OBJECTIVEDiabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODSIn this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTSThe proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P 5 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P 5 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P 5 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONSC-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death

<div><b>OBJECTIVE:</b> Diabetes is one of the most distinct comorbidities of COVID-19. Here, we described the clinical characteristics and outcomes in diabetic patients with confirmed or clinically diagnosed (with typical lung imaging features and symptoms) COVID-19, and their association with glucose lowering or blood pressure lowering medications.</div><div><br></div><div><b>RESEARCH DESIGN AND METHODS: </b>In this retrospective study involving 904 COVID-19 patients (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between diabetic vs non-diabetic groups, and different medication groups. Logistic regression was used to explore risk factors associated with mortality or poor prognosis.</div><div><br></div><div><b>RESULTS:</b> Proportion of comorbid diabetes is similar between confirmed and clinically diagnosed COVID-19 cases. Risk factors for higher mortality of diabetic patients with COVID-19 were elder age (adjusted OR [aOR] 1.09 [95% CI 1.04, 1.15], per year increase, P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24], mg/dL, P = 0.043). Insulin usage (aOR 3.58 [95%CI 1.37, 9.35], P = 0.009) was associated with poor prognosis. Clinical outcomes of ACE inhibitor or angiotensin II type-I receptor blocker (ACEI/ARB) users were comparable to non-ACEI/ARB users in COVID-19 patients with diabetes and hypertension.</div><div><br></div><div><b>CONCLUSIONS: </b>C-reactive protein may help to identify diabetic patients with greater risk. Elder diabetic patients were prone to COVID-19-related fatality. Attentions need to be paid on insulin-using diabetic patients with COVID-19. ACEI/ARB showed no significant impact on COVID-19 patients with diabetes and hypertension.</div>

Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds.

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<div><b>OBJECTIVE:</b> Diabetes is one of the most distinct comorbidities of COVID-19. Here, we described the clinical characteristics and outcomes in diabetic patients with confirmed or clinically diagnosed (with typical lung imaging features and symptoms) COVID-19, and their association with glucose lowering or blood pressure lowering medications.</div><div><br></div><div><b>RESEARCH DESIGN AND METHODS: </b>In this retrospective study involving 904 COVID-19 patients (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between diabetic vs non-diabetic groups, and different medication groups. Logistic regression was used to explore risk factors associated with mortality or poor prognosis.</div><div><br></div><div><b>RESULTS:</b> Proportion of comorbid diabetes is similar between confirmed and clinically diagnosed COVID-19 cases. Risk factors for higher mortality of diabetic patients with COVID-19 were elder age (adjusted OR [aOR] 1.09 [95% CI 1.04, 1.15], per year increase, P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24], mg/dL, P = 0.043). Insulin usage (aOR 3.58 [95%CI 1.37, 9.35], P = 0.009) was associated with poor prognosis. Clinical outcomes of ACE inhibitor or angiotensin II type-I receptor blocker (ACEI/ARB) users were comparable to non-ACEI/ARB users in COVID-19 patients with diabetes and hypertension.</div><div><br></div><div><b>CONCLUSIONS: </b>C-reactive protein may help to identify diabetic patients with greater risk. Elder diabetic patients were prone to COVID-19-related fatality. Attentions need to be paid on insulin-using diabetic patients with COVID-19. ACEI/ARB showed no significant impact on COVID-19 patients with diabetes and hypertension.</div>

Key pointsr Diabetic nephropathy (DN) is a major complication of diabetes, key features of which include glomerular mesangial expansion, hypertrophy, renal inflammation and accumulation of extracellular matrix proteins in the kidney.r Histone acetylation plays an important role in the regulation of inflammation in DN. r We found that apelin-13, the most active member of the adipokine apelin group, decreased glomerular filtration rate, proteinuria, glomerular hypertrophy and mesangial expansion, down-regulated histone acetylation and suppressed renal inflammation in Akita mouse, a spontaneous DN mouse model. r In mesangial cell lines, apelin-13 treatment not only inhibited high glucose-induced histone hyperacetylation and inflammation factors, but also up-regulated histone deacetylase 1. r These results revealed the possible mechanisms underlying the regulation of histone acetylation in DN and provide novel approaches to explore the beneficial effects of apelin-13 on DN.Abstract Diabetic nephropathy is the primary cause of end-stage renal disease. Increasing numbers of patients are suffering from this disease and therefore novel medications and therapeutic approaches are urgently needed. Here, we investigated whether apelin-13, the most active member of the adipokine apelin group, could effectively suppress the development of nephropathy in Akita mouse, a spontaneous type 1 diabetic model. Apelin-13 treatment decreased diabetes-induced glomerular filtration rate, proteinuria, glomerular hypertrophy, mesangial expansion and renal inflammation. The inflammatory factors, activation of NF-κB, histone acetylation and the enzymes involved in histone acetylation were further examined in diabetic kidneys and high glucose-or sodium butyrate-treated mesangial cells in the presence or absence of apelin-13. Apelin-13 treatment inhibited diabetes-, high glucose-and NaB-induced elevation of inflammatory factors, and histone hyperacetylation by upregulation of histone deacetylase 1. Furthermore, overexpression of apelin in mesangial cells induced histone deacetylation under high glucose condition. Thus, apelin-13 may be a novel therapeutic candidate for treatment of diabetic nephropathy via regulation of histone acetylation.

MPHOSPH1 is a critical kinesin protein that functions in cytokinesis. Here, we show that MPHOSPH1 is overexpressed in hepatocellular carcinoma (HCC) cells, where it is essential for proliferation. Attenuating MPHOSPH1 expression with a tumor-selective shRNA-expressing adenovirus (Ad-shMPP1) was sufficient to arrest HCC cell proliferation in a manner associated with an accumulation of multinucleated polyploid cells, induction of postmitotic apoptosis, and increased sensitivity to taxol cytotoxicity. Mechanistic investigations showed that attenuation of MPHOSPH1 stabilized p53, blocked STAT3 phosphorylation, and prolonged mitotic arrest. In a mouse subcutaneous xenograft model of HCC, tumoral injection of Ad-shMPP1 inhibited MPHOSPH1 expression and tumor growth in a manner correlated with induction of apoptosis. Combining Ad-shMPP1 injection with taxol administration enhanced antitumor efficacy relative to taxol alone. Furthermore, Ad-shMPP1 tail vein injection suppressed formation of orthotopic liver nodules and prevented hepatic dysfunction. Taken together, our results identify MPHOSPH1 as an oncogenic driver and candidate therapeutic target in HCC. Cancer Res; 74(22); 6623-34. Ó2014 AACR.

Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury, having a high rate of mortality and no effective therapy currently available. Apelin-13, a bioactive peptide, has been shown to inhibit the early lesions of diabetic nephropathy in several mouse models by us and others. To test whether apelin-13 protects against renal I/R induced injury, male rats were exposed to renal I/R injury with or without apelin-13 treatment for 3 days. Apelin-13 treatment markedly reduced the injury-induced tubular lesions, renal cell apoptosis, and normalized the injury induced renal dysfunction. Apelin-13 treatment inhibited the injury-induced elevation of inflammatory factors and Tgf-β1, as well as apoptosis. Apelin-13 treatment also inhibited the injury-induced elevation of histone methylation and Kmt2d, a histone methyltransferase of H3K4me2, following renal I/R injury. Furthermore, in cultured renal mesangial and tubular cells, apelin-13 suppressed the injury-induced elevation of Tgf-β1, apoptosis, H3K4me2 and Kmt2d under the in vitro hypoxia/reperfusion (H/R) conditions. Consistently, over-expression of apelin significantly inhibited H/R-induced elevation of TGF-β1, apoptosis, H3K4me2 and Kmt2d. The present study therefore suggests apelin-13 may be a therapeutic candidate for treating acute kidney injury.