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Purpose To investigate the expression and re-lationship of phosphatidic acid phosphatase 2 domain 1A(PPAPDC1A),also known as phospholipid phosphatase 4(PLPP4),in colorectal cancer(CRC)tissues and different colorectal cancer cells.Methods Immunohistochemical EnVi-sion method was applied to detect the expression of PPAPDC1A in 60 CRC tissues and paired paracancerous tissues.Stable over-expression and silencing cell lines of PPAPDC1A were success-fully constructed by gene transfection,and the effects of this gene on different colorectal cancer cell lines were investigated by CCK-8,Transwell,subcutaneous tumor formation in nude mice and tail vein injection in nude mice.Results PPAPDC1A ex-pression was upregulated in CRC tissues compared with paracan-cerous tissues,and the intensity of PPAPDC1A expression was negatively correlated with cell differentiation(P=0.011).PPAPDC1A stable overexpression and interference cell lines were successfully constructed.The results of in vitro and in vivo experiments showed that the growth rate(SW480-PPAPDC1A,RKO-PPAPDC1A groups:0.38±0.03,0.25±0.01),the number of cells crossing the compartment(SW480-PPAPDC1 A,RKO-PPAPDC1A groups:218.33±7.09,96.33±1.52),the number of clone formation(SW480-PPAPDC1 A,RKO-PPAP-DC1A groups:174.33±5.03,245.00±7.00),the in vivo tumor volume(4.16±0.91),and the number of lung metasta-sis in nude mice(5.1±3.84)were significantly higher in the PPAPDC1A stably overexpressing cell lines compared with the Vector group(P＜0.05).However,the growth rate(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:0.14±0.02,0.16±0.05),number of cells crossing the chambers(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:13.33±0.57,18.33±0.51),number of clone formation(SW620-shPPAP-DC1A,LOVO-shPPAPDC1A groups:28.33±1.52,8.67± 0.57),tumor volume(0.56±0.21),and number of lung me-tastasis in nude mice(1.2±1.03)were significantly lower(P＜0.05)in the PPAPDC1 A-silenced cell line compared with the NC group.Conclusion Down-regulation of PPAPDC1A expres-sion inhibits the proliferation,invasion,migration and metastatic ability of CRC cells.
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Neurofibromatosis type 1 is a progressive autosomal dominant inherited disease caused by a mutation in neurofibromin 1(NF1)gene located on chromosome 1 7q1 1.2.NF1 can cause systemic peripheral neuropathy,but the clinical manifestations are varied due to the different onset times and lesion sites in different patients.The treatment of NF1 involves multiple disciplines due to different lesion sites.Clinical monitoring and symptomatic treatment are the main methods for NF1 management,while radical treatment is difficult.New drugs targeted at the pathogenic gene-related signaling pathways are expected to improve the therapeutic effect for NF1.This review summarizes the progress in the basic research and clinical diagnosis and treatment of NF1.
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Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.
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Objective:To investigate the effect of ethephon exposure on sperm quality of adolescent male SD rats and the influence mechanism.Methods:A total of 40 45-day-old male SD rats were divided into control group and low, middle and high experimental groups according to the random number table method, 10 rats in each group.The said 4 groups were given 9 g/L normal saline, 100 mg/kg, 200 mg/kg, and 400 mg/kg ethephon aqueous solution for 28 days, respectively.One epididymal tail was taken to prepare sperm suspension, the sperm concentration and motility were detected.The testis and epididymis tissues were stained with HE, and their pathological changes were observed under light microscope.The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) content in the testis were detected.Enzyme linked immunosorbent assay kit was used to mea-sure the epididymal α-glucosidase activity, L-carnitine (LC) content, nuclear factor erythroid 2-related factor 2 (Nrf2) and organic cation transporter 2 (OCTN2) expression levels.Then the oxidative damage caused by ethephon to epididymis was evaluated.SPSS 26.0 software was used for data analysis.Data were compared by One- way ANOVA among groups and LSD method between 2 groups. Results:The sperm concentration of the control group, low, medium and high dose groups were (40.21±1.94)×10 9/L, (35.23±2.53)×10 9/L, (23.61±2.62)×10 9 /L, and (18.86±2.16)×10 9 /L, respectively.The sperm activity rate were (70.98±3.01)%, (57.96±3.75)%, (45.71±2.41)%, and (31.23±2.26)%, respectively.The concentration and vitality of epididymal sperms in the experimental group were significantly lower than those in the control group (all P<0.01). In the control group, low, medium and high dose groups, the SOD activity were (46.48±2.21) U/mg prot, (38.49±2.56)U/mg prot, (33.80±1.73) U/mg prot, and (27.65±2.05) U/mg prot, respectively.The GSH-Px activity in said 4 groups were (21.41±1.95) U/mg prot, (17.32±1.28) U/mg prot, (15.09±0.94) U/mg prot, and (14.08±1.23) U/mg prot, respectively.The MDA content in said 4 groups were (1.41±0.09) nmol/mg prot, (1.59±0.09) nmol/mg prot, (1.81±0.09) nmol/mg prot, and (2.16±0.14) nmol/mg prot, respectively.Compared to the control group, the experimental groups had significantly lower SOD and GSH-Px activities and significantly higher MDA content (all P<0.05). α-glucosidase levels in the control group, low, middle and high experimental groups were (15.46±0.71) U/mL prot, (12.95±0.72) U/mL prot, (11.34±0.65) U/mL prot, and (8.76±0.60) U/mL prot, respectively.LC levels in the control group, low, middle and high dose groups were(6.21±0.31) μg/L, (5.89±0.13) μg/L, (5.02±0.12) μg/L, (4.38±0.07) μg/L, respectively, compared with those of the control group, the concentration of α-glucosidase and LC in experimental groups decreased significantly (all P<0.01). The expression levels of Nrf2 in epididymis of the control group, low, middle and high dose groups were (1.34±0.05) ng/L, (1.25±0.04) ng/L, (1.08±0.06) ng/L, (0.92±0.04) ng/L, respectively; the expression levels of OCTN2 in epididymis of the control group, low, middle and high dose groups were (4.55±0.12) ng/L, (4.23±0.11) ng/L, (3.20±0.24) ng/L, (2.59±0.05) ng/L, respectively, compared with those of the control group, the expression levels of Nrf2 and OCTN2 in experimental groups decreased significantly (all P<0.01). Conclusions:Ethephon exposure leads to excessive generation of reactive oxygen and oxidative stress in reproductive organs.Ethephon exposure may activate the Keap1-Nrf2/ARE signal pathway, resulting in a decrease in the number, vitality and quality of sperms, and impaired fertility.
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Objective:To explore the effects of different doses of Ethephon on testes of male pups.Methods:Thirty-two 45-day-old healthy female Sprague-Dawley (SD) rats were randomly divided into the control group and the low dose, middle dose and high dose Ethephon groups by the random figure table.The female rats in the low dose, middle dose and high dose Ethephon groups were given 200, 400, and 800 mg/kg Ethephon solution, respectively.The control group was treated with 9 g/L saline.After the birth of the offspring, the mother rats were not administrated with any medications, and the male offspring rats were given Ethephon solution instead.Twelve offspring male rats were randomly selected from each group and killed at the age of 0, 14 and 28 days after birth.Fresh testicular tissues were stained with hematoxylin eosin (HE), and the morphological changes of testicular tissues were observed under light microscope.The apoptotic cells were labeled by terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) method and the apoptosis index (AI) of spermatogenic cells was detected by fluorescence microscope.Results:(1) Compared with the newborn rats in the middle dose group, low dose group and control group, se-miniferous tubules in the newborn rats of the high dose group were slightly thicker, and seminiferous cells were arranged slightly in disorder.The AI of the newborn rats in high dose group was significantly higher than that in the control group (1.00±0.06 vs.0.41±0.03, P<0.01). The AI of the newborn rats in the middle dose group was not significantly different from that in the control group and the low dose group ( P>0.05). (2) The seminiferous tubules of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups were significantly thicker and arranged more loosely than those in the control group.Compared with the control group, there were very few seminiferous cells, which were arranged disorderly in the low dose, middle dose and high dose Ethephon groups.The AI of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups was (2.13±0.10), (2.18±0.10) and (3.90±0.23), respectively, which were significantly higher than that in the control group (1.00±0.02) ( F=2 508.36, P<0.01). There was no significant difference in the AI between the middle dose and low dose groups ( P>0.05). (3) Compared with the control group, the seminiferous tubules of the 28-day-old rats in the low dose, middle dose and high dose groups were significantly thicker and arranged much more loosely, and spermatogenic cells were even less and arranged in a severely disordered way.The AI of 28-day-old rats in the low dose group (5.52±0.13), the middle dose group (9.44±0.07) and the high dose group (14.56±0.27) was significantly higher than that in the control group (3.11±0.13) ( F=10 784.69, P<0.01). Conclusions:Ethephon can thicken the seminiferous tubules of newborn and young rats, cause the germ cells to arrange disorderly, promote the apoptosis of spermatogenic cells and reduce the ability of spermatogenesis.Moreover, a longer exposure of the rats to a higher concentration of Ethephon will result in more serious damage to testicular tissues.