261 results on '"Pei-Hsun, Sung"'
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2. ITRI Biofilm Prevented Thoracic Adhesion in Pigs That Received Myocardial Ischemic Induction Treated by Myocardial Implantation of EPCs and ECSW Treatment
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Jiunn-Jye Sheu, Jui-Ning Yeh, Pei-Hsun Sung, John Y. Chiang, Yi-Ling Chen, Yi-Ting Wang, Hon-Kan Yip, and Jun Guo
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Medicine - Abstract
This study tested the hypothesis that ITRI Biofilm prevents adhesion of the chest cavity. Combined extracorporeal shock wave (ECSW) + bone marrow-derived autologous endothelial progenitor cell (EPC) therapy was superior to monotherapy for improving heart function (left ventricular ejection fraction [LVEF]) in minipigs with ischemic cardiomyopathy (IC) induced by an ameroid constrictor applied to the mid-left anterior descending artery. The minipigs ( n = 30) were equally designed into group 1 (sham-operated control), group 2 (IC), group 3 (IC + EPCs/by directly implanted into the left ventricular [LV] myocardium; 3 [+]/3[–] ITRI Biofilm), group 4 (IC + ECSW; 3 [+]/[3] – ITRI Biofilm), and group 5 (IC + EPCs–ECSW; 3 [+]/[3] – ITRI Biofilm). EPC/ECSW therapy was administered by day 90, and the animals were euthanized, followed by heart harvesting by day 180. In vitro studies demonstrated that cell viability/angiogenesis/cell migratory abilities/mitochondrial concentrations were upregulated in EPCs treated with ECSW compared with those in EPCs only (all P s < 0.001). The LVEF was highest in group 1/lowest in group 2/significantly higher in group 5 than in groups 3/4 (all P s < 0.0001) by day 180, but there was no difference in groups 3/4. The adhesion score was remarkably lower in patients who received ITRI Biofilm treatment than in those who did not (all P s
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- 2024
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3. Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat
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Chih‐Chao Yang, Yi-Ling Chen, Pei-Hsun Sung, John Y. Chiang, Chih-Hung Chen, Yi-Chen Li, and Hon-Kan Yip
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Diabetic kidney disease ,Renal function ,Inflammation ,Oxidative stress ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats. Methods: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 105/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 106/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. Results: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p
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- 2024
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4. Prion Protein Overexpression in Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Effectively Protected Rodent Kidney Against Ischemia-Reperfusion Injury Via Enhancing ATP/Mitochondrial Biogenesis—Role of ADMSC Rejuvenation and Proliferation
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Yen-Ta Chen, Chih-Chao Yang, John Y. Chiang, Pei-Hsun Sung, Pei-Lin Shao, Chi-Ruei Huang, Mel S. Lee, and Hon-Kan Yip
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Medicine - Abstract
Background: We tested the hypothesis that overexpression of cellular-prion-protein in adipose-derived mesenchymal stem cells (PrPC OE -ADMSCs) effectively protected the kidney against ischemia-reperfusion (IR) injury in rat. Methods: Part I of cell culture was categorized into A1(ADMSCs)/A2(ADMSCs+p-Cresol)/A3(PrPC OE in ADMSCs)/A4 (PrPC OE in ADMSCs+p-Cresol). Part II of cell culture was divided into B1(ADMSCs)/B2[ADMSCs+lipopolysaccharide (LPS)]/B3(PrPC OE in ADMSCs)/B4(PrPC OE in ADMSCs+LPS). Sprague-Dawley (SD) rats (n = 50) were equally categorized into groups 1 (sham-operated-control)/2 (IR)/3 (IR+ADMSCs/6.0 × 10 5 equally divided into bilateral-renal arteries and 6.0 × 10 5 intravenous administration by 1 h after IR)/4 [IR+PrPC OE -ADMSCs (identical dosage administered as group 3)]/5 [IR+silencing PRNP -ADMSCs (identical dosage administered as group 3)], and kidneys were harvested post-day 3 IR injury. Results: Part I results demonstrated that the cell viability at 24/48/72 h, BrdU uptake/number of mitDNA/APT concentration/mitochondrial-cytochrome-C+ cells and the protein expressions of ki67/PrPC at 72 h-cell culturing were significantly higher in PrPC OE -ADMSCs than in ADMSCs (all P < 0.001). The protein expressions of oxidative-stress (NOX-1/NOX2/NOX4/oxidized protein)/mitochondrial-damaged (p22-phox/cytosolic-cytochrome-C)/inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers were lowest in A1/A3 and significantly higher in A2 than in A4 (all P < 0.001). Part II result showed that the protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers exhibited an identical pattern of part I among the groups (all P < 0.001). The protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/mitochondrial-damaged (cytosolic-cytochrome-C/p22-phox)/apoptotic (cleaved caspase-3/cleaved-PARP/mitochondrial-Bx)/autophagic (beclin-1/ratio of LC3B-II/LC3B-I)/fibrotic (Smad3/TGF-ß) biomarkers and kidney-injury-score/creatinine level were lowest in group 1, highest in group 2, significantly higher in group 5 than in groups 3/4 (all P < 0.0001). Conclusion: PrPC OE in ADMSCs rejuvenated these cells and played a cardinal role on protecting the kidney against IR injury.
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- 2023
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5. Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction
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Kun-Chen Lin, Wen-Feng Fang, Pei-Hsun Sung, Kuo-Tung Huang, John Y. Chiang, Yi-Ling Chen, Chi-Ruei Huang, Yi-Chen Li, Mel S. Lee, and Hon-Kan Yip
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Medicine - Abstract
This study tested whether human umbilical cord–derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 10 5 /co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1β/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-β/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats ( n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO 2 %/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-β/p-NF-κB/IL-1β/TNF-α)/fibrotic (p-SMad3/TGF-β), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO 2 % among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.
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- 2023
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6. Rejuvenated endothelial progenitor cells through overexpression of cellular prion protein effectively salvaged the critical limb ischemia in rats with preexisting chronic kidney disease
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Jui-Po Yeh, Pei‐Hsun Sung, John Y. Chiang, Chi-Ruei Huang, Yi-Ling Chen, Jui-Pin Lai, and Jiunn-Jye Sheu
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Endothelial progenitor cells ,Chronic kidney disease ,Critical limb ischemia ,Rejuvenation ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This study tested the hypothesis that overexpression of cellular prion protein in endothelial progenitor cells (PrPcOE-EPCs), defined as “rejuvenated EPCs,” was superior to EPCs for salvaging the critical limb ischemia (CLI) induced after 28-day chronic kidney disease (CKD) induction in rat. Methods and Results Cell viability and flow cytometric analyses of early/late apoptosis/total-intracellular ROS/cell cycle (sub-G1, G2/M phase) were significantly higher in EPCs + H2O2 than in EPCs that were significantly reversed in PrPcOE-EPCs + H2O2 (all p
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- 2022
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7. Combined therapy with dapagliflozin and entresto offers an additional benefit on improving the heart function in rat after ischemia-reperfusion injury
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Sheung-Fat Ko, Pei Hsun Sung, Chih Chao Yang, John Y. Chiang, and Hon Kan Yip
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Ischemia-reperfusion injury ,Entresto ,Dapagliflozin ,Inflammation ,Oxidative stress ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: This study tested whether combined dapagliflozin and entresto treatment would be superior to either one alone for preserving the left-ventricular ejection-fraction (LVEF) in rat after ischemia-reperfusion (IR) injury. Methods: Cell culture using H9C2 cells and IR injury in rat with dapagliflozin-entresto treatment were conducted in the present study. Results: In vitro flow-cytometric result showed that the intracellular and mitochondrial reactive oxygen species and mitochondrial permeability transition pore, and protein levels of oxidative-stress/DNA-damaged markers [NADPH-oxidase-1 (NOX-1)/NOX-2/oxidized-protein/γ-H2A-histone-family member X (γ-H2AX)] were significantly higher in hydrogen peroxide (H2O2) (300μM)-treated H9C2 cells as compared with the controls that were significantly reversed in sacubitril/valsartan and dapagliflozin therapy in the same H2O2-treated condition, whereas the protein expressions of antioxidants [Sirtuin-1 (SIRT1)/SIRT3/superoxide dismutase/catalase/glutathione peroxidase) exhibited an opposite pattern among the groups (all p
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- 2023
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8. Dose-dependent benefits of iron-magnetic nanoparticle-coated human umbilical-derived mesenchymal stem cell treatment in rat intracranial hemorrhage model
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Kuan-Hung Chen, Han-Tan Chai, Kun-Chen Lin, John Y. Chiang, Pei-Hsun Sung, Chih-Hung Chen, and Hon-Kan Yip
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Intracranial hemorrhage ,Mesenchymal stem cells ,Brain infarct volume ,Inflammatory reaction ,Neurological impairment ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This study tested whether two doses of human umbilical-derived mesenchymal stem cells (hUC-MSCs) were superior to one dose for protecting the brain against intracranial hemorrhage (ICH) induced by intracranial injection collagenase and the capacity of ironic-magnetic-nanoparticles (Ir-MNa) coated hUC-MSCs tracked by MRI. Methods and results Adult male SD rats (n = 40) were equally categorized into group 1 (sham-operated-control), group 2 (ICH), group 3 [ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an extracorporeal magnet over rat head (eCMag)/administered by left internal carotid artery (LICA) at post-3 h ICH], and group 4 (ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an eCMag/administered post-3 h ICH by LICA and 24 h by IV) and euthanized by day 28. The result showed that by day 28 after ICH induction the neurological function was severely impaired in group 2 than in group 1 that was significantly improved in group 3 and further significantly improved in group 4, whereas ICH volume exhibited an opposite pattern of neurological impairment among the groups (all p
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- 2022
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9. Intrarenal arterial administration of human umbilical cord-derived mesenchymal stem cells effectively preserved the residual renal function of diabetic kidney disease in rat
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Ya Yue, Jui-Ning Yeh, John Y. Chiang, Pei-Hsun Sung, Yi-Ling Chen, Fanna Liu, and Hon-Kan Yip
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Diabetic CKD ,Renal function ,Xenogeneic mesenchymal stem cell ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This experimental study was designed as a preclinical study for testing the hypothesis that intrarenal arterial (IRA) transfusion of human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) therapy preserved the residual renal function of diabetic kidney disease (DKD) in rat [induction by 5/6 nephrectomy of left kidney and right nephrectomy, followed by intraperitoneal administration of aminoguanidine (180 mg/kg) and streptozotocin (30 mg/kg)]. Methods Animals (n = 24) were categorized into group 1 (sham-operated control), group 2 (DKD), group 3 [DKD + HUCDMSCs (2.1 × 105/IRA injection at day 28 after CKD induction)] and group 4 [(DKD + HUCDMSCs (6.3 × 105/IRA injection)]. Results By day 60 after DKD induction, the kidneys were harvested and the result showed that the creatinine level, ratio of urine protein/urine creatinine and kidney injury score were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p
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- 2022
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10. Additional benefit of induced pluripotent stem cell-derived mesenchymal stem cell therapy on sepsis syndrome-associated acute kidney injury in rat treated with antibiotic
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Chih-Chao Yang, Pei‐Hsun Sung, Chih-Hung Chen, John Y. Chiang, Pei-Lin Shao, Shun-Cheng Wu, and Hon‐Kan Yip
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Sepsis syndrome ,Acute kidney injury ,Antibiotics ,Induced pluripotent stem cell-derived mesenchymal stem-cells ,Inflammation ,Oxidative stress ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This study tested whether human induced-pluripotent stem-cell-derived mesenchymal-stem-cells (iPS-MSCs) would offer an additional benefit to the rodent with acute kidney injury (AKI) (ischemia for 1 h followed by reperfusion for 120 h) associated sepsis syndrome (SS) (by cecal-ligation-puncture immediately after AKI-induction) undergoing ciprofloxacin therapy. Results Male-adult SD rats (n = 80) were categorized into group 1 (sham-operated-control, n = 10), group 2 (AKI + SS, n = 24), group 3 (AKI + SS + ciprofloxacin/3 mg/kg, orally for 120 h, n = 12), group 4 (AKI + SS + iPS-MSCs/1.2 × 106/intravenously administered by 3 h after AKI, n = 12), group 5 (AKI + SS + iPS-MSCs/1.2 × 106/intravenously administered by 18 h after AKI, n = 12), group 6 (AKI + SS + iPS-MSCs/1.2 × 106/intravenously administered by 3 h after AKI induction + ciprofloxacin, n = 10] and euthanized by 120 h. The result showed that the mortality was significantly higher in group 2 than in other groups (all p
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- 2021
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11. Synergic Effect of Combined Therapy of Hyperbaric Oxygen and Adipose-Derived Mesenchymal Stem Cells on Improving Locomotor Recovery After Acute Traumatic Spinal Cord Injury in Rat Mainly Through Downregulating Inflammatory and Cell-Stress Signalings
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Tsung-Cheng Yin, Pei-Lin Shao, Kuan-Hung Chen, Kun-Chen Lin, John Y. Chiang, Pei-Hsun Sung, Shun-Cheng Wu, Yi-Chen Li, Hon-Kan Yip, and Mel S. Lee
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Medicine - Abstract
This study tested whether combined hyperbaric oxygen (HBO) and allogenic adipose-derived mesenchymal stem cells (ADMSCs) would be superior to either one for improving the locomotor recovery in rat after acute traumatic spinal cord injury (TSCI) in rat. Adult-male Sprague–Dawley rats were equally categorized into group 1 (sham-operated control), group 2 (TSCI), group 3 (TSCI + HBO for 1.5 h/day for 14 consecutive days after TSCI), group 4 (TSCI + ADMSCs/1.2 × 10 6 cells by intravenous injection at 3 h and days 1/2 after TSCI), and group 5 (TSCI + HBO + ADMSCs), euthanized, and spinal cord tissue was harvested by day 49 after TSCI. The protein expressions of oxidative-stress (NOX-1/NOX-2), inflammatory-signaling (TLR-4/MyD88/IL-1β/TNF-α/substance-p), cell-stress signaling (PI3K/p-AKT/p-mTOR), and the voltage-gated sodium channel (Nav1.3/1.8/1.9) biomarkers were highest in group 2, lowest in group 1, and significantly lower in group 5 than in groups 3/4 (all P
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- 2022
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12. Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury
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Yen-Ta Chen, Fei-Chi Chuang, Chih-Chao Yang, John Y. Chiang, Pei-Hsun Sung, Yi-Ching Chu, Chi-Ruei Huang, Kuan-Hui Huang, and Hon-Kan Yip
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Testis ,Ischemia-reperfusion injury ,Melatonin ,Adipose-derived mesenchymal stem cells ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. Methods and results Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001). Conclusion Mel-ADMSCs effectively protected the testis against TTIR injury.
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- 2021
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13. Double overexpression of miR-19a and miR-20a in induced pluripotent stem cell-derived mesenchymal stem cells effectively preserves the left ventricular function in dilated cardiomyopathic rat
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Jiunn-Jye Sheu, Han-Tan Chai, Pei-Hsun Sung, John Y. Chiang, Tien-Hung Huang, Pei-Lin Shao, Shun-Cheng Wu, and Hon-Kan Yip
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Dilated cardiomyopathy ,Double overexpression of microRNAs ,Oxidative stress ,Inflammation ,Mitochondrial damage ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This study tested the hypothesis that double overexpression of miR-19a and miR-20a (dOex-mIRs) in human induced pluripotent stem cell (iPS)-derived mesenchymal stem cells (MSCs) effectively preserved left ventricular ejection fraction (LVEF) in dilated cardiomyopathy (DCM) (i.e., induced by doxorubicin) rat. Methods and results In vitro study was categorized into groups G1 (iPS-MSC), G2 (iPS-MSCdOex-mIRs), G3 (iPS-MSC + H2O2/100uM), and G4 (iPS-MSCdOex-mIRs + H2O2/100uM). The in vitro results showed the cell viability was significantly lower in G3 than in G1 and G2, and that was reversed in G4 but it showed no difference between G1/G2 at time points of 6 h/24 h/48 h, whereas the flow cytometry of intra-cellular/mitochondrial oxidative stress (DCFA/mitoSOX) and protein expressions of mitochondrial-damaged (cytosolic-cytochrome-C/DRP1/Cyclophilin-D), oxidative-stress (NOX-1/NOX2), apoptotic (cleaved-caspase-3/PARP), fibrotic (p-Smad3/TGF-ß), and autophagic (ratio of LC3B-II/LC3BI) biomarkers exhibited an opposite pattern of cell-proliferation rate (all p
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- 2021
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14. Investigation of echocardiographic characteristics and predictors for persistent defects of patent foramen ovale or patent ductus arteriosus in Chinese newbornsAt a glance of commentary
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Zhen Yuan, Long-Zhen Zhang, Bin Li, Hung-Tao Chung, Jin-Xin Jiang, John Y. Chiang, Hsin-Ju Chiang, Hon-Kan Yip, and Pei-Hsun Sung
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Congenital heart disease ,Patent foramen ovale ,Patent ductus arteriosus ,Atrial septal defect ,Ventricular septal defect ,Spontaneous closure ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: Persistent patent foramen ovale (PFO) and patent ductus arteriosus (PDA) increase the adult risk of cryptogenic embolic stroke and chronic pulmonary hypertension. To understand the characteristics of PFO and PDA in newborns, we investigated the spontaneous closure rate and derived the determinants for residual defects. Methods: We utilized the database of congenital heart disease (CHD) in Xiamen ChangGung Memorial Hospital from 2015 to 2017 and allocated 2523 eligible newborns into four groups according to PDA, PFO, both or neither at birth. A total of 574, 1229, 202 and 518 newborns were assigned into the group of PFO and PDA, PFO alone, PDA alone and non-PFO/non-PDA, respectively. Regular echocardiographic follow-ups at baseline, 6, 12 and 24 months after birth were performed for evaluating the spontaneous closure rate in the subjects. Regression analysis was carried out to study the risk factors of residual congenital defects. Results: Newborns with PFO alone had the youngest birth age and lowest birth weight among the four groups. About one in four PDA-alone newborns had concomitant small ASD, i.e.,
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- 2021
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15. Risk of major adverse cardiovascular and cerebrovascular events in Taiwanese women with endometriosis
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Hsin-Ju Chiang, Kuo-Chung Lan, Yao-Hsu Yang, John Y. Chiang, Fu-Tsai Kung, Fu-Jen Huang, Yu-Ju Lin, Yu-Ting Su, and Pei-Hsun Sung
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Endometriosis ,Major adverse cardiovascular and cerebrovascular events ,Population-based cohort study ,Medical and surgical treatment ,Medicine (General) ,R5-920 - Abstract
Background/Purpose: Endometriosis (EM) is linked to cardiovascular disease (CVD). However, whether this finding can be applied to the Taiwanese population remained unanswered. To investigate the association between EM and major adverse cardiovascular and cerebrovascular events (MACCE) and the therapeutic effect on the risk of MACCE in Asian women with EM. A retrospective population-based cohort study was performed. Methods: A total of 17 543 patients with EM aged between 18 and 50 years were identified from a general population of 1 million Taiwanese after excluding diagnoses of major CVD and cerebrovascular accident (CVA) prior to EM. The comparison group (n = 70 172) without EM was selected by matching the study cohort with age, sex, and income and urbanization levels in a 4:1 ratio. Results: During a median follow-up period of 9.2 years, Taiwanese women with EM had a significantly higher frequency of comorbidities, medical and surgical treatment, and MACCE than did their non-EM counterparts (2.76% vs 2.18%, P
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- 2021
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16. Dipeptidyl peptidase 4 promotes peritoneal fibrosis and its inhibitions prevent failure of peritoneal dialysis
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Yi-Chen Li, Pei-Hsun Sung, Yao-Hsu Yang, John Y. Chiang, Hon-Kan Yip, and Chih‐Chao Yang
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Biology (General) ,QH301-705.5 - Abstract
Li et al. show that dipeptidyl peptidase 4 (DPP4) promotes peritoneal fibrosis whereas the inhibition of DPP4 protects the patients from failure of peritoneal dialysis. This study provides mechanistic insights into the effects of DPP4 on peritoneal fibrosis and the translational potential of these effects.
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- 2021
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17. Early Levosimendan Administration Improved Weaning Success Rate in Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock
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Yu-Wen Chen, Wei-Chieh Lee, Po-Jui Wu, Hsiu-Yu Fang, Yen-Nan Fang, Huang-Chung Chen, Meng-Shen Tong, Pei-Hsun Sung, Chieh-Ho Lee, and Wen-Jung Chung
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acute decompensated heart failure (ADHF) ,cardiogenic shock ,venoarterial extracorporeal membrane oxygenation ,levosimendan ,weaning ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used in patients with refractory cardiogenic shock (CS) or out-of-hospital cardiac arrest. It is difficult to perform VA-ECMO weaning, which may cause circulatory failure and death. Levosimendan is an effective inotropic agent used to maintain cardiac output, has a long-lasting effect, and may have the potential benefit for VA-ECMO weaning. The study aimed to explore the relationship between the early use of levosimendan and the rate of VA-ECMO weaning failure in patients on VA-ECMO support for circulatory failure.MethodsAll patients who underwent VA-ECMO in our hospital for CS between January 2017 and December 2020 were recruited in this cohort study and divided into two groups: without and with levosimendan use. Levosimendan was used as an add-on to other inotropic agents as early as possible after VA-ECMO setting. The primary endpoint was VA-ECMO weaning success, which was defined as survival without events for 24 h after VA-ECMO withdrawl. The secondary outcomes were cardiovascular and all-cause mortality at the 30-day and 180-day follow-up periods post-VA-ECMO initialization.ResultsA total of 159 patients were recruited for our study; 113 patients were enrolled in the without levosimendan-use group and 46 patients were enrolled in the levosimendan-use group. In levosimendan-use group, the patients received levosimendan infusion within 24 h after VA-ECMO initialization. Similar hemodynamic parameters were noted between the two groups. Poorer left ventricular ejection fraction and a higher prevalence of intra-aortic balloon pumping were observed in the levosimendan group. An improved weaning rate (without vs. with: 48.7 vs. 82.6%; p < 0.001), lower in-hospital mortality rate (without vs. with: 68.1 vs. 43.5%; p = 0.007), and 180-day cardiovascular mortality (without vs. with: 75.3 vs. 43.2%; p < 0.001) were also noted. Patients administered with levosimendan also presented a lower rate of 30-day (without vs. with: 75.3 vs. 41.3%; p = 0.034) and 180-day (without vs. with: 77.0 vs. 43.2%; p < 0.001) all-cause mortality.ConclusionEarly levosimendan administration may contribute to increasing the success rate of VA-ECMO weaning and may help to decrease CV and all-cause mortality.
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- 2022
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18. Safety and efficacy of intrarenal arterial autologous CD34+ cell transfusion in patients with chronic kidney disease: A randomized, open‐label, controlled phase II clinical trial
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Chih‐Chao Yang, Pei‐Hsun Sung, Ben‐Chung Cheng, Yi‐Chen Li, Yi‐Ling Chen, Mel S. Lee, and Hon‐Kan Yip
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angiogenesis ,CD34+ cell therapy ,chronic kidney disease ,circulating endothelial progenitor cells ,Medicine (General) ,R5-920 ,Cytology ,QH573-671 - Abstract
Abstract Background This was a randomized, open‐label, controlled phase II clinical trial to investigate the safety, efficacy, and outcomes of intrarenal artery infusion of autologous peripheral‐blood‐derived CD34+ cells for patients with chronic kidney disease (CKD; ie, stage III or IV). Materials and Methods Between October 2016 and July 2018, 52 consecutive patients with CKD at stage III or IV were randomly allocated into a treatment group (TG; 2.5 × 107 cells for each intrarenal artery; n = 26) and a control group (CG; standardized pharmacotherapy only; n = 26). The primary endpoints included safety and change of creatinine level/creatinine clearance. The secondary endpoints were 12‐month combined unfavorable clinical outcomes (defined as dialysis or death), improvement in proteinuria, and CD34+ cell‐related adverse events. Results All patients were uneventfully discharged after CD34+ cell therapy. The baseline endothelial progenitor cell (EPC) populations did not differ between TG and CG (P > .5). Flow cytometric analysis showed increases in circulating EPC (ie, CD34+KDR+CD45dim/ CD34+CD133+CD45dim/CD31+CD133+CD45dim/CD34+CD133+KDR+/CD133+) and hematopoietic stem cell (CD34+) populations after granulocyte‐colony stimulating factor treatment (all P .1). Conclusion CD34+ cell therapy was safe and improved 1‐year outcome.
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- 2020
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19. Baseline factors identified for the prediction of good responders in patients with end-stage diffuse coronary artery disease undergoing intracoronary CD34+ cell therapy
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Pei-Hsun Sung, Hsin-Ju Chiang, Yi-Chen Li, John Y. Chiang, Chi-Hsiang Chu, Pei-Lin Shao, Fan-Yen Lee, Mel S. Lee, and Hon-Kan Yip
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CD34+ cell therapy ,Good responders ,Diffuse coronary artery disease ,Refractory angina ,Left ventricular ejection fraction ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Treating patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary intervention remains a clinical challenge. They usually express refractory angina and have a high risk of mortality. Although growing data have indicated cell therapy is an alternative solution to medical or invasive therapy, there are still lacking useful markers to predict whether heart function will improve in the EnD-CAD patients who underwent circulatory-derived CD34+ cell therapy. By utilizing the baseline variables and results from our previous phase I/II clinical trials, the aim of this study tried to elucidate the variables predictive of the “good response” to CD34+ cell therapy. Methods This retrospective study included 38 patients in phase I clinical trial (2011–2014), and 30 patients in phase II clinical trial (2013–2017). These patients were categorized into “good responders” and “non-responders” according to their 1-year improvement of LVEF ≥ 7.0% or
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- 2020
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20. Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke—evaluating the impact of therapeutic time points on prognostic outcomes
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Kun-Chen Lin, Han-Tan Chai, Kuan-Hung Chen, Pei-Hsun Sung, John Y. Chiang, Pei-Lin Shao, Chi-Ruei Huang, Yi-Chen Li, Sheung-Fat Ko, and Hon-Kan Yip
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Ischemic stroke ,Endothelial progenitor cells ,Angiogenesis ,Neurological function ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and results Adult male SD rats (n = 70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2 × 106 cells/by LICA administration 3 h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS), and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2, and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all P
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- 2020
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21. Oxidized-LDL Deteriorated the Renal Residual Function and Parenchyma in CKD Rat through Upregulating Epithelial Mesenchymal Transition and Extracellular Matrix-Mediated Tubulointerstitial Fibrosis—Pharmacomodulation of Rosuvastatin
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Pei-Hsun Sung, Ben-Chung Cheng, Tsuen-Wei Hsu, John Y Chiang, Hsin-Ju Chiang, Yi-Ling Chen, Chih-Chao Yang, and Hon-Kan Yip
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chronic kidney disease ,oxidized low-density lipoprotein ,epithelial mesenchymal transition ,oxidative stress ,Therapeutics. Pharmacology ,RM1-950 - Abstract
This study tested the hypothesis that intrarenal arterial transfusion of oxidized low-density lipoprotein (ox-LDL) jeopardized the residual renal function and kidney architecture in rat chronic kidney disease ((CKD), i.e., induced by 5/6 nephrectomy) that was reversed by rosuvastatin. Cell culture was categorized into A1 (NRK-52E cells), A2 (NRK-52E + TGF-β), A3 (NRK-52E + TGF-β + ox-LDL) and A4 (NRK-52E + TGF-β + ox-LD). The result of in vitro study showed that cell viability (at 24, 48 and 72 h), NRK-52E ox-LDL-uptake, protein expressions of epithelial–mesenchymal–transition (EMT) markers (i.e., p-Smad2/snail/α-SMA/FSP1) and cell migratory and wound healing capacities were significantly progressively increased from A1 to A4 (all p < 0.001). SD rats were categorized into group 1 (sham-operated control), group 2 (CKD), group 3 (CKD + ox-LDL/0.2 mg/rat at day 14 after CKD induction) and group 4 (CKD + ox-LDL-treated as group 3+ rosuvastatin/10 mg/kg/day by days 20 to 42 after CKD induction) and kidneys were harvested at day 42. The circulatory levels of BUN and creatinine, ratio of urine-protein to urine-creatinine and the protein expressions of the above-mentioned EMT, apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial-Bax) and oxidative-stress (NOX-1/NOX-2/oxidized-protein) markers were lowest in group 1, highest in group 3 and significantly higher in group 4 than in group 2 (all p < 0.0001). Histopathological findings demonstrated that the kidney injury score, fibrotic area and kidney injury molecule-1 (KIM-1) displayed an identical pattern, whereas the cellular expression of podocyte components (ZO-1/synaptopodin) exhibited an opposite pattern of EMT markers (all p < 0.0001). In conclusion, ox-LDL damaged the residual renal function and kidney ultrastructure in CKD mainly through augmenting oxidative stress, EMT and fibrosis that was remarkably reversed by rosuvastatin.
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- 2022
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22. Clinical utility of mean platelet volume and immature platelet fraction in acute coronary syndromeAt a glance commentary
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Hsien-Li Huang, Chih-Hung Chen, Chia-Te Kung, Yi-Chen Li, Pei-Hsun Sung, Huey-Ling You, Yu-Hung Lin, and Wan-Ting Huang
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: Platelets play an important role in the pathogenesis of acute coronary syndrome (ACS). Patients with ACS have an increased mean platelet volume (MPV) and immature platelet fraction (IPF) resulting in elevation of thrombotic ability. In this study, we evaluated the diagnostic performance of MPV and IPF in identifying suspected ACS patients at emergency department. Moreover, we investigated the correlation between MPV or IPF with initial troponin I (TnI), one of the current ACS biomarkers. Methods: This was a single-center study recruiting suspected ACS patients who had acute chest pain at the emergency department. Whole blood samples were obtained from all participants and MPV and IPF were measured by Sysmex XE-5000 hematology analyzer within 20 min of blood sampling. The diagnostic values of MPV and IPF in identifying ACS were analyzed retrospectively. Result: In this study, 63 in 104 suspected ACS patients were diagnosed as ACS (65.3%). MPV and IPF were higher in ACS patients compared to non-ACS patients (MPV: 10.7 ± 0.80 fL vs 10.0 ± 0.64 fL, p
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- 2019
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23. Quality and quantity culture effectively restores functional and proliferative capacities of endothelial progenitor cell in end-stage renal disease patients
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Tien-Hung Huang, Mel S. Lee, Pei-Hsun Sung, Yi-Ling Chen, John Y. Chiang, Chih-Chao Yang, Jiunn-Jye Sheu, and Hon-Kan Yip
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Quality and quantity culture ,End-stage renal disease ,Endothelial progenitor cells ,Angiogenesis ,Anti-inflammation ,Biology (General) ,QH301-705.5 - Abstract
Background: Endothelial cell dysfunction plays the crucial role in initiation and propagation of obstructive arteriosclerosis which ultimately causes arterial obstructive syndrome. Additionally, severe endothelial progenitor cells (EPC) dysfunction is always found in those of end-stage renal disease (ESRD) patients. This study tested the hypothesis that a novel method, named “quality and quantity (QQ) culture”, could successfully improve the EPC proliferation and function in ESRD patients. Materials and methods: Peripheral blood mononuclear cells (PBMNCs) were isolated from age-matched control subjects (i.e., normal renal function) (group 1) and ESRD patients (group 2), followed by culture in either conventional EPC culture for one month or in QQ culture for 7 days, respectively. The result showed that as compared to the conventional EPC culture method, the EPC population and M2-like population/ratio (M2/M1) were significantly enriched in QQ culture both in groups 1 and 2 (all p
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- 2021
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24. Jagged/Notch proteins promote endothelial‐mesenchymal transition‐mediated pulmonary arterial hypertension via upregulation of the expression of <scp>GATAs</scp>
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Kun‐Chen Lin, Jui‐Ning Yeh, Pei‐Lin Shao, John Y. Chiang, Pei‐Hsun Sung, Chi‐Ruei Huang, Yi‐Ling Chen, Hon‐Kan Yip, and Jun Guo
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Molecular Medicine ,Cell Biology - Published
- 2023
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25. Adipose‐derived mesenchymal stem cells overexpressing prion improve outcomes via the <scp>NLRP3</scp> inflammasome/ <scp>DAMP</scp> signalling after spinal cord injury in rat
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Tsung‐Cheng Yin, Yi‐Chen Li, Pei‐Hsun Sung, John Y. Chiang, Pei‐Lin Shao, Hon‐Kan Yip, and Mel S. Lee
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Molecular Medicine ,Cell Biology - Published
- 2023
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26. Xenogeneic and Allogeneic Mesenchymal Stem Cells Effectively Protect the Lung Against Ischemia-reperfusion Injury Through Downregulating the Inflammatory, Oxidative Stress, and Autophagic Signaling Pathways in Rat
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Kun-Chen Lin, Jun-Ning Yeh, Yi-Ling Chen, John Y. Chiang, Pei-Hsun Sung, Fan-Yen Lee, Jun Guo, and Hon-Kan Yip
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Medicine - Abstract
This study tested the hypothesis that both allogenic adipose-derived mesenchymal stem cells (ADMSCs) and human inducible pluripotent stem cell-derived MSCs (iPS-MSCs) offered a comparable effect for protecting the lung against ischemia-reperfusion (IR) injury in rodent through downregulating the inflammatory, oxidative stress, and autophagic signaling pathways. Adult male Sprague–Dawley rats ( n = 32) were categorized into group 1 (sham-operated control), group 2 (IRI), group 3 [IRI + ADMSCs (1.0 × 10 6 cells)/tail-vein administration at 0.5/18/36 h after IR], and group 4 [IRI + iPS-MSCs (1.0 × 10 6 cells)/tail-vein administration at 0.5/18/36 h after IR], and lungs were harvested at 72 h after IR procedure. In vitro study demonstrated that protein expressions of three signaling pathways in inflammation (TLR4/MyD88/TAK1/IKK/I-κB/NF-κB/Cox-2/TNF-α/IL-1ß), mitochondrial damage/cell apoptosis (cytochrome C/cyclophilin D/DRP1/ASK1/APAF-1/mitochondrial-Bax/caspase3/8/9), and autophagy/cell death (ULK1/beclin-1/Atg5,7,12, ratio of LCB3-II/LC3B-I, p-AKT/m-TOR) were significantly higher in lung epithelial cells + 6h hypoxia as compared with the control, and those were significantly reversed by iPS-MSC treatment (all P < 0.001). Flow cytometric analysis revealed that percentages of the inflammatory cells in bronchioalveolar lavage fluid and circulation, and immune cells in circulation/spleen as well as circulatory early and late apoptotic cells were highest in group 2, lowest in group 1, and significantly higher in group 3 than in group 4 (all P < 0.0001). Microscopy showed the lung injury score and numbers of inflammatory cells and Western blot analysis showed the signaling pathways of inflammation, mitochondrial damage/cell apoptosis, autophagy, and oxidative stress exhibited an identical pattern of flow cytometric results among the four groups (all P < 0.0001). Both xenogeneic and allogenic MSCs protected the lung against IRI via suppressing the inflammatory, oxidative stress, and autophagic signaling.
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- 2020
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27. Human Umbilical Cord–Derived Mesenchymal Stem Cell Therapy Effectively Protected the Brain Architecture and Neurological Function in Rat After Acute Traumatic Brain Injury
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Kuan-Hung Chen, Pei-Lin Shao, Yi-Chen Li, John Y. Chiang, Pei-Hsun Sung, Hui-Wen Chien, Fu-Yuan Shih, Mel S. Lee, Wu-Fu Chen, and Hon-Kan Yip
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Medicine - Abstract
Intracranial hemorrhage from stroke and head trauma elicits a cascade of inflammatory and immune reactions detrimental to neurological integrity and function at cellular and molecular levels. This study tested the hypothesis that human umbilical cord–derived mesenchymal stem cell (HUCDMSC) therapy effectively protected the brain integrity and neurological function in rat after acute traumatic brain injury (TBI). Adult male Sprague-Dawley rats ( n = 30) were equally divided into group 1 (sham-operated control), group 2 (TBI), and group 3 [TBI + HUCDMSC (1.2 × 10 6 cells/intravenous injection at 3 h after TBI)] and euthanized by day 28 after TBI procedure. The results of corner test and inclined plane test showed the neurological function was significantly progressively improved from days 3, 7, 14, and 28 in groups 1 and 3 than in group 2, and group 1 than in group 3 (all P < 0.001). By day 28, brain magnetic resonance imaging brain ischemic volume was significantly increased in group 2 than in group 3 ( P < 0.001). The protein expressions of apoptosis [mitochondrial-bax positive cells (Bax)/cleaved-caspase3/cleaved-poly(adenosine diphosphate (ADP)-ribose) polymerase], fibrosis (Smad3 positive cells (Smad3)/transforming growth factor-β), oxidative stress (NADPH Oxidase 1 (NOX-1)/NADPH Oxidase 2 (NOX-2)/oxidized-protein/cytochrome b-245 alpha chain (p22phox)), and brain-edema/deoxyribonucleic acid (DNA)–damaged biomarkers (Aquaporin-4/gamma H2A histone family member X ( (γ-H2AX)) displayed an identical pattern to neurological function among the three groups (all P < 0.0001), whereas the protein expressions of angiogenesis biomarkers (vascular endothelial growth factor/stromal cell–derived factor-1α/C-X-C chemokine receptor type 4 (CXCR4)) significantly increased from groups 1 to 3 (all P < 0.0001). The cellular expressions of inflammatory biomarkers (cluster of differentiation 14 (+) cells (CD14+)/glial fibrillary acidic protein positive cells (GFAP+)/ a member of a new family of EGF-TM7 molecules positive cells (F4/80+)) and DNA-damaged parameter (γ-H2AX) exhibited an identical pattern, whereas cellular expressions of neural integrity (hexaribonucleotide Binding Protein-3 positive cells (NeuN+)/nestin+/doublecortin+) exhibited an opposite pattern of neurological function among the three groups (all P < 0.0001). Xenogeneic HUCDMSC therapy was safe and it significantly preserved neurological function and brain architecture in rat after TBI.
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- 2020
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28. Extracorporeal Shock Wave Therapy Salvages Critical Limb Ischemia in B6 Mice through Upregulating Cell Proliferation Signaling and Angiogenesis
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Pei-Hsun Sung, Tsung-Cheng Yin, Han-Tan Chai, John Y. Chiang, Chih-Hung Chen, Chi-Ruei Huang, and Hon-Kan Yip
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critical limb ischemia ,extracorporeal shock wave ,cell proliferation ,cell growth and cell motility signalings ,Biology (General) ,QH301-705.5 - Abstract
(1) This study tests hypothesis whether extracorporeal shock wave (ECSW) therapy effectively salvages mouse critical limb ischemia (CLI). In vitro result demonstrated that the angiogenesis parameters (i.e., tubular length/cluster/network formation) and protein expressions of EGFR/VEGFR2/RAS/c-Raf/MEK/ERK/VEGF/p-PI3K/p-Akt/p-m-TOR were significantly and progressively increased with stepwise augmentation of ECSW energy (0.1/0.14/0.20 mJ/mm2/140 impulses). On the other hand, they were suppressed by administration of Avastin (20 μM). Adult male B6 mice (n = 24) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 [CLI + ECSW (0.12 mJ/mm2/120 impulses/at days 1/3/7 after CLI induction)] and group 4 [CLI + ECSW (0.12 mJ/mm2/120 impulses) + Avastin (1 mg/intramuscular-injection)] at days 1/3/7 after CLI induction] and quadriceps were harvested by day 14. The laser Doppler result showed that the ratio of left (ischemia) to right (normal) limb blood flow was highest in group 1, lowest in group 2, and significantly higher in group 3 than in group 4 by days 7/14 after the CLI procedure (p < 0.0001). The protein expressions of cell proliferation/migration/angiogenesis receptors (EGFR/VEGFR2), angiogenesis biomarkers (VEGF/CXCR4/SDF-1) and cell proliferation/growth/survival (Ras/c-Raf/MEK/ERK)/(PI3K/Akt/m-TOR) and cell motility/proliferation (p-FAK/p-Scr) signaling biomarkers were significantly higher in group 3 than in groups 1/2/4, and significantly lower in group 1 than in groups 2/4, but they did not show a difference between groups 2 and 4 (all p < 0.001). The small vessel density and cellular levels of endothelial cell surface marker (CD31+) exhibited an identical pattern of blood flow, whereas the angiogenesis (CXCR4+/VEGF+) displayed an identical pattern of VEGFR2 among the groups (all p < 0.0001). The in vitro and in vivo studies found ECSW salvaged the CLI mainly through upregulating Ras-Raf-MEK/ERK/cell motility, cell proliferation/growth pathways and angiogenesis.
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- 2022
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29. Cellular Prion Protein Is Essential for Myocardial Regeneration but Not the Recovery of Left Ventricular Function from Apical Ballooning
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Jiunn-Jye Sheu, Han-Tan Chai, John Y. Chiang, Pei-Hsun Sung, Yi-Ling Chen, and Hon-Kan Yip
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takotsubo cardiomyopathy ,cellular prion protein ,Stelazine ,cell stress ,Biology (General) ,QH301-705.5 - Abstract
This study tested the hypothesis that cellular prion protein (PrPC) played an essential role in myocardial regeneration and recovery of left ventricular ejection fraction (LVEF) from apical takotsubo cardiomyopathy (TCM) induced by transaortic constriction (TAC). In vitro study was categorized into G1 (H9C2), G2 (H9C2-overexpression-PrPC), G3 (H9C2-overexpression-PrPC + Stelazine/1 uM), and G4 (H9C2 + siRNA-PrPC), respectively. The results showed that the protein expressions of PrPC, cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) and signal transduction pathway for cell proliferation/division (RAS/c-RAF/p-MEK/p-ERK1/2) were lowest in G1, highest in G2, significantly higher in G3 than in G4 (all p < 0.001). Adult-male B6 mice (n = 30) were equally categorized in group 1 (sham-control), group 2 (TAC) for 14 days, then relieved the knot and administered BrdU (50 ug/kg/intravenously/q.6.h for two times from day-14 after TAC) and group 3 (TAC + Stelazine/20 mg/kg/day since day 7 after TAC up to day 21 + BrdU administered as group 2), and animals were euthanized at day 28. The results showed that by day 28, the LVEF was significantly higher in group 1 than in groups 2/3 and significantly higher in group 3 than in group 2, whereas the LV chamber size exhibited an opposite pattern of LVEF (all p < 0.0001). The protein expressions of PrPC/p-PI3K/p-Akt/p-m-TOR/cyclin D/cyclin E and cellular-proliferation biomarkers (Ki67/PCNA/BrdU) exhibited an opposite pattern of LVEF (all p < 0.0001) among the three groups, whereas the protein expressions of RAS/c-RAF/p-MEK/p-ERK1/2 were significantly and progressively increased from groups 1 to 3 (all p < 0.0001). In conclusion, PrPC participated in regulating the intrinsic response of cell-stress signaling and myocardial regeneration but did not offer significant benefit on recovery of the heart function in the setting of TCM.
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- 2022
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30. Extracorporeal Shock Wave Therapy Protected the Functional and Architectural Integrity of Rodent Urinary Bladder against Ketamine-Induced Damage
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Yen-Ta Chen, Kuan-Hui Huang, John Y. Chiang, Pei-Hsun Sung, Chi-Ruei Huang, Yi-Ching Chu, Fei-Chi Chuang, and Hon-Kan Yip
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extracorporeal shock wave ,ketamine ,urinary bladder dysfunction ,inflammation ,cell stress signaling ,oxidative stress ,Biology (General) ,QH301-705.5 - Abstract
This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + ECSW) and G4 (RBdSMCs + menadione + ECSW). The results showed protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), inflammatory markers (MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-6/IL-1ß/MMP-9/iNOS), and cell-stress response signalings (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38/p-53) were significantly increased in G2 than in G1 and G3, and those were significantly reversed in G4 (all p < 0.0001). Adult-male SD rats (n = 24) were equally categorized into group 1 (sham-control), group 2 (ketamine/30 mg/kg/daily i.p. injection for four weeks), group 3 [ketamine/30 mg/kg + ECSW/optimal energy (0.12 mJ/mm2/120 impulses/at 3 h and days 3/7/14/21/28 after ketamine administration)] and group 4 [(ketamine/30 mg/kg + ECSW/higher energy (0.16 mJ/mm2/120 impulses)] and animals were euthanized by day 42. The results showed the urine levels of pro-inflammatory cytokines (TNF-α/IL-6) were lowest in group 1, highest in group 2 and significantly higher in group 3 than in group 4 at days 1/7/14/28 (all p < 0.0001). The duration of urinary bladder contraction was lowest in group 2, highest in group 1 and significantly higher in group 4 than in group 3, whereas the maximal pressure of urinary bladder exhibited an opposite pattern of bladder contraction among the groups (all p < 0.0001). The histopathological findings of fibrosis/inflammation/keratinization and protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), and inflammatory (TLR-2/TLR-4/MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-1ß/MMP-9/iNOS) and cell-stress response (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38) signalings and apoptotic/fibrotic biomarkers (cleaved-caspas3/cleaved-PARB/Smad3/TFG-ß) exhibited an identical pattern of urine proinflammatory cytokine among the groups (all p < 0.0001). ECSW effectively attenuated ketamine-induced bladder damage and dysfunction.
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- 2021
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31. Extracorporeal Shock Wave Enhanced Exogenous Mitochondria into Adipose-Derived Mesenchymal Stem Cells and Further Preserved Heart Function in Rat Dilated Cardiomyopathy
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Pei-Hsun Sung, Mel S. Lee, Han-Tan Chai, John Y. Chiang, Yi-Chen Li, Yi-Ching Chu, Chi-Ruei Huang, and Hon-Kan Yip
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exogenous mitochondria delivery ,dilated cardiomyopathy ,extracorporeal shock wave ,left ventricular ejection fraction ,angiogenesis ,Biology (General) ,QH301-705.5 - Abstract
This study tested whether extracorporeal shock wave (ECSW) supported-exogenous mitochondria (Mito) into adipose-derived mesenchymal stem cells (ADMSCs) would preserve left-ventricular-ejection-fraction (LVEF) in doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) rat. Adult-male-SD rats were equally categorized into group 1 (sham-control), group 2 (DCM), group 3 (DCM + ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction), group 4 (DCM + ECSW/1.5 mJ/mm2/100 shots-assisted mito delivery (500 μg) into ADMSCs/1.2 × 106 cells, then implanted into LV myocardium day 14 after DCM induction) and group 5 (DCM + ECSW-assisted mito delivery into ADMSCs/1.2 × 106 cells, then implanted into LV, followed by ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction) and euthanized by day 49. Microscopic findings showed mitochondria were abundantly enhanced by ECSW into H9C2 cells. The q-PCR showed a significant increase in relative number of mitDNA in mitochondrial-transferred H9C2 cells than in control group (p < 0.01). The angiogenesis/angiogenesis factors (VEGF/SDF-1α/IG-F1) in HUVECs were significantly progressively increased by a stepwise-increased amount of ECSW energy (0.1/0.25/0.35 mJ/mm2) (all p < 0.001). The 49-day LVEF was highest in group 1 and significantly progressively increased from groups 2 to 5 (all p < 0.0001). Cardiomyocyte size/fibrosis exhibited an opposite pattern of LVEF, whereas cellular/protein levels of angiogenesis factors (VEGF/SDF-1α) in myocardium were significantly progressively increased from groups 1 to 5 (all p < 0.0001). The protein expressions of apoptotic/mitochondrial (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax/cytosolic-cytochrome-C), fibrotic (p-Smad3/TGF-ß), oxidative-stress (NOX-1/NOX-2) and pressure-overload/heart failure (BNP/ß-MHC) biomarkers exhibited an opposite pattern of LVEF among the five groups (all p < 0.0001). ECSW-assisted mitochondrial-delivery into ADMSCs plus ECSW offered an additional benefit for preserving LVEF in DCM rat.
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- 2021
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32. No correlation between body mass index and 30-day prognostic outcome in Asians with acute ST-elevation myocardial infarction undergoing primary coronary intervention
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Po-Jui Wu, Hui-Ting Wang, Pei-Hsun Sung, Meng-Shen Tong, Cheng-Hsu Yang, Chien-Jen Chen, Cheng-Jei Lin, Shu-Kai Hsueh, Sheng-Ying Chung, Wen-Jung Chung, Chi-Ling Hang, Chiung-Jen Wu, and Hon-Kan Yip
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Acute ST-segment elevation myocardial infarction ,Overweight ,Obesity ,Primary PCI ,30-day prognostic outcome ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: This study investigated whether body mass index (BMI) was a risk factor predictive of 30-day prognostic outcome in Asians with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and methods: Data regarding the impact of BMI on the prognostic outcome in Asian populations after acute STEMI is scarce. A number of 925 STEMI patients were divided into three groups according to the BMI: normal weight (
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- 2017
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33. Higher neutrophil counts and neutrophil-to-lymphocyte ratio predict prognostic outcomes in patients after non-atrial fibrillation-caused ischemic stroke
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Yen-Nan Fang, Meng-Shen Tong, Pei-Hsun Sung, Yung-Lung Chen, Chih-Hung Chen, Nei-Wen Tsai, Chih-Jen Huang, Ya-Ting Chang, Shu-Fang Chen, Wen-Neng Chang, Cheng-Hsien Lu, and Hon-Kan Yip
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Acute ischemic stroke ,In-hospital mortality ,Discriminating factor ,Severe stroke ,Tissue plasminogen activator ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: We aimed to determine whether higher neutrophil counts (NC) and neutrophil-to-lymphocyte ratio (NLR) were independently predictive of worse in-hospital outcome in patients after acute ischemic stroke (IS). Methods: A retrospective observational study with prospective manner of IS registration. Between April 2012 and August 2014, a total number of 1731 patients with post-IS were consecutively enrolled in the study. Blood samples were drawn upon admission. Primary endpoint was in-hospital mortality. Secondary endpoint was severe stroke (≥16 NIHSS). Results: The NC progressively increased from mild (NIHSS ≤ 5) to moderate (NIHSS ≥ 6 74% had a 2.54-fold increased risk of severe stroke (OR = 1.82–3.54) compared to patients with NC
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- 2017
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34. Risk of New‐Onset Atrial Fibrillation Among Asian Chronic Hepatitis C Virus Carriers: A Nationwide Population‐Based Cohort Study
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Yao‐Hsu Yang, Hsin‐Ju Chiang, Hon‐Kan Yip, Ko‐Jung Chen, John Y. Chiang, Mel S. Lee, and Pei‐Hsun Sung
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atrial fibrillation ,chronic hepatitis C ,extrahepatic manifestations ,inflammation ,population‐based cohort study ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Hepatitis C virus (HCV) infection not only links closely to systemic inflammation but also has numerous extrahepatic manifestations. Chronic inflammation also increases the risk of new‐onset atrial fibrillation (AF). However, little is known regarding the clinical association between HCV infection and new‐onset AF. Methods and Results We conducted a population‐based cohort study using Taiwan's National Health Insurance Research Database during 1997 to 2013. A total of 11 771 HCV‐infected patients were included in this study, and each of them was matched in a ratio of 1:4. Because of higher mortality among HCV cohorts, we used both Cox proportional hazard regression and competing risk regression models to compute the hazard ratios accompanying 95% CIs after adjustment for relevant confounder. The results demonstrated that the patients with chronic HCV infection had significantly higher incidence rate (332.0 versus 265.8 in 100 000 person‐years, P
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- 2019
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35. Hyperbaric oxygen-assisted melatonin therapy protects the heart from acute ischemia-reperfusion injury
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Hon-Kan Yip, Fan-Yen Lee, John Y Chiang, Pei-Hsun Sung, Jui-Ning Yeh, and Han-Tan Chai
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General Medicine - Abstract
In this study we have examined whether hyperbaric oxygen (HBO)-assisted melatonin (Mel) therapy effectively preserves the heart function against ischemia (40-min)-reperfusion (IR) injury. First, the in vitro study has been performed by use of cell culture. H9C2 cells were treated as groups: A (H9C2) (without any treatment), B (H9C2+IR), C (H9C2+IR+HBO), D [H9C2+IR+Melatonin (50 µM)] and E (H9C2+IR+Melatonin+HBO). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2)/inflammatory (TNF-α/NF-κB)/apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and cellular levels of DNA/mitochondrial-damaged (γ-H2AX/XRCC1-CD90+/cytosolic-cytochrome-C) biomarker were significantly increased in group B compared to control group A. These biomarkers were significantly reduced in group C, D and E compared to groups B with the significantly higher reduction in group E than that in groups C and D (p 4 >1. The significant differences were present between each two matched groups (p
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- 2022
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36. Combined Therapy With Adipose‐Derived Mesenchymal Stem Cells and Ciprofloxacin Against Acute Urogenital Organ Damage in Rat Sepsis Syndrome Induced by Intrapelvic Injection of Cecal Bacteria
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Pei-Hsun Sung, Hsin-Ju Chiang, Chih-Hung Chen, Yi-Ling Chen, Tien-Hung Huang, Yen-Yi Zhen, Meng-Wei Chang, Chu-Feng Liu, Sheng-Ying Chung, Yung-Lung Chen, Han-Tan Chai, Cheuk-Kwan Sun, and Hon-Kan Yip
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Sepsis syndrome ,Adipose-derived mesenchymal stem cells ,Antibiotics ,Inflammation ,Urogenital organ damage ,Medicine (General) ,R5-920 ,Cytology ,QH573-671 - Abstract
We hypothesized that combined treatment with autologous adipose‐derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis‐induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 104 cells per milliliter; total, 5.0 ml). Male Sprague‐Dawley rats (n = 60) equally divided into group 1 (sham‐control), group 2 (SS), group 3 (SS‐ADMSC [5.0 × 105 intravenously at 0.5, 6, and 18 hours after sepsis induction]), group 4 (SS‐ciprofloxacin [3.0 mg/kg, b.i.d.] for 5 days), and group 5 (SS‐ADMSC‐ciprofloxacin) were sacrificed by day 5. Mortality rate and creatinine level were highest in group 2 and lowest in group 1 and significantly higher in groups 3 and 4 than those in group 5, but there was no difference between groups 3 and 4 (all p < .005). The kidney injury score, inflammatory biomarker expressions at protein (tumor necrosis factor‐1α, nuclear factor‐κB, matrix metallopeptidase‐9, regulated on activation, normal T‐cell expressed and secreted, interleukin‐1β) and cellular (CD14+, migratory inhibitor factor positive, CD68+) levels in kidneys and urinary bladder were lowest in group 1 and highest in group 2, higher in group 4 than in groups 3 and 5, and higher in group 3 than in group 5 (all p < .001). Protein expressions of apoptosis (Bax, cleaved caspase 3 and poly[ADP‐ribose] polymerase 1, p21 protein [Cdc42/Rac]‐activated kinase 2) and oxidative stress (oxidized protein, NADPH oxidase (NOX)‐1, NOX‐2) in these organs showed an identical pattern compared with that of inflammation in all groups (all p < .001). In conclusion, ADMSC‐assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rat. Significance Autologous adipose‐derived mesenchymal stem cell‐assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rats.
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- 2016
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37. Prion Protein Overexpression in Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Effectively Protected Rodent Kidney Against Ischemia-Reperfusion Injury - Role of ADMSCs Rejuvenation
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Yen‐Ta Chen, Chih‐Chao Yang, John Y. Chiang, Pei-Lin Shao, Pei-Hsun Sung, Chi-Ruei Huang, Mel S. Lee, and Hon-Kan Yip
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- 2023
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38. Correlation between Therapeutic Efficacy of CD34+ Cell Treatment and Directed In Vivo Angiogenesis in Patients with End-Stage Diffuse Coronary Artery Disease
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Tien-Hung Huang, Cheuk-Kwan Sun, Yi-Ling Chen, Pei-Hsun Sung, Chi-Hsiang Chu, Mel S. Lee, Yuan-Ping Lin, Hon-Kan Yip, and Fan-Yen Lee
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Internal medicine ,RC31-1245 - Abstract
Background. This study was aimed at testing the association between the therapeutic efficacy of CD34+ cell treatment in patients with end-stage diffuse coronary artery disease as reflected in angiographic grading and results of directed in vivo angiogenesis assay (DIVAA) on their isolated peripheral blood mononuclear cell- (PBMC-) derived endothelial progenitor cells (EPCs). Methods. Angiographic grades (0: 75%) which presented the improvement of vessel density pre- and post-CD34+ treatment were given to 30 patients with end-stage diffuse coronary artery disease having received CD34+ cell treatment. The patients were categorized into low-score group (angiographic grade 0 or 1, n=12) and high-score group (angiographic grade 2 or 3, n=18). The percentages of circulating EPCs with KDR+/CD34+/CD45−, CD133+/CD34+/CD45−, and CD34+ were determined in each patient using flow cytometry. PBMC-derived EPCs from all patients were subjected to DIVAA through a 14-day implantation in nude mice. The DIVAA ratio (i.e., mean fluorescent units in angioreactors with EPCs/mean fluorescent units in angioreactors without EPCs) was obtained for each animal with implanted EPCs from each patient. Results and Conclusions. The number of EPCs showed no significant difference among the two groups. The DIVAA ratio in the high-score group was significantly higher than that in the low-score group (p=0.0178). Logistic regression revealed a significant association between the DIVAA ratio and angiographic grading (OR 3.12, 95% CI: 1.14–8.55, p=0.027). The area under the ROC curve (AUC) was 0.8519 (p=0.0013). We proposed that DIVAA may be a reliable tool for assessing coronary vascularization after CD34+ cell treatment.
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- 2018
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39. Shock Wave Therapy Enhances Mitochondrial Delivery into Target Cells and Protects against Acute Respiratory Distress Syndrome
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Kun-Chen Lin, Christopher Glenn Wallace, Tsung-Cheng Yin, Pei-Hsun Sung, Kuan-Hung Chen, Hung-I Lu, Han-Tan Chai, Chih-Hung Chen, Yi-Ling Chen, Yi-Chen Li, Pei-Lin Shao, Mel S. Lee, Jiunn-Jye Sheu, and Hon-Kan Yip
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Pathology ,RB1-214 - Abstract
This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2 for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (all p
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- 2018
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40. Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents
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Kuan-Hung Chen, Hung-Sheng Lin, Yi-Chen Li, Pei-Hsun Sung, Yi-Ling Chen, Tsung-Cheng Yin, and Hon-Kan Yip
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Inflammation ,Caspase 3 ,Tumor Necrosis Factor-alpha ,Probiotics ,Organic Chemistry ,NF-kappa B ,Peripherins ,Mesenchymal Stem Cells ,Rodentia ,General Medicine ,DNA ,Poly(ADP-ribose) Polymerase Inhibitors ,Catalysis ,Computer Science Applications ,Rats ,Inorganic Chemistry ,Rats, Sprague-Dawley ,neuropathic pain ,chronic constriction injury ,probiotics ,adipose-tissue-derived mesenchymal stem cells ,Matrix Metalloproteinase 9 ,Animals ,Neuralgia ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Biomarkers - Abstract
This study investigated the hypothesis that probiotics enhanced the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on alleviating neuropathic pain (NP) due to chronic constriction injury (CCI) mainly through regulating the microbiota in rats. SD rats (n = 50) were categorized into group 1 (sham-control), group 2 (NP), group 3 (NP + probiotics (i.e., 1.5 billion C.F.U./day/rat, orally 3 h after NP procedure, followed by QOD 30 times)), group 4 (NP + ADMSCs (3.0 × 105 cells) 3 h after CCI procedure, followed by QOD six times (i.e., seven times in total, i.e., mimic a clinical setting of drug use) and group 5 (NP + probiotics + ADMSCs (3.0 × 105 cells)) and euthanized by day 60 after NP induction. By day 28 after NP induction, flow-cytometric analysis showed circulating levels of early (AN-V+/PI−) and late (AN-V+/PI+) apoptotic, and three inflammatory (CD11b-c+, Ly6G+ and MPO+) cells were lowest in group 1 and significantly progressively reduced in groups 2 to 5 (all p < 0.0001). By days 7, 14, 21, 28, and 60 after CCI, the thresholds of thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were highest in group 1 and significantly progressively increased in groups 2 to 5 (all p < 0.0001). Numbers of pain-connived cells (Nav1.8+/peripherin+, p-ERK+/peripherin+, p-p38+/peripherin+ and p-p38+/NF200+) and protein expressions of inflammatory (p-NF-κB, IL-1ß, TNF-α and MMP-9), apoptotic (cleaved-caspase-3, cleaved-PARP), oxidative-stress (NOX-1, NOX-2), DNA-damaged (γ-H2AX) and MAPK-family (p-P38, p-JNK, p-ERK1/2) biomarkers as well as the protein levels of Nav.1.3, Nav.1.8, and Nav.1.9 in L4-L5 in dorsal root ganglia displayed an opposite pattern of mechanical PWT among the groups (all p < 0.0001). In conclusion, combined probiotic and ADMSC therapy was superior to merely one for alleviating CCI-induced NP mainly through suppressing inflammation and oxidative stress.
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- 2022
41. Overexpression of miR‐19a and miR‐20a in iPS‐MSCs preserves renal function of chronic kidney disease with acute ischaemia‐reperfusion injury in rat
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Chih-Chao Yang, John Y. Chiang, Yi-Chen Li, Pei-Hsun Sung, Hon-Kan Yip, Mel S. Lee, Kuan-Hung Chen, and Tien-Hung Huang
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0301 basic medicine ,Male ,Apoptosis ,medicine.disease_cause ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,biology ,microRNAs ,iPS‐MSCs ,030220 oncology & carcinogenesis ,Reperfusion Injury ,Molecular Medicine ,Original Article ,medicine.symptom ,Signal Transduction ,medicine.medical_specialty ,Induced Pluripotent Stem Cells ,Renal function ,Inflammation ,Creatine ,Cell Line ,03 medical and health sciences ,Internal medicine ,Animals ,Humans ,Renal Insufficiency, Chronic ,Creatinine ,business.industry ,fibrosis ,Mesenchymal Stem Cells ,Cell Biology ,Original Articles ,medicine.disease ,Rats ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,inflammation ,biology.protein ,ischaemia‐reperfusion injury ,P22phox ,business ,Oxidative stress ,chronic kidney disease ,Kidney disease - Abstract
This study tested the hypothesis that therapy with double overexpression of miR‐19a‐3p and miR‐20a‐5p (miRDOE) to human inducible pluripotent stem cell–derived mesenchymal stem cells (iPS‐MSCs) was superior to iPS‐MSCs alone for preserving renal function in rat with pre‐existing chronic kidney disease (CKD), followed by ischaemia‐reperfusion (IR) injury. In vitro study demonstrated that the protein expressions of oxidative stress (NOX‐1/NOX‐2/NOX4/oxidized protein/p22phox), inflammatory downstream signalling (TLR2&4/MyD88/TRAF6/IKK‐ß/p‐NFκB/IL‐1ß/IL‐6/MMP‐9) and cell apoptosis/death signalling (cleaved caspase‐3/mitochondrial Bax/p‐ERKs/p‐JNK/p‐p38) at time‐points of 24‐hour/48‐hour cell cultures were significantly increased in p‐Cresol‐treated NRK‐52E cells than in the control that was significantly reversed by miR‐19a‐3p‐transfected iPS‐MSC (all P
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- 2021
42. Umbilical cord‐derived MSC and hyperbaric oxygen therapy effectively protected the brain in rat after acute intracerebral haemorrhage
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Pei-Hsun Sung, Re-Wen Wu, Tsung-Cheng Yin, Hon-Kan Yip, Kuan-Hung Chen, Kun-Chen Lin, and John Y. Chiang
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Male ,0301 basic medicine ,CD31 ,medicine.medical_specialty ,CD14 ,Apoptosis ,Inflammation ,Mesenchymal Stem Cell Transplantation ,HMGB1 ,medicine.disease_cause ,Umbilical cord ,neurological function ,Umbilical Cord ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Animals ,Medicine ,Brain Diseases ,Hyperbaric Oxygenation ,mesenchymal stem cells ,biology ,business.industry ,intracerebral haemorrhage ,Original Articles ,Cell Biology ,Rats ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,hyperbaric oxygen ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Original Article ,medicine.symptom ,NeuN ,business ,Intracranial Hemorrhages ,Oxidative stress - Abstract
This study tested the hypothesis that combined therapy with human umbilical cord‐derived mesenchymal stem cells (HUCDMSCs) and hyperbaric oxygen (HBO) was superior to either one on preserving neurological function and reducing brain haemorrhagic volume (BHV) in rat after acute intracerebral haemorrhage (ICH) induced by intracranial injection of collagenase. Adult male SD rats (n = 30) were equally divided into group 1 (sham‐operated control), group 2 (ICH), group 3 (ICH +HUCDMSCs/1.2 × 106 cells/intravenous injection at 3h and days 1 and 2 after ICH), group 4 (ICH +HBO/at 3 hours and days 1 and 2 after ICH) and group 5 (ICH +HUCDMSCs‐HBO), and killed by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2‐5 than in group 1 (P
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- 2021
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43. Investigation of echocardiographic characteristics and predictors for persistent defects of patent foramen ovale or patent ductus arteriosus in Chinese newborns
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Pei-Hsun Sung, John Y. Chiang, Long-Zhen Zhang, Jin-Xin Jiang, Zhen Yuan, Hung-Tao Chung, Hsin-Ju Chiang, Bin Li, and Hon-Kan Yip
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0301 basic medicine ,Male ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,China ,Heart disease ,health care facilities, manpower, and services ,Birth weight ,education ,Patent ductus arteriosus ,Foramen Ovale, Patent ,Ventricular septal defect ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,health services administration ,Internal medicine ,Ductus arteriosus ,medicine ,Humans ,Ductus Arteriosus, Patent ,Spontaneous closure ,Congenital heart disease ,business.industry ,Infant, Newborn ,General Medicine ,medicine.disease ,Pulmonary hypertension ,Patent foramen ovale ,Embolic stroke ,030104 developmental biology ,medicine.anatomical_structure ,Treatment Outcome ,Echocardiography ,030220 oncology & carcinogenesis ,Concomitant ,Cardiology ,Atrial septal defect ,Original Article ,Female ,business - Abstract
Background Persistent patent foramen ovale (PFO) and patent ductus arteriosus (PDA) increase the adult risk of cryptogenic embolic stroke and chronic pulmonary hypertension. To understand the characteristics of PFO and PDA in newborns, we investigated the spontaneous closure rate and derived the determinants for residual defects. Methods We utilized the database of congenital heart disease (CHD) in Xiamen ChangGung Memorial Hospital from 2015 to 2017 and allocated 2523 eligible newborns into four groups according to PDA, PFO, both or neither at birth. A total of 574, 1229, 202 and 518 newborns were assigned into the group of PFO and PDA, PFO alone, PDA alone and non-PFO/non-PDA, respectively. Regular echocardiographic follow-ups at baseline, 6, 12 and 24 months after birth were performed for evaluating the spontaneous closure rate in the subjects. Regression analysis was carried out to study the risk factors of residual congenital defects. Results Newborns with PFO alone had the youngest birth age and lowest birth weight among the four groups. About one in four PDA-alone newborns had concomitant small ASD, i.e.
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- 2021
44. Dipeptidyl peptidase 4 promotes peritoneal fibrosis and its inhibitions prevent failure of peritoneal dialysis
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Hon-Kan Yip, Yao-Hsu Yang, Chih-Chao Yang, John Y. Chiang, Pei-Hsun Sung, and Yi-Chen Li
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Male ,0301 basic medicine ,medicine.medical_treatment ,030232 urology & nephrology ,Medicine (miscellaneous) ,Pharmacology ,medicine.disease_cause ,End-stage renal disease ,0302 clinical medicine ,Medicine ,Biology (General) ,Peritoneal Fibrosis ,Aged, 80 and over ,Middle Aged ,Mechanisms of disease ,Treatment Outcome ,medicine.anatomical_structure ,Sitagliptin ,Female ,Peritoneum ,Rats, Transgenic ,medicine.symptom ,General Agricultural and Biological Sciences ,medicine.drug ,Adult ,Epithelial-Mesenchymal Transition ,Adolescent ,QH301-705.5 ,Dipeptidyl Peptidase 4 ,Peritoneal dialysis ,Mutation, Missense ,Taiwan ,Inflammation ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,End stage renal disease ,Young Adult ,03 medical and health sciences ,Animals ,Humans ,Dipeptidyl peptidase-4 ,Aged ,Retrospective Studies ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Translational research ,Rats, Inbred F344 ,Disease Models, Animal ,030104 developmental biology ,Kidney Failure, Chronic ,business ,Oxidative stress - Abstract
Peritoneal dialysis (PD) possesses multiple advantages for end stage renal disease. However, long-term PD triggers peritoneal fibrosis (PF). From the nationwide analysis of diabetic PD patients (n = 19,828), we identified the incidence of PD failure was significantly lower in diabetic patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors. Experimental study further showed high concentration of glucose remarkably enhanced DPP4 to promote epithelial-mesenchymal transition (EMT) in the mesothelial cells. In chlorhexidine gluconate (CG)-induced PF model of rats, DPP4 expression was enriched at thickening peritoneum. Moreover, as to CG-induced PF model, DPP4 deficiency (F344/DuCrlCrlj strain), sitagliptin and exendin-4 treatments significantly inhibited DPP4 to reverse the EMT process, angiogenesis, oxidative stress, and inflammation, resulting in the protection from PF, preservation of peritoneum and the corresponding functional integrity. Furthermore, DPP4 activity was significantly correlated with peritoneal dysfunction. Taken together, DPP4 caused peritoneal dysfunction/PF, whereas inhibition of DPP4 protected the PD patients against PD failure., Li et al. show that dipeptidyl peptidase 4 (DPP4) promotes peritoneal fibrosis whereas the inhibition of DPP4 protects the patients from failure of peritoneal dialysis. This study provides mechanistic insights into the effects of DPP4 on peritoneal fibrosis and the translational potential of these effects.
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- 2021
45. Risk of major adverse cardiovascular and cerebrovascular events in Taiwanese women with endometriosis
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Yu-Ting Su, Yao-Hsu Yang, John Y. Chiang, Yu-Ju Lin, Fu-Tsai Kung, Pei-Hsun Sung, Hsin-Ju Chiang, Kuo-Chung Lan, and Fu-Jen Huang
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Adult ,medicine.medical_specialty ,Adolescent ,Population ,Endometriosis ,Disease ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,education ,Surgical treatment ,Retrospective Studies ,lcsh:R5-920 ,education.field_of_study ,business.industry ,Therapeutic effect ,General Medicine ,Middle Aged ,medicine.disease ,Medical and surgical treatment ,Cerebrovascular Disorders ,Population-based cohort study ,Increased risk ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Cohort ,Female ,030211 gastroenterology & hepatology ,Major adverse cardiovascular and cerebrovascular events ,lcsh:Medicine (General) ,business ,Cohort study - Abstract
Background/Purpose: Endometriosis (EM) is linked to cardiovascular disease (CVD). However, whether this finding can be applied to the Taiwanese population remained unanswered. To investigate the association between EM and major adverse cardiovascular and cerebrovascular events (MACCE) and the therapeutic effect on the risk of MACCE in Asian women with EM. A retrospective population-based cohort study was performed. Methods: A total of 17 543 patients with EM aged between 18 and 50 years were identified from a general population of 1 million Taiwanese after excluding diagnoses of major CVD and cerebrovascular accident (CVA) prior to EM. The comparison group (n = 70 172) without EM was selected by matching the study cohort with age, sex, and income and urbanization levels in a 4:1 ratio. Results: During a median follow-up period of 9.2 years, Taiwanese women with EM had a significantly higher frequency of comorbidities, medical and surgical treatment, and MACCE than did their non-EM counterparts (2.76% vs 2.18%, P
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- 2021
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46. Levosimendan Administration May Provide More Benefit for Survival in Patients with Non-Ischemic Cardiomyopathy Experiencing Acute Decompensated Heart Failure
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Wei-Chieh Lee, Po-Jui Wu, Hsiu-Yu Fang, Yen-Nan Fang, Huang-Chung Chen, Meng-Shen Tong, Pei-Hsun Sung, Chieh-Ho Lee, and Wen-Jung Chung
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acute decompensated heart failure ,levosimendan ,ischemic cardiomyopathy ,non-ischemic cardiomyopathy ,mortality ,General Medicine - Abstract
Background: Acute decompensated heart failure (ADHF) is a life-threatening condition with a high mortality rate. Levosimendan is an effective inotropic agent used to maintain cardiac output and a long-lasting effect. However, only few studies have compared the clinical outcomes, after levosimendan therapy, among etiologies of ADHF. Methods: Between July 2014 and December 2019, 184 patients received levosimendan therapy for ADHF at our hospital. A total of 143 patients had ischemic cardiomyopathy (ICM), and 41 patients had non-ICM (NICM). Data on comorbidities, echocardiographic findings, laboratory findings, use of mechanical devices, consumption of other inotropic or vasopressor agents, frequency of HF hospitalization, cardiovascular (CV) mortality, and all-cause mortality were compared between the ICM and NICM groups. Results: Patients with ICM were older with higher prevalence of diabetes mellitus when compared to patients with NICM. Patients with NICM had a poorer left ventricular ejection fraction (LVEF) and higher left ventricular end-systolic volume when compared to patients with ICM. At the 30 day follow-up period, a lower CV mortality (ICM vs. NICM: 20.9% vs. 5.1%; log-rank p = 0.033) and lower all-cause mortality (ICM vs. NICM: 28.7% vs. 9.8%; log-rank p = 0.018) was observed in the NICM patients. A significantly lower all-cause mortality was noted at 180 day (ICM vs. NICM: 39.2% vs. 22.0%; log-rank p = 0.043) and 1 year (ICM vs. NICM: 41.3% vs. 24.4%; log-rank p = 0.046) follow up in the NICM subgroup. NICM (hazard ratio (HR): 0.303, 95% confidence interval (CI): 0.108–0.845; p = 0.023) and ECMO use (HR: 2.550, 95% CI: 1.385–4.693; p = 0.003) were significant predictors of 30 day all-cause mortality. Conclusions: In our study on levosimendan use for ADHF patients, better clinical outcomes were noted in the NICM population when compared to the ICM population. In the patients with cardiogenic shock or ventilator use, significantly lower incidence of 30 day mortality presented in the NICM population when compared with the ICM population.
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- 2022
47. Decreased Ankyrin Expression Is Associated with Repressed eNOS Signaling, Cell Proliferation, and Osteogenic Differentiation in Osteonecrosis of the Femoral Head
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Rio L.C. Lin, Pei-Hsun Sung, Chen-Ta Wu, Yuan-Kun Tu, Yu-Der Lu, Hon-Kan Yip, and Mel S. Lee
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Ankyrins ,Cell Differentiation ,Femur Head ,Mesenchymal Stem Cells ,General Medicine ,Femur Head Necrosis ,Osteogenesis ,Humans ,Orthopedics and Sports Medicine ,Surgery ,Hyaluronic Acid ,Proto-Oncogene Proteins c-akt ,Cell Proliferation ,Signal Transduction - Abstract
Reduced nitric oxide synthase (NOS) activity and decreased reparative potentials in stem cells may be involved in the pathogenesis of osteonecrosis of the femoral head (ONFH), but the underlying mechanism is not clear. Ankyrin, a cytoskeletal protein, can promote NOS expression and many cellular functions when it interacts with the CD44 receptors on the stem cells. This study investigated whether ankyrin is involved in the pathogenesis of ONFH.Bone marrow stem cells (BMSCs) from ONFH patients were compared with cells from patients with proximal femoral fracture and BMSC cell lines (PT-2501, Lonza, NC, USA). Differences in the expression levels and downstream signal pathway of ankyrin-Akt-eNOS in BMSCs were studied between ONFH and control. The involvement of ankyrin in the signal cascade, cell proliferation, and differentiation were further investigated by silencing ankyrin using small interfering (si)RNA.We found the basal mRNA levels of ankyrin and CD44 in BMSCs from the ONFH group were significantly lower as compared with those from the control group. The signal transduction of CD44-ankyrin-Akt-eNOS was significantly repressed in the ONFH group as compared with the control group after hyaluronic acid treatment. Knockdown of ankyrin by siRNA could attenuate the eNOS signaling as well as the BMSCs proliferation and osteogenic differentiation. The proliferation ability and osteogenic differentiation potential of the BMSCs from the ONFH group were significantly reduced as compared with the control group, but they can be enhanced to the baseline levels of the control group by hyaluronic acid treatment.The aberrant eNOS signaling, reduced cell proliferation, and osteogenic differentiation potential in BMSCs from ONFH patients are associated with the decreased ankyrin expression.Altered signal transduction, proliferation, and osteogenic differentiation ability in BMSCs may be involved in the pathogenesis of ONFH. These need further studies especially in BMSC-based cell therapy.
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- 2022
48. Impact of chronic obstructive pulmonary disease on patient with acute myocardial infarction undergoing primary percutaneous coronary intervention
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Pei-Hsun Sung, Sheng-Ying Chung, Cheuk-Kwan Sun, Cheng-Hsu Yang, Shyh-Ming Chen, Chi-Ling Hang, Chien-Jen Chen, Kuo-Ho Yeh, Yung-Lung Chen, Chiung-Jen Wu, Hsuen-wen Chang, Tzu-Hsien Tsai, and Hon-Kan Yip
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Acute myocardial infarction ,chronic obstructive lung disease ,clinical outcome ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: This study reported the incidence and prognostic outcome of chronic obstructive lung disease (COPD) patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Between January 2002 and May 2011, totally 1554 consecutive patients who experienced STEMI undergoing primary PCI were enrolled into the study. Results: Of the 1554 patients, 124 (9.7%) with diagnosis of COPD and 1430 (90.3%) without COPD were categorized into group 1 and group 2. Although no difference in in-hospital mortality was noted between the two groups (p = 0.726). However, the hospitalization duration was notably longer (p = 0.003), the incidences of recurrent MI and re-hospitalization for congestive heart failure were significantly higher in group 1 than in group 2 (all p < 0.02). Although Kaplan-Meier analysis demonstrated that the incidence of freedom from one-year major adverse clinical outcome (MACO) (defined as recurrent MI, re-admission for congestive heart failure was significantly lower in group 1 than group 2 (p = 0.012), multivariate Cox regression analysis showed COPD was not an independent predictor of MACO-free time after adjusting traditional risk factors. Conclusion: COPD was not an independent predictor of short-term and medium-term MACO in patients with STEMI undergoing primary PCI.
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- 2013
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49. Hepatic 31 P‐magnetic resonance spectroscopy identified the impact of melatonin‐pretreated mitochondria in acute liver ischaemia‐reperfusion injury
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Yi-Ching Chu, John Y. Chiang, Sheung-Fat Ko, Hon-Kan Yip, Chung-Cheng Huang, Yi-Ling Chen, Pei-Hsun Sung, and Chi-Ruei Huang
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0301 basic medicine ,Liver injury ,medicine.medical_specialty ,Adult male ,business.industry ,Ischaemia-reperfusion injury ,Liver protein ,Cell Biology ,Nuclear magnetic resonance spectroscopy ,Mitochondrion ,medicine.disease ,medicine.disease_cause ,Melatonin ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,030220 oncology & carcinogenesis ,Internal medicine ,Molecular Medicine ,Medicine ,business ,Oxidative stress ,medicine.drug - Abstract
Acute liver ischaemia-reperfusion injury (IRI), commonly encountered during liver resection and transplantation surgery, is strongly associated with unfavourable clinical outcome. However, a prompt and accurate diagnosis and the treatment of this entity remain formidable challenges. This study tested the hypothesis that 31 P-magnetic resonance spectroscopy (31 P-MRS) findings could provide reliable living images to accurately identify the degree of acute liver IRI and melatonin-pretreated mitochondria was an innovative treatment for protecting the liver from IRI in rat. Adult male SD rats were categorized into group 1 (sham-operated control), group 2 (IRI only) and group 3 (IRI + melatonin [ie mitochondrial donor rat received intraperitoneal administration of melatonin] pretreated mitochondria [10 mg/per rat by portal vein]). By the end of study period at 72 hours, 31 P-MRS showed that, as compared with group 1, the hepatic levels of ATP and NADH were significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1. The liver protein expressions of mitochondrial-electron-transport-chain complexes and mitochondrial integrity exhibited an identical pattern to 31 P-MRS finding. The protein expressions of oxidative stress, inflammatory, cellular stress signalling and mitochondrial-damaged biomarkers displayed an opposite finding of 31 P-MRS, whereas the protein expressions of antioxidants were significantly progressively increased from groups 1 to 3. Microscopic findings showed that the fibrotic area/liver injury score and inflammatory and DNA-damaged biomarkers exhibited an identical pattern of cellular stress signalling. Melatonin-pretreated mitochondria effectively protected liver against IRI and 31 P-MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals.
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- 2020
- Full Text
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50. Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome
- Author
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Hon-Kan Yip, Fan-Yen Lee, Mel S. Lee, Chen-Hsiang Lee, Wen-Feng Fang, Sung-Nan Pei, Yi-Chen Li, Pei-Hsun Sung, Kuan-Hung Chen, and Ming-Chun Ma
- Subjects
medicine.medical_specialty ,biology ,Septic shock ,business.industry ,Mesenchymal stem cell ,CD44 ,CD34 ,Phases of clinical research ,030208 emergency & critical care medicine ,Critical Care and Intensive Care Medicine ,medicine.disease ,Stem cell marker ,Umbilical cord ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,Internal medicine ,medicine ,biology.protein ,CD90 ,business - Abstract
OBJECTIVES: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. DESIGN: Prospective phase I clinical trial. SETTING: Medical center in Kaohsiung, Taiwan. PATIENTS: Moderate-to-severe acute respiratory distress syndrome with a PaO2/FIO2 ratio less than 200. INTERVENTIONS: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10 cells/kg), the next three patients with intermediate dose (5.0 × 10 cells/kg), and the final three patients with high dose (1.0 × 10 cells/kg) between December 2017 and August 2019. MEASUREMENTS AND MAIN RESULTS: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+) and mesenchymal stem cell markers (CD26+CD45-/CD29+CD45-/CD34+CD45-/CD44+CD45-/CD73+CD45-/CD90+CD45-/CD105+CD45-/CD26+CD45-) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cell/Cytotoxity-T-cell/Regulatory-T-cell) were notably increased (p for trend < 0.001) after cell infusion. CONCLUSIONS: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.
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- 2020
- Full Text
- View/download PDF
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