As a neuropeptide, neurotensin (NTS) is widely expressed in central and peripheral nervous system, which is mainly mediated byneurotensin receptor1 (NTSR1) to activate the related downstream signaling pathways. After summarized the function and mechanism of NTS/NTSR1 in various malignant tumors, we found that NTS/NTSR1 played essential roles during tumor initiation and development. NTS/NTSR1 regulates tumor initiation, proliferation, apoptosis, metastasis and differentiation mainly through three pathways, including IP3/Ca2+ /PKC/MAPKs pathway, MMPs/EGFR/MAPKs (PI3K/Akt) pathway, or Rho-GTPsaes and non-receptor tyrosine kinase pathway. Besides, NTS/NTSR1 is also regulated by some upstream pathways and some traditional Chinese medicine preparations and traditional Chinese medicine therapies. In this article, we summarized the function of NTS/NTSR1 and its mechanisms, and discussed the prospective in its application to clinical diagnosis and drugs targeting.
Animals ; Humans ; Medicine, Chinese Traditional ; Neoplasms ; etiology ; Neurotensin ; chemistry ; physiology ; Receptor, Epidermal Growth Factor ; physiology ; Receptors, Neurotensin ; chemistry ; physiology ; Signal Transduction ; physiology ; rhoA GTP-Binding Protein ; physiology

AIM:To investigate the effect of phosphatidylinostiol 3-kinase ( PI3K) inhibitor GDC-0032 on cell viability, cell cycle and DNA damage in human glioma U 251 cells.METHODS:The cell viability was analyzed by MTT assay.The cell cycle distribution of U251 cells was examined by flow cytometry .The protein expression was examined by Western blot.The expression and localization of γ-H2AX were determined by laser-scanning confocal microscopy .RE-SULTS:GDC-0032 inhibited the cell viability in a dose-dependent manner .U251 cells showed G 1 phase arrest accompa-nied with upregulation of p 27 protein after exposure to GDC-0032, while the expression of cell division cycle protein 2 (Cdc2) was inhibited.GDC-0032 treatment increased the formation of γ-H2AX foci and histone H2AX phosphorylation in the U251 cells.In addition, GDC-0032 upregulated the phosphorylation levels of mitogen-activated protein kinases , inclu-ding extracellular signal-regulated kinase ( ERK) and c-Jun N-terminal kinase ( JNK) , in the glioma cells , while the ex-pression of survivin was inhibited .CONCLUSION:GDC-0032 inhibits U251 cell growth by inhibition of cell viability and cell cycle progression.GDC-0032 also induces DNA damage of U251 cells.The anticancer activity of GDC-0032 is associ-ated with increasing the activity of ERK and JNK and downregulating the expression of survivin .

OBJECTIVETo study the expression level and significance of glucose transporter 1 (Glut-1) in normal breast tissue, adenosis, adenoma and breast carcinoma.

METHODSA total of 147 cases of female breast tissue samples, including 92 cases of invasive ductal carcinoma, 26 cases of breast fibroadenoma, 24 cases of breast adenosis and 5 cases of normal breast tissues, were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry (EnVision method) and Western blot, and its mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSIn normal breast tissue and benign lesions of the breast, Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia. In contrast, the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P = 0.0002) with protein expression predominantly in cellular membrane and lesser in cytoplasm. Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma (P =0.001 for protein; P <0.05 for mRNA) and adenosis (P =0.001 for protein; P < 0.05 for mRNA). There was a significant difference among groups (P = 0.0002 for protein; P = 0.0001 for mRNA).

CONCLUSIONSGlucose transport activity, as indicated by Glut-1 protein and its mRNA expression, significantly increases in breast carcinoma than non-cancerous lesions. The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation, invasion and metastasis, implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.

Breast Neoplasms ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; physiology ; Glucose Transport Proteins, Facilitative ; genetics ; metabolism ; Glucose Transporter Type 1 ; genetics ; metabolism ; Humans ; Prognosis

OBJECTIVETo study the relationship between Helicobacter pylori (Hp) infection and histopathological features of nodular gastritis (NG) in children.

METHODSA total of 213 children who had undergone gastroscopy due to upper gastrointestinal symptoms were enrolled and were divided into NG and non-NG groups according to endoscopic appearance. The histopathological features of gastric mucosa were evaluated using the updated Sydney System. The rates of Hp infection, moderate to severe inflammation and lymphoid follicles formation of gastric mucosa were compared between the two groups.

RESULTSThirty-eight (17.8%) of the subjects were diagnosed with NG. The NG group had significantly increased rates of Hp infection (86.8% vs 14.3%; P<0.01), moderate to severe inflammation (81.6% vs 15.4%; P<0.01) and lymphoid follicles formation of gastric mucosa (52.6% vs 10.3%; P<0.01) compared with the non-NG group. NG had a high specificity (96.8%) and a positive predictive value (86.8%) for the diagnosis of Hp infection. NG was observed in 33 (56.9%) of 58 Hp-positive children and in 5 (3.2%) of 155 Hp-negative children (P<0.01). Hp-positive children had higher rates of moderate to severe inflammation (86.2% vs 5.2%, P<0.01) and lymphoid follicles formation of gastric mucosa (84.2% vs 14.9% P<0.01) compared with Hp-negative children. There were significant differences in Hp colonization, degree of inflammation and inflammation activity in gastric tissues between the NG and non-NG groups (P<0.01).

CONCLUSIONSNG is a special sign of Hp infection in children, which mostly shows moderate to severe inflammation of gastric mucosa, and can be used as an endoscopic indicator of Hp infection. Hp eradication therapy should be considered in the treatment of NG.

Adolescent ; Child ; Child, Preschool ; Female ; Gastric Mucosa ; pathology ; Gastritis ; pathology ; Helicobacter Infections ; pathology ; Helicobacter pylori ; Humans ; Male

OBJECTIVETo evaluate the clinical value of sweat function examination in early diagnosis of diabetic peripheral neuropathy (DPN).

METHODSNinety-eight hospitalized type 2 diabetic patients with or without DPN (DN and DC groups) according to Michigan Diabetic Neruopathy Score (DNS) and 40 healthy volunteers (NC group) were evaluated for their sweat function of the feet in relation to the peripheral autonomic nerve with sweat printing method using Neuropad. The Neuropad color-changing time was recorded to assess the sensitivity and specificity of sweat printing methods relative to DNS for DNP evaluation, and the correlation of the Neuropad color-changing time to DNS score was analyzed.

RESULTSThe average Neuropad color-changing time was 4.0-/+0.6, 4.3-/+1.2 and 23.0-/+6.1 min in NC, DC, and DN groups, respectively, showing significant differences between the 3 groups (P<0.05). The morbidity rate detected by sweat printing method was 62.2%, similar to that detected by DNS (57.1%, P>0.05). The sensitivity of the sweat printing method for DPN diagnosis was 92.8%, with specificity of 78.5%, positive predictive value of 93.2%, and negative predictive value of 78.6%. DNS showed significant positive correlation with the Neuropad color-changing time (r=0.46, P<0.05).

CONCLUSIONSweat printing method provides an objective, simple and reliable method for sweat function evaluation of the feet of type 2 diabetic patients to help in early DPN diagnosis, and quantification of the results of sweat printing method can be indicative of the DPN severity.

Case-Control Studies ; Color ; Diabetic Neuropathies ; diagnosis ; physiopathology ; Early Diagnosis ; Foot ; physiopathology ; Humans ; Male ; Middle Aged ; Sweating ; physiology ; Time Factors

OBJECTIVETo analyze the association between hypertension and tobacco exposure Luoping county of Yunnan province and estimate the direct cost attributable to hypertension .

METHODSUsing Probability proportional to size (PPS) sampling method, 5000 rural residents aged over 18 years were selected from 12 townships in Luoping county, Yunnan province in April 2011, from which 4611 subjects completed the survey. Self-designed questionnaires were used to collect general information, smoking status, costs for outpatient consultation, inpatient, treatment, medication, travel, accommodation and extra-nutrition caused by hypertension as well as the information of health-related behavior. Their height, weight, waist circumference, hip circumference and blood pressure were measured. The direct economic burden of hypertension was calculated. Chi-square (χ(2)) test was used to compare gender differences of hypertension prevalence, smoking and passive smoking. And t test was used to compare the differences of direct economic burden of hypertension among different gender, smoking and passive smoking status. Multivariable logistic regression model was used to analyze the influence factors of hypertension.

RESULTSAmong the 4611 subjects, the age was (46.90 ± 16.74) years old. Male accounted for 49.8% (2294/4611) and female 50.2% (2317/4611) . The smoking rate was higher in males (75.7% (1736/2294)) than in females(1.6% (38/2317)) (χ(2) = 2669.21, P < 0.01). The passive smoking rate was lower in males (10.0% (230/2294)) than in females (46.2% (1070/2317)) (χ(2) = 744.27, P < 0.05). Non-tobacco exposure rate in males (14.3% (328/1537)) was lower than in females (52.2% (1209/1537)) (χ(2) = 744.37, P < 0.05) . The risk of hypertension in smokers and passive smokers were higher than those without tobacco exposure, OR (95%CI) was 1.41 (1.15-1.71) (P < 0.05) and 1.31 (1.07-1.63) (P < 0.05) respectively. The per capita direct cost of hypertension was (3444.09 ± 3067.83) Yuan. Of this, tobacco exposure (4552.46 ± 3189.05) Yuan was higher than non-tobacco exposure (1907.71 ± 1383.94) Yuan (t = -3.81, P < 0.05) . Moreover, smokers were (6951.71 ± 3422.87) Yuan higher than passive smokers (3128.09 ± 2083.17) Yuan (t = 3.19, P < 0.05) and males (5827.39 ± 3240.50) Yuan were higher than females (2633.03 ± 2569.01) Yuan (t = 3.22, P < 0.05) . The total direct costs of hypertension attributable to smoking and SHS was 41 million and 38 million, respectively.

CONCLUSIONBoth smoking and SHS had significant impact on prevalence and economic burden of hypertension in Luoping county. Implementing effective strategies to control tobacco exposure is useful to reduce the economic burden of hypertension in the study region.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Cost of Illness ; Female ; Humans ; Hypertension ; economics ; epidemiology ; Male ; Middle Aged ; Rural Population ; Tobacco Smoke Pollution ; economics ; statistics & numerical data ; Young Adult

Using Sepharose CL-6B as support, 3-Chloro-1, 2-epoxypropane as activated agent, carboxymethylated aspartate (CM-Asp) as chelating ligand, A chelate affinity chromatographic medium based on Co2+, named Co-CM-Asp-Sepharose, was prepared and used to purify 6 x His-tagged fusion proteins. The amount of Co-CM-Asp-Sepharose reacted with 200 microL of lysate, the incubation time, wash condition and the imidazole concentration in the elution buffer were optimized. The purification results using Co-CM-Asp-Sepharose and Ni-NTA-Agarose (product of Qiagen) were compared. The CD155D1 fusion protein was also purified from 5mL of lysate and the amount of protein was determined by Bradford method. The results show that 60 microL of Co-CM-Asp-Sepharose (50% suspension) was suitable for the protein purification from 200 microL of lysate, the optimal incubation time of medium and lysate was 30 min, the optimal imidazole concentration in the eluting buffer was 200 mmol/L, and 200 microg of fusion protein was obtained. In a big scale experiment, 4.6 mg of fusion protein was obtained from 5 mL of lysate using 1.5 mL of Co-CM-Asp-Sepharose (50% suspension). Compared with Ni-NTA-Agarose, the Co-CM-Asp-Sepharose medium exhibits higher selectivity and the protein possesses higher purity.
Aspartic Acid ; chemistry ; Chelating Agents ; chemistry ; Chromatography, Affinity ; methods ; Epoxy Compounds ; chemistry ; Histidine ; biosynthesis ; chemistry ; genetics ; Polymers ; chemistry ; Recombinant Fusion Proteins ; isolation & purification ; Sepharose ; chemistry

OBJECTIVESTo evaluate the efficacy of a hybrid artificial liver support system in the treatment of chronic severe hepatitis.

METHODSThe hybrid artificial liver support system (HALSS) consisted of a bioreactor containing more than 5 x 10(9) porcine hepatocytes and plasma exchange device. 15 patients with chronic severe viral hepatitis were treated with the hybrid system.

RESULTSAll the patients experienced a reduction in symptoms, such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly (from 493.5 micromol/L+-139.8 micromol/L to 250.9 micromol/L+-91.3 micromol/L, t=8.695, P<0.001), while prothrombin activity increased (from 24.5%+-8.4% to 30.6%+-6.3%, t=3.325, P<0.01). There were 11 patients whose progress of hepatocytes necrosis stopped after HALSS treatment, and finally they recovered completely. Four patients died of their worsen conditions. No serious adverse events were noted in the 15 patients.

CONCLUSIONHALSS is a reliable hepatic support device for chronic severe hepatitis.

Adult ; Animals ; Animals, Newborn ; Bioreactors ; Female ; Hepatitis B, Chronic ; complications ; therapy ; Humans ; Liver Failure ; therapy ; Liver, Artificial ; Male ; Middle Aged ; Plasma Exchange ; instrumentation ; methods ; Swine ; Swine, Miniature ; Treatment Outcome

AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis (AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D3 (VD3) and feeding with high-fat diet.The rats were randomly divided into normal control group, AS model group, positive medicine group and urantide group.The liver function indexes of the rats were measured by biochemical test, and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin (HE) staining.The mRNA expression of urotensinⅡ (UII) and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot.RESULTS:The levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , γ-glutamyltransferase (γ-GT) , lactate dehydrogenase (LDH) , total bilirubin (TBIL) , indirect bilirubin (IBIL) and alkaline phosphatase (ALP) in AS model group were significantly increased compared with normal control group (P<0.05).The above indexes in urantide group were remarkably decreased compared with AS model group (P<0.05).No change of the levels of direct bilirubin (DBIL) , total protein (TP) , globulin (GLB) and albumin (ALB) in each group was observed.Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats.Compared with normal control group, the mRNA and protein levels of UII and GPR14 in the liver were significantly increased in AS model group (P<0.05).With the prolongation of dosing time, the mRNA and protein levels of UII and GPR14 in the liver were significantly decreased in urantide group compared with AS model group (P<0.05).CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.

Langerhans cell histiocytosis (LCH) is a rare proliferative disease dominated by the proliferation of Langerhans cells, which is inflammatory myeloid neoplasms. Its clinical manifestations are variable, occurring at any age and at any site, and it is rarer in adults than in children. The gold standard for diagnosis is histopathological biopsy. Due to the rarity of adult LCH and the heterogeneity of this disease, treatment of adult LCH should be developed according to the extent of the disease and risk stratification. With the discovery of MAPK, PI3K and c-KIT signaling pathway activation, especially BRAF V600E and MAP2K1 mutations, targeted therapy has become a hot spot for therapeutic research. Meanwhile, the discovery of high expression of M2-polarized macrophages and Foxp3⁺ regulatory T cells (Treg) in LCH has provided an important basis for the immunotherapy. In this article, we will focus on reviewing the latest research progress in the treatment of adult LCH in recent years, and provide a reference for clinical research on the treatment of adult LCH patients.
Adult ; Child ; Histiocytosis, Langerhans-Cell/therapy* ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf/metabolism* ; Signal Transduction ; T-Lymphocytes, Regulatory/pathology*