Two new dammarane-type triterpenoids from the green walnut husks of Juglans mandshurica Maxim.

Two new dammarane-type triterpenoids, dammar-3α,12(R),20(S)-triol-12,32(R);20,32-diepoxy-25-methy-25-en-tridecacyclic ether (1) and (23E)-12ß,20(R),25(S),26-tetrahydroxydammar-23-en-3-one (2) were isolated from the green walnut husks of Juglans mandshurica Maxim together with six known compounds. Their structures were elucidated through extensive spectroscopic analyses and by comparison with the literature, and the cytotoxic activities of these compounds were evaluated.

miR-122 Inhibits the Cervical Cancer Development by Targeting the Oncogene RAD21.

Cervical cancer (CC) is one of the most frequently diagnosed tumors in female. miR-122 has been proved to be dominant in CC. The particular role of miR-122 in CC is unclear. Thus, we attempted to investigate the prognostic role of miR-122 in CC. We used the database of Kaplan-Meier curve plot. Growth and apoptosis of C33A cells were detected by CCK-8, colony formation assay, transwell assays and flow cytometry analysis. The target gene of miR-122 was identified using bioinformatics, q-PCR, western blot and luciferase assay. It showed that CC patients with overexpression of miR-122 have a better prognosis in the Kaplan-Meier plot database analysis. Overexpressed miR-122 inhibited the malignant growth and induced apoptosis of CC. miR-122 targeting of RAD21 cohesin complex component (RAD21) was identified using bioinformatics, Q-PCR, western blot and luciferase assay analyses. Moreover, we found miR-122 conduct its functions via RAD21 via the PI3K/AKT signaling pathway. Importantly, overexpression of RAD21 restored the roles of miR-122 in CC. Our data suggested that miR-122 could block malignant growth and promoted apoptosis by targeting RAD21 in CC. Our finding indicates miR-122 could potentially participate in the pathogenesis and be a biomarker or the potential therapeutic target of CC.

SPINT1-AS1 Drives Cervical Cancer Progression via Repressing miR-214 Biogenesis.

Accumulating evidences have revealed the dysregulated expressions and critical roles of non-coding RNAs in various malignancies, including cervical cancer. Nevertheless, our knowledge about the vast majority of non-coding RNAs is still lacking. Here we identified long non-coding RNA (lncRNA) SPINT1-AS1 as a novel cervical cancer-associated lncRNA. SPINT1-AS1 was increased in cervical cancer and correlated with advanced stage and poor prognosis. SPINT1-AS1 was a direct downstream target of miR-214, a well-known tumor suppressive microRNA (miRNA) in cervical cancer. Intriguingly, SPINT1-AS1 was also found to repress miR-214 biogenesis via binding DNM3OS, the primary transcript of miR-214. The interaction between SPINT1-AS1 and DNM3OS repressed the binding of DROSHA and DGCR8 to DNM3OS, blocked DNM3OS cleavage, and therefore repressed mature miR-214 biogenesis. The expression of SPINT1-AS1 was significantly negatively correlated with miR-214 in cervical cancer tissues, supporting the reciprocal repression between SPINT1-AS1 and miR-214 in vivo. Through downregulating mature miR-214 level, SPINT1-AS1 upregulated the expression of ß-catenin, a target of miR-214. Thus, SPINT1-AS1 further activated Wnt/ß-catenin signaling in cervical cancer. Functionally, SPINT1-AS1 drove cervical cancer cellular proliferation, migration, and invasion in vitro, and also tumorigenesis in vivo. Deletion of the region mediating the interaction between SPINT1-AS1 and DNM3OS, overexpression of miR-214, and inhibition of Wnt/ß-catenin signaling all reversed the roles of SPINT1-AS1 in cervical cancer. Collectively, these findings identified SPINT1-AS1 as a novel cervical cancer-associated oncogenic lncRNA which represses miR-214 biogenesis and activates Wnt/ß-catenin signaling, highlighting its potential as prognostic biomarker and therapeutic target for cervical cancer.

α-Tetralone glycosides from the green walnut husks of Juglans mandshurica Maxim. and their cytotoxic activities.

Five new α-tetralone glycosides, juglanbiosides A-E (1-5), together with an α-tetralone derivative (15) and nine known 1,4-naphthoquinones (6-14) were isolated from the 95% EtOH extract of green walnut husks of Juglans mandshurica Maxim. Their structures were elucidated by comprehensive spectroscopic methods (1H, 13C NMR, DEPT, HSQC, HMBC, CD, HR-ESI-MS). In vitro cytotoxicities of all the isolated compounds were evaluated against BGC-823, HCT-15 and K562 cancer cell lines.[Formula: see text].

Long non-coding RNA LINC01535 promotes cervical cancer progression via targeting the miR-214/EZH2 feedback loop.

Long non-coding RNAs (lncRNAs) have shown critical roles in multiple cancers via competitively binding common microRNAs. miR-214 has been proved to play tumour suppressive roles in various cancers, including cervical cancer. In this study, we identified that lncRNA LINC01535 physically binds miR-214, relieves the repressive roles of miR-214 on its target EZH2, and therefore up-regulates EZH2 protein expression. Intriguingly, we also found that EZH2 directly represses the expression of miR-214. Thus, miR-214 and EZH2 form double negative regulatory loop. Through up-regulating EZH2, LINC01535 further represses miR-214 expression. Functional experiments showed that enhanced expression of LINC01535 promotes cervical cancer cell growth, migration and invasion in vitro and cervical cancer xenograft growth in vivo. Reciprocally, LINC01535 knockdown suppresses cervical cancer cell growth, migration and invasion. Activation of the miR-214/EZH2 regulatory loop by overexpression of miR-214 or silencing of EZH2 reverses the roles of LINC01535 in promoting cervical canc`er cell growth, migration and invasion in vitro and cervical cancer xenograft growth in vivo. Clinically, LINC01535 is significantly up-regulated in cervical cancer tissues and correlated with advanced clinical stage and poor prognosis. Moreover, the expression of LINC01535 is reversely associated with the expression of miR-214 and positively associated with the expression of EZH2 in cervical cancer tissues. In conclusion, this study reveals that LINC01535 promotes cervical cancer progression via repressing the miR-214/EZH2 regulatory loop.

A new triterpene from the green walnut husks of Juglans mandshurica Maxim.

A new triterpene named klodorol B (1), together with six known compounds, were isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were determined using spectroscopic methods on the basis of 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry. The isolated compounds were evaluated for their cytotoxic activities on human gastric carcinoma (BGC-823), human liver cancer (HepG-2) and human lung cancer (A549) cell lines. .

Two new tetralone glycosides from the green walnut husks of Juglans mandshurica Maxim.

Two new tetralone glycosides, 4(S)-5-methoxy juglanoside A (1), 4(S)-5-methoxy juglanoside D (2), together with ten known compounds (3-12) have been isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were elucidated on the basis of their ESI-MS, 1 D and 2 D NMR spectroscopic data. In addition, all compounds were evaluated for their cytotoxic activities against the cancer BGC-823 (human gastric carcinoma), HCT-15 (human colorectal carcinoma) and K562 (human chronic myeloid leukemia) cell lines. The results showed aglycones of naphthoquinones had stronger cytotoxic activities than glycosides of tetralone.

microRNA-214 suppresses the growth of cervical cancer cells by targeting EZH2.

A number of studies have revealed the significance of microRNAs (miRs) in tumorigenesis. Cervical cancer (CC) is one of the most malignant cancer types and is associated with a poor overall survival rate. A previous study demonstrated a critical role of miR-214 in the development of multiple cancer types, but its role in CC remains elusive. In the current study, miR-214 was observed to be downregulated in CC tissues compared with the adjacent non-cancerous tissue. Overexpression of miR-214 reduced the proliferation of CC cells, whereas inhibiting its expression resulted in enhanced proliferation. Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR-214 in CC. An MTT assay demonstrated that upregulating miR-214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. Low expression of miR-214 was positively associated with tumor differentiation (P=0.037) and tumor stage (P=0.012). Notably, low expression of miR-214 predicted poor prognosis of patients with CC. Consequently, the results of the current study demonstrated that miR-214 functions as a tumor suppressor in CC and may be regarded as a potential therapeutic target in CC.

Therapeutic Drug Monitoring of Teicoplanin in Haematological Malignancy Patients with Febrile Neutropenia and Optimizing Dosage Regimens.

This study used high-performance liquid chromatography to measure 202 teicoplanin plasma trough concentrations (Cmin ) in 114 haematological malignancy patients with febrile neutropenia. Patients were divided into two groups according to the mean initial dose (MID) over the first 3 days of treatment: (i) MID = 533.33 mg/day (loading dose group, 400 mg q12h for three doses followed by 400 mg qd, n = 62) and (ii) MID < 533.33 mg/day (unloaded or underloaded group, n = 52). During the first 3 days after treatment, the overall Cmin was higher in group 1 than in group 2 (10.96 ± 5.44 mg/L versus 6.31 ± 3.73 mg/L, mean ± S.D.; p = 0.002), as was the qualifying rate of Cmin > 10 mg/L (54.5% versus 11.1%, p = 0.001), and the probability of Cmin < 5 mg/L was lower in group 1 than in group 2 (13.6% versus 40.7%, p = 0.037). After 3 days, the average Cmin and qualifying rates did not differ significantly between the two groups, and the average Cmin was <10 mg/L in both groups. Binary logistic regression analysis revealed that creatinine clearance (p = 0.004) and MID (p = 0.010) could affect Cmin during the first 3 days of treatment and that age (p = 0.022) only could affect Cmin after 3 days. In conclusion, it is necessary to apply loading dose to achieve teicoplanin Cmin > 10 mg/L rapidly and, from a pharmacokinetic/pharmacodynamic perspective, 600 mg is recommended as loading and maintenance dose for these patients when AUC24 /minimum inhibitory concentration > 345.

RECK inhibits cervical cancer cell migration and invasion by promoting p53 signaling pathway.

The present study was conducted to investigate the effects of RECK on cervical cancer cell migration and invasion to help understand relevant molecular mechanisms. QRT-PCR and western blot were respectively utilized to examine the transcriptional and translational levels of RECK in cervical cancer cell lines (HELA and C33A) and normal cell line (H8). After transfection with RECK overexpressing vectors, the expression of RECK mRNA, RECK and p53 signaling pathway-related proteins (p21, p53, bcl-2, and Bax) in cervical cancer cells were respectively examined using qRT-PCR and western blot. Cervical cancer cell migration after transfection was detected by wound healing assay and transwell assay. RECK expression was much lower in cervical cancer cell lines compared with normal cell line. Results of wound-healing assay results indicated that RECK could inhibit cervical cancer cell migration, and transwell assay results demonstrated that cell invasion was suppressed by RECK overexpression. Furthermore, western blot indicated that the overexpression of RECK could promote the activation of p53 signaling pathway by influencing related protein expression; whereas its inhibition by PFT-α could antagonize the effect of RECK on migrative and invasive abilities of cervical cancer cells. RECK could inhibit the migration and invasion of cervical cancer cells by activating p53 signaling pathway.

LncRNA SNHG1 enhances cell proliferation, migration, and invasion in cervical cancer.

OBJECTIVE: This study investigated the effects of lncRNA SNHG1 on the proliferation, migration, and invasiveness of cervical cancer cells. METHODS: Three pairs of cervical cancer tissue samples and their corresponding adjacent samples were analyzed using Human LncRNA Microarray V3.0 chip for differential analysis. The expression of SNHG1 in cervical cancer cell lines was verified by qRT-PCR. CCK8 assays and colony formation assays were used to study the changes in cell proliferation. Cell migration and Transwell assays were used to study changes in cell migration and invasiveness. RESULTS: SNHG1 was highly expressed in cervical cancer tissues and cervical cancer cell lines. SNHG1 siRNA could knock-down the expression level of SNHG1 in cervical cancer cell lines HeLa and C33-A. After knock-down of SNHG1, cell proliferation and migration as well as invasiveness in HeLa and C-33A cells decreased. CONCLUSION: LncRNA SNHG1 promotes the development of cervical cancer cells.

Vaginal Stump Ligation for Cervical Cancer.

BACKGROUND: We aimed to investigate the effect of vaginal stump ligation in laparoscopic cervical cancer surgery on the prevention of cancer cell detachment. METHODS: The study was conducted from 2010 to 2015, in Xuzhou Maternity and Child Health Care Hospital, Jiangsu Province, China. Seventeen cases of laparoscopic surgery of cervical cancer in control group were observed, and the vaginal stump was irrigated with normal saline after the operation and the washing fluid was searched for cancer cells. Moreover, 43 cases of cervical cancer patients received the same operational procedure, and the vaginal stump was ligated in the surgery and the vagina was incised below the ligature. RESULTS: The number of cancer cells in the vaginal washing fluid of the experimental group was significantly more than that of the control group. Furthermore, there was no significant difference in the operation time, intraoperative blood loss, the number of pelvic lymph node dissected, vaginal resection length and parametrium resection length. By comparing the postoperative recovery indicators and complications, we found no significant difference in anal exsufflation time, the incidence of vaginal stump infection, the recovery time of postoperative urinary function and incidence of lymphocysts. Finally, there was no significant difference in the quality of life scores between the two groups. CONCLUSION: Vaginal stump ligation can reduce cancer cell detachment in cervical cancer surgery, and therefore can help preventing cancer cell implantation and tumor recurrence caused by cancer cell detachment.

The proteomic analysis of human neonatal umbilical cord serum by mass spectrometry.

AIM: To investigate the proteome composition and function of human neonatal arterial umbilical cord. METHODS: Serum proteomic analyses were performed on samples from both males and females by using a combination of techniques: (1) removal of six high-abundance proteins, (2) tryptic digestion of low-abundance proteins, (3) separation of peptide mixtures by reverse-phase high-performance liquid chromatography (RP-HPLC), and (4) peptide identification using electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS: A total of 837 non-redundant proteins were identified, with 213 male-specific and 239 female-specific proteins. Among them, 319 proteins were identified by at least 2 distinct peptides. The subcellular localization, function, and pathway involvement for each of the identified proteins were analyzed. A comparison of this neonatal proteome to that of adult serum proteome revealed novel biomarkers, such as alpha-fetoprotein and periostin that were specific to newborn infants. CONCLUSION: These data will contribute to a better understanding of the composition of umbilical cord serum and aid the discovery of novel biomarkers for the prenatal diagnosis of fetal abnormalities.