In the long history of traditional Chinese medicine, single herbs and complex formulas have been suggested to increase lifespan. However, the identification of single molecules responsible for ...lifespan extension has been challenging. Here, we collected a list of traditional Chinese medicines with potential longevity properties from pharmacopeias. By utilizing the mother enrichment program, we systematically screened these traditional Chinese medicines and identified a single herb, Psoralea corylifolia, that increases lifespan in Saccharomyces cerevisiae. Next, twenty-two pure compounds were isolated from Psoralea corylifolia. One of the compounds, corylin, was found to extend the replicative lifespan in yeast by targeting the Gtr1 protein. In human umbilical vein endothelial cells, RNA sequencing data showed that corylin ameliorates cellular senescence. We also examined an in vivo mammalian model, and found that corylin extends lifespan in mice fed a high-fat diet. Taken together, these findings suggest that corylin may promote longevity.
Objectives This study aimed to evaluate the association of statin exposure and incident diabetes, and subsequent outcomes in the general population. Background Cardiovascular events as consequences ...of atherosclerosis and diabetes are reduced by statins. However, statins are associated with excessive risk of diabetes occurrence according to clinical trial analyses. From daily-practice perspectives, it remains unclear whether statin use increases risk; prognoses of diabetes after exposure require further clarification. Methods From Taiwan National Health Insurance beneficiaries age ≥45 years (men) and ≥55 years (women) before 2004, subjects continuously treated with statins ≥30 days during 2000 to 2003 and nonusers before 2004 were identified. Among nondiabetic individuals at the cohort entry, controls were matched to statin users on a 4:1 ratio by age, sex, atherosclerotic comorbidities, and year of their entry. Outcomes as diabetes, major adverse cardiovascular events (MACE, the composite of myocardial infarction and ischemic stroke), and in-hospital deaths were assessed. Results Over a median of 7.2 years, annual rates of diabetes were significantly higher in statin users (2.4% vs. 2.1%, p < 0.001), whereas MACE (hazard ratio HR: 0.82; 95% confidence interval CI: 0.68 to 0.98 for myocardial infarction; HR: 0.94; 95% CI: 0.86 to 1.03 for ischemic stroke; HR: 0.91; 95% CI: 0.84 to 0.99 for MACE) and in-hospital mortality (HR: 0.61; 95% CI: 0.55 to 0.67) were less. The risk–benefit analyses suggested that statin treatment was favorable in high-risk (HR: 0.89; 95% CI: 0.83 to 0.95) and secondary prevention (HR: 0.89; 95% CI: 0.83 to 0.96) populations. Among diabetic patients, prior statin use was associated with fewer MACE (HR: 0.75; 95% CI: 0.59 to 0.97). In-hospital deaths were similar in statin-related diabetes among high-risk (HR: 1.11; 95% CI: 0.83 to 1.49) and secondary prevention (HR: 1.08; 95% CI: 0.79 to 1.47) subjects compared with nondiabetic controls. Conclusions Risk of diabetes was increased after statins, but outcomes were favorable.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The link between elevated serum uric acid (SUA) levels and cardiovascular disease (CVD)–related mortality in the elderly population remains inconclusive. Nutritional status influences both ...SUA and CVD outcomes. Therefore, we investigated whether SUA‐predicted mortality and the effect‐modifying roles of malnourishment in older people.
Methods and Results
A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA. Low SUA (<4 mg/dL) strata was categorized by malnourishment status defined as Geriatric Nutritional Risk Index <98, serum albumin <38 g/L, or body mass index <22 kg/m2. Study outcomes were all‐cause and CVD‐related mortality. Cox models were used to estimate hazard ratios (HRs) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD‐related deaths. Compared with the reference SUA strata of 4 to <5 mg/dL, all‐cause mortality was significantly higher at SUA <4 mg/dL (HR, 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL (HR, 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD‐related mortality was found at the SUA level <4 mg/dL (HR, 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL (HR, 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (<4 mg/dL) strata, only malnourished participants had greater all‐cause and CVD‐related mortality. This modifying effect of malnourishment remained consistent across subgroups.
Conclusions
SUA ≥8 or <4 mg/dL independently predicts higher all‐cause and CVD‐related mortality in the elderly, particularly in those with malnourishment.
As an intracellular pathogen, the reproduction of the hepatitis B virus (HBV) depends on the occupancy of host metabolism machinery. Here we test a hypothesis if HBV may govern intracellular ...biosynthesis to achieve a productive reproduction. To test this hypothesis, we set up an affinity purification screen for host factors that interact with large viral surface antigens (LHBS). This identified pyruvate kinase isoform M2 (PKM2), a key regulator of glucose metabolism, as a binding partner of viral surface antigens. We showed that the expression of viral LHBS affected oligomerization of PKM2 in hepatocytes, thereby increasing glucose consumption and lactate production, a phenomenon known as aerobic glycolysis. Reduction of PKM2 activity was also validated in several different models, including HBV-infected HepG2-NTCP-C4 cells, adenovirus mediated HBV gene transduction and transfection with a plasmid containing complete HBV genome on HuH-7 cells. We found the recovery of PKM2 activity in hepatocytes by chemical activators, TEPP-46 or DASA-58, reduced expressions of viral surface and core antigens. In addition, reduction of glycolysis by culturing in low-glucose condition or treatment with 2-deoxyglucose also decreased expressions of viral surface antigen, without affecting general host proteins. Finally, TEPP-46 largely suppressed proliferation of LHBS-positive cells on 3-dimensional agarose plates, but showed no effect on the traditional 2-dimensional cell culture. Taken together, these results indicate that HBV-induced metabolic switch may support its own translation in hepatocytes. In addition, aerobic glycolysis is likely essential for LHBS-mediated oncogenesis. Accordingly, restriction of glucose metabolism may be considered as a novel strategy to restrain viral protein synthesis and subsequent oncogenesis during chronic HBV infection.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND—Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation, although data on the survival ...benefits of rate control are lacking. The goal of the present study was to investigate whether patients receiving rate-control drugs had a better prognosis compared with those without rate-control treatment.
METHODS AND RESULTS—This study used the National Health Insurance Research Database in Taiwan. There were 43 879, 18 466, and 38 898 patients with atrial fibrillation enrolled in the groups receiving β-blockers, calcium channel blockers, and digoxin, respectively. The reference group consisted of 168 678 subjects who did not receive any rate-control drug. The clinical end point was all-cause mortality. During a follow-up of 4.9±3.7 years, mortality occurred in 88 263 patients (32.7%). After adjustment for baseline differences, the risk of mortality was lower in patients receiving β-blockers (adjusted hazard ratio=0.76; 95% confidence interval=0.74–0.78) and calcium channel blockers (adjusted hazard ratio=0.93; 95% confidence interval=0.90–0.96) compared with those who did not receive rate-control medications. On the contrary, the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 (95% confidence interval=1.10–1.14). The results were observed consistently in subgroup analyses and among the cohorts after propensity matching.
CONCLUSIONS—In this nationwide atrial fibrillation cohort, the risk of mortality was lower for patients receiving rate-control treatment with β-blockers or calcium channel blockers, and the use of β-blockers was associated with the largest risk reduction. Digoxin use was associated with greater mortality. Prospective, randomized trials are necessary to confirm these findings.
Although the CHA2DS2-VASc (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, ...female) score is recommended by both American and European guidelines for stroke risk stratification in atrial fibrillation (AF), the treatment recommendations for a CHA2DS2-VASc score of 1 are less clear.
This study aimed to investigate the risk of ischemic stroke in patients with a single additional stroke risk factor (i.e., CHA2DS2-VASc score = 1 males or 2 females) and the impact of different component risk factors.
We used the National Health Insurance Research Database in Taiwan. Among 186,570 AF patients not on antiplatelet or anticoagulant therapy, we evaluated males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2. The clinical endpoint was the occurrence of ischemic stroke.
Among 12,935 male AF patients with a CHA2DS2-VASc score of 1, 1,858 patients (14.4%) experienced ischemic stroke during follow-up (5.2 ± 4.3 years), with an annual stroke rate of 2.75%. Ischemic stroke risk ranged from 1.96%/year for men with vascular disease to 3.50%/year for those 65 to 74 years of age. For 7,900 females with AF and a CHA2DS2-VASc score of 2, 14.9% experienced ischemic stroke for an annual stroke rate of 2.55%. Ischemic stroke risk increased from 1.91%/year for women with hypertension to 3.34%/year for those 65 to 74 years of age.
Not all risk factors in CHA2DS2-VASc score carry an equal risk, with age 65 to 74 years associated with the highest stroke rate. Oral anticoagulation should be considered for AF patients with 1 additional stroke risk factor given their high risk of ischemic stroke.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cerebrovascular complications after hematopoietic stem cell transplantation (HSCT) cause serious morbidity and often contribute to mortality. The incidence, risk factors, and outcome of ...cerebrovascular disease (CVD) after allogeneic HSCT remain poorly defined. We retrospectively evaluated 459 adult patients who underwent allogeneic HSCT at a tertiary medical center between January 2003 and December 2015. A total of 20 patients (4.4%) developed post-transplant CVD. All cerebrovascular accidents occurred in the first two years post-transplant. The two-year incidences of post-transplant CVD, intracranial hemorrhage, and cerebrovascular infarction were 6.1%, 3.2%, and 3.2%, respectively. The incidence rate of CVD within two years after HSCT was 34.7 (95% CI 22.3 to − 53.7) per 1000 person-years, which was about tenfold higher than the general Taiwanese population. The only significant risk factor associated with post-transplant CVD is prior exposure to three or more courses of high-dose cytarabine. Post-transplant CVD is associated with dismal outcome and early mortality. The median overall survival of patients with post-transplant CVD was markedly reduced compared with those without CVD (8.0 vs. 60.6 months). Most patients with post-transplant CVD died within two months after the CVD events. Our study demonstrates that CVD remains a devastating complication after allogeneic HSCT in the modern era.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Effective DNA repair enables cancer cells to survive DNA damage induced by chemotherapeutic or radiotherapeutic treatments. Therefore, inhibiting DNA repair pathways is a promising therapeutic ...strategy for increasing the efficacy of such treatments. In this study, we found that dihydrocoumarin (DHC), a flavoring agent, causes deficiencies in double-stand break (DSB) repair and prolonged DNA damage checkpoint recovery in yeast. Following DNA damage, Rad52 recombinase was revealed to be inhibited by DHC, which results in deficiencies in DSB repair and prolonged DNA damage checkpoint recovery. The deletion of
, a class I histone deacetylase (HDAC), was found to mimic DHC-induced suppression of Rad52 expression, suggesting that the HDAC inhibitor activity of DHC is critical to DSB repair and DNA damage sensitivity. Overall, our findings delineate the regulatory mechanisms of DHC in DSB repair and suggest that it might potentially be used as an inhibitor of the DNA repair pathway in human cells.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
