Regulation of the Catabolic Cascade in Osteoarthritis by the Zinc-ZIP8-MTF1 Axis

SummaryOsteoarthritis (OA), primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. Here, we investigated the role of zinc (Zn2+) homeostasis, Zn2+ transporters, and Zn2+-dependent transcription factors in OA pathogenesis. Among Zn2+ transporters, the Zn2+ importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn2+ in chondrocytes. ZIP8-mediated Zn2+ influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn2+ influx and matrix-degrading enzymes. Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn2+/ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. We propose that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis

Effect of Ascorbic acid on EPO-hyporesponsive anemia in Hemodialysis patients

We performed the present study to evaluate the efficacy of intravenous and oral ascorbic acid in improving anemia and iron availability on EPO-hyporesponsive anemia in hemodialysis patients with hyperferritinemia. This study of three months duration was conducted in 49 patients with Hb <11 g/dL and ferritin levels greater than 300 ng/ml. Blood samples for measurement of Hb, Hct, serum iron, ferritin, TIBC, transferrin saturation, EPO dose were obtained after baseline and at the end of study after three months. Patients were randomly divided into three groups. 16 patients had received standard care(group 1), 17 patients had received standard care and daily oral ascorbic acid at a dose of 500 mg/day(group 2), and 16 patients had received standard care and 300mg of intravenous vitamin C with each dialysis session(group 3). Forty-seven patients completed the study. All of patients dialyzed 4 hours, 3 times a week with similar kt/V. Hb, serum iron, serum ferritin, transferrin saturation and EPO dose was similar in the three groups at baseline. After 3 month, Hemoglobin and hematocrit and transferrin saturation significantly increased in group 2,3. but not changed in group 1. EPO dose and ferritin level decreased in group 2,3. but not changed in group 1. There was no difference between group 2 and 3. In conclusion, intravenous or oral ascorbic acid therapy can improve hyperferritinemia and EPO hyporesponsive anemia in hemodialysis patients. And The effect of intravenous and oral ascorbic acid are similar.Table 1 Baseline and 3 month Data Group1(n=16) Group2(n=17) Group3(n=14) baseline After3month baseline After3month baseline After3month Hb(g/dl 8.9+1.4 8.8+1.3 8.8+1.3 9.5+1.2 9.0+1.2 9.6+1.2 Fe(u/L) 55.84+23 58.6+19 58.57+25 63.7+22 61.12+21 6729+19 EPOdose(unit/week) 14729 14538 15584 12369 14986 11345 Ferritin(ug/l) 764+217 781+192 783+191 646+189 754+220 634+231 Transferrin saturation(%) 18+6.4 18+5.8 20.6+5.5 26.4+4.4 19.8+4.9 24.5+3.2 *is p<0.

Risk of Post-Myocardial Infarction Pneumonia with Proton Pump Inhibitors, H2 Receptor Antagonists and Mucoprotective Agents: A Retrospective Nationwide Cohort Study

Patients with myocardial infarction (MI) are at high risk of developing pneumonia. Proton pump inhibitors (PPI) and H2-receptor antagonists (H2RA) are commonly used acid-suppressive medications to the patients with MI for gastrointestinal (GI) protection, which may increase the risk for pneumonia. We evaluated whether PPI, H2RA, and mucoprotective agents without anti-acid properties increase the risk of post-MI pneumonia. We performed a retrospective cohort study based on the National Health Insurance Service&mdash;National Sample Cohort in Korea. The study included 3701 patients discharged with MI without prior history of pneumonia. During follow-up, treatments with PPI, H2RA, and mucoprotective agents were collected as time-dependent variables based on the prescription records. We performed multivariate time-dependent Cox regression analyses for the development of post-MI pneumonia. During the mean 4.85 &plusmn; 3.75 years follow-up, 999 participants developed pneumonia. In the multivariate analyses (adjusted hazard ratio; 95% confidence interval), the risk for pneumonia was significantly increased in treatment with PPI (2.25; 1.57&ndash;3.21) and H2RA (1.50; 1.16&ndash;1.93). Meanwhile, the risk for pneumonia was not increased in treatment with mucoprotective agents. When we evaluated GI bleeding event according to the medications as a secondary outcome analysis, mucoprotective agents were associated with increased GI bleeding risk, but PPI and H2RA were not. In the use of the GI medications in the treatment of patients with MI, the influence of these drugs on bleeding and pneumonia should be considered

Mercury exposure is associated with obesity: a systematic review and meta-analysis

Objectives: Previous studies have evaluated the association between mercury exposure and obesity but have yielded mixed conclusions. The aim of this study was to systematically review and summarize scientific evidence regarding the association between mercury exposure and obesity in the human population. Methods: We conducted a systematic search of PubMed, Web of Science, Scopus, and Science Direct for articles related to mercury exposure and obesity. Meta-analyses of the highest and lowest categories of mercury levels were evaluated using a random effects model. Begg’s test was used to detect publication bias. Results: A total of 9 articles were included. The pooled random effects odds ratio (OR) for mercury exposure and obesity of all 9 studies was 1.66 (95% confidence interval [CI]: 1.16-2.38). This positive association was evident in adults (OR: 1.61, 95% CI: 1.02-2.54) and among studies with Asian populations (OR: 2.00, 95% CI: 1.53-2.59), but not among those with North America/African populations (OR: 0.90, 95% CI: 0.50-1.65). Conclusions: The present meta-analysis identified a positive association between mercury exposure and obesity. These findings suggest that toxic environmental metals such as mercury may be an important risk factor for obesity along with dietary habits and lifestyles

Effects of Consuming Calcium-Rich Foods on the Incidence of Type 2 Diabetes Mellitus

The effect of calcium consumption in the prevention of type 2 diabetes mellitus (T2DM) remains controversial, and depends on food calcium sources. This prospective study aimed to evaluate the association between calcium-rich food consumption and T2DM incidence among Korean adults. We analyzed the data of 8574 adults aged 40&ndash;69 years, without a history of T2DM, cardiovascular disease, and cancer at the baseline from the Korean Genome and Epidemiology Study. The consumption of calcium-rich foods was assessed using a validated semi-quantitative food frequency questionnaire. T2DM-related data were collected using biennial questionnaires, health examinations, and clinical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. In the multivariate-adjusted model, yogurt intake was inversely associated with T2DM risk (HR: 0.73; 95% CI: 0.61&ndash;0.88 in the fourth quartile as compared to the first quartile). However, the intakes of other calcium-rich foods, including milk and anchovies, were not significantly associated with T2DM risk. Yogurt may provide protective effects against T2DM in Korean adults, owing to the beneficial effects of probiotics. Further prospective large-scale cohort studies should be conducted to validate these findings

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study

Abstract Introduction Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. Methods This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014–2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. Results From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61–0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64–0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66–1.22; p = 0.492). Conclusions In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione

Association of triglyceride/high-density lipoprotein cholesterol ratio with severe complications of COVID-19

Background: The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can lead to serious complications such as respiratory failure, requiring mechanical ventilation or ICU care, and can even result in death, especially in older patients with comorbidities. The ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), a biomarker of atherosclerotic dyslipidemia and insulin resistance, is related to cardiovascular mortality and morbidity. We aimed to evaluate the link between serious complications of COVID-19 and TG/HDL in the general population. Methods: We conducted a comprehensive analysis of 3,933 COVID-19 patients from a nationwide cohort in Korea spanning from January 1 to June 4, 2020. TG/HDL ratio was calculated from the national health screening examination data underwent before the COVID-19 infection. Serious complications of COVID-19 were defined as a composite of high-flow oxygen therapy, mechanical ventilation, admission to the intensive care unit (ICU), and mortality. We employed logistic regression analysis to investigate the relationship between the TG/HDL ratio and the likelihood of developing severe complications within 2 months of the diagnosis. To visualize this association, we used a smoothing spline plot based on the generalized additive regression model. Multivariate analysis was performed with adjustment for age, gender, body mass index, lifestyle measures, and comorbidities. Results: Among the 3,933 COVID-19 patients, the proportion of serious complications was 7.53%. Regarding individual outcomes, the number of patients who received high-flow oxygen therapy, mechanical ventilation, ICU care, and died was 84 (2.14%), 122 (3.10%), 173 (4.40%), and 118 (3.00%), respectively. In the multivariable logistic regression, a positive association was found between TG/HDL ratio and serious complications of COVID-19 (adjusted OR, 1.09; 95% CI [1.03–1.15], p = 0.004). Conclusion: Our study revealed a significant positive association between TG/HDL ratio and the risk of developing severe complications in COVID-19-infected patients. While this finding provides valuable insight into the potential prognostic role of TG/HDL ratio in COVID-19, further studies are needed to fully elucidate the underlying mechanisms behind this relationship

Impact of statin treatment on cardiovascular events in patients with retinal vein occlusion: a nested case-control study in Korea

OBJECTIVES Retinal vein occlusion (RVO) is associated with an increased risk of future cardiovascular events. Statin therapy is a key cornerstone in prevention for patients at high cardiovascular risk. However, little is known about the role of statin therapy for patients with RVO. This study evaluated whether statin treatment in patients with RVO was associated with a lower risk of cardiovascular events. METHODS A population-based, nested case-control study was conducted with a cohort of newly diagnosed RVO patients without prior cardiovascular disease between 2008 and 2020 using a nationwide health claims database in Korea. From this cohort of RVO patients, we identified cases of cardiovascular events (stroke or myocardial infarction) after RVO and matched controls based on sex, age, insurance type, antiplatelet use, and underlying comorbidities using 1:2 incidence density sampling. RESULTS Using a cohort of 142,759 patients with newly diagnosed RVO, we selected 6,810 cases and 13,620 matched controls. A significantly lower risk of cardiovascular events (adjusted odds ratio, 0.604; 95% confidence interval, 0.557 to 0.655) was observed in RVO patients with statin treatment than in those without statin treatment. Statin treatment was associated with a reduced risk for both stroke and myocardial infarction after RVO. Longer statin treatment after RVO was associated with a lower risk for cardiovascular events. CONCLUSIONS Statin treatment was associated with a lower risk for future cardiovascular events in patients with newly diagnosed RVO. Further studies are warranted to clarify the potential cardiovascular preventive role of statins in patients with RVO