ADCY6 is a potential prognostic biomarker and suppresses OTSCC progression via Hippo signaling pathway.

Oral tongue squamous cell carcinoma (OTSCC) is a malignant tumor. Recently, studies have found that adenylate cyclase 6 (ADCY6) plays a pivotal role in many lethal tumors formation processes. The role of ADCY6 in OTSCC remains unknown. The expression of ADCY6 in OTSCC tissue samples was detected. The clinical significance of ADCY6 in OTSCC was analyzed by statistical methods. OTSCC cell lines were selected to analyze the biological function of ADCY6. Meanwhile, the effect of ADCY6 on the growth of OTSCC in vivo was explored using subcutaneous tumorigenesis assay. WB assay was used to detect the underlying signaling pathway. Cell function recovery test used to investigate the mechanism of ADCY6-promoting OTSCC malignant biological behavior via Hippo signaling pathway. We report that ADCY6 was obviously downregulated in OTSCC tissue samples and cell lines. Importantly, lower expression of ADCY6 indicates a poorer prognosis in patients with OTSCC, and its expression is significantly correlated with TNM stage and tumor size. Functionally, forced expression of ADCY6 can significantly inhibit the proliferation, migration, invasion, and promote apoptosis of OTSCC cells. Mechanistically, we demonstrated that ADCY6 upregulation impaired Hippo signaling pathway to reduce the malignant biological behavior of OTSCC. Generally, our findings suggest that ADCY6 suppressed Hippo signaling pathway to regulate malignant biological behavior in OTSCC, which provide new cues for further exploring the mechanism of occurrence and development of OTSCC.

FoxO3 Regulates the Progress and Development of Aging and Aging-Related Diseases.

Aging is an inevitable risk factor for many diseases, including cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes. Investigation into the molecular mechanisms involved in aging and longevity will benefit the treatment of age-dependent diseases and the development of preventative medicine for agingrelated diseases. Current evidence has revealed that FoxO3, encoding the transcription factor (FoxO)3, a key transcription factor that integrates different stimuli in the intrinsic and extrinsic pathways and is involved in cell differentiation, protein homeostasis, stress resistance and stem cell status, plays a regulatory role in longevity and in age-related diseases. However, the precise mechanisms by which the FoxO3 transcription factor modulates aging and promotes longevity have been unclear until now. Here, we provide a brief overview of the mechanisms by which FoxO3 mediates signaling in pathways involved in aging and aging-related diseases, as well as the current knowledge on the role of the FoxO3 transcription factor in the human lifespan and its clinical prospects. Ultimately, we conclude that FoxO3 signaling pathways, including upstream and downstream molecules, may be underlying therapeutic targets in aging and age-related diseases.

Survey on occupational hazards of enterprises in Pingshan district of Shenzhen City / 中国职业医学

@#Abstract: Objective To analyze the occupational hazards of enterprises in Pingshan district of Shenzhen in 2017. Methods Occupational hazards were analyzed in 200 enterprises in Pingshan district of Shenzhen City selected using stratified Results random sampling method. A total of 24 industries were involved in the 200 enterprises. The declaration rate of ， occupational hazards was 91.5% and the exposure rate of occupational hazards among workers was 49.2%. The regular monitoring rate of occupational hazard factors in workplaces of the enterprises was 79.5%. There were 129 kinds of occupational ， ， hazard factors of which 19 factors exceeded the national occupational exposure limit accounting for 14.7%. The over standard ， ， ， ， ， ， ， ， rates of noise silica dust cotton dust methanol toluene and other dust were 28.7% 13.6% 11.8% 5.86% 0.5% and ， ， 0.4% respectively. There were 13 kinds of occupational hazard factors in the workplace of metal products industry all of which （ ） exceeded the occupational exposure limit. The exposure rate 56.7% of occupational hazard factors in workers was the highest. Conclusion ， ， The main occupational hazard factors were noise dust and chemical factor and the major occupational hazard industry was metal manufacturing in Pingshan district of Shenzhen City.

[Therapeutic mechanism of Psammosilene tunicoides extract on rheumatoid arthritis based on NLRP3 inflammasome].

In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1ß and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1ß and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA.

Degradation of non-oxidizing biocide benzalkonium chloride and bulk dissolved organic matter in reverse osmosis concentrate by UV/chlorine oxidation.

Non-oxidizing biocide that is used to inhibit the microorganism growth on RO membrane, are observed to be high concentration and toxic in RO concentrate. The synergistic oxidation process (SOP) of UV/chlorine was investigated to simultaneously reduced the content (60.2 %) and toxicity (57.0 %) of a representative biocide dodecylbenzyldimethylammonium chloride (DDBAC) in real RO concentrate, with a UV fluence 1080 mJ/cm2 and chlorine dose 20 mg/L. Besides eliminating the DDBAC, UV/chlorine reduced the UVA254 and fluorescence of the dissolved organic matters (DOM). The oxidation mechanism was verified to be the radical electrophilic addition rather than the chlorine-electrophilic substitution through the decay of electron-donation moiety and UVA254. As results, high molecular weight fractions of DOM (>2k Da, 79.2 %) was cleaved into low molecular weight fractions (<0.4k Da, 18.4 %) and organic halide was formed. Parallel-factor analysis of the fluorescence components suggested that decomposition of the protein-like fluorophore is most likely to surrogate the biocide removal and organic halide formation compared to other fluorophore components and UVA254. Accordingly, a portable fluorescence probe with 400 nm excitation and 410-600 nm emission wavelengths was developed as an online surrogate for the DDBAC removal and organic halide formation.

Genetic inhibition of an ATP synthase subunit extends lifespan in C. elegans.

Mild inhibition of mitochondrial respiration leads to longevity. Disruption of mitochondrial respiratory components extends lifespan in Caenorhabditis elegans, but the effects appear to be complex and the underlying mechanism for lifespan regulation by mitochondrial respiratory genes is still not fully understood. Here, we investigated the role of Y82E9BR.3, a worm homolog of the ATP synthase subunit C, in modulating longevity in C. elegans. We found that the Y82E9BR.3 protein is localized in mitochondria and expressed in various tissues throughout development. RNAi knockdown of Y82E9BR.3 extends lifespan, decreases the accumulation of lipofuscin, and affects various physiological processes, including development delay, reproduction impairment and slow behavior. Further tissue-specific RNAi analysis showed that the intestine is a crucial organ for the longevity effects conferred by Y82E9BR.3 RNAi. Moreover, we demonstrated that lifespan extension by Y82E9BR.3 RNAi is associated with reduced mitochondrial function, as well as the suppression of complex I activity in mitochondria. Unexpectedly, Y82E9BR.3 RNAi knock down did not influence the whole-worm ATP level. Our findings first reveal the crucial role of Y82E9BR.3 in mitochondrial function and the underlying mechanism of how Y82E9BR.3 regulates lifespan in C. elegans.

Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction.

CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.

Transition of LINE-1 DNA methylation status and altered expression in first and third trimester placentas.

DNA methylation plays a critical role in the regulation of gene expression, genomic DNA stability, cell proliferation, and malignant transformation. Common cellular features including fast tissue expansion, invasive growth, and active angiogenesis, have been noticed between placental development and tumorigenesis by many investigators. While the DNA hypomethylation and transcriptional activation of LINE-1 has been found to be a feature of tumorigenesis, it is not clear if similar changes could be involved in placental development. In this study, we assessed LINE-1 methylation in human placentas from different gestational ages and observed a significant decrease of LINE-1 methylation levels in third trimester placentas compared to first trimester placentas. Accompanying with this change is the significantly increased LINE-1 mRNA levels in third trimester placentas. Since no global DNA methylation change was detected between first and third trimesters, LINE-1 methylation changes appeared to be a specific epigenetic entity contributing to placental development. Indeed, further analyses showed that LINE-1 upregulation was correlated with higher levels of PCNA, suggesting a link between LINE-1 activation and fast proliferation of certain cellular components in third trimester placentas. Measurement of the DNMT1, DNMT3A, and DNMT3B expression found a significant reduction of DNMT3B between third and first trimesters, pointing to the possible involvement of this enzyme in the regulation of LINE-1 methylation. Taken together these results provided evidence for a dynamic temporal regulation of LINE-1 methylation and activation during placental development. These studies have laid a foundation for future investigation on the function of LINE-1 expression in human placenta under different patho-physiological conditions.

[Intrauterine growth characteristics of twins and those twins discordant birthweight].

OBJECTIVE: To investigate the intrauterine growth characteristics of twins and birthweight discordant twins (discordant twins). METHODS: Total of 1010 twin pregnancies (2020 fetuses) with complete delivery records from the Department of Obstetrics and Gynecology, the First and Third Affiliated Hospital of SUN Yat-sen University between January 1, 2000 and July 31, 2010 were studied retrospectively. One handred and ninteen cases (238 fetuses) with intrapair birthweight difference ≥ 25% were determined as the discordant twins group, and the other 891 cases (1782 fetuses) with intrapair birthweight difference < 25% were identified as the concordant twins group. The singleton control group included 4042 singleton pregnancies in the same period. RESULTS: (1) Comparison of clinical data between the twins groups: the birthweight of larger-twin, smaller-twin and intrapair birthweight difference in the discordant twins group and the concordant twins group were (2090 ± 827) g, (1392 ± 592) g, (33.9 ± 9.3)%, and (2408 ± 543) g, (2191 ± 505) g, (8.9 ± 6.5)%, respectively, with significant differences (P < 0.01). The incidence of discordant twins was 11.78% (119/1010). Compared with the concordant twins group, the discordant twins group had higher proportion of monochorionic twins, and higher prevalence of pregnancy complications such as late miscarriage, abnormal umbilical insertion, twin-twin transfusion syndrome and hypertensive disorders in pregnancy (P < 0.05). (2) The characteristics of twin birthweight distribution: 1) In all the 2020 twins, 80.05% (1617/2020) fetuses had birthweight below the 50(th) percentile of the singleton control group, while 23.71% (479/2020) feeuses got birthweight below the 10(th) percentile of the singleton control group. 2) After 19(th) gestational week, the 50(th) and 90(th) percentile of all twins' birthweight were lower than those of singletons. After 38(th) gestational week, the birthweight of singletons kept increasing and reached its peak at 41(th) week, while the birthweight of twins reached its peak at 38(th) week, followed by a decline at 39 weeks, which was even lower than the 10(th) percentile of the singleton control group. 3) The distribution of birthweight of larger- and smaller-twin in the discordant twins group: 65 (54.6%, 65/119) larger-twins and one (0.8%, 1/119) smaller-twin had birthweight above the 50(th) percentile of all twins, while 5 (4.2%, 5/119) larger-twins and 97 (81.5%, 97/119) smaller-twins got birthweight below the 10(th) percentile of all twins. CONCLUSIONS: (1) The patterns of birthweight curves for each gestational week are different between twins and singletons. In order to evaluate the growth of twins, birthweight reference for twins should be employed. (2) According to the reference of twins birthweight, the most discordant twins are complicated with fetal growth restriction at least in one twin.

[Expression and methylated regulation of HERVWE1 in placenta of monozygotic discordant twins].

OBJECTIVE: To explore the HERVWE1 gene expression in the placentas of discordant monozygotic twins and identify its regulation by methylation. METHODS: Fetuses from 21 pairs of monozygotic discordant twins were marked as "smaller" or "larger" according to birth weight. Placental HERVWE1 mRNA and protein expression profiles were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) stain. Methylation profiles of the HERVWE1 promoter region were analyzed by COBRA, MSP-PCR and pyrosequencing assay. RESULTS: In discordant twins group, the mean methylation level of the HERVWE1 promoter region decreased in smaller fetuses (P < 0.05). And there were increased mRNA and protein levels of HERVWE1 in smaller fetuses versus larger counterparts (P < 0.05). CONCLUSION: In discordant monozygotic twins, the HERVWE1 expression is higher in smaller fetuses and lower in larger counterparts. Methylation of HERVWE1 gene promoter region may participate in the regulation of HERVWE1 gene expression in twins.

Fetal reduction by bipolar cord coagulation in managing complicated monochorionic multiple pregnancies: preliminary experience in China.

BACKGROUND: Monochorionic multiple pregnancies (MMPs) are associated with higher rates of perinatal morbidity and mortality caused by interfetal vascular anastomoses in the monochorionic placenta, which can lead to fetal health interactions. In some circumstances, selective feticide of the affected fetus is necessary to save the healthy co-twin. We evaluated the effects and safety of our initial experiences using bipolar cord coagulation for the management of complicated MMPs. METHODS: Using ultrasound-guided bipolar cord coagulation, we performed selective feticide on 14 complicated MMPs (5 with twin-twin transfusion syndrome, 4 with acardia, 3 with discordant structural anomalies, and 2 with severe selective intrauterine growth restriction). One patient with monochorionic triplets received the procedure twice to terminate 2 affected fetuses for different indications. Data regarding the operations, complications and neonatal outcomes were analyzed. RESULTS: Cord occlusions were successfully performed in 13/14 (93%) cases. The failure happened in an acardiac fetus and the pregnancy was terminated by induction. The included cases delivered at a mean gestational age of 35.4 weeks with a perinatal survival rate of 11/13 (85%). Three operation-related complications occurred (21%), including membrane rupture of the terminated sac (1 case), preterm labor at 28 weeks gestation (1 case), and chorioamniotic membrane separation (1 case). Amnioinfusion was indicated in 11 procedures to expand the target sacs for entering the trocar and obtaining sufficient working space. However, in all 4 cases of acardia, the acardiac sacs showed extreme oligohydramnios and could not be well expanded by infusion; thus, the trocar had to be inserted from the sac of the preserved co-twin. CONCLUSIONS: The application of bipolar cord coagulation in complicated MMPs is safe and improves the prognosis. Amnioinfusion is useful in helping to expand the target sac when the working space is limited.

[Bipolar coagulation used in selective feticide of monochorionic twins with one twin anomaly].

OBJECTIVE: To summarize our preliminary experience of selective feticide with bipolar coagulation in complicated monochorionic twins (MCT), and discuss the clinical application of feticide in discordant MCT. METHODS: Three MCT with one twin anomaly, in which 2 had severe twin-twin transfusion syndrome (TTTS), stage IV, and 1 had acardiac twin, were identified in the second trimester of pregnancy. To terminate the abnormal twin and isolate the co-twin's circulation completely, selective feticide was performed by umbilical cord occlusion with bipolar coagulation under guidance of ultrasound and fetoscopy. After each invasive procedure, serial monitoring was performed, including procedural complications, Doppler of fetal middle cerebral artery and umbilical artery. Pregnancies were followed up every 2 weeks for fetal growth until delivery. After birth the placentas and the terminated fetuses were examined. RESULT: Cord occlusion was successfully accomplished in all 3 targeted fetuses, at 21, 22 and 24 weeks of gestation respectively. One case with TTTS was complicated with rupture of the membrane in the terminated fetus the 7th day after the procedure, and a healthy baby was born at 32 weeks. The other case with TTTS delivered a boy by cesarean section at 38 weeks. The third case with TRAP is at 35 weeks of gestations and under regular follow-up. Monochorionicity was confirmed by placental examination after delivery, and the effects of bipolar coagulation were observed at the cord of terminated fetuses. CONCLUSIONS: Umbilical cord occlusion with bipolar coagulation is an effective procedure for selective feticide in MCT with one twin anomaly. The outcome of normal fetus can be favorable.