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Simple Summary: Epithelial ovarian cancer (EOC) is the fifth-leading cause of cancer-related deaths in women worldwide and the most lethal gynecologic malignancy. Seventy-five percent of patients are diagnosed at an advanced stage, accompanied by extensive pelvic and abdominal metastases, and thus have a poor prognosis. We first screened for critical genes in EOC in the GEO database. LLGL2 was upregulated in ovarian cancer tissue, while low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients, implying that LLGL2 may function as a tumor suppressor gene. Our data demonstrated that overexpression of LLGL2 inhibited the ovarian cancer cell migration and invasion abilities in vivo and in vitro. Mechanistically, LLGL2 altered the intracellular localization and function of ACTN1 by interacting with ACTN1 and regulating cytoskeleton remodeling to inhibit the invasion and metastasis of ovarian cancer cells. Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Background: Streptococcus mutans is a well-known oral pathogen that plays a critical role in the development of dental caries. Many studies have been directed to discover the chemical compounds present in natural products to inhibit the growth and biofilm formation activity of S. mutans. Thymus essential oils exhibit good inhibition on the growth and pathogenesis of S. mutans. However, details about the active compounds in Thymus essential oil and the inhibition mechanism still remain unclear. The aim of this study was to investigate the antimicrobial activity of 6 Thymus species (Three samples of Thymus vulgaris, two samples of Thymus zygis, and one sample of Thymus satureioides essential oils) on S. mutans, to identify the potential active components, and to reveal the underlying mechanism. Methods: The composition of Thymus essential oils was analyzed by gas chromatography-mass spectrometry. And its antibacterial effect was evaluated based on the bacterial growth, acid production, biofilm formation and genetic expression of virulence factors by S. mutans. Potential active components of the Thymus essential oil were identified using molecular docking and correlation analysis. Results: GC–MS analysis showed that the major components in the 6 Spain Thymus essential oils were linalool, α-terpineol, p-cymene, thymol and carvacrol. MIC and MBC analysis showed that 3 Thymus essential oils showed very sensitive antimicrobial activity, and were chosen for further analysis. The 3 Thymus essential oil exhibited a significant inhibitory effect on acid production, adherence and biofilm formation of S. mutans and the expression of virulence genes, such as brpA, gbpB, gtfB, gtfC, gtfD, vicR, spaP and relA. Correlation analysis showed that phenolic components, such as carvacrol and thymol, were positively related to DIZ value, which suggests that they are the potential antimicrobial components. Molecular docking between the Thymus essential oil components and virulence proteins also found that carvacrol and thymol exhibited strong binding affinity with functional domains of virulence genes. Conclusions: Thymus essential oil showed significant inhibition against the growth and pathogenesis of S. mutans depending on their composition and concentration. And phenolic compounds, such as carvacrol and thymol, are the major active components. Thymus essential oil could be used in oral healthcare products as a potential anti-caries ingredient. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate two advanced diffusion models, diffusion kurtosis imaging and the newly proposed mean apparent propagation factor-magnetic resonance imaging, in the grading of gliomas and the assessing of their proliferative activity. Methods: Fifty-nine patients with clinically diagnosed and pathologically proven gliomas were enrolled in this retrospective study. All patients underwent DKI and MAP-MRI scans. Manually outline the ROI of the tumour parenchyma. After delineation, the imaging parameters were extracted using only the data from within the ROI including mean diffusion kurtosis (MK), return-to-origin probability (RTOP), Q-space inverse variance (QIV) and non-Gaussian index (NG), and the differences in each parameter in the classification of glioma were compared. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of these parameters. Results: MK, NG, RTOP and QIV were significantly different amongst the different grades of glioma. MK, NG and RTOP had excellent diagnostic value in differentiating high-grade from low-grade glioma, with largest areas under the curve (AUCs; 0.929, 0.933 and 0.819, respectively; P < 0.01). MK and NG had the largest AUCs (0.912 and 0.904) when differentiating grade II tumours from III tumours (P < 0.01) and large AUCs (0.791 and 0.786) when differentiating grade III from grade IV tumours. Correlation analysis of tumour proliferation activity showed that MK, NG and QIV were strongly correlated with the Ki-67 LI (P < 0.001). Conclusion: MK, RTOP and NG can effectively represent the microstructure of these altered tumours. Multimodal diffusion-weighted imaging is valuable for the preoperative evaluation of glioma grade and tumour proliferative activity. [ABSTRACT FROM AUTHOR]

One novel naphthalene derivative, 2-octa-2′,4′,6′-atriynenaphthalene (1), together with eighteen known compounds (2–19) were isolated from the aerial parts of Dracocephalum moldavica L. Compounds 2, 8, 10, 13, 15–17 and 19 were obtained from the family Lamiaceae for the first time, and compounds 11 and 18 were firstly identified from the genus of Dracocephalum. All the isolates were evaluated for anti-complementary activities through the classical and alternative pathways, and the targets of the most active compounds on the complement activation cascade were also investigated. [ABSTRACT FROM AUTHOR]

Two new stilbene glucosides, trans-3,5-dihydroxy-4-methoxystilbene 3-O-β-D-glucopyranoside (1), cis-3,5-dihydroxy-4-methoxystilbene 3-O-β-D-glucopyranoside (2), one new benzoic acid derivative, cis-4-hydroxy-3-hydroxymethyl-2-butenyl benzoate 4-O-β-D-glucopyranoside (3), and four known compounds (4 − 7) were isolated from Tournefortia sibirica L. The structures of these compounds were elucidated on the basis of spectral data. Anti-inflammatory effects of compounds (1 − 7) were evaluated in terms of inhibition on production of NO, TNF-α and IL-6 in LPS-induced RAW 264.7 cells. Compounds 1, 2 and 5 − 7 could inhibit the levels of NO, TNF-α and IL-6 in LPS-induced RAW264.7 cells with IC50 values ranging from 40.96 to 88.76 µM. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common neurodegenerative diseases, and mild cognitive impairment (MCI) is considered a prodromal stage of clinical AD. Animal studies have shown that probiotics can improve cognitive function and mitigate inflammatory response, however, results from randomized controlled trials in humans are still unclear. Objectives: A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of probiotic therapy on cognitive function, oxidative stress, and gastrointestinal function in patients with AD, MCI, and PD. Methods: We searched the electronic databases such as PubMed, EMBASE, Cochrane Library until October 2020 for the eligible randomized controlled trials, as well as the unpublished and ongoing trials. Our primary endpoints were cognitive function, inflammatory and oxidative stress biomarkers, gastrointestinal function, and adverse events. Results: After screening 2,459 titles and abstracts about AD or MCI, we selected 6 eligible studies (n = 499 patients). After screening 1,923 titles and abstracts about PD, we selected 5 eligible studies (n = 342 patients). Compared with the control group, treatment with probiotics improved the cognitive function of patients with AD in the intervention group (P = 0.023). Cognitive function also improved in MCI patients (P = 0.000). Inflammation-related indicators: Malondialdehyde (MDA) was significantly reduced (P = 0.000); and hs-CRP decreased (P = 0.003). Lipid-related indicators: VLDL decreased (P = 0.026); triglyceride decreased (P = 0.009); and insulin resistance level improved: decreased Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P = 0.019). Conclusion: Our analyses suggest that probiotics can improve cognitive and gastrointestinal symptoms in patients with AD, MCI, and PD, which is possibly through reducing inflammatory response and improving lipid metabolism. The safety has also been proven. However, more RCTs with rigorous study design are needed to support our findings. Systematic Review Registration: PROSPERO, Identifier: CRD42021231502. [ABSTRACT FROM AUTHOR]

Two new phenolic glycosides (1–2) and eleven known compounds (3–13) were isolated from the fruits of Illicium verum Hook.f. using silica-gel column and preparative middle pressure liquid chromatography (MPLC). The structures of the compounds were elucidated by NMR spectroscopic data. Among them, compounds 3, 5, and 10 were isolated from the family Magnoliaceae for the first time. Additionally, all the compounds were evaluated for their anti-complementary activities against the classical pathway (CP) and the alternative pathway (AP). [ABSTRACT FROM AUTHOR]

Two new labdane-type diterpenes, named viterotulin C (1) and vitexilactone D (2), together with five known diterpenes (3–7), were isolated from the fruits of Vitex trifolia L. var. simplicifolia Cham. Their structures were elucidated by detailed analysis of spectroscopic data. All the compounds were evaluated for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in HEK 293 cell line. These compounds presented inhibition on TNF-α-induced NF-κB activation, with inhibition rates ranging from 42.52 ± 10.69% to 68.86 ± 10.76% at the concentration of 50 μM. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of Croton crassifolius roots afforded five sesquiterpenes (1–5), including two new sesquiterpenes 6S-hydroxy-cyperenoic acid (1) and crassifterpenoid A (5), together with three known compounds (2–4). The structures of the new compounds were determined by comprehensive spectroscopic methods, and their absolute configurations were determined by quantum chemical ECD calculation. Crassifterpenoid A (5) is the first germacrane-type sesquiterpene isolated from C. crassifolius, which enriched the diversity of chemical constituents in Croton crassifolius. In addition, the cytotoxicities of all compounds against human liver cancer lines HepG2 and Hep3B were determined, but none showed significant activity. [ABSTRACT FROM AUTHOR]

This study investigates the effectiveness of information technology–based 2-way referral in the diagnosis and management of cervical lesions in Minhang District, Shanghai, China. Women who underwent screening for cervical lesions in 4 community health centers constituted the intervention group, whereas women from the other 9 community health centers were included as controls. The diagnosis rate of cervical lesions was higher in the intervention group (7.61%) than in the control group (0.36%; P = .000). The diagnosis rate of early cervical lesion was 97.11% in the intervention group and 85.71% in the control group, showing no statistically significant differences (P = .080). However, early diagnosis rate of precancerous lesion was much higher in the intervention group (95.45%) compared with the control group (64.29%; P = .001). In conclusion, higher effectiveness of early diagnosis and management of cervical lesions was observed in the intervention group compared with the control group. [ABSTRACT FROM AUTHOR]

Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for theirin vitroantibacterial activities against a panel of respiratory pathogens.8band8eexhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules,21showed the best antibacterial activities. [ABSTRACT FROM PUBLISHER]

Two new phenolic acid compounds, asparoffin C (1) and asparoffin D (2), together with four known compounds, asparenyol (3), gobicusin B (4), 1-methoxy-2-hydroxy-4-[5-(4-hydroxyphenoxy)-3-penten-1-ynyl] phenol (5), and asparinin A (6), have been isolated from the stems ofAsparagus officinalis. The structures were established by extensive spectroscopic methods (MS and 1D and 2D NMR). Compound6has obvious antitumor activities bothin vitroandin vivo. [ABSTRACT FROM PUBLISHER]

Introduction: The characteristics of endocardial electrograms needed to detect the overlying abnormal epicardial substrates in arrhythmogenic right ventricular cardiomyopathy with epicardial ventricular tachycardia (VT) remain unclear. This study investigated which of the endocardial electrogram characteristics could predict the overlying abnormal epicardial substrates. Methods and Results: In 20 consecutive patients (median age: 46 years, 11men) undergoing epicardial VT ablation, detailed endocardial and epicardial mappings were obtained by using the CARTO 3 system. The endocardial electrographic characteristics (unipolar peak-to-peak voltage, unipolar peak-negative-voltage, bipolar voltage, and bipolar electrogram duration) of the opposite endocardium and epicardium in RV were retrospectively investigated (N = 1,697 paired points, 84 ± 60 pairs/patient). Endocardial predictors of the presence of epicardial dense scar (<0.5 mV), low voltage zones (LVZ; ⩽1.5 mV), and ablation targets (by using activation mapping, entrainment mapping, and pace mapping) were analyzed. Results: In the multivariable analysis, (1) unipolar peak-negative voltage independently predicted the presence of epicardial LVZ, epicardial dense scar, and ablation targets; (2) bipolar voltage could not predict epicardial lesions; and (3) bipolar electrogram duration predicted epicardial LVZ, but not dense scar or ablation targets. The endocardial unipolar peak-negative voltage of <1.66 mV (89% sensitivity and 53% specificity) was the optimal cutoff point for predicting epicardial dense scar. Conclusions: In patients with RV epicardial VT, the presence of unipolar peak-negative voltage of <1.66 mV in the endocardium predicted the presence of epicardial dense scar (<0.5 mV) and potential ablation targets in the overlying epicardium. [ABSTRACT FROM AUTHOR]

Background. Interferon-γ release assays (IGRAs) have been widely used for the diagnosis of latent and active tuberculosis in adults, but their role in diagnosing latent tuberculosis infection (LTBI) in children younger than 5 years remains unclear. Objective. To evaluate the diagnostic performance of IGRAs for LTBI in children younger than 5 years. Methods. We searched the PubMed, EMBASE, Cochrane Library, and Web of Knowledge databases. According to inclusion criteria, the diagnostic studies of IGRAs for LTBI in children younger than 5 years were included. The study quality was assessed using the 14-item Quality Assessment of Diagnostic Accuracy Studies instrument. The Meta-Analyst software was used to analyze the data. Results. Seven studies (627 patients) were included. Meta-analysis showed that compared with tuberculin skin test (TST), the pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), accuracy and diagnosis odds ratio (DOR), and summary receiver operating characteristic (SROC) curve of QuantiFERON-TB (values in parentheses are 95% confidence intervals) were 0.841 (0.733-0.911), 0.895 (0.861-0.922), 8.046 (5.953-10.876), 0.192 (0.113-0.326), 0.622 (0.527-0.709), 0.970 (0.946-0.983), 0.891 (0.861-0.916), 50.718 (24.201-106.287), and 0.809 respectively. The pooled Sen, Spe, PLR, NLR, PPV, NPV, accuracy, DOR, and SROC curve of T-SPOT.TB test were 0.931 (0.760-0.983), 0.767 (0.684-0.833), 3.947 (2.854-5.459), 0.095 (0.026-0.354), 0.523 (0.398-0.645), 0.977 (0.914-0.994), 0.806 (0.737-0.860), 65.270 (13.463-316.434), and 0.855, respectively. Conclusion. This meta-analysis showed that the sensitivity and specificity of IGRAs were slightly higher than TST and can be used as supporting tools to detect LTBI in children younger than 5 years. The methodological quality of diagnostic test needs to be improved. [ABSTRACT FROM PUBLISHER]

Substrate Modification in Persistent Atrial Fibrillation Introduction The optimal substrate ablation approach in patients with persistent atrial fibrillation (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE: <60 milliseconds) versus extensive (continuous CFAE plus variable CFAE: <120 milliseconds) atrial substrate modification in Per AF patients. Methods and Results We enrolled 120 Per AF patients in the study, and 30 patients with AF termination after pulmonary vein isolation (PVI) were excluded. In the remaining 90 patients, 45 were treated with limited approach (Group 1) and 45 with an extensive approach (Group 2). The end point of the study was the incidence of an atrial arrhythmia recurrence postblanking period. The patients were followed up for 15 months with 3-month clinical reviews, electrograms (ECGs), Holter recordings, and echocardiographic monitoring. Procedural AF termination and the single procedural efficacy were statistically comparable between the 2 groups (48.9% vs. 63.4% in Groups 1 and 2, respectively, P = 0.289). During the follow-up, patients who received limited ablation had a lower incidence of recurrent AFL (P = 0.04), and better reverse remodeling of the left atrium (LA, P = 0.04). After 2 procedures, the freedom from any atrial arrhythmia was better in Group 2 (62.2% vs. 87.8%, P = 0.009). Those with longstanding AF and a larger baseline LA size responded better to the extensive ablation. Conclusions In the Per AF patients who failed to achieve AF termination after PVI alone, a specific atrial substrate modification approach targeting only continuous CFAEs could be considered as an initial ablation strategy. [ABSTRACT FROM AUTHOR]

Objective: To observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction (桂枝汤) on cardiac autonomic nervous (CAN) imbalance. Methods: A radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay. Results: (1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly ( P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased ( P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group ( P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group ( P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased ( P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group ( P<0.05); GAP-43 increased, NGF decreased, and CNTF increased ( P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group ( P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group ( P<0.05). Conclusion: Guizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage. [ABSTRACT FROM AUTHOR]

The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (-1.41 cm 95% CI [-1.61, -1.21]), SF-MPQ at the 3-month followup (WMD -2.33, 95% CI [-4.11, -0.54]) and 6-month followup (WMD -4.67, 95% CI [-7.30, -2.04]), and MDQ at the 3-month followup (WMD -2.31, 95% CI [-3.74, -0.87]) and 6-month followup (WMD -4.67, 95% CI [-7.30, -2.04]). All trials did not report adverse events. These results were limited by the methodological flaws of trials. [ABSTRACT FROM AUTHOR]

Modified Pulmonary Vein Isolation in AF Ablation. Introduction: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high-frequency AF nests may have a higher efficacy. Methods and Results: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0-1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy-guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time-domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow-up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log-rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I. Conclusion: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1155-1162, November 2012) [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of Er'zhi Tiangui Granule (二至天癸颗粒, ETG) on sequential expressions of integrinβ3 and its ligand osteopontin in the mouse endometrium during controlled ovarian hyperstimulation (COH) and implantation period. Methods: Seventy-five Mature female Kunming mice were randomly divided into 3 groups, a normal control group, a model group, and a treatment group administrated with ETG for 10 days, 25 in each group. After mated with male mice, every 5 mice were sacrified in each group at the 0, 2nd, 4th, 6th, and 8th days to take their endometrium. In-situ hybridization was used to detect the expressions of integrinβ3 and osteopontin in the endometrium. Results: mRNA expressions of integrinβ3 and osteopontin in the endometrium during implantation period showed similar time sequence rules in the treatment group to those in the normal control group; the peak values of them were a little lower in the treatment group than the normal control without significant differences. In the model group, integrinβ3 mRNA expression was higher at the 2nd day, obviously lower at the 4th and 6th days, and insignificantly lower at the 8th day; and osteopontin expression was remarkably lower at the 4th, 6th, and 8th days, compared with the normal control and the treatment groups ( P<0.05, P<0.01). Conclusions: COH might influence the sequential expressions of integrinβ3 and its ligand osteopontin, bring forward the integrinβ3 expression peak, impact on the cooperation of integrinβ3 and osteopontin, so as to damage the endometrial receptivity. ETG could regulate the sequential expressions of integrinβ3 and its ligand osteopontin to improve the mouse endometrial receptivity during COH. [ABSTRACT FROM AUTHOR]

Objective. To investigate the differential protein profile of human lung squamous carcinoma (HLSC) and normal bronchial epithelium (NBE) and provide preliminary results for further study to explore the carcinogenic mechanism of HLSC. Methods. Laser capture microdissection (LCM) was used to purify the target cells from 10 pairs of HLSC tissues and their matched NHBE, respectively. A stable-isotope labeled strategy using iTRAQ, followed by 2D-LC/Q-STAR mass spectrometry, was performed to separate and identify the differential expression proteins. Results. A total of 96 differential expression proteins in the LCM-purified HLSC and NBE were identified. Compared with NBE, 49 proteins were upregulated and 47 proteins were downregulated in HLSC. Furthermore, the expression levels of the differential proteins including HSPB1, CKB, SCCA1, S100A8, as well as S100A9 were confirmed by western blot and tissue microarray and were consistent with the results of quantitative proteomics. Conclusion. The different expression proteins in HLSC will provide scientific foundation for further study to explore the carcinogenic mechanism of HLSC. [ABSTRACT FROM AUTHOR]

The effect of dipyridamole (DP) on the cellular retention of 1-beta-D-arabinofuranosylcytosine (ara-C) and its metabolites was examined in leukemic blasts that had been isolated directly from bone marrow aspirates from patients afflicted with acute myeloid leukemia (AML). When AML cells were loaded for 2 h with 1 microM [3H]-ara-C and then transferred to ara-C-free medium, total intracellular concentrations of radiolabel and [3H]-ara-C 5'-triphosphate [3H]-ara-C-CTP rapidly declined. After 8 h, total intracellular levels of tritium were 4.4 times higher if 10 microM was included in the washout medium; however, the majority of this intracellular radiolabel corresponded to [3H]-uridine arabinoside ([3H]-ara-U) and [3H]-ara-C. DP significantly increased the mean t1/2 for [3H]-ara-CTP from 102 to 136 min (P less than 0.01), but this effect was much less pronounced than that obtained for total tritium and the increase was quite variable (0-70%; median, 19%). The presence of DP in the washout medium also increased the incorporation of ara-C into DNA and the formation of ara-CDP-choline. The level of ara-CDP-choline continued to increase in both DP-containing and DP-free media for the first 4 h following drug removal and the formation of ara-CDP-choline continued during the first few hours in ara-C-free medium. At the end of the 8-h wash in DP-containing medium, the cellular concentration of ara-CDP-choline was equivalent to that found at the beginning of the washout period. Although statistically significant, the effect of DP on ara-CTP retention in AML blasts was much less pronounced than that previously observed in L5178Y leukemia. The former cells exhibited only 10% as many nucleoside transport carriers as did the L5178Y cells as measured by their capacity to bind [3H]-nitrobenzylmercaptopurine riboside (NBMPR). The effect of DP in prolonging ara-CTP retention was proportional to the number of [3H]-NBMPR binding sites. This suggests that in patients cells that exhibit extremely low transport capacity, most of the net catabolism occurs via deamination, and further inhibition of transport by DP in an effort to improve cellular retention of ara-C has little effect on ara-CTP catabolism. [ABSTRACT FROM AUTHOR]

Sequential treatment of murine leukemia L5178Y with cytosine arabinoside (ara-C) followed by dipyridamole (DP) resulted in synergistic cytotoxicity. Viability of cells exposed to 1 microM ara-C for 4 h was 88% of control values, but if DP was included in the cloning medium, cell viability was reduced to only 30%. When cells exposed to 1 microM ara-C were resuspended in ara-C-free medium containing 10 microM DP, intracellular ara-C and its metabolites were retained for a significantly longer period than when cells were resuspended in drug-free medium. At 4 h after resuspension in ara-C-free medium, total intracellular [3H] was 1.9 pmol/10(6) cells in control cells but amounted to 6.2 pmol/10(6) cells in DP-treated cells. Unchanged ara-C was 5.5-fold higher in the DP-treated cells. Presumably because of its effect on the concentration of intracellular ara-C, DP increased the half-life for ara-CTP from 97 to 250 min. Ara-CDP-choline declined with a half-life of 76 min on the transfer of cells to control medium, but levels of this metabolite remained constant or increased slightly in cells transferred to medium containing DP. After 4 h in ara-C-free medium with DP, [3H]-ara-C incorporated into the acid-insoluble fraction was 140% of the level attained when cells were transferred to control medium. The increased levels of ara-C metabolites presumably represent the basis for the enhancement of ara-C cytotoxicity by sequential DP treatment. [ABSTRACT FROM AUTHOR]

One new pseudoguaianolide (1), one new megastigmane (6), and one new ent -abietane diterpene (9), together with seven known compounds (2 – 5 , 7 , 8 , and 10) were isolated from the aerial parts of Euphorbia thymifolia. The structures of the new compounds and their relative configurations were determined by spectroscopic data analysis. The absolute configurations of compounds 1 , 6 , and 9 were determined by single-crystal X-ray crystallographic analysis, modified Mosher's method and calculated ECD experiment, respectively. All compounds were tested for their inhibitory effects against LPS-induced NO production in BV-2 microglial cells, and pseudoguaianolides (1 – 5) showed significant activity with IC 50 values of 0.41–15.32 μM. Unlabelled Image [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Adolescents with cardiac disease are at risk for life-changing complications and premature death. The importance of advance care planning (ACP) in adults with congenital heart disease and in pediatric patients with HIV and cancer has been demonstrated. ACP preferences of adolescents with heart disease have not been evaluated. We describe ACP preferences of adolescents with heart disease and compare with those of their caregivers. METHODS: Outpatient adolescents aged 12 to 18 years with heart failure, cardiomyopathy, heart transplantation, or who were at risk for cardiomyopathy, as well as their caregivers, completed self-administered questionnaires which evaluated participants' opinions regarding content and timing of ACP discussions, preferences for end-of-life communication, and emotional responses to ACP. RESULTS: Seventy-eight adolescents and 69 caregivers participated, forming 62 adolescent-caregiver dyads. Adolescents and caregivers reported that adolescent ACP discussions should occur early in the disease course (75% and 61%, respectively). Adolescents (92%) wanted to be told about terminal prognosis, whereas only 43% of caregivers wanted the doctor to tell their child this information. Most adolescents (72%) and caregivers (67%) anticipated that discussing ACP would make the adolescent feel relieved the medical team knew their wishes. Most caregivers (61%) believed that adolescents would feel stress associated with ACP discussions, whereas only 31% of adolescents anticipated this. CONCLUSIONS: Adolescents and their caregivers agree that ACP should occur early in disease course. There are discrepancies regarding communication of prognosis and perceived adolescent stress related to ACP discussions. Facilitated conversations between patient, caregiver, and providers may align goals of care and communication preferences. [ABSTRACT FROM AUTHOR]

Abstract: Microbial transformation of ursolic acid (UA, 3β-hydroxy-urs-12-en-28-oic acid, 1) by filamentous fungus Syncephalastrum racemosum CGMCC 3.2500 was conducted. Five metabolites 3β, 7β, 21β-trihydroxy-urs-12-en-28-oic acid (2); 3β, 21β-dihydroxy-urs-11-en-28-oic acid-13-lactone (3); 1β, 3β, 21β-trihydroxy-urs-12-en-28-oic acid (4); 3β, 7β, 21β-trihydroxy-urs-1-en-28-oic acid-13-lactone (5); and 21-oxo-1β, 3β-dihydroxy-urs-12-en-28-oic acid (6) were afforded. Elucidation of the structures of these metabolites was primarily based on 1D and 2D NMR and HR-MS data. Metabolite 2 was a new compound. In addition, the anti-HCV activity of compounds 1–6 was evaluated. [Copyright &y& Elsevier]

The acquisition of a mesenchymal phenotype is a critical step in the metastatic progression of epithelial carcinomas. Adherens junctions (AJs) are required for suppressing this epithelial-mesenchymal transition (EMT) but less is known about the role of tight junctions (TJs) in this process. Here, we investigated the functions of blood vessel epicardial substance (BVES, also known as POPDC1 and POP1), an integral membrane protein that regulates TJ formation. BVES was found to be underexpressed in all stages of human colorectal carcinoma (CRC) and in adenomatous polyps, indicating its suppression occurs early in transformation. Similarly, the majority of CRC cell lines tested exhibited decreased BVES expression and promoter DNA hypermethylation, a modification associated with transcriptional silencing. Treatment with a DNA-demethylating agent restored BVES expression in CRC cell lines, indicating that methylation represses BVES expression. Reexpression of BVES in CRC cell lines promoted an epithelial phenotype, featuring decreased proliferation, migration, invasion, and anchorage-independent growth; impaired growth of an orthotopic xenograft; and blocked metastasis. Conversely, interfering with BVES function by expressing a dominant-negative mutant in human corneal epithelial cells induced mesenchymal features. These biological outcomes were associated with changes in AJ and TJ composition and related signaling. Therefore, BVES prevents EMT, and its epigenetic silencing may be an important step in promoting EMT programs during colon carcinogenesis. [ABSTRACT FROM AUTHOR]