The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.

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BackgroundThe aim of the present study was to investigate the association between matrix metalloproteinase-9 (MMP-9) expression with BRAF V600E mutation and clinicopathological features, in Iranian papillary thyroid cancer (PTC) patients.MethodsIn total, 90 participants including 60 PTC patients (15 males and 45 females) and 30 individuals with benign multinodular goiter (MNG) (5 males and 25 females) which were confirmed by surgical pathology, were investigated. MMP-9 was evaluated at both mRNA and protein levels, using SYBR-Green Real-Time PCR and enzyme-linked immune sorbent assay (ELISA), respectively. BRAF V600E mutation was detected by sequencing.ResultsMean age of PTC and MNG patients was 37.6 ± 12.6 and 48.1 ± 13.3 years, respectively (P = 0.001). BRAF V600E mutation was found in 24 of the 60 (40%) PTC cases, with mean tumor size of 1.59 ± 1.20 cm. MMP-9 mRNA levels were elevated in tumoral compared to the adjacent non-tumoral tissues (P = 0.039); moreover, this rise was also observed in PTC patients compared to MNG patients (P = 0.001). The mRNA levels of MMP-9 increased in patients aged≥45 years (P = 0.015), those with lymphovascular invasion (P = 0.003), and higher tumor stages (III and IV) (P = 0.011). The protein level of MMP-9 increased in tumoral compared to adjacent non-tumoral tissues (P < 0.001); this increase was also found in PTC patients compared to MNG participants (P = 0.004). MMP-9 protein level was higher in patients aged≥45 years (P = 0.001), those with lymphovascular invasion (P = 0.036) and higher TNM stages (III and IV) (P = 0.001). Area under the ROC curve (AUC) was 0.70 (95%CI: 0.57–0.83, P = 0.003), with 91.4% sensitivity and 51.9% specificity at the cutoff value of 0.50.ConclusionThe mRNA and protein levels of MMP-9 had no association with BRAF V600E mutation in Iranian PTC patients. These levels were associated with age, TNM stages, and lymphovascular invasion, being defined as malignant factors. Thus, elevated levels of MMP-9 in PTC patients compared to MNG participants illustrated that it can be used as a potential biomarker to differentiate PTC patients from those with MNG.

IntroductionOrthodontic treatment has many advantages such as esthetic improvement, function and self-estimation enhancement. 1Orthodontic appliances make oral hygiene more difficult and increase plaque accumulation. After installing fix orthodontic appliances in the mouth, Streptococcus mutans and Lactobacillus species increase. These bacteria release organic acid that causes dissolution of ions of calcium and phosphate from the enamel surface, which can lead to white spot lesions and this process can occur in 4 weeks.2 White spot lesions are defined as enamel decalcification due to subsurface mineral loss; while 10 to 30 µm of enamel surface remains intact. 3,4 The opaque appearance of the lesion is due to variations in light scattering of decalcified porous enamel. Years after orthodontic treatment, white spot lesions may develop into esthetic problems, because demineralized enamel may absorb colors from drinks and foods. 5,6 When the lesion progresses, remineralization gets tough and sometimes impossible 5,7 ; hence, it is important to prevent the formation of these lesions. Øgaard reported that 5 years after treatment, white spot lesions were more Orthodontic treatment has many advantages such as esthetic improvement and self-esteem enhancement; yet it has some disadvantages such as increasing the risk of formation of white spot lesions, because it makes oral hygiene more difficult. It is rational to implement procedures to prevent these lesions. The present study was aimed to assess the effect of CO 2 laser and fluoride varnish on the surface of the enamel surface microhardness around the orthodontic braces. Methods: Eighty extracted premolar teeth were selected, scaled, polished with nonfluoridated pumic and metal brackets were bonded to them. Then, they were randomly allocated to 5 groups: control (neither fluoride nor laser is used on enamel surfaces), fluoride (4 minutes fluoride varnish treatment of the enamel surfaces), CO 2 laser (10.6 µm CO 2 laser irradiation of the teeth), laserfluoride (fluoride application after laser irradiation) and fluoride-laser (fluoride was applied and then teeth were irradiated with laser). After surface treatment around brackets on enamel, the samples were stored in 0.1% thymol for less than 5 days and then they were exposed to a 10-day microbiological caries model. Microhardness values of enamel were evaluated with Vickers test. One sample of each group (5 teeth from 80 samples) was prepared for SEM (scanning electron microscopy) and the data from 75 remaining teeth were analyzed with analysis of variance (ANOVA) and chi-square tests (α = 0.05). Results:Microhardness mean values from high to low were as follow: fluoride-laser, laser-fluoride, laser, fluoride and control. Microhardness in fluoride-laser group was significantly higher compared with that of the control group. Distribution adhesive remnant index (ARI) scores were significantly different between groups and most of bond failures occurred at the enamel-adhesive interface in groups 2 to 5 and at the adhesive-b...

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