The effects of ALK5 inhibition and simultaneous inhibition or activation of HIF-1α in melanoma tumor growth and angiogenesis.

BACKGROUND: Hypoxia is the most common signature of the tumor microenvironment that drives tumorigenesis through the complex crosstalk of a family of transcription factors called hypoxia-inducible factors (HIFs), with other intercellular signaling networks. Hypoxia increases transforming growth factor-beta (TGF-ß) expression. TGF-ß and HIF-1α play critical roles in several malignancies and their interactions in melanoma progression remain unknown. Therefore, the aim of this study was to assess the impact of inhibiting activin receptor-like kinase-5 (ALK5), a TGF-ß receptor, on the response to HIF-1α activation or inhibition in melanoma tumor progression. MATERIALS AND METHODS: Tumors were induced in C57BL/6J mice by subcutaneous inoculation with B16F10 melanoma cells. Mice were divided into HIF-1α inhibitor, ALK5 inhibitor (1 mg/kg) and HIF-1α inhibitor (100 mg/kg), ALK5 inhibitor, HIF-1α activator (1000 mg/kg), HIF-1α activator and ALK5 inhibitor, and control groups to receive inhibitors and activators through intraperitoneal injection. The expression of E-cadherin was evaluated by RT-qPCR. Vessel density and platelet-derived growth factor receptor beta (PDGFR)-ß+ cells around the vessels were investigated using immunohistochemistry. RESULTS: The groups receiving HIF-1α inhibitor and activator showed lower and higher tumor growth compared to the control group, respectively. E-cadherin expression decreased in all groups compared to the control group, illustrating the dual function of E-cadherin in the tumor microenvironment. Vascular density was reduced in the groups given HIF-1α inhibitor, ALK5 inhibitor, and ALK5 and HIF-1α inhibitor simultaneously. The percentage of PDGFR-ß+ cells was reduced in the presence of HIF-1α inhibitor, ALK5 inhibitor, HIF-1α and ALK5 inhibitors, and upon simultaneous treatment with HIF-1α activator and ALK5 inhibitor. CONCLUSION: Despite increased expression and interaction between TGF-ß and HIF-1α pathways in some cancers, in melanoma, inhibition of either pathway alone may have a stronger effect on tumor inhibition than simultaneous inhibition of both pathways. The synergistic effects may be context-dependent and should be further evaluated in different cancer types.

Antibacterial and pH-sensitive methacrylate poly-L-Arginine/poly (ß-amino ester) polymer for soft tissue engineering.

During the last decade, pH-sensitive biomaterials containing antibacterial agents have grown exponentially in soft tissue engineering. The aim of this study is to synthesize a biodegradable pH sensitive and antibacterial hydrogel with adjustable mechanical and physical properties for soft tissue engineering. This biodegradable copolymer hydrogel was made of Poly-L-Arginine methacrylate (Poly-L-ArgMA) and different poly (ß- amino ester) (PßAE) polymers. PßAE was prepared with four different diacrylate/diamine monomers including; 1.1:1 (PßAE1), 1.5:1 (PßAE1.5), 2:1 (PßAE2), and 3:1 (PßAE3), which was UV cross-linked using dimethoxy phenyl-acetophenone agent. These PßAE were then used for preparation of Poly-L-ArgMA/PßAE polymers and revealed a tunable swelling ratio, depending on the pH conditions. Noticeably, the swelling ratio increased by 1.5 times when the pH decreased from 7.4 to 5.6 in the Poly-L-ArgMA/PßAE1.5 sample. Also, the controllable degradation rate and different mechanical properties were obtained, depending on the PßAE monomer ratio. Noticeably, the tensile strength of the PßAE hydrogel increased from 0.10 ± 0.04 MPa to 2.42 ± 0.3 MPa, when the acrylate/diamine monomer molar ratio increased from 1.1:1 to 3:1. In addition, Poly-L-ArgMA/PßAE samples significantly improved L929 cell viability, attachment and proliferation. Poly-L-ArgMA also enhanced the antibacterial activities of PßAE against both Escherichia coli (~5.1 times) and Staphylococcus aureus (~2.7 times). In summary, the antibacterial and pH-sensitive Poly-L-ArgMA/PßAE1.5 with suitable mechanical, degradation and biological properties could be an appropriate candidate for soft tissue engineering, specifically wound healing applications.

Morphine upregulates Toll-like receptor 4 expression and promotes melanomas in mice.

BACKGROUND: Morphine and other opioids are used to manage cancer-related pain; however, the role of these drugs in cancer progression remains controversial. Emerging evidence indicates that morphine can activate Toll-like receptor 4 (TLR4) and its signaling pathways, by the way the activation and expression of TLR4 can promote melanoma. In this study, we investigated the effects of morphine on the expression of TLR4 and promotion of melanoma in mice. METHODS: Mice melanoma cells (B16F10) were cultured with morphine (0.1, 1 and 10 µM) for 24 h. In the other experiment, cells were treated with morphine with or without TLR4 agonist (LPS) or antagonist (TAK-242). In in-vivo model, B16F10 cells were subcutaneously injected to C57BL/6 mice, and morphine was administrated in three different treatment protocols after developing palpable tumors (acute treatment, chronic daily injections, escalating doses of morphine). In another set of experiments, B16F10 cells were pretreated with LPS (5 µg/ml) 24 h before injection into mice. Control group received normal saline. We measured cell proliferation, the expression level of Tlr4, Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (Nf-κb1) genes, TLR4 protein expression, and tumor volume. RESULTS: Chronic, acute, and escalating doses of morphine increased tumor. Morphine increased the expression of Tlr4 and Nf-κb1 regardless of the treatment protocol used. CONCLUSION: Morphine increases the progression of melanoma cancer and may be related to the increased expression of TLR4. Our results suggest that morphine should be used with caution in patients with melanoma.HighlightsMorphine increases the expression of TLR4 in melanoma.Morphine increases melanoma progression.These effects are mostly observed with chronic and escalating morphine administration.

Effect of serum magnesium levels on outcomes of patients hospitalized with COVID-19.

BACKGROUND:  The coronavirus disease 2019 (COVID-19) causes acute respiratory illness and multi-organ failure. The critical roles of magnesium in human health suggest that it could have an active role in the prevention and treatment of COVID-19. We measured magnesium levels in hospitalized COVID-19 patients concerning disease progression and mortality. MATERIALS AND METHODS:  This study was conducted in 2321 hospitalized COVID-19 patients. Clinical characteristics from each patient were recorded, and blood samples were collected from all patients upon their first admission to the hospital to determine serum magnesium levels. Patients were divided into two groups based on discharge or death. The effects of magnesium on death, severity, and hospitalization duration were estimated by crude and adjusted odds ratio using Stata Crop (version 12) software. RESULTS:  Mean magnesium levels in patients who died were higher than in discharged patients (2.10 vs 1.96 mg/dl, p 0.05). CONCLUSIONS: We found no relation between hypomagnesaemia on COVID-19 progression, although hypermagnesaemia could affect COVID-19 mortality (Tab. 4, Ref. 34).

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity.

The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2-ΔCt values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group (P = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

Risk and severity of SARS-CoV-2 reinfection among patients with multiple sclerosis vs. the general population: a population-based study.

BACKGROUND: We conducted this study to compare the risk of reinfection between multiple sclerosis (MS) patients and a control group without MS. METHOD: In this retrospective study, data of all SARS-CoV-2 tests (n = 793,301) and almost all MS patients (n = 10,639) in Isfahan province were collected from January 01, 2020 to August 22, 2021. Of the 2196 MS patients and 793,301 persons from the general population who had been tested at least once, 3 control for each MS patient were identified, leaving 1560 MS patients and 4680 controls without MS. We compared the risk of reinfection after 90 days of a primary infection between those with and without a previous positive COVID-19 test. RESULTS: 736 (47.2%) MS patients and 2013 (43.0%) control individuals had at least one positive test. A total of 17 (2.3%) and 22 (1.1%) possible reinfections in MS and control groups were observed. The estimated protection against reinfection in all MS patients, MS patients on rituximab, MS patients on DMTs rather than rituximab, and controls were 68.2% (46.2, 81.2%), 57.4% (- 0.1, 83.1%), 71.5% (45.5, 85.2%), and 82.1% (72.1, 88.5%), respectively. We found no statistically significant difference in estimated protection (p = 0.123) and odd of reinfection (adjusted OR: 2.01 [0.98, 4.08]) between all MS patients and control group. Two patients were hospitalized at first infection but none required hospitalization at reinfection event. CONCLUSIONS: MS patients on rituximab may be at a greater risk of reinfection. Further studies are required to assess the risk of the second reinfection among the MS population.

Clinical characteristics of COVID-19-infected cancer patients, Isfahan, Iran.

Background: Cancer patients, as a highly vulnerable population, are receiving a great deal of attention in the current crisis of coronavirus 2019 (COVID-19). To date, shreds of evidence are not sufficient to the description of COVID-19 outcomes in patients with cancer. This study was performed to evaluate the demographic and clinical characteristics and subsequent outcomes of COVID-19 in cancer patients. Materials and Methods: A hospital-based study was conducted involving 66 cancer patients with a confirmed diagnosis of COVID-19 from January 15, 2020, to December 21, 2020, in Isfahan, Iran. The clinical information was collected by interview and medical records. The statistical analyses were performed to describe categorical variables as well as mean, standard deviation, median, and the interquartile range for quantitative variables. Results: In our study, 66 cancer patients with confirmed COVID-19 (age: 17-97 years; 50% female) were included. Leukemia and bone marrow cancer with a frequency of 25.7% were the most common types of cancer among them. Cancer patients mostly complained of fever, cough and fatigue, and shortness of breath. Among 76.9% of patients discharged from the hospital with relative recovery, 23% died; the most common cause of death was acute respiratory distress syndrome. Age, gender, and type of cancer did not affect cancer mortality. COVID-19 had no potential effect to increase the risk of side effects of anticancer therapies. Conclusion: The results of our studies revealed that cancer is an important risk factor for the higher rate of mortality in patients with COVID-19. These findings could help physicians for the management, treatment, and supportive care of COVID-19 cancer patients.

Isfahan COVID cohort study: Rationale, methodology, and initial results.

Background: The Isfahan COVID Cohort (ICC) study was designed to investigate the short- and long-term consequences of patients with COVID-19 in Iran. This report presents the rationale, methodology, and initial results of ICC. Materials and Methods: ICC is a 5-year multicentric prospective cohort study that is ongoing on two groups including 5000 patients hospitalized with moderate or severe and 800 nonhospitalized patients with mild or asymptomatic COVID-19 in Isfahan. The ICC endpoints are morbidity, mortality, incident cases, or worsening of underlying noncommunicable diseases (NCDs) and their risk factors. In the current analysis, we examined the persistent symptoms and incident NCDs or risk factors in 819 previously hospitalized patients who completed 1-year follow-up. Results: The two most common symptoms were joint pain/myalgia (19.7%) and dry cough/dyspnea (18.7%). Around 60% of patients had at least one symptom which was more common among women than men and in middle aged than younger or older patients. Female (odds ratio [OR] =1.88, 95% confidence interval [CI]: 1.39-2.55) and highly-educated patients (OR = 2.18, 95% CI: 1.56-3.04) had higher risk of having any symptom in 1-year follow-up. New cases of hypertension followed by diabetes then coronary heart disease (CHD) were the most common incident NCDs. Conclusion: During 1-year follow-up after hospital discharge, about 60% of patients experienced persistent symptoms. Incident hypertension, diabetes, and CHD were the most common events seen. Close monitoring and extensive health services with integrative approaches are needed to improve the health status of these patients.

A meta-analysis of microRNA expression profiling studies in heart failure.

Heart failure (HF) is a major consequence of many cardiovascular diseases with high rate of morbidity and mortality. Early diagnosis and prevention are hampered by the lack of informative biomarkers. The aim of this study was to perform a meta-analysis of the miRNA expression profiling studies in HF to identify novel candidate biomarkers or/and therapeutic targets. A comprehensive literature search of the PubMed for miRNA expression studies related to HF was carried out. The vote counting and robust rank aggregation meta-analysis methods were used to identify significant meta-signatures of HF-miRs. The targets of HF-miRs were identified, and network construction and gene set enrichment analysis (GSEA) were performed to identify the genes and cognitive pathways most affected by the dysregulation of the miRNAs. The literature search identified forty-five miRNA expression studies related to CHF. Shared meta-signature was identified for 3 up-regulated (miR-21, miR-214, and miR-27b) and 13 down-regulated (miR-133a, miR-29a, miR-29b, miR-451, miR-185, miR-133b, miR-30e, miR-30b, miR-1, miR-150, miR-486, miR-149, and miR-16-5p) miRNAs. Network properties showed miR-29a, miR-21, miR-29b, miR-1, miR-16, miR-133a, and miR-133b have the most degree centrality. GESA identified functionally related sets of genes in signaling and community pathways in HF that are the targets of HF-miRs. The miRNA expression meta-analysis identified sixteen highly significant HF-miRs that are differentially expressed in HF. Further validation in large patient cohorts is required to confirm the significance of these miRs as HF biomarkers and therapeutic targets.

Magnesium intake and lung cancer risk: A systematic review and meta-analysis.

Magnesium may reduce the risk of lung cancer by affecting cell proliferation, inflammation and by preserving lung function; however, the results of epidemiological studies on the potential benefits of magnesium in lung pathology are inconclusive. We conducted this meta-analysis to investigate the association between magnesium intake and the risk of lung cancer. A total of 5 studies were extracted from PubMed, SCOPUS, and the Cochrane Review (to May 2018). These studies involved 58,5821 participants with 8,977 lung cancer cases. The pooled relative risk (RR) indicated a significant association between lung cancer incidence and magnesium intake (RR = 0.88, 95% CI = 0.79 to 0.98; p = 0.018). To investigate the cause of heterogeneity of these studies (I2 = 75.8%, p < 0.001), we performed a subgroup analysis which was affected by the mean dose of magnesium intake, where doses of magnesium intake lower than 300 mg/d significantly decreased lung cancer risk (RR = 0.83, 95% CI = 0.70 to 0.99; p = 0.034). Increasing magnesium intake doses to over 300 mg/d did not reduce the incidence of lung cancer (RR = 0.89, 95% CI = 0.78 to 1.01; p = 0.076). Our meta-analysis suggests that magnesium intake of less than 300 mg/d may have protective effects in lung cancer.

Challenges and opportunities of digital health in a post-COVID19 world.

Digital health as a rapidly growing medical field relies comprehensively on human health data. Conventionally, the collection of health data is mediated by officially diagnostic instruments, operated by health professionals in clinical environments and under strict regulatory conditions. Mobile health, telemedicine, and other smart devices with Internet connections are becoming the future choices for collecting patient information. Progress of technologies has facilitated smartphones, wearable devices, and miniaturized health-care devices. These devices allow the gathering of an individual's health-care information at the patient's home. The data from these devices will be huge, and by integrating such enormous data using Artificial Intelligence, more detailed phenotyping of disease and more personalized medicine will be realistic. The future of medicine will be progressively more digital, and recognizing the importance of digital technology in this field and pandemic preparedness planning has become urgent.

Psychological impact of COVID-19 on health-care workers: A multicenter cross-sectional study.

BACKGROUND: Health-care workers (HCWs) as frontline soldiers are involved in the war against COVID-19. Not only their protection from COVID-19 is important but also their mental health is a concern. This study aimed to measure the psychological distress among HCWs in the time of COVID-19 in Isfahan, Iran. MATERIALS AND METHODS: A cross-sectional study was conducted in the 2nd month of the spread of COVID-19 in Isfahan, Iran (March 16 to April 3). A total of 321 HCWs participated in an online survey and answered the General Health Questionnaire, the Insomnia Severity Index, and the Medical Outcomes Study Social Support Survey. t-test and ANOVA were used for comparing variables between groups. Multiple linear regression was used to evaluate the predictive factors of psychological distress. RESULTS: About 34% of our HCWs suffer from some levels of psychological distress. The result of multiple linear regression (R 2: 0.41) shows that the predictive variables with the highest value were insomnia, working as a medical resident, and lack of social support (standardized coefficient of beta: 0.51, 0.25, and 0.16, respectively; P < 0.05). CONCLUSION: The result of our study shows that about one-third of HCWs in COVID-19 special hospitals have some psychological problems. Being a medical resident, suffering from insomnia, and lack of social support are predictive variables.

Co-infection between the severe acute respiratory syndrome coronavirus 2 and the influenza Type B in Isfahan, Iran.

BACKGROUND: Some studies have been reported the rates of co-infection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus in the different regions. In this study, we report the co-infection rates between SARS-CoV-2 and influenza type B in Isfahan, Iran. MATERIALS AND METHODS: All patients with a definite diagnosis of coronavirus disease 2019 (COVID-19) from Isfahan COVID-19 registry (I-core) study were enrolled from February 2020. RESULTS: Of the 1639 laboratory COVID-19 confirmed in Isfahan province, only two persons were positive for Influenza B from Isfahan COVID-19 registry (I-core). Both patients were symptom-free after 3 months' follow-up. CONCLUSION: During influenza season, differentiating other causes of respiratory illness from COVID-19 is difficult, because common clinical manifestations of COVID-19 mimic those of influenza. It seems that evaluating for co-infection with different types of influenza viruses in patients with specific settings should be considered.

Apolipoprotein B gene mutation related to familial hypercholesterolemia in an Iranian population: With or without hypothyroidism.

BACKGROUND: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol (LDL-C) levels in plasma. Mutations of its related gene; apolipoprotein B (APOB) is seen in about two percent of the patient with FH. Thyroid disease is usually part of the exclusion criteria for the detection of FH which alters the lipid profile. We evaluated mutations in the APOB gene in patients with high LDL-C levels. MATERIALS AND METHODS: Patients aged between 2 and 80 years with at least one LDL-C level of more than 190 mg/dl were selected (120 patients) from Isfahan Laboratories. Blood samples were obtained from all patients. Genomic DNA was extracted. Primer sequences were designed by Oligo 7.60 to amplify the desired 844 bp region of exon 26 of the APOB gene containing R3500Q and R3500W variants associated with FH. RESULTS: Overall, two patients showed a heterozygous form of a common pathogenic variant in exon 26 named c. 10579 C > T (R3500W, cDNA.10707), and one patient was hypothyroidism. We also recognized another nonpathognomonic variant c. 10913G > A (rs1801701, cDNA.11041) in 13 patients, two of them were hypothyroidism. CONCLUSION: This study for the first time shows the coexistence of APOB mutation in hypothyroidism, which emphasis screening of patients with hypothyroid for FH detection.

Therapeutic inhibition of microRNA-21 (miR-21) using locked-nucleic acid (LNA)-anti-miR and its effects on the biological behaviors of melanoma cancer cells in preclinical studies.

BACKGROUND: Melanoma is a cancer that has a high mortality rate in the absence of targeted therapy. Conventional therapies such as surgery, chemotherapy, and radiotherapy are associated with poor prognosis. The expression of miR-21 appears to be of clinical importance, and the regulation of its expression appears to be an opportunity for treatment. METHODS: In this current study, we aimed to evaluate the effects of miR-21 inhibition in- vitro and in-vivo. In-vitro studies have investigated LNA-anti-miR-21 in mouse melanoma cells (B16F10), and in-vivo studies have proposed a model of melanoma in male C57BL/6 mice. To evaluate the anticancer effects of LNA-anti-miR-21, a QRT-PCR analysis was performed using the 2-ΔΔCT method to determine the degree of inhibition of oncomiR-21. The MTT test, propidium iodide/AnnexinV in-vitro, and tumor volume measurement using the QRT-PCR test with the 2-ΔΔCT method were used to estimate the inhibition of miR-21 and the expression of downstream genes including: SNAI1, Nestin (Nes), Oct-4, and NF-kB following miR-21 inhibition. Finally, immunohistochemistry was conducted for an in-vivo animal study. RESULTS: MiR-21 expression was inhibited by 80% after 24 h of B16F10 cell line transfection with LNA-anti-miR-21. The MTT test showed a significant reduction in the number of transfected cells with LNA-anti-miR-21. The transfected cells showed a significant increase in apoptosis in comparison with the control and scrambled LNA groups. According to our in vivo findings, anti-miR-21 could reduce tumor growth and volume in mice receiving intraperitoneal anti-miR after 9 days. The expression of the SNAI1gene was significantly reduced compared to the controls. Immunohistochemical analysis showed no change in CD133 and NF-kB markers. CONCLUSION: Our findings suggest LNA-anti-miR-21 can be potentially used as an anticancer agent for the treatment of melanoma.

Isfahan and Covid-19: Deep spatiotemporal representation.

The coronavirus COVID-19 is affecting 213 countries and territories around the world. Iran was one of the first affected countries by this virus. Isfahan, as the third most populated province of Iran, experienced a noticeable epidemic. The prediction of epidemic size, peak value, and peak time can help policymakers in correct decisions. In this study, deep learning is selected as a powerful tool for forecasting this epidemic in Isfahan. A combination of effective Social Determinant of Health (SDH) and the occurrences of COVID-19 data are used as spatiotemporal input by using time-series information from different locations. Different models are utilized, and the best performance is found to be for a tailored type of long short-term memory (LSTM). This new method incorporates the mutual effect of all classes (confirmed/ death / recovered) in the prediction process. The future trajectory of the outbreak in Isfahan is forecasted with the proposed model. The paper demonstrates the positive effect of adding SDHs in pandemic prediction. Furthermore, the effectiveness of different SDHs is discussed, and the most effective terms are introduced. The method expresses high ability in both short- and long- term forecasting of the outbreak. The model proves that in predicting one class (like the number of confirmed cases), the effect of other accompanying numbers (like death and recovered cases) cannot be ignored. In conclusion, the superiorities of this model (particularity the long term predication ability) turn it into a reliable tool for helping the health decision-makers.

In vitro versus in vivo models of kidney fibrosis: Time-course experimental design is crucial to avoid misinterpretations of gene expression data.

BACKGROUND: In vitro models are common tools in nephrology research. However, their validity has rarely been scrutinized. MATERIALS AND METHODS: Considering the critical role of transforming growth factor (TGF)-ß and hypoxia pathways in kidney fibrosis, kidney-derived cells were exposed to TGF-ß and/or hypoxic conditions and the expression levels of some genes related to these two signaling pathways were quantified in a time-course manner. Furthermore, a unilateral ureteral obstruction mouse model was generated, and the expressions of the same genes were assessed. RESULTS: In all in vitro experimental groups, the expression of the genes was noisy with no consistent pattern. However, in the animal model, TGF-ß pathway-related genes demonstrated considerable overexpression in the ureteral obstruction group compared with the sham controls. Interestingly, hypoxia pathway genes had prominent fluctuations with very similar patterns in both animal groups, suggesting a periodical pattern not affected by the intervention. CONCLUSION: The findings of this study suggest that in vitro findings should be interpreted cautiously and if possible are substituted or supported by animal models that are more consistent and reliable. Furthermore, we underscore the importance of time-course evaluation of both case and control groups in gene expression studies to avoid misconceptions caused by gene expression noise or intrinsic rhythms.

Isfahan COvid-19 REgistry (I-CORE): Design and methodology.

Health authorities usually exploit after-action reports to collect data on their experience in responding to public health emergencies. To develop an effective approach to manage and learning from health emergencies, we have launched Isfahan COvid-19 REgistry for data collection during routine clinical care as a first "critical incident registry" in Iran. Registries can be employed to explain the natural history of the disease, learn about a particular disease in terms of patient outcomes, the cost-effectiveness of clinical management, monitoring the quality of health-care service, and developing research hypotheses.

Current status of COVID-19 pandemic; characteristics, diagnosis, prevention, and treatment.

Humans have always been encountered to big infectious diseases outbreak throughout the history. In December 2019, novel coronavirus (COVID-19) was first noticed as an agent causing insidious pneumonia in Wuhan, China. COVID-19 was spread rapidly from Wuhan to the rest of the world. Until late June 2020, it infected more than 10,000,000 people and caused more than 500,000 deaths in almost all of countries in the world, creating a global crisis worse than all previous epidemics and pandemics. In the current review, we gathered and summarized the results of various studies on characteristics, diagnosis, treatment, and prevention of this pandemic crisis.

Maprotiline inhibits COX2 and iNOS gene expression in lipopolysaccharide-stimulated U937 macrophages and carrageenan-induced paw edema in rats.

Maprotiline, a tetracyclic antidepressant, is used for the management of mental disorders and various types of chronic pain. In our previous work, we found the inhibitory effect of maprotiline on inflammatory mediator's expression like tumor necrosis factor α (TNF-α and interleukin 1ß (IL-1ß. As part of that study, we sought to evaluate the effect of maprotiline on the expression of some inflammatory mediators such as cyclooxygenases 2 (COX2) and inducible nitric oxide synthase (iNOS). For this reason we used an in vitro model system of lipopolysaccharide (LPS)-stimulated human U937 macrophages and also an in vivo model of carrageenan-induced paw edema in rats. We measured the expression of these genes by quantitative RT-real time PCR. The expression of COX2 and iNOS significantly decreased by maprotiline in U937 macrophages and carrageenan-induced paw inflammation in rats. Our finding also confirmed that intraperitoneal (i.p.) injection of maprotiline inhibited carrageenan-induced paw edema. Moreover, maprotiline significantly decreased the migration of polymorphonuclear (PMN) leukocytes to the site of inflammation. The results of the present study provide further evidence for the anti-inflammatory effect of maprotiline. This effect appears to be mediated by down regulation of inflammatory genes. Further studies are needed to evaluate the complex cellular and molecular mechanisms of maprotiline.