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1.
Mol Cell Proteomics ; 22(1): 100481, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36496143

RESUMO

Meiotic maturation is an intricate and precisely regulated process orchestrated by various pathways and numerous proteins. However, little is known about the proteome landscape during oocytes maturation. Here, we obtained the temporal proteomic profiles of mouse oocytes during in vivo maturation. We successfully quantified 4694 proteins from 4500 oocytes in three key stages (germinal vesicle, germinal vesicle breakdown, and metaphase II). In particular, we discovered the novel proteomic features during oocyte maturation, such as the active Skp1-Cullin-Fbox pathway and an increase in mRNA decay-related proteins. Using functional approaches, we further identified the key factors controlling the histone acetylation state in oocytes and the vital proteins modulating meiotic cell cycle. Taken together, our data serve as a broad resource on the dynamics occurring in oocyte proteome and provide important knowledge to better understand the molecular mechanisms during germ cell development.


Assuntos
Proteoma , Proteômica , Camundongos , Animais , Proteoma/metabolismo , Oogênese , Oócitos/metabolismo , Núcleo Celular/metabolismo , Meiose
2.
J Org Chem ; 89(7): 5170-5180, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38545893

RESUMO

A chiral NHC-catalyzed [3 + 3] cycloaddition reaction of 3-aminobenzofurans with isatin-derived enals has been documented, furnishing 3,4'-piperidinoyl spirooxindoles bearing a quaternary stereocenter with good yields and excellent enantioselectivities. Further gram-scale preparation and synthetic transformation of the cycloadducts to δ-amino acid derivative demonstrated good practicality and applicability of this reaction.

3.
J Org Chem ; 89(10): 7339-7346, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38662477

RESUMO

NHC-catalyzed [4+2] annulation of 2H-azirine-2-carbaldehydes with ketimines and isocyanates has been developed, providing straightforward synthetic protocols for constructing structurally intriguing pyrimido[1,2-a]indolediones and pyrimidinediones under mild conditions with excellent yields. This protocol can be used to synthesize the core skeleton of pharmaceutically important drugs and pyrimido[1,2-a]indoledione-containing natural products, making it potentially valuable for creating biologically active derivatives.

4.
Int J Neurosci ; 127(6): 493-500, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27323873

RESUMO

OBJECTIVES: The aim of this study was to investigate the cognitive impairments of occipital periventricular hyperintensity (OPVH) patients and their brain-wide functional alterations in large scale. METHODS: The Mini-Mental State Examination (MMSE) was performed in 15 OPVH patients and 12 age-matched healthy controls to distinguish the cognitive impairment features of OPVH. Functional magnetic resonance imaging (fMRI) was applied with a delayed digital match memory task to identify the brain-wide functional alterations in OPVH patients. RESULTS: The two groups were not statistically different in terms of demographic or cardiovascular risk factors. The OPVH group had significantly lower scores in global cognitive abilities, immediate memory and delayed memory as determined by the MMSE (p < 0.05). The fMRI results demonstrated that the insula, precentral gyrus and Heschl's gyrus of the OPVH group had decreased activation compared to the control group (p < 0.005, uncorrected). Multivariate analysis also showed that OPVH was negatively correlated with reduced activation in the insula, precentral gyrus and Heschl's gyrus (p < 0.005). CONCLUSION: OPVH affects the immediate and delayed memory. These changes are accompanied with decreased functional responses in the insula and Heschl's gyrus.


Assuntos
Leucoencefalopatias/complicações , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Vias Neurais/diagnóstico por imagem , Lobo Occipital/patologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Estatísticas não Paramétricas
5.
Int J Cancer ; 135(7): 1687-91, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24585490

RESUMO

Gliomas represents more than 80% of all malignant brain tumors. However, the etiology still remains largely unknown. Human WW domain-containing oxidoreductase (WWOX), which is located at 16q23.1-16q23.2, the common fragile site 16D (FRA16D), an area with a high frequency of gene deletions or chromosomal alterations, has been identified as a tumor suppressor gene in multiple cancers. In current study, we analyzed the WWOX deletion (CNV-67048) in a large, case-control study of 3,622 adult Chinese people (including 1,798 glioma cases and 1,824 healthy controls). All participants were genotyped using real-time qualitative PCR (qPCR), and its biological effect was validated with mRNA expression assays. The deletion was significantly associated with glioma risk, with ORs (95% CIs) of 1.21 (1.05-1.41) associated with 1 copy deletion and 1.94 (1.37-2.75) associated with 2 copy deletion as compared with subjects with no deletion (p for trend = 8.05 × 10(-6)). Additional adjustments and stratified analyses did not change the results materially. The mRNA levels of WWOX in glioma tissues were significantly lower than that of their border tissues (p = 0.007), especially in the loss genotyped subjects. Our data suggest that the loss genotypes of CNV-67048 in WWOX gene predispose their carriers to gliomas, and WWOX gene deletion may be a new biomarker for predicting risk of gliomas.


Assuntos
Neoplasias Encefálicas/genética , Variações do Número de Cópias de DNA/genética , DNA/genética , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Oxirredutases/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Oxidorredutase com Domínios WW
6.
Int Psychogeriatr ; : 1-7, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25362894

RESUMO

ABSTRACT Background: The Montreal Cognitive Assessment (MoCA) is used for screening mild cognitive impairment (MCI), and the Beijing version (MoCA-BJ) is widely used in China. We aimed to develop a computerized tool for MoCA-BJ (MoCA-CC). Methods: MoCA-CC used person-machine interaction instead of patient-to-physician interaction; other aspects such as the scoring system did not differ from the original test. MoCA-CC, MoCA-BJ and routine neuropsychological tests were administered to 181 elderly participants (MCI = 96, normal controls [NC] = 85). Results: A total of 176 (97.24%) participants were evaluated successfully by MoCA-CC. Cronbach's α for MoCA-CC was 0.72. The test-retest reliability (retesting after six weeks) was good (intraclass correlation coefficient = 0.82; P < 0.001). Significant differences were observed in total scores (t = 9.38, P < 0.001) and individual item scores (t = 2.18-8.62, P < 0.05) between the NC and MCI groups, except for the score for "Naming" (t = 0.24, P = 0.81). The MoCA-CC total scores were highly correlated with the MoCA-BJ total scores (r = 0.93, P < 0.001) in the MCI participants. The area under receiver-operator curve for the prediction of MCI was 0.97 (95% confidence interval = 0.95-1.00). At the optimal cut-off score of 25/26, MoCA-CC demonstrated 95.8% sensitivity and 87.1% specificity. Conclusion: The MoCA-CC tool developed here has several advantages over the paper-pencil method and is reliable for screening MCI in elderly Chinese individuals, especially in the primary clinical setting. It needs to be validated in other diverse and larger populations.

7.
Int J Neurosci ; 124(11): 834-40, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24397500

RESUMO

Sex, hypertension, diabetes, dyslipidemia, smoking, age and metabolic syndrome (MetS) are major vascular risk factors for intracranial or extracranial atherosclerotic stenosis (ICAS or ECAS) in Asian population. Here, we performed a meta-analysis to evaluate the different influence of these factors on ICAS compared to ECAS in Asian population, by searching PUBMED, EMBASE and Web of Science databases. Sensitivity analysis was performed by repeating the fixed or random effects model meta-analysis with removing each study individually. All statistical analysis was conducted with Stata 11.0. Finally, 15 studies including 3787 patients were identified, 2661 patients in ICAS group and 1126 patients in ECAS group, respectively. Our results showed that female or the patients with MetS were more likely to suffer from ICAS than ECAS, which pooled ORs of ICAS versus ECAS were 2.16 (95% CI: 1.65-2.83, p < 0.0001) and 1.68 (95% CI: 1.32-2.12, p < 0.0001), respectively. Meanwhile, the smoker or the patients with dyslipidemia were more likely to suffer from ECAS than ICAS, which pooled ORs of ICAS versus ECAS were 0.71 (95% CI: 0.61-0.84, p < 0.0001) and 0.75 (95% CI: 0.63-0.90, p = 0.002), respectively. However, age, hypertension and diabetes had not different influence on the location of atherosclerotic stenosis, and the pooled MD and ORs were -0.69 (95% CI: -1.52-0.15, p = 0.11), 1.08 (95% CI: 0.92-1.27, p = 0.34) and 1.02 (95% CI: 0.88-1.19, p = 0.76), respectively. Our results suggested that female sex and MetS were more associated with ICAS, while smoking and dyslipidemia were more associated with ECAS. There was no significant difference between ICAS and ECAS in terms of age, hypertension and diabetes.


Assuntos
Povo Asiático/estatística & dados numéricos , Estenose das Carótidas/etiologia , Arteriosclerose Intracraniana/etiologia , Adulto , Idoso , Artéria Carótida Externa/patologia , Estenose das Carótidas/patologia , Estenose das Carótidas/fisiopatologia , Dislipidemias/complicações , Feminino , Humanos , Arteriosclerose Intracraniana/patologia , Arteriosclerose Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fatores de Risco , Caracteres Sexuais , Fumar
8.
Oncol Lett ; 27(3): 107, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38304172

RESUMO

Breast acinic cell carcinoma (ACC) is a rare subtype of breast cancer. Accurate diagnosis of ACC using core needle biopsy (CNB) is pivotal for the use of effective treatments and patient prognosis. In the present study, a detailed analysis of the morphological, immunohistochemical and gene mutation features of 2 cases of ACC was performed. CNB was performed prior to surgical excision. The breast ACC in the present cases exhibited overt burrowing labyrinthine networks or 'hand-holding-hand' features. The tumor cells in both of the present cases expressed cytokeratin (CK)7, S100 and CK5/6, but were negative for p63, estrogen receptor and progesterone receptor. GATA binding protein 3 was positive in case 1 but negative in case 2. Fluorescence in situ hybridization indicated no ETS variant transcription factor 6 break-apart probe detection. Next-generation sequencing results revealed the same mutation and a similar abundance in exon 27 (NM_005120.2; c.3817G>T; p.A1273S) of the mediator of RNA polymerase II transcription, subunit 12 homolog (MED12) gene in both patients. To conclude, the findings of the present study suggested that recognition of this rare 'hand-holding-hand' structure could potentially be beneficial for avoiding patient misdiagnosis. In addition, it could be suggested that a mutation in the MED12 exon 27 was associated with the formation of a burrowing labyrinthine network or 'hand-holding-hand' feature.

9.
Exp Ther Med ; 25(2): 93, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36761009

RESUMO

Lipidized fibrous histiocytoma (FH) is a rare type of FH. The present study aimed to describe the clinical and pathological features of lipidized FH. A total of eight patients diagnosed with lipidized FH were retrospectively reviewed in the present study. The cohort included three male and five female patients (male to female ratio, 1.7:1) with a mean age of 48 years (range, 38-62 years). In total, four tumors were located on the buttock, three on the lower leg and one on the forearm. Histological, lipidized FH showed a wide spectrum. Some cases included prominent stromal hyalinization and hyalinized vessels with scant lipid-laden histiocytes. Other cases exhibited the prominent lipid-laden histiocytes and scant stromal hyalinization. Overall, lipidized FH must be differentiated from other benign and malignant tumors, taking into account the therapeutic and prognostic differences between these different entities.

10.
Muscle Nerve ; 44(2): 252-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21698648

RESUMO

INTRODUCTION: Prompt identification of the rare cranial variant of Guillain-Barré syndrome (GBS) is crucial, but the clinical characteristics remain poorly defined. METHODS: We conducted a retrospective review of 12 GBS patients hospitalized from 1995 to 2009 with multiple cranial nerve (CN) impairment at disease onset. RESULTS: Eight patients had impairment of CN IX and X; 3 of CN VII; and 1 of CN VII, IX, and X. All patients had areflexia or hyporeflexia, 6 had Lasegue sign, and 5 required tracheostomy and mechanical ventilation. All patients had cerebrospinal fluid (CSF) albuminocytologic dissociation within 2-3 weeks after onset. Electrophysiological studies showed motor conduction velocity and F-wave abnormalities in 10 of 12 and 10 of 11 patients, respectively. Treatment with intravenous immunoglobulin was effective. CONCLUSIONS: Bilateral CN IX, X, and/or VII impairment with areflexia or hyporeflexia, early abnormal F-wave response, nerve conduction abnormalities, and CSF albuminocytologic dissociation support a diagnosis of this GBS cranial variant.


Assuntos
Doenças dos Nervos Cranianos/fisiopatologia , Nervos Cranianos/fisiopatologia , Síndrome de Guillain-Barré/fisiopatologia , Condução Nervosa/fisiologia , Adulto , Idoso , Criança , Doenças dos Nervos Cranianos/diagnóstico , Eletrodiagnóstico , Feminino , Síndrome de Guillain-Barré/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
11.
Int J Clin Exp Pathol ; 14(2): 261-266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33564359

RESUMO

Gastritis cystica profunda (GCP) is a rare lesion characterized by hyperplasia and cystic dilatation of the gastric glands in the submucosal layer. Here we report seven cases of GCP. The patients are 5 women and 2 men with a mean age of 62 (range, 42-82) years at the time of diagnosis. The patients presented with abdominal distension, sour regurgitation, and heartburn. One case had the previous gastric surgery and the other six cases had no special history. The lesions were located in the fundus (4/7), corpus (1/7), cardia (1/7), and antrum (1/7). Endoscopic analysis revealed pedunculated polyps, or a dome-shaped polyp. Histologically, all cases showed dilated tubular glands, mainly located in the submucosa, among the muscularis mucosa, and occasionally in the lamina propria. The glands were lined by bland single columnar epithelium with infolding features in some areas. Mitotic activity and marked cellular atypia were not present. The stroma in some cases was mildly edematous with infiltrated lymphocytes and plasma cells. There was no epithelial dysplasia in the overlying mucosa. Immunohistochemically, the Ki-67 index was < 1%. P53 immunostaining was generally characterized as wild type in all cases. Based on the morphology of the glands and the cells and the possible mechanism of hyperplasia and cystic dilatation of the gastric glands, it is easy to differentiate GCP from a well-differentiated adenocarcinoma.

12.
Medicine (Baltimore) ; 100(10): e25063, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725895

RESUMO

RATIONALE: Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease that frequently affects various organs. Neuropsychiatric manifestations in SLE patients, known as neuropsychiatric SLE, are clinically common. However, the principal manifestation of cranial neuropathy in patients with SLE and comorbidities is relatively rare. PATIENT CONCERNS: In this report, we describe a 51-year-old Chinese woman who was admitted with a chief complaint of chronic-onset facial paresthesia, dysphagia, and choking cough when drinking water, accompanied by slurred speech, salivation, and limb weakness. The blood autoantibody test results showed that many SLE-associated antibodies were positive. Meanwhile, anti-nuclear matrix protein 2 (NXP2) antibody was strongly positive in the idiopathic inflammatory myopathy (IIM) spectrum test from the serum. Muscle biopsy indicated inflammatory infiltration of the muscle fiber stroma. DIAGNOSES: Taking into account the clinical manifestations and laboratory tests of the present case, the diagnosis of SLE and probable IIM was established. INTERVENTIONS: Corticosteroids and additional gamma globulin were administered and the clinical symptoms were relieved during the treatment process. OUTCOMES: Unfortunately, the patient experienced sudden cardiac and respiratory arrest. Multiple system dysfunctions exacerbated disease progression, but in the present case, we speculated that myocardial damage resulting from SLE could explain why she suddenly died. LESSONS: To our knowledge, multiple neurological manifestations in patients with SLE and anti-NXP2-positive myositis are rare. Note that SLE is still a life-threatening disease that causes multiple system dysfunctions, which requires increasing attention.


Assuntos
Doenças dos Nervos Cranianos/imunologia , Transtornos de Deglutição/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Parestesia/imunologia , Polimiosite/diagnóstico , Adenosina Trifosfatases/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biópsia , Doenças dos Nervos Cranianos/diagnóstico , Doenças dos Nervos Cranianos/tratamento farmacológico , Proteínas de Ligação a DNA/imunologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/tratamento farmacológico , Quimioterapia Combinada/métodos , Evolução Fatal , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-Idade , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Parestesia/diagnóstico , Parestesia/tratamento farmacológico , Polimiosite/complicações , Polimiosite/tratamento farmacológico , Polimiosite/imunologia , Pulsoterapia
13.
Front Cell Dev Biol ; 9: 617225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553179

RESUMO

Maternal obesity impairs oocyte quality and embryo development. However, the potential molecular pathways remain to be explored. In the present study, we examined the effects of obesity on telomere status in oocytes and embryos obtained from mice fed with high-fat diet (HFD). Of note, telomere shortening was observed in both oocytes and early embryos from obese mice, as evidenced by the reduced expression of telomerase reverse transcriptase and activity of telomerase. Moreover, quantitative analysis of telomere dysfunction-induced foci (TIFs) revealed that maternal obesity induces the defective telomeres in oocytes and embryos. Meanwhile, the high frequency of aneuploidy was detected in HFD oocytes and embryos as compared to controls, accompanying with the increased incidence of apoptotic blastocysts. In conclusion, these results indicate that telomere dysfunction might be a molecular pathway mediating the effects of maternal obesity on oocyte quality and embryo development.

14.
Front Cell Dev Biol ; 9: 625805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553183

RESUMO

FK506 binding proteins 25 (FKBP25) has been shown to function in ribosome biogenesis, chromatin organization, and microtubule stability in mitosis. However, the role of FKBP25 in oocyte maturation has not been investigated. Here, we report that oocytes with FKBP25 depletion display abnormal spindle assembly and chromosomes alignment, with defective kinetochore-microtubule attachment. Consistent with this finding, aneuploidy incidence is also elevated in oocytes depleted of FKBP25. Importantly, FKBP25 protein level in old oocytes is significantly reduced, and ectopic expression of FKBP25 could partly rescue the aging-associated meiotic defects. In addition, by employing site-specific mutagenesis, we identify that serine 163 is a major, if not unique, phosphorylation site modulating the action of FKBP25 on meiotic maturation. In summary, our data indicate that FKBP25 is a pivotal factor for determining oocyte quality, and may mediate the effects of maternal aging on female reproduction.

15.
Cell Prolif ; 54(1): e12940, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33107080

RESUMO

OBJECTIVES: It has been widely reported that maternal diabetes impairs oocyte quality. However, the responsible mechanisms remain to be explored. In the present study, we focused on whether SIRT3-GSK3ß pathway mediates the meiotic defects in oocytes from diabetic mice. MATERIALS AND METHODS: GSK3ß functions in mouse oocyte meiosis were first detected by targeted siRNA knockdown. Spindle assembly and chromosome alignment were visualized by immunostaining and analysed under the confocal microscope. PCR-based site mutation of specific GSK3ß lysine residues was used to confirm which lysine residues function in oocyte meiosis. siRNA knockdown coupled with cRNA overexpression was performed to detect SIRT3-GSK3ß pathway functions in oocyte meiosis. Immunofluorescence was performed to detect ROS levels. T1DM mouse models were induced by a single intraperitoneal injection of streptozotocin. RESULTS: In the present study, we found that specific depletion of GSK3ß disrupts maturational progression and meiotic apparatus in mouse oocytes. By constructing site-specific mutants, we further revealed that acetylation state of lysine (K) 15 on GSK3ß is essential for spindle assembly and chromosome alignment during oocyte meiosis. Moreover, non-acetylation-mimetic mutant GSK3ß-K15R is capable of partly preventing the spindle/chromosome anomalies in oocytes with SIRT3 knockdown. A significant reduction in SIRT3 protein was detected in oocytes from diabetic mice. Of note, forced expression of GSK3ß-K15R ameliorates maternal diabetes-associated meiotic defects in mouse oocytes, with no evident effects on oxidative stress. CONCLUSION: Our data identify GSK3ß as a cytoskeletal regulator that is required for the assembly of meiotic apparatus, and discover a beneficial effect of SIRT3-dependent GSK3ß deacetylation on oocyte quality from diabetic mice.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Meiose , Oócitos/citologia , Oócitos/metabolismo , Sirtuína 3/metabolismo , Acetilação , Animais , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Feminino , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos ICR , Estreptozocina/administração & dosagem
16.
Aging (Albany NY) ; 12(2): 1610-1623, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980591

RESUMO

It has been widely reported that advanced maternal age impairs oocyte quality. To date, various molecules have been discovered to be involved in this process. However, prevention of fertility issues associated with maternal age is still a challenge. In the present study, we find that both in vitro supplement and in vivo administration of melatonin are capable of alleviating the meiotic phenotypes of aged oocytes, specifically the spindle/chromosome disorganization and aneuploidy generation. Furthermore, we identify SIRT2 as a critical effector mediating the effects of melatonin on meiotic structure in old oocytes. Candidate screening shows that SIRT2-controlled deacetylation of histone H4K16 is essential for maintaining the meiotic apparatus in oocytes. Importantly, non-acetylatable-mimetic mutant H4K16R partially rescues the meiotic deficits in oocytes from reproductive aged mice. In contrast, overexpression of acetylation-mimetic mutant H4K16Q abolishes the beneficial effects of melatonin on the meiotic phenotypes in aged oocytes. To sum up, our data uncover that melatonin alleviates advanced maternal aged-associated meiotic defects in oocytes through the SIRT2-depenendet H4K16 deacetylation pathway.


Assuntos
Envelhecimento/metabolismo , Histonas/metabolismo , Meiose/efeitos dos fármacos , Melatonina/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Sirtuína 2/metabolismo , Acetilação , Fatores Etários , Envelhecimento/genética , Animais , Suplementos Nutricionais , Expressão Gênica , Idade Materna , Camundongos , Modelos Biológicos
17.
Aging (Albany NY) ; 11(7): 1965-1976, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926765

RESUMO

It has been well recognized that oocyte quality declines in aging animals. However, to date, the underlying mechanism remains to be explored. In the present study, we report that oocytes and embryos from aged mice (42-45 weeks old) display the reduced expression of SIRT6 protein, accompanying with telomere shortening and DNA lesions. Moreover, we demonstrate that specific depletion of SIRT6 in oocytes induces dysfunctional telomeres and apoptosis of the resultant early embryos, leading to the developmental delay and cytoplasmic fragmentation. Importantly, we further find that overexpression of SIRT6 in aged oocytes promotes the telomere elongation in 2-cell embryos and lowers the incidence of apoptotic blastomeres. In summary, our data indicate a role for SIRT6 in modulating telomere function during oocyte maturation and embryonic development, and discover that SIRT6 reduction is an important point connecting maternal aging and quality control of oocyte/embryos.


Assuntos
Oócitos/metabolismo , Sirtuínas/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Apoptose/fisiologia , Senescência Celular/fisiologia , Fase de Clivagem do Zigoto/citologia , Fase de Clivagem do Zigoto/metabolismo , Dano ao DNA , Feminino , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Endogâmicos ICR , Oócitos/citologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sirtuínas/antagonistas & inibidores , Sirtuínas/genética , Encurtamento do Telômero/fisiologia , Regulação para Cima
18.
Int J Clin Exp Pathol ; 11(5): 2497-2505, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31938362

RESUMO

Background and aim: Hemosiderotic fibrolipomatous tumor (HFLT) is a locally invasive tumor composed of mature adipocytes accompanied by spindle cells containing hemosiderin deposition. In 2013, it was categorized by WHO as a soft tissue tumor with uncertain differentiation. So far, the literature has reported 60 cases but primary HFLT in bone has never before been reported. We set out to investigate the clinicopathological features of primary HFLT in bone. Methods: We retrospectively reviewed the clinical, imaging, histological, and immunophenotypic features and treatment of 1 case of primary HFLT in bone, and combined this with literature discussion. Results: HFLT occurred in the lateral femoral condyle of a 50-year-old male patient, which might have been overlooked were it not for the knee-joint pain and dysfunction. CT and MRI showed osteolytic bone destruction with a clear 4.0-cm diameter boundary, diagnosed as cystic damage of the lateral condyle of the left femur. SPECT metabolism was not active. Histologically, the lesion was composed of different proportions of mature fat cells, spindle cells, and hemosiderin. Immunohistochemistry revealed spindle cells expressing vimentin, p63, but not CD34, calponin, and others. The tumor tissue was thoroughly removed by curetting, and a bone graft was carried out after immersion in anhydrous ethanol. At the 11-month postoperative follow-up, the patient was recovering well. Conclusions: Primary HFLT in bone is extremely rare. In imaging, it can easily be misdiagnosed as a bone cyst. Histological morphology of the current case is similar to that of soft tissue HFLT.

19.
Cancer Biomark ; 21(2): 439-447, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29125480

RESUMO

OBJECTIVE: This study aims to investigate the significance of combined detection of HER2 gene amplification and chemosensitivity in gastric cancer. METHODS: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and fluorescence reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of HER2 protein, HER2 gene amplification and the mRNA expression of ERCC1, TUBB3 and TYMS genes in 135 cases of gastric carcinoma. RESULTS: The expression rate of HER2 protein was 39.3% (53/135). Among these positive cases, patients with HER2 protein (3+) accounted for 9.6% (13/135), patients with HER2 protein (2+) accounted for 13.3% (18/135), and patients with HER2 protein (1+) accounted for 16.3% (22/135). The amplification rate of the HER2 gene was 35.8% (19/53). In the detection of the mRNA expression of ERCC1, TUBB3 and TYMS, 45 patients had low and moderate single gene expression, 50 patients had low and moderate double gene expression, 22 patients had low and moderate mRNA expression for ERCC1, TUBB3 and TYMS, and 18 patients had no low and moderate expression. Among the 53 patients with HER2 protein expression and 22 patients with low and moderate mRNA expression of ERCC1, TUBB3 and TYMS, 12 patients received chemotherapy and trastuzumab. Follow-up results revealed that HER2 gene status was positively correlated with the therapeutic effect of the combined treatment in patients with low mRNA expression of ERCC1, TUBB3 and TYMS. Among these patients, five patients with extensive HER2 (3+), HER2 cluster-specific amplification, and low mRNA expression of ERCC1, TUBB3 and TYMS had a total survival of up to 19.1 months. CONCLUSIONS: The detection of HER2 in gastric cancer is highly heterogeneity, and the combined detection of HER2 protein expression, HER2 gene amplification and chemosensitivity can provide important reference markers for the benefit of antitumor drugs.


Assuntos
Genes erbB-2 , Receptor ErbB-2/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Adulto , Idoso , Feminino , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/enzimologia
20.
World J Gastroenterol ; 12(13): 2120-4, 2006 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-16610068

RESUMO

AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a hypobaric chamber simulating 5,000 m high altitude for 23 h every day for 0 (H0), 1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP, ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS: Compared with H0 group, intra-mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group reached the lowest point (70.6%) (P<0.01) when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in H0 group. In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups. Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly lower than that in H0 group, whereas H1 group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P<0.01) when compared to H0 group. ANT activity in H30 group was higher than in H15 group, but still lower than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0 group decreased significantly, which in H5 group was the lowest, being 27.1% of that in H0 group (P<0.01). ANT protein level in H30 group was higher than in H15 group, but still lower than in H0 group. CONCLUSION: Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure. The lower level of extra-mitochondrial ATP may be related to the decrease of ANT activity during hypoxia exposure.


Assuntos
Nucleotídeos de Adenina/análise , Metabolismo Energético , Hipóxia/metabolismo , Mitocôndrias Hepáticas/metabolismo , Translocases Mitocondriais de ADP e ATP/análise , Animais , Masculino , Ratos , Ratos Wistar
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