1.L-Theanine-Treated Adipose-Derived Mesenchymal Stem Cells Alleviate the Cytotoxicity Induced by N-Nitrosodiethylamine in Liver
Yun-Ju LAI ; Yi-Ting SUNG ; Yi-An LAI ; Li-Nian CHEN ; Tung-Sheng CHEN ; Chiang-Ting CHIEN
Tissue Engineering and Regenerative Medicine 2022;19(6):1207-1221
BACKGROUND:
Liver inflammation is the main cause of severe liver diseases, including liver fibrosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Cell therapy topics are receiving increasingly more attention. The therapeutic applications of mesenchymal stem cells (MSC) have become one of the most discussed issues. While other stem cells have therapeutic effects, they have only one or two clinical applications. MSCs are responsible for repairing a variety of tissue injuries. Moreover, MSCs could be derived from several sources, including adipose tissue. MSCs are usually more abundant and easier to obtain compared to other stem cells.
METHODS:
To prove the concept that MSCs have homing ability to the injured tissue and assist in tissue repair, we examined the effects of intravenous injected adipose-derived mesenchymal stem cells (ADSCs) in a N-nitrosodiethylamine (DEN)-induced liver injury rat model.
RESULTS:
The significant repairing ability of ADSCs was observed. The levels of fibrosis, apoptosis, and tumorigenesis in the DEN-injured liver tissues all decreased after ADSC treatment. Furthermore, to enhance the therapeutic effects of ADSCs, we pretreated them with L-theanine, which promotes the hepatocyte growth factor secretion of ADSC, and therefore improved the healing effects on injured liver tissue.
CONCLUSION
ADSCs, especially L-theanine-pretreated ADSCs, have anti-inflammation, anti-apoptosis, and anti-tumorigenesis effects on the N-nitrosodiethylamine-induced liver injury rat model.
2.Survival Benefit of Tamoxifen in Estrogen Receptor-Negative and Progesterone Receptor-Positive Low Grade Breast Cancer Patients.
Li Heng YANG ; Hsin Shun TSENG ; Che LIN ; Li Sheng CHEN ; Shou Tung CHEN ; Shou Jen KUO ; Dar Ren CHEN
Journal of Breast Cancer 2012;15(3):288-295
PURPOSE: This study aimed to analyze the efficacy and prognostic significance of adjuvant tamoxifen in breast cancer patients with various hormone receptor statuses. METHODS: Typically, 1,260 female breast cancer patients were recruited in this study. The correlation between estrogen receptor (ER)/progesterone receptor (PR) phenotypes and clinical characteristics was investigated, and the survival rate was assessed after 5-year follow-up. RESULTS: The 5-year overall survival (85%) was better in women under the age of 50 years. Patients with ER+/PR+ tumors had a better 5-year survival rate (94%); those with ER-/PR- tumors experienced the worst outcome (74% survival rate); whereas single-positive cases were in between. In 97 out of 128 patients with ER-/PR+ tumors, tamoxifen was given as adjuvant hormonal therapy, and it increased the survival benefit in the lower grade group in terms of overall survival and disease-free survival (p=0.01 and p=0.03, respectively). CONCLUSION: For high-grade tumors with ER-/PR+, adjuvant tamoxifen therapy may have no survival benefit, whereas for the patients with low-grade ER-/PR+ tumors, adjuvant tamoxifen therapy is highly suggestive.
Breast
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Breast Neoplasms
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Disease-Free Survival
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Estrogens
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Female
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Humans
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Phenotype
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Progesterone
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Receptors, Progesterone
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Survival Rate
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Tamoxifen
3.Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis
Che-Sheng CHU ; Shu-Li CHENG ; Ya-Mei BAI ; Tung-Ping SU ; Shih-Jen TSAI ; Tzeng-Ji CHEN ; Fu-Chi YANG ; Mu-Hong CHEN ; Chih-Sung LIANG
Psychiatry Investigation 2023;20(9):861-869
Objective:
Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk.
Methods:
This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate.
Results:
With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3.
Conclusion
Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.
4.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.