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Yi Lu Lin Zheng Wen Zhang Tingting Feng Juan Liu Xiao Wang Yuan Yu Mei Qi Weiming Zhao Xiuping Yu Wei Tang 《Gynecologic oncology》2014
Objective
The growth factor progranulin (PGRN) is overexpressed in a number of tumors. We aimed to investigate the expression and role of PGRN in cervical cancer tumorigenesis.Methods
PGRN expression and secretion was assessed in cells and normal and cancerous cervical tissues by Western blot analysis, ELISA or immunohistochemistry. The role of PGRN in cervical carcinogenesis was explored by cell-proliferation, colony-formation and tumor-growth assays. We assessed the role of PGRN-mediated signaling in the cervical cell with specific inhibitors.Results
PGRN expression was upregulated in cervical cancer cell lines and tissue. PGRN promoted the transformation of human cervical mucosa epithelial H8 cells in vitro and tumor formation in vivo. Knockdown of PGRN expression in cervical cancer cells in vivo decreased cell proliferation and slowed tumor growth. PGRN stimulated cervical cell proliferation, and transformation was mediated, at least in part, by Akt and Erk signaling.Conclusions
PGRN is overexpressed in cervical cancer and promotes the malignant growth and transformation of cervical cells. Therefore, PGRN plays a critical role in carcinogenesis of cervical cancer and shows promise for therapeutic strategies for cervical cancer. 相似文献53.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The mortality rate of in-hospital patients whose conditions are complicated by sepsis remains high in spite of intensive-care treatment, therefore placing a significant financial burden on the health care system. In recent years, progranulin (PGRN), a cysteine-rich secretory protein (CRISP), has been found to play a crucial role in sepsis. PGRN participates in the pathogenesis of sepsis via diverse pathways, including bacterial clearance, cell growth and survival, tissue repair, and the regulation of inflammation. PGRN knockout mice suffer from serious infectious processes, whereas therapeutic administration of recombinant PGRN to such mice enhances bacterial clearance and reduces organ injury and mortality rate. Even though PGRN plays an important role in regulating sepsis, its potential mechanisms have not been completely clarified. In this review, we summarize the most recent research advances in the study of PGRN and its role in sepsis. 相似文献
54.
Neuronal ceroid lipofuscinosis (NCL) is a group of progressive neurodegenerative disorders characterized by intracellular accumulation of ceroid lipopigments. Based on gene defect of NCL-associated proteins, 14 types of NCL have been described till date. NCL type 11 was first described in 2014 in two siblings as adult-onset NCL and was found to be due to a homozygous progranulin gene mutation. These siblings had progressive retinopathy, recurrent generalized seizures, moderate ataxia and subtle cognitive dysfunction. Palinopsia was present and MRI showed selective and severe cerebellar atrophy which was progressive with age. There have been no further reports of NCL 11 in literature. We here present a 14-year old girl born to second degree consanguineous couple who presented with gradually increasing frequency of seizures for the past 1?year without any signs of visual abnormalities and dementia. She had an elder sister who had progressive seizures and dementia from 8?years of age and died after few years. Her electroencephalogram showed frequent generalized epileptiform discharges and magnetic resonance imaging (MRI) showed pure cerebellar atrophy mainly affecting the vermis. MRI findings suggested a neurodegenerative disorder like NCL and prompted us to go for whole exome screen which revealed NCL type 11 due to homozygous mutation c.912G>A (p.Trp304Ter) in exon 9 of GRN gene (OMIM#614706). To the best of our knowledge this is the third case of NCL 11 and the first from Asia. 相似文献
55.
Cairns NJ Bigio EH Mackenzie IR Neumann M Lee VM Hatanpaa KJ White CL Schneider JA Grinberg LT Halliday G Duyckaerts C Lowe JS Holm IE Tolnay M Okamoto K Yokoo H Murayama S Woulfe J Munoz DG Dickson DW Ince PG Trojanowski JQ Mann DM;Consortium for Frontotemporal Lobar Degeneration 《Acta neuropathologica》2007,114(1):5-22
The aim of this study was to improve the neuropathologic recognition and provide criteria for the pathological diagnosis in
the neurodegenerative diseases grouped as frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent
advances in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest Consortium for Frontotemporal
Lobar Degeneration and experts at other centers to review and revise the existing neuropathologic diagnostic criteria for
FTLD. The proposed criteria for FTLD are based on existing criteria, which include the tauopathies [FTLD with Pick bodies,
corticobasal degeneration, progressive supranuclear palsy, sporadic multiple system tauopathy with dementia, argyrophilic
grain disease, neurofibrillary tangle dementia, and FTD with microtubule-associated tau (MAPT) gene mutation, also called FTD with parkinsonism linked to chromosome 17 (FTDP-17)]. The proposed criteria take into account
new disease entities and include the novel molecular pathology, TDP-43 proteinopathy, now recognized to be the most frequent
histological finding in FTLD. TDP-43 is a major component of the pathologic inclusions of most sporadic and familial cases
of FTLD with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Molecular genetic
studies of familial cases of FTLD-U have shown that mutations in the progranulin (PGRN) gene are a major genetic cause of FTLD-U. Mutations in valosin-containing protein (VCP) gene are present in rare familial forms of FTD, and some families with FTD and/or MND have been linked to chromosome 9p,
and both are types of FTLD-U. Thus, familial TDP-43 proteinopathy is associated with defects in multiple genes, and molecular
genetics is required in these cases to correctly identify the causative gene defect. In addition to genetic heterogeneity
amongst the TDP-43 proteinopathies, there is also neuropathologic heterogeneity and there is a close relationship between
genotype and FTLD-U subtype. In addition to these recent significant advances in the neuropathology of FTLD-U, novel FTLD
entities have been further characterized, including neuronal intermediate filament inclusion disease. The proposed criteria
incorporate up-to-date neuropathology of FTLD in the light of recent immunohistochemical, biochemical, and genetic advances.
These criteria will be of value to the practicing neuropathologist and provide a foundation for clinical, clinico-pathologic,
mechanistic studies and in vivo models of pathogenesis of FTLD. 相似文献
56.
Frontotemporal degeneration (FTD) in its behavioral variant (bvFTD) is probably one of the conditions that best illustrates the links between psychiatry and neurology. It is indeed admitted that between a third and half of patients with this condition, especially in early-onset forms, receive an initial diagnosis of psychiatric disorder (depression, schizophrenia, bipolar disorder) and are then referred to a psychiatric ward. BvFTD can thus be considered a neurological disorder with a psychiatric presentation. Among psychiatric symptoms reported in this disease, psychotic symptoms (hallucinations, delusions, especially of persecution), which have long been underestimated in bvFTD and are not part of the current diagnostic criteria, are present in about 20% of cases and may be inaugural. They are particularly common in the genetic forms related to a mutation in the C9orf72 gene (up to 50%), and to a lesser extent in the GRN gene (up to 25%). C9orf72 gene mutation is often associated with a family history of dementia or motor neuron disease but also of psychiatric disorders. It has also been described in sporadic presentation forms. Sometimes, the moderate degree of brain atrophy on MRI described in patients carrying this mutation may complicate the differential diagnosis with late-onset psychiatric diseases. In the present article, we underline the importance of considering that psychiatric – especially psychotic – symptoms are not rare in bvFTD, which should lead to a revision of the diagnostic criteria of this disease by taking greater account of this fact. We also propose a diagnostic chart, based on concerted evaluation by neurologists and psychiatrists for cases of atypical psychiatric symptoms (late-onset or pharmacoresistant troubles) leading to consider the possibility of a neurological disorder, in order to shed a new light on these difficult clinical situations. In the field of research, bvFTD may constitute a model to explore the neural basis of certain psychiatric disorders, and a possible molecular link between bvFTD and psychoses, which could eventually lead to new therapeutic approaches, has been recently suggested. Thus, bvFTD illustrates how the links between neurology and psychiatry are close and tend to evolve with the progress of scientific knowledge. It is necessary to strengthen collaboration between the two disciplines both to improve the care – diagnosis and management of these patients – and to promote the emergence of innovative clinical research. 相似文献
57.
《Surgery for obesity and related diseases》2020,16(11):1655-1660
BackgroundBariatric surgery stands out as the most effective long-term intervention for sustainable weight loss and metabolic improvement in patients with severe obesity. Progranulin was recently identified as an adipokine related to obesity and inflammation, revealing a metabolic function and proinflammatory properties.ObjectiveTo evaluate plasma progranulin levels before and after 6 months of bariatric surgery in Roux-en-Y gastric bypass (RYGB).SettingTertiary referral hospital, southern Brazil.MethodsThis was a prospective longitudinal study, including 23 obese patients who underwent RYGB. Demographic and clinical characteristics, body composition, and resting energy expenditure were evaluated. Plasma progranulin was determined with enzyme-linked immunosorbent assays in a peripheral blood sample collected before and 6 months after the surgical procedure.ResultsThe participants were mostly women (78.3%), with a mean age of 42.3 ± 10.8 years and baseline body mass index of 48.8 ± 10.4 kg/m2. Regarding the anthropometric parameters, there were differences in the pre- and post-RYGB values, with reduction of weight, body mass index, body fat percentage, and cervical and abdominal circumferences. All laboratory parameters improved, such as lipid profile and fasting glycemia, and resting energy expenditure values decreased significantly. Plasma progranulin levels decreased from 47.6 ± 13.5 ng/mL before RYGB to 40.4 ± 9.9 ng/mL after 6 months of surgery (P = .005). The reduction of progranulin did not correlate with body composition or laboratory data.ConclusionsPlasma progranulin levels significantly reduced 6 months after RYGB, but it could not be explained by changes in anthropometry, body composition, or glycemic or lipid profile. 相似文献
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Skoglund L Brundin R Olofsson T Kalimo H Ingvast S Blom ES Giedraitis V Ingelsson M Lannfelt L Basun H Glaser A 《Neurogenetics》2009,10(1):27-34
Mutations in the progranulin (PGRN) gene have recently been identified in families with frontotemporal lobar degeneration and ubiquitin-positive brain inclusions linked to chromosome 17q21. We have previously described a Swedish family displaying frontotemporal dementia with rapid progression and linkage to chromosome 17q21. In this study, we performed an extended clinical and neuropathological investigation of affected members of the family and a genetic analysis of the PGRN gene. There was a large variation of the initial presenting symptoms in this family, but common clinical features were non-fluent aphasia and loss of spontaneous speech as well as personality and behavioural changes. Mean age at onset was 54 years with disease duration of close to 4 years. Neuropathological examination revealed frontotemporal neurodegeneration with ubiquitin and TAR DNA binding protein-43 immunoreactive intraneuronal inclusions. Mutation screening of the PGRN gene identified a 1 bp deletion in exon 1 causing a frameshift of the coding sequence and introducing a premature termination codon in exon 2 (Gly35GlufsX19). Analysis of PGRN messenger RNA (mRNA) levels revealed a considerable decrease in lymphoblasts from mutation carriers and fragment size separation, and sequence analysis confirmed that the mutated mRNA allele was almost absent in these samples. In conclusion, the PGRN Gly35fs mutation causes frontotemporal dementia with variable clinical presentation in a large Swedish family, most likely through nonsense-mediated decay of mutant PGRN mRNA and resulting haploinsufficiency. 相似文献
59.
背景与目的:颗粒蛋白前体(progranulin,PGRN)是一种新型生长因子,在细胞迁移、细胞周期进展及肿瘤形成过程中发挥着重要作用。PGRN在多种恶性肿瘤细胞中高表达,不仅参与肿瘤的生长过程,还与肿瘤的发生、演变过程关系密切。本研究旨在探讨PGRN在胃癌组织中的表达,及其对胃癌BGC823细胞增殖与衰老的影响。方法:利用免疫组化方法检测胃癌组织及癌旁组织中PGRN的表达;利用实时定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)干扰胃癌细胞株BGC823中PGRN的表达;通过四甲基偶氮唑盐(MTT)法、细胞克隆形成和细胞衰老检测实验,探讨PGRN对BGC823细胞增殖与衰老的影响。结果:PGRN在胃癌组织中高表达。PGRN表达降低后,胃癌细胞的增殖与克隆形成能力均显著降低。PGRN-siRNA细胞的克隆形成率为(25.3±3.1)%,对照组细胞的克隆形成率为(72.1±5.7)%,正常组细胞的克隆形成率为(80.3±4.0)%。两两比较,对照组与正常组间差异无统计学意义(P>0.05),实验组与其他两组间差异均有统计学意义(P均<0.05)。干扰PGRN表达能够明显促进BGC823细胞衰老。PGRN-siRNA细胞衰老阳性率为(27.6±2.1)%,对照组细胞衰老阳性率为(3.2±1.3)%,正常组细胞衰老阳性率为(1.9±1.2)%。两两比较,对照组与正常组间差异无统计学意义(P>0.05),实验组与其他两组间差异均有统计学意义(P均<0.05)。结论:PGRN可作为新的胃癌标志物,为临床胃癌的靶向治疗提供新的思路。 相似文献
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The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic. Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure. The pathophysiologic states of hypertension, including obesity, are regulated by the production of adipocyte-derived factors. Increased body mass index was closely linked to elevated blood pressure. Mostly the hypertensive subjects were obese as well as overweight. There are numerous adipokines, however, this review article only focuses on the major adipokines including chemerin, visfatin, retinol-binding protein 4, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, omentin-1, lipocalin-2, vaspin, progranulin, complement c1q tumor necrosis factor-related protein, and nesfatin-1 role in the pathogenesis of hypertension. This review article concludes the significant association of major adipokines in the pathogenesis of hypertensives. New research should be focused on other newly reported adipokine roles in hypertensive subjects and the management of these adipokines in hypertensive subjects. The discovery of this information could result in the creation of antihypertensive medications, particularly those that focus on obesity-related hypertension. 相似文献