Mesenchymal Stem Cell Secreted-Extracellular Vesicles are Involved in Chondrocyte Production and Reduce Adipogenesis during Stem Cell Differentiation

Tsai Yu-Chen,Cheng Tai-Shan,Liao Hsiu-Jung,Chuang Ming-Hsi,Chen Hui-Ting,Chen Chun-Hung,Zhang Kai-Ling,Chang Chih-Hung,Lin Po-Cheng,Huang Chi-Ying F. 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.6

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. CONCLUSION: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

High-Performance Bottom-Contact Organic Thin-Film Transistors Based on Benzo[<i>d</i>,<i>d</i>′]thieno[3,2-<i>b</i>;4,5-<i>b</i>′]dithiophenes (BTDTs) Derivatives

Huang, Peng-Yi,Chen, Liang-Hsiang,Kim, Choongik,Chang, Hsiu-Chieh,Liang, You-jhih,Feng, Chieh-Yuan,Yeh, Chia-Ming,Ho, Jia-Chong,Lee, Cheng-Chung,Chen, Ming-Chou American Chemical Society 2012 ACS APPLIED MATERIALS & INTERFACES Vol.4 No.12

<P>Three benzo[<I>d</I>,<I>d</I>′]thieno[3,2-<I>b</I>;4,5-<I>b</I>′]dithiophene (<B>BTDT</B>) derivatives, end-functionalized with benzothiophenyl (<B>BT-BTDT</B>; <B>2</B>), benzothieno[3,2-b]thiophenyl (<B>BTT-BTDT</B>; 3), and benzo[<I>d</I>,<I>d</I>′]thieno[3,2-<I>b</I>;4,5-<I>b</I>′]dithiophenyl (<B>BBTDT</B>; <B>4</B>), were prepared for bottom-contact/bottom-gate organic thin-film transistors (OTFTs). An improved one-pot [2 + 1 + 1] synthetic method of <B>BTDT</B> with improved synthetic yield was achieved, which enabled the efficient realization of new <B>BTDT</B>-based semiconductors. All of the <B>BTDT</B> compounds exhibited high performance p-channel characteristics with carrier mobilities as high as 0.34 cm<SUP>2</SUP>/(V s) and a current on/off ratio of 1 × 10<SUP>7</SUP>, as well as enhanced ambient stability. The device characteristics have been correlated with the film morphologies and microstructures of the corresponding compounds.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2012/aamick.2012.4.issue-12/am3022448/production/images/medium/am-2012-022448_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am3022448'>ACS Electronic Supporting Info</A></P>

Conjugation of mono-sulfobetaine to alkyne-PPX films via click reaction to reduce cell adhesion

Chien, Hsiu-Wen,Keng, Ming-Chun,Chen, Hsien-Yeh,Huang, Sheng-Tung,Tsai, Wei-Bor Techno-Press 2016 Biomaterials and biomedical engineering Vol.3 No.1

A surface resisting protein adsorption and cell adhesion is highly desirable for many biomedical applications such as diagnostic devices, biosensors and blood-contacting devices. In this study, a surface conjugated with sulfobetaine molecules was fabricated via the click reaction for the anti-fouling purpose. An alkyne-containing substrate (Alkyne-PPX) was generated by chemical vapor deposition of 4-ethynyl-[2,2]paracyclophane. Azide-ended mono-sulfobetaine molecules were synthesized and then conjugated on Alkyne-PPX via the click reaction. The protein adsorption from 10% serum was reduced by 57%, while the attachment of L929 cells was reduced by 83% onto the sulfobetaine-PPX surface compared to the protein adsorption and cell adhesion on Alkyne-PPX. In conclusion, we demonstrate that conjugation of mono-sulfobetaine molecules via the click chemistry is an effective way for reduction of non-specific protein adsorption and cell attachment.

Clinical Features of Patients with Esophageal and Second Primary Cancers

Tsai, Huang-Wen,Chang, Chih-Chun,Sun, Jen-Tang,Liou, Ching-Biau,Lin, Hsiu-Chen,Lin, I-Hsin,Yu, Yun-Chieh,Weng, Wei-Ling,Leong, Ka-I,Yen, Tzung-Hai,Wu, Jiann-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population. Materials and Methods: Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified. Results: The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006). Conclusions: The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.

Conjugation of mono-sulfobetaine to alkyne-PPX films via click reaction to reduce cell adhesion

Chien, Hsiu-Wen,Keng, Ming-Chun,Chen, Hsien-Yeh,Huang, Sheng-Tung,Tsai, Wei-Bor Techno-Press 2016 Biomaterials and Biomechanics in Bioengineering Vol.3 No.1

A surface resisting protein adsorption and cell adhesion is highly desirable for many biomedical applications such as diagnostic devices, biosensors and blood-contacting devices. In this study, a surface conjugated with sulfobetaine molecules was fabricated via the click reaction for the anti-fouling purpose. An alkyne-containing substrate (Alkyne-PPX) was generated by chemical vapor deposition of 4-ethynyl-[2,2]paracyclophane. Azide-ended mono-sulfobetaine molecules were synthesized and then conjugated on Alkyne-PPX via the click reaction. The protein adsorption from 10% serum was reduced by 57%, while the attachment of L929 cells was reduced by 83% onto the sulfobetaine-PPX surface compared to the protein adsorption and cell adhesion on Alkyne-PPX. In conclusion, we demonstrate that conjugation of mono-sulfobetaine molecules via the click chemistry is an effective way for reduction of non-specific protein adsorption and cell attachment.

Impact of Adjuvant Chemotherapy in Elderly Breast Patients in Taiwan, A Hospital-Based Study

Lee, Hsiu Chuan,Chen, Wei Yu,Huang, Wen Tsung,Cheng, Kuo Chen,Tian, Yu Feng,Ho, Chung Han,Tsao, Chao Jung,Feng, Yin Hsun Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

Purpose: Decisions as to whether to provide adjuvant treatment in older breast cancer patients remains challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty. To aid decision-making, we retrospectively analyzed 110 women with breast cancer treated with a curative intention from 2006 to 2012. Survival data with clinical and pathological parameters were evaluated to address the role of adjuvant chemotherapy in this study population. Method: A total of 110 elderly (>70 years) patients that received mastectomy at two hospitals in Taiwan were observed retrospectively for a medium of 51 months. After mastectomy, patients received conservative treatment or adjuvant chemotherapy, or hormone therapy following clinical guidelines or physician's preference. Data were collected from the cancer registry system. Results: Median age at diagnosis was 75.7 years. Thirty-five percent of patients received adjuvant chemotherapy, these having a significantly younger age ($mean=74.0{\pm}5.3$ vs $77.5{\pm}5.3$, p<0.001) and higher tumor staging (p=0.003) compared with their non-chemotherapy counterparts.Five-year overall survival was non-significantly higher in patients who received adjuvant chemotherapy (with chemotherapy 64.2% vs without chemotherapy 62.6%, p=0.635), while five-year recurrence free survival was non-significantly lower (with chemotherapy 64.1% vs without chemotherapy 90.5%, p=0.80). Conclusions: In this analysis, adjuvant chemotherapy tended to be given to patients with a younger age and higher tumor staging at our institute. It was not associated with any statistically significant improvement in survival and recurrence rate. Until age specific recommendations are available, physicians must use their clinical judgment and assess the tumor biology with the patient's comorbidities to make the best choice. Clinical trials focusing on this critical issue are warranted.

Current Indications for Spinal Endoscopic Surgery and Potential for Future Expansion

Kuo-Tai Chen,김진성,Abel Po-Hao Huang,Martin Hsiu-Chu Lin,Chien-Min Chen 대한척추신경외과학회 2023 Neurospine Vol.20 No.1

Endoscopic spine surgery (ESS) has evolved as a safe, effective, and efficient alternative for minimally invasive spine surgery (MISS). The innovation of full-endoscopic systems makes definitive decompression surgery through different approaches feasible. The approach can be determined according to the location of the target lesion or the surgeon's preference. During the past 2 decades, ESS has expanded its indications from lumbar to cervical spines. Except for decompression, endoscopy-assisted fusion surgery is also developing. However, ESS is still evolving and has a steep learning curve. The revolution of technologies and ESS techniques will enable surgeons to treat various spinal diseases more practically. In recent years, the application of the computer-assisted navigation system and augmented reality have reformed imaging quality and interpretation. The endoscopic rhizotomy techniques have opened a new way for MISS of chronic low back pain. This review introduces the current indications of ESS and its potential future expansion.

Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages

Yuan-Shen Chen,Wei-Chu Chuang,Hsiu-Ni Kung,Ching-Yuan Cheng,Duen-Yi Huang,Ponarulselvam Sekar,Wan-Wan Lin 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.4

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

The Presence of Borrelia valaisiana-Related Genospecies in Ticks and a Rodent in Taiwan

Chun-Man Huang,Hsi-Chieh Wang,Ying-Chun Lin,Shih-Hui Chiu,Ying-Shun Kao,Pei-Lung Lee,Hsiu-I Wang,Ruei-Chen Hung,Huang-I Chan,Ho-Sheng Wu,Chuen-Sheue Chiang,Jung-Jung Mu 한국미생물학회 2010 The journal of microbiology Vol.48 No.6

A field survey was conducted to investigate the presence of Borrelia burgdorferi sensu lato (s.l.) in six counties of Taiwan. Spirochetes were successfully isolated from one rodent ear sample out of 485 rodent ears and 53live, fed tick (Ixodes granulatus) samples. The spirochetes were confirmed to be B. burgdorferi s.l. by real-time PCR. In addition, 23 of 113 tick samples were tested positive for Borrelia DNA according to real-time PCR. The Borrelia isolate from the rodent and the 23 Borrelia DNA samples from the ticks were identified as B. valaisiana-related genospecies by phylogenetic analysis based on flagellin gene sequences. These findings suggest that the Borrelia valaisiana-related strains are maintained in a zoonotic cycle between tick vectors and reservoir hosts in Taiwan.