Relationship between anxiety and quality of life in the presence of other factors in adult celiac patients; a nationwide study.

Aim: This study aimed to detect relationships among quality of life (QoL) and anxiety and demographic factors in patients with celiac disease (CD). Background: CD is a type of autoimmune small intestine diseases caused by gluten ingestion. In Iran, the prevalence of CD is considered to be 1% in the general population. As physical problems and behavioral disorders of CD can lead to a reduction in QoL. Methods: This cross-sectional study was performed on 533 patients with Celiac Disease from 9 cities of Iran. Data collected were analyzed by SPSS version 22. Quality of life and anxiety respectively evaluated by (GHQ-28) and SAS questionnaires. Predictors of quality of life (sex, age, age of diagnosis, city of life, education level, family history of celiac, occupation and anxiety) were tested by multiple linear regression. Results: Our results showed a significant relationship between poor quality of life and anxiety (correlation= -0.143, P=0.001). The mean of the quality of life index in celiac diseases was 126.2±30.4 and women had a lower quality of life than men (P=0.003) importantly in emotions and worries scores. There was no significant difference between male and female in terms of anxiety level. Conclusion: According to the results, both quality of life and anxiety correlated together and women seem to suffer more than men from celiac disease. Therefore, greater attention to women who have celiac disease are suggested.

Following up of Surgical Treated Human Liver Cystic Echinococcosis: A Proteomics Approach.

BACKGROUND: Cystic echinococcosis (CE) is one of the most important parasitic zoonosis in the world. Post-surgery follow up in CE patients is an important non-solved problem up to now. Therefore, the investigations on this problematic issue would be very applicable in the view of CE clinical treatment. METHODS: A total of 24 confirmed liver CE patients sera including eight sera before surgery (BS), eight sera three months post-surgery (3MPS), and eight sera six months post-surgery (6MPS) were used in the present study. Proteomics methods including 2DE and LC-MS/MS were performed on the specimens followed by bioinformatics analysis such as Gene Ontology (GO) and Protein-Protein Interaction (PPI) network analysis. RESULTS: A total of 235 proteins were detected of which 12 differentially expressed proteins (DEP) were identified by LC-MS/MS in all sera. The proteins were presented in BS and suppressed after surgery as follows: HPX, SERPINA1, SERPINC1, CP, HBD, and HBA2. Comparisons of the protein expression in sera of patients BS, 3MPS, and 6MPS revealed that GC, IGJ, AHSG, CD5L, FGG, and APOC3 have been overexpressed in 3MPS and 6MPS. PPI network analysis demonstrated that SERPINC1 and AHSG with more connection in the network could be considered as hub proteins and potential prognostic biomarkers in response to surgical treatment of liver CE. CONCLUSION: Application of proteomics methods on patient's sera could be used as a novel biomarker tool for following-up liver CE patients. In this regards, proteomics and, application of bioinformatics analysis including GO and PPI showed that SERPINC1, AHSG and HPX are of more value as a potential follow up biomarkers in response to surgical treatment.

The Prognostic Value of Thrombocytopenia in COVID-19 Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: Multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases. Thus, to provide a well-conceptualized viewpoint demonstrating the prognostic value of thrombocytopenia in COVID-19, we performed a meta-analysis of pertinent literature. METHODS: The keywords "platelet" OR "thrombocytopenia" AND "COVID-19" OR "coronavirus 2019" OR "2019-nCoV" OR "SARS-CoV-2" were searched in National Library of Medicine Medline/PubMed and Scopus between December 30, 2019, and May 9, 2020 in English without any restriction. The initial search results were first screened by title and abstract, and then full texts of relevant articles representing information on the platelet count (main outcome) with a clinically validated definition of COVID-19 severity were finally selected. To assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. Also, the heterogeneity among the included studies was tested using the Chi-square test. RESULTS: The results of our meta-analysis of 19 studies, totaling 3383 COVID-19 patients with 744 (21.9%) severe cases, revealed that non-severe cases have a significantly higher number of platelets and showed that the probability of the emergence of thrombocytopenia is significantly higher in the severe cases with the pooled mean difference of -21.5 (%95 CI: -31.57, -11.43). CONCLUSION: Decreased number of platelets more commonly associates with severe COVID-19; however, whether the emergence of thrombocytopenia may result in diseases severity or the severity of the disease may decrease platelets, is open to debate.

Proteome profiling of low grade serous ovarian cancer.

BACKGROUND: Serous carcinoma, the subtype of ovarian cancer has the highest occurrence and mortality in women. Proteomic profiling using mass spectrometry (MS) has been used to detect biomarkers in tissue s obtained from patients with ovarian cancer. Thus, this study aimed at analyzing the interactome (protein-protein interaction (PPI)) and (MS) data to inspect PPI networks in patients with Low grade serous ovarian cancer. METHODS: For proteome profiling in Low grade serous ovarian cancer, 2DE and mass spectrometry were used. Differentially expressed proteins which had been determined in Low grade serous ovarian cancer and experimental group separately were integrated with PPI data to construct the (QQPPI) networks. RESULTS: Six Hub-bottlenecks proteins with significant centrality values, based on centrality parameters of the network (Degree and between), were found including Transgelin (TAGLN), Keratin (KRT14), Single peptide match to actin, cytoplasmic 1(ACTB), apolipoprotein A-I (APOA1), Peroxiredoxin-2 (PRDX2), and Haptoglobin (HP). DISCUSSION: This study showed these six proteins were introduced as hub-bottleneck protein. It can be concluded that regulation of gene expression can have a critical role in the pathology of Low-grade serous ovarian cancer.

Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-κB axis: Shedding new light on resistance to Aprepitant.

While a batch of efforts are fastened on synthesizing the novel targeted anti-cancer agents, recent investigations have achieved a breakthrough in identifying a favorable anti-tumor activity for some supportive drugs, which their safety have been confirmed thus far. The results of the present study highlighted the efficacy of Aprepitant, an oral antagonist of the neurokinin-1 receptor (NK1R), against both APL (NB4) and pre-B ALL (Nalm-6) cell lines; however, a differential sensitivity pattern was found in these cells. To the best of our knowledge, this is the first time that the molecular mechanisms of resistance to Aprepitant have been investigated and, herein, we proposed that the effectiveness of Aprepitant could be overshadowed, at least partially, through over-activated nuclear factor-κB in Nalm-6 pre-B ALL cells. In contrast to Nalm-6, the cytotoxic property of Aprepitant in NB4 was divulged at the lower concentrations. Of particular interest, we found that the cytotoxicity of the inhibitor became even more evident in the synergistic experiments, where an enhanced reduction in viability was noted after treatment of NB4 cells with ATO-plus-Aprepitant. The stimulatory effect of NK1R inhibition on ATO cytotoxicity is probably mediated through up-regulation of p73, which can subsequently engage p21 and NF-κB pathway via transcriptional suppression of c-Myc. Taken together, the present study suggests that inhibition of NK1R using Aprepitant, either alone or in combination with chemotherapeutic drugs, could be a novel therapeutic strategy for the treatment of acute leukemia, especially APL, that may be clinically accessible in the near future.

Proteome evaluation of human cystic echinococcosis sera using two dimensional gel electrophoresis.

AIM: Detection of protein expression changes in human cystic echinococcosis sera by 2D gel electrophoresis. BACKGROUND: Diagnosis and successful treatment of cystic echinococcosis (CE) is a major challenge, up to now. Identification of related expressed proteins using proteomics tools and bioinformatics analysis of patients' sera have not been investigated, so far. METHODS: Sera from eight confirmed CE patients and three healthy controls were collected, tested by 2-DE for total protein separation of serum and analyzed using proteomics and bioinformatics methods. The gels were stained by Coomassie blue followed by scan imaging of the gels. The protein spots in each gel were analyzed using progenesis same spots software. Proteins names were obtained from TagIdent server. RESULTS: A total of 263 protein spots with different expression were detected in both normal and diseased samples. Comparison between diseased and normal gels showed the expression of 45 up-regulated protein spots with fold≥2 in diseased gel of which 10 were new proteins with statistical difference by normal gel (p-value<0.05). On the other hand, the expression of 50 down-regulated protein spots were observed of which 11 proteins have been suppressed. Clustering of all detected sera proteins (263) using correlation analysis, divided the proteins into 2 clusters based on up-regulated and down-regulated expression of proteins. Clustering results were approved by principal component analysis (PCA). CONCLUSION: Significant protein expression changes in human CE sera which is demonstrable by application of proteomics and bioinformatics analysis makes it an impressing tool for diagnosis of CE patients.

Prediction of Leishmania major Key Proteins Via Topological Analysis of Protein-Protein Interaction Network.

BACKGROUND: Although leishmaniasis is regarded as a public health problem, no effective vaccine or decisive treatment has been introduced for this disease. Therefore, representing novel therapeutic proteins is essential. Protein-protein Interaction network analysis is a suitable tool to discover novel drug targets for leishmania major. To this aim, gene and protein expression data is used for instructing protein network and the key proteins are highlighted. MATERIALS AND METHODS: In this computational and bioinformatics study, the protein/gene expression data related to leishmania major were studied, and 252 candidate proteins were extracted. Then, the protein networks of these proteins were explored and visualized by using String database and Cytoscape software. Finally, clustering and gene ontology were performed by MCODE and PANTHER databases, respectively. RESULTS: Based on gene ontology analysis, most of the leishmania major proteins were located in cell compartments and membrane. Catalytic activity and binding were regarded as the relevant molecular functions and metabolic and cellular processes were the significant biological process. In this network analysis, UB-EP52, EF-2, chaperonin, Hsp70.4, Hsp60, tubulin alpha and beta chain, and ENOL and LACK were introduced as hub-bottleneck proteins. Based on clustering analysis, Lmjf.32.3270, ENOL and Lmjf.13.0290 were determined as seed proteins in each cluster. CONCLUSION: The results indicated that hub proteins play a significant role in pathogenesis and life cycle of leishmania major. Further studies of hubs will provide a better understanding of leishmaniasis mechanisms. Finally, these key hub proteins could be a suitable and helpful potential for drug targets and treating leishmaniasis by considering their validation.

Stimulatory Effect of Indolic Hormone on As2O3 Cytotoxicity in Breast Cancer Cells: NF-κB-dependent Mechanism of Action of Melatonin.

The advent of combination therapy unprecedentedly shifted the paradigm of cancer treatment by reconstructing the conventional protocols. By identifying the anti-tumoral activity for different natural products, recent interest has focused on inventing the combined- modality strategies to increase the cure rates of cancer, while reducing the toxic side effects of current intensive regimens. To evaluate whether melatonin, indolic hormone produced mainly by the pineal gland, could enhance the pro-apoptotic effect of arsenic trioxide (As2O3) in breast cancer, MCF-7 cells were treated with As2O3-plus- melatonin and then the survival, proliferative rate, caspase-3 activity, and mRNA expression level of anti- apoptosis target genes of NF-κB were investigated. Our results delineated that exposure of MCF-7 cells to As2O3 not only reduced the survival of the cells, but also induced a caspsase-3-dependent apoptotic cell death. Noteworthy, an enhanced induction of apoptosis was found using As2O3 in combination with melatonin. Moreover, RQ-PCR analysis revealed that the enhanced cytotoxic effect of As2O3 in the presence of melatonin is mediated, at least partly, through suppressing the expression of NF-κB anti-apoptotic target genes such as MCL-1, BCL-2, survivin, XIAP, and c-IAP1 in breast cancer cells. The resulting data showed that As2O3, either alone or in combination with melatonin, exerted significant cytotoxic effect against MCF-7 cells. However, further investigations are needed to provide valuable clues for expediting this combination as a therapeutic strategy for breast cancer.

Proteomic Analysis of the Effect of Extremely Low-Frequency Electromagnetic Fields (ELF-EMF) With Different Intensities in SH-SY5Y Neuroblastoma Cell Line.

Introduction: During the last 3 decades, human is exposed to extremely low frequency electromagnetic fields (ELF-EMF) emitted by power lines and electronic devices. It is now well accepted that ELF-EMF are able to produce a variety of biological effects, although the molecular mechanism is unclear and controversial. Investigation of different intensities effects of 50 Hz ELF-EMF on cell morphology and protein expression is the aim of this study. Methods: SH-SY5Y human neuroblastoma cell line was exposed to 0.5 and 1 mT 50 Hz (ELF-EMF) for 3 hours. Proteomics techniques were used to determine the effects of these fields on protein expression. Bioinformatic and statistical analysis of proteomes were performed using Progensis SameSpots software. Results: Our results showed that exposure to ELF-EMF changes cell morphology and induces a dose-dependent decrease in the proliferation rate of the cells. The proteomic studies and bioinformatic analysis indicate that exposure to 50 Hz ELF-EMF leads to alteration of cell protein expression in both dose-dependent and intensity dependent manner, but the later is more pronounced. Conclusion: Our data suggests that increased intensity of ELF-EMF may be associated with more alteration in cell protein expression, as well as effect on cell morphology and proliferation.

Effect of ELF-EMF Exposure on Human Neuroblastoma Cell Line: a Proteomics Analysis.

BACKGROUND: Extremely low frequency electromagnetic fields (ELF-EMF) have been common in daily life all over the world. They have produced by power lines and electrical appliances, but higher levels of them have raised a lot of concerns about their carcinogenesis. Both epidemiological and laboratory studies have suggested that EMFs might increase cancer incidence, including acute childhood leukemia, brain and breast cancer. METHODS: In the present study, SH-SY5Y human neuroblastoma cell line has exposed to 2mT, 50 Hz magnetic field for 3 h. Next, effect of this exposure on protein expression including over-expression or under-expression has assessed by proteomics. RESULTS: Bioinformatics and statistical analysis using progenesis same spot software on the obtained 2D electrophoresis has shown that expression of 189 proteins in exposed group has changed relative to control. Besides, PCA analysis has verified results of clustering, and has shown that protein data has clustered according to experimental conditions. CONCLUSION: The results of this study have shown that ELF-EMF changes cell morphology via altering protein expression, but more profound studies have needed to determine the kind of proteins altered.

Effect of essential oil of Rosa Damascena on human colon cancer cell line SW742.

AIM: In this study, we report the effect of the essential oil of Rosa Damascena on human colon cancer cell line (SW742) and human fibroblast cells. BACKGROUND: Colon cancer is the second most common fatal malignancy. Owing to the existence of many side effects and problems related to common treatments such as surgery, chemotherapy and radiotherapy, alternative treatments are being investigated. Some herbal medicines have shown promising results against different types of cancers. Herbal medicines used have included the use naturally occurring essential oils. PATIENTS AND METHODS: The essential oil of Rosa Damascena was obtained by distillation and its effect on SW742 cell-line and fibroblast cells were investigated with cell culture. The cells were cultured and different volumes of essential oil were induced to the cells. After48hincubation, cell survival was measured and using statistical analysis, the findings were evaluated and reported. RESULTS: This study showed that soluble part of Rosa Damascena oil increases cell proliferation in high volumes and the non-soluble component decreases cell proliferation. CONCLUSION: The effects of essential oils, such as Rosa Damascena, on cell proliferation require more thorough investigation.

Proteomics analysis of MKN45 cell line before and after treatment with Lavender aqueous extract.

AIM: In this study the anticancer activity of Lavender aqueous extract against MKN45 cell line was evaluated. BACKGROUND: Plant-based drugs are regarded as promising therapies. Lavender is a plant that has been cultivated from ancient times. An aqueous extract of Lavender has shown therapeutic effects on the nervous system in the high doses based on in-vivo studies. Gastric cancer is one of the frequent cancers in Iranian population. We therefore assessed the effect of Lavender upon a gastric cancer cell line. PATIENTS AND METHODS: The MKN45 cancer cell line was selected for treatment with aqueous extract of Lavender. Survival of MKN45 cell line was studied in the presence of various concentrations of Lavender extract by MTT assay method. Morphological studies were performed via microscopic analyses. Flow cytometry and proteomics techniques were applied to determining pharmaceutical mechanism of lavender cytotoxic effects. RESULTS: The survival and morphological studies revealed anticancer characteristics of extract. Flow cytometry findings indicate that Lavender extract had a cytotoxic effect upon the cell line. Proteomics analysis identified a significant alternation in gastric cellular proteome expression after treating with the extract. Among 1000 spots, more than 700 spots showed changes in protein expression levels by informatics analysis. Of these proteins, expression of three cancer biomarkers, Annexin1, Anolase1 and HSP70 were suppressed by extract. CONCLUSION: This study suggests that Lavender extract is cytotoxic and alter protein expression in a gastric cancer cell line.

Study of Anti Cancer Property of Scrophularia striata Extract on the Human Astrocytoma Cell Line (1321).

There are considerable efforts to identify naturally occurring substances as new drugs in cancer therapy. Many components of medicinal plants have been identified that possess substantial anticancerous properties. This prompted us to investigate the effect of Scrophularia striata (an Iranian species belonging to the Scrophulariace family) extract on the growth of astrocyte cancer cell line (1321). The 1321 cell line were seeded in 96-well culture plates in the presence and absence of various concentrations of either leaf and seed filtered and unfiltered extract of Scrophularia striata to determine their probable anticancer effects in comparison with etoposide (chemical anticancer reagent). filtered leaf extract of S. Striata showed strong anticancer effect on 1321cell line as compared to control group (cells not exposed to extracts), and even the group (adenocarcinoma gastric cell line) exposed to etoposide. Unlike the leaf extract, the seed extract activated cell proliferation in all experiments. Flow cytometry findings indicated that apoptosis is the mechanism by which the leaf extract inhibits cell proliferation. Our findings indicate that both leaves and seeds of S. Striata contain both anti cancer and cell growth enhancing agents.