Prenatal maternal inactivated COVID-19 vaccination: the maternal and neonatal outcomes, a retrospective cohort study.

Background: Despite the widespread adoption of COVID-19 vaccination, a comprehensive understanding of potential vaccine-induced adverse effects, particularly in the context of pregnancy, remains a critical area of investigation. Elevated concerns surround the maternal and neonatal outcomes subsequent to prenatal maternal COVID-19 vaccination. While existing studies have provided insights into the safety profile of COVID-19 mRNA vaccines, the extrapolation of these conclusions to inactivated COVID-19 vaccines poses uncertainties. Notably, limited data are available regarding the maternal and neonatal effects associated with inactivated COVID-19 vaccines. Objective: To evaluate the prenatal maternal inactivated COVID-19 vaccination and the impact on maternal and neonatal outcomes. Methods: This was a retrospective cohort study of women who delivered between January and June 2022 at a single university-affiliated hospital. Those who have completed at least one dose of inactivated vaccine before or during pregnancy were included in "vaccinated group," and those who were not vaccinated were included in "unvaccinated group," the maternal, pregnancy and neonatal outcomes were evaluated. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups. Results: A total of 1926 women were enrolled in this study, 827 (42.94%) women were prenatally vaccinated, and 1099 (57.06%) unvaccinated. The gestational week of delivery were slightly lower in the vaccinated group, 38.61 ± 1.89 weeks in the vaccinated group and 38.93 ± 1.49 weeks in the unvaccinated group. There was a higher rate of overall preterm delivery in the vaccinated group (aOR 1.61, 95% CI 1.07-2.42; p = 0.02), however, the probability of delivery before 34 weeks and before 32 weeks (early preterm delivery) were similar (p > 0.05). A total of 2009 infants were born, 851 in the vaccinated group and 1158 in the unvaccinated group. There were similar neonatal outcomes in the two groups. Conclusion: Although we found a slightly lower gestational week of delivery and a possible increased rate of late preterm birth in the vaccination group, there was no difference in mean neonatal weight, incidence of low birth weight infants and other neonatal adverse complications. Meanwhile, there was no difference in pregnancy and maternal outcomes between the two groups.

Chiral zinc oxide functionalized quartz crystal microbalance sensor for enantioselective recognition of amino acids.

Chiral transition metal oxides with tunable structures and multiple physicochemical features have been increasingly applied for chiral sensing and detection. In this work, chiral zinc oxide (ZnO) was first applied as selector to construct quartz crystal microbalance (QCM) sensor for enantioselective recognition of amino acids. The chiral ZnO was prepared by a methionine-induced self-assembly strategy and its high topological chirality was confirmed by several techniques such as circular dichroism spectrum. The chiral discrimination factors were calculated by frequency shifts in response to aspartic acid, phenylalanine, lysine and arginine on L-ZnO surface, achieving 1.89 ± 0.04, 1.76 ± 0.11, 1.66 ± 0.07 and 1.54 ± 0.09, respectively. Notably, L-enantiomers preferred stronger absorptions on L-ZnO surface as compared to D-forms. It was further found that this sensor was appropriate for quantitative analysis and enantiomer excess analysis and adsorption kinetics study. Furthermore, molecular docking revealed the recognition mechanism, where chiral distinction was caused by the different steric interactions between enantiomers and chiral ZnO. This method enjoyed merits of high enantioselectivity, simple preparation and low cost, offering newly chiral sensing method for other molecules.

Berberine Ameliorates Insulin Resistance by Inhibiting IKK/NF-κB, JNK, and IRS-1/AKT Signaling Pathway in Liver of Gestational Diabetes Mellitus Rats.

Introduction: Berberine is derived from rhizoma coptidis, a well-known Traditional Chinese herbal Medicine that has been found to be effective in the treatment of type 2 diabetes mellitus in recent years. The aim of the present study was to investigate the effects of berberine on a gestational diabetes mellitus (GDM) rat model and the related mechanisms. Methods: GDM was induced in Sprague-Dawley rats using a high-fat diet before and during pregnancy. Berberine (100 mg/kg/day) was administered from the 7th to 20th day of pregnancy. Insulin resistance (IR), glucose tolerance, and maternal, fetal, and placental weight were determined. Liver histopathological analysis, as well as analysis of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), inhibitor kappa B kinaseß (IKKß), nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1), and protein kinase B (AKT), was performed at the end of pregnancy. Results: Treatment of GDM rats with berberine markedly decreased IR, the number of dead and absorptive fetuses, maternal body weight gain, and fetal and placental weight compared with GDM without berberine. Furthermore, berberine decreased CRP and TNF-α levels, IKKß expression, NF-κB P65 nuclear translocation, and changed the phosphorylation of JNK, IRS-1, and AKT in the liver of GDM rats. Conclusions: Berberine improved IR and maternal-fetal outcomes of GDM rats, possibly through modulation of IKK/NF-κB, JNK, and IRS-1/AKT signaling pathways in the liver. Therefore, berberine may be a potential GDM treatment.

Long-noncoding RNA HOXA transcript at the distal tip ameliorates the insulin resistance and hepatic gluconeogenesis in mice with gestational diabetes mellitus via the microRNA-423-5p/wingless-type MMTV integration site family member 7A axis.

Long-noncoding RNA HOXA transcript at the distal tip (HOTTIP) has been probed to exert essential effects on diabetes progression, while its function in gestational diabetes mellitus (GDM) remains unclear. This study was committed to unravel the effects of HOTTIP on GDM progression via the microRNA (miR)-423-5p/wingless-type MMTV integration site family member 7A (WNT7A) axis. The GDM mouse model was established. HOTTIP, miR-423-5p and WNT7A levels in GDM mice were examined. The saline with dissolved various constructs altering HOTTIP, miR-423-5p and WNT7A expression was injected into GDM mice to detect the levels of GDM-related biochemical indices, HOMA indices, liver gluconease: expression levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase), glucose transporter 2 (GLUT2) and pathological changes of pancreatic tissues, and the apoptosis rate of pancreatic cells in GDM mice. The relations among HOTTIP, miR-423-5p and WNT7A were validated. HOTTIP and WNT7A levels were decreased while miR-423-5p was elevated in GDM mice. The enriched HOTTIP or silenced miR-423-5p alleviated the levels of GDM-relatedbiochemical indices, enhanced the insulin homeostasis, elevated GLUT2 expression and decreased G-6-pase and PEPCK expression, mitigated the pathological changes of pancreatic tissues, and hindered the apoptosis of pancreatic cells. MiR-143-5p upregulation abrogated the effects of elevated HOTTIP on repressing GDM; whereas WNT7A deletion reversed the therapeutic effects of reduced miR-423-5p. HOTTIP sponged miR-423-5p that targeted WNT7A. HOTTIP ameliorates insulin resistance and hepatic gluconeogenesis in GDM mice via the modulation of the miR-423-5p/WNT7A axis. This study affords novel therapeutic modalities for GDM treatment.

Serum Metabolomics Based on GC-MS Reveals the Antipyretic Mechanism of Ellagic Acid in a Rat Model.

Ellagic acid (EA) is a polyphenol dilactone that has been reported to have antipyretic, anti-inflammatory, anti-tumor, and antioxidant activities, but the mechanism of action has not been reported. In this study, serum metabolomics was used to explore the mechanism of EA on rat fever induced by beer yeast, and to screen out marker metabolites to provide a reference for the antipyretic effect of EA. The acute fever model of male Sprague Dawley rats involved subcutaneous injection with 20% aqueous suspension of yeast (15 mL/kg) in their back. At the same time of modeling, EA was given orally by 10 mL/kg intragastric administration for treatment. During the experiment, the temperature and its change values of rats were recorded, and Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Prostaglandin E2 (PGE2), Cyclic Adenosine Monophosphate (cAMP), Superoxide Dismutase (SOD) and Malondialdehyde (MDA)­six physiological and biochemical indexes of rats­were detected after the experiment. In addition, the hypothalamus of each rat was analyzed by Western blot (WB), and the levels of Phospho Nuclear Factor kappa-B (P-NF-κB P65) and IkappaB-alpha (IKB-α) were detected. Then, the serum metabolites of rats in each group were detected and analyzed by gas chromatograph mass spectrometry and the multivariate statistical analysis method. Finally, when screening for differential metabolites, the potential target metabolic pathway of drug intervention was screened for through the enrichment analysis of differential metabolites. Pearson correlation analysis was used to systematically characterize the relationship between biomarkers and pharmacodynamic indicators. EA could reduce the temperature and its change value in yeast induced fever rats after 18 h (p < 0.05). The level of IL-6, TNF-α, PGE2, cAMP, SOD and MDA of the Model group (MG) increased significantly compared to the Normal group (NG) (p < 0.001) after EA treatment, while the levels of the six indexes in the serum and cerebrospinal fluid of yeast-induced rats decreased. The administration of yeast led to a significant increase in Hypothalamus P-NF-κB P65 and IKB-α levels. Treatment with EA led to a significant decrease in P-NF-κB P65 levels. Moreover, combined with VIP > 1 and p < 0.05 as screening criteria, the corresponding retention time and characteristic mass to charge ratio were compared with the NIST library, Match score > 80%, and a total of 15 differential metabolites were screened. EA administration significantly regulated 9 of 15 metabolites in rat serum. The 15 differential metabolites involved linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, galactose metabolism, biosynthesis of unsaturated fatty acids and glycerolipid metabolism. Pharmacodynamic correlation analysis was conducted between 15 different metabolites and six detection indexes. There was a significant correlation between 13 metabolites and six detection indexes. D-(−)-lactic acid, glycerin, phosphoric acid, 5-oxo-L-proline were negatively correlated with TNF-α, and p values were statistically significant except for L-tyrosine. In addition, glycerin was negatively correlated with IL-6, PGE2 and MDA, while phosphoric acid was negatively correlated with IL-6. In conclusion, EA may play an antipyretic anti-inflammatory role through the inhibition of the IKB-α/NF-κB signaling pathway and five metabolic pathways, which may contribute to a further understanding of the therapeutic mechanisms of the fever of EA.

The Potential Antipyretic Mechanism of Ellagic Acid with Brain Metabolomics Using Rats with Yeast-Induced Fever.

Fever is caused by an increase in the heat production process when the body is under the action of a heat source or the dysfunction of the temperature center. Ellagic acid (EA) is a polyphenol dilactone that has anti-inflammatory, anti-tumor, and antioxidant activities. Male Sprague-Dawley rats were injected yeast to reproduce an experimental fever model (150 ± 20 g), and the rectal temperature and its change values were subsequently taken 19 h later; the excessive production of interleukin-1ß (IL-1ß) and prostaglandin2 (PGE2) induced by yeast was regulated to normal by EA administration. Rat brain metabolomics investigation of pyrexia and the antipyretic anti-inflammatory effect of EA was performed using Ultra-High-Performance Liquid Chromatography-Mass spectrometry (UPLC-MS). Twenty-six metabolites, as potential biomarkers, significantly altered metabolites that were found in pyretic rats, and eleven metabolites, as biomarkers of the antipyretic mechanism of EA, were significantly adjusted by EA to help relieve pyrexia, which was involved in glycerophospholipid metabolism and sphingolipid metabolism, etc. In conclusion, potential metabolic biomarkers in the brain shed light on the mechanism of EA's antipyretic effects, mainly involving metabolic pathways, which may contribute to a further understanding of the therapeutic mechanisms of fever and therapeutic mechanism of EA.

Polyphyllin I alleviates inflammatory injury in mice with gestational diabetes through AMPK pathway.

Our study aimed to detect the effects of polyphyllin I (PPI) on relieving gestational diabetes mellitus (GDM), and the possible mechanism. A mouse model of GDM was constructed. The effects of PPI on GDM mice were evaluated by detecting blood glucose, insulin level, glucose tolerance test, and insulin tolerance test. The inflammation response in GDM and GDM+PPI group were evaluated by enzyme-linked immunosorbent assay (ELISA). The effect of PPI on the offspring of GDM mice was analyzed. In addition, immunoblot assays were performed to investigate the effects of PPI on the AMPK pathway. We found that PPI improved diabetes-related symptoms and decreased serum inflammatory response in GDM mice. In addition, we also found that PPI reduced the tissue damage of GDM mice. We noticed that PPI alleviated inflammatory injury in GDM mice through targeting AMPK pathway. Our findings showed that PPI has the potential to be explored as the drug for GDM treatment.

[Analysis of chemical constituents in ethyl acetate extract of Taxilli Herba by UPLC-Q-Exactive-MS and screening of potential xanthine oxidase inhibitors].

The present study analyzed and identified the chemical constituents from ethyl acetate(EA) extract of Taxilli Herba with UPLC-Q-Exactive-MS and screened active xanthine oxidase(XO) inhibitors with HPLC. The analysis was performed on an Hypersil GOLD C_(18) reversed-phase column(2.1 mm×50 mm, 1.9 µm), with the mobile phase of water containing 1% formic acid(A) and methanol(B) under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 5 µL. ESI source was used for MS and the compounds were collected in positive and negative ion modes. Xcalibur 4.1 was used to analyze the retention time, accurate relative molecular weight, and fragmentation of the compounds. The inhibitory activity of some known compounds on XO was screened by HPLC. Thirty chemical constituents were identified, including phenolic acids and flavonoids by experimental data combined with information of standards, data reported previously, and databases, such as MzCloud and ChemSpider. The activities of 10 chemical components were screened. Gallic acid and naringenin chalcone had strong inhibitory activities on XO with IC_(50) of 57 µg·mL~(-1) and 108 µg·mL~(-1). UPLC-Q-Exactive-MS allows the accurate, rapid, and comprehensive identification of main chemical constituents from Taxilli Herba. Gallic acid and naringenin chalcone may be the active components of XO inhibitors.

Metabolomics Study of Flavonoids of Taxilluschinensis on Different Hosts Using UPLC-ESI-MS/MS.

The goal of this study was to identify and compare the main biomarkers of Taxillus chinensis from different hosts. A metabolomics approach utilizing ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS), including cluster analysis, sample correlation analysis and orthogonal partial least squares discriminant analysis, was used to explore the flavonoid metabolites of Taxillus chinensis growing on different hosts. Results: The total flavonoids content (up to 30.08 mg/g) in Taxillus chinensis from Morus alba (CSG) was significantly higher than that from growth on Liquidambar formosana (CFG) or Clausena lansium (CHG) (p < 0.01). There were 23 different metabolites between CSG and CHG, 23 different metabolites between CSG and CFG, and 19 different metabolites between CHG and CFG. The results demonstrated that different hosts exerted a large influence on the metabolites of Taxillus chinensis; it was found that CSG differed from CFG and CHG in eleven metabolic compounds, ten of which were upregulated and one of which was downregulated. Most of these metabolites derive from compounds contained in the host plant, white mulberry (Morus alba); many feature potent anti-cancer effects. Differences in host can influence the type and abundance of flavonoids in parasitic plants such as Taxillus chinensis, which is of great significance to researchers seeking to understand the formation mechanism of Taxillus chinensis metabolites. Therefore, attention should be paid to the species of host plant when studying the Taxillus chinensis metabolome. Plants grown on Morus alba offer the greatest potential for the development of new anti-cancer drugs.

Modified Grisotti flap technique in centrally located breast cancer: case report.

Traditionally, breast cancer patients with centrally located mass always receive mastectomy or the combination of central excision and primary closure. With the development of modern oncoplastic breast-conserving techniques, these patients can conserve their breast, and achieve satisfactory cosmetic outcome as well as clear margin. A variety of techniques are available to deal with centrally located breast cancers (CLBCs). Among these techniques, Grisotti flap technique is special, because it is easy to handle, and only causes minor injury by using a local rotational dermoglandular flap to fill the defection of central part. However, in our clinical practice, we find a lot of women in south China have special properties. Such as short distance from inframammary liner to the nipple, long distance from midclavicular to the nipple, and large breast diameter. Simply apply the Grisotti flap technique to those patients is not very suitable that drive us to modify this technique to suit our patients. We adopt the idea that use pedicled skin flap with skin island to replace the central defection to modify Grisotti flap technique. And applied this technique to two patients. We find modified Grisotti flap technique for Paget's disease or CLBC had good cosmetic results as well as safety in suitable patients. In the future, we can use superior pedicle with skin island for ptotic breasts, and lateral pedicle is suitable for patients without large and ptotic breasts.

Research on Location Algorithm Based on Beacon Filtering Combining DV-Hop and Multidimensional Support Vector Regression.

The DV-Hop algorithm is widely used because of its simplicity and low cost, but it has the disadvantage of a large positioning error. In recent years, although some improvement measures have been proposed, such as hop correction, distance-weighted correction, and improved coordinate solution, there is room for improvement in location accuracy, and the accuracy is affected in anisotropic networks. A location algorithm based on beacon filtering combining DV-Hop and multidimensional support vector regression (MSVR) is proposed in this paper. In the process of estimating the coordinates of unknown nodes, received signal strength indication (RSSI), MSVR, and weighted least squares method are combined. In addition, the verification error of beacon nodes is proposed, which can select the beacon nodes with smaller errors to reduce the location error. Simulation results show that in different distributions, the location accuracy of the proposed algorithm is at least 34% higher than that of the classical DV-Hop algorithm and at least 28% higher than that of the localization based on multidimensional support vector regression (LMSVR) algorithm. The proposed algorithm has the potential of application in small-scale anisotropic networks.

Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation.

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

The role of surgical intervention for isolated breast cancer liver metastasis: Results of case-control study with comparison to medical treatment.

BACKGROUND: Combined with systemic therapy, the surgical intervention for breast cancer liver metastases (BCLM) is increasingly accepted but lacks convincing evidence. The aim of this study was to evaluate the disease control efficacy of hepatic surgery in isolated BCLM patients. METHODS: Between 2012 and 2017, metastatic breast cancer patients with isolated liver metastasis and regular follow-up were identified. Cohort design was conducted to compare the progression-free survival (PFS) between the surgical and nonsurgical BCLM patients. Univariate analysis and multivariate Cox regression survival analyses were performed to identify significant prognostic factors. RESULT: In all, 148 isolated BCLM patients were enrolled and 95 participants received hepatic surgery for metastatic lesions. With median follow-up of 36.47 months, there was no significant difference between hepatic surgical group and nonsurgical group for PFS (median PFS: 11.17 months vs 10.10 m, P = .092). Based on the multivariate analysis, the disease-free interval (DFI) was an independent prognostic factor for isolated BCLM patients. Among the surgical group, BCLM patients who had ideal response after first salvage systemic treatment experienced the best long-term survival (median PFS: 14.20 months). CONCLUSION: For isolated BCLM patients with ideal response in first-line medical treatment, surgical intervention (hepatectomy, radiofrequency ablation) combining with systemic treatment could bring improved progression-free survival compared to sole systemic treatment, indicating that hepatic surgery may be considered as a therapeutic choice for selected isolated BCLM patients in clinical practice.

Traditional Chinese Medicine Extract from Huaier Increases the Expression of Duffy Antigen Receptor for Chemokines and Reduces the Expression of Its Ligands.

AIMS: The aim of the present study is to investigate whether the aqueous extract from Huaier, a traditional Chinese medicine (TCM), can affect the expression of Duffy antigen receptor for chemokines (DARC) and its ligands. Moreover, we compare the status of DARC in primary and metastatic breast cancer tissues from the same patient. METHODS: Immunohistochemistry was used to detect the expression of DARC in primary and metastatic focuses in 30 patients with breast cancer. The effect of Huaier aqueous extract on the expression of DARC and its ligands was investigated by quantitative real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. RESULTS: The expression score of DARC in primary focuses was significantly higher than that in metastatic focuses, while changes of ER, PR, and HER2 receptors were not significantly different between primary and metastatic focuses. Huaier aqueous extract promoted the expression of DARC and reduced the secretion of CC chemokine ligand 2 (CCL-2), CXC chemokine ligand 8 (CXCL-8, IL-8), matrix metalloproteinase 2 (MMP-2), and CXC chemokine ligand 1 (CXCL-1). CONCLUSION: The present study demonstrates that difference in expression level of DARC between primary and metastatic focuses of breast cancer was significant, while differences in expression of ER, PR, and HER2 between primary and metastatic focuses were not significant. DARC may play a negative role in the metastasis of breast cancer. Traditional Chinese medicine extract from Huaier can increase DARC expression and reduce the expression of its ligands such as CCL-2, IL-8, MMP-2, and CXCL-1.

Trillium tschonoskii maxim extract attenuates abnormal Tau phosphorylation.

Large-scale epidemiological studies have found that hyperhomocysteinemia is a powerful, independent risk factor for Alzheimer's disease. Trillium tschonoskii maxim is a traditional Chinese medicine that is used to promote memory. However, scientific understanding of its mechanism of action is limited. This report studied the potential neuroprotective effects of Trillium tschonoskii maxim extract against homocysteine-induced cognitive deficits. Rats were intravenously injected with homocysteine (400 µg/kg) for 14 days to induce a model of Alzheimer's disease. These rats were then intragastrically treated with Trillium tschonoskii maxim extract (0.125 or 0.25 g/kg) for 7 consecutive days. Open field test and Morris water maze test were conducted to measure spontaneous activity and learning and memory abilities. Western blot assay was used to detect the levels of Tau protein and other factors involved in Tau phosphorylation in the hippocampus. Immunohistochemical staining was used to examine Tau protein in the hippocampus. Golgi staining was applied to measure hippocampal dendritic spines. Our results demonstrated that homocysteine produced learning and memory deficits and increased levels of Tau phosphorylation, and diminished the activity of catalytic protein phosphatase 2A. The total number of hippocampal dendritic spines was also decreased. Trillium tschonoskii maxim extract treatment reversed the homocysteine-induced changes. The above results suggest that Trillium tschonoskii maxim extract can lessen homocysteine-induced abnormal Tau phosphorylation and improve cognitive deterioration such as that present in Alzheimer's disease.

Visual and Colorimetric High-Throughput Analysis of Chiral Carboxylic Acids Based on Enantioselective Charge Shielding of Gold Nanoparticles.

Because chiral carboxylic acids (CCAs) are a class of important biological molecules and common functional moieties found in pharmaceutical molecules, the chiral analysis of CCAs has received much attention. Herein, we developed a simple, rapid, and cost-effective method for visual and colorimetric high-throughput analysis of CCAs using chiral di-imine structure-modified gold nanoparticles (C-AuNPs) as the probe. The C-AuNPs are positively charged in the presence of zinc ion, and they can be enantioselectively shielded by the negatively charged CCA enantiomers. Therefore, upon the addition of different concentrations and enantiomeric excess (ee) of CCAs, the C-AuNP-based sensor shows the different levels of aggregation along with the visual changes in solution color, which can achieve simultaneous analysis of the concentration and ee of CCAs. The chiral recognition mechanism based on C-AuNPs was investigated by the determination of binding constants ( K) and molecular simulation methods. Our approach is expected to have the wide-ranging applications in the developing region for enantio-sensing of various chiral drugs and biomolecules.

Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.

Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells. Crizotinib also increases the intracellular reactive oxidative species (ROS) levels, and pretreating with ROS scavenger N-acety-L-cysteine partially reverses crizotinib-induced apoptosis. Moreover, crizotinib can synergistically inhibit ovarian cancer cells growth in vitro and in vivo when combines with cisplatin. Altogether, crizotinib potently potentiates the activity of cisplatin in ovarian cancer, suggesting the synergistic effect of crizotinib and cisplatin may be valuable for ovarian cancer patients' treatment.

Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752.

OBJECTIVE: Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. METHODS: Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). RESULTS: MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. CONCLUSION: Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer.

[Volatile Oil Analysis of Piper hongkongense form Different Hatbitats by GC-MS].

OBJECTIVE: To analyze the volatile oil in Piper hongkongense from five different habitats. METHODS: The volatile oil was analyzed by GC-MS. RESULT: The volatile components oil of each sample varied significantly. Caryophyllene, α-caryophyllene and nerolidol 2 were common constituents of five samples. The volatile oil and chemical constituent contents of fresh sample were higher than that of the old sample. CONCLUSION: The volatile oil and chemical constituent contents of Piper hongkongense from different habitats have sig- nificant differences, which are affected by habitats, harvest season, storage time and so on.

Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer.

Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. In this study, we investigated the anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular ROS levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine significantly blocked ROS generation but only partially rescued apoptosis triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin synergistically promoted cell cycle arrest and apoptosis, and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether, dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer, indicating this beneficial combinational therapy may be a promising strategy for treatment of ovarian cancer.