Publications by authors named "Yu-Jen Chen"

343 Publications

Correction to: Association of bowel radiation dose-volume with skeletal muscle loss during pelvic intensity-modulated radiotherapy in cervical cancer.

Support Care Cancer 2021 Nov 25. Epub 2021 Nov 25.

Department of Radiation Oncology, MacKay Memorial Hospital, 92, Section 2, Chung Shan North Road, Taipei, 10449, Taiwan.

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http://dx.doi.org/10.1007/s00520-021-06709-5DOI Listing
November 2021

Effects of laser therapy on chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.

Clin Rehabil 2021 Nov 10:2692155211057435. Epub 2021 Nov 10.

Department of Physical Medicine and Rehabilitation, 159518Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

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http://dx.doi.org/10.1177/02692155211057435DOI Listing
November 2021

Comparative outcomes between all-inside arthroscopic suture anchor technique versus arthroscopic transosseous suture technique in patients with triangular fibrocartilage complex tear: a retrospective comparative study.

J Orthop Surg Res 2021 Oct 14;16(1):600. Epub 2021 Oct 14.

Department of Orthopedics, Fu Jen Catholic University Hospital, Fu Jen Catholic University , New Taipei City, 24352, Taiwan, ROC.

Background: Triangular fibrocartilage complex (TFCC) has become an interest over the last few decades, discovering its understanding in anatomy, pathomechanism, biomechanics, and management in treatments. Currently, TFCC does not have a golden standard procedure, and not one surgical procedure is superior to the other. This study is to evaluate the comparative outcomes in TFCC patients that underwent either in all-inside arthroscopic suture anchors or the arthroscopic transosseous suture technique.

Method: From 2017 to 2019, 30 patients were analyzed. Eight patients were in an arthroscopic transosseous group and 22 patients were in an all-inside arthroscopic group. Comparison between patients' flexion and extension range of motion (ROM), grip strength, and visual analog pain scale (VAS) preoperative and six-month follow-up were analyzed.

Result: There were significant increases in flexion ROM, extension ROM, and VAS between preoperative and postoperative in all-inside arthroscopic and arthroscopic transosseous. Only the all-inside arthroscopic group had a significant increase in grip strength. Postoperative flexion ROM had a significant difference between all-inside arthroscopic and arthroscopic transosseous.

Conclusion: Both the all-inside arthroscopic suture anchor technique and the arthroscopic transosseous suture technique are appropriate treatments to treat patients with TFCC. Both procedures have achieved the ultimate goal of improved longevity and optimal function.

Level Of Evidence: Level III; retrospective comparative cohort study.
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http://dx.doi.org/10.1186/s13018-021-02752-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515735PMC
October 2021

The clinical significance of esophagogastric varices in patients with advanced pancreatic cancer.

J Chin Med Assoc 2021 10;84(10):917-922

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taiwan, ROC.

Background: The prevalence of esophagogastric varices (EGV) in patients with advanced pancreatic cancer is not rare. However, its clinical significance has never been investigated. This study was aimed to explore the clinical implication and outcomes of these patients.

Methods: A retrospective analysis comprising 224 patients with advanced pancreatic cancer managed from October 2012 to December 2019 at a tertiary medical center identified 35 patients who had presented with EGV. Clinical characteristics and outcomes were analyzed with special emphasis on comparison between patients with early-onset and late-onset EGV.

Results: Patients with EGV had lower platelet count and a higher proportion of splenomegaly but no difference in overall survival in comparison to those without EGV. Patients with early-onset EGV had a poorer bleeding survival (hazard ratio, 8.347; CI, 2.509-27.772; p = 0.001) in comparison to those with late-onset EGV. On multivariate analysis, initial serum bilirubin, γ-Glutamyltransferase, lactate dehydrogenase, cancer stage, and the response to cancer treatment determine the patient's survival. Patients with tumor invasion to superior mesenteric and portal vein are more likely to have esophageal varices (EV) (EV: 13/15 vs gastric varices [GV]: 4/20; p < 0.001); those with splenic vein invasion are more likely to have GV (EV: 4/15 vs GV: 20/20; p < 0.001).

Conclusion: Patients with advanced pancreatic cancer and early-onset EGV had poorer bleeding-free survival than those with late-onset EGV. Further studies are needed to clarify the benefits of the prophylactic intervention.
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http://dx.doi.org/10.1097/JCMA.0000000000000609DOI Listing
October 2021

Combination of 35-Gene Mutation Profile and Radiotherapy Dosimetry Predicts the Therapeutic Outcome of Definitive Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma.

Front Oncol 2021 27;11:729418. Epub 2021 Aug 27.

Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.

Esophageal cancer is a common malignancy worldwide and a leading cause of cancer-related mortality. Definitive concurrent chemoradiotherapy (CCRT) has been widely used to treat locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we evaluated the predictive power of a 35-gene mutation profile and radiation parameters in patients with ESCC. Data from 44 patients with ESCC who underwent definitive CCRT were retrospectively reviewed. A 35-gene mutation profile, derived from reported ESCC-specific next-generation sequencing results, and radiation dosimetry parameters were examined using the Kaplan-Meier curve and Cox proportional hazards model. All patients were native Chinese and underwent CCRT with a median follow-up time of 22.0 months. Significant prognostic factors affecting progression-free survival in the multivariable Cox regression model were clinical nodal staging ≥2 (hazard ratio, HR: 2.52, 95% CI: 1.15-5.54, = 0.022), ≥10% lung volume receiving ≥30 Gy (V30) (HR: 2.36, 95% CI: 1.08-5.17, = 0.032), and mutation of fibrous sheath interacting protein 2 () (HR: 0.08, 95% CI: 0.01-0.58, = 0.013). For overall survival, significant prognostic factors in the multivariable Cox regression model were lung V30 ≥10% (HR: 3.71, 95% CI: 1.48-9.35, = 0.005) and mutation of spectrin repeat containing nuclear envelope protein 1 () (HR: 2.95, 95% CI: 1.25-6.97, = 0.014). Our cohort showed higher (79.5% vs. 5.7%), (18.2% vs. 6.2%), and (38.6% vs. 11.0%) mutation rates and lower (38.6% vs. 68.7%) mutation rates than the ESCC cohorts from The Cancer Genome Atlas. In conclusion, by using a combination of a 35-gene mutation profile and radiotherapy dosimetry, mutations in and as well as lung V30 were identified as potential predictors for developing a prediction model for clinical outcomes in patients with ESCC administered definitive CCRT.
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http://dx.doi.org/10.3389/fonc.2021.729418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430340PMC
August 2021

Association of Patient-Reported Outcomes and Nutrition with Body Composition in Women with Gynecologic Cancer Undergoing Post-Operative Pelvic Radiotherapy: An Observational Study.

Nutrients 2021 Jul 29;13(8). Epub 2021 Jul 29.

Department of Radiation Oncology, MacKay Memorial Hospital, Taipei 104215, Taiwan.

Pelvic radiotherapy is associated with gastrointestinal toxicities and deterioration of nutritional status. This study aimed to investigate the association of patient-reported outcomes (PROs) and nutritional status with body composition changes in women who underwent hysterectomy and post-operative radiotherapy for gynecologic cancer. We analyzed data of 210 patients treated with post-operative pelvic radiotherapy for gynecologic cancer between 2013 and 2018. The PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was used for gastrointestinal toxicity assessment. The Patient-Generated Subjective Global Assessment (PG-SGA) was used for nutritional assessment. Skeletal muscle index was measured from computed tomography scans at the L3 vertebral level. A reduction in skeletal muscle index ≥ 5% was classified as muscle loss. Odds ratios were calculated through logistic regression models. The PG-SGA score increased from the beginning to the end of radiotherapy (1.4 vs. 3.7, < 0.001). Patients with PRO-CTCAE scores ≥ 3 had significantly higher PG-SGA scores at the end of radiotherapy than those with PRO-CTCAE scores ≤ 2 (8.1 vs. 2.3, < 0.001). On multivariable analysis, PRO-CTCAE scores ≥ 3 and PG-SGA scores ≥ 4 at the end of radiotherapy were independently associated with increased risk of muscle loss (odds ratio: 8.81, < 0.001; odds ratio: 72.96, < 0.001, respectively). PROs and PG-SGA may be considered as markers of muscle loss after post-operative pelvic radiotherapy for gynecologic cancer.
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http://dx.doi.org/10.3390/nu13082629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399258PMC
July 2021

Delta-volume radiomics of induction chemotherapy to predict outcome of subsequent chemoradiotherapy for locally advanced hypopharyngeal cancer.

Tumori 2021 Aug 21:3008916211039018. Epub 2021 Aug 21.

Department of Radiation Oncology, MacKay Memorial Hospital, Taipei.

Introduction: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC.

Methods: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score).

Results: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<-0.16) was associated with improved PFS ( < 0.05).

Conclusions: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.
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http://dx.doi.org/10.1177/03008916211039018DOI Listing
August 2021

Docosahexaenoic Acid Suppresses Expression of Adipogenic Tetranectin through Sterol Regulatory Element-Binding Protein and Forkhead Box O Protein in Pigs.

Nutrients 2021 Jul 5;13(7). Epub 2021 Jul 5.

Department of Animal Science and Technology, National Taiwan University, Taipei 10672, Taiwan.

Tetranectin (TN), a plasminogen-binding protein originally involved in fibrinolysis and bone formation, was later identified as a secreted adipokine from human and rat adipocytes and positively correlated with adipogenesis and lipid metabolism in adipocytes. To elucidate the nutritional regulation of adipogenic TN from diets containing different sources of fatty acids (saturated, -6, -3) in adipocytes, we cloned the coding region of porcine TN from a cDNA library and analyzed tissue expressions in weaned piglets fed with 2% soybean oil (SB, enriched in -6 fatty acids), docosahexaenoic acid oil (DHA, an -3 fatty acid) or beef tallow (BT, enriched in saturated and -9 fatty acids) for 30 d. Compared with tissues in the BT- or SB-fed group, expression of TN was reduced in the adipose, liver and lung tissues from the DHA-fed group, accompanied with lowered plasma levels of triglycerides and cholesterols. This in vivo reduction was also confirmed in porcine primary differentiated adipocytes supplemented with DHA in vitro. Then, promoter analysis was performed. A 1956-bp putative porcine TN promoter was cloned and transcription binding sites for sterol regulatory-element binding protein (SREBP)-1c or forkhead box O proteins (FoxO) were predicted on the TN promoter. Mutating binding sites on porcine TN promoters showed that transcriptional suppression of TN by DHA on promoter activity was dependent on specific response elements for SREBP-1c or FoxO. The inhibited luciferase promoter activity by DHA on the TN promoter coincides with reduced gene expression of TN, SREBP-1c, and FoxO1 in human embryonic kidney HEK293T cells supplemented with DHA. To conclude, our current study demonstrated that the adipogenic TN was negatively regulated by nutritional modulation of DHA both in pigs in vivo and in humans/pigs in vitro. The transcriptional suppression by DHA on TN expression was partly through SREBP-1c or FoxO. Therefore, down-regulation of adipogenic tetranectin associated with fibrinolysis and adipogenesis may contribute to the beneficial effects of DHA on ameliorating obesity-induced metabolic syndromes such as atherosclerosis and adipose dysfunctions.
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http://dx.doi.org/10.3390/nu13072315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308646PMC
July 2021

Portable self-flowing platform for filtration separation of samples.

Anal Methods 2021 08 26;13(32):3605-3613. Epub 2021 Jul 26.

Institute of Mechatronic Engineering, National Taipei University of Technology, Taipei, Taiwan.

A portable self-flow filtration and separation platform was designed using soft lithography to create a polydimethylsiloxane (PDMS) microfluidic channel cover combined with a matching acrylic substrate. The separation zone was filled with microbeads of appropriate sizes to achieve universal filtration and separation. This simple structure requires only 20 μl of the sample for filtration separation. A vacuum of 760 torr is applied to the porous PDMS cover to drive the sample during testing. The average time required for a 20 μl sample of blood to pass through the separation zone is about 56 s, while the filling time for the detection zone of volume 6 μl is about 319 s. When the hematocrit of the blood sample is about 20-25%, the separation efficiency is 99.98%. Further, the separation efficiency of fat globules from raw milk is close to 100%, whereas almost all impurities are filtered out from juice and stool samples. It is also observed that E. coli in the stool can pass from the separation to detection zone at a maximum rate of about 81.21%, with an average of about 68.18%.
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http://dx.doi.org/10.1039/d1ay00716eDOI Listing
August 2021

Influence of Antibiotic-Loaded Acrylic Bone Cement Composition on Drug Release Behavior and Mechanism.

Polymers (Basel) 2021 Jul 8;13(14). Epub 2021 Jul 8.

Accelerator for Happiness and Health Industry, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd., Taipei 10608, Taiwan.

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery.
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http://dx.doi.org/10.3390/polym13142240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309450PMC
July 2021

Impact of the Time Interval Between Primary Debulking Surgery and Start of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

Cancer Manag Res 2021 6;13:5413-5422. Epub 2021 Jul 6.

Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Aim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC).

Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O'Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival.

Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (<23 days), intermediate (23-43 days) and late (>43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10-0.83, =0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group.

Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3-6 weeks post-operatively. Initiating chemotherapy early (<23 days) did not appear to benefit PFS.
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http://dx.doi.org/10.2147/CMAR.S313013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275047PMC
July 2021

Metronomic Therapy in Oral Squamous Cell Carcinoma.

J Clin Med 2021 Jun 26;10(13). Epub 2021 Jun 26.

Department of Nursing, MacKay Junior College of Medicine, Nursing and Management, Taipei City 112021, Taiwan.

Metronomic therapy is characterized by drug administration in a low-dose, repeated, and regular manner without prolonged drug-free interval. The two main anticancer mechanisms of metronomic therapy are antiangiogenesis and immunomodulation, which have been demonstrated in several delicate in vitro and in vivo experiments. In contrast to the traditional maximum tolerated dose (MTD) dosing of chemotherapy, metronomic therapy possesses comparative efficacy but greatlydecreases the incidence and severity of treatment side-effects. Clinical trials of metronomic anticancer treatment have revealed promising results in a variety cancer types and specific patient populations such as the elderly and pediatric malignancies. Oral cavity squamous cell carcinoma (OCSCC) is an important health issue in many areas around the world. Long-term survival is about 50% in locally advanced disease despite having high-intensity treatment combined surgery, radiotherapy, and chemotherapy. In this article, we review and summarize the essence of metronomic therapy and focus on its applications in OCSCC treatment.
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http://dx.doi.org/10.3390/jcm10132818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269021PMC
June 2021

From Genetic Mutations to Molecular Basis of Heart Failure Treatment: An Overview of the Mechanism and Implication of the Novel Modulators for Cardiac Myosin.

Int J Mol Sci 2021 Jun 21;22(12). Epub 2021 Jun 21.

Institute of Public Health, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.

Heart failure (HF) is a syndrome encompassing several important etiologies that lead to the imbalance between oxygen demand and supply. Despite the usage of guideline-directed medical therapy for HF has shown better outcomes, novel therapeutic strategies are desirable, especially for patients with preserved or mildly reduced left ventricular ejection fraction. In this regard, understanding the molecular basis for cardiomyopathies is expected to fill in the knowledge gap and generate new therapies to improve prognosis for HF. This review discusses an evolutionary mechanism designed to regulate cardiac contraction and relaxation through the most often genetically determined cardiomyopathies associated with HF. In addition, both the myosin inhibitor and myosin activator are promising new treatments for cardiomyopathies. A comprehensive review from genetic mutations to the molecular basis of direct sarcomere modulators will help shed light on future studies for a better characterization of HF etiologies and potential therapeutic targets.
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http://dx.doi.org/10.3390/ijms22126617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234187PMC
June 2021

Chest pain in a heart transplant recipient: A case report.

World J Clin Cases 2021 Jun;9(16):3966-3970

Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.

Background: Heart transplantation is recommended for the treatment of patients with refractory heart failure. Chest pain after heart transplantation is usually considered noncardiac owing to the denervated heart. However, data from case reports on tacrolimus-induced achalasia after heart transplantation are limited. We aimed to present a case of tacrolimus-induced achalasia that developed after heart transplantation, which was successfully relieved by laparoscopic Heller myotomy.

Case Summary: A 67-year-old man with a history of Type 2 diabetes mellitus, hyperlipidemia, and dilated cardiomyopathy had congestive heart failure following orthotopic heart transplantation with tacrolimus treatment 12 years ago. At the 10-year follow-up after the heart transplantation, the patient presented with persistent cough, dysphagia, heartburn, and retrosternal chest pain lasting for 2 wk. Upper endoscopy revealed no specific findings. Two years later, the patient experienced the same symptoms, including chest pain lasting for 4 wk. Esophagogram and manometry confirmed the presence of achalasia. Previous reports showed that discontinuing calcineurin inhibitor (CNI) treatment and endoscopic botulinum toxin injection could treat CNI-induced achalasia. Owing to the risk of rejection of the transplanted heart and considering the temporary benefits of botulinum toxin injection in achalasia, the patient underwent laparoscopic Heller myotomy. Dysphagia was relieved without complications. Eight months later, he had no signs of recurrence of the achalasia.

Conclusion: In transplant patients with chest pain and gastrointestinal symptoms, CNI-induced achalasia may be one of the differential diagnoses. Esophagogram/manometry is useful for diagnosis.
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http://dx.doi.org/10.12998/wjcc.v9.i16.3966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180230PMC
June 2021

Analyzing the Expression of Biomarkers in Prostate Cancer Cell Lines.

In Vivo 2021 May-Jun;35(3):1545-1548

Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan, R.O.C.;

Background/aim: CD44 and CD133 have been implicated as biomarkers of cancer cells and their expression could be analyzed to identify circulating tumor cells. Although CD44 and CD133 have been shown to be expressed in prostate cancer cells, a differential expression pattern has been reported depending on the tumor stage and cell line examined. We further investigated CD44 and CD133 expression in different prostate cancer cell lines to confirm whether their expression is distinguishable among patients with various tumor stages.

Materials And Methods: CWR22Rv1, PC3, LNCaP, and DU145 cell lines were cultured and the cell morphology was observed for three days. The single expression of CD44 or CD133 and their combined expression were analyzed by flow cytometry.

Results: We report that the single expression of CD133 was less than 5% in all cell lines examined here. PC3 and DU145 cells displayed a high expression of CD44 (>93%), while the expression of CD44 was less than 4% in CWR22Rv1 and LNCaP cells. CWR22Rv1 was the only cell line that demonstrated a high co-expression of both CD44 and CD133.

Conclusion: Both single and combined expression of CD44 and CD133 should be considered when validating the detection of prostate cancer cells in circulating tumor cells.
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http://dx.doi.org/10.21873/invivo.12408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193287PMC
June 2021

NM23-H1 Expression of Head and Neck Squamous Cell Carcinoma in Association With the Response to Irradiation.

Front Oncol 2021 30;11:646167. Epub 2021 Mar 30.

Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.

A low NM23-H1 expression in head and neck squamous cell carcinoma (HNSCC) was found to be associated with poor clinical outcome. Therefore, we investigated the role of NM23-H1 in the susceptibility of HNSCC cells to irradiation and its clinical significance. An study was also conducted to validate the results. Furthermore, we used immunohistochemistry to analyze NM23-H1 expression found in specimens of 50 HNSCC patients with cervical metastases receiving postoperative radiotherapy. Low tumor NM23-H1 expression was associated with locoregional recurrence of HNSCC (p=0.040; Hazard ratio=5.62) and poor clinical outcome (p=0.001; Hazard ratio=4.90). To confirm the effect of NM23-H1 on radiation-induced cytotoxicity, we generated several stable clones derived from a human HNSCC cell line (SAS) using knockdown and overexpression of NM23-H1. Knockdown of NM23-H1 decreased the radio-sensitivity of SAS cells, possibly associated with a decrease in the radiation-induced G2/M-phase accumulation and upregulation of cyclin B1. On the contrary, overexpression of NM23-H1 can reverse the aforementioned adverse results. Consequently, we suggest that NM23-H1 expression may be considered as a potential therapeutic treatment option for HNSCC patients.
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http://dx.doi.org/10.3389/fonc.2021.646167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042278PMC
March 2021

Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation.

Front Immunol 2021 29;12:630380. Epub 2021 Mar 29.

Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.

Activation of the Nod-like receptor 3 (NLRP3) inflammasome is important for activation of innate immune responses, but improper and excessive activation can cause inflammatory disease. We previously showed that glycolysis, a metabolic pathway that converts glucose into pyruvate, is essential for NLRP3 inflammasome activation in macrophages. Here, we investigated the role of metabolic pathways downstream glycolysis - lactic acid fermentation and pyruvate oxidation-in activation of the NLRP3 inflammasome. Using pharmacological or genetic approaches, we show that decreasing lactic acid fermentation by inhibiting lactate dehydrogenase reduced caspase-1 activation and IL-1β maturation in response to various NLRP3 inflammasome agonists such as nigericin, ATP, monosodium urate (MSU) crystals, or alum, indicating that lactic acid fermentation is required for NLRP3 inflammasome activation. Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production. By contrast, decreasing the activity of pyruvate oxidation by depletion of either mitochondrial pyruvate carrier 2 (MPC2) or pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) enhanced NLRP3 inflammasome activation, suggesting that inhibition of mitochondrial pyruvate transport enhanced lactic acid fermentation. Moreover, treatment with GSK2837808A reduced MSU-mediated peritonitis in mice, a disease model used for studying the consequences of NLRP3 inflammasome activation. Our results suggest that lactic acid fermentation is important for NLRP3 inflammasome activation, while pyruvate oxidation is not. Thus, reprograming pyruvate metabolism in mitochondria and in the cytoplasm should be considered as a novel strategy for the treatment of NLRP3 inflammasome-associated diseases.
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http://dx.doi.org/10.3389/fimmu.2021.630380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039150PMC
September 2021

Impact of Local Liver Irradiation Concurrent Versus Sequential with Lenvatinib on Pharmacokinetics and Biodistribution.

Cancers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.

Concurrent and sequential regimens involving radiotherapy (RT) and lenvatinib were designed with off-target or stereotactic body radiation therapy (SBRT) doses in a freely moving rat model to evaluate the effect of RT on the pharmacokinetics (PK) of lenvatinib. Liver RT concurrent with lenvatinib decreased the area under the concentration-time curve of lenvatinib concentration (AUC) by 51.1% with three fractions of 2 Gy (RT, = 0.03), and 48.9% with RT ( = 0.03). The AUC increased by 148.8% ( = 0.008) with RT, and 68.9% ( = 0.009) with RT in the sequential regimen compared to the concurrent regimen. There were no differences in the AUC between RT and RT in the concurrent or sequential regimen. Both the RT and RT concurrent regimens markedly decreased the biodistribution of lenvatinib in the heart, liver, lung, spleen, and kidneys, which ranged from 31% to 100% for RT, and 11% to 100% for RT, compared to the sham regimen. The PK and biodistribution of lenvatinib can be modulated by simultaneous off-target irradiation and SBRT doses. The timing of lenvatinib administration with respect to RT, impacted the PK and biodistribution of the drug. Additionally, off-target and SBRT doses had a similar ability to modulate the effect of systemic therapy.
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http://dx.doi.org/10.3390/cancers13071598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037784PMC
March 2021

Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation.

Pharmaceutics 2021 Mar 13;13(3). Epub 2021 Mar 13.

Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT-PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC) by 74% ( = 0.001) in the RT group and by 69% ( = 0.001) in the RT group. The AUC was increased by 182.8% ( = 0.011) in the sequential RT group and by 213.2% ( = 0.016) in the sequential RT group. Both concurrent regimens, RT and RT, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib ) group. The concurrent regimens, both RT and RT, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).
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http://dx.doi.org/10.3390/pharmaceutics13030386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035703PMC
March 2021

Association of bowel radiation dose-volume with skeletal muscle loss during pelvic intensity-modulated radiotherapy in cervical cancer.

Support Care Cancer 2021 Sep 12;29(9):5497-5505. Epub 2021 Mar 12.

Department of Radiation Oncology, MacKay Memorial Hospital, 92, Section 2, Chung Shan North Road, Taipei, 10449, Taiwan.

Background: Radiation-induced bowel damage may compromise nutrient absorption and digestion and affect body composition during pelvic radiotherapy in patients with locally advanced cervical cancer (LACC). This study aimed to evaluate the relationship between bowel radiation dose-volume and body composition changes during pelvic radiotherapy.

Methods: Data of 301 LACC patients treated with chemoradiotherapy were analyzed. Changes in skeletal muscle index (SMI) and density (SMD), and total adipose tissue index (TATI) were measured from computed tomography images at the L3 vertebral level. A reduction in SMI, SMD, or TATI of ≥10% was classified as "loss." Bowel V45 indicates the bowel volume (mL) receiving a radiation dose of ≥45 Gy. The relationship between body composition and bowel V45 was analyzed using logistic regression models.

Results: After treatment, 61 (20.3%), 81 (26.9%), and 97 (32.2%) patients experienced SMI, SMD, and TATI loss, respectively. Increased bowel V45 was independently associated with increased odds of SMI loss (odds ratio [OR]: 1.012; 95% confidence interval [CI]: 1.007-1.018; p<0.001) and TATI loss (OR: 1.006; 95% CI: 1.001-1.010; p=0.01), but not with SMD loss (OR: 1.005; 95% CI: 1.000-1.009; p=0.054). The cut-off value with the highest accuracy for predicting SMI loss was V45 ≥222 mL; a higher rate of SMI loss was noted in 40.0% of patients with V45 ≥222 mL than in 13.7% of patients with V45 <222 mL (p<0.001).

Conclusions: Higher bowel dose-volume was significantly associated with muscle loss during pelvic radiotherapy. Bowel dose-volume consideration is required in individualized nutritional counseling and supportive care in clinical practice.
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http://dx.doi.org/10.1007/s00520-021-06131-xDOI Listing
September 2021

Integrity of the Prefronto-striato-thalamo-prefrontal Loop Predicts Tai Chi Chuan Training Effects on Cognitive Task-switching in Middle-aged and Older Adults.

Front Aging Neurosci 2020 15;12:602191. Epub 2021 Feb 15.

Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan.

Tai Chi Chuan (TCC) exercise has been shown to improve cognitive task-switching performance in older adults, but the extent of this positive effect varies among individuals. Past research also shows that brain white matter integrity could predict behavioral gains of cognitive and motor learning. Therefore, in this randomized controlled trial (NCT02270320), we examined whether baseline integrity of three target white matter tract groups was predictive of task-switching improvement after 12-week TCC training in middle-aged and older adults. Thirty-eight eligible participants were randomly assigned to a TCC group ( = 19) and a control group ( = 19). Cognitive task-switching and physical performances were collected before and after training. Brain diffusion spectrum MR images were acquired before training and the general fractional anisotropy (GFA) of each target white matter tract group was calculated to indicate baseline white matter integrity of that group. Correlation and regression analyses between these GFAs and post-training task-switching improvement were analyzed using adjusted -values. After 12 weeks, significant task-switching and physical performance improvements were found only in the TCC group. Moreover, higher baseline GFA of the prefronto-striato-thalamo-prefrontal loop fibers ( = -0.63, = 0.009), but not of the prefronto-parietal/occipital ( = -0.55, = 0.026) and callosal ( = -0.35, = 0.189) fiber groups, was associated with greater reductions of task-switching errors after the TCC training. Multiple regression analysis revealed that baseline GFA of the prefronto-striato-thalamo-prefrontal loop fibers was the only independent white matter integrity predictor of task-switching error reductions after TCC training (β = -0.620, adjusted R change = 0.265, = 0.009). These findings not only highlight the important role of baseline integrity of the prefronto-striatal circuits in influencing the extent of positive cognitive task-switching effects from short-term TCC training, but also implicate that preserving good white matter integrity in the aging process may be crucial in order to gain the best cognitive effects of exercise interventions.
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http://dx.doi.org/10.3389/fnagi.2020.602191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917054PMC
February 2021

Prophylactic clipping after endoscopic mucosal resection of large nonpedunculated colorectal lesions: A meta-analysis.

J Gastroenterol Hepatol 2021 Jul 3;36(7):1778-1787. Epub 2021 Mar 3.

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background And Aim: It is not clear whether prophylactic clipping after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions (LNPCLs) prevents delayed bleeding (DB). We aimed to conduct a meta-analysis to clarify the efficacy of prophylactic clipping in prevention of DB following EMR of LNPCLs.

Methods: We searched PubMed, EMBASE, Web of Science, ScienceDirect, Cochrane Library databases, and ClinicalTrials.gov for studies that compared clipping versus (vs) nonclipping in prevention of DB following EMR of LNPCLs. Pooled odds ratio (OR) was determined using a random effects model. The pooled ORs of DB, perforation, and post-polypectomy syndrome in the clipping group compared with the nonclipping group comprised the outcomes. Subgroup analyses based on study design, polyp location, and completeness of wound closure were performed.

Results: Five studies with a total of 3112 LNPCLs were extracted. Prophylactic clipping reduced the risk of DB compared with nonclipping (3.3% vs 6.2%, OR: 0.494, P = 0.002) following EMR of LNPCLs. In subgroup analysis, prophylactic clipping reduced DB of LNPCLs at proximal location (3.8% vs 9.8%, P = 0.029), but not of them at distal location (P = 0.830). Complete wound closure showed superior efficacy to prevent DB compared with partial closure (2.0% vs 5.4%, P = 0.004). No benefit of clipping for preventing perforation or post-polypectomy syndrome was observed (P = 0.301 and 0.988, respectively).

Conclusions: Prophylactic clipping can reduce DB following EMR of LNPCLs at proximal location. Besides, complete wound closure showed superior efficacy to prevent DB compared with partial closure. Further cost analyses should be conducted to implement the most cost-effective strategies.
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http://dx.doi.org/10.1111/jgh.15472DOI Listing
July 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Progressive muscle loss is an independent predictor for survival in locally advanced oral cavity cancer: A longitudinal study.

Radiother Oncol 2021 05 20;158:83-89. Epub 2021 Feb 20.

Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan.

Background And Purpose: To investigate the association between progressive muscle loss and survival outcomes of patients with advanced-stage oral squamous cell carcinoma (OSCC) undergoing surgery and adjuvant (chemo)radiotherapy.

Methods: We analyzed the computed tomography (CT) scans of 155 patients with stage III-IVB OSCC at baseline, at simulation CT for radiotherapy, and at 3- and 9-months post-treatment. Skeletal muscle index (SMI) was measured using CT at the C3 vertebral level. The predictors of overall survival (OS) and recurrence-free survival (RFS) were evaluated using Cox regression models.

Results: The median follow-up period was 75.0 months. Fifty-one patients (32.9%) developed recurrence, with the median time from the fourth CT to recurrence being 9.1 months. The SMI progressively decreased from baseline to simulation CT by 1.1% (p = 0.006), to 3 months post-treatment by 5.1% (p < 0.001), and to 9 months post-treatment by 15.6% (p < 0.001) in patients developing recurrence. Patients without recurrence lost SMI at the simulation CT by 0.7% (p = 0.001) and at 3 months post-treatment by 2.1% (p < 0.001); their SMI returned to the baseline level at 9 months post-treatment. SMI changes were weakly correlated with changes in body mass index (BMI) (Spearman ρ, 0.13; p = 0.11). In multivariate analysis, SMI changes (per 5% decrease) were independently associated with significantly worse OS (hazard ratio: 1.88, 95% confidence interval: 1.58-2.23; p < 0.001) and RFS (hazard ratio: 1.89, 95% confidence interval: 1.61-2.20; p < 0.001).

Conclusion: Progressive muscle loss was independently associated with worse survival outcomes in patients with stage III-IVB OSCC. Muscle loss might not be detected by changes in BMI.
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http://dx.doi.org/10.1016/j.radonc.2021.02.014DOI Listing
May 2021

Anti-inflammatory effects of Radix Aucklandiae herbal preparation ameliorate intestinal mucositis induced by 5-fluorouracil in mice.

J Ethnopharmacol 2021 May 7;271:113912. Epub 2021 Feb 7.

Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, 404, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. Electronic address:

Ethnopharmacological Relevance: 5-Fluorouracil (5-FU) is a chemotherapy agent that is widely used in clinical oncologic practice. However, intestinal mucositis is the most frequently occurring side effect of cancer therapy with 5-FU. Based on a literature survey, Radix Aucklandiae herbal preparation potentially ameliorates intestinal mucositis in 5-FU-treated mice.

Aim Of The Study: The aim of this study was to investigate the inflammation and gastrointestinal regulation of intestinal mucositis induced by 5-FU, including the intestinal morphology, as well as the reduction in food intake, body weight loss, and diarrhea.

Materials And Methods: Intestinal mucositis was induced in mice by 5-FU (30 mg/kg, i.p., for 5 consecutive days). The dose-dependent Radix Aucklandiae herbal preparation (0.3, 1, and 3 g/kg/day, p.o.), loperamide (3 mg/kg/day, p.o.) or celecoxib (40 mg/kg/day, p.o.) was concurrently administered until the 7th day. Physical status observation, diarrhea assessment, serum proinflammatory cytokine levels, intestinal villus height and crypt depth, and total goblet cells from tissues were assessed.

Results: The dosage regimen of 5-FU administration caused severe intestinal mucositis in mice, including damage to the intestinal morphology, accompanied by a reduction in food intake, body weight loss, and diarrhea. The high-dose Radix Aucklandiae herbal preparation significantly relieves 5-FU-induced intestinal mucositis by enhancing proliferative activity in epithelial crypts; improving anepithymia, body weight loss, and diarrhea; and displaying protective effects on goblet cells in intestinal mucosal epithelia. Activation of NF-κB in the intestinal mucositis model was also suppressed by the Radix Aucklandiae herbal preparation, suggesting that it is a potent inhibitor of NF-κB and proinflammatory cytokines, such as IL-1β, IL-6, TNF-α, and COX-2.

Conclusions: Our data support the conclusion that the Radix Aucklandiae herbal preparation could effectively ameliorate 5-FU-induced gastrointestinal toxicity and be applied clinically for the prevention of intestinal mucositis during chemotherapy.
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http://dx.doi.org/10.1016/j.jep.2021.113912DOI Listing
May 2021

Selective Atrophy of the Vastus Medialis: Does It Exist in Women With Nontraumatic Patellofemoral Pain?

Am J Sports Med 2021 03 26;49(3):700-705. Epub 2021 Jan 26.

Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, USA.

Background: A commonly cited theory related to the pathomechanics of patellofemoral pain (PFP) states that atrophy of the vastus medialis (VM) muscle leads to lateral tracking of the patella. However, isolated atrophy of the VM or atrophy of the quadriceps muscle group as a whole, has not been consistently reported in this population.

Purpose: To compare individual and total quadriceps muscle volumes between women with nontraumatic PFP and women without PFP as measured on magnetic resonance imaging scans.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: A total of 52 women with nontraumatic PFP and 64 women without PFP between the ages of 18 and 45 years participated. Magnetic resonance imaging scans of the thigh were obtained from the anterior inferior iliac spine to the tibial plateau. Individual quadriceps muscle cross-sectional area measurements were obtained from each image, and muscle volumes for the VM, vastus lateralis, vastus intermedius, and rectus femoris were calculated. Muscle volume measurements were expressed in absolute values and normalized to body mass. Separate 2-way mixed-factorial analysis of variance (group × muscle) were used to compare absolute and normalized individual muscle volumes between groups. Independent tests were used to compare absolute and normalized total quadriceps volumes between groups.

Results: There was no difference in absolute and normalized individual muscle volumes between individuals with and those without PFP. Additionally, absolute and normalized total muscle volumes did not differ between groups.

Conclusion: Our findings do not support the concept of preferential atrophy of the VM or generalized quadriceps atrophy in women with nontraumatic PFP.
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http://dx.doi.org/10.1177/0363546520982244DOI Listing
March 2021

Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice.

Int J Mol Sci 2021 Jan 18;22(2). Epub 2021 Jan 18.

Institute of Biotechnology, National Taiwan University, Taipei 10617, Taiwan.

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing "healthy obese" by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [F] fluorodeoxyglucose-PET/CT (F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic , BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic , BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.
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http://dx.doi.org/10.3390/ijms22020906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831094PMC
January 2021

Lactobacillus Attenuate the Progression of Pancreatic Cancer Promoted by Porphyromonas Gingivalis in Transgenic Mice.

Cancers (Basel) 2020 Nov 26;12(12). Epub 2020 Nov 26.

Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.

Accumulating evidence suggests that there is a link between the host microbiome and pancreatic carcinogenesis, and that increases the risk of developing pancreatic cancer. The aim of the current study was to clarify the role of in the pathogenesis of pancreatic cancer and the potential immune modulatory effects of probiotics. The six-week-old LSL-K-rasG12D; Pdx-1-cre (KC) mice smeared P. gingivalis on the gums, causing pancreatic intraepithelial neoplasia (PanIN) after four weeks to be similar to the extent of lesions in untreated KC mice at 24 weeks. The oral inoculation of of six-week-old ; (KC) mice caused significantly pancreatic intraepithelial neoplasia (PanIN) after treatment four weeks is similar to the extent of lesions in untreated KC mice at 24 weeks. The pancreas weights of plus probiotic-treated mice were significantly lower than the mice treated with alone ( = 0.0028). The histological expressions of Snail-1, ZEB-1, collagen fibers, Galectin-3, and PD-L1 staining in the pancreas were also notably lower. In addition, probiotic administration reduced the histological expression of Smad3 and phosphorylated Smad3 in treated KC mice. We demonstrated that oral exposure to can accelerate the development of PanIN lesions. Probiotics are likely to have a beneficial effect by reducing cancer cell proliferation and viability, inhibiting PanIN progression, and cancer cell metastasis (Epithelial-mesenchymal transition, EMT). The transforming growth factor-β signaling pathway may be involved in the tumor suppressive effects of probiotics.
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http://dx.doi.org/10.3390/cancers12123522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760978PMC
November 2020

A decentralized framework for cultivating research lifecycle transparency.

PLoS One 2020 18;15(11):e0241496. Epub 2020 Nov 18.

Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan.

Research transparency has been advocated as a key means of addressing the current crisis of reproducibility. This article proposes an enhanced form of research transparency, termed lifecycle transparency. Over the entire lifecycle of a research effort, this approach captures the syntactical contexts of artifacts and stakeholders, such as timestamps, agreements, and/or dependency requirements for completing each research phase. For example, such contexts might include when, where, and from whom patients' consent and institutional review board approvals were received before a clinical trial was carried out. However, as existing open-science tools are often dedicated to certain research phases or disciplines, and thus insufficient to support lifecycle transparency, we propose a novel decentralized framework to serve as a common medium for interaction among open-science tools, and produces irrefutable and immutable proofs of progress that can be verified automatically.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241496PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673512PMC
December 2020

Sarcopenia and Systemic Inflammation Synergistically Impact Survival in Oral Cavity Cancer.

Laryngoscope 2021 05 2;131(5):E1530-E1538. Epub 2020 Nov 2.

Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan.

Objectives: Sarcopenia and systemic inflammation can affect survival of advanced-stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated.

Study Design: Retrospective review at a tertiary cancer center.

Methods: Patients with stage III-IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex-specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C-reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models.

Results: A total of 174 patients were included in the study. The cut-off values for sarcopenia were set at SMI <52.4 cm /m (men) and < 36.2 cm /m (women) corresponding to the lowest sex-specific tertile. An mGPS 1-2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06-3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1-2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17-3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7-16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1-2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01-46.99; P < .001).

Conclusions: Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced-stage OSCC patients.

Level Of Evidence: 4 Laryngoscope, 131:E1530-E1538, 2021.
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http://dx.doi.org/10.1002/lary.29221DOI Listing
May 2021
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