1.Evaluation of the relationship between cardiac calcification and cardiovascular disease using the echocardiographic calcium score in patients undergoing peritoneal dialysis: a cross-sectional study.
Ho-Kwan SIN ; Ping-Nam WONG ; Kin-Yee LO ; Man-Wai LO ; Shuk-Fan CHAN ; Kwok-Chi LO ; Yuk-Yi WONG ; Lo-Yi HO ; Wing-Tung KWOK ; Kai-Chun CHAN ; Andrew Kui-Man WONG ; Siu-Ka MAK
Singapore medical journal 2023;64(6):379-384
INTRODUCTION:
An echocardiographic calcium score (ECS) predicts cardiovascular disease (CVD) in the general population. Its utility in peritoneal dialysis (PD) patients is unknown.
METHODS:
This cross-sectional study assessed 125 patients on PD. The ECS (range 0-8) was compared between subjects with CVD and those without.
RESULTS:
Among the subjects, 54 had CVD and 71 did not. Subjects with CVD were older (69 years vs. 56 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (81.5% vs. 45.1%, P < 0.001). They had lower diastolic blood pressure (72 mmHg vs. 81 mmHg, P < 0.001), lower phosphate (1.6 mmol/L vs. 1.9 mmol/L, P = 0.002), albumin (30 g/L vs. 32 g/L, P = 0.001), parathyroid hormone (34.4 pmol/L vs. 55.8 pmol/L, P = 0.002), total cholesterol (4.5 vs. 4.9, P = 0.047), LDL cholesterol (2.4 mmol/L vs. 2.8 mmol/L, P = 0.019) and HDL cholesterol (0.8 mmol/L vs. 1.1 mmol/L, P = 0.002). The ECS was found to be higher in subjects with CVD than in those without (2 vs. 1, P = 0.001). On multivariate analysis, only DM and age were independently associated with CVD.
CONCLUSION
The ECS was significantly higher in PD patients with CVD than in those without, reflecting a higher vascular calcification burden in the former. It is a potentially useful tool to quantify vascular calcification in PD patients.
Humans
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Cardiovascular Diseases/diagnostic imaging*
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Cross-Sectional Studies
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Calcium
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Peritoneal Dialysis/adverse effects*
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Vascular Calcification/epidemiology*
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Echocardiography
2.Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien TSAI ; Chung-Feng HUANG ; Ming-Lun YEH ; Meng-Hsuan HSIEH ; Hsing-Tao KUO ; Chao-Hung HUNG ; Kuo-Chih TSENG ; Hsueh-Chou LAI ; Cheng-Yuan PENG ; Jing-Houng WANG ; Jyh-Jou CHEN ; Pei-Lun LEE ; Rong-Nan CHIEN ; Chi-Chieh YANG ; Gin-Ho LO ; Jia-Horng KAO ; Chun-Jen LIU ; Chen-Hua LIU ; Sheng-Lei YAN ; Chun-Yen LIN ; Wei-Wen SU ; Cheng-Hsin CHU ; Chih-Jen CHEN ; Shui-Yi TUNG ; Chi‐Ming TAI ; Chih-Wen LIN ; Ching-Chu LO ; Pin-Nan CHENG ; Yen-Cheng CHIU ; Chia-Chi WANG ; Jin-Shiung CHENG ; Wei-Lun TSAI ; Han-Chieh LIN ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Jee-Fu HUANG ; Chia-Yen DAI ; Wan-Long CHUNG ; Ming-Jong BAIR ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(3):468-486
Background/Aims:
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods:
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results:
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
3.Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.
Dexiu YAN ; Jemma ARAKELYAN ; Teng WAN ; Ritvik RAINA ; Tsz Ki CHAN ; Dohyun AHN ; Vladimir KUSHNAREV ; Tsz Kiu CHEUNG ; Ho Ching CHAN ; Inseo CHOI ; Pui Yi HO ; Feijun HU ; Yujeong KIM ; Hill Lam LAU ; Ying Lo LAW ; Chi Seng LEUNG ; Chun Yin TONG ; Kai Kap WONG ; Wing Lam YIM ; Nikolay S KARNAUKHOV ; Richard Y C KONG ; Maria V BABAK ; Yudai MATSUDA
Acta Pharmaceutica Sinica B 2024;14(1):421-432
A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.