Development of a Cavitation Generator Mimicking Pistol Shrimp.

Pistol shrimp generate cavitation bubbles. Cavitation impacts due to bubble collapses are harmful phenomena, as they cause severe damage to hydraulic machinery such as pumps and valves. However, cavitation impacts can be utilized for mechanical surface treatment to improve the fatigue strength of metallic materials, which is called "cavitation peening". Through conventional cavitation peening, cavitation is generated by a submerged water jet, i.e., a cavitating jet or a pulsed laser. The fatigue strength of magnesium alloy when treated by the pulsed laser is larger than that of the jet. In order to drastically increase the processing efficiency of cavitation peening, the mechanism of pistol shrimp (specifically when used to create a cavitation bubble), i.e., Alpheus randalli, was quantitatively investigated. It was found that a pulsed water jet generates a cavitation bubble when a shrimp snaps its claws. Furthermore, two types of cavitation generators were developed, namely, one that uses a pulsed laser and one that uses a piezo actuator, and this was achieved by mimicking a pistol shrimp. The generation of cavitation bubbles was demonstrated by using both types of cavitation generators: the pulsed laser and the piezo actuator.

A Tricyclic Aromatic Polyketide Isolated from the Marine-Derived Fungus Curvularia aeria.

A novel tricyclic polyketide, curvulanone (1), was isolated from the marine-derived fungus Curvularia aeria. The structure of 1 was determined by NMR and single-crystal X-ray crystallography. 1 had a cyclopentabenzopyranone with 3-acetic acid structure that is rarely found in natural compounds. Monoamine oxidase and sirtuin 1 inhibitory test was exhibited and 1 showed their inhibitory activity.

2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral ribonucleoside analogue that exhibited antiviral activity against several positive-sense single-stranded RNA (ssRNA+) viruses, such as DENV, SARS-CoV-2, and its variants of concern, including the currently circulating Omicron subvariants. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with DENV2 or SARS-CoV-2 in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against DENV and SARS-CoV-2 but other ssRNA+ viruses.

Effect of Human Cytochrome P450 2D6 Polymorphism on Progesterone Hydroxylation.

BACKGROUND AND OBJECTIVES: Herein, hydroxylation activities at the 6ß-position and 21-position of progesterone mediated by human cytochrome P450 (CYP) 2D6 and its variants and the effects of psychotropic drugs on these hydroxylation activities were compared to clarify whether CYP2D6 polymorphisms and psychotropic drugs impact neurosteroid levels in the brain. METHODS: Progesterone was incubated with CYP2D6.1, CYP2D6.2 (Arg296Cys, Ser486Thr), CYP2D6.10 (Pro34Ser, Ser486Thr), and CYP2D6.39 (Ser486Thr) in the absence or presence of typical psychotropic drugs (fluvoxamine, fluoxetine, paroxetine, fluphenazine, and milnacipran) and endogenous steroids (testosterone and cortisol). Then, 6ß- and 21-hydroxyprogesterone levels were determined by high-performance liquid chromatography. RESULTS: Although the Michaelis-Menten constants (Km) for progesterone 6ß- and 21-hydroxylation reactions mediated by the different CYP2D6 variants were similar, the maximal velocity (Vmax) values of the reactions mediated by CYP2D6.1 and CYP2D6.2 were the highest, followed by those mediated by CYP2D6.39 and CYP2D6.10. Thus, the of progesterone 6ß- and/or 21-hydroxylation reactions mediated by CYP2D6.1 and CYP2D6.2 showed the highest Vmax/Km values, followed by the reactions mediated by CYP2D6.39. All investigated compounds inhibited progesterone 21-hydroxylation mediated by CYP2D6 variants at high concentrations. Interestingly, at low concentrations, fluoxetine increased progesterone 21-hydroxylation mediated by CYP2D6.1, but not that mediated by CYP2D6.2 or CYP2D6.10. In addition, the Km value for CYP2D6.2 was elevated in the presence of fluoxetine, whereas the value for CYP2D6.1 was unaltered; however, Vmax values of both CYP2D6.1 and CYP2D6.2 were increased. Paroxetine competitively inhibited CYP2D6.1- and CYP2D6.2-mediated progesterone 21-hydroxylation. CONCLUSIONS: These results suggest that CYP2D6 polymorphism can affect the stimulation/inhibition of progesterone 21-hydroxylation.

Structure of junctional epithelium is maintained by cell populations supplied from multiple stem cells.

The junctional epithelium (JE) is an epithelial component that attaches directly to the tooth surface and performs the unique function of protecting against bacterial infections; its destruction causes inflammation of the periodontal tissue and loss of alveolar bone. A recent study that used the single-color lineage tracing method reported that JE is maintained by its stem cells. However, the process by which individual stem cells form the entire JE around a whole tooth remains unclear. Using a 4-color lineage tracing method, we performed a detailed examination of the dynamics of individual stem cells that constitute the entire JE. The multicolor lineage tracing method showed that single-color areas, which were derived from each cell color, replaced all the constituent JE cells 168 d after the administration of tamoxifen. The horizontal section of the first molar showed that the single-color areas in the JE expanded widely. We detected putative stem cells at the external basal layer farthest from the enamel. In this study, JE cells that were supplied from different stem cells were visualized as individual monochromatic regions, and the JE around the first molar was maintained by several JE-specific stem cells. These findings indicated that the JE consisted of several cell populations that were supplied from their multiple stem cells and could help to explore the mechanisms involved in periodontal tissue homeostasis.

Antibacterial Activity of the Mixed Systems Containing 1,2-Dodecanediol against Staphylococcus aureus and Staphylococcus epidermidis.

1,2-Alkanediols are characteristic cosmetic ingredients because these moisturizers exhibit the antibacterial activity against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). However, the antimicrobial behavior in mixed systems containing several active ingredients is unclear because previous reports focus on an antibacterial system containing only 1,2-alkanediol. In this study, the minimal inhibitory concentration (MIC) and the fractional inhibitory concentration (FIC) were evaluated for 1,2-dodecanediol/lactic acid, 1,2-dodecanediol/myristic acid, 1,2-dodecanediol/methylparaben, and 1,2-dodecanediol/isopropyl methylphenol mixed systems to show the effect of the addition of other antimicrobial components to 1,2-dodecanediol. The antibacterial property of 1,2-dodecanediol/lactic acid mixed system was almost similar compared to 1,2-dodecanediol monomeric system. On the other hand, the antimicrobial activity of 1,2-dodecanediol against S. epidermidis was inhibited in the 1,2-dodecanediol/myristic acid mixed system. Because the selective antimicrobial activity of myristic acid against S. aureus was demonstrated in the mixed system. The present findings are useful for designing formulations of cosmetics and body cleansers containing 1,2-dodecanediol.

Cancer chemoprevention by citrus pulp and juices containing high amounts of ß-cryptoxanthin and hesperidin.

ß-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP) and citrus juices (MJ2 and MJ5) from a satsuma mandarin (Citrus unshiu Mar.) juice (MJ). They contain high amounts of ß-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs.

Oral carcinogenesis and oral cancer chemoprevention: a review.

Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

Biomarkers for colorectal cancer.

Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers.

Colorectal cancer chemoprevention by 2 beta-cyclodextrin inclusion compounds of auraptene and 4'-geranyloxyferulic acid.

The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with beta-cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Male CD-1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/beta-CD or AUR/beta-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/beta-CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 +/- 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/beta-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/beta-CD and AUR/beta-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-alpha, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1beta, which were induced in the adenocarcinomas. Our findings indicate that GOFA/beta-CD and AUR/beta-CD, especially GOFA/beta-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.

Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats.

The inhibitory effects of exogenous melatonin (MEL) on colon oncogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) rat model. Male F344 rats initiated with a single intraperitoneal injection of AOM (20mg/kg bw) were promoted by 1% (w/v) DSS in drinking water for 7 days. They were then given 0.4, 2 or 10ppm MEL in drinking water for 17 weeks. At week 20, the development of colonic adenocarcinoma was significantly inhibited by the administration with MEL dose-dependently. MEL exposure modulated the mitotic and apoptotic indices in the colonic adenocarcinomas that developed and lowered the immunohistochemical expression of nuclear factor kappa B, tumor necrosis factor alpha, interleukin-1beta and STAT3 in the epithelial malignancies. These results may indicate the beneficial effects of MEL on colitis-related colon carcinogenesis and a potential application for inhibiting colorectal cancer development in the inflamed colon.