Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis

Background@#It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD).Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). @*Methods@#In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVS_Q1–4) was used to determine visit-to-visit HbA1c variability. @*Results@#Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4%; 104/1,109 patients).The highest incidence of CVD of 26.7% (8/30 patients) was found in HVS [≥ 9.0%]_Q3, which was significantly higher than that in HVS [6.0–6.9%]_Q1 (P = 0.006), HVS [6.0–6.9%]_Q2 (P = 0.013), HVS [6.0–6.9%]_Q3 (P = 0.018), and HVS [7.0–7.9%]_Q3 (P = 0.040). @*Conclusion@#To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.

Impact of the COVID-19 Pandemic on Gender Differences in Depression Based on National Representative Data

Background@#Restrictions on daily life and changes in economic structure due to coronavirus disease 2019 (COVID-19) likely would have affected men and women differently. However, there is still a lack of research on the difference between men and women in the amount of change in depression during COVID-19 compared to before COVID-19. Therefore, the researchers investigated gender differences in the magnitude of increase in the prevalence of depression with its severity and individual symptoms during COVID-19 compared with prepandemic levels. @*Methods@#The Korea National Health and Nutrition Examination Survey (KNHANES) 2016 and 2018 were used to assess depression levels pre-pandemic and the KNHANES 2020 for pandemic depression levels. Depression was evaluated using the Patient Health Questionnaire-9 (PHQ-9). To analyze the differences between men and women in the magnitude of the mental health impact of COVID-19, the researchers analyzed the weighted differences in depression prevalence, severity, and individual symptoms during the COVID-19 pandemic compared to before COVID-19 stratified by gender. @*Results@#In men, there were significant increases in weighted prevalence for depression (1.2% percentage point; 95% confidence interval [CI], 0.0–2.3) and severe symptoms of depression (2.6-fold; 95% CI, 1.2–5.7). Among the individual symptoms of depression, significant increases during the pandemic compared to before were: little interest or pleasure in doing things, 1.26-fold; feeling tired or having little energy, 2.2-fold; and suicidal thoughts, 1.7-fold. However, there was no significant difference in prevalence, symptoms severity, and any symptom before and during COVID-19 in women. @*Conclusions@#Because the pandemic is likely to increase mental problems of the affected over time due to such problems as financial stress and joblessness or post-infection health issues, the researchers anticipate an increase in the prevalence of some mental illnesses. In particular, since the suicide rate of men is higher than that of women, from a public health perspective, active interventions are needed to prevent an increase in the suicide rate due to COVID-19. It is also necessary to establish national policies to overcome the psychological, social, and economic losses resulting from COVID-19.

Viscum album and its Constituents Downregulate MMP-13 Expressionin Chondrocytes and Protect Cartilage Degradation

Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs)including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanolextract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yieldedfive constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2),syringin (3), homoflavoyadorinin B (4), and 4,4′-dihydroxy-3,6′-dimethoxychalcone-2′-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 – 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

Viscum album and its Constituents Downregulate MMP-13 Expressionin Chondrocytes and Protect Cartilage Degradation

Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs)including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanolextract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yieldedfive constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2),syringin (3), homoflavoyadorinin B (4), and 4,4′-dihydroxy-3,6′-dimethoxychalcone-2′-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 – 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

Autophagy localization and cytoprotective role in cisplatin-induced acute kidney injury / 대한수의학회지

Autophagy is a fundamental cellular process that maintains homeostasis and cell integrity, under stress conditions. Although the involvement of autophagy in various conditions has been elucidated, the role of autophagy in renal structure is not completely clarified. Our aim was to investigate the cytoprotective effect of autophagy against acute kidney injury (AKI) through cisplatin deteriorative pathway, which leads to AKI via renal cell degradation. For in vivo experiments, male Sprague Dawley rats were divided in to 2 groups (n = 6/group) as control, Cis-5D. Following a single intraperitoneal injection of cisplatin, rats were sacrificed after 5 days. Blood urea nitrogen (BUN), creatinine (Cr) and histological alterations were examined. Further, expression of key regulators of autophagy, light-clain 3 (LC3), p62, and Beclin1, was evaluated by immunohistochemistry (IHC). The rats exhibited severe renal dysfunction, indicated by elevated BUN, Cr. Hematoxylin and eosin staining revealed histological damages in cisplatin-treated rats. Furthermore, IHC analysis revealed increased expression of LC3, Beclin1 and decreased expression of p62. Furthermore, expression of aforementioned autophagy markers was restricted to proximal tubule. Taken together, our study demonstrated that cisplatin can cause nephrotoxicity and lead to AKI. This phenomenon accelerated autophagy in renal proximal tubules and guards against AKI.

NAD(P)H-quinone oxidoreductase-1 silencing modulates cytoprotection related protein expression in cisplatin cytotoxicity

NAD(P)H-quinone oxidoreductase-1 (NQO1) is a down-stream target gene of nuclear factor erythroid 2-related factor 2 (Nrf2), and performs diverse biological functions. Recently, NQO1 is recognized as an effective gene for the cytotoxic inserts with its diverse biological functions, which is focused on antioxidant properties. The aim of present study was to assess the impact of NQO1 knockdown on cytoprotection-related protein expression in cisplatin cytotoxicity by using small interfering (si) RNA targeted on NQO1 gene. Cytotoxicity of cisplatin on ACHN cells was assessed in a dose- and time-dependent manner after siScramble or siNQO1 treatment. After cisplatin treatment, cells were subjected to cell viability assay, western-blot analysis, and immunofluorescence study. The cell viability was decreased in the siNQO1 cells (50%) than the siScramble cells (70%) after 24 h of cisplatin (20 µM) treatment. Moreover, cytoprotection-related protein expressions were markedly suppressed in the siNQO1 cells after cisplatin treatment. The expression of Nrf2 and Klotho were decreased by 20% and 40%, respectively, of that in siScramble cells. Nrf2 and Klotho activation were also decreased in cisplatin treated siNQO1 cells, confirmed by cytoplasm-to-nuclear translocation. Our findings demonstrate that the increased cisplatin-induced cytotoxicity was accompanied by suppressed Nrf2 activation and Klotho expression in siNQO1 cells.