Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

Serotonin Receptors and Acetylcholinesterase Gene Expression Alternations: The Potential Value on Tumor Microenvironment of Gastric Cancer.

INTRODUCTION: Gastric cancer is one of the common causes of cancer-related death in the world. Neurotransmitters have recently been related to the proliferation of cancer cells, but the role of neurotransmitters in the progression of gastric cancer is still unexplored. The cross-talk between the nervous system and immune cells through serotonin and its receptors in the tumor microenvironment can impact tumor progress. Our purpose is to expose probable changes in serotonin receptors, acetylcholinesterase, and monoamine oxidase A gene expression in gastric cancer. METHODS: Transcript of serotonin receptors (5-HTR2A, 5-HTR2B, 5-HTR3A, 5-HTR7) and monoamine oxidase A genes in the peripheral blood mononuclear cells (40 patients and 40 control) and tissue (21 tumors and 21 normal adjacent tissues) were assessed. The gene expression was analyzed by quantitative real-time PCR using suitable primers. Statistical analysis was performed using appropriate software (REST, Prism). RESULTS: Significantly higher amounts of 5-HTR2A, 5-HTR2B, 5-HTR3A, 5-HTR7, and acetylcholinesterase gene transcripts were found in the peripheral blood of gastric cancer patients compared with healthy individuals. The expression of 5-HTR2B and 5-HTR3A genes was significantly higher (p = 0.0250, p = 0.0005, respectively) and the acetylcholinesterase gene was lower in the tissue of patients (p = 0.0119) compared with adjacent normal tissue. CONCLUSION: This study highlights the role of serotonin receptors in gastric cancer that might have suggestions for the development of novel therapeutics and defensive approaches that target factors associated with the link between the nervous system, cancer cells, and the tumor microenvironment.

Dopamine receptors gene overexpression in the microenvironment of invasive gastric cancer and its potential implications.

BACKGROUND: Gastric cancer (GC) is the fifth most common cancer worldwide and the most commonly diagnosed cancer in Iran. The nervous system provides proximity to tumor cells by releasing neurotransmitters such as dopamine and presenting them to the corresponding receptor-bearing tumors. While nerve fibers infiltrate the tumor microenvironment, little is known about the expression levels of dopamine (DA), dopamine receptors (DRs), and catechol-O-methyltransferase (COMT) in GC patients. METHODS: DRs and COMT expression were analyzed in 45 peripheral blood mononuclear cells (PBMCs) and 20 paired tumor and adjacent tissue of GC patients by quantitative polymerase chain reaction. DA was measured in plasma specimens using enzyme-linked immunosorbent assay. Protein-protein interaction analysis was carried out to identify GC-related hub genes. RESULTS: Increased expression of DRD1-DRD3 was found in tumor specimens compared with adjacent non-cancerous specimens (P < 0.05). A positive correlation was found between DRD1 and DRD3 expression (P = 0.009); DRD2 and DRD3 expression (P = 0.04). Plasma levels of dopamine were significantly lower in patients (1298 pg/ml) than in controls (4651 pg/ml). DRD1-DRD4 and COMT were up-regulated in PBMCs of patients compared with controls (P < 0.0001). Bioinformatic analyses showed 30 hub genes associated with Protein kinase A and extracellular signal-regulated kinase signaling pathways. CONCLUSIONS: The findings indicated dysregulation of DRs and COMT mRNA expression in GC and suggest that the brain- gastrointestinal axis may mediate gastric cancer development. Network analysis revealed that combination treatments could be considered for optimizing and improving the precision treatment of GC.

Mental health status and psychosocial issues during Nationwide COVID-19 quarantine in Iran in 2020: A cross-sectional study in Mazandaran Province.

The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly, and its psychosocial impact remains a big challenge. In this respect, quarantine has been recommended, as a significant practice, to prevent the given condition. Therefore, the present study was to determine the prevalence rates of depression, anxiety, and stress and to reflect on the impact of COVID-19, as a traumatic stressor event, on individuals. This web-based survey was fulfilled via an online questionnaire, completed by respondents selected through the cluster sampling technique, from March 24 to April 10, 2020, living in Mazandaran Province, Northern Iran. Accordingly, the data regarding demographic characteristics, physical health status, quarantine compliance, contact with COVID-19, and additional information were collected. The psychosocial impact of the pandemic was then assessed by the Impact of Event Scale-Revised (IES-R), and the respondents' mental health status was evaluated using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Data analysis was further performed by linear regression. The study findings, from 1075 respondents, revealed that 22.5% of the cases had moderate-to-severe depression, 38.5% of the individuals were suffering from moderate-to-severe anxiety, and 47.2% of the participants were experiencing moderate-to-severe stress. In 14.5% of the respondents, the psychosocial impact of COVID-19 also varied from the possibility of post-traumatic stress disorder (PTSD) to immunosuppression (p < 0.01). With the high prevalence rates of depression, anxiety, and stress, mental health professionals are suggested to develop psychosocial interventions and support plans for the general population to reduce the impact of the COVID-19 pandemic on public mental health status.

Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial.

This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation. Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.

Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial.

INTRODUCTION: Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection. METHODS: This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1. RESULTS: Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001. CONCLUSIONS: In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.

Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data.

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial.

BACKGROUND: New therapeutic options are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). Repurposing existing pharmaceuticals provides an immediate treatment opportunity. We assessed the efficacy of sofosbuvir and daclatasvir with ribavirin for treating patients with COVID-19. METHODS: This was a single-centre, randomized controlled trial in adults with moderate COVID-19 admitted to the Ghaem Shahr Razi Hospital in Mazandaran Province, Iran. Patients were randomly assigned to 400 mg sofosbuvir, 60 mg daclatasvir and 1200 mg ribavirin (intervention group) or to standard care (control group). The primary endpoint of this study was length of hospital stay. This study is registered by IRCT.ir under the ID: IRCT20200328046886N1. RESULTS: Between 20 March 2020 and 8 April 2020, 48 patients were recruited; 24 patients were randomly assigned to the intervention group and 24 to the control group. The median duration of hospital stay was 6 days in both groups (P = 0.398). The number of ICU admissions in the sofosbuvir/daclatasvir/ribavirin group was not significantly lower than the control group (0 versus 4, P = 0.109). There was no difference in the number of deaths between the groups (0 versus 3, P = 0.234). The cumulative incidence of recovery was higher in the sofosbuvir/daclatasvir/ribavirin arm (Gray's P = 0.033). CONCLUSIONS: This randomized trial was too small to make definitive conclusions. There were trends in favour of the sofosbuvir/daclatasvir/ribavirin arm for recovery and lower death rates. However, there was an imbalance in the baseline characteristics between the arms. Larger randomized trials should be conducted to investigate this treatment further.

Prevalence of BRAF gene mutation in samples of primary and metastatic colorectal cancer: A meta-analysis.

INTRODUCTION: Understanding the prevalence and biology of BRAF gene can improve the treatment methods of cancerous patients. This study aims to estimate the prevalence of BRAF gene mutation in samples of primary and metastatic colorectal cancer using meta-analysis method. METHODS: We searched PubMed, Scopus, ScienceDirect, Ovid and Google Scholar motor engine using MeSH terms of relevant keywords. During the screening phase, titles, abstracts and full texts were reviewed and risk of bias was assessed for all selected papers based on Newcastle-Ottawa Scale (NOS) checklist. The results of the primary studies were combined using meta-analysis. RESULTS: Of 95 eligible studies entered into the meta-analysis, prevalence of BRAF gene mutation had been assessed among 19,484 primary tumour samples as well as 12,256 metastatic samples. The total prevalence of BRAF gene mutation among primary tumour samples was estimated as of 10.16% (8.09-12.22) in the world, 0.41% (0-1.89) in EMRO region, 10.06% (7.54-12.59) in EURO region, 10.33% (7.24-13.43) in SEARO region and 11.33% (7.29-15.37) in WPRO region. The pooled estimates for BRAF gene mutation in metastatic samples were 6.53% (5.09-7.96), 8.07% (5.57-10.56), 5.38% (3.75-7.02) and 5.55% (1.72-9.38) for all regions, EURO, WPRO and PAHO regions respectively. CONCLUSION: Our results showed evidences of BRAF gene mutation in one-tenth of primary colorectal tumour samples in EURO, PAHO, SEARO and WPRO regions which was considerably higher than that of the EMRO region.

Pseudogene-free amplification of HPRT1 in quantitative reverse transcriptase polymerase chain reaction.

Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) provides a powerful tool for precise gene expression analysis. The accuracy of the results highly depends on careful selection of a reference gene for data normalization. HPRT1 (hypoxanthine phosphoribosyl transferase 1) is a frequently used housekeeping gene for normalizing relative expression values. However, the existence of processed pseudogenes for HPRT1 might interfere with reliable results obtained in qRT-PCR due to amplification of unintended products. Here, we designed a primer pair for pseudogene-free amplification of HPRT1 in qRT-PCR. We demonstrate that this primer pair specifically amplified HPRT1 messenger RNA (mRNA) sequence while avoiding coamplification of the pseudogenes.

The effect and side effect of hydroxyurea therapy on patients with ß-thalassemia: a systematic review to December 2012.

Hydroxyurea (HU) is being used for patients with transfusion-dependent ß-thalassemia major (ß-TM) as well as non transfusion-dependent ß-TM. As controversy exists regarding efficacy and safety of HU, we searched the published literature on efficacy, effectiveness and toxicity of HU in patients with ß-TM. The research sources we used were: Medline, SID, PubMed, Scopus, Request, Web of Knowledge, Springer, Ovid, Cochrane searched up to October 2012. Using search terms sensitive to studies of clinical trials combined with searches on terms related to thalassemia and HU. We selected studies on randomized trials, quasi experimental trials (before and after design), case reports (with 1-5 cases), side effect studies in patients with ß-TM, studies related to the mechanism of action and toxicity when used in patients with other hemoglobinopathies. We researched studies in English and Persian. Eligible articles were reviewed by two independent reviewers. Patient's characteristics, duration of trial, outcome and side effects were extracted. The main outcomes were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic, Tau(2) and I(2). Subgroup analyses were performed and the statistics data (STATA) software used. More than 500 articles were reviewed. No randomized clinical trial was found. Seventeen trials with before and after designs were found, 16 case reports (1-5 cases), 19 articles for mechanism of action and 16 studies for side effects were published from 1969 to October 2012. Hemoglobin levels after treatment showed modest but significant increase in non transfusion-dependent ß-TM (p < 0.0001) and in transfusion-dependent ß-TM (p < 0.0001).

The prevalence and determinants of diabetes mellitus and thyroid disorder comorbidity in Tabari cohort population.

Studies have shown that the co-occurrence of diabetes mellitus (DM) and thyroid dysfunction (TD) exacerbates diabetes complications and imposes a financial burden on the healthcare system. Therefore, this study aimed to investigate the prevalence of TD-DM comorbidity and its associated risk factors. This cross-sectional study was conducted on enrollment phase data of the TABARI cohort population which consisted of 10,255 adults aged between 35 to 70 years old residing in Sari, Mazandaran, Iran from 2015 to 2017. A total of 9939 out of 10,255 individuals (96.92%) entered the study. The prevalence of TD among T2DM patients was 13.2%. The prevalence of T2DM among patients with TD was 9.2%. Furthermore, the prevalence of TD-DM comorbidity in the overall population was 2.2%. Logistic regression analysis revealed that the odds of TD-DM comorbidity was significantly higher in women (OR 2.85; 95% CI 1.58-5.11), in the age group of 60-70 years (OR 9.62; 95% CI 3.69-25.10), in smokers (OR 2.32; 95% CI 1.19-4.52), in individuals with high waist circumference (WC) (OR 2.22; 95% CI 1.32-3.75), in individuals with low high-density lipoprotein (HDL) (OR 1.60; 95% CI 1.20-2.14), in individuals with high total cholesterol (TC) (OR 1.71; 95% CI 1.21-2.41), in individuals with high triglycerides (TG) (OR 1.79; 95% CI 1.27-2.51), and significantly lower in individuals with higher physical activity (PA) (OR 0.67; 95% CI 0.49-0.93). The present study demonstrated a prevalence of 2.2% in patients with both TD and T2DM. Additionally, female gender, older age, smoking, high WC, low HDL, high TC, high TG, and low PA were predictors of TD-DM comorbidity.

Revealing New Prospects: Antipsychotic Drugs Exert Anti-Tumor Effects against Gastric Cancer through Inducing Apoptosis.

BACKGROUND AND OBJECTIVE: Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC. METHODS: The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining. RESULTS: Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells. CONCLUSION: Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer.

Repurposing naproxen as a potential nucleocapsid antagonist of beta-coronaviruses: targeting a conserved protein in the search for a broad-spectrum treatment option.

Ongoing mutations in the coronavirus family, especially beta-coronaviruses, raise new concerns about the possibility of new unexpected outbreaks. Therefore, it is crucial to explore new alternative treatments to reduce the impact of potential future strains until new vaccines can be developed. A promising approach to combat the virus is to target its conserved parts such as the nucleocapsid, especially via repurposing of existing drugs. The possibility of this approach is explored here to find a potential anti-nucleocapsid compound to target these viruses. 3D models of the N- and C-terminal domains (CTDs) of the nucleocapsid consensus sequence were constructed. Each domain was then screened against an FDA-approved drug database, and the most promising candidate was selected for further analysis. A 100 ns molecular dynamics (MD) simulation was conducted to analyze the final candidate in more detail. Naproxen was selected and found to interact with the N-terminal domain via conserved salt bridges and hydrogen bonds which are completely conserved among all Coronaviridae members. MD analysis also revealed that all relevant coordinates of naproxen with N terminal domain were kept during 100 ns of simulation time. This study also provides insights into the specific interaction of naproxen with conserved RNA binding pocket of the nucleocapsid that could interfere with the packaging of the viral genome into capsid and virus assembly. Additionally, the in-vitro binding assay demonstrated direct interaction between naproxen and recombinant nucleocapsid protein, further supporting the computational predictions.Communicated by Ramaswamy H. Sarma.

Significance of Serum Apelin Levels as a Biomarker for Gastric Cancer Diagnosis.

OBJECTIVES: Gastric cancer (GC) is one of the common lethal disease and the most common cancers worldwide and in Iran. North of Iran is known as a common area of gastric cancer and a high-risk zone in Iran. Apelin is a biomolecule that plays roles in various types of cancers. This study was designed to investigate the serum apelin-12 levels in patients with gastric cancer as a predictive marker and affordable noninvasive alternative. METHODS: In this case-control study, the case group included 42 patients with gastric cancer who were diagnosed by endoscopy and pathological findings. The participants in the case group were compared with the control group including 43 healthy individuals with no history of gastric cancer in their first-degree relatives and visiting the lab for routine tests. Apelin-12 serum level was assessed using ELISA kit. Data were analyzed in SPSS V16.0 applying Fisher's exact test, Mann-Whitney U test, and t-test. RESULTS: Serum apelin-12 in patients with gastric cancer was found to be statistically lower than that in healthy individuals (p< 0.05). There were no significant differences between clinicopathological characteristics and apelin-12 expression. The median survival time in experimental and control groups was 16.0 months. CONCLUSIONS: In the current study, serum levels of apelin were significantly different between cases and controls.

Neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios, any association with metabolic syndrome?

Background: Metabolic syndrome is a critical health concern associated with an elevated risk of chronic health problems including cardiovascular disease and diabetes. There are shreds of evidence that novel inflammatory ratios including neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios serve as prognostic biomarkers for metabolic syndrome (MetS). This hypothesis was investigated in a cohort of the Iranian population. Methods: selection of MetS + subjects was based on the National Cholesterol Education Program Adult Treatment Panel III criteria 3 (NCEP ATP 3). The control group consisted of participants negative for any of the five MetS criteria. Demographic and laboratory data were extracted from the Tabari cohort study. Results: A total of 1930 subjects including 965 Mets positive and 965 MetS criteria negative participants were evaluated. Diabetes (84.8%), hypertension (48.9%), hypertriglyceridemia (81.7%), low HDL cholesterol (70.3%), and high waist circumference (78.9%) were observed in patients. There were no differences between NLR (1.66±0.71 vs. 1.69±0.72 P=0.42), LMR (11.23±3.13 vs. 11.30±11.99, P= 0.86) and PLR (113.85±68.67 vs 114.11±35.85, P=0.91) between case and control groups, respectively. Logistic regression analysis revealed no association between ratios and MetS risk even after adjusting for potential confounders including age, gender, living place, and BMI. Conclusion: In a relatively large population from Northern Iran, no association was observed between CBC-derived inflammatory ratios and the presence of MetS.

Comparing mental health status and COVID-19 event impact between survivors and the general population during the second wave of the pandemic in Iran.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) pandemic has to date overwhelmed the survivors and the general population. The present study aimed to compare the mental health status and the COVID-19 event impact between the survivors and the general population in Mazandaran Province, Northern Iran. DESIGN: A web-based cross-sectional survey was used. METHODS: This study was performed using convenience sampling. RESULTS: In total, 1,766 participants were included in this study. The findings revealed that the posttraumatic stress disorder (PTSD) severity in both outpatient and hospitalized groups was significantly higher than that in the general population. Besides, the levels of anxiety and depression in the group receiving inpatient care and treatment had significantly elevated than those in the general population. CONCLUSION: Given the high prevalence rate of mental disorders, healthcare professionals are recommended to plan for various interventions and support services to boost community mental health status.

The Psychometric Properties of the Fear of Progression Questionnaire (FoP-Q) for Cancer Patients in Iran.

PURPOSE: Fear of progression or recurrence is assumed as a rational response to the threat of cancers and types of cancer treatment. However, the elevated levels of fear in cancer patients can become dysfunctional. Therefore, a valid and reliable questionnaire is unquestionably required for this purpose. This study aimed to translate the Fear of Progression Questionnaire and evaluate its psychometric properties for patients with gastrointestinal cancers in Iran. METHODS: In this study with a methodological research design, a total number of 430 patients affected with gastrointestinal cancers referring to Northern Iran completed the 43-item Fear of Progression Questionnaire. The psychometric properties of the questionnaire were evaluated, including the face validity and content validity. Then construct validity was assessed using exploratory and confirmatory factor analyses. Finally, the reliability was assessed using internal consistency (Cronbach's alpha) and stability (intraclass correlation coefficient). RESULTS: Based on the result of the face and content validity, no items were revised and removed. The five extracted factors included were emotional response, employment, and loss of independence, economy/family, and coping. These factors explained 37% of the total variance of Fear of Progression Questionnaire. Reliability (by Cronbach's alpha) and stability (test retest was evaluated by intraclass correlation coefficient) were more than 0.7. CONCLUSION: The study results revealed that the Persian version of the Fear of Progression Questionnaire had acceptable reliability and validity for cancer patients in Iran. Emotional responses explained the most variance of the concept of fear of progression among cancer patients.

Differential gene expression of SARS-CoV-2 transcriptome provides insight into the design of more sensitive diagnostic tests.

The Coronavirus disease 2019 (COVID-19) pandemic is being addressed through RT-PCR, a frontline diagnostic technique. We evaluated gene expression patterns to improve the accuracy and sensitivity of current diagnostic tests. We downloaded relevant next-generation sequencing (NGS) data from the Sequence Read Archive (SRA) database, checked for quality, and mapped them onto the target reference sequence. It was determined that ORF1ab, N, S, and ORF8 genes are mainly expressed based on the results of the quantitative evaluation after normalization by HPRT and elimination of insufficient expression data. ORF8, ORF3a, and M genes were found to have higher expression values than the E gene as a routine RT-PCR detector gene (p*0.05). M gene expression values are also close to ORF8 values. Taking into account the importance of differential expression of genes in the design of diagnostic kits as well as the findings of from this study, it is likely that the M gene is worth further investigation due to its high expression and low mutation rate.

Association between Serum Progastrin Biomarker Level and Gastric Cancer.

BACKGROUND AND OBJECTIVE: gastric cancer is the fifth most prevalent cancer and the fourth cause of death because of cancer. In Iran, northern and northwestern regions are considered gastric cancer hot spots. Identifying serum biomarkers could be helpful in early diagnosis of patients with gastric adenocarcinoma (GAC). Increase in progastrin level has been reported in different cancers. Given the diagnostic value of this biomarker, this study aimed to determine the diagnostic role of progastrin serum biomarker in patients with gastric cancer. METHODOLOGY: In this case-control study, forty patients with gastric cancer who were diagnosed by endoscopy and pathologic findings and visited Mazandaran Comprehensive Cancer Center. The participants had received no treatment yet and entered this study. The participants in case group were compared with the control group including forty-two individuals with no history of gastrointestinal cancer in their first-degree relatives and visiting the lab for routine tests. Progastrin serum level was assessed using ELISA kit. The Kruskal-Wallis test and Mann Whitney test, both non-parametric) were used for statistical analysis and the relation between the variables was examined using Pearson's correlation coefficient at 95% confidence level in SPSS 16. FINDINGS: In this study, progastrin serum level was significantly higher in patients with gastric cancer compared with normal participants (P = 0.035). Progastrin serum level had no significant relation with tumor clinicopathologic parameters (p-value > 0.05). CONCLUSION: Increase in progastrin may be utilized as a predictive factor for gastric cancer.