4.Comparison of the Infant and Adult Adipose-Derived Mesenchymal Stem Cells in Proliferation, Senescence, Antioxidative Ability and Differentiation Potential
Szu-Hsien WU ; Jin-Huei YU ; Yu-Ting LIAO ; Kuo-Hao LIU ; En-Rung CHIANG ; Ming-Chau CHANG ; Jung-pan WANG
Tissue Engineering and Regenerative Medicine 2022;19(3):589-601
BACKGROUND:
Infant adipose-derived mesenchymal stem cells (ADSCs) collected from excised polydactyly fat tissue, which was surgical waste, could be cultured and expanded in vitro in this study. In addition, the collecting process would not cause pain in the host. In this study, the proliferation, reduction of senescence, anti-oxidative ability, and differentiation potential in the infant ADSCs were compared with those in the adult ADSCs harvested from thigh liposuction to determine the availability of infant ADSCs.
METHODS:
Proliferation was determined by detecting the fold changes in cell numbers and doubling time periods.Senescence was analyzed by investigating the age-related gene expression levels and the replicative stress. The superoxide dismutase (SOD) gene expression, adipogenic, neurogenic, osteogenic, and tenogenic differentiation were compared by RTqPCR. The chondrogenic differentiation efficiency was also determined using RT-qPCR and immunohistochemical staining.
RESULTS:
The proliferation, SOD (SOD1, SOD2 and SOD3) gene expression, the stemness-related gene (c-MYC) and telomerase reverse transcriptase of the infant ADSCs at early passages were enhanced compared with those of the adults’Cellular senescence related genes, including p16, p21 and p53, and replicative stress were reduced in the infant ADSCs. The adipogenic genes (PPARγ and LPL) and neurogenic genes (MAP2 and NEFH) of the infant ADSC differentiated cells were significantly higher than those of the adults’ while the expression of the osteogenic genes (OCN and RUNX) and tenogenic genes (TNC and COL3A1) of both demonstrated opposite results. The chondrogenic markers (SOX9, COL2 and COL10) were enhanced in the infant ADSC differentiated chondrogenic pellets, and the expression levels of SODs were decreased during the differentiation process.
CONCLUSION
Cultured infant ADSCs demonstrate less cellular senescence and replicative stress, higher proliferation rates, better antioxidant defense activity, and higher potential of chondrogenic, adipogenic and neurogenic differentiation.
5.Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors
Jian-Hua HONG ; Ming-Chieh KUO ; Yung-Ting CHENG ; Yu-Chuan LU ; Chao-Yuan HUANG ; Shih-Ping LIU ; Po-Ming CHOW ; Kuo-How HUANG ; Shih-Chieh Jeff CHUEH ; Chung-Hsin CHEN ; Yeong-Shiau PU
The World Journal of Men's Health 2024;42(3):587-599
Purpose:
Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS.
Materials and Methods:
This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model.
Results:
A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL2 predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17–2.88) and conversion (HR 1.56, 95% CI 1.05–2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91–2.18; ≥50%: HR 1.97, 95% CI 1.1453–3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06–6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years).
Conclusions
AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.
6.Frequent association of malignant effusions in plasmablastic lymphoma:a single‑institutional experience of nine cases in Taiwan
Bo‑Jung CHEN ; Yu‑Ting KUO ; Sheng‑Tsung CHANG ; Khin‑Than WIN ; Shang‑Wen CHEN ; Sheng‑Yen HSIAO ; Yin‑Hsun FENG ; Yen‑Chuan HSIEH ; Shih‑Sung CHUANG
Blood Research 2025;60():22-
Purpose:
Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare.
Methods:
This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024.
Results:
We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse.
Conclusion
In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.
7.In-room cytologic evaluation by trained endosonographer for determination of procedure end in endoscopic ultrasound-guided fine needle biopsy of solid pancreatic lesions: a prospective study in Taiwan
Weng-Fai WONG ; Yu-Ting KUO ; Wern-Cherng CHENG ; Chia-Tung SHUN ; Ming-Lun HAN ; Chieh-Chang CHEN ; Hsiu-Po WANG
Clinical Endoscopy 2025;58(3):465-473
Background/Aims:
Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE).
Methods:
A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE).
Results:
We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%.
Conclusions
In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.
8.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
9.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
10.Frequent association of malignant effusions in plasmablastic lymphoma:a single‑institutional experience of nine cases in Taiwan
Bo‑Jung CHEN ; Yu‑Ting KUO ; Sheng‑Tsung CHANG ; Khin‑Than WIN ; Shang‑Wen CHEN ; Sheng‑Yen HSIAO ; Yin‑Hsun FENG ; Yen‑Chuan HSIEH ; Shih‑Sung CHUANG
Blood Research 2025;60():22-
Purpose:
Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare.
Methods:
This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024.
Results:
We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse.
Conclusion
In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.