Association between index finger and ring finger length ratios and polymorphism of homeobox A11 gene locus among Ningxia college students / 解剖学报

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Effects of electroacupuncture at "Jiaji" (EX-B 2) combined with neurodynamic mobilization on gastrocnemius muscle atrophy and expression of NF-κB and MuRF1 in rabbits after sciatic nerve injury / 中国针灸

OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1).@*METHODS@#A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected.@*RESULTS@#After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05).@*CONCLUSIONS@#Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.

RNF43 inhibits PD-L1 expression via β-catenin in melanoma cells and promotes CD8 + T cell-mediated anti-tumor immune reaction / 国际肿瘤学杂志

Objective:To investigate the regulatory effects of ring finger protein 43 (RNF43) on CD8 + T cell-mediated anti-tumor immune reaction in melanoma. Methods:RNF43 gene was over-expressed and knockdown in mouse melanoma cells line B16-OVA by lentivirus infection; In vivo proliferation of mouse melanoma cells line B16-OVA in the Lv-Ctrl-OE, Lv-RNF43-OE, Lv-Ctrl-KD and Lv-RNF43-KD groups was detected by subcutaneous tumorigenesis assay in mice, and the expression levels of CD8 + T cells perforin and interferon γ (IFN-γ) in tumor immune microenvironment of melanoma were detected by flow cytometry; The expression levels of β-catenin and programmed death-ligand 1 (PD-L1) mRNA in cells were detected by quantitative real-time PCR assay; The effect of RNF43 on the transcriptional regulation of PD-L1 was detected by dual-luciferase reporter gene assay. Results:Stable RNF43 over-expressing and RNF43 knockdown mouse melanoma cells lines Lv-RNF43-OE and Lv-RNF43-KD were successfully constructed. The results of subcutaneous tumorigenesis experiment in mice showed that the tumor mass of the Lv-RNF43-OE group was (0.08±0.06) g, which was significantly smaller than that of the Lv-Ctrl-OE group [ (1.04±0.52) g], with a statistically significant difference ( t=3.71, P=0.032) ; The tumor mass of Lv-RNF43-KD group was (1.94±0.29) g, with no statistically significant difference ( t=-1.70, P=0.164) compared with that of the Lv-Ctrl-KD group (1.15±0.74) g. The flow cytometry results showed that the fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-OE group was 9 034 ± 2 628, which was significantly higher than that in the Lv-Ctrl-OE group (3 847 ±1 637), with a statistically significant difference ( t=-3.35, P=0.015) ; The fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-KD group was 966±247, which was significantly lower than that in the Lv-Ctrl-KD group (2 226±646), with a statistically significant difference ( t=3.16, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-OE group was 2 422±429, which was significantly higher than that of 1 688±324 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=-2.73, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-KD group was 614 (454, 863), with a statistically significant difference ( Z=-1.96, P=0.050) compared with 1 159 (1 152, 2 068) in the Lv-Ctrl-KD group. The results of quantitative real-time PCR showed that the relative expression level of β-catenin mRNA in the Lv-RNF43-OE group was 0.67±0.16, which was significantly lower than that of 1.00±0.11 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=2.98, P=0.041) ; The relative expression level of PD-L1 mRNA in the Lv-RNF43-OE group was 0.32±0.09, which was significantly lower than that of 1.00±0.09 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=9.13, P=0.001). The results of the dual-luciferase reporter gene assay showed that the PD-L1 promoter luciferase activity in the pCMV6-NC, RNF43, RNF43+β-catenin and β-catenin groups were 1.00±0.00, 0.84±0.00, 1.49±0.00 and 1.57±0.03 ( F=2 218.33, P<0.001). Further pairwise comparison showed that compared with the pCMV6-NC group, PD-L1 promoter luciferase activity was significantly lower in the RNF43 group ( P<0.001) and significantly higher in the RNF43+β-catenin and β-catenin groups ( P<0.001; P=0.003) ; compared with the RNF43 group, PD-L1 promoter luciferase activity was significantly higher in the RNF43+β-catenin group ( P<0.001) . Conclusion:RNF43 may reduce the expression of PD-L1 mRNA in melanoma by inhibiting the expression of β-catenin and promote CD8 + T cell-mediated anti-tumor immune reaction.

Effects of ring finger and tryptophan-aspartic acid 2 on dendritic spines and synapse formation in cerebral cortex neurons of mice / 南方医科大学学报

OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.

Effect of silencing ring finger protein 187 on malignant biological behaviors of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To investigate the effect of ring finger protein 187 (RNF187) on cell pro-liferation, migration and invasion of hepatocellular carcinoma (HCC).Methods:Messenger RNA (mRNA) level of RNF187 in HCC was analyzed by bioinformatics. Huh7 cells transfected with small interfering RNA (siRNA) of negative control or target gene respectively were classified as non-transfection (NC) group and RNF187 knockdown group. After 24 hours of transfection, the above two groups dimethyl sulfoxide (DMSO) were used as NC+ DMSO group and RNF187 knockdown + DMSO group. 24 hours after transfection with siRNA of target gene, the cells dealt with bafliomycin A1 (BFA) were set as RNF187 knockdown + BFA group. The regulation of RNF187 on malignant biological behavior and autophagy level of HCC cells were explored by cell counting kit-8 (CCK8) proliferation assay, cell scratch assay, transwell assay and western blot.Results:Compared with normal liver tissue, the mRNA level of RNF187 was higher in HCC tissue ( P<0.05). Compared with NC group, the absorbance at 48 h and 72 h and the scratch healing rate at 12 h and 24 h of RNF187 knockdown group were all lower, the differences were statistically significant (all P<0.001). The number of transmembrane cells in RNF187 knockdown group (39.50±5.57) at 24 h was lower than that in NC group (128.25±17.35), the differences were statistically significant ( t=9.74, P<0.001). Compared with NC group, the relative expression of total LC3 and Beclin-1 in RNF187 knockdown group all increased, while the relative expression of phosphorylated mammalian target of rapamycin decreased, the difference were statistically significant (all P<0.05). Compared with RNF187 knockdown+ DMSO group, the autophagy flow level, the 48 h and 72 h absorbance, the scratch healing rate at 24 h in RNF187 knockdown + BFA group were higher, the differences were statistically significant (all P<0.001). The number of transmembrane cells in RNF187 knockdown + BFA group (119.00±2.65) was more than that in RNF187 knockdown + DMSO group (57.67±2.52), the differences were statistically significant ( t=29.09, P<0.001). Conclusion:RNF187 is highly expressed in HCC tissue and knockdown of RNF187 inhibits the malignant biological behavior of HCC by enhancing the level of autophagy.

Identification of potential genetic markers in prognosis of oral squamous cell carcinoma patients by bioinformatic analysis / 口腔疾病防治

Objective@#To analyze the differentially expressed genes of patients with oral squamous cell carcinoma (OSCC) from paracarcinoma through biological information analysis to preliminarily identify OSCC-associated genes. @*Methods@#GSE23558, GSE37991 and GSE30784 were downloaded from the Gene Expression Omnibus (GEO), which is the mRNA expression profile dataset. The differentially expressed genes (DEGs) were identified based on the gene ontology and the Kyoto Encyclopedia of Genes and Genomes. Then, the protein-protein interaction (PPI) network was constructed using the STRING online tool, and Cytoscape was used to filter the critical genes. Furthermore, key genes involved in the survival of patients with OSCC were analyzed using Kaplan-Meier analysis. The expression of hub genes was validated based on GEPIA（http://gepia.cancer-pku.cn/）. @*Results @#A total of 212 DEGs were screened, and further analysis revealed 16 core genes, among which the core genes associated with prognosis included aurora kinase A (AURKA), aurora kinase B (AURKB), apoptosis inhibiting factor 5 (BIRC5), cell division cycle 6 (CDC6), E2F transcription factor 7 (E2F7), ubiquitin-like with PHD and ring finger domains 1 (UHRF1). These key genes were highly expressed in patients with oral squamous cell carcinoma, and the survival time of patients was short; the difference was statistically significant (P < 0.05).@*Conclusion @# AURKA, AURKB, BIRC5, CDC6, E2F7 and UHRF1 may be useful as potential biomarkers for OSCC prognosis prediction.

miR-338-3p Targets and Regulates RNF121 to Promote the Proliferation and Invasion of Human Lung Cancer A549 Cells / 中国生物化学与分子生物学报

Recent studies have shown that miR-338-3p plays an important role in the proliferation and invasion of lung cancer, but whether miR-338-3p regulates lung cancer proliferation and invasion through targeting ring finger protein 121 (RNF121) is still unclear. In order to explore its mechanism, the normal lung cell line MRC-5 and the non-small cell lung cancer line A549 were cultured in vitro. Using qRTPCR and Western blotting detection, we found that the expression of miR-338-3p in A549 lung cancer cells was lower than that in MRC-5 cells, while RNF121 expression increased (P0. 05). In summary, miR-338-3p can target the expression of RNF121 to inhibit the proliferation and invasion of A549 cells and inhibit the growth of subcutaneous transplanted tumors in nude mice. RNF121 is expected to become a new target for the treatment of non-small cell lung cancer.

Estimation of Stature from Ring Finger Length in Haryanavi Population: An Anthropometric Study

Introduction: Stature helps to determine a person’s identity. In dead and mutilated bodies, height can be estimated from body parameters using a regression equation or multiplication factor.Materials and Methods: The present study was conducted to find the multiplication factor between percutaneous ring finger length (RFL) and stature in the Haryana region, for which 145 medical students (80 males and 65 females) of Post Graduate Institute of Medical Sciences, Rohtak, Haryana, were measured. The correlation coefficient between height and RFL was found to be positive.Results: Stature can be accurately estimated from RFL using simple regression equation or multiplication factor. The regression equation determined for male was Height = 1.798 × RFL + 158.6 and for female was Height = 0.919 × RFL + 152.3.Conclusions: Our study has a great importance to estimate stature from RFL among Haryana region from the anatomical and medicolegal point of view.

Knock-down of UHRF1 expression enhances the radiosensitivity of Eca-109 cells / 西安交通大学学报(医学版)

Objective To investigate the effect of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) on the radiosensitivity of esophageal squamous carcinoma cells and explore its mechanism. Methods The shRNA sequence was designed with human UHRF1 as the target, and the UHRF1-shRNA was transfected into Eca-109 cells mediated by lentivirus. The expressions of UHRF1 mRNA and protein before and after transfection were determined by fluorescence quantitative PCR and Western blotting. The radiosensitivity of Eca-109 cells after down-regulation of UHRF1 gene was assessed by colony formation assay. The effect of silencing UHRF1 on the apoptosis of Eca-109 cells before and after X-ray irradiation was detected by flow cytometry. Western blotting was used to detect the effects of UHRF1 silencing and X-ray irradiation on the expressions of apoptosis-related proteins Bcl-2, caspase-3 and proteins related to AKT/mTOR signaling pathway in Eca-109 cells. Results We successfully constructed an Eca-109 shUHRF1 cell line with UHRF1 stablely down-regulated. Colony formation assays showed that the radiosensitivity of Eca-109 cells was increased after down-regulation of UHRF1 expression compared with the NC group. The proportion of apoptotic cells in Eca-109 cells was increased, while this change was more obvious after irradiation. Compared with NC group, down-regulation of UHRF1 expression increased the level of active caspase-3 protein and decreased the level of the apoptosis inhibitory protein Bcl-2; the expression levels of p-AKT and p-mTOR protein were decreased. The changes in these four proteins in Eca-109 cells with down-regulation of UHRF1 combined with 6 Gy X-ray irradiation were more obvious compared with the NC group. Conclusion UHRF1 knock-down increased the radiosensitivity of ESCC via inhibiting the Akt/mTOR signaling pathway activity and inducing the apoptosis of the cells.

Effects of ring finger protein 43 on matrix metalloproteinases secreted by fibroblast-like synoviocytes from rheumatoid arthritis / 中华风湿病学杂志

Objective To explore the effects of ring finger protein 43 (RNF43) on fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods Synovial tissues from patients with RA treated by knee arthroplasty were used to isolate FLSs by type 2 collagenase.RNF43 lentivirus overexpressing plasmid was constructed and transfected in to RA-FLS.After successful transfection,RNA and super natant of RA-FLS were extracted.QRT-polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)-1,MMP-3 and MMP-13.Data were analyzed with Student's t test.Results Transfection efficiency could meet the test requirements when the multiplicity of infection was 40 and was in conjunction with appropriate concentration of polybrene.The mRNA of RNF43 increased for 26158-fold than the control group.In vitro,compared with the control group,RNF43 could significantly inhibit the mRNA of MMP-1,MMP-3 and MMP-13 and MMP-13 [(0.19±0.06),t=28.314,P＜0.05;(0.28±0.07),t=23.413,P＜0.05;(0.21±0.09),t=18.365,P＜0.05]and the protein of MMP-1,MMP-3 and MMP-13 and MMP-13 [(31.0±9.4) pg/ml,(17.1±2.1) pg/ml,t=3.198,P=0.029],MMP-3 [(38.7±8.1) pg/ml,(24.9±3.5) pg/ml,t=3.514,P=0.015],MMP-13 [(35.9±5.4) pg/ml,(20.6±2.9) pg/ml,t=5.632,P=0.001].Conclusion The results of study suggest that RNF43 could inhibit the secretion of MMPs in RA-FLS by suppressing the activity of Wnt signal pathway.

RNA interference targeting gene of RING finger protein inhibits proliferation and migration of pancreatic cancer cell line PANC-1 / 基础医学与临床

Objective To investigate the effect of siRNA-mediated silencing of RNF2 on cell proliferation , migra-tion, cell cycle and apoptosis in human pancreatic cancer PANC-1 cells and its possible mechanism .Methods The siRNA interference was used to down-regulate RNF2 expression.Meanwhile, there were also empty transfection group whose cells were transfected with the control siRNA and mock group without any treatment .The result of transfection was evaluated by fluorescence microscope .The expression of RNF2 mRNA was detected by RT-qPCR. Western blot was applied to detect the expression of RNF 2 and p53.Cell proliferation and migration were analyzed by MTS assay and cell scratch assay , respectively .The transient transfection efficiency , apoptosis rate and cell cy-cle were measured by flow cytometry .Results Compared to the normalized human pancreatic duct epithelial cells , RNF2 expression in pancreatic cancer cells were higher ( P<0.05) .The expression of RNF2 mRNA and protein was decreased in PANC-1 cells by siRNA-RNF2 at 48 h post-transfection.Transfection with siRNA-RNF2 inhibited the proliferation and migration of PANC-1 cells (P<0.05), induced cell apoptosis (P<0.05), increased cell counts in phase G0/G1 and decreased in S and G2/M phase (P<0.05).What's more, after siRNA-RNF2 transfec-tion, the expression of p 53 protein was decreased .Conclusions siRNA-RNF2 can specifically knockdown the ex-pression of RNF2 gene and then inhibit the proliferation and migration of PANC-1 cells.These results indicate RNF2 may be a potential target of gene therapy for pancreatic cancer .

Relationship of PAHs metabolites,DNA oxidative damage and RING2 expression in coke oven workers / 中国职业医学

OBJECTIVE: To investigate the relationship of polycyclic aromatic hydrocarbons( PAH) metabolites,DNA oxidative damage and ring finger protein 2( RING2) expression in coke oven workers. METHODS: A judgment sampling method was used to select 497 coke oven workers in a steel plant as exposure group and 175 water treatment workers in the same plant as control group. The levels of urinary 1-hydroxypyrene, 2-hydroxynathalene, 2-hydroxyfluorene,9-hydroxyphenanthrene and 8-hydroxy deoxyguanosine(8-OHd G) were detected by high performance liquid chromatography.The RING2 expression in whole blood was measured by reverse transcription-polymerase chain reaction. RESULTS: The relative expression of urinary 1-hydroxypyrene,2-hydroxynathalene,2-hydroxyfluorene,9-hydroxyphenanthrene and RING2 in exposure group were higher than that in control group( P < 0. 01). The logistic regression analysis indicated that the higher the level of 1-hydroxypyrene,the higher the risk of high-RING2 expression( P < 0. 05) after adjusting for factors such as sex,age,smoking status,alcohol drinking,2-hydroxynathalene,2-hydroxyfluorene and 9-hydroxyphenanthrene.In 1-hydroxypyrene middle and high level groups,the 8-OHd G concentration of high-RING2 expression workers was significantly higher than those of low-RING2 expression workers( P < 0. 05). CONCLUSION: With the increase of urinary1-hydroxypyrene,the risk of high-RING2 expression was elevated,the degree of DNA oxidative damage was gradually increased.

Saponins from Paris forrestii(Takht.)H.Li displays potent activity against acute myeloid leukemia by suppressing RNF6/AKT/mTOR signaling pathway / 中国药理学与毒理学杂志

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Changes of serum UHRF1 levels in perioperative patients with esophageal squamous cell carcinoma / 临床检验杂志

Objective To detect serum ubiquitin-like with PHD and ring finger domains 1 (UHRF1) levels in the patients with esophageal squamous cell carcinoma (ESCC),and analyze their differences among different clinicopathological features subgroups and changes during the perioperative period.Methods Serum samples from 130 preoperative ESCC patients,62 patients 1 week after operation,14 patients 1 week and 2 weeks after operation and 67 healthy controls,and clinicopathological data from ESCC patients were collected.Serum UHRF1 levels were detected by ELISA,and the differences among different groups were analyzed with independent t test,paired t test or one-way ANOVA.Results Serum UHRF1 levels in 130 preoperative ESCC patients were significantly higher than that in healthy controls (t =7.680,P ＜ 0.01),and they were related to the ESCC patients' tumor size,differentiation degree,tumor invasion,lymph nodes metastasis and pTNM stage (P ＜ 0.05),but unrelated to the patients' age,gender,tumor location and types (P ＞ 0.05).Serum UHRF1 levels in 62 postoperative patients were significantly lower than that before operation (t =5.530,P ＜ 0.01),but similar to that in healthy controls (t =1.622,P ＞ 0.05).The serum UHRF1 levels before operation,1 week after operation and 2 weeks after operation in 14 ESCC patients decreased gradually (F =7.595,P ＜ 0.01).Conclusion Serum UHRF1 levels may be a potential biomarker for dynamically monitoring perioperative ESCC patients.

The Morphometric Study of Sexual Dimorphism in Index & Ring Finger Length Ratio in Indian Population.

Background: Anthropometry is a science which deals with method and techniques of measurement of living as well as skeletons of individuals. The morphometry of different parts of human body helps in personal identification and also sexual dimorphism. Methods: Total number of students (200=Male & 200=Female) of age 17-25 years of Teerthanker Mahaveer University were examined for one year. With the help of vernier caliper, the lengths of index and ring fingers were measured and then ratio was calculated in both the genders. The data was tabulated & mean & standard deviation was calculated. The paired t- test was used and P- value was calculated. P value < 0.05 was considered significant. Results: The mean values of male population were found to be right 2D 7.04cm, right 4D 7.20cm, right 2D:4D ratio 0.97cm respectively, while in females the mean value were found to be right 2D 6.52cm, right 4D 6.72cm, right 2D:4D Ratio 0.96 cm respectively. Using t-test, in males and females the 2D:4D ratio was statistically insignificant for the right hand with p>0.05. Conclusion: The anthropometric ratios help in establishing the gender and race of the individual, thus plays an important role in forensic science.

Ring finger protein 43 gene and its function in digestive system cancer / 国际肿瘤学杂志

Ring finger protein 43 (RNF43) is a ring-type E3 ubiquitin ligase.As a negative regulater of Wnt signaling pathway, RNF43 has an important anti-tumor effect.The mutation of RNF43 may cause abnormal activation of Wnt signaling pathway, and then promote invasion, metastasis and proliferation of tumor cell.In addition, the act of RNF43 protein in the Wnt signal pathway is expected to be a molecular target in the therapy of cancer.In recent years, with the gradual deepening of related research, the molecular structure of RNF43 protein and its mechanism of action with the Wnt pathway-related proteins have been gradually clear.In clinical, RNF43 protein analogs and related vaccine also show the important position in the therapy of cancer.

Expressions of UHRF1, P53 and their clinical significances in colon carcinoma / 国际肿瘤学杂志

Objective To investigate the expression levels and clinical significances of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) and P53 in colon carcinoma.Methods The expressions of UHRF1 and P53 in 70 colon cancer tissues and 30 normal colon ones were detected by means of immunohistochemistry to analyze the correlation of these two proteins in the occurrence and development of colon carcinoma,and the relationship between their expressions and clinico-pathological factors as well as prognosis was discussed.Results The expression levels of UHRF1 and P53 in cancer tissues were significantly higher than those of cancer-adjacent tissues (87.1％ vs.56.7％,x2 =11.366,P =0.001;64.3％ vs.6.7％,x2 =27.988,P =0.000) and showed a positive correlation between the two proteins (r =0.248,P =0.038).Both UHRF1 and P53 were associated with TNM stages (x2 =4.426,P =0.049;x2 =6.000,P =0.016) and the depth of invasion (x2 =12.553,P =0.002;x2 =4.904,P =0.036).However,they were irrelevant with the age (x2 =0.473,P=0.494;x2 =0.090,P=0.799) and gender (x2 =2.297,P=0.166;x2 =0.512,P=0.617) of patients,as well as the size (x2 =0.638,P =0.481;x2 =2.392,P =0.215) and histological grading of tumors (x2 =2.088,P =0.352;0.303,P =0.859).Kaplan-Meier analysis showed that the median survival time of patients with UHRF1,P53 positive expression was 21.83 months that was lower than patients with UHRF1 positive expression of 24.49 months (Z =-0.624,P =0.533).Both former of which was distinctly lower than that of negative ones of 37.33 months (Z =-2.856,P =0.004;Z =-2.694,P =0.007).Conclusion Both UHRF1 and P53 are highly expressed in colon cancer tissues,which imply that UHRF1 and P53 may be strongly related with colon cancer development and can be a predictor for colon cancer prognosis.

Ring finger protein 43 gene and cancer / 国际肿瘤学杂志

Ring finger protein 43 (RNF43) gene is closely associated with the development of various types of human tumors.The mainly mechanisms of RNF43 gene are mutation and aberrant expression.Activated RNF43 protein participates in the proliferation, apoptosis, metastasis through some signal pathways and influences the tumorigenesis and development in colorectal cancer, hepatocellular carcinoma, which plays a role of oncogene.However, it is considered as a tumor suppressor gene in mucinous ovarian tumors and intraductal papillary mucinous neoplasms of the pancreas.

Construction of the lentivirus vector over-expressing PCGF1 and establishment of A549 cell line stably over-expressing PCGF1 / 解放军医学杂志

Objective To construct lentiviral over-expression vector of polycomb group ring finger 1(PCGF1) and get the A549 cell stably over-expressing PCGF1. Methods The primers were designed according to human PCGF1 sequence. The target gene was amplified by PCR with the template of the A549 cDNA. The target gene was digested and then inserted into the pLVX-IRES-puro plasmid. After the lentiviral vector was packaged, A549 cell line infected by the packaged virus was selected by puromycin, and the expression of PCGF1 was verified by Western blotting. Results The DNA sequence of recombinant plasmid was verified to be correct, and then transfected into 293T cells. Western blotting showed the remarkably escalated expression of PCGF1 gene in 293T cells. After lentivirus infection, Western blotting supported that the PCGF1 was stably over-expressed in A549 cells after puromycin selection. Conclusion The lentiviral over-expression vector pLVX-IRES-PCGF1-puro has been successfully constructed, and the recombinant virus can effectively infect A549 cells and the PCGF1 is stably over-expressed.