Genome-wide association of individual vulnerability with alcohol-associated liver disease: A Korean genome and epidemiology study.

BACKGROUND AND AIMS: The quantity of alcohol leading to alcohol-associated liver disease (ALD) varies individually. Genetic backgrounds contributing to the divergence in individual susceptibility to alcohol-induced liver damage have not been elucidated in detail. APPROACH AND RESULTS: Based on the Korean Genome and Epidemiology Study Health Examination (KoGES_HEXA) cohort data, 21,919 participants (40-79 years old) were included and divided into cases and controls based on the ALD diagnostic criteria proposed by the American College of Gastroenterology. Data generated by a genome wide-association study were analyzed using logistic regression to assess the risk of ALD development in nondrinkers, light drinkers, and heavy drinkers. We detected three loci, gamma-glutamyltransferase 1 (GGT1), zinc protein finger 827 (ZNF827) and HNF1 homeobox A (HNF1A), which were significantly associated with ALD risk. The GGT1 rs2006227 minor allele was strongly associated with all groups. Among the minor alleles of single nucleotide polymorphisms (SNPs) in HNF1A, rs1183910 had the strongest association with a protective effect from ALD in light drinkers. However, this association was not observed in heavy drinkers. Five SNPs on chromosome 11 showed suggestive significance in protective effects against ALD. CONCLUSIONS: SNPs, including HNF1A rs1183910 minor allele, are the most promising genetic candidates for protection against ALD. The expression of genes contributing to ALD development may be altered by the amount of alcohol consumed.

Discordance in Secular Trends of Bone Mineral Density Measurements in Different Ages of Postmenopausal Women.

BACKGROUND: Age-adjusted bone mineral density (BMD) in postmenopausal women decreases in developed countries whereas incidence of osteoporotic fracture decreases or remains stable. We investigated secular trends of bone density from 2008 to 2017 among different age groups of postmenopausal women. METHODS: We analyzed BMD data obtained from health check-ups of 4,905 postmenopausal women during three survey cycles from 2008 to 2017. We divided them into 3 groups by age (50-59 years, 60-69 years, and 70 years or more) and observed the transition of lumbar and femoral BMD in each group, before and after adjusting for variables that may affect BMD. RESULTS: Age-adjusted BMD, bone mineral content (BMC), and T-score demonstrated a declining trend over the survey period at lumbar spine (-2.8%), femur neck (-3.5%) and total femur (-4.3%), respectively. In the analysis for the age groups, the BMD, BMC, and T-score presented linear declining trend (-6.1%) in younger postmenopausal women while women aged over 70 or more showed linear increasing trends (+6.3%) at lumbar spine during the survey period. Femoral neck and total femur BMD demonstrated a declining linear trend only in the 50-59 and 60-69 years groups (-5.5%, -5.2%, respectively), but not in the 70 years or more group. CONCLUSION: BMD in younger postmenopausal women has decreased considerably but has increased or plateaued in elderly women. This discordance of BMD trends among different age groups may contribute to decreased incidence of osteoporotic fracture despite a recent declining BMD trend in postmenopausal women.

Alterative effects of an oral alginate extract on experimental rabbit osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly. However, few agents with high efficacy and low side effects have been developed to treat OA. In this study, we evaluated the effects of the alginate extract named CTX in OA cell and rabbit models. RESULTS: CTX was formulated by hydrolyzing sodium alginate polymers with alginate lyase and then mixing with pectin. HPLC was used to analyze the CTX content. Human chondrosarcoma SW1353 cells treated with interleukin-1ß were used as OA model cells to investigate the effects of CTX on chondrocyte inflammation and anabolism. CTX at concentrations up to 1000 µg/ml exerted low cytotoxicity. It inhibited the gene expression of proinflammatory matrix metalloproteinases (MMPs) including MMP1, MMP3 and MMP13 in a dose-dependent manner and increased the mRNA level of aggrecan, the major proteoglycan in articular cartilage, at 1000 µg/ml. Thirteen-week-old New Zealand White rabbits underwent a surgical anterior cruciate ligament transection and were orally treated with normal saline, glucosamine or CTX for up to 7 weeks. Examinations of the rabbit femur and tibia samples demonstrated that the rabbits taking oral CTX at a dosage of 30 mg/kg/day suffered lesser degrees of articular stiffness and histological cartilage damage than the control rabbits. CONCLUSIONS: The gene expression profiles in the cell and the examinations done on the rabbit cartilage suggest that the alginate extract CTX is a pharmaco-therapeutic agent applicable for OA therapy.

In vitro and in vivo antimicrobial activity of water-soluble chitosan oligosaccharides against Vibrio vulnificus.

Vibrio vulnificus is a Gram-negative bacterium that induces severely rapid pathological progress. In this study, we evaluated the antibacterial activity of two water-soluble chitosan oligosaccharides, COS A (MW, 10,000 Da) and COS B (MW, 1,000 Da), from 90-95% deacetylated chitosan, against V. vulnificus in vitro and in vivo. Treatment with COS A resulted in significantly higher suppressive effects on the growth of V. vulnificus than treatment with COS B. The growth of V. vulnificus was inhibited within 1 h of treatment with water-soluble COS A in concentrations ranging from 0.5 to 10 mg/ml. Additionally, treatment with COS A completely inhibited V. vulnificus-induced cytotoxicity in human intestinal epithelial INT-407 cells, while COS B did not. Furthermore, the administration of COS A (0.1-0.5 mg per mouse) significantly increased the survival period of V. vulnificus-infected mice. The number of viable V. vulnificus in the spleen, liver, small intestine, and blood was significantly lower in COS A-treated mice than in untreated mice. Here, we clearly demonstrate that COS A is a potential agent for the prevention and treatment of infection with V. vulnificus.