Mutations in SARS-CoV-2; Consequences in structure, function, and pathogenicity of the virus.

The third pandemic of coronavirus infection, called COVID-19 disease, began recently in China. The newly discovered coronavirus, entitled SARS-CoV-2, is the seventh member of the human coronaviruses. The main pathogenesis of SARS-CoV-2 infection is severe pneumonia, RNAaemia, accompanied by glass turbidity, and acute cardiac injury. It possesses a single-stranded positive-sense RNA genome which is 60-140 nm in diameter, and has a size of 26-32 kbp. Viral pathogenesis is accomplished with spike glycoprotein through the employment of a membrane-bound aminopeptidase, called the ACE2, as its primary cell receptor. It has been confirmed that various factors such as different national rules for quarantine and various races or genetic backgrounds might influence the mortality and infection rate of COVID-19 in the geographic areas. In addition to various known and unknown factors and host genetic susceptibility, mutations and genetic variabilities of the virus itself have a critical impact on variable clinical features of COVID-19. Although the SARS-CoV-2 genome is more stable than SARS-CoV or MERS-CoV, it has a relatively high dynamic mutation rate with respect to other RNA viruses. It's noteworthy that, some mutations can be founder mutations and show specific geographic patterns. Undoubtedly, these mutations can drive viral genetic variability, and because of genotype-phenotype correlation, resulting in a virus with more/lower/no decrease in natural pathogenic fitness or on the other scenario, facilitating their rapid antigenic shifting to escape the host immunity and also inventing a drug resistance virus, so converting it to a more infectious or deadly virus. Overall, the detection of all mutations in SARS-CoV-2 and their relations with pathological changes is nearly impossible, mostly due to asymptomatic subjects. In this review paper, the reported mutations of the SARS-CoV-2 and related variations in virus structure and pathogenicity in different geographic areas and genotypes are widely investigated. Many studies need to be repeated in other regions/locations for other people to confirm the findings. Such studies could benefit patient-specific therapy, according to genotyping patterns of SARS-CoV-2 distribution.

Using content-based image retrieval of dermoscopic images for interpretation and education: A pilot study.

BACKGROUND: Dermoscopic content-based image retrieval (CBIR) systems provide a set of visually similar dermoscopic (magnified and illuminated) skin images with a pathology-confirmed diagnosis for a given dermoscopic query image of a skin lesion. Although recent advances in machine learning have spurred novel CBIR algorithms, we have few insights into how end users interact with CBIRs and to what extent CBIRs can be useful for education and image interpretation. MATERIALS AND METHODS: We developed an interactive user interface for a CBIR system with dermoscopic images as a decision support tool and investigated users' interactions and decisions with the system. We performed a pilot experiment with 14 non-medically trained users for a given set of annotated dermoscopic images. RESULTS: Our pilot showed that the number of correct classifications and users' confidence levels significantly increased with the CBIR interface compared with a non-CBIR interface, although the timing also increased significantly. The users found the CBIR interface of high educational value, engaging and easy to use. CONCLUSION: Overall, users became more accurate, found the CBIR approach provided a useful decision aid, and had educational value for learning about skin conditions.

The Vitamins Involved in One-Carbon Metabolisms are Associated with Reduced Risk of Breast Cancer in Overall and Subtypes.

Background: Some micronutrients like folate, vitamin B12, B6, and B2 are the source of coenzymes, which participate in one-carbon metabolism. Any disruption in this metabolism can interfere with DNA replication, repair and regulation of gene expression and ultimately promote the likelihood of carcinogenesis. This study aimed at investigating the relationship between the intakes of micronutrients involved in one-carbon metabolism with breast cancer (BrCa) and its subtype's odds. Methods: Nutrients' intake from diet and supplements were collected through interviewing 151 cases and 154 controls by a 168-item semiquantitative food frequency questionnaire. Logistic regression was used to determine the relationship between dietary and/or total intake of studied nutrients and odds of BrCa and its subtypes. Results: After adjusting the effects of confounding variables in the models, the odds of BrCa was significantly lower in the highest intake quartile compared with the lowest quartile for total intake of vitamin B2 (OR = 0.17, 95% CI, 0.07-0.39; Ptrend < 0.001), vitamin B6 (OR = 0.11, 95% CI, 0.05-0.27; Ptrend < 0.001), vitamin B12 (OR = 0.20, 95% CI, 0.09-0.43; Ptrend < 0.001) and folate (OR = 0.09, 95% CI, 0.04-0.21; Ptrend < 0.001). Also, those with the highest quartile of vitamin B6, B12, B2 and folate intake compared with the lowest quartile were less likely to develop estrogen receptor (ER)+ and progesterone receptor (PR)+ subtypes, ER- status, PR- and human epidermal growth factor receptor 2 (HER2)+ subtypes and HER2- status. Conclusion: High intakes of vitamins B2, B6 and folate are associated with reduced odds of BrCa in overall and all ER, PR and HER2 subtypes. Also, high intakes of vitamin B12 reduced the odds of all subtypes of BrCa except ER- subtype.

The Association between Dietary Patterns and Breast Cancer Pathobiological Factors Progesterone Receptor (PR) and Estrogen Receptors (ER): New Findings from Iranian Case-Control Study.

Background: Breast cancer (BrCa) is the most frequently diagnosed cancer among females and second cancer after lung cancer in many societies. Ignoring the phenotypes of the BrCa can affect the interpretation of the association between diet and BrCa. The aim of this study was to determine the association between dietary patterns and estrogen receptor (ER), and progesterone receptor (PR) status in women with BrCa. Methods: This study includes 150 cases of BrCa. Controls were 150 healthy adults, frequency matching based on age. The individual information, food frequency questionnaire, and physical activity were completed while interviews. Information about the pathologic factors obtained from patients' files. Factor analysis method used to determine the dietary patterns; logistic regression used to measure the odds ratios. Results: Getting upper median intake of unhealthy diet had a strong association with BrCa-positive ER and positive PR (OR: 4.98, 95% CI: 2.65-9.34 and OR: 4.99, 95% CI: 2.56-9.75, respectively) compared to under median intake of unhealthy diet. In addition, the protective effect of the healthy diet was stronger on BrCa-negative ER, negative PR (OR: 0.11, 95% CI: 0.04-0.34 and OR: 0.10, 95% CI: 0.03-0.25, respectively). Conclusion: The protective effect of a healthy dietary pattern was stronger on BrCa negative ER and negative PR. The unhealthy dietary pattern had a strong association with BrCa positive ER and positive PR.

The association between index of nutritional quality and ulcerative colitis: A case-control study.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Recent studies have shown that dietary factors play an important role in the development of UC. Index of Nutritional Quality (INQ) is a suitable method that analyzes quantitatively and qualitatively single foods, meals, and diets. The aim of this study was to determine the association between INQ and UC. MATERIALS AND METHODS: Overall, 62 newly diagnosed cases with UC and 124 healthy age- and sex-matched controls were studied in a referral hospital in Tabriz, Iran. INQ scores were calculated based on information on the usual diet that was measured by a valid and reliable Food Frequency Questionnaire consisting of 168 food items. Logistic regression analysis adjusting for age, gender, body mass index, education, smoking, Helicobacter pylori, family history of UC, appendectomy, alcohol, and total energy intake was used to estimate multivariable odds ratios (ORs). RESULTS: After controlling for several covariates, we found inverse associations between UC risk and INQs of Vitamin C (OR = 0.34 [0.16-0.73]) and folate (OR = 0.11 [0.01-0.99]). In crude model of analysis, cases had a higher intake of total energy, protein, carbohydrate, total fat, saturated fatty acid, monounsaturated fatty acid, polyunsaturated fatty acid, niacin, Vitamin B6, Vitamin B12, magnesium, zinc, copper, selenium, and iron compared to controls, whereas controls had higher intakes of Vitamin C, Vitamin D, folate, and biotin compared to cases. CONCLUSION: Our results indicate that enough consumption of Vitamin C and folate was associated with lower risk of UC.

Functional synergy of anti-mir221 and nanohydroxyapatite scaffold in bone tissue engineering of rat skull.

An appropriate cell source, effective cell modification, and proper supportive matrices are the main bases of tissue engineering. The effectiveness of anti-mir221 or hydroxyapatite (HA) in improving the osteogenic differentiation of mesenchymal stem cells (MSCs) has been reported previously. Herein, simultaneous application of these osteogenic inducers was investigated in vivo. The Poly-caprolactone (PCL)/HA nanofibers were characterized using contact angle measurement, tensile test, Fourier transform infrared spectroscopy, and electron microscopy. Rat MSCs were isolated, characterized and transfected with anti-mir221. The rats were divided into 4 groups and an 8 mm defect were created in the mid-calvaria of each rat by trephine bur. Group 1 received (PCL)/HA nanofibers, group 2 received (PCL)/HA nanofibers plus autologous MSCs, group 3 received (PCL)/HA nanofibers plus MSCs transfected with anti-mir221, and group 4 rats were left empty as an additional control group. Histomorphometric and radiomorphometric evaluation after 4 and 8 weeks revealed more new bone formation in the cell-treated groups compared to the scaffold alone group. There was evidence for a combination of increased osteoclasts and osteoblast vascular lake containing red blood cells in the anti-mir221 transfected group. New bone penetration into the scaffolds empirically demonstrated the capability of this combination for efficient osteointegration. Altogether, the co-application of HA and anti-mir221 transfected cells can enhance bone healing of the rat skull.

Transcriptomic and in vivo approaches introduced human iPSC-derived microvesicles for skin rejuvenation.

The skin undergoes the formation of fine lines and wrinkles through the aging process; also, burns, trauma, and other similar circumstances give rise to various forms of skin ulcers. Induced pluripotent stem cells (iPSCs) have become promising candidates for skin healing and rejuvenation due to not stimulating inflammatory responses, low probability of immune rejection, high metabolic activity, good large-scale production capacity and potentials for personalized medicine. iPSCs can secrete microvesicles (MVs) containing RNA and proteins responsible for the normal repairing process of the skin. This study aimed to evaluate the possibility, safety and effectiveness of applying iPSCs-derived MVs for skin tissue engineering and rejuvenation applications. The possibility was assessed using the evaluation of the mRNA content of iPSC-derived MVs and the behavior of fibroblasts after MV treatment. Investigating the effect of microvesicle on stemness potential of mesenchymal stem cells was performed for safety concerns. In vivo evaluation of MVs was done in order to investigate related immune response, re-epithelialization and blood vessel formation to measure effectiveness. Shedding MVs were round in shape distributed in the range from 100 to 1000 nm in diameter and positive for AQP3, COL2A, FGF2, ITGB, and SEPTIN4 mRNAs. After treating dermal fibroblasts with iPSC-derived MVs, the expressions of collagens Iα1 and III transcripts (as the main fibrous extracellular matrix (ECM) proteins) were upregulated. Meanwhile, the survival and proliferation of MV treated fibroblasts did not change significantly. Evaluation of stemness markers in MV treated MSCs showed negligible alteration. In line with in vitro results, histomorphometry and histopathology findings also confirmed the helpful effect of MVs in skin regeneration in the rat burn wound models. Conducting more investigations on hiPSCs-derived MVs may lead to produce more efficient and safer biopharmaceutics for skin regeneration in the pharmaceutical market.

The association between the Index of Nutritional Quality (INQ) and breast cancer and the evaluation of nutrient intake of breast cancer patients: A case-control study.

OBJECTIVE: Breast cancer (BrCa) is the most frequently diagnosed cancer among females and second cancer after lung cancer in many societies. In Iran, the risk for BrCa is 1 in 35 and each year, 8000 new patients have been diagnosed with BrCa. Studies have shown that dietary components are implicated in the etiology of BrCa. The Index of Nutritional Quality (INQ) is a method of quantitative and qualitative analysis of single foods, meals, and diets. The aim of this study was to determine the usefulness of INQs in predicting BrCa risk. METHODS: Our case-control study was conducted from March 2015 to February 2016. The study included 145 cases and 148 controls who attended the Shahid Beheshti University of Medical Sciences Cancer Research Center. INQ scores were computed based on dietary intake using a validated 168-item food frequency questionnaire. Logistic regression models were used to estimate multivariable odds ratios adjusted body mass index, education, employment, marital status, menarche age, childbirth number, smoking, menopause status, and physical activity. RESULTS: Vitamins A, C, B1, B2, and B12 and selenium INQs as a continuous variable in relation to risk for BrCa showed a significant association after multivariate adjustment (odds ratio [OR]vitA, 0.41 [0.27-0.64]; ORvitC, 0.30 [0.20-0.47]; ORvitB1, 0.08 [0.04-0.17]; ORvitB2, 0.19 [0.11-0.34]; ORvitB12, 0.44 [0.31-0.61]; and ORselenium, 0.42 [0.26-0.67]). CONCLUSION: Women who consumed a healthier diet including vitamin A, ß-carotene, vitamin C, and folate and low-fat milk were at decreased risk for developing BrCa compared with those whose diet included more high fat and lamb meat.

Association between Dietary Inflammatory Index (DII) and Risk of Breast Cancer: a Case-Control Study

Background: Breast cancer (BrCa) is the most common cancer among women worldwide and is the second leading cause of cancer-related death in women, in developed countries. This cancer is among the top five most common cancers in Iran. Studies have shown that dietary components are implicated in the etiology of BrCa. The existence of molecular connections between inflammation and BrCa has been demonstrated via different bimolecular events. Methods: We examined the ability of the dietary inflammatory index (DIITM) to predict the risk of BrCa. This included 145 cases and 148 controls, who attended the specialized centers. DII scores were computed based on dietary intake assessed using a 168-item FFQ. Logistic regression models were used to estimate multivariable ORs. Results: Modeling DII as a continuous variable in relation to risk of BrCa showed a positive association after adjustment for age and energy (OR=1.76; 95% CI=1.43-2.18); and were nearly identical in the multivariable analyses (OR=1.80; 95% CI=1.42-2.28). DII as tertiles, and adjusting for age and energy, subjects in tertile 3 had an OR of 6.94 (95% CI= 3.26-14.79; P-trend ≤0.0001) in comparison to subjects in tertile 1. After multivariable adjustment, results were essentially identical as in the model adjusting for age and energy (OR tertile 3vs1=7.24; 95% CI=3.14-16.68; P-trend ≤0.001). Sub group analyses revealed similar positive associations with HER 2 receptor +ve, progesterone receptor +ve, estrogen receptor +ve and lymph node invasive cases. Conclusion: Subjects who consumed a more pro-inflammatory diet were at increased risk of BrCa compared to those who consumed a more anti-inflammatory diet.