PubMed | University of Texas Health Science Center at San Antonio, Cincinnati Childrens Hospital Medical Center, Beijing University of Chinese Medicine, The Third Affiliated Hospital and Zhejiang University
Type: Journal Article | Journal: Human molecular genetics | Year: 2016
Lebers hereditary optic neuropathy (LHON) is the most common mitochondrial disease. Mitochondrial modifiers are proposed to modify the phenotypic expression of primary LHON-associated mitochondrial DNA (mtDNA) mutations. In this study, we demonstrated that the LHON susceptibility allele (m.14502T > C, p. 58I > V) in the ND6 gene modulated the phenotypic expression of primary LHON-associated m.11778G > A mutation. Twenty-two Han Chinese pedigrees carrying m.14502T > C and m.11778G > A mutations exhibited significantly higher penetrance of optic neuropathy than those carrying only m.11778G > A mutation. We performed functional assays using the cybrid cell models, generated by fusing mtDNA-less
Gao X.,The Third Affiliated Hospital |
Luo Y.,The Third Affiliated Hospital |
Wang Y.,The Third Affiliated Hospital |
Pang J.,The Third Affiliated Hospital |
And 3 more authors.
International Journal of Nanomedicine | Year: 2012
Background: We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer. Methods: Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid), docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs), a multilayer shell formed by poly(allylamine hydrochloride) and two different sized poly(ethylene glycol) molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery. Results: Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001). Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo. © 2012 Gao et al, publisher and licensee Dove Medical Press Ltd.
Lu Z.,the Third Affiliated Hospital |
Qiu W.,the Third Affiliated Hospital |
Zou Y.,Sun Yat Sen University |
Lv K.,the Third Affiliated Hospital |
And 4 more authors.
Journal of the Neurological Sciences | Year: 2010
Objective: To investigate the characteristics of the linear lesions and longitudinally extensive spinal cord (LESC) lesions in Chinese patients with neuromyelitis optica (NMO). Methods: The medical records and magnetic resonance imaging (MRI) scans of 29 patients with NMO were reviewed. The frequencies and distributions of linear and LESC lesions were compared against those displayed by 22 multiple sclerosis (MS) patients. Furthermore, the association of lesions with aquaporin-4 IgG (AQP4-IgG) antibody was investigated. Results: The NMO patients had significantly more linear lesions than MS patients (48.3 vs 0%, p < 0.001). In the NMO group, linear lesions were found in the medulla in 34.5% (10/29) of patients, across the medullospinal region in 10.3% (3/29) and in the spinal cord in 13.8% (4/29). LESC lesions can be seen more frequently in NMO than MS (72.4 vs 22.7%, p < 0.001). In 93.1% (27/29) of the NMO cases, the axial section of the spinal MRI showed lesions on the central gray matter only, whilst the spinal lesions in MS were usually located in the peripheral white matter (72.7%, 16/22). The AQP4-IgG antibody was found to be associated with both linear and LESC lesions in NMO cases. Conclusions: High frequency of linear lesions and LESC lesions were found in Chinese patients with NMO and linear lesions were correlated with AQP4-IgG antibody. © 2010 Elsevier B.V. All rights reserved.
PubMed | The Third Affiliated Hospital, Xingtai Eye Hospital, Wenzhou University, Zhejiang University and 2 more.
Type: Journal Article | Journal: Investigative ophthalmology & visual science | Year: 2015
To investigate the prevalence and spectrum of mitochondrial ND4 mutations in subjects with Lebers hereditary optic neuropathy (LHON).A cohort of 1281 Chinese Han probands and 478 control subjects underwent clinical and genetic evaluation, and sequence analysis of mitochondrial (mt) DNA, as well as enzymatic assay of NADH:ubiquinone oxidoreductase.In this cohort, 503 probands had a family history of optic neuropathy and 778 subjects were sporadic cases. Mutational analysis of ND4 gene identified 149 (102 known and 47 novel) variants. The prevalence of known m.11778G>A mutation was 35.36%. Furthermore, we identified the known m.11696G>A and m.11253T>C mutations and five novel putative LHON-associated mutations. These mutations accounted for 2.74% of cases of LHON subjects. By enzymatic assay, we showed a mild decrease in the activity of NADH:ubiquinone oxidoreductase in mutant cell lines carrying only one putative mtDNA mutation. The low penetrance of optic neuropathy and mild biochemical defects in these pedigrees carrying only m.11696G>A mutation and one putative LHON-associated mutation suggested that the mutation(s) is(are) necessary but is(are) itself(themselves) insufficient to produce a visual failure. Moreover, mtDNAs in 169 probands carrying the LHON-associated mutation(s) were widely dispersed among 13 Eastern Asian haplogroups. In particular, the frequencies of haplogroups D, M8, M10, M11, and H in probands carrying the LHON-associated mtDNA mutation(s) were higher than those in Chinese controls.These results suggested that the ND4 gene is the hot spot for mutations associated with LHON. Thus, these findings may provide valuable information for the further understanding of pathogenic mechanism of LHON.
PubMed | The Third Affiliated Hospital, Wenzhou University, Hebei Provincial Eye Hospital, Beijing University of Chinese Medicine and Zhejiang University
Type: Journal Article | Journal: Investigative ophthalmology & visual science | Year: 2016
The purpose of this study was to investigate the mutational incidence and spectrum of mitochondrial ND1 gene in subjects with Lebers hereditary optic neuropathy (LHON).A cohort of 1281 Han Chinese probands and 478 control subjects underwent sequence analysis of mitochondrial (mt)DNA. Resultant variants were evaluated for evolutionary conservation, allelic frequencies, and structural and functional consequences. Respiratory complex activities were measured using lymphoblastoid cell lines derived from 25 probands carrying the mtDNA mutation and 3 controls.Mutational analysis identified 178 (70 missense and 108 silent) variants in the MT-ND1 gene. The incidences of known m.3460G>A, m.3635G>A, m.3733G>A, m.3866T>C, and m.3394T>C mutations were 1.33%, 0.86%, 0.08%, 0.55%, and 2.97%, respectively. Fifteen novel putative mutations were identified in 27 probands, translated into 2.1% cases of this cohort. The activity of complex I in mutant cell lines carrying one of putative mutations ranged from 66% to 76% of the average values in control cell lines, whereas activities of complexes II, III, and IV in mutant cells were comparable with those in controls. The low penetrances of optic neuropathy were observed in pedigrees carrying novel putative mutation(s). Moreover, mtDNAs in 101 probands carrying the MT-ND1 mutation(s) were widely dispersed among 15 Eastern Asian haplogroups. In particular, the occurrences of haplogroups M, M9, and M10 in patients carrying the ND1 mutations were higher than those in controls.These data demonstrated that the MT-ND1 gene is a hot spot for mutations associated with LHON. Our findings may provide valuable information for pathophysiology, management, and genetic counseling of LHON.
PubMed | Pacific Research Fisheries Center, The Third Affiliated Hospital and Beijing University of Chinese Medicine
Type: | Journal: Neuropsychiatric disease and treatment | Year: 2016
The Yi-nao-jie-yu decoction (YNJYD) is a herbal preparation widely used in the clinics of traditional Chinese medicine and has been recently used as an important new therapeutic agent in poststroke anxiety (PSA). The neuroendocrine-immune system plays an important role in PSA mechanisms, although the modulating effects of YNJYD remain unknown. This study investigated the potential effects of YNJYD on the neuroendocrine-immune system in a rat model of PSA.The PSA model was induced by injecting collagenase (type VII) into the right globus pallidus, accompanied by empty water bottle stimulation for 2 weeks. The sham group and the PSA model group were gavaged with saline, while the treatment groups received buspirone (BuSpar) or YNJYD. Behavior was evaluated with the open field test and elevated plus maze once a week. Pathological changes were observed by hematoxylin and eosin staining. Serum levels of tumor necrosis factor, interleukin (IL)-6, adrenocorticotropic hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, IL-1, and cortisol were detected by radioimmunoassay. Expression of the -aminobutyric acid type A receptor (GABAYNJYD-treated rats exhibited significantly better recovery than BuSpar-treated rats at 21 days and 28 days in the open field test and elevated plus maze. Hematoxylin and eosin staining revealed neural repair in the hippocampus in the treatment groups. Serum levels of IL-1 in the YNJYD group were significantly less than those in the model group and the BuSpar group. GABAYNJYD alleviated the symptoms of PSA mainly by decreasing IL-1 levels and downregulating GABA
Guo C.-L.,The Third Affiliated Hospital |
Yang X.-H.,Harbin Medical University |
Cheng W.,The Third Affiliated Hospital |
Xu Y.,The Third Affiliated Hospital |
And 5 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014
Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that Foxp3+T cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, CD8+T cells and Foxp3+T cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in CD8+T lymphocytes and Foxp3+T cells in patients with HCC. Methods: CD8+T cells and CD3+Foxp3+T cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in CD8+T cells and FasL in CD3+Foxp3+T cells were evaluated. Serum TGF-β1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in CD3+Foxp3+T cells was then evaluated. Results: The frequency of CD8+T cells binding annexin V and Fas expression in CD8+T cells, were all higher in HCC patients than normal controls and the proportion of apoptotic CD8+T cells correlated with their Fas expression. Serum TGF-β1 levels correlated inversely with CD3+Foxp3+T cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of CD8+T cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in Fas+CD8+T cells in vitro are required.
Ran J.,The Third Affiliated Hospital |
Wang D.-W.,The Third Affiliated Hospital
World Chinese Journal of Digestology | Year: 2014
Aim: To compare the value of bedside index for severity in acute pancreatitis (BISAP) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scoring systems in early prediction of severity of acute pancreatitis (AP).Methods: Clinical data for 120 patients with AP treated from June 2012 to December 2013 were retrospectively analyzed. The receiver operating characteristic curve and the area under the curve (AUC) were used to compare the ability of BISAP and APACHE Ⅱ to predict the severity and prognosis of AP.Results: The severity, complications, organ failure and death of AP patients became significantly wore as the scores of BISAP and APACHE Ⅱ increased (P < 0.05). The AUCs of BISAP and APACHE Ⅱ scores in the prediction of AP severity were 0.821 and 0.903, respectively; The sensitivity, specificity, positive predictive value and negative predictive value of BISAP were significantly lower than those of APACHE Ⅱ score (74.5% vs 87.5%, 71.3% vs 87.5%, 57.1% vs 87.5%, 84.6% vs 83.0%, P < 0.05).Conclusion: Both BISAP and APACHE Ⅱ scoring systems can predict the severity of AP, with BISAP being more simple and easier. © 2014 Baishideng Publishing Group Inc. All rights reserved.
PubMed | The Third Affiliated Hospital
Type: Journal Article | Journal: International heart journal | Year: 2015
Adriamycin (ADR) is a potent antineoplastic agent, but long-term treatment is limited by its cumulative, life-threatening cardiomyopathy. Recently, a few reports have shown that pentoxifylline (PTX) might produce cardioprotection in cardiac dysfunction. Here, we investigated the protective effects of PTX on ADR-induced cardiomyopathy in rats. Male rats were randomly assigned either to saline, ADR (adriamycin, 5 mg/kg/week), or A (adriamycin, 5 mg/kg/week) + PTX (pentoxifylline, 50 mg/kg/day) groups. After 3 weeks, these animals were sacrificed and the heart tissue was harvested for histological analysis and assessment of hepatocyte growth factor (HGF) and caspase-3 expression. Histopathological findings showed that PTX can alleviate myocardial damage caused by ADR. Cardiac fibrosis was significantly suppressed in the A+PTX group compared to that in the ADR group. The HGF gene expression was decreased significantly in the ADR group compared with the control group, but was increased in the A+PTX group. Caspase-3 was up-regulated in the ADR group, and down-regulated in the A+PTX group. These results show that treatment with PTX exerts a protective effect against ADR-induced myocardial fibrosis via regulation of HGF and caspase-3 gene expression. PTX may thus represent a useful new clinical tool for the treatment of ADR-induced cardiomyopathy.
PubMed | The Third Affiliated Hospital
Type: Journal Article | Journal: Ultrastructural pathology | Year: 2013
Ischemic acute kidney injury (AKI) is a common complication during inpatient hospitalization, and often induces acute lung injury (ALI). A lot of studies have concentrated on the relevance between AKI and ALI, but the underlying mechanisms of AKI- associated ALI have remained unclear until now. One reason is that evidence of the ultrastructural pathology of AKI-associated ALI has been scarce and needed to be accumulated. The aims of present study are to observe ultrastructural changes, and to reveal leukocyte trafficking of ALI induced by ischemic AKI in rats. For this purpose light microscopy (LM) and electron microscopy (EM), as well as morphometric analysis, were employed in present study. LM observations revealed distinct regions of collapsed alveoli, hemorrhage in alveoli, and interstitial edema in AKI-induced ALI. EM examinations provided facts that alveolar epithelial cells, including type I and type II cells, were necrotic, and endothelia cells undergoing apoptosis as well as interstitial cells undergoing necroptosis were noted in AKI lungs. In addition, shrinkage and decreased or disappeared lamellar bodies were evident in alveolar type II cell of AKI rat lungs. Leukocyte numerical density on area (NA) in AKI lungs was significantly more than that in sham lungs. Based on the morphological criteria from EM examinations and morphometric analysis, a conclusion was that necrosis, including necroptosis, and apoptosis were involved in damaged lung induced by AKI. And inflammation also contributed to acute lung injury of rats with AKI.