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1.
Eur Rev Med Pharmacol Sci ; 25(5): 2403-2408, 2021 03.
Article in English | MEDLINE | ID: mdl-33755976

ABSTRACT

OBJECTIVE: To evaluate the curative effect of hemoperfusion therapy on central nervous system injury in patients with 2,4-dichlorophenoxyacetic acid poisoning. PATIENTS AND METHODS: A total of 60 patients with 2,4-dichlorophenoxyacetic acid poisoning were enrolled in this study. They were admitted to the Emergency Department of Qinghai Provincial People's Hospital from 2015 to 2018 and were randomly divided into two groups by random number table method. One group was control group (routine treatment group), and the other group was the treatment group (hemoperfusion therapy was added on the basis of routine treatment). Glasgow coma score (GCS), APACHE II score, and MMSE score were used to evaluate the effects before treatment and 7 days after treatment. The results were statistically analyzed. RESULTS: After treatment, GCS in the treatment group was higher than that in the control group, while APACHE II score was lower than that in the control group, and MMSE score was significantly higher than that in the control group, with statistically significant difference (p<0.05). The effective rate in the control group was only 26.67%, and that in the treatment group was 86.67%, with statistically significant difference (c2=19.62, p<0.001). CONCLUSIONS: Hemoperfusion therapy can promote the recovery of central nervous system in patients with 2,4-dichlorophenoxyacetic acid poisoning, reduce the injury of other organs, and significantly reduce the mortality of patients.


Subject(s)
2,4-Dichlorophenoxyacetic Acid/isolation & purification , Central Nervous System/injuries , Hemoperfusion , 2,4-Dichlorophenoxyacetic Acid/poisoning , Adolescent , Adult , Aged , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Young Adult
2.
Eur Rev Med Pharmacol Sci ; 22(13): 4107-4114, 2018 07.
Article in English | MEDLINE | ID: mdl-30024598

ABSTRACT

OBJECTIVE: To investigate the potential effects of miR-613 on the development of cervical cancer (CC) and the relevant mechanism. PATIENTS AND METHODS: The expression level of miR-613 was detected in CC tissues and cells (siHa) by comparing with corresponding adjacent normal tissues and normal human embryonic kidney cells (293T). Luciferase assay was performed to evaluate the interaction between miR-613 and PTPN9. The effects of the miR-613 on siHa cells were determined by subsequent experiments including cell proliferation, invasion and migration. RESULTS: In our study, miR-613 was found up-regulated in CC tissues and the same result was found at cellular level. The potential target of miR-613 was analyzed by three public databases. We found that tyrosine-protein phosphatase non-receptor type 9 (PTPN9) was a direct target of miR-613, and Luciferase assays confirmed our hypothesis. The subsequent experiments showed that decreased expression of PTPN9 resulting from up-regulation of miR-613 could promote the cell proliferation, invasion and migration of CC cells. CONCLUSIONS: We showed the promotion function of miR-613 on CC by targeting PTPN9 and revealed that miR-613/PTPN9 axis might be a potential therapeutic target for the treatment of CC.


Subject(s)
MicroRNAs/genetics , Protein Tyrosine Phosphatases, Non-Receptor/metabolism , Uterine Cervical Neoplasms/genetics , Cell Movement/physiology , Cell Proliferation/physiology , Female , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness/genetics , Phosphoprotein Phosphatases/metabolism , Up-Regulation
3.
Eur Rev Med Pharmacol Sci ; 22(7): 2044-2051, 2018 04.
Article in English | MEDLINE | ID: mdl-29687861

ABSTRACT

OBJECTIVE: Elevated apoptosis of vascular smooth muscle cell (VSMC) is correlated with the occurrence of aortic dissection (AD). Mammalian ste20-like protein kinase 1 (MST1) is one important component of Hippo-YAP signal pathway for activation and cell apoptosis facilitation. Whether MST1 plays a role in AD pathogenesis is unclear yet. This study established an AD rat model to investigate the role of MST1 in regulating VSMC apoptosis and AD pathogenesis. MATERIALS AND METHODS: Cell apoptosis was compared between AD vascular tissues and normal rats, in addition to Caspase-3 activity, and expression of MST1, p-LATS1, p-YAP1, YAP1. In vitro cultured VSMCs from AD rats were treated with siRNA-MST1 to test apoptotic rate and Caspase-3 activity. AD model rats were treated with pGLVU6/GFP-MST1 for comparing MST1, p-LATS1, p-YAP1, and YAP1 expression, along with Caspase-3 activity, cell apoptosis, AD formation rate, diameter, and length. RESULTS: Compared to control group, AD rats had elevated vascular cell apoptosis, Caspase-3 activity, expressions of MST1, p-LATS1, and p-YAP1, plus lower YAP1 expression. siRNA interference of MST1 significantly inhibited apoptosis of in vitro cultured VSMC. shRNA lentivirus targeting MST1 pGLVU6/GFP-MST1 remarkably decreased expression of MST1, p-LATS1, and p-YAP1 in AD rat vascular tissues, increased YAP1 expression, decreased VSMC apoptosis, AD formation rate, AD diameter/length. CONCLUSIONS: MST1 up-regulation plays a role in facilitating VSMC apoptosis and AD pathogenesis. Down-regulation of MST1 decreased VSMC apoptosis and AD formation.


Subject(s)
Aortic Dissection/pathology , Apoptosis , Hepatocyte Growth Factor/physiology , Myocytes, Smooth Muscle/pathology , Proto-Oncogene Proteins/physiology , Aortic Dissection/etiology , Animals , Apoptosis/physiology , Down-Regulation , Male , Protein Serine-Threonine Kinases/physiology , Rats , Rats, Sprague-Dawley
4.
Eur Rev Med Pharmacol Sci ; 22(2): 417-421, 2018 01.
Article in English | MEDLINE | ID: mdl-29424899

ABSTRACT

OBJECTIVE: The aim of this study was to explore FOXM1-related LncRNA 1(FRLnc1) expression level in gastric cancer (GC) and demonstrate its association with the prognosis. PATIENTS AND METHODS: A total of 173 GC patients from Affiliated Hospital of Jining Medical University were enrolled in the study. GC tissue samples were quantified for FRLnc1 expression level using quantitative PCR (qPCR) method. The relevance between FRLnc1 expression and clinicopathological features was determined by x2-test. The association between FRLnc1 expression and overall survival was estimated by the Kaplan-Meier method. Multivariate and univariate analysis were performed to explore whether FRLnc1 was an independent prognostic factor for GC patients. RESULTS: We found that FRLnc1 expression was higher in GC tissues than corresponding adjacent tissues (p < 0.01). Increased FRLnc1 expression was associated with depth of tumor (p = 0.004), differentiation degree (p = 0.032), distant metastasis (p = 0.007), TNM stage (p = 0.006) and lymph node metastasis (p = 0.012). More importantly, Kaplan-Meier survival analysis demonstrated that overall patient survival for those with low FRLnc1 expression was significantly longer than those patients with high FRLnc1 expression (p < 0.001). Multivariate analysis suggested that FRLnc1 expression was an independent prognostic marker for survival in patients with GC. CONCLUSIONS: The data presented in this work firstly suggested that FRLnc1 may be a prognostic predictor in GC.


Subject(s)
Forkhead Box Protein M1/metabolism , RNA, Long Noncoding/metabolism , Stomach Neoplasms/pathology , Biomarkers, Tumor/genetics , Female , Forkhead Box Protein M1/genetics , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , RNA, Long Noncoding/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism
5.
Eur Rev Med Pharmacol Sci ; 21(12): 2934-2939, 2017 06.
Article in English | MEDLINE | ID: mdl-28682422

ABSTRACT

OBJECTIVE: To study the application timing and effect of intra-aortic balloon pump (IABP) in the emergency PCI treatment of patients with combined acute myocardial infarction (AMI) and cardiogenic shock (CS). PATIENTS AND METHODS: 84 cases of patients with combined AMI and CS under PCI in emergency treatment were randomly divided into the control group (n=42) and observational group (n=42). The control group underwent IABP again, after the invalidation of internal medicine drug treatment, while the observational group underwent IABP before the operation. We compared the effects of treatment. RESULTS: After the intervention, the averages of arterial pressure and urine volume were increased in both groups than before (p <0.05). The average of heart rate was decreased, and the improvement in the observational group was more significant (p <0.05). However, the mortality rate in the observational group during the perioperative period was decreased than the control group as well as, the success rate of off-respirator was significant (p <0.05). The comparison of IABP complication occurrence rate as well as the survival rate after 1-year follow-up between both groups was not significantly different. Additionally, whereas the NYHA grouping in two groups was gradually improved, the difference was not statistically significant between both groups. However, in the observational group, the LVEF after one-month follow-up was significantly higher than in the control group (p <0.05), but not when comparing 1-year. VEDd at each time point in two groups were also similar. CONCLUSIONS: The early IABP can improve hemodynamics of patients with combined AMI and CS under emergency PCI. It can reduce perioperative mortality rate, improve the success rate of off-respirator, but cannot increase IABP complication incidence rate while having little influence on the long-term survival rate and cardiac function indicator.


Subject(s)
Emergency Treatment/methods , Intra-Aortic Balloon Pumping/methods , Myocardial Infarction/surgery , Percutaneous Coronary Intervention/methods , Shock, Cardiogenic/surgery , Aged , Emergency Treatment/instrumentation , Female , Heart-Assist Devices , Hemodynamics/physiology , Humans , Intra-Aortic Balloon Pumping/instrumentation , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/physiopathology , Percutaneous Coronary Intervention/instrumentation , Shock, Cardiogenic/complications , Shock, Cardiogenic/physiopathology , Time Factors
6.
Article in English | MEDLINE | ID: mdl-28181311

ABSTRACT

Whether upper-limb swelling is associated with axillary web syndrome (AWS) is unknown. We recruited unilateral breast cancer (BC) patients who were scheduled for surgical intervention and lymph node dissection. The pre-operative assessment and post-operative assessment 3-4 weeks after surgery evaluated the upper-limb circumferential measurements, segmental limb volume, pain scores, grasp, shoulder range of motion (ROM), shoulder muscle power and quality-of-life scores. In the control group, the peri-elbow volume and upper-arm volume were significantly higher post-operatively than pre-operatively. In the AWS group, no significant difference was found. In comparison with the control group, the AWS group had significantly more pain, less active ROM in shoulder abduction and a lower upper-limb volume at 0-10 cm proximal to the lateral epicondyle. The incidence of lymphedema was 9.9% and was not associated with AWS. AWS is a common morbidity of lymph node dissection and causes significant pain and restricted shoulder abduction in the affected limb in BC survivors. This study is the first to investigate post-operative upper-limb volumetric changes in BC survivors with and without AWS. Our findings are of great value for the clinical effect of AWS in BC survivors, for patient education, and for developing diagnostic tools for detecting AWS.


Subject(s)
Breast Neoplasms/surgery , Lymph Node Excision , Lymphedema/epidemiology , Postoperative Complications/epidemiology , Quality of Life , Range of Motion, Articular/physiology , Upper Extremity/pathology , Adult , Anthropometry , Axilla , Female , Hand Strength , Humans , Incidence , Middle Aged , Muscle Strength/physiology , Organ Size , Pain , Shoulder , Shoulder Joint/physiopathology , Syndrome , Upper Extremity/physiopathology
7.
Mucosal Immunol ; 10(1): 104-116, 2017 01.
Article in English | MEDLINE | ID: mdl-27118489

ABSTRACT

In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7ΔCD11c mice when compared with Atg7f/f mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7ΔCD11c mice compared with those of control Atg7f/f mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7ΔCD11c mice, B6 mice transferred with fecal microbiota of Atg7ΔCD11c mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.


Subject(s)
Adipose Tissue/physiology , Bacteroides/immunology , Gastrointestinal Microbiome/immunology , Insulin Resistance/immunology , Intestines/physiology , Obesity/microbiology , Adipose Tissue/microbiology , Animals , Autophagy-Related Protein 7/genetics , Cells, Cultured , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Feces/microbiology , Gene Expression Regulation , Glucagon-Like Peptide 1/blood , Humans , Insulin/blood , Intestines/microbiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Obesity/immunology , PPAR alpha/genetics , PPAR alpha/metabolism , Symbiosis
8.
Colorectal Dis ; 18(12): O445-O452, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27611180

ABSTRACT

AIM: Anastomotic leakage is the most serious complication following low anterior resection for rectal cancer and is a major cause of postoperative morbidity and mortality. The object of the present study was to investigate whether rectal tube drainage can reduce anastomotic leakage after minimally invasive rectal cancer surgery. METHOD: Three hundred and seventy-four patients who underwent laparoscopic or robotic LAR for tumours located ≤ 15 cm above the anal verge between 1 April 2012 and 31 October 2014 were assessed retrospectively. Of these, 107 with intermediate risk of anastomotic leakage received transanal rectal tube drainage. The rectal tube group was matched by propensity score analysis with patients not having rectal tube drainage, giving 204 patients in the study. Covariates for propensity score analysis included age, sex, body mass index, tumour height from the anal verge and preoperative chemoradiation. RESULTS: Patient demographics, tumour location, preoperative chemoradiation and operative results were similar between the two groups. The overall leakage rate was 10.8% (22/204), with no significant difference between the rectal tube group (9.8%) and the nonrectal tube group (11.8%, P = 0.652). Of the patients with anastomotic leakage, major leakage requiring reoperation developed in 11.8% of those without and 3.9% of those with a rectal tube. On multivariate analysis, age over 65 years and nonuse of a rectal tube were found to be independent risk factors for major anastomotic leakage. CONCLUSION: Rectal tube placement may be a safe and effective method of reducing the rate of major anastomotic leakage, alleviating the clinical course of leakage following minimally invasive rectal cancer surgery.


Subject(s)
Anastomosis, Surgical/methods , Anastomotic Leak/prevention & control , Drainage/methods , Intubation, Gastrointestinal/methods , Rectal Neoplasms/surgery , Anastomotic Leak/surgery , Female , Humans , Laparoscopy/methods , Male , Middle Aged , Propensity Score , Rectum/surgery , Reoperation/statistics & numerical data , Retrospective Studies , Risk Factors
9.
Oncogene ; 34(25): 3264-72, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25151963

ABSTRACT

Blockade of fatty acid synthase (FASN), a key enzyme involved in de novo lipogenesis, results in robust death of ovarian cancer cells. However, known FASN inhibitors have proven to be poor therapeutic agents due to their ability to induce cachexia. Therefore, we sought to identify additional targets in the pathway linking FASN inhibition and cell death whose modulation might kill ovarian cancer cells without the attendant side effects. Here, we show that the initiator caspase-2 is required for robust death of ovarian cancer cells induced by FASN inhibitors. REDD1 (also known as Rtp801 or DDIT4), a known mTOR inhibitor previously implicated in the response to FASN inhibition, is a novel caspase-2 regulator in this pathway. REDD1 induction is compromised in ovarian cancer cells that do not respond to FASN inhibition. Inhibition of FASN induced an ATF4-dependent transcriptional induction of REDD1; downregulation of REDD1 prevented orlistat-induced activation of caspase-2, as monitored by its cleavage, proteolytic activity and dimerization. Abrogation of REDD1-mediated suppression of mTOR by TSC2 RNAi protected FASN inhibitor-sensitive ovarian cancer cells (OVCA420 cells) from orlistat-induced death. Conversely, suppression of mTOR with the chemical inhibitors PP242 or rapamycin-sensitized DOV13, an ovarian cancer cell line incapable of inducing REDD1, to orlistat-induced cell death through caspase-2. These findings indicate that REDD1 positively controls caspase-2-dependent cell death of ovarian cancer cells by inhibiting mTOR, placing mTOR as a novel upstream regulator of caspase-2 and supporting the possibility of manipulating mTOR to enhance caspase-2 activation in ovarian cancer.


Subject(s)
Caspase 2/metabolism , Cysteine Endopeptidases/metabolism , Fatty Acid Synthases/antagonists & inhibitors , Ovarian Neoplasms/enzymology , Ovarian Neoplasms/pathology , Activating Transcription Factor 4/metabolism , Caspase 2/chemistry , Cell Death/drug effects , Cell Line, Tumor , Cysteine Endopeptidases/chemistry , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Female , Humans , Lactones/pharmacology , Orlistat , Protein Multimerization/drug effects , Protein Structure, Quaternary , RNA Interference , TOR Serine-Threonine Kinases/antagonists & inhibitors , Transcription Factors/metabolism , Tuberous Sclerosis Complex 2 Protein , Tumor Suppressor Proteins/deficiency , Tumor Suppressor Proteins/genetics
10.
Br J Cancer ; 110(10): 2496-505, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24714752

ABSTRACT

BACKGROUND: Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells. METHODS: Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT-PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay. RESULTS: Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice. CONCLUSIONS: This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma.


Subject(s)
Adenoviridae/physiology , Defective Viruses/physiology , Melanoma/therapy , Oncolytic Virotherapy , Adenoviridae/genetics , Adenovirus E1B Proteins/deficiency , Adenovirus E1B Proteins/genetics , Animals , Apoptosis , Cell Division , Cell Line, Tumor , Cell Movement , Defective Viruses/genetics , Gene Expression Regulation, Viral , Genes, Synthetic , Humans , Interleukins/genetics , Interleukins/physiology , Ki-67 Antigen/genetics , Male , Melanoma/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Promoter Regions, Genetic , Recombinant Fusion Proteins , Virus Replication/genetics , Xenograft Model Antitumor Assays
11.
Oncogene ; 33(28): 3660-7, 2014 Jul 10.
Article in English | MEDLINE | ID: mdl-23995785

ABSTRACT

Mutations in the PTEN tumor suppressor gene are found in a high proportion of human prostate cancers, and in mice, Pten deletion induces high-grade prostate intraepithelial neoplasia (HGPIN). However, progression from HGPIN to invasive cancer occurs slowly, suggesting that tumorigenesis is subject to restraint. We show that Pten deletion, or constitutive activation of the downstream kinase AKT, activates the transforming growth factor (TGF)ß pathway in prostate epithelial cells. TGFß signaling is known to have a tumor suppressive role in many cancer types, and reduced expression of TGFß receptors correlates with advanced human prostate cancer. We demonstrate that in combination either with loss of Pten or expression of constitutively active AKT1, inactivation of TGFß signaling by deletion of the TGFß type II receptor gene relieves a restraint on tumorigenesis. This results in rapid progession to lethal prostate cancer, including metastasis to lymph node and lung. In prostate epithelium, inactivation of TGFß signaling alone is insufficient to initiate tumorigenesis, but greatly accelerates cancer progression. The activation of TGFß signaling by Pten loss or AKT activation suggests that the same signaling events that have key roles in tumor initiation also induce the activity of a pathway that restrains disease progression.


Subject(s)
Disease Progression , PTEN Phosphohydrolase/genetics , Prostate/metabolism , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Epithelial Cells/pathology , Gene Deletion , Homozygote , Humans , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Mice , Neoplasm Invasiveness , PTEN Phosphohydrolase/deficiency , Prostate/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Protein Serine-Threonine Kinases/deficiency , Protein Serine-Threonine Kinases/genetics , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/deficiency , Receptors, Transforming Growth Factor beta/genetics
12.
Cell Death Differ ; 21(4): 604-11, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24362437

ABSTRACT

Deubiquitinating enzymes (DUBs) counteract ubiquitin ligases to modulate the ubiquitination and stability of target signaling molecules. In Drosophila, the ubiquitin-proteasome system has a key role in the regulation of apoptosis, most notably, by controlling the abundance of the central apoptotic regulator DIAP1. Although the mechanism underlying DIAP1 ubiquitination has been extensively studied, the precise role of DUB(s) in controlling DIAP1 activity has not been fully investigated. Here we report the identification of a DIAP1-directed DUB using two complementary approaches. First, a panel of putative Drosophila DUBs was expressed in S2 cells to determine whether DIAP1 could be stabilized, despite treatment with death-inducing stimuli that would induce DIAP1 degradation. In addition, RNAi fly lines were used to detect modifiers of DIAP1 antagonist-induced cell death in the developing eye. Together, these approaches identified a previously uncharacterized protein encoded by CG8830, which we named DeUBiquitinating-Apoptotic-Inhibitor (DUBAI), as a novel DUB capable of preserving DIAP1 to dampen Drosophila apoptosis. DUBAI interacts with DIAP1 in S2 cells, and the putative active site of its DUB domain (C367) is required to rescue DIAP1 levels following apoptotic stimuli. DUBAI, therefore, represents a novel locus of apoptotic regulation in Drosophila, antagonizing cell death signals that would otherwise result in DIAP1 degradation.


Subject(s)
Apoptosis , Drosophila Proteins/metabolism , Drosophila/enzymology , Endopeptidases/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Animals , Animals, Genetically Modified , Caspase Inhibitors/metabolism , Drosophila/metabolism , Drosophila Proteins/antagonists & inhibitors , Drosophila Proteins/genetics , Endopeptidases/chemistry , Endopeptidases/genetics , Eye/cytology , Eye/growth & development , Eye/physiopathology , Inhibitor of Apoptosis Proteins/antagonists & inhibitors , Inhibitor of Apoptosis Proteins/genetics , Protein Binding , Protein Structure, Tertiary , RNA Interference , Temperature , Ubiquitination
13.
Eye (Lond) ; 27(3): 374-81, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23222565

ABSTRACT

PURPOSE: To assess the prevalence of astigmatism and its relationship with biometric optic components in preterm school children with diode laser-treated threshold retinopathy of prematurity (ROP). METHODS: A prospective, cross-sectional study in which cycloplegic keratometry, refraction, and ultrasound biometric measurement of optic components were performed on 24 consecutive preterm children with diode laser-treated threshold ROP at the age of 9 years. The study results were compared with data on 1021 age-matched full-term control children from a national survey. RESULTS: The laser-treated eyes had a mean astigmatism of 3.47 D, with a mean spherical equivalent of -4.49 D. Of the 46 eyes studied, 98% of eyes showed astigmatism ≥0.5 D and 50% had high astigmatism (>3.0 D). Most astigmatic eyes (97.7%) showed with-the-rule astigmatism, with the mean plus cylinder axis at 89.30(o). Further correlation analysis showed the astigmatism in refraction was highly correlated with the corneal astigmatism (r=0.921, P<0.001) and the vertical corneal curvature (r=0.405, P=0.005). There was significantly steeper vertical corneal curvature (P=0.003) and flatter horizontal corneal curvature (P=0.031) in eyes with laser-treated ROP when compared with age-matched full-term controls. The eyes with laser-treated ROP also show significantly thicker lens (3.93 mm) and shallower anterior chamber depth (ACD; 2.92 mm) than full-term controls (P<0.001). CONCLUSIONS: There is significantly higher prevalence and greater magnitude of astigmatism in eyes with laser-treated threshold ROP compared with full-term controls. The steeper vertical corneal curvature component contributes to the increased astigmatism in eyes with laser-treated ROP.


Subject(s)
Astigmatism/physiopathology , Cornea/pathology , Laser Coagulation , Lasers, Semiconductor/therapeutic use , Retinopathy of Prematurity/surgery , Astigmatism/epidemiology , Biometry , Child , Cross-Sectional Studies , Female , Gestational Age , Humans , Infant, Newborn , Male , Microscopy, Acoustic , Myopia/epidemiology , Myopia/physiopathology , Premature Birth , Prevalence , Prospective Studies , Refraction, Ocular/physiology , Taiwan/epidemiology , Visual Acuity/physiology
14.
Br J Cancer ; 107(3): 501-7, 2012 Jul 24.
Article in English | MEDLINE | ID: mdl-22782341

ABSTRACT

BACKGROUND: Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins. METHODS AND RESULTS: In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1-Sema5A-ECD; control cells - Panc1-control) significantly increases their invasion in vitro via enhanced ERK phosphorylation. Interestingly, orthotopic injection of Panc1-Sema5A-ECD cells into athymic nude mice results in a lower primary tumour burden, but enhances the micrometastases to the liver as compared with Panc1-control cells. Furthermore, there is a significant increase in proliferation of endothelial cells treated with conditioned media (CM) from Panc1-Sema5A-ECD cells and a significant increase in microvessel density in Panc1-Sema5A-ECD orthotopic tumours compared with those from Panc1-control cells, suggesting that the increase in liver micrometastases is probably due to increased tumour angiogenesis. In addition, our data demonstrate that this increase in endothelial cell proliferation by Sema5A-ECD is mediated through the angiogenic molecules - interleukin-8 and vascular endothelial growth factor. CONCLUSION: Taken together, these results suggest that a bioactive, secreted form of Sema5A-ECD has an intriguing and potentially important role in its ability to enhance pancreatic tumour invasiveness, angiogenesis and micrometastases.


Subject(s)
Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Angiogenesis Inducing Agents/metabolism , Animals , Cell Growth Processes/physiology , Disease Progression , Endothelial Cells/metabolism , Endothelial Cells/pathology , Extracellular Signal-Regulated MAP Kinases/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Interleukin-8/genetics , Interleukin-8/metabolism , Liver Neoplasms/secondary , Male , Membrane Proteins/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Neoplasm Micrometastasis , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Nerve Tissue Proteins/genetics , Pancreatic Neoplasms/genetics , Phosphorylation/genetics , Semaphorins , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
16.
Climacteric ; 14(4): 472-81, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21469973

ABSTRACT

OBJECTIVES: Drospirenone is a novel progestogen that, combined with 17ß-estradiol, reduces the frequency and severity of menopausal vasomotor symptoms (VMS) in different populations. This double-blind, multicenter study compared the efficacy, safety and tolerability of 2 mg drospirenone/1 mg estradiol (DRSP/E2) vs. placebo in Chinese postmenopausal women with moderate to severe VMS. METHODS: Women, aged 45-65 years, were randomized to DRSP/E2 (n=183) or placebo (n=61) once daily for four 28-day cycles. Changes in the frequency and severity of hot flushes were analyzed as primary variables, together with other climacteric and urogenital symptoms, clinical global improvement, adverse events and physical/gynecological parameters. RESULTS: Relative changes in numbers of hot flushes/week were -80.4% for DRSP/E2 vs. -51.9% for placebo (treatment difference -28.5%, p<0.0001). There were trends toward a greater reduction in severity of hot flushes with DRSP/E2 treatment. Patients treated with DRSP/E2 were more often free from sweating episodes (p<0.0001) and vaginal dryness (p=0.0008). Other climacteric symptoms, including nervousness and pollakisuria, followed a trend of greater response with DRSP/E2. Similar to other combination HRT regimens, DRSP/E2 increased occurrences of bleeding, but these decreased over time. Adverse events in patients treated with DRSP/E2 were mostly mild to moderate and withdrawal rates were low. CONCLUSIONS: Daily treatment of postmenopausal Chinese women with DRSP/E2 for 16 weeks significantly reduced the incidence of hot flushes and demonstrated advantages vs. placebo for other climacteric symptoms. These results indicate that DRSP/E2 is effective, safe and well tolerated in postmenopausal Chinese women.


Subject(s)
Androstenes/administration & dosage , Estradiol/administration & dosage , Estrogen Replacement Therapy/methods , Postmenopause , Aged , China , Double-Blind Method , Drug Combinations , Female , Hot Flashes/drug therapy , Humans , Middle Aged , Mineralocorticoid Receptor Antagonists/administration & dosage , Placebos , Vaginal Diseases/drug therapy
17.
Methods Inf Med ; 49(3): 254-68, 2010.
Article in English | MEDLINE | ID: mdl-20135079

ABSTRACT

BACKGROUND: Microarray data with reference to gene expression profiles have provided some valuable results related to a variety of problems, and contributed to advances in clinical medicine. Microarray data characteristically have a high dimension and small sample size, which makes it difficult for a general classification method to obtain correct data for classification. However, not every gene is potentially relevant for distinguishing the sample class. Thus, in order to analyze gene expression profiles correctly, feature (gene) selection is crucial for the classification process, and an effective gene extraction method is necessary for eliminating irrelevant genes and decreasing the classification error rate. OBJECTIVE: The purpose of gene expression analysis is to discriminate between classes of samples, and to predict the relative importance of each gene for sample classification. METHOD: In this paper, correlation-based feature selection (CFS) and Taguchi-binary particle swarm optimization (TBPSO) were combined into a hybrid method, and the K-nearest neighbor (K-NN) with leave-one-out cross-validation (LOOCV) method served as a classifier for ten gene expression profiles. RESULTS: Experimental results show that this hybrid method effectively simplifies feature selection by reducing the number of features needed. The classification error rate obtained by the proposed method had the lowest classification error rate for all of the ten gene expression data set problems tested. For six of the gene expression profile data sets a classification error rate of zero could be reached. CONCLUSION: The introduced method outperformed five other methods from the literature in terms of classification error rate. It could thus constitute a valuable tool for gene expression analysis in future studies.


Subject(s)
Gene Expression Profiling/classification , Oligonucleotide Array Sequence Analysis/classification , Gene Expression Profiling/statistics & numerical data , Humans , Models, Statistical , Oligonucleotide Array Sequence Analysis/statistics & numerical data
18.
Eye (Lond) ; 24(1): 14-20, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19343053

ABSTRACT

PURPOSE: To assess the long-term visual outcomes and refractive status in patients with diode laser-treated threshold retinopathy of prematurity (ROP), and to investigate the causes of impaired visual function. METHOD: A total of 60 eyes of 30 consecutive patients with diode laser-treated threshold ROP were recalled for assessment at the age of 7 years or more. RESULTS: There were 38 eyes (65.5%) achieving 6/12 or better vision, however, an unfavourable visual outcome (6/60 or worse) occurred in four eyes (6.9%). One eye (1.7%) had unfavourable structural outcome. Of these 60 laser-treated eyes, 46 eyes (77.0%) were myopic, the overall mean spherical equivalent was -3.87 D. Anisometropia (>or=1.5 D) was also noted in 14 patients (46.7%). Strabismus was present in nine patients (30.0%). Perinatal neurological events of intraventricular haemorrhage (IVH) were identified in eight children (26.7%), periventricular leucomalacia (PVL) in eight children (26.7%), and cerebral palsy (CP) in four children (13.3%). There was a statistically significant association of the presence of strabismus with PVL (P=0.002). The presence of anisometropia was a significant risk factor associated with poor visual outcome of 6/15 or worse in laser-treated ROP (P=0.002). CONCLUSION: The majority of patients with diode laser-treated threshold ROP had favourable anatomical and visual outcomes. However, anisometropia, advanced refractive error, strabismus, and perinatal neurological events remain important causes of impaired visual function. Long-term follow-up is very important for early detection and timely treatment of these ocular morbidities.


Subject(s)
Laser Coagulation/methods , Lasers, Semiconductor/therapeutic use , Refraction, Ocular/physiology , Retinopathy of Prematurity/physiopathology , Retinopathy of Prematurity/surgery , Child , Female , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Male , Risk Factors , Treatment Outcome , Visual Acuity/physiology
19.
Int J Clin Pract ; 63(8): 1167-76, 2009 Aug.
Article in English | MEDLINE | ID: mdl-18422591

ABSTRACT

BACKGROUND: The diagnosis of diabetic nephropathy (DN) is always based on clinical grounds. However, the necessity for renal biopsy of type 2 diabetes mellitus (DM) patients with renal disease to establish the diagnosis remains unclear. METHODS: We retrospectively studied 50 type 2 diabetic patients performed with renal biopsy between December 2002 and December 2006. Based on renal pathology, patients were divided into group I: DN alone, group II: non-diabetic renal disease (NDRD) superimposed on DN and group III: isolated NDRD. Factors like DM > 10 years, retinopathy, previous minimal proteinuria without sudden heavy proteinuria, no glomerular haematuria and non-small-sized kidney were collected to evaluate their sensitivity, specificity, positive predictive value and negative predictive value for prediction of DN or NDRD in type 2 diabetic patients. RESULTS: Group I consisted of 24 patients, group II 15 patients and group III 11 patients. Acute interstitial nephritis was the most prevalent second renal disease in our study. Sensitivity and specificity for group I was poor in five features except high sensitivity in no sudden heavy proteinuria (83.3%) and non-small-sized kidney (95.8%). Comparable retinopathy, sudden heavy proteinuria and haematuria (p > 0.05) was noted between the three groups. Significant biopsy indicators included higher serum albumin, lower urinary daily protein excretion and lower 24-h creatinine clearance (C(Cr)) rate (p < 0.05). CONCLUSION: Our study demonstrated that DM > 10 years and retinopathy did not exclude NDRD in type 2 DM patients, and need for renal biopsy. Higher serum albumin, lower urinary daily protein and 24-h C(Cr) were indicative for biopsy to exclude NDRD.


Subject(s)
Diabetes Mellitus, Type 2/pathology , Diabetic Nephropathies/pathology , Kidney/pathology , Adult , Biopsy , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/physiopathology , Diabetic Retinopathy/complications , Female , Glomerular Filtration Rate/physiology , Hematuria/etiology , Humans , Kidney/physiopathology , Male , Middle Aged , Proteinuria/etiology , Sensitivity and Specificity
20.
Eye (Lond) ; 22(2): 282-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17721498

ABSTRACT

BACKGROUND AND OBJECTIVE: To investigate the cytotoxic effects of silicone oil on the cultivated human corneal endothelial cells (CEs). METHODS: We cultured human CE and passed them in insert wells that allowed the apical side of CE monolayer in contact with the silicone oil. The tested silicone oils were of two different viscosities, 1,000 and 5,000 centistoke (CS). MTS proliferation bioassay and calcein-acetoxymethyl ester (CAM)-ethidium homodimer staining were performed to evaluate cell viability after CEs were co-cultured with silicone oils for 48 h. Apoptosis of CEs was evaluated by TdT-mediated dUTP nick-end labelling (TUNEL) stain. RESULTS: The MTS bioassay showed that contact of silicone oil inhibited CE proliferation. The higher viscosity (5,000 CS) silicone oil suppressed cell cycling significantly more than the lower viscosity (1,000 CS) silicone oil. CAM-ethidium homodimer staining revealed CE death, 9.1+/-0.1% (1,000 CS silicone oil) and 41.6+/-0.4% (5,000 CS), but apoptosis played only minor role in silicone oil toxicity, 1.7+/-0.1% (1,000 CS silicone oil) and 9.4+/-0.1% (5,000 CS). CONCLUSIONS: Silicone oil is cytotoxic to cultivated human CEs. Avoiding the forward migration of silicone oil to the anterior chamber and corneal CE contact is critical in preventing silicone oil-associated keratopathy. Silicone oil should be removed as early as possible once the goal of tamponade has been achieved.


Subject(s)
Endothelium, Corneal/drug effects , Silicone Oils/toxicity , Aged , Aged, 80 and over , Apoptosis/drug effects , Biological Assay/methods , Cell Death/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Colorimetry/methods , Endothelium, Corneal/cytology , Humans , In Situ Nick-End Labeling/methods , Middle Aged , Silicone Oils/chemistry , Viscosity
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