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1.
Sci Rep ; 13(1): 12424, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37528172

ABSTRACT

GBM (Glioblastoma) is the most lethal CNS (Central nervous system) tumor in adults, which inevitably develops resistance to standard treatments leading to recurrence and mortality. TRIB1 is a serine/threonine pseudokinase which functions as a scaffold platform that initiates degradation of its substrates like C/EBPα through the ubiquitin proteasome system and also activates MEK and Akt signaling. We found that increased TRIB1 gene expression associated with worse overall survival of GBM patients across multiple cohorts. Importantly, overexpression of TRIB1 decreased RT/TMZ (radiation therapy/temozolomide)-induced apoptosis in patient derived GBM cell lines in vitro. TRIB1 directly bound to MEK and Akt and increased ERK and Akt phosphorylation/activation. We also found that TRIB1 protein expression was maximal during G2/M transition of cell cycle in GBM cells. Furthermore, TRIB1 bound directly to HDAC1 and p53. Importantly, mice bearing TRIB1 overexpressing tumors had worse overall survival. Collectively, these data suggest that TRIB1 induces resistance of GBM cells to RT/TMZ treatments by activating the cell proliferation and survival pathways thus providing an opportunity for developing new targeted therapeutics.


Subject(s)
Brain Neoplasms , Glioblastoma , Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Drug Resistance, Neoplasm/genetics , Temozolomide/pharmacology , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Apoptosis/genetics , Mitogen-Activated Protein Kinase Kinases , Cell Line, Tumor , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/pathology
2.
Endokrynol Pol ; 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37577996

ABSTRACT

INTRODUCTION: The objective was to observe the expression of miR-23a-3p in the serum of patients with type 2 diabetic nephropathy (T2DN) and to explore its clinical significance. MATERIALS AND METHODS: 112 patients with type 2 diabetes were divided into a simple diabetes mellitus (NON) group, T2DN microalbuminuria (MIC) group, and T2DN macroalbuminuria (MAC) group, according to the urinary protein-creatinine ratio (uACR). Clinical data were collected, miR-23a-3p levels in serum were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and clinical parameters were measured by an automatic biochemical analyser; the influencing factors of diabetic kidney disease (DKD) and the correlation between miR-23a-3p expression and clinical parameters were analysed. RESULTS: The expression of miR-23a-3p in the serum of the DKD group was lower than that of the normal control (CON) and NON groups. Correlation analysis showed that miR-23a-3p was positively correlated with urinary albumin (Albu), glycosylated haemoglobin (HbA1c), total cholesterol (CHOL), glycated albumin (GA-L), serum creatinine (Scr), fasting blood glucose (GLU), and uric acid (UA), negatively correlated with uACR and high-density lipoprotein cholesterol (HDL-C), but not correlated with urinary creatinine (CREA). The area under the receiver operating characteristic (ROC) curve (AUC) of miR-23a-3p for the diagnosis of DKD was 0.686 [95% confidence interval (CI): 0.599-0.773], with a sensitivity of 64.5% and a specificity of 71.2%; the AUC for differentiating NON from DKD was 0.700 (95% CI: 0.598-0.802), with a sensitivity of 61.8% and a specificity of 77.8%. Multivariate logistic regression analysis showed that serum miR-23a-3p levels were not associated with the development of DKD after adjusting for other levels of influence and were not significant for the differentiation of NON and DKD. CONCLUSION: Serum miR-23a-3p levels are decreased in T2DN patients, and this change becomes more significant with the severity of the disease, which may be a marker for the early diagnosis and progression of T2DN.

3.
J Biol Chem ; 298(5): 101938, 2022 05.
Article in English | MEDLINE | ID: mdl-35429501

ABSTRACT

Mitogen-activated protein kinase phosphatase 1 (Mkp-1) KO mice produce elevated cytokines and exhibit increased mortality and bacterial burden following systemic Escherichia coli infection. To understand how Mkp-1 affects immune defense, we analyzed the RNA-Seq datasets previously generated from control and E. coli-infected Mkp-1+/+ and Mkp-1-/- mice. We found that E. coli infection markedly induced programmed death-ligand 1 (PD-L1) expression and that Mkp-1 deficiency further amplified PD-L1 expression. Administration of a PD-L1-neutralizing monoclonal antibody (mAb) to Mkp-1-/- mice increased the mortality of the animals following E. coli infection, although bacterial burden was decreased. In addition, the PD-L1-neutralizing mAb increased serum interferon (IFN)-γ and tumor necrosis factor alpha, as well as lung- and liver-inducible nitric oxide synthase levels, suggesting an enhanced inflammatory response. Interestingly, neutralization of IFN-α/ß receptor 1 blocked PD-L1 induction in Mkp-1-/- mice following E. coli infection. PD-L1 was potently induced in macrophages by E. coli and lipopolysaccharide in vitro, and Mkp-1 deficiency exacerbated PD-L1 induction with little effect on the half-life of PD-L1 mRNA. In contrast, inhibitors of Janus kinase 1/2 and tyrosine kinase 2, as well as the IFN-α/ß receptor 1-neutralizing mAb, markedly attenuated PD-L1 induction. These results suggest that the beneficial effect of type I IFNs in E. coli-infected Mkp-1-/- mice is, at least in part, mediated by Janus kinase/signal transducer and activator of transcription-driven PD-L1 induction. Our studies also support the notion that enhanced PD-L1 expression contributes to the bactericidal defect of Mkp-1-/- mice.


Subject(s)
B7-H1 Antigen , Dual Specificity Phosphatase 1 , Escherichia coli Infections , Gene Expression Regulation , Interferon Type I , Animals , B7-H1 Antigen/genetics , Dual Specificity Phosphatase 1/metabolism , Escherichia coli/genetics , Escherichia coli/immunology , Escherichia coli Infections/immunology , Gene Expression Regulation/immunology , Interferon Type I/genetics , Mice
4.
Physiol Rep ; 8(17): e14559, 2020 09.
Article in English | MEDLINE | ID: mdl-32914566

ABSTRACT

Phosphodiesterase 3 (PDE3), of which there are two isoforms, PDE3A and PDE3B, hydrolyzes cAMP and cGMP-cyclic nucleotides important in the regulation of pulmonary vascular tone. PDE3 has been implicated in pulmonary hypertension unresponsive to nitric oxide (NO); however, contributions of the two isoforms are not known. Furthermore, adenosine monophosphate-activated protein kinase (AMPK), a critical regulator of cellular energy homeostasis, has been shown to be modulated by PDE3 in varying cell types. While AMPK has recently been implicated in pulmonary hypertension pathogenesis, its role and regulation in the pulmonary vasculature remain to be elucidated. Therefore, we utilized human pulmonary artery smooth muscle cells (hPASMC) to test the hypothesis that NO increases PDE3 expression in an isoform-specific manner, thereby activating AMPK and inhibiting hPASMC proliferation. We found that in hPASMC, NO treatment increased PDE3A protein expression and PDE3 activity with a concomitant decrease in cAMP concentrations and increase in AMPK phosphorylation. Knockdown of PDE3A using siRNA transfection blunted the NO-induced AMPK activation, indicating that PDE3A plays an important role in AMPK regulation in hPASMC. Treatment with a soluble guanylate cyclase (sGC) stimulator increased PDE3A expression and AMPK activation similar to that seen with NO treatment, whereas treatment with a sGC inhibitor blunted the NO-induced increase in PDE3A and AMPK activation. These results suggest that NO increases PDE3A expression, decreases cAMP, and activates AMPK via the sGC-cGMP pathway. We speculate that NO-induced increases in PDE3A and AMPK may have implications in the pathogenesis and the response to therapies in pulmonary hypertensive disorders.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism , Myocytes, Smooth Muscle/metabolism , Nitric Oxide/metabolism , Protein Kinases/metabolism , Pulmonary Artery/cytology , AMP-Activated Protein Kinase Kinases , Cells, Cultured , Cyclic AMP/metabolism , Humans , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/drug effects , Nitric Oxide/pharmacology
5.
Ann Diagn Pathol ; 36: 12-20, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29966831

ABSTRACT

Spinal cord paralysis is relatively common after surgical repair of thoraco-abdominal aortic aneurysm (TAAA) and its etiology is unknown. The present study was designed to examine the histopathology of the disease and investigate whether miR-155 ablation would reduce spinal cord ischemic damage and delayed hindlimb paralysis induced by aortic cross-clamping (ACC) in our mouse model. The loss of locomotor function in ACC-paralyzed mice correlated with the presence of extensive gray matter damage and central cord edema, with minimal white matter histopathology. qRTPCR and Western blotting showed that the spinal cords of wild-type ACC mice that escaped paralysis showed lower miR-155 expression and higher levels of transcripts encoding Mfsd2a, which is implicated in the maintenance of blood-brain barrier integrity. In situ based testing demonstrated that increased miR-155 detection in neurons was highly correlated with the gray matter damage and the loss of one of its targets, Mfsd2a, could serve as a good biomarker of the endothelial cell damage. In vitro, we demonstrated that miR-155 targeted Mfsd2a in endothelial cells and motoneurons and increased endothelial cell permeability. Finally, miR-155 ablation slowed the progression of central cord edema, and reduced the incidence of paralysis by 40%. In sum, the surgical pathology findings clearly indicated that the epicenter of the ischemic-induced paralysis was the gray matter and that endothelial cell damage correlated to Mfsd2a loss is a good biomarker of the disease. MiR-155 targeting therefore offers new therapeutic opportunity for edema caused by traumatic spinal cord injury and diagnostic pathologists, by using immunohistochemistry, can clarify if this mechanism also is important in other ischemic diseases of the CNS, including stroke.


Subject(s)
Ischemia/metabolism , Membrane Transport Proteins/genetics , MicroRNAs/genetics , Spinal Cord Injuries/genetics , Animals , Disease Models, Animal , Immunohistochemistry/methods , Ischemia/genetics , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/metabolism , Nervous System Diseases/genetics , Neurons/metabolism , Spinal Cord/pathology , Spinal Cord Injuries/physiopathology , Symporters , Tumor Suppressor Proteins/genetics
6.
Sci Rep ; 8(1): 5103, 2018 03 23.
Article in English | MEDLINE | ID: mdl-29572456

ABSTRACT

This retrospective consecutive case series aimed to evaluate spectral-domain optical coherence tomography (SD-OCT) for occult macular disease recognition preoperatively in patients scheduled for routine cataract surgery. All patients scheduled for cataract surgery underwent macular SD-OCT. Scans were reviewed for retinal, retinal pigment epithelium and vitreomacular interface abnormalities. For the subgroup analysis, the following information was collected: age; sex; and diabetes, hypertension, myopia, glaucoma, post intra-ocular surgery, endophotocoagulation, retinal vasculopathy and uveitis statuses. One-thousand-one-hundred-seventy-six consecutive scans were acquired from 1,176 patients. Macular pathology was found in 294 eyes. The most common macular disorders were an epiretinal membrane (n = 130), myopia atrophy (n = 61) and a dome-shaped macular with pathologic myopia (n = 32). One-hundred-thirty eyes (11.05%) presented macular epiretinal membranes not detected by dilated fundus examination, accounting for 44.22% of the abnormalities in diseased eyes and was higher than in previous Chinese studies. Some had multiple macular disorders. The most common ocular history was myopia, including high myopia. The pooled prevalence rate of macular diseases detected by OCT was 0.24 (95% CI 0.14-0.34) using meta-analysis. SD-OCT should be performed for routine cataract surgery patients to evaluate visual outcomes, especially in myopic patients and those considering advanced-technology intraocular lenses.


Subject(s)
Cataract Extraction , Macula Lutea/diagnostic imaging , Tomography, Optical Coherence , Adult , Aged , Aged, 80 and over , Aging , Cataract/epidemiology , Cataract Extraction/methods , China/epidemiology , Female , Humans , Male , Middle Aged , Preoperative Period , Retinal Diseases/diagnostic imaging , Retinal Diseases/epidemiology , Retrospective Studies , Tomography, Optical Coherence/methods
7.
Sci Rep ; 7(1): 8936, 2017 08 21.
Article in English | MEDLINE | ID: mdl-28827524

ABSTRACT

The purpose of the present study was to investigate the vascular flow density (VD) of macular superficial (SCP), deep capillary plexus (DCP), and choriocapillaris and the size of the foveal avascular zone (FAZ) area in healthy children using optical coherence tomography angiography (OCTA). The potential associations of age, sex, intraocular pressure, body mass index, spherical equivalent, and axial length with OCTA parameters were also investigated. A total of 75 eyes from 75 healthy children were included for analysis, with the mean age 11.51 ± 1.91 years (range, 8-16 years). At the level of the SCP, mean VD and mean FAZ area were, respectively, 54.29 ± 2.25% and 0.290 ± 0.109 mm2. At the level of the DCP and choriocapillaris, mean VD were 60.19 ± 1.76% and 66.58 ± 1.33%, respectively. After adjustment on the signal strength index, there was no significant correlation between age and all OCTA parameters. Intra-observer repeatability was 0.91, 0.82, and 0.88 in the SCP, DCP and choriocapillaris, respectively. In healthy eyes of children, only sex has a significant influence on the FAZ area. OCTA may provide a noninvasive and reliable approach for evaluating macular perfusion in children, although sex-related variations should be considered.


Subject(s)
Macula Lutea/diagnostic imaging , Tomography, Optical Coherence/methods , Adolescent , Child , Cross-Sectional Studies , Female , Healthy Volunteers , Humans , Male , Observer Variation , Optical Imaging/methods , Reproducibility of Results , Sex Factors
8.
Biochem Biophys Res Commun ; 491(1): 72-78, 2017 09 09.
Article in English | MEDLINE | ID: mdl-28698135

ABSTRACT

Thyroid cancer has long been considered to arise in middle age and progress to more aggressive and lethal cancers after its repeated proliferation. In this research, we aimed at investigating the biological function and the underlying molecular mechanism of Melanoregulin (MREG) in thyroid cancer. It was found that the expression of MREG was significantly downregulated in thyroid cancer tissues. The downregulation of MREG expression was caused by epigenetic methylation. MREG overexpression could suppress the invasion and proliferation of thyroid cancer cells. While MREG knockdown promoted the invasion and proliferation of thyroid cancer cells. Furthermore, the phosphorylation of Akt or mTOR was decreased by MREG overexpression and increased by MREG knockdown. Moreover, Dactolisib (the inhibitor of mTOR) could abrogate silenced MREG induced thyroid cancer cell invasion and proliferation. Taken together, MREG regulates thyroid cancer cell invasion and proliferation through PI3K/Akt-mTOR signaling pathway. MREG may serve as a promising therapeutic strategy for thyroid cancer.


Subject(s)
Carrier Proteins/metabolism , Cell Proliferation , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Adaptor Proteins, Vesicular Transport , Humans , Neoplasm Invasiveness , Signal Transduction , Tumor Cells, Cultured
9.
Neurol Res ; 39(6): 559-565, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28460563

ABSTRACT

Sleep disorders are a group of conditions that affect the ability to sleep well on a regular basis and cause significant impairments in social and occupational functions. Although currently approved medications are efficacious, they are far from satisfactory. Benzodiazepines, antidepressants, antihistamines and anxiolytics have the potential for dependence and addiction. Moreover, some of these medications can gradually impair cognition. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone produced by the pineal gland and released exclusively at night. Exogenous melatonin supplementation is well tolerated and has no obvious short- or long-term adverse effects. Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep. It is centrally involved in anti-oxidation, circadian rhythmicity maintenance, sleep regulation and neuronal survival. This narrative review aims to provide a comprehensive overview of various therapeutic functions of melatonin in insomnia, sleep-related breathing disorders, hypersomnolence, circadian rhythm sleep-wake disorders and parasomnias. Melatonin offers an alternative treatment to the currently available pharmaceutical therapies for sleep disorders with significantly less side effects.


Subject(s)
Circadian Rhythm/drug effects , Melatonin/metabolism , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Wake Disorders/drug therapy , Sleep/physiology , Animals , Circadian Rhythm/physiology , Humans , Neurons/cytology , Sleep/drug effects , Sleep Wake Disorders/metabolism , Sleep Wake Disorders/physiopathology
10.
Int J Oncol ; 50(4): 1330-1340, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28259944

ABSTRACT

Cervical cancer is a cause of cancer death, making it one of the most common causes of death among women globally. Previously, a variety of studies have revealed the molecular mechanisms by which cervical cancer develops. However, there are still limitations in treatment for cervical cancer. Ursolic acid is a naturally derived pentacyclic triterpene acid, exhibiting broad anticancer effects. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of ursolic acid nanoparticles is thought to be sufficient to lead to considerable suppression of cervical cancer progression. We loaded gold-ursolic acid into poly(DL-lactide-co-glycolide) nanoparticles to cervical cancer cell lines due to the properties of ursolic acid in altering cellular processes and the easier absorbance of nanoparticles. In addition, in this study, ursolic acid nanoparticles were administered to cervical cancer cells to find effective treatments for cervical cancer inhibition. In the present study, ELISA, western blotting, flow cytometry and immunohistochemistry assays were carried out to calculate the molecular mechanism by which ursolic acid nanoparticles modulated cervical cancer progression. Data indicated that ursolic acid nanoparticles, indeed, significantly suppress cervial cancer cell proliferation, invasion and migration compared to the control group, and apoptosis was induced by ursolic acid nanoparticles in cervical cancer cells through activating caspases, p53 and suppressing anti-apoptosis-related signals. Furthermore, tumor size was reduced by treatment of ursolic acid nanoparticles in in vivo experiments. In conclusion, this study suggests that ursolic acid nanoparticles inhibited cervical cancer cell proliferation via apoptosis induction, which could be a potential target for future therapeutic strategy clinically.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Proliferation/drug effects , Triterpenes/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Biocompatible Materials/chemistry , Caspases/metabolism , Drug Carriers/chemistry , Female , Gold/chemistry , HeLa Cells , Humans , Injections, Intraperitoneal , Male , Mice, Nude , Nanoparticles/chemistry , Polyglactin 910/chemistry , Triterpenes/administration & dosage , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor Assays , Ursolic Acid
11.
Pathol Res Pract ; 213(4): 359-363, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28214211

ABSTRACT

Bone morphogenetic protein 4 (BMP-4) is a member of the BMP protein family. BMP-4 was reported to induce epithelial-mesenchymal transition (EMT) and promote tumor cell immigration and invasion. This study aimed to investigate the expression of BMP-4 in papillary thyroid carcinoma (PTC) and its correlation with the patients' clinicophathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 82 patients admitted to the Department of Thyroid Surgery of Yantai Yuhuangding Hospital between Feb 1st and May 31st, 2016 were collected. The expression level of BMP-4 in PTC tissues was examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between BMP-4 expression and the clinical pathological features of PTC. Our result showed that BMP-4-positive cell rate and staining intensity were positively correlated with the patient's age (P=0.031, 0.037), tumor size (P=0.033, 0.019), capsular invasion (P=0.001, 0.002) and TNM stage (P=0.001, 0.004), while not correlated with gender, multicentricity of tumor or lymphatic metastasis. In conclusion, this study identified BMP-4 as a potential molecular marker for predicting the invasion and progression of PTC.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma/pathology , Neoplasm Invasiveness/pathology , Thyroid Neoplasms/pathology , Adult , Aged , Bone Morphogenetic Protein 4/analysis , Bone Morphogenetic Protein 4/biosynthesis , Carcinoma, Papillary , Disease Progression , Female , Humans , Immunohistochemistry , Male , Middle Aged , Thyroid Cancer, Papillary , Young Adult
12.
Exp Ther Med ; 12(2): 1097-1102, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27446326

ABSTRACT

Insulin resistance and reduced ß-cell glucose sensitivity are present in patients with type 2 diabetes. In the present study, we investigated the changes in ß-cell function in patients with type 2 diabetes during a 3-year follow-up study. A total of 48 patients with early-onset type 2 diabetes (EOD) and 55 patients with late-onset type 2 diabetes (LOD) were enrolled. Weight, height, waist circumference, hip circumference, blood pressure and plasma levels of lipids, glucose, fasting serum C-peptide (CPR0) and serum C-peptide 6 min after glucagon stimulation (CPR6) were measured. In addition, islet ß-cell secretory activity was detected. Subjects with EOD had lower Systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting CPR0, CPR6 and greater glycated hemoglobin A1c (HbA1c), triglyceride (TG) compared with subjects with LOD. CPR0, CPR6 and TG were decreased in both EOD and LOD groups 3 years later. The ratio of ß-cell function failure was 29.17 and 10.91% in the EOD and LOD groups, respectively, and there was significant difference between the two groups. A positive correlation was identified between the CPR0 and waist-hip ratio, HbA1c in the EOD group. A similar positive correlation was observed between CPR0 and BMI in the LOD group. Collectively, islet ß-cell function has declined in patients with EOD, and this change may be more evident when compared with those with LOD.

13.
Clin Cancer Res ; 22(24): 6142-6152, 2016 Dec 15.
Article in English | MEDLINE | ID: mdl-27358488

ABSTRACT

PURPOSE: Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore, we asked whether adding already established effective drugs such as topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML. EXPERIMENTAL DESIGN: The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML. RESULTS: Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared with each single therapy. CONCLUSIONS: Aberrant nuclear export and cytoplasmic localization of Topo IIα has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of patients with AML that express cytoplasmic Topo IIα, selinexor treatment results in nuclear retention of Topo IIα protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC-dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML. Clin Cancer Res; 22(24); 6142-52. ©2016 AACR.


Subject(s)
Antineoplastic Agents/pharmacology , DNA Repair/drug effects , DNA Topoisomerases, Type II/metabolism , Hydrazines/pharmacology , Karyopherins/antagonists & inhibitors , Leukemia, Myeloid, Acute/drug therapy , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Triazoles/pharmacology , Active Transport, Cell Nucleus/drug effects , Animals , Cell Line, Tumor , Cell Nucleus/drug effects , DNA Damage/drug effects , Drug Resistance, Neoplasm/drug effects , Female , Humans , Leukemia, Myeloid, Acute/metabolism , Mice , Mice, SCID , Proto-Oncogene Proteins c-myc/metabolism , RNA, Messenger/metabolism , Topoisomerase II Inhibitors/pharmacology , Exportin 1 Protein
14.
Int J Gynaecol Obstet ; 133(2): 202-5, 2016 May.
Article in English | MEDLINE | ID: mdl-26868068

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of uterine artery embolization (UAE) for the treatment of adenomyosis. METHODS: A prospective study was performed at Yuhuangding Hospital, China, between January 2012 and December 2013, enrolling premenopausal patients diagnosed with adenomyosis. All patients were treated with bilateral UAE using 500-700-µm tris-acryl gelatin microspheres. At baseline, and 3, 6, and 12months after UAE, magnetic resonance imaging was used to assess uterine volume and patient-assessed improvements in dysmenorrhea were recorded. Any complications and adverse events were reported. RESULTS: In total, 117 patients with adenomyosis were enrolled. The bilateral UAE procedure was successful in 115 (98.3%) patients, who were able to return to normal activity within 1week of treatment. At 12-month follow-up, a median 51.0% reduction in uterine volume from baseline was recorded (P=0.005). Marked and moderate improvements in dysmenorrhea symptoms were reported by 64 (55.7%) and 31 (27.0%) participants, respectively. Pelvic pain of varying intensity was reported by 112 (97.4%) patients but was managed with analgesia. Persistent amenorrhea was experienced by 2 (1.7%) individuals following treatment. Patients did not encounter any new gynecologic or general complications following UAE treatment. CONCLUSION: UAE could be considered as a minimally invasive treatment option for patients with adenomyosis. Further research to compare the efficacy and safety of UAE with conventional hysterectomy is warranted.


Subject(s)
Acrylic Resins/therapeutic use , Adenomyosis/therapy , Dysmenorrhea/therapy , Gelatin/therapeutic use , Uterine Artery Embolization , Uterus/diagnostic imaging , Adenomyosis/pathology , Adult , China , Female , Follow-Up Studies , Humans , Length of Stay , Magnetic Resonance Imaging , Middle Aged , Pain Measurement , Pelvic Pain/etiology , Prospective Studies , Treatment Outcome , Uterus/pathology
15.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(3): 1804-5, 2016 05.
Article in English | MEDLINE | ID: mdl-25317643

ABSTRACT

We sequenced a diabetic Rattus norvegicus Wistar strain mitochondrial genome for the first time (GenBank Accession No. KM114608). Its mitogenome was 16,311 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. This mitogenome sequence will provide definite genetic information for diabetes disease.


Subject(s)
Diabetes Mellitus/genetics , Genome, Mitochondrial , Animals , Base Composition/genetics , Base Pairing/genetics , Base Sequence , DNA, Mitochondrial/genetics , Disease Models, Animal , Gene Order , Male , Polymorphism, Single Nucleotide/genetics , Rats, Wistar
16.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(3): 1997-8, 2016 05.
Article in English | MEDLINE | ID: mdl-25350740

ABSTRACT

In the present work we undertook the complete mitochondrial genome sequencing of an important insulin resistance model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.


Subject(s)
Genome, Mitochondrial , Insulin Resistance/genetics , Mutation/genetics , Animals , Base Sequence , Disease Models, Animal , Genes, Mitochondrial , Mice, Inbred C57BL , RNA, Transfer/genetics
17.
Int J Clin Exp Med ; 8(2): 2471-5, 2015.
Article in English | MEDLINE | ID: mdl-25932191

ABSTRACT

The signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphism has been indicated to be correlated with type 1 diabetes (T1D) susceptibility, but study results are still debatable. Thus, a meta-analysis was conducted. The electronic databases PubMed, Embase, CNKI, and Web of Science (ISI) were searched to find eligible studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A significant association was found between STAT4 rs7574865 polymorphism and T1D risk (OR=1.30; 95% CI, 1.13-1.48; P<0.01; I(2) =73%). Significant associations were also found in Asians (OR=1.33; 95% CI, 1.04-1.71; P=0.02; I(2) =60%) and Caucasians (OR=1.26; 95% CI, 1.08-1.47; P<0.01; I(2) =74%), respectively. This association was also positive in the pediatric patients (OR=1.41; 95% CI, 1.19-1.68; P<0.01; I(2) =46%). Moreover, we found that STAT4 rs7574865 polymorphism was associated with early-onset T1D risk (OR=1.43; 95% CI, 1.16-1.77; P<0.01; I(2) =0%). This meta-analysis suggested that the STAT4 rs7574865 polymorphism may be associated with T1D development.

18.
Invest Ophthalmol Vis Sci ; 56(4): 2631-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25788648

ABSTRACT

PURPOSE: To investigate the longitudinal changes in choroidal thickness of the eyes of diabetic retinopathy patients during 12 weeks after panretinal photocoagulation (PRP). METHODS: This prospective, comparative study included 46 eyes undergoing four-session PRP. At baseline and 1, 4, 8, and 12 weeks after completion of the PRP treatments, subfoveal choroidal thickness (SFCT) was measured by using enhanced depth imaging optical coherence tomography. Also measured were central macular thickness (CMT) and best-corrected visual acuity (BCVA). RESULTS: The mean SFCT at baseline was 309 ± 77 µm, changing to 323 ± 78 µm, 315 ± 75 µm, 299 ± 68 µm, and 289 ± 71 µm at 1, 4, 8, and 12 weeks, respectively. This constituted a statistically significant increase at 1 week and a significant decrease at 12 weeks. The mean baseline CMT was 294 ± 92 µm, which increased significantly 1 week after PRP to 344 ± 123 µm, remaining higher at 4 weeks (340 ± 117 µm) and 8 weeks (318 ± 100 µm), but subsiding to baseline at 12 weeks (311 ± 96 µm). The mean BCVA at baseline and the last visit were 0.63 ± 0.28 logMAR and 0.53 ± 0.42 logMAR, respectively. There was no significant difference in BCVA between eyes with and without central-involved diabetic macular edema at all time points. Compared with the baseline, the mean BCVA dropped at 1 week and 4 weeks but recovered by 12 weeks. CONCLUSIONS: Choroidal thickness decreased 12 weeks after PRP, suggesting that PRP may reduce choroidal vascular permeability or cause atrophy of choroidal vessels over a 12-week period.


Subject(s)
Choroid/pathology , Diabetic Retinopathy/surgery , Laser Coagulation , Visual Acuity , Adult , Aged , Diabetic Retinopathy/pathology , Diabetic Retinopathy/physiopathology , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Male , Middle Aged , Prospective Studies , Retina/pathology , Retina/surgery , Time Factors , Tomography, Optical Coherence , Treatment Outcome
20.
PLoS One ; 9(7): e102198, 2014.
Article in English | MEDLINE | ID: mdl-25009980

ABSTRACT

BACKGROUND: Human pancreatic islet transplantation is a prospective curative treatment for diabetes. However, the lack of donor pancreases greatly limits this approach. One approach to overcome the limited supply of donor pancreases is to generate functional islets from human embryonic stem cells (hESCs), a cell line with unlimited proliferative capacity, through rapid directed differentiation. This study investigated whether pancreatic insulin-producing cells (IPCs) differentiated from hESCs could correct hyperglycemia in severe combined immunodeficient (SCID)/non-obese diabetic (NOD) mice, an animal model of diabetes. METHODS: We generated pancreatic IPCs from two hESC lines, YT1 and YT2, using an optimized four-stage differentiation protocol in a chemically defined culture system. Then, about 5-7 × 10(6) differentiated cells were transplanted into the epididymal fat pad of SCID/NOD mice (n = 20). The control group were transplanted with undifferentiated hESCs (n = 6). Graft survival and function were assessed using immunohistochemistry, and measuring serum human C-peptide and blood glucose levels. RESULTS: The pancreatic IPCs were generated by the four-stage differentiation protocol using hESCs. About 17.1% of differentiated cells expressed insulin, as determined by flow cytometry. These cells secreted insulin/C-peptide following glucose stimulation, similarly to adult human islets. Most of these IPCs co-expressed mature ß cell-specific markers, including human C-peptide, GLUT2, PDX1, insulin, and glucagon. After implantation into the epididymal fat pad of SCID/NOD mice, the hESC-derived pancreatic IPCs corrected hyperglycemia for ≥ 8 weeks. None of the animals transplanted with pancreatic IPCs developed tumors during the time. The mean survival of recipients was increased by implanted IPCs as compared to implanted undifferentiated hESCs (P<0.0001). CONCLUSIONS: The results of this study confirmed that human terminally differentiated pancreatic IPCs derived from hESCs can correct hyperglycemia in SCID/NOD mice for ≥8 weeks.


Subject(s)
Cell Differentiation , Diabetes Mellitus, Experimental/therapy , Embryonic Stem Cells/transplantation , Insulin-Secreting Cells/transplantation , Animals , Blood Glucose , C-Peptide/blood , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/pathology , Disease Models, Animal , Humans , Insulin/metabolism , Insulin Secretion , Islets of Langerhans Transplantation , Mice , Mice, Inbred NOD , Pancreas/metabolism , Pancreas/pathology
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