Arf6 as a therapeutic target: Structure, mechanism, and inhibitors

ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.

miRNA-mediated regulation of auxin signaling pathway during plant development and stress responses

Auxin is one of the most important plant growth hormones, playing a crucial role in development as well as instress responses. Auxin biosynthesis and signaling pathway comprises a series of events including auxinperception by the receptor, activation, and function of auxin response factors and control by auxin repressors.All these factors are regulated by several different microRNAs during leaf, flower and fruit development,anther development, nodulation, lateral and adventitious root development, potato tuber development as wellas during heat stress, submergence, boron toxicity, aluminium stress responses, etc., as depicted in the availableliterature. In this review a thorough study on miRNA-mediated regulation of auxin biosynthesis and signalinghas been done in various plant species. The data gathered can be utilized to point out the particular miRNAmediated regulation module which can be utilized to modulate the expression of the miRNA and therebymodulation of the auxin pathway. Information in this review would be beneficial to utilize the miRNAexpression to generate the protocol for engineering plants with altered auxin signaling pathway to obtain betteryield and improved stress tolerance.

Effects and mechanism of high ARNO expression on the permeability of human renal glomerular endothelial cells under high glucose condition / 解放军医学杂志

Objective: To explore the effects and mechanism of high expression of ARNO (ARF nucleotide-binding-site opener) on the permeability of human renal glomerular endothelial cells (HRGECs) under high glucose conditions. Methods: HRGECs were cultured in vitro, and ARNO expression and endothelial permeability were detected in high glucose time gradient (15, 30, 45 and 60 min) and concentration gradient (10, 20, 30 and 40 mmol/L) experiments, respectively. Cell lines of HRGECs with ARNO and Arf6 gene silencing were obtained by infecting HRGECs with ARNO siRNA and Arf6 siRNA recombinant lentivirus vectors, respectively. The effects of ARNO and Arf6 gene silencing on endothelial permeability were observed. Results: In the time gradient experiments, compared with control group, ARNO expressions increased significantly in the groups with high glucose for 15, 30, 45 and 60 min (0.670±0.051, 0.960±0.106, 0.716±0.026, 0.531±0.030 vs. 0.242±0.029. P<0.05). Compared with high glucose 15 min group, ARNO expression increased in high glucose 30 min group (P<0.05); Compared with high glucose 30 min group, ARNO expression decreased in high glucose 45 min group (P<0.05); Compared with high glucose 45 min group, ARNO expression decreased in high glucose 60 min group (P<0.05). Compared with control group, endothelial permeability increased significantly in the groups with high glucose for 15, 30, 45 and 60 min (1.196±0.004, 1.399±0.012, 1.301±0.052, 1.184±0.030 vs. 1.000, P<0.05). Compared with high glucose 15 min group, endothelial permeability increased in high glucose 30 min group (P<0.05); Compared with high glucose 30 min group, endothelial permeability decreased in high glucose 45 min group (P<0.05); Compared with high glucose 45 min group, endothelial permeability decreased in high glucose 60 min group (P<0.05). In the concentration gradient experiments, compared with normal concentration glucose group, ARNO expressions increased significantly in the groups with high glucose of 20, 30 and 40 mmol/L (0.632±0.031, 0.927±0.041, 1.183±0.098 vs. 0.169±0.033, P<0.05), and the ARNO expression level was increased along with the increase of glucose concentration (P<0.05). Compared with normal concentration glucose group, endothelial permeability increased significantly in the groups with high glucose of 10, 20, 30 and 40 mmol/L (1.147±0.015, 1.237±0.023, 1.351±0.015, 1.444±0.019 vs. 1.000, P<0.05), and the endothelial permeability increased along with the increase of glucose concentration (P<0.05). After transfection with lentivirus, compared with normal concentration glucose untransfected group and normal concentration glucose empty vector group, ARNO mRNA transcription reduced significantly (0.255±0.056 vs. 1.000, 1.183±0.297), and ARNO protein expression also reduced significantly (0.088±0.005 vs. 0.246±0.011, 0.237±0.009) in normal concentration glucose ARNO siRNA group (P<0.05). In addition, compared with those groups, Arf6 mRNA transcription was reduced significantly (0.314±0.090 vs. 1.000, 1.140±0.236), and Arf6 protein expression was also reduced significantly (0.690±0.012 vs. 0.917±0.009, 0.919±0.009) in the normal concentration glucose Arf6 siRNA group (P<0.05). After silencing ARNO, compared with high-glucose untransfected group and high-glucose empty vector group, the ARNO protein expression was reduced significantly (0.572±0.021 vs. 0.915±0.005, 0.916±0.012), Arf6 activity was reduced significantly (0.263±0.007 vs. 0.484±0.014, 0.490±0.008), and endothelial permeability was also decreased (0.718±0.017 vs. 1.000, 0.978±0.040) in high-glucose ARNO siRNA group (P<0.05). Besides, after silencing Arf6, compared with high-glucose untransfected group and high-glucose empty vector group, Arf6 protein expression was reduced significantly (0.673±0.015 vs. 0.932±0.020, 0.899±0.022), and endothelial permeability was also decreased (0.768±0.050 vs. 1.000, 0.978±0.040) in high-glucose Arf6 siRNA group (P<0.05). Conclusion: High-glucose induced high permeability of HRGECs is related to the activation of ARNO/Arf6 signal, and inhibition of ARNO expression and Arf6 activity may inhibit the glomerular endothelial hyperpermeability in diabetic nephropathy, and is expected to be a new direction for the treatment of glomerular endothelial dysfunction in diabetic nephropathy.

Epigallocatechin gallate induces gene demethylation to promote acute myeloid leukemia cell apoptosis by regulating p19-p53-p21 signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which epigallocatechin gallate (EGCG) induces gene demethylation and promotes the apoptosis of acute myeloid leukemia KG-1 and THP-1 cell lines.@*METHODS@#KG-1 and THP-1 cells treated with 25, 50, 75, 100 or 150 μg/mL EGCG for 48 h were examined for gene methylation using MSP and for cell proliferation using MTT assay. The changes in cell cycle and apoptosis of the two cell lines after treatment with EGCG for 48 h were detected using flow cytometry. The mRNA and protein expressions of DNMT1, CHD5, p19, p53 and p21 in the cells were detected using RT-quantitative PCR and Western blot.@*RESULTS@#EGCG dose-dependently reversed hypermethylation of gene and reduced the cell viability in both KG-1 and THP-1 cells ( < 0.05). EGCG treatment caused obvious cell cycle arrest in G1 phase, significantly increased cell apoptosis, downregulated the expression of DNMT1 and upregulated the expressions of CHD5, p19, p53 and p21 in KG-1 and THP-1 cells ( < 0.05).@*CONCLUSIONS@#EGCG reduces hypermethylation of gene in KG-1 and THP-1 cells by downregulating DNMT1 to restore its expression, which results in upregulated expressions of p19, p53 and p21 and induces cell apoptosis.

Cytotoxic Effects of Xanthohumol and Its Combination with Cisplatin on Human Metastatic Lung Cancer H1299 Cells

Aims:Non-small cell lung cancer (NSCLC) accounts for high lung cancer death that is mostly associated with advanced disease stage at diagnosis and resistance to chemotherapy. In the present study, we investigated whether xanthohumol, a prenylated flavonoid of hop plant, induces metastatic lung cancer H1299 cell death, and whether in combination with cisplatin there are additive effects. Methodology:H1299 cells were grown and treated with xanthohumol (6.25, 12.5, or 25 μM), cisplatin (12.5, 25, or 50 μM) and the combination of cisplatin and xanthohumol for 24 h. Cell viability, cell morphology, chromatin condensation, ɣH2AX, cPARP-1, capsase-3, p21WAF1/CIP1and p14ARFgenes were analyzed Results:Xanthohumol, cisplatin, and the combination of cisplatin and xanthohumol inhibited H1299 cells viability. Cisplatin growth inhibitory effects were potentiated by xanthohumol. Xanthohumol induced chromatin condensation and apoptosis and potentiated cisplatin’s effect vs cisplatin alone. Further investigation of growth inhibitory effects, xanthohumol alone induced γH2AX foci formation and the combination potentiated γH2AX foci formation. Cisplatin, xanthohumol at 25 μM, and the combination of cisplatin and xanthohumol at 6.25 and 12.5 μM increased cPARP-1 level. Active caspase-3 was increased by cisplatin, 12.5 μM of xanthohumol, and the combination of xanthohumol and cisplatin. Xanthohumol at 6.25 or 12.5 μM potentiated cisplatin effect on active caspase-3 and cPARP-1, respectively. Xanthohumol at 25 μM significtly induced the expression cell cycle control genes p21WAF1/CIP1and p14ARF. These results indicate that xanthohumol inhibits proliferation of H1299 cells and induces cell death through cleavage of PARP-1 and activation of caspase-3. The combination of cisplatin and xanthohumol potentiated cytotoxic effects of each other compound.Conclusion:The present study suggests that xanthohumol poses apoptotic effects and potentiates cisplatin’s growth inhibitory effects on metastatic lung cancer cells

A clinical observational study in cases of eclampsia

Background: Eclampsia is a life threatening condition and one of the leading causes of maternal deaths worldwide. It is also associated with complications like acute renal failure, DIC, postpartum hemorrhage, etc. and adverse fetal outcomes.  Hence we aimed to study fetomaternal outcomes in cases of Eclampsia.Methods: A total of 75 cases of eclampsia out of 13524 deliveries were evaluated, from 1st January 2016 to 30th June 2017 at RZ Hospital, a government tertiary referral centre. Maternal outcomes were studied for its complications, effectiveness of magnesium sulphate treatment, fetal outcome and mode of delivery.Results: Incidence rate of eclampsia was 0.55%, 62.66% of all cases were primigravida, 76% of cases were in age group of 21-26 years, 84% cases were from lower socio economic status, maternal mortality occurred in 2 of 75 cases. 66.67% of patients were of term pregnancy (37 to 42 weeks). 71%(53) patients delivered vaginally out of which 9 deliveries were spontaneous and 44 deliveries were induced vaginal delivery. 22 patients required caesarean section.Conclusions: Early detection and prevention of pregnancy induced hypertension and pre-eclampsia and other associated risk factors for eclampsia might help to reduce the incidence of eclampsia. Maternal adverse outcomes in this study were magnesium toxicity, acute renal failure (ARF), disseminated intravascular coagulation (DIC) and post partum hemorrhage (PPH) while 92% patients had no complications.

Sequential Organ Failure Assessment (SOFA) score in predicting morbidity and mortality in community and hospital acquired acute renal failure patient requiring dialysis

Background: The Sequential Organ Failure Assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study was planned to compare outcome and organ failure status of community (CAARF) and hospital acquired acute renal failure (HAARF) patients requiring dialysis using SOFA score.Methods: The present prospective observational study was conducted on fifty consecutive acute renal failure patients age more than 18 years of either sex requiring dialysis. Patients who developed ARF after 24 hours of admission were referred as HAARF and patients who had acute renal failure on admission were considered as CAARF. The Sequential Organ Failure Assessment (SOFA) score was used to track a patient's status during the stay in an intensive care unit in both HAARF and CAARF patients.Results: Out of 50 patients, 31(62%) patients had community acquired renal failure and 19 (38%) patients had hospital acquired renal failure. Mean SOFA in HAARF patients was high (8.84±3.13) compare to CAARF patients (6.16± 2.80). The p value calculated was 0.003 which was significant. High SOFA Score (>11) were seen predominantly in HAARF (83.3%) patients compare to CAARF (16.7%), followed by 57.1% of patients in HAARF and 42.9% of patients in CAARF had SOFA score between 9 to11.Conclusions: High SOFA Score were seen predominantly in HAARF patients compare to CAARF and so poor outcome compare to CAARF. So, SOFA score may be used in explaining prognosis and outcome of ARF patients.

Ayurvedic Management Of Rheumatic Fever: A Successful Case Report

Rheumatic fever is a rare but potentially life-threatening disease that may occur as complication of untreated infection caused by bacteria called group Astreptococcus. The main clinical features are -fever, myalgia, swollen and painful joints, and in some cases, a red, grille like rash typically manifest two to four weeks after a bout of streptococcal infection. In some cases, though, the infection might be too mild to recognize clinically. A 27year old male case was admitted in SSANH on 27/5/2015 with following chief complaints - severe pain and stiffness over multiple joints symmetrically since 2years, swelling of larger joints of both upper and lower limbs symmetrically since 2 years and recurrent episodes of fever accompanied with dyspnoea and body pain. The case was diagnosed as Rheumatic fever and treated with Rasnasapthakamkashayam, Rasasindhooram, Yogarajaguggulu as main internal medications and treatments like choornakizhi, Choornavasthi and Lavana Kizhi. The Ayurvedic management provided better relief in subjective and as well as objective parameters.

Bioinformatics analysis and expressed level of Auxin response factor genes in Scutellaria baicalensis / 药学学报

Auxin response factor (ARF) is an important transcription factor for auxin signal transduction pathway, which regulates virtually every aspect of plant growth and development from embryogenesis to senescence. Nine full-length genes of ARF transcription factors were obtained from transcriptome dataset of Scutellaria baicalensis Georgi using the bioinformatics methods. The nucleotide and protein characteristics, subcellular localization, senior structural domains and conservative forecasts of those ARF transcription factors were analyzed. The phylogenetic tree showed that the nine ARFs in S. baicalensis were clustered together with ARF transcription factors in Arabidopsis thaliana, Oryza sativa subsp. Japonica and Nicotiana attenuate. The results of gene expression showed that:① The expression levels of ARF1, ARF3, ARF4, ARF8, ARF20 and ARF24 were upregulated after 100 μmol·L-1 GA3 treatment. However, the expression levels of ARF6 and ARF18 were downregulated; ② Those ARF genes were mainly expressed in the flowers of S. baicalensis; ③ There was a significant correlation between ARF genes and the genes involved in flavonoid biosynthesis. Our results provide a basis for further understanding the molecular regulation mechanism of flavonoid biosynthesis in S. baicalensis.

Over-expression of ROBO4 reduces permeability of human renal glomerular endothelial cells in high glucose medium / 解放军医学杂志

Objective To investigate the effect of over-expression of ROBO4 on permeability of human renal glomerular endothelial cells (HRGECs) in high glucose medium.Methods HRGECs infected with recombinant lentiviral vector ROBO4 were cultured in high glucose or low glucose medium in vitro.The protein levels of ROBO4 and ARF6 in each group were detected by Western blotting.The endothelial permeability was measured by the effiux of fluorescein isothiocyanate-dextran (FITC-Dextran)permeated through the monolayer endothelial cells using Transwell cell model system.The cell viability after lentivirus transfection was measured by CCK8 assay.Results The transfection rate of lentiviruses in HRGECs reached 80％ 72h after,and obvious overexpression of ROBO4 protein was in transformed cells compared with the empty vector group (P＜0.05).The lentivirus-mediated ROBO4 transfection did not affect cell viability of HRGECs.Compared with the low glucose group,the expression of ROBO4 increased obviously after 12h,but declined after 24h (P＜0.05),and reached to minimun after 72h (P＜0.05).On the contrary,the expression of ARF6 increased after 12h,and the increase reached to the maximum after 72h (P＜0.05).Furthermore,the vascular permeability increased gradually after 24h,and reached to the maximum after 72h (P＜0.05) in high glucose group.Compared with the empty vector group,the over-expression of ROBO4 inhibited the expression of ARF6 significantly,and the FITC-Dextran permeability reduced obviously.Conclusion Over-expression of ROBO4 may significantly enhance the barrier functions of HRGEC in high glucose medium,and ROBO4 activation may be a potential therapeutic approach in diabetic nephropathy.

Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis

Endocytosis is a process by which cells absorb extracellular materials via the inward budding of vesicles formed from the plasma membrane. Receptor-mediated endocytosis is a highly selective process where receptors with specific binding sites for extracellular molecules internalize via vesicles. G protein-coupled receptors (GPCRs) are the largest single family of plasma-membrane receptors with more than 1000 family members. But the molecular mechanisms involved in the regulation of GPCRs are believed to be highly conserved. For example, receptor phosphorylation in collaboration with β-arrestins plays major roles in desensitization and endocytosis of most GPCRs. Nevertheless, a number of subsequent studies showed that GPCR regulation, such as that by endocytosis, occurs through various pathways with a multitude of cellular components and processes. This review focused on i) functional interactions between homologous and heterologous pathways, ii) methodologies applied for determining receptor endocytosis, iii) experimental tools to determine specific endocytic routes, iv) roles of small guanosine triphosphate-binding proteins in GPCR endocytosis, and v) role of post-translational modification of the receptors in endocytosis.

Expression and clinical significance of ROBO4/ARF6 signal pathway in renal glomerulus tissue of patients with diabetic kidney disease / 解放军医学杂志

Objective To investigate the expression of ROBO4/ARF6 and its correlation to glomerular endothelial cells (MGECs) permeability at each pathological stage of diabetic kidney disease (DKD). Methods Thirty patients with DKD were enrolled (patient group), and their renal tissues obtained by biopsy were divided into incipient, manifest and advanced stages (10 each) with Tervaert pathological staging, and confirmed normal renal tissues adjacent to the renal angiomyolipoma were assigned as control group. Immunohistochemistry method of MaxVision was used to detect the expression of ROBO4/ARF6 in the specimens, and then the correlation of the expression with the clinicopathological parameters (patients' HbA1c, albuminuria, serum creatinine, eGFR) were determined using statistical software SPSS 21.0. Results ROBO4 was abundantly but ARF6 rarely expressed in normal MGECs. In DKD patients, ROBO4 was mainly expressed in MGECs, while ARF6 was expressed in both MGECs and renal tubular epithelial cells. Compared with the control group, the positive intensity of ROBO4 in patient group decreased significantly (P0.05), but was positively correlated with 24h-urinary albumin (r=0.603, P<0.01) and HbA1c (r=0.582, P<0.01). Conclusion The low expression of ROBO4 and high expression of ARF6 in MGECs of DKD patients suggest that ROBO4/ARF6 signaling pathway may participate in the DKD glomerular endothelial and vascular pathological injury and urinary protein increase.

Clinical profile of pregnancy related acute renal failure: An experience at a tertiary level hospital in Mumbai

Background: Pregnancy-related acute renal failure (ARF) can be caused by any of the disorders leading to ARF in the general population. We aimed to study the clinical profile of pregnancy related acute renal failure, management and clinical outcomes. Materials and methods: After obtaining ethical committee’s approval, a prospective observational study was carried out on hospitalized patients in our hospital from 1st August 2007 till 30th September 2008, where all pregnant females referred to nephrology unit were enrolled. Results: A total of 41 patients were included in the study in which oliguria was the commonest symptom (58.53%). Fluid overload was the most common complication encountered (33.33%). Respiratory system involvement was associated with increased mortality. No correlation between serum creatinine level and mortality was observed. Neonatal deaths were seen in 2.43% of patients while IUFD was seen in 19.51% of patients. Conclusions: Incidence of PR-ARF is still high in our country as compared to western countries. Multigravidas were more commonly affected than primigravidas. More than two organ involvement was associated with higher mortality and majority of the patients were treated conservatively. Maternal and fetal mortality were high, 17.07% and 2.43% respectively.

Serum Creatinine, Urea and Their CD4+ T-lymphocyte Count among HIV Positive Patients before and after Initiation of HAART at St. Paul’s General Specialized Hospital In Addis Ababa, Ethiopia.

Objective: To describe the serum level of urea and creatinine, and as well as CD4+ T cell count of blood among HIV positive patients before and after initiation of HAART in St. Paulo’s general specialized hospital. Methods: A retrospective follow up study was conducted among HIV infected individuals who take HAART drug combination regimens such as (TDF/3TC/EFV), (TDF/3TC/NVP), (AZT/3TC/NVP), (D4T/3TC/EFV) and (D4T/3TC/NVP) and visit St. Paulo’s generalized hospital laboratory for renal function testing from 2007-2009G.C. Results: A total of 2026 HIV positive patients started HAART between 2007-2009G.C in St. Paulo’s ART clinic. Among them 380 HIV patients, with two and three visits for CD4+ and renal function test (creatinine & urea), were recruited to the study. Of whom 240 (63.2%) were female and 140(36.8%) male. Out of 380 patients, 104(27.4%) were taking 1b30, 94(24.7%) were using 1a30, 77(20.3%) were taking 1d, 57(15%) 1c, 14(3.7%) tdf/3tc/efv, 12(3.2%) use tdf/3tc/nvp and 22(5.7%) were taking other drug types. The statuses of CD4+ T cell count of patients become improved as they are using HAART drug through visit. These were 115, 266 and 298 out of 380 have greater than 200 CD4+ T cell count on 6th, 12th, 18th months time difference respectively. But the numbers of patients who have renal dysfunction were increased as they were using HAART drug as treatment through visits. These might indicate that, use of HAART drug combination may improve the immune status HIV positive patients even though some renal side effects are there. Therefore, patients (HAART drug user) should have a follow up on renal function to monitor side effects of drug. Conclusion: HAART resulted in improved Immune status of HIV patients with remarkable increase in CD4 T lymphocyte count but at the same time there was an increase in Azotemia after the introduction part of HAART which suggests the impact of drug in renal function. This is especially true for TDF containing drug regimens (TDF/3TC/NVP) which dramatically improve CD4 T lymphocyte count and show significant Azotemia over times.

Expression and prognostic role of ADP-ribosylation factor 6 in human endometrial carcinoma / 中华内分泌外科杂志

Objective To investigate the expression and prognostic role of ADP-ribosylation factor 6 (ARF6) in human endometrial carcinoma.Methods 51 endometrial carcinoma tissues and matched tumor-adjacent tissues were collected from Jan.2010 to Dec.2011 in People's Hospital of Linzi District of Zibo City and Penglai People's Hospital.mRNA expression of ARF6 was detected by qRT-PCR,and the protein expression of ARF6 was detected by immunohistochemistry.The correlation between ARF6 and clinicopathological features was analyzed by chi-square test,and the Kaplan-Meier survival curves were drawn to describe the prognostic effects of ARF6 expression.Results Both mRNA and protein expression of ARF6 were down-regulated in endometrial carcinoma tissues than those in matched tumor-adjacent tissues (P＜0.05).Positive expression of ARF6 was associated with lynphatic metastasis (P＜0.05) and advanced TNM stage (Ⅲ+Ⅴ,P＜0.05).Both the 3-year overall survival rate and disease-free survival rate were lower in ARF6 positive expression group than in ARF6 negative expression group(P＜0.05).Conclusion Positive expression of ARF6 in human endometrial carcinoma is related to the malignant clinicopathological features and poor prognosis.

Expressions of antisense non-coding RNA in INK4 locus and tumor suppressors in peripheral blood lymphocytes of patient with cirrhosis and hepatocellular carcinoma / 中国中西医结合急救杂志

Objective To investigate the clinical diagnostic and differential diagnostic values of antisense non-coding RNA in the INK4 locus (ANRIL) and tumor suppressors (p14ARF, p15INK4b and p16INK4a) mRNA expression levels in peripheral blood lymphocytes of patients with cirrhosis and hepatocellular carcinoma. Methods The patients with hepatocellular carcinoma and cirrhosis admitted in Shantou Central Hospital from October 2013 to April 2014 were selected. The real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect ANRIL, p14ARF, p15INK4b and p16INK4a mRNA expression levels of peripheral blood lymphocytes. The subjects having taken physical health examinations in outpatient clinics were assigned in the healthy control group. Results During the study period, 19 cases of hepatocellular carcinoma, 24 cases of cirrhosis, and 31 healthy controls were finally enrolled. In the hepatocellular carcinoma group, the mRNA expression level of ANRIL was significantly higher than that of the healthy control group (?Ct:13.07±0.62 vs. 12.45±0.84, P0.05). There were also no statistically significant differences in p14ARF and p16INK4a mRNA expressions among the three groups (all P>0.05). Conclusion The elevation of ANRIL and descent of p15INK4b mRNA expression levels in peripheral blood lymphocytes in patients with liver lesion can be used as the reference indicators for the early diagnosis of hepatocellular carcinoma and to predict their prognoses.

Expression of Bmi-1, p14 ARF and Mdm2 and their clinical significance in colorectal carcinoma / 临床与实验病理学杂志

Purpose To explore the expression of Bmi-1, p14ARF and Mdm2 in colorectal carcinoma and to find out their association with clinicopathological features. Methods The expression of Bmi-1, p14ARF and Mdm2 was detected by immunohistochemistry in 125 cases of colorectal carcinoma and 20 cases of normal colorectal tissues. Results ( 1 ) The positive rates of Bmi-1 and Mdm2 were 56. 8% and 62. 4% in colorectal carcinoma, respectively, which were much higher than that in normal colorectal tissues (20. 0% and 15. 0%). The positive rates of p14ARF was 47. 2% in colorectal carcinoma, which was much lower than that 75. 0% in normal colorec-tal tissues ( P<0. 05 ) . ( 2 ) The expression of Bmi-1 was significantly correlated with serosal invasion, lymph node metastasis and Dukes stage. The expression of p14ARF was significantly correlated with serosal invasion and Dukes stage. The expression of Mdm2 was significantly correlated with histologic grade, lymph node metastasis and Dukes stage (P<0. 05). (3) In colorectal carcinoma, the expression of Bmi-1 and Mdm2 was negatively correlated with p14ARF, respectively (P<0. 05). Conclusions Abnormal expression of Bmi-1, p14ARF and Mdm2 is involved in the occurrence, development and metastasis of colorectal carcinoma, which could be as the reference factors in judgement of biological behavior and provide a new target for clinical treatment.

Research progress of p14ARF in cervical carcinoma and cervical intraepithelial neoplasia / 肿瘤研究与临床

Cervical cancer is one of the most common gynecological malignancies and is the only one which has certain pathogenesis in all malignancies currently.p14ARF is one of the tumor suppressor gene discovered recently and highly expressed in almost all cervical cancer.p14ARF has high specificity and sensitivity and it is related to invasion and prognosis of cervical cancer.Therefore,p14ARF is an ideal maker that can be used to early diagnose,screening precancerous lesions and predict prognosis in cervical cancer.

Isolation and analysis of differentially expressed genes from peanut in response to challenge with Ralstonia solanacearum

Background: Bacterial wilt caused by Ralstonia solanacearum is the most devastating disease in peanut. Planting resistant peanut cultivars is deemed as the sole economically viable means for effective control of the disease. To understand the molecular mechanism underlying resistance and facilitate breeding process, differences in gene expression between seeds of Rihua 1 (a Virginia type peanut variety resistant to bacterial wilt) inoculated with the bacterial pathogen suspension (10(9) cfu ml-1) and seeds of the same cultivar treated with water (control), were studied using the GenefishingTM technology. Results: A total of 25 differentially expressed genes were isolated. Expression of genes encoding cyclophilin and ADP-ribosylation factor, respectively, were further studied by real time RT-PCR, and full length cDNAs of both genes were obtained by rapid amplification of cDNA ends. Conclusions: The study provided candidate genes potentially useful for breeding peanut cultivars with both high yield and bacterial wilt resistance, although confirmation of their functions through transgenic studies is still needed.

Cyclooxygenase-2 and hypoxia-regulated proteins are modulated by basic fibroblast growth factor in acute renal failure

Acute renal failure (ARF) can be caused by injuries that induce tissue hypoxia, which in turn can trigger adaptive or inflammatory responses. We previously showed the participation of basic fibroblast growth factor (FGF-2) in renal repair. Based on this, the aim of this study was to analyze the effect of FGF-2 signaling pathway manipulation at hypoxia-induced protein levels, as well as in key proteins from the vasoactive systems of the kidney. We injected rat kidneys with FGF-2 recombinant protein (r-FGF) or FGF-2 receptor antisense oligonucleotide (FGFR2-ASO) after bilateral ischemia, and evaluated the presence of iNOS, EPO and HO-1, in representation of hypoxia-induced proteins, as well as COX-2, renin, kallikrein, and B2KR, in representation of the vasoactive systems of the kidney. A reduction in iNOS, HO-1, EPO, renin, kallikrein, B2KR, and in renal damage was observed in animals treated with r-FGF. The opposite effect was found with FGF-2 receptor down-regulation. In contrast, COX-2 protein levels were higher in kidneys treated with r-FGF and lower in those that received FGFR2-ASO, as compared to saline treated kidneys. These results suggest that the protective role of FGF-2 in the pathogenesis of ARF induced by I/R is a complex process, through which a differential regulation of metabolic pathways takes place.