Prognostic value of serum progranulin in de novo adult acute myeloid leukemia patients

Abstract Background Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. Methods Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. Results The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p= 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p= 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p= 0.789). Moreover, the serum PGRN level was associated with inferior OS (p= 0.024) on multivariate analysis. Conclusion Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

Expression of progranulin in mononuclear cells in the peripheral blood of patients with post-stroke aphasia / 中华物理医学与康复杂志

Objective:To document the expression of aphasia-related progranulin gene (GRN) in mononuclear cells in the peripheral blood (PBMC) of patients with post-stroke aphasia (PSA).Methods:PC12 cells at the logarithmic-growth stage were cultured and divided into a non-specific interference group (the gene control group) and a specific interference group (the gene silencing group) when the cell density reached 30 to 50%. After the expression of GRN was knocked down in the cells, the occurrence of variable splicing events was analyzed using high-throughput transcriptome sequencing (RNA-seq). Meanwhile, 10 PSA patients were selected into a patient group and 10 healthy counterparts were chosen as a control group. Blood was collected from both groups and real-time fluorescence quantitative polymerase chain reactions (RT-qPCR) were employed to determine any changes in GRN mRNA expression and the occurrence of variable splicing events in the nuclear factor related to kappa-B-binding protein (NFRKB) in their PBMCs. The patient group received conventional speech therapy, and immediately after their first and second blood collections their speech functioning was assessed using the Chinese Aphasia Battery (ABC). Pearson correlation coefficients were then computed relating the GRN expression and ABC scores.Results:After knocking down GRN in the PC12 cells, the expression of GRN in the gene knockdown group was significantly different from that in the control group. There were 237 genes with significant differences in variable splicing between the two samples. The number of genes with variable splicing events at the 5′ end was the largest. There were also significant differences between the groups in the average occurrence of NFRKB variable splicing events. And significant diffe-rences were observed in the mRNA expression of GRN between the two blood collections from the patient group, as well as between the first collection from the patient group and the controls. The average oral expression score of the PSA patients improved significantly, particularly the retelling score. The changes in the GRN expression level were positively correlated with the recovery of oral expression ability.Conclusion:GRN can promote the recovery of speech function in PSA patients by regulating the variable splicing of NFRKB.

Progranulin concentration in relation to bone mineral density among obese individuals

ABSTRACT Objective Adipose tissue, particularly visceral adipose tissue, secretes a variety of cytokines, among which progranulin is a glycoprotein related to the immune system. Along with other secreted proteins, progranulin may be associated with bone mineral density. The aim of this study was to find out whether there are associations between the progranulin and bone mineral density among obese people. Subjects and methods This cross-sectional study was conducted on 244 obese participants (aged 22-52). Serum progranulin, high sensitive C-reactive protein, oxidised-low dencity lipoprotein, tumor necrosis factor-α, parathormone, vitamin D, and interleukins of 1 β, 4, 6, 10, 13, and 17 concentrations were measured. Anthropometric measurements, body composition and bone mineral density were also assessed. Results Serum progranulin was directly associated with interleukin-6 and interleukin-1β, while it had a negative association with interleukin-17 and tumor necrosis factor-α. We also observed a statistically significant direct association between progranulin concentration and visceral fat, abdominal fat, waist, abdominal and hip circumferences, hip T-score, and Z-score and T-score for the lumbar region. A partial correlation test has also shown a significant positive correlation regarding serum progranulin and the hip Z-score. Moreover, progranulin level is inversely associated with ospteopenia (P = 0.04 and CI: 0.17,0.96). Conclusion Our study revealed that central obesity may be related to increased progranulin concentration. In addition, progranulin concentration was directly related to bone formation parameters, which indicates the protective effects of progranulin on bone density. Further studies are needed to clarify the exact mechanisms underlying these associations.

Progranulin promotes tamoxifen-resistance of breast cancer cells by enhancing proliferation and anti-apoptosis / 肿瘤

Objective: To investigate the mechanism of progranulin (PGRN) in the development of tamoxifen resistance of human breast cancer cells. Methods: The breast cancer MCF-7 and T47D cells as well as tamoxifen-resistant MCF-7R and T47DR cells were treated by 4-hydroxytamoxifen (OHT). The 50% inhibitory concentration (IC50) of OHT was detected by CCK-8. The expressions of C-myc, Cyclin D1 and Bcl-2 were determined by Western blotting. The cell proliferation was detected by CCK-8, the apoptosis was detected by FCM. The expression levels of PGRN mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The expression of PGRN in MCF-7R and T47DR cells was interfered by transfection of PGRN-siRNA. Then the changes of PGRN, C-myc, Cyclin D1 and Bcl-2 expressions were detected by Western blotting. Furthermore, the PGRN-interfered MCF-7R and T47DR cells were stimulated by OHT, then the apoptosis was tested by FCM again. Results: The IC50 of OHT in tamoxifen-induced MCF-7R or T47DR cells was higher than that of MCF-7 or T47D cells (both P < 0.001). As compared with MCF-7 or T47D cells, the proliferation of MCF-7R or T47DR cells was enhanced (both P < 0.01), the apoptotic rate was decreased (both P < 0.01), the expressions of proliferation-related proteins C-myc and Cyclin D1 as well as apoptosis-related protein Bcl-2 were significantly increased (all P < 0.01), and the mRNA and protein levels of PGRN were significantly increased in MCF-7R and T47DR cells (both P < 0.05). After the transfection of PGRN-siRNA into MCF-7R and T47DR cells, the protein levels of PGRN, C-myc, Cyclin D1 and Bcl-2 were significantly decreased (all P < 0.01). After stimulation with OHT, the apoptosis rate of PGRN-downregulated MCF-7R and T47DR cells was increased (both P < 0.01). Conclusion: PGRN is overexpressed in human breast cancer MCF-7R and T47DR cells with tamoxifen-resistance. Interference of PGRN gene expression can enhance the sensibility of breast cancer cells to tamoxifen.

PGRN over-expression inhibits LPS-induced alveolar epithelial cell injury / 中国病理生理杂志

AIM:To investigate the effects of progranulin (PGRN) on the proliferation, apoptosis and inflammatory responses in lipopolysaccharide (LPS)-induced human alveolar epithelial A549 cells and HPAEpiC cells.METHODS:The cells were divided into 4 groups:control group (the normal cultured cells), LPS group [the cells were treated with LPS (10 mg/L)], PGRN+LPS group (the cells were transfected with pcDNA3.1-PGRN plasmids and then treated with LPS), and pcDNA3.1+LPS group (the cells were transfected with pcDNA3.1-EGFP plasmids and then treated with LPS).The cell viability was measured by MTT assay, cell proliferation was measured by BrdU incorporation assay, and cell apoptosis was analyzed by flow cytometry.The expression of PGRN at mRNA and protein levels was detected by RT-qPCR and Western blot.The protein levels of caspase-3, Bcl-2, Bax, IL-1β, IL-6, TNF-α, p65 and p-IκB-α were determined by Western blot.RESULTS:Compared with control group, the cell proliferation rate was decreased (P<0.05), and the apoptotic rate was increased (P<0.05) in LPS group.The protein levels of caspase-3 and Bax were significantly up-regulated (P<0.05), and the expression of Bcl-2 was down-regulated (P<0.05).The protein levels of IL-1β, IL-6 and TNF-α were significantly up-regulated (P<0.05), and the protein levels of p65 and p-IκB-α were enhanced (P<0.05).Compared with LPS group, the cell proliferation rate was increased (P<0.05), and the apoptotic rate was decreased (P<0.05) in PGRN+LPS group.The protein levels of caspase-3 and Bax were significantly down-regulated (P<0.05), and the expression of Bcl-2 was up-regulated (P<0.05).The protein levels of IL-1β, IL-6 and TNF-α were significantly down-regulated (P<0.05), and the protein levels of p65 and p-IκB-α were decreased (P<0.05).CONCLUSION:PGRN over-expression may alleviate LPS-induced abnormal proliferation, apoptosis and inflammatory cytokine production in the A549 cells and HPAEpiC cells, which may be associated with the regulation of NF-κB signaling pathway.

Variation of serum progranulin levels in patients with type 2 diabetes and nonalcoholic fatty liver disease / 第二军医大学学报

Objective To investigate the changes of serum progranulin in type 2 diabetic (T2DM) patients with nonalcoholic fatty liver disease (NAFLD) and the relevant clinical significance. Methods The clinical data were subjected to cross-sectional analysis. Totally 116 T2DM patients were randomly selected and assigned to the NAFLD group (n=68) and non-NAFLD group (n=48). The levels of serum progranulin, glycosylated hemoglobin Alc (Hb Ale), liver enzymes (ALT, AST, AKP), uric acid (UA), lipids (TG, TC, LDL-C, HDL-C), fasting blood-glucose (FBG), and fasting insulin (FINS) were assessed. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The height, weight, waist circumference and hip circumference were measured, and the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. The multiple stepwise regression analysis was used to detect the association of progranulin with the above metabolic parameters. The logistic regression was used to analyze the factors influencing NAFLD in patients with T2DM. Results (1) Compared with non-NAFLD group, the levels of BMI, waist circumference, hip circumference, WHR and serum FINS, HOMA-IR, TG, ALT, and AST were significantly higher in the NAFLD group (P<0. 05), While the level of HDL-C was significantly lower (P<0. 05) in NAFLD group. (2) Serum levels of progranulin were significantly higher in patients with NAFLD than in those with non-NAFLD (P<0. 01). (3) Multiple stepwise regression analysis suggested that BMI, HOMA-IR and TG were the independent factors influencing serum progranulin level. (4) Logistic regression analysis showed that progranulin, BMI and ALT were the independent risk factors influencing NAFLD in T2DM patients. Conclusion Serum progranulin level is increased in T2DM patients combined with NAFLD. High level of progranulin is an independent risk factor for the presence of NAFLD in T2DM patients. Progranulin might be an important serological marker of NAFLD in T2DM patients.

A Voxel Based Morphometric Analysis of Longitudinal Cortical Gray Matter Changes in Progranulin Mutation Carriers At-Risk for Frontotemporal Dementia: Preliminary Study

BACKGROUND AND PURPOSE: One of the most common genetic causes of frontotemporal dementia (FTD) is mutation in the progranulin (PGRN) gene. The aim of this study is to assess the early effects of the PGRN mutations on brain volumes by longitudinal voxel based morphometric (VBM) evaluation in asymptomatic mutation carriers. METHODS: We recruited 17 asymptomatic members of families with FTD caused by PGRN mutations; 7 mutation carriers (51.0+/-11.6 yr) and 10 non-carriers (55.2+/-6.0 yr, p=0.404). The MRI follow-up intervals of carriers and non-carriers were 788.6+/-103.8 and 922.0+/-225.1 days (p=0.124) respectively. We performed cross-sectional and longitudinal VBM analysis on both groups. RESULTS: At baseline, the carriers had lower white matter (WM) volumes in left frontal regions (p<0.001, uncorrected), but had no gray matter (GM) volume reduction. The carrier's global GM (p=0.924) and WM volume (p=0.364) reduction rate were not different from the non-carrier's. However, statistical parametric mapping T-maps showed differentially increased GM volume reductions in the bilateral parietal areas of carriers (p<0.001, uncorrected). CONCLUSIONS: The findings from this study to examine WM and GM cross-sectional and longitudinal changes in PGRN mutation carriers suggest that WM atrophic changes could precede both GM changes and symptom onset in FTD. Asymptomatic PGRN mutation carriers have measurably higher rates of regional GM atrophy than non-carriers even in the pre-dementia stages.

The regulation of adenovirus type 36 infection and progranulin expression in Uygur obese patients / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the regulation of adenovirus type 36 infection on precursor protein particles progranulin expression in Uygur obese patients.Methods Based on the diagnostic criteria of obesity,the samples were divided into obese group and non-obese group.Serum neutralization test was used to detect the antibody of Ad36.The progranulin mRNA expressions in abdominal omental and subcutaneous adipose tissues were detected by real-time quantitative PCR.ELISA method was used to determine serum progranulin protein levels. CD68 protein expression of macrophage was detected by immunohistochemistry. Results ① In the Uygur population of our study,compared with that in the non-obese group (38/1 1 7,32.5%),the number of obese patients (54/1 1 5,47.0%)infected with Ad36 was significantly higher than that in non-obese group (P <0.05 ).② Serum progranulin was significantly increased in the Ad36-infected obese group (408.45±1 56.92)than in non-obese group (326.1 1±1 58.60)(P <0.05).The mRNA expression of progranulin did not differ between the two groups.③ The macrophage infiltration was significantly higher in the Ad36-infected obese group (14 730.1 6 ± 2 227.39 )than in non-obese group (10 786.50 ± 2 772.80 )(P < 0.05 ).Conclusion Ad36 infection may be associated with the occurrence of obesity in Uygur population,and adenovirus type 36 infection may regulate the expression of serum progranulin at the protein level.

Effects of progranulin on proliferation and senescence in gastric cancer cells / 中国癌症杂志

Background and purpose:Progranulin (PGRN) is a novel growth factor that plays an important role in the tumorigenicity, tumor cell migration and cell cycle. Its expression in many malignant tumor cells is high. It is not only involved in tumor cell growth, but also closely related with the occurrence and evolution of tumor. This study was to investigate the expression of PGRN in gastric cancer and the effects on proliferation and senescence in gastric cancer cell line BGC823. Methods:Immunohistochemical method was used to detect the expression of PGRN in gastric cancer tissues and adjacent normal tissues; Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of PGRN in PGRN-siRNA BGC823 cells;MTT method, cell colony formation and cell senescence experiments were used to explore the effects of PGRN on proliferation and senescence in BGC823 cell. Results:PGRN protein levels were high in gastric cancer tissues;Knocking down the PGRN gene in BGC823 decreased the proliferation and clonogenic capacity, cloning efifciency in PGRN-siRNA group was (25.3±3.1)%, in the control group was (72.1±5.7)%, and in the normal cells was (80.3±4.0)%, there was no signiifcant difference between normal group and control group, but there were signiifcant differences among PGRN-siRNA group and the other two groups (P<0.05);Knocking down the PGRN gene in BGC823 cells could promote cell senescence. The positive rate of aging in PGRN-siRNA group was (27.6±2.1)%, in the control group was (3.2±1.3)%, and in the normal group was (1.9±1.2)%, there was no signiifcant difference between normal group and control group. But there were signiifcant differences among PGRN-siRNA group and the other two groups (P<0.05). Conclusion:PGRN can be used as a new marker for gastric cancer, and provide new ideas to the treatment of gastric cancer.

New discovery rarely runs smooth: an update on progranulin/TNFR interactions

Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al, in Science 332:478-484, 2011); however, Chen et al. reported their inability to demonstrate the PGRN-TNFR interactions under their own conditions (Chen et. al, in J Neurosci 33:9202-9213, 2013). A letter-to-editor was then published by the original group in response to the Chen et al. paper that discussed the reasons for the latter's inability to recapitulate the interactions. In addition, the group published follow-up studies that further reinforced and dissected the interactions of PGRN-TNFR. Recently, the dispute about the legitimacy of PGRN-TNFR interactions appears to be finally settled with independent confirmations of these interactions in various conditions by numerous laboratories. This review presents a chronological update on the story of PGRN-TNFR interactions, highlighting the independent confirmations of these interactions in various diseases and conditions.

Primary progressive aphasia: a dementia of the language network / Afasia progressiva primária: uma demência da rede de linguagem

Primary progressive aphasia (PPA) is a clinical syndrome diagnosed when three core criteria are met. First, there should be a language impairment (i.e., aphasia) that interferes with the usage or comprehension of words. Second, the neurological work-up should determine that the disease is neurodegenerative, and therefore progressive. Third, the aphasia should arise in relative isolation, without equivalent deficits of comportment or episodic memory. The language impairment can be fluent or non-fluent and may or may not interfere with word comprehension. Memory for recent events is preserved although memory scores obtained in verbally mediated tests may be abnormal. Minor changes in personality and behavior may be present but are not the leading factors that bring the patient to medical attention or that limit daily living activities. This distinctive clinical pattern is most conspicuous in the initial stages of the disease, and reflects a relatively selective atrophy of the language network, usually located in the left hemisphere. There are different clinical variants of PPA, each with a characteristic pattern of atrophy. The underlying neuropathological diseases are heterogeneous and can include Alzheimer's disease as well as frontotemporal lobar degeneration. The clinician's task is to recognize PPA and differentiate it from other neurodegenerative phenotypes, use biomarkers to surmise the nature of the underlying neuropathology, and institute the most fitting multimodal interventions.

A afasia progressiva primária (APP) é uma síndrome clínica diagnosticada quando três critérios centrais são preenchidos. Inicialmente deve haver comprometimento da linguagem (afasia) que interfere com o uso ou a compreensão das palavras. Em segundo lugar, os métodos diagnósticos devem determinar que a doença é neurodegenerativa e, portanto, progressiva. Por último, a afasia deve emergir de forma relativamente isolada, sem alterações equivalentes de comportamento ou memória episódica. O comprometimento da linguagem pode ser de tipo fluente ou não fluente, e pode ou não interferir com a compreensão de palavras. A memória para eventos recentes está preservada, embora escores de memória em testes verbais possam ser anormais. Alterações discretas de personalidade e comportamento podem estar presentes, mas não são os fatores que levam o paciente ao atendimento médico ou que o limitam em suas atividades de vida diária. Este padrão distinto é mais evidente nas fases iniciais da doença e reflete a atrofia relativamente seletiva da rede de linguagem, geralmente localizada no hemisfério cerebral esquerdo. Há diferentes variantes clínicas da APP, cada uma com padrão de atrofia característico. Os substratos neuropatológicos são heterogêneos e podem incluir a doença de Alzheimer e a degeneração lobar frontotemporal. A tarefa do clínico é reconhecer a APP e diferenciá-la de outros fenótipos neurodegenerativos, utilizar biomarcadores para inferir a natureza da neuropatologia subjacente e instituir as intervenções multimodais cabíveis.

Relationship between plasma progranulin and insulin resistance in patients with type 2 diabetes mellitus and obesity / 中华内分泌代谢杂志

Objective To detect plasma progranulin (PGRN) level in subjects with newly diagnosed type 2 diabetes mellitus and to investigate the relationship of plasma PGRN level with glycolipid metabolism,inflammation,and insulin resistance.Methods Eighty patients with newly diagnosed type 2 diabetes (T2DM) and 88 subjects with normal glucose tolerance (NGT) were recruited in the study.Both of them were divided into normal weight (NW)subgroup and obesity (OB) subgroup.Obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to the World Health Organization-Western Pacific Region diagnostic criteria(2000).Body fat parameters were measured and BMI,waist-to-hip ratio were determined.Fasting plasma PGRN and interleukin-6 (IL-6) levels were determined by ELISA,fasting plasma glucose (FPG),2 h plasma glucose after glucose loading (2hPG),HbA1C,fasting insulin (FINS),and lipids were also detected.Insulin resistance and pancreas β cell function were assessed by homeostasis model assessment (HOMA-IR,HOMA-β).Results Plasma PGRN level was significantly higher in T2DM group than that in NGT group(P＜0.01).Within groups of T2DM and NGT,plasma PGRN level in OB subgroups was higher than that in NW subgroups [(225.22 ± 34.39 vs 195.59 ± 50.47 and 183.79 ± 61.63 vs 148.69 ± 55.27) ng/ml,P＜0.05].Bivariate correlation analysis showed that plasma PGRN level was positively correlated with weight,waist circumference,BMI,systolic blood pressure,FPG,2hPG,HbA1C,triglyceride(TG),IL-6,FINS,and HOMA-IR (P＜0.05 or P＜0.01),and was negatively correlated with HOMA-β (P＜0.05).Multiple linear regression analysis showed that BMI,HbA1C,IL-6,and TG were independently related to plasma PGRN level(P＜0.05).Conclusions Plasma PGRN level was increased in patients with type 2 diabetes as well as in obesity,and was closely related with glycolipid metabolism,inflammation,and insulin resistance.

Expression of progranulin during the first stages of liver development in rat Fischer 344 / Expressão da progranulina durante os primeiros estágios de desenvolvimento hepático em ratos Fischer 344

Transplants are the only effective therapy for the treatment of advanced liver diseases such as cirrhosis. Given the limited number of organ donors, regenerative medicine has sought for sources of cells and tissues for replacement therapy. Embryonic stem cells are a promising source of material for transplantation vecause of their exclusive property of being expanded indefinitely in culture, thus they are a source of replacement tissue. Morcover, they are capable of differentiating into practically all cell types, and may be utilized in replacement therapy in various diseases. The liver bud has bipotent stem cells that gave not yet differentiated into hepatocytes or bibliary duct-cells: however, they have great potential of proliferation and differentiation. Thus, the challenge is to identify methods that promote their differentiation tential of proliferation and and differentiation is specific and functional strains.

Os transplantes são a única terapia para o tratamento de doenças hepáticas avançadas como a cirrose. Dado o número limitado de doadores de orgões, á medicina regenerativa tem procurado fontes de células para a terapia de substituição. As células embrionárias são uma fonte promissora de matéria para o transplante devido à sua propriedade exclusiva de ser expandida indefinidamente em cultura, assim, elas são uma fonte de tecidos de substituição. Além disso, são capazes de se diferenciar em pratimcante todos os tipos celulares, e podem ser utilizadas na terapia de substituição em várias doenças. O broto hepático tem células tronco (CT) bipotenciais que ainda não se diferenciam em hepatócitos ou células do dueto biliar, contudo, elas têm um grande potencial de proliferação e de diferenciação.Desse modo, o desafio é identificar métidis que promovam sua diferenciação em linhagens específicas e funcionais.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53 percent), TIMP-1 (-31.7 percent), TGF-β1 (-57.7 percent), and MMP-2 (-41.6 percent), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1 percent), ALT (-17.6 percent), and AST (-12.2 percent) serum levels; c) increased liver weight (11.3 percent), and reduced liver collagen (-37.1 percent), regenerative nodules size (-22.1 percent), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

Genética de la demencia frontotemporal / Genetics of Frontotemporal Dementia

Introducción: La demencia frontotemporal (DFT) es una enfermedad neurodegenerativa, caracterizada por la atrofia circunscrita de los lóbulos frontales y temporales. Se acompaña de cambios en el comportamiento o alteraciones del lenguaje. Su inicio es insidioso, y su curso, progresivo. Objetivo: Revisar de manera general la DFT, haciendo hincapié en sus bases genéticas. Métodos: Revisión de la literatura médica actual sobre el tema. Resultados: Últimamente se han estudiado familias con herencia autosómica dominante de esta enfermedad, entre las cuales se han hallado diferentes genes causales. De estos los más importantes son el gen de la proteína asociada con los microtúbulos tau y el gen de la progranulina. Conclusión: Es necesario considerar un abordaje genético en el momento de enfrentarse a un paciente con DFT, para así indagar profundamente en los antecedentes familiares, con el fin de brindar una adecuada asesoría genética que permita aclarar las principales dudas de los pacientes y sus familias sobre este aspecto.

Introduction: Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by the circumscribed atrophy of the frontal and temporal lobes along with progressive and insidious changes in behaviour and/or language impairment. Objective: To review FTD, emphasizing its genetic bases. Methods: Review of the current medical literature about the subject. Results: Families with a dominant autosomic inheritance pattern of this disease have been recently studied and different causal genes have been found, the most important being the microtubule associated protein tau gene and the progranulin gene, among others. Conclusions: It is important to consider a genetic approach in the assessment of a patient with FTD, investigating deeply into his family background. This way a proper genetic counseling can be performed thus solving the main doubts that the patient and relatives may have.

Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance / 中国实用内科杂志

Objective To investigate the expression of PC cell-derived growth factor(PCDGF or progranulin)and vascular endothelial growth factor(VEGF)and the relationships between them and clinicopathologic features in esophageal squamous cell carcinoma(ESCC),helping to determine the role of PCDGF(progranulin)and VEGF in angiogenesis.Methods The expression of PCDGF(progranulin)and VEGF in 50 surgical specimens from patients with ESCC and 20 with normal esophageal mucosa were detected by immunohistochemistry.The vascular endothelial cells in tumor tissue were labeled by antibody to CD105 for counting microvessel density(MVD).Results The expressions of PCDGF(progranulin)and VEGF in ESCC were obviously higher than normal mucosa.Their expression had positive correlation with depth of tumor invasion,lymph node metastasis,and TNM classification.In ESCC,both the expression level of PCDGF(progranulin)and VEGF had significant positive correlation with MVD and the expression of PCDGF had direct correlation with the expression of VEGF.Conclusion PCDGF marks tumor tissues with so high sensitivity that it can be a novel ESCC marker hopefully.The expression of both PCDGF(progranulin)and VEGF in ESCC has close relationship with angiogenesis,and they may take part in tumor growth,infiltration and metastasis through promoting tumor angiogenesis.