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1.
J Am Chem Soc ; 146(25): 16996-17002, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38875709

ABSTRACT

A highly regio- and enantioselective hydrosulfonylation using commercially available sodium sulfinates is reported, providing the first direct asymmetric rhodium-catalyzed hydrosulfonylation of allenes/alkynes to synthesize chiral allylic sulfones. Ligand screening studies demonstrated the indispensable role of the C1-symmetric P,N-ligand (Rax,S,S)-StackPhim for achieving both high regioselecitivity (>20:1) and enantioselectivity (up to 97% ee). Notably, the operationally simple method and mild conditions allow for the rapid preparation of chiral allylic sulfones with a wide scope of functional groups. Moreover, the use of sodium tert-butyldimethylsilyloxymethanesulfinate enables the collective synthesis of various chiral sulfone derivatives after simple transformations of the protected hydroxymethyl product.

2.
J Chin Med Assoc ; 86(12): 1096-1100, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37748030

ABSTRACT

BACKGROUND: This study aimed to investigate the changes in the bladder neck (BN) and urinary symptoms using extracorporeal magnetic innervation (ExMI) therapy before and after performing passive pelvic floor exercises. METHODS: Twenty women with stress urinary incontinence (SUI) were assessed by transperineal ultrasound and questionnaires before and after the ExMI therapy from January 2011 to February 2021. RESULTS: The incidence of urinary frequency and SUI were significantly decreased after the therapy (McNemar test, p < 0.01). The therapeutic efficacy of SUI was 75%. A significant decrease was noted in pad test results (paired t test, p < 0.05). At the same time, there was a considerable difference in Urinary Distress Inventory-6 scale measures (paired t test, p < 0.001). However, results for the Incontinence Impact Questionnaire-7 showed a marginally significant difference (paired t test, p = 0.066). Three domains of lubrication, orgasm, and satisfaction in the Female Sexual Function Index showed significant differences (paired t test, p < 0.05). Transperineal ultrasound found that BN mobility and Q-tip straining angle were not statistically significant (paired t test, p > 0.05). CONCLUSION: The ExMI is effective for SUI by strengthening the pelvic floor muscle without significantly decreasing BN mobility.


Subject(s)
Urinary Bladder , Urinary Incontinence, Stress , Female , Humans , Urinary Bladder/diagnostic imaging , Pelvic Floor/innervation , Urinary Incontinence, Stress/therapy , Exercise Therapy , Magnetic Phenomena , Treatment Outcome , Quality of Life
3.
Front Cardiovasc Med ; 10: 1037392, 2023.
Article in English | MEDLINE | ID: mdl-37560115

ABSTRACT

Background: The optimal revascularization strategy for elderly patients with acute coronary syndrome (ACS) remains uncertain. We evaluated the impact of complete revascularization (CR) vs. incomplete revascularization (IR) in elderly ACS patients with multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI). Methods: Using registry data from 2011 to 2019, we conducted a propensity-score matched cohort study. Elderly patients (≥75 years) with ACS and MVD who underwent PCI were divided into CR and IR groups based on angiography during index hospitalization. Major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent non-fatal myocardial infarction, and any revascularization, were assessed at 3-year follow-up. Results: Among 1,018 enrolled patients, 496 (48.7%) underwent CR and 522 (51.3%) received IR. After 1:1 propensity-score matching, we analyzed 395 pairs. At 3-year follow-up, CR was significantly associated with lower MACE risk compared to IR (16.7% vs. 25.6%, HR = 0.65, 95% CI: 0.47-0.88, p = 0.006), driven by reduced all-cause mortality. This benefit was consistent across all pre-specified subgroups, particularly in ST segment elevation (STE)-ACS patients. In non-STE (NSTE)-ACS subgroup analysis, CR was also associated with a lower risk of cardiac mortality compared to IR (HR = 0.30, 95% CI: 0.12-0.75, p = 0.01). Conclusion: In elderly ACS patients with MVD undergoing PCI, CR demonstrates superior long-term outcomes compared to IR, irrespective of STE- or NSTE-ACS presentation.

4.
J Clin Med ; 12(12)2023 Jun 09.
Article in English | MEDLINE | ID: mdl-37373634

ABSTRACT

BACKGROUND: To report our experiences of a tape-releasing suture with "long-loop" in women with iatrogenic urethral obstruction following the mid-urethral sling procedure. METHODS: A total of 149 women underwent a tape-releasing suture with "Long Loop" during the operation. Post-void residual volume was evaluated after Foley removal. Lower urinary tract symptoms and urodynamic studies were assessed before and six months postoperatively. RESULTS: Nine women out of 149 who underwent mid-urethral sling surgery were found to have iatrogenic urethral obstruction post-operatively based on their urinary symptoms and ultrasound findings. There was no apparent difference between tested groups in mid-urethral sling products and concomitant procedures. 77.8% had successful releases after the first Long-loop manipulation procedure, and 22.2% required two or more releases. However, the SUI cure rate is similar in groups receiving the Long-loop manipulation or not (88.9% and 87.1%, respectively). CONCLUSIONS: We are convinced of the practicability and efficacy of the tape-releasing suture "Long-loop." We adopted subjective and objective means to evaluate both groups before and after a six-month follow-up. The Long-loop manipulation procedure can successfully resolve the iatrogenic urethral obstruction without compromising the effectiveness of mid-urethral sling for the treatment of SUI.

5.
Acta Cardiol Sin ; 39(3): 469-479, 2023 May.
Article in English | MEDLINE | ID: mdl-37229327

ABSTRACT

Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue disease (CTD). CTD-associated PAH (CTD-PAH) is the most common subgroup of PAH in East Asia. We prospectively collected 41 patients with CTD-PAH and followed them for a mean period of 43 ± 36 months. The long-term survival rates of the CTD-PAH patients at 1, 2, 3 and 5 years were 90%, 80%, 77%, and 60%, respectively. The non-survivors had more dilated main pulmonary arteries, higher pulmonary artery pressure and pulmonary vascular resistance (PVR). PAH-specific therapy resulted in improvements in functional class, 6-minute walk distance, serum uric acid, right ventricular function and PVR. Increased C-reactive protein during follow-up, indicating inflammatory processes, was also crucial for the management of CTD-PAH. Therefore targeting both PAH and inflammation is important in this specific subgroup of PAH. The results of this study may help develop treatment strategies for CTD-PAH patients.

6.
Exp Neurol ; 362: 114338, 2023 04.
Article in English | MEDLINE | ID: mdl-36717014

ABSTRACT

Treatment-resistant depression (TRD) is a condition wherein patients with depression fail to respond to antidepressant trials. A new form of repetitive transcranial magnetic stimulation (rTMS), called theta-burst stimulation (TBS), which includes intermittent theta-burst stimulation (iTBS) and continuous theta-burst stimulation (cTBS), is non-inferior to rTMS in TRD treatment. However, the mechanism of iTBS and cTBS underlying the treatment of TRD in the prefrontal cortex (PFC) remains unclear. Hence, we applied foot-shock stress as a traumatic event to develop a TRD rat model and investigated the different mechanisms of iTBS and cTBS. The iTBS and cTBS treatment were effective in depressive-like behavior and active coping behavior. The iTBS treatments improved impaired long-term potentiation and long-term depression (LTD), whereas the cTBS treatment only improved aberrant LTD. Moreover, the decrease in mature brain-derived neurotrophic factor (BDNF)-related protein levels were reversed by iTBS treatment. The decrease in proBDNF-related protein expression was improved by iTBS and cTBS treatment. Both iTBS and cTBS improved the decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and downregulation of mammalian target of the rapamycin (mTOR) signaling pathway. The iTBS produces both excitatory and inhibitory synaptic effects, and the cTBS only produces inhibitory synaptic effects in the PFC.


Subject(s)
Depression , Depressive Disorder, Treatment-Resistant , Rats , Animals , Neuronal Plasticity/physiology , Long-Term Potentiation , Transcranial Magnetic Stimulation , Depressive Disorder, Treatment-Resistant/therapy , Theta Rhythm/physiology , Evoked Potentials, Motor/physiology , Mammals
7.
Front Cardiovasc Med ; 9: 860346, 2022.
Article in English | MEDLINE | ID: mdl-35498029

ABSTRACT

Background: Coronary perfusion pressure (CPP) and coronary artery stenosis are responsible for myocardial perfusion. However, how CPP-related survival outcome affects revascularization is unclear. Objective: The aim of this study is to investigate the prognostic role of CPP in patients with left ventricular systolic dysfunction (LVSD) undergoing percutaneous coronary intervention (PCI) with complete revascularization (CR) or reasonable incomplete revascularization (RIR). Methods: We retrospectively screened 6,076 consecutive patients in a registry. The residual synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (rSS) was used to define CR (rSS = 0) and RIR (0 42 mmHg. Moreover, 101 pairs of RIR and CR were present in patients with CPP ≤ 42 mmHg. In patients with CPP > 42 mmHg, RIR was not significantly different from CR in long-term mortality [hazard ratio (HR) 1.20; 95% confidence interval (CI):0.70-2.07; p = 0.513]; However, in patients with CPP≤42 mmHg, RIR had a significantly higher mortality risk than CR (HR 2.39; 95% CI: 1.27-4.50; p = 0.007). Conclusions: The CPP had a risk stratification role in selecting different revascularization strategies in patients with LVSD. When patients with LVSD had CPP > 42 mmHg, RIR was equivalent to CR in survival. However, when patients with LVSD had CPP ≤ 42 mmHg, RIR had a significantly higher mortality risk than CR.

8.
Org Biomol Chem ; 20(31): 6193-6195, 2022 08 10.
Article in English | MEDLINE | ID: mdl-35467680

ABSTRACT

Described is a total synthesis of racemic mersicarpine from diethyl 4-oxopimelate. The synthetic route takes advantage of a 2-indolyl radical cyclization to construct the pyrido[1,2-a]indole scaffold bearing the all-carbon quaternary stereocenter.


Subject(s)
Indole Alkaloids , Cyclization , Molecular Structure , Stereoisomerism
9.
Medicine (Baltimore) ; 100(48): e28114, 2021 Dec 03.
Article in English | MEDLINE | ID: mdl-35049240

ABSTRACT

ABSTRACT: Body mass index (BMI) is positively associated with survival in heart failure (HF) patients with reduced ejection fraction (HFrEF). However, emerging evidence shows that this benefit may not exist in diabetic patients with HFrEF. As this relationship has not been investigated in Asian patients, the aim of this study was to examine the association between obesity and outcomes in HrEFF patients with and without diabetes mellitus (DM), and discuss the potential underlying mechanisms.The analysis included 900 patients with acute decompensated HF from the Taiwan Society of Cardiology-Heart Failure with Reduced Ejection Fraction Registry, of whom 408 had DM (45%). The association between BMI and all-cause mortality was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan-Meier survival analysis. Echocardiography parameters were also analyzed in patients with different BMI and DM status.After adjusting for confounding factors, BMI was a significant independent predictive factor for all-cause mortality in the non-diabetic patients (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81-0.95) and in Kaplan-Meier survival analysis (log-rank test, P = .034). For diabetic patients, BMI was not a significant predictive factor for all-cause mortality (HR, 0.96; 95% CI, 0.90-1.02) and in Kaplan-Meier survival analysis (log-rank test P = .169). Both DM (47.8 vs 45.4 mm, P = .014) and higher BMI (48.6 vs 44.9 mm, P < .001) are independently associated with higher left atrial size. Patients with a higher BMI had a lower proportion of severe mitral regurgitation (10.0% vs 14.1%, P < .001).In non-diabetic patients with HFrEF, BMI was a significant predictor of survival. However, in diabetic patients with HF, BMI was not a significant predictor of survival. Diastolic dysfunction in patients with DM and obesity may have played a role in this finding.


Subject(s)
Body Mass Index , Diabetes Mellitus/epidemiology , Heart Failure/mortality , Obesity/epidemiology , Adult , Aged , Aged, 80 and over , Female , Heart Failure/complications , Humans , Male , Middle Aged , Obesity/complications , Stroke Volume , Taiwan/epidemiology , Ventricular Dysfunction, Left
10.
Chin J Physiol ; 63(4): 149-155, 2020.
Article in English | MEDLINE | ID: mdl-32859881

ABSTRACT

Resveratrol (RSV) has been demonstrated to ameliorate nonalcoholic fatty liver disease (NAFLD) in animal studies. However, RSV was given with the dosage that ranged from 7 to 300 mg/kg body weight (BW). Hence, the study aimed to investigate the efficacy of RSV at a lower dosage on high cholesterol-fructose diet (HCFD)-induced rat model of NAFLD. In the study, male Sprague-Dawley rats were fed with HCFD for 15 weeks. RSV was also given at a daily dose of 1 mg/kg BW for 15 days or 15 weeks by oral delivery. At sacrifice, plasma and liver specimens were acquired for detections of alanine and aspartate aminotransferases, proinflammatory cytokines, and lipid contents. Histological examinations and Western blotting analysis were performed using liver tissues. The results showed that RSV administration reduced plasma levels of aminotransferases and proinflammatory cytokines including interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-α) in HCFD-induced NAFLD. RSV also mitigated hepatic lipid accumulation and expression of IL-1ß, IL-6, and TNF-α. Besides, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was reduced with RSV supplementation in the liver of HCFD-fed rats. We concluded that low-dose RSV supplementation attenuated hepatic inflammation and lipid accumulation in HCFD-induced NAFLD. The ameliorative effect of RSV on NAFLD could be associated with downregulation of phosphorylated STAT3.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Diet, High-Fat , Fructose , Inflammation , Lipids , Liver , Male , Rats , Rats, Sprague-Dawley , Resveratrol
11.
J Interv Cardiol ; 2020: 9506124, 2020.
Article in English | MEDLINE | ID: mdl-32774190

ABSTRACT

BACKGROUND: Patients with multivessel disease (MVD) often pursue complete revascularization (CR) during percutaneous coronary intervention (PCI) to improve prognosis. However, angiographic CR is not always feasible and is associated with some procedure-related complications in heart failure (HF) patients with MVD. Clinical selective incomplete revascularization (IR) may be reasonable for these high-risk patients, but its role in long-term outcomes remains uncertain. METHODS: Six hundred patients with HF and MVD submitted to PCI were enrolled. Major adverse cardiac events (MACEs) were defined as a composite of recurrent myocardial infarction, any revascularization, and all-cause mortality at 5 years. RESULTS: During a mean follow-up period of 3.7 ± 1.9 years, there was no significant difference in 5-year MACEs between selective IR and successful angiographic CR in HF patients with MVD. However, patients who failed CR had a significantly greater incidence of 5-year MACEs than those in the other two groups (failed CR: 46.4% vs. selective IR: 27.7% vs. successful CR: 27.8%, p < 0.001). CONCLUSIONS: Long-term outcomes of selective IR were comparable with those of successful angiographic CR in HF patients with MVD. However, patients that failed CR showed 2.53-fold increased risk of MACEs compared to patients undergoing either selective IR or successful angiographic CR. A more comprehensive planning strategy should be devised before PCI in HF patients with MVD.


Subject(s)
Coronary Angiography , Coronary Artery Disease , Heart Failure/complications , Percutaneous Coronary Intervention , Aged , Clinical Decision-Making , Coronary Angiography/adverse effects , Coronary Angiography/methods , Coronary Artery Disease/complications , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Female , Humans , Incidence , Male , Outcome and Process Assessment, Health Care , Patient Selection , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Prognosis , Severity of Illness Index , Taiwan/epidemiology , Time , Treatment Outcome
12.
Eur J Pediatr Surg ; 30(1): 104-110, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31910450

ABSTRACT

INTRODUCTION: The study aimed to compare 1-year outcomes for primary versus multiple-staged (three operations with colostomy) repairs in Hirschsprung's disease (HD). MATERIALS AND METHODS: Retrospective analysis of a large national administrative database (Hospital Episode Statistics) including all the neonates born with HD in England between 2003 and 2015. Main outcomes were: 1-year mortality, postoperative readmissions, and reoperations. SECONDARY OUTCOMES: cumulative length of hospital stay (cLOS) and hospital volume-outcome relationship. RESULTS: A total of 1,333 neonates with HD were treated in 21 specialist pediatric surgical centers; 874 (65.5%) patients had a primary repair for HD. One-year mortality was 2.8%. The overall readmission rate was 70.2%, with a significant difference between primary and multiple-staged repair (79.9 vs. 90.1%, p < 0.01). There was no difference in reoperation. Primary pull-through was associated with a significantly lower probability of postoperative readmission (odds ratio [OR] = 0.08, 95% confidence interval [CI] = 0.06-0.11, p < 0.001) and cLOS (OR = 0.38, 95% CI = 0.28-0.52, p < 0.001) compared with multiple-staged repair. There were no significant difference in outcomes between patients treated in low-volume (<37 cases/year) and high-volume (> 55 cases/year) specialist centers. CONCLUSION: Whenever clinically indicated, primary repair should be used in HD as this is associated with fewer readmissions and shorter time spent in the hospital.


Subject(s)
Digestive System Surgical Procedures/methods , Hirschsprung Disease/surgery , Colostomy , Digestive System Surgical Procedures/adverse effects , England/epidemiology , Female , Hirschsprung Disease/mortality , Hospitals, Pediatric/statistics & numerical data , Humans , Infant, Newborn , Length of Stay , Male , Patient Readmission , Postoperative Complications , Reoperation , Retrospective Studies , Treatment Outcome
13.
Cancer Res ; 79(15): 3797-3805, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31300476

ABSTRACT

The TGFß cytokine plays dichotomous roles during tumor progression. In normal and premalignant cancer cells, the TGFß signaling pathway inhibits proliferation and promotes cell-cycle arrest and apoptosis. However, the activation of this pathway in late-stage cancer cells could facilitate the epithelial-to-mesenchymal transition, stemness, and mobile features to enhance tumorigenesis and metastasis. The opposite functions of TGFß signaling during tumor progression make it a challenging target to develop anticancer interventions. Nevertheless, the recent discovery of cellular contextual determinants, especially the binding partners of the transcription modulators Smads, is critical to switch TGFß responses from proapoptosis to prometastasis. In this review, we summarize the recently identified contextual determinants (such as PSPC1, KLF5, 14-3-3ζ, C/EBPß, and others) and the mechanisms of how tumor cells manage the context-dependent autonomous TGFß responses to potentiate tumor progression. With the altered expression of some contextual determinants and their effectors during tumor progression, the aberrant molecular prometastatic switch might serve as a new class of theranostic targets for developing anticancer strategies.


Subject(s)
Neoplasms/metabolism , Transforming Growth Factor beta/metabolism , Humans , Neoplasms/genetics , Neoplasms/pathology , Transforming Growth Factor beta/genetics
14.
Chem Commun (Camb) ; 55(8): 1116-1119, 2019 Jan 25.
Article in English | MEDLINE | ID: mdl-30624438

ABSTRACT

The direct N1-selective allylation of indoles with allylic alcohols has been accomplished by synergistic functions of palladium catalysts and titanium tetraisopropoxide. The site selectivity is notably different from that observed in other related transition metal-catalyzed approaches. This chemistry provides a facile route to a variety of allylated indoles in synthetically useful yields. The utility of this simple allylation reaction was demonstrated with the first total synthesis of (+)-N-(4'-hydroxyprenyl)-cyclo(alanyltryptophyl), which was completed in five steps, starting from l-tryptophan methyl ester hydrochloride.

15.
J Org Chem ; 83(11): 6217-6224, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29767507

ABSTRACT

A method is reported for the catalytic direct coupling of allylic alcohols and nitroalkanes. In the allylation process, the synergistic action of palladium complexes and titanium(IV) alkoxide facilitates the formation of nitronate and π-allylpalladium intermediate. In the cases of reluctant allylations, typically with sterically demanding nitroalkanes, we found the addition of substoichiometric amount of DBU greatly facilitates the desired transformation. We also accomplished a total synthesis of (±)-adalinine through a homoallyl nitroalkane derived from Seebach's reagent.

16.
Nat Cell Biol ; 20(4): 479-491, 2018 04.
Article in English | MEDLINE | ID: mdl-29593326

ABSTRACT

Activation of metastatic reprogramming is critical for tumour metastasis. However, more detailed knowledge of the underlying mechanism is needed to enable targeted intervention. Here, we show that paraspeckle component 1 (PSPC1), identified in an aberrant 13q12.11 locus, is upregulated and associated with poor survival in patients with cancer. PSPC1 promotes tumorigenesis, epithelial-to-mesenchymal transition (EMT), stemness and metastasis in multiple cell types and in spontaneous mouse cancer models. PSPC1 is the master activator for transcription factors of EMT and stemness and accompanies c-Myc activation to facilitate tumour growth. PSPC1 increases transforming growth factor-ß1 (TGF-ß1) secretion through an interaction with phosphorylated and nuclear Smad2/3 to potentiate TGF-ß1 autocrine signalling. Moreover, PSPC1 acts as a contextual determinant of the TGF-ß1 pro-metastatic switch to alter Smad2/3 binding preference from tumour-suppressor to pro-metastatic genes. Having validated the PSPC1-Smads-TGF-ß1 axis in various cancers, we conclude that PSPC1 is a master activator of pro-metastatic switches and a potential target for anti-metastasis drugs.


Subject(s)
Autocrine Communication , Cell Movement , Epithelial-Mesenchymal Transition , Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Nuclear Proteins/metabolism , RNA-Binding Proteins/metabolism , Signal Transduction , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , A549 Cells , Animals , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Male , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Neoplasm Metastasis , Neoplasms/genetics , Neoplasms/pathology , Neoplastic Stem Cells/pathology , Nuclear Proteins/genetics , PC-3 Cells , Phenotype , Phosphorylation , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA-Binding Proteins/genetics , Smad2 Protein/genetics , Smad3 Protein/genetics , Time Factors , Transforming Growth Factor beta1/genetics
17.
Oncotarget ; 9(17): 13193-13205, 2018 Mar 02.
Article in English | MEDLINE | ID: mdl-29568350

ABSTRACT

Targeting tumor angiogenesis is a common strategy against human hepatocellular carcinoma (HCC). However, identification of molecular targets as biomarker for elevating therapeutic efficacy is critical to prolong HCC patient survival. Here, we showed that EIF3C (eukaryotic translation initiation factor 3 subunit C) is upregulated during HCC tumor progression and associated with poor patient survival. Expression of EIF3C did not alter proliferation and expression of other tumor progressive genes such as HIF1A, TGFß1 and VEGF, but reduced cell migration in HCC cells. Nevertheless, expression of EIF3C in HCC cells significantly increase secretion of extracellular exosomes confirmed by increased exosomes labelling by PKH26 fluorescent dye, vesicles in exosome size detected by electronic microscopy and nanoparticle tracking analysis, and expression of divergent exosome markers. The EIF3C-increased exosomes were oncogenic to potentiate tumor angiogenesis via tube formation of HUVEC cells and growth of vessels by plugs assays on nude mice. Subcutaneous inoculation of EIF3C-exosomes mixed with Huh7 HCC cells not only promoted growth of vessels but also increased expression of EIF3C in tumors. Conversely, treatment of exosome inhibitor GW4869 reversed aforementioned oncogenic assays. We identified EIF3C activated expression of S100A11 involved in EIF3C-exosome increased tube formation in angiogenesis. Simultaneous high expression of EIF3C and S100A11 in human HCC tumors for RNA level in TCGA and protein level by IHC are associated with poor survival of HCC patients. Collectively, our results demonstrated that EIF3C overexpression is a potential target of angiogenesis for treatment with exosome inhibitor or S100A11 reduction to suppress HCC angiogenesis and tumorigenesis.

18.
Oncotarget ; 8(44): 77734-77751, 2017 Sep 29.
Article in English | MEDLINE | ID: mdl-29100421

ABSTRACT

Cellular metabolism of cancer cell is generally recognized to provide energy for facilitating tumor growth, but little is known about the aberrant metabolism in tumor progression and its prognostic value. Here, we applied integrated genomic approach to uncover the aberrant expression of metabolic enzymes in poorly-differentiated human hepatocellular carcinoma (HCC) for revealing targets against HCC malignancy. A total of 135 upregulated (22 are rate-limiting enzymes (RLEs)) and 362 down-regulated (77 are RLEs) metabolic genes were identified and associated with poor patient survival in large-cohorts of HCC patients in TCGA-LIHC and two other independent transcriptomic studies. Ten out of 22 upregulated RLEs in poorly-differentiated HCC are critical enzymes in pyrimidine metabolism pathways in association with stemness features by gene enrichment analysis and upregulated in ALDH1+ stem-like HCC subpopulations. By focusing on three RLEs including TK1, TYMS and DTYMK of dTTP biosynthesis pathway, expression of 3 RLEs in well-differentiated HCC cells increased ALDH1+ and spheroid stemness population but reversed by knockdown in poorly-differentiated HCC cells. Up-regulated 3 RLEs in HCC were associated with poor patient survival in multiple cohorts. Together, we identified aberrant pyrimidine pathway in poorly-differentiated HCC promotes cancer stemness served as potential theranostic target for battling HCC tumor progression.

19.
J Diabetes ; 6(1): 60-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23786522

ABSTRACT

BACKGROUND: This study aimed to investigate the differential protective effect of resveratrol (RSV) on oxidative stress and metabolic signaling pathways in fast- and slow-twitch skeletal muscles of rats with diabetes. METHODS: Diabetic rats were induced by streptozotocin (STZ) for 2 weeks and then administered with RSV (1, 10 and 100 µg/kg per day) for 1 week. We determined oxidative stress and protein expression by lucigenin-mediated chemiluminescence and Western immunoblot. RESULTS: The superoxide anion production and copper-zinc superoxide dismutase (CuZnSOD) protein level were increased in fast-twitch muscle than in slow-twitch muscle of diabetes. The Akt and glycogen synthase kinase 3 (GSK-3) phosphorylations were reduced in both fast- and slow-twitch muscles of diabetes. Oxidative stress and GSK-3 dephosphorylation were corrected by RSV treatment in both fast- and slow-twitch muscles of diabetes. Furthermore, RSV treatment downregulated CuZnSOD protein level in diabetic fast-twitch muscle. In diabetic slow-twitch muscle, RSV treatment elevated manganese SOD (MnSOD) and phosphorylated Akt protein levels and reduced acetyl-CoA carboxylase (ACC) phosphorylation. CONCLUSIONS: Our results suggested that fast-twitch muscle incurred more oxidative stress, whereas slow-twitch muscle altered metabolic signaling molecules activities under diabetic status. The antidiabetic effect of RSV on fast- and slow-twitch skeletal muscles was mediated by different antioxidative and metabolic signals.


Subject(s)
Antioxidants/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Muscle Fibers, Fast-Twitch/drug effects , Muscle Fibers, Slow-Twitch/drug effects , Stilbenes/pharmacology , Acetyl-CoA Carboxylase/metabolism , Animals , Blood Glucose/metabolism , Blotting, Western , Body Weight , Cholesterol/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Glycogen Synthase Kinase 3/metabolism , Insulin/metabolism , Male , Oxidative Stress/drug effects , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Long-Evans , Resveratrol , Signal Transduction/drug effects , Superoxide Dismutase/metabolism , Superoxides/metabolism , Triglycerides/metabolism
20.
Chin J Physiol ; 55(3): 192-201, 2012 Jun 30.
Article in English | MEDLINE | ID: mdl-22784284

ABSTRACT

"It has been well known that both oxidative stress and inflammatory activity play crucial roles in the pathogenesis of type 1 diabetes mellitus (T1DM). Resveratrol (RSV), a naturally occurring polyphenol found in grapes and red wine, has recently been shown to exert potent anti-diabetic, anti-oxidative and anti-inflammatory actions. In the present study, we investigated the effect of RSV on oxidative stress and inflammatory response in the liver and spleen of streptozotocin (STZ)-induced type 1 diabetic animal models. Male Long-Evans rats were injected with 65 mg/kg STZ to induce diabetes for 2 weeks, and subsequently administrated with the dosage of 0.1 or 1 mg/kg/day RSV for 7 consecutive days. Hepatic and splenic tissues were dissected for evaluation of oxidative and inflammatory stress. Oxidative stress was assessed by quantification of oxidative indicators including superoxide anion content, lipid and protein oxidative products, as well as manganese superoxide dismutase (Mn-SOD) and nitro-tyrosine protein expression levels. Inflammatory stress was evaluated by the levels of nuclear factor κB (NF-κB) and the proinflammatory cytokine tumor necrosis factorα (TNF-α), interleukin 1 ß (IL-1 ß ) and IL-6. The experimental results indicated that RSV significantly decreased oxidative stress (superoxide anion content, protein carbonyl level and Mn-SOD expression) in both tissues and hepatic inflammation (NF- κB and IL-1 ß ), but implicated proinflammatory potential of RSV in diabetic spleen (TNF-α and IL-6). The results of this study suggest that RSV may serve as a potent antioxidant, but RSV possesses a proinflammatory potential in certain circumstances in diabetes."


Subject(s)
Diabetes Mellitus, Experimental , Streptozocin , Animals , Diabetes Mellitus, Experimental/metabolism , Liver/drug effects , Oxidative Stress/drug effects , Rats , Rats, Long-Evans , Spleen
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