Recently, the SARS-CoV-2 induced disease COVID-19 has spread all over the world. Nearly 20% of the patients have severe or critical conditions. SARS-CoV-2 exploits ACE2 for host cell entry. ACE2 plays an essential role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and fluid balance. ACE2 also protects organs from inflammatory injuries and regulates intestinal functions. ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs. SARS-CoV-2 infection-caused ACE2 dysfunction worsens COVID-19 and could initiate multi-organ failure. Here, we will explain the role of ACE2 in the pathogenesis of severe and critical conditions of COVID-19 and discuss auspicious strategies for controlling the disease.Viruses 2020, 12, 491 2 of 10 Profile of ACE2Human angiotensin-converting enzyme-related carboxypeptidase ACE2 is encoded by the ACE2 gene which maps to chromosome Xp22 [6]. ACE2 is a type I transmembrane protein, comprised of an extracellular heavily N-glycosylated N-terminal domain containing the carboxypeptidase site and a short intracellular C-terminal cytoplasmic tail [7]. The N-terminal peptidase domain is also the SARS-CoV binding site [8]. There are two forms of ACE2 protein: cellular (membrane-bound) form and circulating (soluble) form. Cellular ACE2 protein is the full-length protein which is expressed abundantly in pneumocytes and enterocytes of the small intestine [9]. ACE2 is also expressed in vascular endothelial cells of the heart, the kidneys, and other organs, such as the brain. However, ACE2 is absent in the spleen, thymus, lymph nodes, bone marrow, and cells of the immune system (including B and T lymphocytes, and macrophages) [10,11].Circulating ACE2 (with the N-terminal peptidase domain) is cleaved from the full-length ACE2 on the cell membrane by the metalloprotease ADAM17 and then released into the extracellular environment [7]. The type II transmembrane serine protease, TMPRSS2 was found to compete with ADAM17 for ACE2 shedding but cleaves ACE2 differently. Both ADAM17 and TMPRSS2 remove a short C-terminal fragment from ACE2. Arginine and lysine residues within amino acids 652 to 659 are critical for ADAM17 shedding, whereas arginine and lysine residues within amino acids 697 to 716 are essential for TMPRSS2 shedding. Only cleavage by TMPRSS2 results in augmented SARS-CoV cell entry [12][13][14][15]. There are two ways for SARS-CoV to enter the target cell: endocytosis, and fusion of the viral membrane with a membrane of the target cell, which is 100 times more efficient than endocytosis for viral replication [16]. With the help of TMPRSS2, ADAM17-regulated ectodomain shedding of ACE2 could induce SARS-CoV cell entry through endocytosis [7,12]; however, ADAM17 activity is not required for SARS-CoV cell entry through fusion [12]. As the N-terminal domain is the coronavirus binding site, circulating ACE2 also binds to the virus. Iwata-Yoshikawa et al. infected both ...

Background Mfa1 fimbriae of the periodontal pathogen Porphyromonas gingivalis are responsible for biofilm formation and comprise five proteins: Mfa1–5. Two major genotypes, mfa1 70 and mfa1 53 , encode major fimbrillin. The mfa1 70 genotype is further divided into the mfa1 70A and mfa1 70B subtypes. The properties of the novel mfa1 70B remain unclear. Methods Fimbriae were purified from P. gingivalis strains JI-1 (mfa1 70A ), 1439 (mfa1 70B ), and Ando (mfa1 53 ), and their components and their structures were analyzed. Protein expression and variability in the antigenic specificity of fimbrillins were compared using Coomassie staining and western blotting using polyclonal antibodies against Mfa1 70A , Mfa1 70B , and Mfa1 53 proteins. Cell surface expression levels of fimbriae were analyzed by filtration enzyme-linked immunosorbent assays. Results The composition and structures of the purified Mfa1 fimbriae of 1439 was similar to that of JI-1. However, each Mfa1 protein of differential subtype/genotype was specifically detected by western blotting. Mfa1 70B fimbriae were expressed in several strains such as 1439, JKG9, B42, 1436, and Kyudai-3. Differential protein expression and antigenic heterogeneities were detected in Mfa2–5 between strains. Conclusion Mfa1 fimbriae from the mfa170A and mfa170B genotypes indicated an antigenic difference suggesting the mfa170B, is to be utilized for the novel classification of P. gingivalis.

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Determining how to apply hydrogen as a therapeutic/preventive antioxidant for oxidative-stress-related diseases practically in daily life has not been studied. The effects of bathtubs and buckets filled with hydrogen water (41 °C, >10 min bathing) were investigated on six subjects, without a medical prescription, suffering from skin roughness on the foot, hand, finger, or elbow. They were also treated with an electrolyzer composed of a lattice-shaped, microscopically flat, platinum-plated three-layer electrode, except for one subject who was treated with a micro-porous emittance terminal hydrogen-jetting apparatus, resulting in improvements in both cases. For another subject with similar skin roughness on both hands, immersing the right hand in an electrolytically generated hydrogen water bucket showed more marked improvement than immersing the left hand in a bucket with normal water. The nano-bubbles (average, mode, and median sizes of 157 nm, 136 nm, and 94 nm, respectively) increased 3.79 fold to 2.20 × 108/mL after 30 min electrolysis with 2 L of tap water and were boiling (98 °C, 2 min)-resistant, with heat stability in nano-bubbles as small as 69–101 nm, as evaluated by laser-beam-based Brownian movement trailing Nano-Sight analysis. The marked increase in nano-bubbles caused by electrolysis correlated with an increase in dissolved hydrogen (<15 μg/L to 527 μg/L) but not a decrease in dissolved oxygen (9.45 mg/L to 6.94 mg/L). Thus, the present study proposed the novelty of hydrogen regarding its contribution to health from the perspective that hydrogen-nano-bubble-rich water in a foot bucket, which was additively used together with a conventional bathtub and can be frequently used in daily life, improved diverse types of skin roughness.