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Sniffer dogs as a screening/diagnostic tool for COVID-19: a proof of concept study
Get PDFBackground: Sniffer dogs are able to detect certain chemical particles and are suggest to be capable of helping diagnose some medical conditions and complications, such as colorectal cancer, melanoma, bladder cancer, and even critical states such as hypoglycemia in diabetic patients. With the global spread of COVID-19 throughout the world and the need to have a real-time screening of the population, especially in crowded places, this study aimed to investigate the applicability of sniffer dogs to carry out such a task. Methods: Firstly, three male and female dogs from German shepherd (Saray), German black (Kuzhi) and Labrador (Marco) breeds had been intensively trained throughout the classical conditioning method for 7 weeks. They were introduced to human specimens obtained from the throat and pharyngeal secretions of participants who were already reported positive or negative for SARS-COV-2 infection be RT-PCR. Each dog underwent the conditioning process for almost 1000 times. In the meantime another similar condition process was conducted on clothes and masks of COVID-19 patient using another three male and female dogs from Labrador (Lexi), Border gypsy (Sami), and Golden retriever (Zhico) breeds. In verification test for the first three dogs, 80 pharyngeal secretion samples consisting of 26 positive and 54 negative samples from different medical centers who underwent RT-PCR test were in a single-blind method. In the second verification test for the other three dogs, masks and clothes of 50 RT-PCR positive and 70 RT-PCR negative cases from different medical center were used. Results: In verification test using pharyngeal secretion, the sniffer dogs� detection capability was associated with a 65 of sensitivity and 89 of specificity and they amanged to identify 17 out of the 26 positive and 48 out of the 54 true negative samples. In the next verification test using patients� face masks and clothes, 43 out of the 50 positive samples were correctly identified by the dogs. Moreover, out of the 70 negative samples, 65 samples were correctly found to be negative. The sensitivity of this test was as high as 86 and its specificity was 92.9. In addition, the positive and negative predictive values were 89.6 and 90.3, respectively. Conclusion: Dogs are capable of being trained to identify COVID-19 cases by sniffing their odour, so they can be used as a reliable tool in limited screening. © 2021, The Author(s)
Clinical and prognostic significances of cancer stem cell markers in gastric cancer patients: a systematic review and meta-analysis
Get PDFBackground: Gastric cancer (GC) is considered one of the most lethal malignancies worldwide, which is accompanied by a poor prognosis. Although reports regarding the importance of cancer stem cell (CSC) markers in gastric cancer progression have rapidly developed over the last few decades, their clinicopathological and prognostic values in gastric cancer still remain inconclusive. Therefore, the current meta-analysis aimed to quantitatively re-evaluate the association of CSC markers expression, overall and individually, with GC patients� clinical and survival outcomes. Methods: Literature databases including PubMed, Scopus, ISI Web of Science, and Embase were searched to identify the eligible articles. Hazard ratios (HRs) or odds ratios (ORs) with 95 confidence intervals (CIs) were recorded or calculated to determine the relationships between CSC markers expression positivity and overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS), disease-specific survival (DSS)/ cancer-specific survival (CSS), and clinicopathological features. Results: We initially retrieved 4,425 articles, of which a total of 66 articles with 89 studies were considered as eligible for this meta-analysis, comprising of 11,274 GC patients. Overall data analyses indicated that the overexpression of CSC markers is associated with TNM stage (OR = 2.19, 95 CI 1.84�2.61, P = 0.013), lymph node metastasis (OR = 1.76, 95 CI 1.54�2.02, P < 0.001), worse OS (HR = 1.65, 95 CI 1.54�1.77, P < 0.001), poor CSS/DSS (HR = 1.69, 95 CI 1.33�2.15, P < 0.001), and unfavorable DFS/RFS (HR = 2.35, 95 CI 1.90�2.89, P < 0.001) in GC patients. However, CSC markers expression was found to be slightly linked to tumor differentiation (OR = 1.25, 95 CI 1.01�1.55, P = 0.035). Sub-analysis demonstrated a significant positive relationship between most of the individual markers, specially Gli-1, Oct-4, CD44, CD44V6, and CD133, and clinical outcomes as well as the reduced survival, whereas overexpression of Lgr-5, Nanog, and sonic hedgehog (Shh) was not found to be related to the majority of clinical outcomes in GC patients. Conclusion: The expression of CSC markers is mostly associated with worse outcomes in patients with GC, both overall and individual. The detection of a combined panel of CSC markers might be appropriate as a prognostic stratification marker to predict tumor aggressiveness and poor prognosis in patients with GC, which probably results in identifying novel potential targets for therapeutic approaches. © 2021, The Author(s)
Psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS)
Get PDFObjectives: This study was conducted to assess the psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS), a measure designed to evaluate the severity and functional impairments associated with clinical and subsyndromal anxiety. Methods: Using a descriptive-analytic framework, first, the OASIS was translated into Persian according to the forward-backward translation guidelines. Then, a total of 463 students of Guilan University of Medical Sciences in the academic year 2017 - 18 were selected using the convenience sampling method. Participants completed seven measures (i.e., OASIS, anxiety and stress subscales of depression anxiety stress scales-21, Beck anxiety inventory, openness subscale of NEO five-factor inventory, positive affect and negative affect scales, Connor-Davidson resilience scale, and state subscale of state-trait anxiety inventory), and the data were analyzed by SPSS V. 20.0 for windows and Lisrel V. 8.80. Results: Internal consistency reliability of the OASIS was acceptable (Cronbach�s α = 0.877). The exploratory factor analysis indicated that all items were loaded on a single factor (loadings = 0.799 - 0.849). The confirmatory factor analysis revealed that the single-factor model has resulted in an adequate model fit. The OASIS was positively correlated with the anxiety- and negative affect-related scales, whereas it was negatively correlated with the resilience- and positive affect-related scales. Correlations with the openness subscale were not significant. Conclusions: In line with previous studies, the findings showed that the psychometric properties of the Persian version of the OASIS are acceptable. Therefore, it seems that the measure can be used in clinical practices and research studies in Iran. Copyright © 2020, Author(s)
Design and synthesis of novel quinazolinone-pyrazole derivatives as potential α-glucosidase inhibitors: Structure-activity relationship, molecular modeling and kinetic study
No full textIn this study, a new series of quinazolinone-pyrazole hybrids were designed, synthesized and screened for their α-glucosidase inhibitory activity. The results of the in vitro screening indicated that all the molecular hybrids exhibited more inhibitory activity (IC50 values ranging from 60.5 ± 0.3 µM-186.6 ± 20 μM) in comparison to standard acarbose (IC50 = 750.0 ± 10.0 µM). Limited structure�activity relationship suggested that the variation in the inhibitory activities of the compounds affected by different substitutions on phenyl rings of diphenyl pyrazole moiety. The enzyme kinetic studies of the most potent compound 9i revealed that it inhibited α-glucosidase in a competitive mode with a Ki of 56 μM. Molecular docking study was performed to predict the putative binding interaction. As expected, all pharmacophoric moieties used in the initial structure design playing a pivotal role in the interaction with the binding site of the enzyme. In addition, by performing molecular dynamic investigation and MM-GBSA calculation, we investigated the difference in structural perturbation and dynamic behavior that is observed over α-glycosidase in complex with the most active compound and acarbose relative to unbound α-glycosidase enzyme. © 202
Development of a recombinant anti-VEGFR2-EPCAM bispecific antibody to improve antiangiogenic efficiency
No full textTumor progression and metastasis, especially in invasive cancers (such as triple-negative breast cancer TNBC), depend on angiogenesis, in which vascular epithelial growth factor (VEGF)/vascular epithelial growth factor receptor 1 has a decisive role, followed by the metastatic spread of cancer cells. Although some studies have shown that anti-VEGFR2/VEGF monoclonal antibodies demonstrated favorable results in the clinic, this approach is not efficient, and further investigations are needed to improve the quality of cancer treatment. Besides, the increased expression of epithelial cell adhesion molecule (EpCAM) in various cancers, for instance, invasive breast cancer, contributes to angiogenesis, facilitating the migration of tumor cells to other parts of the body. Thus, the main goal of our study was to target either VEGFR2 or EpCAM as pivotal players in the progression of angiogenesis in breast cancer. Regarding cancer therapy, the production of bispecific antibodies is easier and more cost-effective compared to monoclonal antibodies, targeting more than one antigen or receptor; for this reason, we produced a recombinant antibody to target cells expressing EpCAM and VEGFR2 via a bispecific antibody to decrease the proliferation and metastasis of tumor cells. Following the cloning and expression of our desired anti-VEGFR2/EPCAM sequence in E. coli, the accuracy of the expression was confirmed by Western blot analysis, and its binding activities to VEGFR2 and EPCAM on MDA-MB-231 and MCF-7 cell lines were respectively indicated by flow cytometry. Then, its anti-proliferative potential was indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assay to evaluate inhibitory effects of the antibody on tumor cells. Subsequently, the data indicated that migration, invasion, and angiogenesis were inhibited in breast cancer cell lines via the bispecific antibody. Furthermore, cytokine analysis indicated that the bispecific antibody could moderate interleukin 8 (IL-8) and IL-6 as key mediators in angiogenesis progression in breast cancer. Thus, our bispecific antibody could be considered as a promising candidate tool to decrease angiogenesis in TNBC. © 2021 Elsevier Inc
Evaluation of local and circulating osteopontin in malignant and benign primary bone tumors
Get PDFPurpose: The development of novel and efficient biomarkers for primary bone cancers is of grave importance. Methods: The expression pattern of osteopontin (OPN) was investigated in the 153 patients with benign (n = 72) and malignant (n = 81) primary bone cancers. Both local and circulating OPN mRNA expression levels and their protein concentration in serum and tumor site were assessed using real-time qRT-PCR, ELISA, and immunohistochemistry techniques, respectively. As a control, 29 healthy individuals were considered. The number of 153 tumor tissue specimens and the 153 paired margins were taken on surgical resection from the patients. 153 blood samples were also drained from all participants, then peripheral blood mononuclear cells (PBMC) and sera were separated. Results: The mean mRNA expression was significantly higher in all of the cancerous tissues than the paired margins and the PBMC of the patients than the controls. Consistently, the protein concentrations of OPN in serum and tumor tissues were significantly higher in the patients. Furthermore, the malignant cases had significantly elevated the mRNA levels and the protein compared to the benign cases. OPN could potentially differentiate the patients from the controls with 100 sensitivity and specificity in serum. Moreover, OPN could predict some of the malignant cases' clinicopathological features, including metastasis, recurrence, grade, and response to chemotherapy. Conclusions: In conclusion, OPN might be involved in the pathogenesis of primary bone tumors and can be considered as a potential biomarker to bone cancer diagnosis. © 202
Association between circulating rotavirus genotypes and histo-blood group antigens in the children hospitalized with acute gastroenteritis in Iran
No full textRotaviruses are the dominant cause of severe acute gastroenteritis in children under 5 years of age. Previous studies showed that some children are less susceptible to rotavirus gastroenteritis. It has been shown that this resistance depends on the rotavirus genotype and also human histo-blood group antigens (HBGAs), which works as a receptor for rotavirus surface protein (VP4). The present study aimed to evaluate the human genetic susceptibility to rotavirus gastroenteritis in Iran and to obtain a comparative analysis between rotavirus gastroenteritis and secretor or Lewis status in case and control groups in the Iranian population. The study was performed on fecal specimens from 108 children with acute rotavirus gastroenteritis from 2015 to 2017. A total of 50 fecal specimens from children with acute gastroenteritis of unknown etiology were also used as a control group. After the genotyping of positive rotavirus cases and human HBGAs by Sanger sequencing, the phylogenetic tree analysis showed that all rotavirus strains from Iran belonged to PII. The most common genotype was P8 (n = 102; 94.4%), while the remaining belonged to P4 (n = 3; 2.8%) and P6 (n = 3; 2.8%) genotypes. The P8 genotype was found to be associated with secretor and Lewis positive status (p <.05). © 2021 Wiley Periodicals LL
Emerging advances of nanotechnology in drug and vaccine delivery against viral associated respiratory infectious diseases (VARID)
Get PDFViral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
Nuclear overexpression levels of MAGE-A3 predict poor prognosis in patients with prostate cancer
No full textMelanoma antigen gene A3 (MAGE-A3) is one of the most immunogenic cancer testis antigens and is common in various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE-A3 in 153 prostate tissue samples including prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HPIN). Increased both nuclear and cytoplasmic expression of MAGE-A3 was significantly found in PCa tissues compared with both HPIN and BPH tissues (nuclear expression at p = 0.011, and cytoplasmic expression at p = 0.034; for both comparisons p 7) was independent predictors of the DFS (both; p = 0.019). Nuclear expression of MAGE-A3 was also significantly related to BCR-FS (p = 0.015). MAGE-A3 can be considered as a predictor for poor prognosis and an option for vaccine immunotherapy in patients with PCa. © 2021 Scandinavian Societies for Medical Microbiology and Patholog