the direct oxidation of L-tyrosine or L-DOPA into L-DOPAquinone., Objectives: In present study, we aimed to obtain a recombinant tyrosinase with enhanced catecholase activity through site-directed mutagenesis., Materials and Methods: The coding sequence of human tyrosinase along with native signal sequence was cloned into pET-28a (+). BL-21 was used as expression host and recombinant protein was purified by Ni-NTA resins. Site-directed mutagenesis was performed on M374 residue to achieve four mutants: M374D, M374T, M374K and M374R. Chloride ions (Cl - ) were removed from all solutions, and an extra amount of Cu 2+ ions was added to recombinant tyrosinases by a novel technique during the purification process. Removal of Cl - ions and addition of extra Cu 2+ ions tripled catecholase activity of the recombinant protein. Therefore, all mutants were obtained under similar conditions., Results: Although all the mutants presented higher catecholase activity in comparison to the wild-type enzyme, a significant increase in catecholase activity of the M374D mutant was observed ‒ 13.2-fold. In silico modeling suggested that a de novo hydrogen bond occurs between side chain carboxyl oxygens of D374 and H367 in M374D. In the wild-type tyrosinase, the peptide oxygen atom of M374 is responsible for hydrogen bonding with H367., Conclusions: Our data suggests that M374D mutational variant has applications in different areas such as agriculture, industry, and medicine., (Copyright: © 2020 The Author(s); Published by Iranian Journal of Biotechnology.)

YKL-40 is an important protein that plays a critical role in chronic inflammation in hypersensitivity disease. In this study, the expression of YKL-40 was investigated among patients with moderate/severe persistent allergic rhinitis (M/S PAR), patients with mild (M) PAR and healthy individuals. Moreover, the association between YKL-40 and immunopathogenesis of M/S PAR was meticulously surveyed. For this purpose, surgical samples were tested by real-time polymerase chain reaction to evaluate YKL-40 mRNA expression. The presence and location of YKL-40 protein in the tissue samples were determined by immunohistochemistry. Additionally, we measured the number of eosinophils per field in the tissue samples, blood eosinophils, total serum IgE, specific serum IgE, total nasal syndrome score (TNSS) and YKL-40 serum levels. The data indicated that production of YKL-40 in patients with M/S PAR increased significantly when compared with the control group. Furthermore, local production of YKL-40 correlated with specific IgE, nasal eosinophil count and TNSS. The results of the present study indicate that YKL-40, for its correlation with allergic clinical manifestations and symptom severity in M/S PAR patients, should be considered as a trigger factor in AR.

T cell acute lymphoblastic leukemia (T-ALL) is one of the most frequent malignancies in children, and the CXCR4 receptor plays an important role in the metastasis of this malignancy. Ghrelin is a hormone with various functions including stimulation of the release of growth hormone and autophagy in cancer cells. Moreover, SIRT1 and AMPK (AMP-activated protein kinase) stimulate expression of proteins involved in autophagy. On the other hand, autophagic cell death can be an alternative target for cancer therapy, in the absence of apoptosis. The relationship between ghrelin and the SIRT1/AMPK axis and the resulting effects on autophagy, apoptosis, proliferation, and expression of CXCR4 and the ghrelin receptor (GHS-R1a), in Jurkat and Molt-4 human lymphoblastic cell lines was not previously clear. Here we demonstrate that SIRT1 expression is upregulated during the induction of autophagy by ghrelin, an effect that is inhibited by inactivation of SIRT1/AMPK axis. In addition, ghrelin can affect CXCR4 and GHS-R1a expression. In conclusion, this work reveals that ghrelin induces autophagy, invasion, and downregulation of ghrelin receptor expression via the SIRT1/AMPK axis in lymphoblastic cell lines. However, in these cell lines ghrelin-induced autophagy does not lead to cell death due to weak induction of apoptosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Helicobacter pylori (H. pylori) has been shown to be one of the leading causes of peptic ulcer diseases (PUDs) and gastritis. T helper-22 (Th22) cells and its most important cytokine, interleukin-22 (IL-22) are importantly active in inflammation and inflammatory tissues. Since inflammation is one of the main attributes of infection caused by H. pylori and resulting complications (gastritis and gastrointestinal ulcer), this study was designed to evaluate the Th22 cells count and the IL-22 protein expression in people suffering from PUD and gastritis. The present study was conducted on 55 patients with gastritis, 47 patients with PUD and 48 uninfected subjects. After preparation of section and extraction of protein from antral biopsies, immunohistochemistry and western blot methods were used to evaluate the Th22 cells and IL-22 protein expression level, respectively. According to findings, the Th22 cells count and the IL-22 protein expression level in the infected subjects were siginficantly more than in the uninfected subjects. It should be noted that the Th22 cells count and the IL-22 protein expression level in the infected subjects with PUD were significantly greater than those in the infected subjects with gastritis. In addition, the Th22 cells count had positive correlation with the density of H. pylori, chronic inflammation score and acute inflammatory score in the infected subjects with PUD. The Th22 cells count had positive correlation with the Th17 cells count and inverse correlation with the Treg cells count in the infected subjects with PUD and gastritis. Our data demonstrated that abnormal hyper-activation of Th22 cells as well as its correlation with the Th17 cells during infection caused by H. pylori might damage tissues through immunopathological responses.

Objective: This study sought to assess the clinical signs and subjective symptoms of TMD, including the occlusal condition. Methods: Recruited individuals included 123 patients (58 men, 65 women) aged 15 to 65 years (mean 38.6 years) who had been referred to the TMD department. Helkimo dysfunction, occlusal, and anamnestic indices were used to assess signs of TMD, occlusal condition, and symptoms, respectively. Relationships of occlusal factors with signs and symptoms of TMD were evaluated by Spearman's correlation test. Associations of TMD with sex and age distributions were assessed by Mann-Whitney and Spearman's test, respectively. Results: The prevalence of signs and symptoms was as high as 75%. Occlusal factors had significant associations with signs and symptoms of TMD. Conclusion: Prevalence of TMD in the study population was high, without preference for age or sex. Occlusal factors may play a role in the etiology of TMD.

Background: Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells., Methods: In this study we investigated the MSCs frequency in peripheral blood of Relapsing-Remitting Multiple Sclerosis (RRMS) patients in clinically active and not on disease-modifying therapy (DMT) (n = 22) and clinically stable on DMT (Interferon-β (IFN-β) therapy) for at least 6 months (n = 22) in comparison to sex and age-matched healthy controls (n = 25) using flow cytometry. The serum and gene expression levels of IP-10 and SDF-1a were also measured in studied groups by ELISA and Real time- PCR., Results: We obtained significant high levels of circulating CD45 - CD34 - CD90 + and CD45 - CD34 - CD105 + cells in clinically active patients, not on DMT and patients under IFNβ therapy compared with control group. Furthermore, a significant increase in the percentage of circulating CD45 - CD34 - CD105 + CD90 + cells was found in clinically active patients and not on DMT compared with control group. Serum analysis of IP-10 and SDF-1α showed a significant increase in IP10 concentration in both clinically active not on DMT (P = 0.02) and on DMT (P = 0.005) RRMS patients in comparison with controls. The expression level of SDF-1α mRNA significantly increased in clinically active not on DMT (P = 0.03), while decreased in patients under IFNβ therapy (P = 0.04). The mRNA expression of IP-10 only increased in patients on DMT compared with controls (P = 0.05)., Conclusion: Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-β therapy reduced circulating MSCs and SDF-1α levels., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: The roles of Fas in immune system are multifaceted, and the interaction between Fas receptor and Fas ligand is essential for maintaining the immune tolerance. We aimed to assess the level of the expression of Fas receptor on nasal inferior turbinate mucosa in patients with mild persistent allergic rhinitis (M PAR) and moderate to severe (M/S) PAR and determined the relationship between disease severity and production of Fas., Methods: A total of 70 patients with M/S PAR, 70 patients with M PAR, and 70 healthy individuals were enrolled in this study. We obtained biopsies of nasal inferior turbinate mucosa from the participants. The expression of Fas mRNA was evaluated by real-time polymerase chain reaction. The presence and location of Fas were determined by immunohistochemistry. The number of eosinophils per field, blood eosinophils, total serum IgE levels, and specific serum IgE levels were measured. Clinical manifestations of patients were assessed by Total Nasal Syndrome Score (TNSS)., Results: The expression of Fas in patients with M/S PAR was decreased significantly compared to the control group and patients with M PAR. Local mucosal expression of Fas was correlated with specific IgE, nasal eosinophil count, and TNSS., Conclusion: According to the results of this study, there might be a relationship between the expression of Fas receptor on nasal turbinate mucosa and the severity of persistent allergic rhinitis.

Background: Peptic ulcer disease (PUD) is a common disease worldwide moreover known as stomach ulcer or peptic ulcer. Increased the number of T CD4 + helper cells in response to gastric infection by Helicobacter pylori (H. pylori) play an important role in the development of PUD. The aim of this study was to determine the frequency of T-bet + cells in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection., Methods: A total of 63 patients with PUD, 89 patients with gastritis and 48 H. pylori-negative subjects were enrolled in this study. The number of T-bet + cells were determined by immunohistochemistry., Results: The numbers of T-bet + cells and INF-γ expression in infected patients were significantly higher than uninfected. Moreover, the number of T-bet + cells and INF-γ expression in infected patients with PUD were significantly higher than infected patients with gastritis. Additionally, the number of T-bet + cells and INF-γ expression were found to be inversely correlated with degree of H. pylori density and chronic inflammation score (CIS) in infected patients with gastritis disease, but this correlation was positive in the infected patients with PUD. The number of T-bet + cells was found to be positively correlated with the number of Th17 cells and inversely correlated with the number of Treg cells in infected patients with gastritis and PUD., Conclusion: Abnormal hyper-activation of T-bet + cells during H. pylori-infection may lead to tissue damage caused by immunopathologic reactions., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

Purpose: Several reactions leading to numerous effects are regulated by IL-22. However, the relationship between IL-22 and immunopathogensis of allergic rhinitis (AR) has been rarely investigated. The aim of the present study was to investigate the levels of IL-22 and IL-17A in AR patients and their association with clinical severity of persistent allergic rhinitis (PAR)., Materials and Methods: Thirty mild persistent allergic rhinitis (M PAR) patients, thirty moderate/severe persistent allergic rhinitis (M/S PAR) patients, and thirty healthy controls were enrolled in this study. Local production of IL-22 and IL-17A in PAR patients and healthy controls' nasal mucosa was examined by immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) techniques. Serum levels of IL-22, IL-17A, specific immunoglobulin E (sIgE), and total IgE (tIgE) in PAR patients and healthy controls were determined by ELISA. In addition, blood eosinophil, nasal eosinophils per field, and total nasal syndrome score (TNSS) were also assessed., Results: In comparison with healthy controls, production of IL-22 and IL-17A in M/S PAR patients increased significantly. Furthermore, serum levels as well as the mean number of IL-22 + and IL-17A + cells in nasal mucosa correlated with sIgE, nasal eosinophil count, and TNSS., Conclusion: The results of the present study provide the first evidence that local production of IL-22 might be expressed in PAR patients. The expression of IL-22 and IL-17A, and their correlations with clinical parameters in PAR patients suggest the role of these cytokines in the events involved in the development of PAR., (Copyright © 2018. Published by Elsevier Inc.)

Cell-based biosensors (CBBs) are becoming important tools for biosecurity a lications and rapid diagnostics in food microbiology for their unique capability of detecting hazardous materials. Pollutants, such as heavy metals and chemicals, are now considered as a global threat and are associated with detrimental health outcomes. Fast and accurate detection of pollutants is essential to reduce these threats. In this study, the enhancer sequence of human cytomegalovirus (hCMV) IE genes cloned upstream of luc gene in PGL4.26 plasmid, in order to increase basal luciferase activity. This recombinant vector was transfected into Huh7 cell line and after 21 days of treatment with Hygromycin B selectable marker, stable cell line was generated. After several passages, cells containing this vector showed high luciferase activity in normal conditions without any induction following to overexpression of luc gene. Huh7-CMV-luc cell line was able to detect the slightest changes in ATP level, due to the effect of different toxins on the cell which disrupt cellular respiration and ATP production processes. In order to investigate the sensitivity of the cell line, the cells were incubated with 0.1-10 μM of chemical toxins affecting ATP production. These toxins affect luciferase activity in a dose dependent manner, with maximal sensitivity approximately about 0.2 μM to toxin concentrations. Additionally, this biosensor provided a rapid detection as early as 4 h in response to the toxicants. Whole cell biosensors like huh7-CMV-luc cell line can be considered as a powerful tool for the sensitive and efficient monitoring of general toxins, drugs, and environmental pollutants.

Purpose: Local corticosteroid injection is one of the most prevalent methods in treating carpal tunnel syndrome (CTS). However, the most efficient substance and its appropriate dosage remain controversial. In the present double-blind randomized controlled trial, the efficacy and safety of local injection of two corticosteroids (triamcinolone and methylprednisolone) were compared at two different dosages, 20 and 40 mg., Patients and Methods: We consecutively included 80 patients with mild or moderate CTS and randomly assigned them to four groups: 20 or 40 mg triamcinolone (T20 or T40) and 20 or 40 mg methylprednisolone (M20 or M40) groups; each patient received a single injection of steroid using conventional approach. The four groups were relatively comparable and did not show any significant difference initially in their baseline measurements including pain intensity measured using VAS, pain-free grip strength (PFGS), nerve conduction study (NCS), and two parts of Boston Carpal Tunnel Syndrome Questionnaire: symptom severity scale (SSS) and functional status scale (FSS); the latter was our primary outcome measure. Three months after injection, they were reassessed to evaluate the clinical and electrodiagnostic changes., Results: Almost all NCS parameters, VAS, and PFGS significantly improved after treatment in all the groups ( P <0.05). Compound motor action potential amplitude significantly improved only in T40 group ( P =0.032), while there was no significant improvement in other groups. Furthermore, SSS remarkably decreased in all the four groups, without any significant difference between the groups ( P =0.87). A similar significant decrease was found in FSS, with a higher improvement in T40 group ( P =0.009). There was no significant difference between the four groups in other variables after treatment., Conclusion: Based on the current data, the efficacy and safety of local injection of triamcinolone and methylprednisolone at doses of 20 and 40 mg were associated with a significant improvement in pain, functional status, and strength. Although, there was no remarkable superiority, 40 mg injection, especially for triamcinolone, yielded better NCS results and functional status., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Treatment of acute lymphoblastic leukemia (ALL) has been promising in last decades, but side effects still persist and searching for the least toxic agents continue. Pterostilbene (PTE) is a natural compound with several anti-cancer and anti-oxidant properties. Fas, as a member of death inducing family of tumor necrosis factor (TNF) receptors with an intracellular death domain, can initiate the extrinsic apoptosis signaling pathway. Here after the half maximal inhibitory concentration (IC 50 ) determination in cell lines, we searched for PTE effects on Fas, both in mRNA and surface levels in two ALL cell lines, Jurkat and Molt-4. After harvesting cells in optimum situations, MTS assay was used to determine IC 50 concentrations. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were performed for Fas mRNA and surface expression variations after exposure to PTE. The findings showed that PTE decreases cell viability with different extent in two ALL cell lines. In addition to inducing apoptosis, it can increase Fas in both gene and cell surface expression in the same concentrations. Pterostilbene as a natural anti-cancer agent can increase Fas expression both in mRNA and surface levels that results in apoptosis signal transduction improvement which sensitizes cells to apoptosis by immune effector cells. As a result, abnormal cells removal would be more efficiently with the minimum side effects on normal cells.

Some medicinal herbs and compounds are known to target cancer cells, but the success of them as anticancer compounds depends to a large extent on their ability to activate pathways that kill cancer cells by arresting cell cycle and inducing apoptosis. The aim of the present study was to determine the anticancer effects of Euphorbia szovitsii Fisch. & C.A.Mey. on the breast cancer cells to reveal the underlying mechanism of its anti-breast cancer properties. In this experimental study, triple negative breast cancer cell line (MDA-MB-231) was cultivated in RPMI-1640 medium. Hydroalcoholic extract (70:30) of aerial parts of the plant was prepared. The cultured cells were treated with different concentrations (0-1000 μg/ml) of E. szovitsii extract for 24 and 48 h. Toxicity of the extract on MDA-MB-231 cells was examined using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) test. The Annexin V-FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to differentiate different phases of the cell cycle in the cells. Data were analyzed by GraphPad Prism and SPSS software. After 24 and 48 h, the IC50 values were respectively 76.78 (95% CI = 60.75-97.05; R = 0.8588) and 59.71 (95% CI = 46.25-77.09; R = 0.8543) μg/ml for E. szovitsii The extract exhibited antiproliferative effects against MDA-MB-231 cells in a dose-dependent manner. Annexin V-FITC/PI assay confirmed that the extract was able to induce apoptosis in MDA-MB-231 cells. Moreover, treatment with the extract resulted in cell cycle arrest at G1 phase. Therefore, E. szovitsii could induce apoptosis and cycle arrest in the MDA-MB-231 cell line. It might be a good resource of natural products for producing anti-breast cancer drugs., (© 2019 The Author(s).)

Tamoxifen is routinely used for treatment of Estrogen-positive breast carcinoma. Approximately, 50% of patients with metastatic cancer will develop resistance to Tamoxifen. In this research, Tamoxifen was combined with the anti-cancer compound Curcumin. Diblocknanopolymer was used to package the new formulation of Curcumin and Tamoxifen. Anti-cancer efficacy of the obtained compound was evaluated in Tamoxifen-sensitive (TS). MCF-7, Tamoxifen-resistant (TR) MCF-7 cancer cells and Fibroblast cells. MTT assay was used to evaluate anti-proliferation and toxicity. Flow cytometry and Annexin-V-FLUOS were used to assay anti-proliferation and induction of apoptosis respectively. Our results indicate that the obtained nano-compound is less toxic to normal cells compared to Tamoxifen alone, and has higher anti-proliferation and pro-apoptotic activity on TS-MCF-7 and TR-MCF-7. The nanopolymer reduces the Tamoxifen toxicity in normal cells and counters the developed resistance to the drug in cancer cells.

Background and Study Aims: Helicobacter pylori (H. pylori) has been implicated in the pathogenesis of most important gastro-duodenal diseases, such as gastritis, peptic ulcer disease (PUD) and gastric cancer. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in the gastric mucosa, but the role of MMP-3 and MMP-9 in infected patients with H. pylori have not been clearly defined yet. We examined mucosal MMP-3 and MMP-9 mRNA levels in gastric mucosa of H. pylori infected patients and evaluated the effects of virulence factors cagA and vacA allelic variants on these levels. We also determined correlation between mucosal MMP-3 and MMP-9 mRNA levels and types of disease., Patients and Methods: Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 H. pylori-negative patients. Mucosal MMP-3 and MMP-9 mRNA expression level in H. pylori-infected and non-infected gastric biopsies were determined by real time-polymerase chain reaction (PCR). Presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR., Results: The levels of MMP-3 in gastric mucosa were not different between H. pylori-positive and H. pylori-negative patients. There was no correlation between MMP-3 mRNA expression and virulence factor (cagA and vacA allelic variants) and the different types of disease (gastritis and PUD) in infected patients. But MMP-9 mRNA expression was significantly higher in biopsies of H. pylori-infected patients compared to H. pylori-negative patients. Also mucosal MMP-9 mRNA expression in H. pylori-infected patients was significantly associated with cagA status PUD., Conclusion: Our results suggest that MMP-9 might be involved in the pathogenesis of H. pylori. PUD could be associated with cag PAI-dependent MMP-9 upregulation., (Copyright © 2018. Published by Elsevier B.V.)

Helicobacter pylori (H. pylori) is a human pathogen affecting over 50% of the world population. This pathogen is usually associated with chronic inflammation of the gastric mucosa that can lead to peptic ulcer disease (PUD) and gastric cancer (GC), especially in susceptible individuals. These outcomes have been attributed to the interaction of several factors, including host genetic susceptibility, local innate and adaptive immune responses, virulence factors of H. pylori, and environmental factors. T helper (Th) cell subsets and their signature cytokines especially IFN-γ, contribute to anti-bacterial response, but at the mean time sustaining chronic inflammatory responses in the site of infection. It has been acknowledged that H. pylori-infection results in a Th1-dominant response and that inflammation of the gastric mucosa depends mainly on Th1 cell responses. But, the mechanism of the role of Th1 cell responses in H. pylori-infection has not yet been clearly explained. In this review, we will focus on the role of Th1 involved in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine histologically characterized by indistinct sustained inflammatory responses. Genetical susceptibility and environmental factors' effects play the roles in disease occurrence and it can be life threatening if remains untreated. It seems that intensification of inflammatory responses in this condition is not restricted to a specific cell line of T lymphocytes. Our aim was to determine the number of T helper 9 (Th9) cells in inflamed colonic biopsies of UC patients. We also correlated it with interleukin (IL)-9 protein level in addition to certain genes expressions associated with Th9 phenotype., Methods: Expression of CD4 and IL-9 were evaluated by immunohistochemical staining. Enzyme linked immunosorbent assay (ELISA) was performed to determine the colonic expression of IL-9 protein and finally mRNA expressions of interferon regulatory factor 4 (Irf4), Smad2, and Smad3 were measured by real-time polymerase chain reaction (RT-PCR) as critical transcription factors of Th9 differentiation., Results: Number of Th9 cells was significantly increased in inflamed samples as compared with normal tissues. Also quantitative measurement of IL-9 by ELISA and mRNA expressions of Irf4, Smad2, and Smad3 showed notable correlative enhancements in patient's samples., Conclusion: Function and number of Th9 cells are up-regulated in the inflamed mucosa of UC patients as with the protein secretion of IL-9 and mRNA expressions of Irf4, Smad2, and Smad3, so Th9 cells and IL-9 may become remarkable therapeutic targets for IBD treatment in the future.

Secreted inflammatory cytokines are considered as critical mediators in the tumor microenvironment. Cancer cells play a significant role in the differentiation of effector T cells to exhausted T cells through mediator production. Effector T cells that undergo tumor microenvironment become terminally differentiated into exhausted T cells. These changes create an opportunity for tumorigenesis and invasion of cancer cells. Despite having some characteristics of effector T cells, the exhausted T cells lose their antitumor properties. In this article, the phenotypes and function of exhausted T cells were reviewed and the expression pattern of inflammatory cytokines in tumor tissues and peripheral blood of cancer patients were described. Additionally, the effects of inflammatory cytokines on intracellular factors and signals of T lymphocyte cells were explained. In conclusion, the authors referred to probable approaches that could be used to improve the antitumor activity of T cells and intervention into T cell exhaustion.

Background: Reactive oxygen species (ROS) is one of the pathogenic factors responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A protein in the inflamed mucosa of patients with ulcerative colitis. The gene expression of Nrf2 was also correlated with GST-A4 and PRDX1., Materials and Methods: A total of 20 patients and 20 healthy controls with definite UC based on the clinical criteria were enrolled for this study. The expression pattern of Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic biopsies by immunohistochemical staining. Nrf2, GST-A4 and PRDX1 gene expression were determined by real-time polymerase chain reaction (RT-PCR)., Results: In inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear cells in mucosa and lamina propria regions. A significant increase of Nrf2, GST-A4 gene expression was observed in both mild and severe patients with ulcerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression., Conclusion: Oxidative stress in inflamed colonic tissue can induce Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2 function in the gut plays a role in arresting both inflammatory response and oxidative damages of UC., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Brucellosis or Malta fever is a contagious infection common between human and domestic animals. Many antibiotics are used for brucellosis treatment, but they are not efficient and put heavy burden on society. Co-trimoxazole and rifampicin are two candidates for brucellosis treatment. In this study, we aimed to enhance the efficacy of these antibiotics using designed nanoparticles., Methods: Different concentrations of co-trimoxazole and rifampicin were used for loading onto a nanostructure of synthesized monomethoxy poly(ethylene glycol)-oleate (mPEG-OA). The solubility, cytotoxicity, and efficacy of these nano-packed antibiotics on Brucella-infected murine phagocytic cells were examined, as compared with free antibiotics. Then the release nanoparticles was increased approximately 3.5 and 1.5fold, respectively, which is considerable in comparison with free insoluble ones., Results: Despite acceptable loading percentage, the application of co-trimoxazole-loaded nanoparticle on Brucella-infected J774A.1 murine macrophage-like cells did not lead to reduction in the number of bacteria; however, the efficacy of rifampicin on Brucella-infected murine phagocytic cells enhanced., Conclusion: In the current study, the efficacy of rifampicin on reducing the number of Brucella melitensis increased by the novel synthesized nanostructure. In contrast, since co-trimoxazole efficacy did not enhance by loading onto nanoparticles, the co-trimoxazole inefficiency is most likely not due to its low penetration or insolubility, and probably there are other factors that remain to be clarified in the future investigations.

Background: Fra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression., Materials and Methods: We enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11., Results: An increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group., Conclusion: Oxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients.

Background: Multiple sclerosis is an immune-mediated inflammatory disease of central nervous system. MicroRNAs play important roles in autoimmune diseases such as MS., Objectives: The aim was to evaluate the expression pattern of miR-34a, miR-199a, miR-30c and miR-19a in peripheral blood derived CD4+ T lymphocytes of both relapsing and remitting phases of MS., Methods: Blood samples from 40 RRMS patients (20 in relapsing and 20 in remitting phase) and 20 healthy volunteers were taken. CD4+ T cells were isolated. The expression level of miR-34a, miR-199a, miR-30c and miR-19a, and the percentage of Th17 and Treg cells were measured. Expression of master transcription factors of Th17 and Treg cells and several targets of these miRNAs were also evaluated., Results: Data indicated an increased expression of miR-34a, miR-30c and miR-19a in relapsing phase and decreased expression of miR-199a in remitting phase. ROC curve data add other prestigious information of miR-34a, miR-199a, miR-30c and miR-19a by defining relapsing and remitting phase and also healthy cases with high specificity and sensitivity at a proposed optimum cut-off point., Conclusion: Collectively, we showed a correlation between the four miRNAs with different phases of MS and their possible involvement in differentiation pathways of Th17 cells, as the most important players in MS., (Copyright © 2018 Elsevier B.V. All rights reserved.)