Sirtuin 6 Overexpression Improves Rotator Cuff Tendon-to-Bone Healing in the Aged.

Aging is an independent risk factor for recurrent tearing after surgical repair of rotator cuff ruptures around the tendon-to-bone area. However, aging signature factors and related mechanisms involved in the healing of the rotator cuff are still unknown. We hypothesized that differences in proteins involved in the rotator cuff according to age may affect tendon-to-bone healing. The proteome analysis performed to identify the signature aging proteins of the rotator cuff confirmed the sirtuin signal as an age-specific protein. In particular, the expression of SIRT6 was markedly down-regulated with age. Ingenuity pathway analysis of omics data from age-dependent rat rotator cuffs and linear regression from human rotator cuffs showed SIRT6 to be closely related to the Wnt/ß-catenin signal. We confirmed that overexpression of SIRT6 in the rotator cuff and primary tenocyte regulated canonical Wnt signaling by inhibiting the transcriptional expression of sclerostin, a Wnt antagonist. Finally, SIRT6 overexpression promoted tendon-to-bone healing after tenotomy with reconstruction in elderly rats. This approach is considered an effective treatment method for recovery from recurrent rotator cuff tears, which frequently occur in the elderly.

Bean Extract-Based Gargle for Efficient Diagnosis of Active COVID-19 Infection Using Rapid Antigen Tests.

The antigen-based rapid diagnostic test (Ag-RDT) using saliva specimens is fast, noninvasive, and suitable for SARS-CoV-2 self-testing, unlike nasopharyngeal swab (NPS) testing. We evaluated a novel Beanguard gargle (BG)-based virus collection method that can be applied to Ag-RDT as an alternative to the current RT-PCR with an NPS for early diagnosis of COVID-19. This clinical trial comprised 102 COVID-19-positive patients hospitalized after a governmental screening process and 100 healthy individuals. Paired NPS and BG-based saliva specimens from COVID-19 patients and healthy individuals were analyzed using NPS-RT-PCR, BG-RT-PCR, and BG-Ag-RDTs, whose diagnostic performance for detecting SARS-CoV-2 was compared. BG-Ag-RDTs showed high sensitivity (97.8%) and specificity (100%) in 45 patients within 6 days of illness and detected all cases of SARS-CoV-2 Alpha and Delta variants. In 11 asymptomatic active COVID-19 cases, both BG-Ag-RDTs and BG-RT-PCR showed sensitivities and specificities of 100%. Sensitivities of BG-Ag-RDT and BG-RT-PCR toward salivary viral detection were highly concordant, with no discrimination between symptomatic (97.0%), asymptomatic (100%), or SARS-CoV-2 variant (100%) cases. The intermolecular interactions between SARS-CoV-2 spike proteins and truncated canavalin, an active ingredient from the bean extract (BE), were observed in terms of physicochemical properties. The detachment of the SARS-CoV-2 receptor-binding domain from hACE2 increased as the BE concentration increased, allowing the release of the virus from hACE2 for early diagnosis. Using BG-based saliva specimens remarkably enhances the Ag-RDT diagnostic performance as an alternative to NPS and enables noninvasive, rapid, and accurate COVID-19 self-testing and mass screening, supporting efficient COVID-19 management. IMPORTANCE An Ag-RDT is less likely to be accepted as an initial test method for early diagnosis owing to its low sensitivity. However, our self-collection method, Ag-RDT using BG-based saliva specimens, showed significantly enhanced detection sensitivity and specificity toward SARS-CoV-2 including the Alpha and Delta variants in all patients tested within 6 days of illness. The method represents an attractive alternative to nasopharyngeal swabs for the early diagnosis of symptomatic and asymptomatic COVID-19 cases. The evidence suggests that the method could have a potential for mass screening and monitoring of COVID-19 cases.

A novel assessment of nefazodone-induced hERG inhibition by electrophysiological and stereochemical method.

Nefazodone was used widely as an antidepressant until it was withdrawn from the U.S. market in 2004 due to hepatotoxicity. We have investigated methods to predict various toxic effects of drug candidates to reduce the failure rate of drug discovery. An electrophysiological method was used to assess the cardiotoxicity of drug candidates. Small molecules, including withdrawn drugs, were evaluated using a patch-clamp method to establish a database of hERG inhibition. Nefazodone inhibited hERG channel activity in our system. However, nefazodone-induced hERG inhibition indicated only a theoretical risk of cardiotoxicity. Nefazodone inhibited the hERG channel in a concentration-dependent manner with an IC50 of 45.3nM in HEK-293 cells. Nefazodone accelerated both the recovery from inactivation and its onset. Nefazodone also accelerated steady-state inactivation, although it did not modify the voltage-dependent character. Alanine mutants of hERG S6 and pore region residues were used to identify the nefazodone-binding site on hERG. The hERG S6 point mutants Y652A and F656A largely abolished the inhibition by nefazodone. The pore region mutant S624A mildly reduced the inhibition by nefazodone but T623A had little effect. A docking study showed that the aromatic rings of nefazodone interact with Y652 and F656 via π-π interactions, while an amine interacted with the S624 residue in the pore region. In conclusion, Y652 and F656 in the S6 domain play critical roles in nefazodone binding.

Synthesis of LipidGreen2 and its application in lipid and fatty liver imaging.

We have developed LipidGreen2, a second generation small molecule probe for lipid imaging. LipidGreen2 has a better fluorescence signal compared with the previous LipidGreen, and selectively stains neutral lipids in cells and fat deposits in live zebrafish. We also demonstrate the application of LipidGreen2 for detecting fatty liver.

Metabolic profiling of an alcoholic fatty liver in zebrafish (Danio rerio).

Zebrafish (Danio rerio) is becoming a popular developmental biology model to study diseases and for drug discovery. In this study, we performed proton nuclear magnetic resonance spectroscopy ((1)H-NMR)- and gas chromatography-mass spectrometry (GC/MS)-based metabolic profiling of an alcoholic fatty liver using a zebrafish disease model. We examined metabolic differences between the control and alcoholic fatty liver groups in zebrafish to determine how metabolism in an alcoholic fatty liver is regulated. Multivariate statistical analysis showed a significant difference between the control and alcoholic fatty liver groups. The alcoholic fatty liver group showed increased excretion of isoleucine, acetate, succinate, choline, creatine, acetoacetate, 3-hydroxybutyrate (3HB), ethyl glucuronide (EtG), lactate/pyruvate ratio, fatty acids, and cholesterol, and decreased excretion of citrate, aspartate, tyrosine, glycine, glucose, alanine, betaine, and maltose. Metabolites identified in the fatty liver groups were associated with long-term alcohol consumption, which causes both oxidation-reduction (redox) changes and oxidative stress. This study suggests that global metabolite profiling in a zebrafish model can provide insights into the metabolic changes in an alcoholic fatty liver.

Molecular characterization, immune responses and DNA protection activity of rock bream (Oplegnathus fasciatus), peroxiredoxin 6 (Prx6).

In this study, we describe the molecular characterization, immune responses of rock bream, Oplegnathus fasciatus peroxiredoxin 6 cDNA (RbPrx6) and DNA protection activity of its recombinant protein. The full-length cDNA sequence of RbPrx6 was identified after pyrosequencing of rock bream cDNA library. RbPrx6 consists of 663 bp open reading frame (ORF) that codes for a putative protein of 221 amino acids with predicted molecular mass of 27 kDa. It showed characteristic peroxiredoxin super-family domain similar to vertebrate Prx counterparts. In the pair-wise comparison, RbPrx6 showed the highest amino acid identity (92.8%) to Scophthalmus maximus Prx6. Real-time RT-PCR analysis revealed that constitutive expression of RbPrx6 transcripts in eleven tissues selected from un-challenged fish showing the highest level in liver. Synthetic polyinosinic:polycytidylic acid (poly I:C) and iridovirus containing supernatant, up-regulated the RbPrx6 mRNA in liver. Purified recombinant RbPrx6 protein was able to protect supercoiled plasmid DNA from damages that is induced by metal-catalyzed generation of reactive oxygen species. Our results suggest that RbPrx6 may play an important role in regulating oxidative stress by scavenging of ROS, involving immune reactions and minimizing the DNA damage in rock bream.

Anti-obesity effects of a mixture of thiamin, arginine, caffeine, and citric acid in non-insulin dependent diabetic KK mice.

Anti-obesity effects of a mixture of thiamin, arginine, caffeine, and citric acid (TACC) were investigated in non-insulin dependent diabetic KK mice. Feeding of either arginine or caffeine significantly suppressed an increase in hepatic lipid contents in fasted-refed KK mice. In addition, each component admixed with a low-calorie diet effectively reduced adipose tissue weight in KK mice previously fed a high-calorie diet. The decrease in adipose tissue weight was greater with a mixture of arginine and caffeine, and much greater with TACC than with arginine or caffeine alone. Moreover, plasma insulin concentration was significantly lower in mice fed TACC than in control mice. The anti-obesity effects of TACC were also shown when it was supplemented with a tea beverage. Adipose tissue weight, hepatic triglyceride contents, and plasma insulin concentration were significantly lower in mice given TACC-supplemented tea than in control mice. These results suggest that TACC is effective in reducing adipose tissue mass as well as improving disorders in lipid metabolism.

Effects of Telephone Consulting Program on Self-efficacy and Self-care in NIDDM Patients / 성인간호학회지

PURPOSE: This study was intended to examine the effects of a telephone consulting program on self-efficacy and self-care in NIDDM patients. METHOD: Sixty-eight NIDDM patients participated. Thirty-six were assigned to the experimental group and received the telephone consulting program from one to two times per week for 4 weeks. This program was undertaken by base on small booklet relating to diabetic disease summary, diet, drug, exercise, foot management, prevention and treatment of complications, and insulin injection methods. RESULT: 1. Hypothesis 1 that "the experimental group who receives the telephone consulting program will have higher self-efficacy score than the control group who does not have the telephone consulting" was supported (t=5.12, p= .000). 2. Hypothesis 2 that "the experimental group who receives the telephone consulting program will have higher self-care score than the control group who does not have the telephone consulting" was supported(t=5.29, p= .000). CONCLUSION: The telephone consulting program improved self-efficacy and self-care in NIDDM patients. Accordingly, this program can be adopted as an effective nursing intervention in the care of the diabetic patients.