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Tumor growth and metastasis rely on angiogenesis. In recent years, long non-coding RNAs have been shown to play an important role in regulating tumor angiogenesis. Here, we review the multidimensional modes and relevant molecular mechanisms of long non-coding RNAs in regulating tumor angiogenesis. In addition, we summarize new strategies for tumor anti-angiogenesis therapies by targeting long non-coding RNAs. The aim of this study is to provide new diagnostic targets and treatment strategies for anti-angiogenic tumor therapy.

Background Hepatocellular carcinoma (HCC) is a serious health concern because of its high morbidity and mortality. The prognosis of HCC largely depends on the disease stage at diagnosis. Computed tomography (CT) image textural analysis is an image analysis technique that has emerged in recent years. Objective To probe the feasibility of a CT radiomic model for predicting early (stages 0, A) and intermediate (stage B) HCC using Barcelona Clinic Liver Cancer (BCLC) staging. Methods A total of 190 patients with stages 0, A, or B HCC according to CT-enhanced arterial and portal vein phase images were retrospectively assessed. The lesions were delineated manually to construct a region of interest (ROI) consisting of the entire tumor mass. Consequently, the textural profiles of the ROIs were extracted by specific software. Least absolute shrinkage and selection operator dimensionality reduction was used to screen the textural profiles and obtain the area under the receiver operating characteristic curve values. Results Within the test cohort, the area under the curve (AUC) values associated with arterial-phase images and BCLC stages 0, A, and B disease were 0.99, 0.98, and 0.99, respectively. The overall accuracy rate was 92.7%. The AUC values associated with portal vein phase images and BCLC stages 0, A, and B disease were 0.98, 0.95, and 0.99, respectively, with an overall accuracy of 90.9%. Conclusion The CT radiomic model can be used to predict the BCLC stage of early-stage and intermediate-stage HCC.

Objectives: This study aimed to explore the role of inhibin subunit beta A (INHBA) in the progression of cervical cancer (CCa) and investigate its potential as a therapeutic target. Specifically, the objectives were to assess the expression levels of INHBA in CCa, examine its correlation with patient survival, and elucidate its impact on CCa cell proliferation, cell cycle regulation, migration, invasion, and in vivo tumor growth and metastasis. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. INHBA expression in CCa was analyzed, and its association with patient survival was assessed using clinical data. In vitro experiments involved the investigation of INHBA's effects on CCa cell proliferation, cell cycle dynamics, migration, and invasion through the epithelial–mesenchymal transition (EMT) process. Additionally, in vivo experiments were performed to evaluate the influence of INHBA on CCa growth and lung metastasis. Results: The results of this study revealed upregulated expression of INHBA in CCa, with a significant association between high INHBA expression and poor patient survival. Functionally, INHBA was found to promote the proliferation of CCa cells, regulate the cell cycle, and enhance migration and invasion through the EMT process in vitro. Moreover, in vivo experiments demonstrated that INHBA facilitated the growth and lung metastasis of CCa. Conclusion: In conclusion, our findings suggest that INHBA plays a crucial role in the progression of cervical cancer. The upregulation of INHBA is associated with poor patient survival, and its involvement in promoting key aspects of cancer progression makes it a potential therapeutic target for CCa treatment. These results provide valuable insights into the molecular mechanisms underlying CCa and offer a foundation for further exploration of targeted therapeutic interventions.

Background Previous studies have failed to investigate the specific effects of advanced age on survival outcomes by considering the Charlson Comorbidity Index (CCI) and age permutation in patients with T1a renal cell carcinoma (T1a RCC) treated by microwave ablation (MWA). Notably, RCC guidelines recommended radiofrequency ablation (RFA) and active surveillance (AS) are both treatment options for elderly T1a RCC, but whether MWA is superior to AS in light of higher heating efficiency and larger ablation zone compared with RFA is not clear. This study aimed to investigate the specific effects of advanced age on survival outcomes of T1a RCC patients stratified by CCI score and indicate better intervention for elderly T1a RCC between MWA and AS. Methods This was a retrospective study. We retrospectively reviewed 237 patients with T1a RCC who had undergone MWA over the last 16 years. Data were analyzed by Cox regression and Landmark analysis. Interaction tests and propensity score matching were used to account for potential biases. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of patients ≥75 years in our study with corresponding figures from 4251 counterparts undergoing AS in published articles. Results Using patients ＜75 years with a CCI ≤2 as a reference, the hazard ratio (HR) and 95% confidence interval (CI) of OS for patients＜75 years with a CCI ≥3, patients ≥75 years with a CCI ≤2, and patients ≥75 years with CCI ≥3, were 2.954 (1.139-7.663), 3.48 (1.487-8.146), and 3.357 (1.162-9.698), respectively. The adverse effect of an age ≥75 years on OS was attenuated in patients with a CCI ≥3. The attenuation lasted for 62.5 months of follow-up ( P = .017). Notably, advanced age exerted a protective effect on progression-free survival (PFS) in patients with a CCI ≥3, increasing the 8-year PFS from 67.8% to 100% ( P = .049). Relative to 1-, 3-, 5-, and 8-year survival data for patients aged ≥75 undergoing AS, the OS rates for 5-year follow-up were always better in MWA. However, beyond 5 years, the OS rates dropped to levels that were similar to AS. Conclusions Advanced age exerts adverse effects and significantly protective effects on OS and PFS, respectively, in T1a RCC patients with a CCI ≥ 3. According to our study, elderly patients with T1a RCC underwent radical MWA may yield a better medium-term OS relative to AS.

Objective: To evaluate the recent practice of design and statistical analysis of ophthalmic randomized clinical trials (RCTs). Design: Review of 96 ophthalmic RCTs. Methods: Two authors (R.D., G.S.Y.) reviewed primary result papers published from January 2020 through December 2021 in Ophthalmology, JAMA Ophthalmology, American Journal of Ophthalmology, and British Journal of Ophthalmology. Data were extracted and analyzed for the characteristics of design (1-eye design, 2-eye design, paired-eye design, and subject design), sample size and power, and statistical analysis for intereye correlation adjustment, missing data, and correction for multiplicity. Main Outcome Measures: Characteristics of trial design and statistical analysis. Results: Among 96 RCTs, 50 (52%) used 1-eye design, 21 (22%) 2-eye design, 10 (10%) paired-eye design, and 15 (16%) subject design. In 31 trials of 2-eye design or paired-eye design, 18 (58%) trials had suboptimal analysis of data from both eyes by analyzing data from 1 eye (n = 10), taking the average of 2 eyes (n = 2), analyzing 2 eyes separately (n = 1), ignoring intereye correlation (n = 3), or not specifying how 2-eye data were analyzed (n = 2), and 13 trials (42%) properly adjusted the intereye correlation by using the mixed-effects model (n = 6), paired t test (n = 5), generalized estimating equations (n = 1), or marginal Cox regression model (n = 1). Among 96 trials, 75 (78%) provided both sample size and statistical power estimation, and 16 (17%) trials described statistical test for sample size or power estimation. Missing data in primary outcome occurred in 86 (90%) trials with a median missing data rate of 8%, 32 (37%) trials applied statistical methods for missing data, including last value carried forward (n = 10), multiple imputation (n = 14), or other approaches (n = 8). Among 25 trials with > 2 arms, 16 (64%) corrected for multiplicity using the Bonferroni procedure (n = 8), Hochberg procedure (n = 2), Gatekeeping procedure (n = 2), or hierarchical procedure (n = 4). Among 16 trials with multiple primary outcomes, 4 (25%) corrected for multiplicity by the Bonferroni procedure. Conclusions: There are opportunities for improvement in the design and statistical analyses of ophthalmic trials, particularly in the aspects of adjustment for intereye correlation, missing data, and multiplicity. Continuing education in ophthalmology and vision research community may improve the quality of ophthalmic trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Cancer is a public health problem that threatens human health. Due to the lack of specific and rapid diagnosis and treatment methods, the 5-year survival rate of patients has not been effectively improved in the past 10 years. Abnormal gene expression is closely related to the occurrence and development of cancer. Cancer diagnosis and treatment methods based on genetic testing have received extensive attention in recent years. It is essential to explore specific and rapid cancer genetic testing methods. Taking ovarian cancer as an example, we reviewed the progress of specific and rapid nucleic acid detection methods related to cancer risk assessment, low-abundance mutation detection, and methylation detection, to provide new strategies and ideas for related research.

Wnt/β-catenin signaling plays important role in cancers. Compound 759 is one of the compounds previously screened to identify inhibitors of the Wnt/β-catenin pathway in A549 cells [Lee et al. in Bioorg Med Chem Lett 20:5900-5904, 2010]. However, the mechanism by which Compound 759 induces the inhibition of the Wnt/β-catenin pathway remains unknown. In our study, we employed various assays to comprehensively evaluate the effects of Compound 759 on lung cancer cells. Our results demonstrated that Compound 759 significantly suppressed cell proliferation and Wnt3a-induced Topflash activity and arrested the cell cycle at the G1 stage. Changes in Wnt/β-catenin signaling-related protein expression, gene activity, and protein stability including Axin, and p21, were achieved through western blot and qRT-PCR analysis. Compound 759 treatment upregulated the mRNA level of p21 and increased Axin protein levels without altering the mRNA expression in A549 cells. Co-treatment of Wnt3a and varying doses of Compound 759 dose-dependently increased the amounts of Axin1 in the cytosol and inhibited β-catenin translocation into the nucleus. Moreover, Compound 759 reduced tumor size and weight in the A549 cell-induced tumor growth in the in vivo tumor xenograft mouse model. Our findings indicate that Compound 759 exhibits potential anti-cancer activity by inhibiting the Wnt/β-catenin signaling pathway through the increase of Axin1 protein stability., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The response variability to repetitive transcranial magnetic stimulation (rTMS) challenges the effective use of this treatment option in patients with schizophrenia. This variability may be deciphered by leveraging predictive information in structural MRI, clinical, sociodemographic, and genetic data using artificial intelligence. We developed and cross-validated rTMS response prediction models in patients with schizophrenia drawn from the multisite RESIS trial. The models incorporated pre-treatment sMRI, clinical, sociodemographic, and polygenic risk score (PRS) data. Patients were randomly assigned to receive active (N = 45) or sham (N = 47) rTMS treatment. The prediction target was individual response, defined as ≥20% reduction in pre-treatment negative symptom sum scores of the Positive and Negative Syndrome Scale. Our multimodal sequential prediction workflow achieved a balanced accuracy (BAC) of 94% (non-responders: 92%, responders: 95%) in the active-treated group and 50% in the sham-treated group. The clinical, clinical + PRS, and sMRI-based classifiers yielded BACs of 65%, 76%, and 80%, respectively. Apparent sadness, inability to feel, educational attainment PRS, and unemployment were most predictive of non-response in the clinical + PRS model, while grey matter density reductions in the default mode, limbic networks, and the cerebellum were most predictive in the sMRI model. Our sequential modelling approach provided superior predictive performance while minimising the diagnostic burden in the clinical setting. Predictive patterns suggest that rTMS responders may have higher levels of brain grey matter in the default mode and salience networks which increases their likelihood of profiting from plasticity-inducing brain stimulation methods, such as rTMS. The future clinical implementation of our models requires findings to be replicated at the international scale using stratified clinical trial designs., (© 2024. The Author(s).)

Predictive modeling strategies are increasingly studied as a means to overcome clinical bottlenecks in the diagnostic classification of autism spectrum disorder. However, while some findings are promising in the light of diagnostic marker research, many of these approaches lack the scalability for adequate and effective translation to everyday clinical practice. In this study, our aim was to explore the use of objective computer vision video analysis of real-world autism diagnostic interviews in a clinical sample of children and young individuals in the transition to adulthood to predict diagnosis. Specifically, we trained a support vector machine learning model on interpersonal synchrony data recorded in Autism Diagnostic Observation Schedule (ADOS-2) interviews of patient-clinician dyads. Our model was able to classify dyads involving an autistic patient (n = 56) with a balanced accuracy of 63.4% against dyads including a patient with other psychiatric diagnoses (n = 38). Further analyses revealed no significant associations between our classification metrics with clinical ratings. We argue that, given the above-chance performance of our classifier in a highly heterogeneous sample both in age and diagnosis, with few adjustments this highly scalable approach presents a viable route for future diagnostic marker research in autism., (© 2024. The Author(s).)

Autism spectrum disorder is characterized by impaired social communication and interaction. As a neurodevelopmental disorder typically diagnosed during childhood, diagnosis in adulthood is preceded by a resource-heavy clinical assessment period. The ongoing developments in digital phenotyping give rise to novel opportunities within the screening and diagnostic process. Our aim was to quantify multiple non-verbal social interaction characteristics in autism and build diagnostic classification models independent of clinical ratings. We analyzed videos of naturalistic social interactions in a sample including 28 autistic and 60 non-autistic adults paired in dyads and engaging in two conversational tasks. We used existing open-source computer vision algorithms for objective annotation to extract information based on the synchrony of movement and facial expression. These were subsequently used as features in a support vector machine learning model to predict whether an individual was part of an autistic or non-autistic interaction dyad. The two prediction models based on reciprocal adaptation in facial movements, as well as individual amounts of head and body motion and facial expressiveness showed the highest precision (balanced accuracies: 79.5% and 68.8%, respectively), followed by models based on reciprocal coordination of head (balanced accuracy: 62.1%) and body (balanced accuracy: 56.7%) motion, as well as intrapersonal coordination processes (balanced accuracy: 44.2%). Combinations of these models did not increase overall predictive performance. Our work highlights the distinctive nature of non-verbal behavior in autism and its utility for digital phenotyping-based classification. Future research needs to both explore the performance of different prediction algorithms to reveal underlying mechanisms and interactions, as well as investigate the prospective generalizability and robustness of these algorithms in routine clinical care., (© 2024. The Author(s).)

Background: Formal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level., Methods: Two hundred thirty-three individuals with recent-onset psychosis were drawn from the multisite European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multiband fractional amplitude of low frequency fluctuations, gray matter volume and white matter volume data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up., Results: Cross-sectionally, multivariate patterns of gray matter volume within the salience, dorsal attention, visual, and ventral attention networks separated the FThD severity subgroups (balanced accuracy [BAC] = 60.8%). Longitudinally, distributed activations/deactivations within all fractional amplitude of low frequency fluctuation sub-bands (BAC slow-5  = 73.2%, BAC slow-4  = 72.9%, BAC slow-3  = 68.0%), gray matter volume patterns overlapping with the cross-sectional ones (BAC = 62.7%), and smaller frontal white matter volume (BAC = 73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multimodal balanced accuracy of BAC = 77%., Conclusions: We report the first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open up avenues for the development of neuroimaging-based diagnostic, prognostic, and treatment options for the early recognition and management of FThD and associated poor outcomes., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant variables rather than specific psychiatric symptoms. We employed a new data-driven method (Orthogonal Projective Non-Negative Matrix Factorization) to delineate novel gyrification-based networks of structural covariance in 308 healthy controls. Gyrification within the networks was then compared to 713 patients with recent onset psychosis or depression, and at clinical high-risk. Associations with diagnosis, symptoms, cognition, and functioning were investigated using linear models. Results demonstrated 18 novel gyrification networks in controls as verified by internal and external validation. Gyrification was reduced in patients in temporal-insular, lateral occipital, and lateral fronto-parietal networks (pFDR < 0.01) and was not moderated by illness group. Higher gyrification was associated with better cognitive performance and lifetime role functioning, but not with symptoms. The findings demonstrated that gyrification can be parsed into novel brain networks that highlight generalized illness effects linked to developmental vulnerability. When combined, our study widens the window into the etiology of psychiatric risk and its expression in adulthood., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biologically active bacterial cellulose (BC) was efficiently synthesized in situ using wine pomace and its hydrolysate. The structural and biomechanical properties together with the biological functions of the BC were investigated. Functional BC from wine pomace and its enzymatic hydrolysate were of high purity and had higher crystallinity indexes (90.61% and 89.88%, respectively) than that from HS medium (82.26%). FTIR results proved the in-situ bindings of polyphenols to the functionalized BC. Compared to BC from HS medium, wine pomace-based BC had more densely packed ultrafine fibrils, higher diameter range distributions of fiber ribbon, but lower thermal decomposition temperatures, as revealed by the SEM micrographs and DSC data. Meanwhile, wine pomace-based BC exhibited higher loads in tensile strength and higher hardness (4.95 ± 0.31 N and 5.13 ± 0.63 N, respectively) than BC in HS medium (3.43 ± 0.14 N). Furthermore, BC synthesized from wine pomace hydrolysate exhibited a slower release rate of phenolic compounds, and possessed more antioxidant activities and better bacteriostatic effects than BC from wine pomace. These results demonstrate that BC synthesized in situ from wine pomace (especially from enzymatic hydrolysate) is a promising biomolecule with a potential application in wound dressing, tissue engineering, and other biomedical fields., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A cellulose-producing bacterium Komagataeibacter rhaeticus K15 was isolated from kombucha tea, and its metabolic pathways and cellulose synthesis operon were analyzed by genome sequencing. Different from the reported K. rhaeticus, the K15 produced little gluconic acid (2.26 g/L) when glucose was the sole carbon source and has the capacity for high cellulose production (4.76 g/L) with other carbon sources. Furthermore, six nitrogen-fixing genes were found to be responsible for the survival of K15 on a nitrogen-free medium. Based on its fermentation characteristics, K15 was cultured in a kitchen waste medium as a strategy for green and sustainable bacterial cellulose production. The SEM, XRD, and FTIR results indicated that synthesized cellulose has a mean diameter of 40-50 nm nanofiber, good crystallinity, and the same chemical structure. The K15 strain provides a highly viable alternative strategy to reduce the costs of bacterial cellulose production using agro-industrial residues as nutrient sources., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The conjugate prepared from (-)-epigallocatechin gallate (EGCG) and soy protein isolate (SPI) under alkaline and aerobic conditions was analyzed using a Nano-LC-Q-Orbitrap-MS/MS technique. The sulfhydryl and free amino groups of SPI were involved in covalent binding. Fifty-one peptides were conjugated with EGCG. Fifty-nine modified sites were identified, located on Cys, His, Arg, and Lys, respectively. It is the first time to confirm that each of the two phenolic rings of EGCG contained a reactive site that bound to an amino acid residue. The amino acid residue reactivity, amino acid sequence and composition affected the EGCG binding site in SPI. Lys and Arg residues are the most likely sites for modification, and modification appears to reduce IgE binding. This study is helpful to elucidate the pattern of covalent binding of polyphenols to proteins in food systems and provides a theoretical basis for the directional modification of soy proteins with polyphenols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context., Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels., Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample., Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The beneficial effects of bee pollen on prostate diseases are well known. Clinicians confirm that, in nonbacterial prostate diseases, bee pollen improves the condition of patients effectively. However, there is insufficient evidence to rate effectiveness of bee pollen on prostate cancer., Aim of the Study: High hydrostatic pressure (HHP), an effective non-thermal technique to improve the nutritional quality and bio-functionality of plant-based foods, was used to increase the anti-proliferative properties of Lotus (Nelumbo nucifera) bee pollen (LBP) in prostate cancer PC-3 cells via enhancement of bioactive compounds., Materials and Methods: Freeze-dried lotus bee pollen produced from Fu Zhou city, Jiangxi province, China, was processed by high hydrostatic pressure (HHP). The anti-proliferative activities, apoptosis of ethanol and methanol extracts in prostate cancer PC-3 cells was evaluated using MTT method and Annexin-V/PI cell apoptosis assay kit, respectively. The changes of metabolites were determined using UPLC-Triple-TOF-MS analysis platform., Results: HHP treatment enhanced anti-proliferative activities, cell apoptosis, cell cycle disruption, glutathione-depletion in prostate cancer PC-3 cells. The metabolomics analysis showed that some metabolites such as chaetoglobosin A, glutathione oxidized, cyanidin 3-rutinoside, brassicoside, sophoranone, curcumin II, soyasaponin II were significantly increased (p < 0.05) after the HHP treatment, PCA results shown that these bioactive components have quite correlation with anti-proliferative activities of lotus bee pollen on the PC-3 cells. The results indicated that HHP enhances the anti-prostate cancer activity of lotus bee pollen via increased metabolites., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: This study evaluates the efficacy of osimertinib for the treatment of previously epidermal growth factor receptor tyrosine kinase inhibitors (EFGR-TKI) treated non-small cell lung cancer (NSCLC) patients., Method: Research articles reporting the efficacy of osimertinib for NSCLC patients were identified from literature databases (Embase, Ovid, PubMed and Scopus) by following pre-determined eligibility criteria. Response and survival data were extracted from study reports and were pooled under random-effects model to obtain overall/subgroup effect sizes of selected efficacy outcomes., Results: Nine studies (950 patients; age 60.1 years [95% confidence interval: 57.2, 63.1]; 65% [95% CI: 62, 69] females; 69% [35, 100] with T790M; 61% [53, 68] with ex19del; and 35% [29, 41] with L858R mutations). Osimertinib treatment was associated with a PFS of 11.17 months [7.80, 14.55] which was longer in treatment-naïve (20.30 [15.37, 25.23]) than in prior EGFR-TKI-treated (10.20 [9.60, 10.80]) patients. 1-year survival was 81.29% [73.25, 89.32]. Complete response rate was 1.48% [1.19, 1.76]. PR was achieved in 53.18% [24.18, 82.18] patients which differed between treatment-naïve and prior EGFR-TKI-treated patients (74.48 [65.59, 83.37] and 67.99% [62.68, 73.30], respectively. Objective response rate and disease control rates were 69.80% [64.84, 74.77] and 92.43% [89.42, 95.43], respectively, which did not differ between treatment-naïve and prior EGFR-TKI-treated patients., Conclusion: Osimertinib treatment yields approximately 10 months PFS in prior EGFR-TKI-treated and 20 months in treatment-naïve NSCLC patients. Partial response rate is also higher in treatment-naïve patients. However, objective response rate (ORR) and disease control rate (DCR) did not differ between groups of patients.

The present study was aimed to investigate the effects of non-covalent and covalent interactions between soy protein isolate (SPI) and different concentrations (1, 2 and 5 mM) of (-)-epigallocatechin gallate (EGCG) regarding the structural and functional properties of the complex. The combination with EGCG caused changes in the secondary structure of SPI. The covalent complexes formed at low concentrations of EGCG tended to form a network structure. Compared with the SPI-EGCG non-covalent complexes, the covalent complexes exhibited higher thermal stability and oxidation resistance and a polyphenol-protective effect. In addition, the corresponding anti-digestive ability of the covalent complexes was strong and would therefore be more stable in the intestinal tract. The findings of this study provide a theoretical reference and research basis for the use of different SPI-polyphenol complexes as functional food ingredients or as bioactive materials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Eurotium cristatum, a beneficial fungus isolated from Fuzhuan tea, was used to ferment Angelica dahurica for the first time. The antioxidant capacities of the extracts before and after fermentation were compared using ABTS, DPPH and FRAP assays. The results showed that the antioxidant capacities of the extracts acquired using organic solvents were greater after fermentation. Moreover, based on a comparison of the HPLC chromatograms, the chemical composition of Angelica dahurica changed substantially during fermentation. To further understand the changes in its antioxidant constituents, an on-line HPLC-PDA-Triple-TOF-MS/MS-ABTS system was employed. Twelve antioxidants belonging to three different classes were detected and identified, and their antioxidant capacities were preliminarily evaluated. The results indicated that the substances produced during the fermentation of Eurotium cristatum played important roles in enhancing the antioxidant capacity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We aimed to investigate the influence of long non-coding RNA (lncRNA) PTEN pseudogene-1 (PTENP1) on the proliferation, migration and cycle of breast cancer cells and its mechanism. Lentiviral vectors expressing PTENP1 were synthesized and breast cancer cells MCF7 were transfected with LV003-GFP-PTENP1 and LV003-GFP, respectively. The proliferation capacities of breast cancer cells were detected using CCK-8 assay, and the migration capacities of breast cancer cells were detected using scratch assay; flow cytometry was used to detect the cell cycles and Western blot was used to detect the expression levels of cyclin A2, CDK2, p-p44/42 MAPK, t-p44/42 MAPK, p-p38 MAPK, t-p38 MAPK, p-AKT, t-AKT in AKT and MAPK pathways. The absorbance values (A450) of cells in experimental group at 48 and 72 h were 1.4±0.3 and 2.3±0.47, respectively, which were significantly lower than those in control group (3.2±0.39, 3.4±0.58) (P<0.05). The number of cell colonies in experimental group was (48±13), which was significantly lower than that in control group (159±16) (P<0.01). The cell migration rate in experimental group was 22.8±3.3%, which was significantly lower than that in control group 61.8±5.2% (P<0.01). Western blot detection showed that the expression levels of cyclin A2, CDK2, p-AKT, p-p44/42 MAPK and p-p38 MAPK in experimental group were significantly decreased compared with those in control group. LncRNA PTENP1 can inhibit the proliferation and migration of breast cancer cells via the AKT and MAPK signaling pathways.

Irradiation can extend the shelf-life of fish, but it may cause unacceptable change on quality. Since rose polyphenols have high antioxidant and antibacterial activities, this study evaluated the combined effect of polyphenol-chitosan coatings and irradiation (3 kGy) on the microbial and sensory qualities of carp fillets during storage at 4 °C. A dose of 3 kGy irradiation reduced the initial total viable counts (TVC) and psychrophiles, and increased the initial b * and thiobarbituric acid reactive substance (TBARS) values. During storage, TBARS, TVC and psychrophiles of nonirradiated samples increased faster and were higher than those irradiated. Regardless of irradiation treatment, samples coated with chitosan containing rose polyphenols had lower TBARS, pH and bacteria than that in no coating or chitosan coating batches. Carp treated with combined treatment could preserve an acceptable sensory quality at the end of storage. The result indicated that polyphenol-chitosan coating combined with irradiation can maintain fish quality by preventing bacterial growth, oxidation, and changes in color and sensory acceptability., (© 2017 Institute of Food Technologists®.)

Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing to the need for therapeutic drugs without side effects, natural extracts containing various polyphenolic compounds that may exert estrogenic effects have been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a traditional herbal medicine for centuries in Korea, was recently revealed to exert estrogenic effects attributable to its bioactive ingredients sulfuretin and butein, which have strong estrogen receptor-binding affinities. In this study, the protective potential of RVS in PMO was evaluated by using an experimental animal model of PMO, which was established by ovariectomy (OVX) of female Sprague Dawley rats. The oral administration of RVS at 20 mg/kg or 100 mg/kg for 8 weeks markedly protected against OVX-induced atrophy of the uterine tube and reversed the elevation in the ratio of serum receptor activator of nuclear factor-κB ligand to osteoprotegerin, which is a marker of disease severity. In addition, RVS inhibited OVX-induced tibia bone loss, activated osteogenic activity, and suppressed osteoclastic activity in the tibial epiphyseal plate, a region of bone remodeling. Collectively, these factors indicated that the oral intake of RVS might be beneficial for the prevention of PMO.

Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs). The anticancer effect of gemcitabine combined with sclareolide was then assessed. Epithelial to mesenchymal transition (EMT), human equilibrative nucleoside transporter 1 (hENT1) and ribonucleoside diphosphate reductase 1 (RRM1) were detected in the HPCCs and GR‑HPCCs, and the mechanisms were investigated. Sclareolide resensitized the GR‑HPCCs to gemcitabine. The expression levels of hENT1 and RRM1 were lower and higher, respectively, in GR‑HPCCs, compared with HPCCs. Sclareolide upregulated hENT1, downregulated RRM1 and inhibited gemcitabine‑induced EMT through the TWIST1/Slug pathway in the GR‑HPCCs. In addition, sclareolide mediated the NOTCH 1 intracellular cytoplasmic domain (NICD)/glioma‑associated oncogene 1 (Gli1) pathway, which triggered TWIST1/Slug‑hENT1/RRM1 signaling and resensitized GR‑HPCCs to gemcitabine. Finally, sclareolide resensitized GR‑HPCCs to gemcitabine through inducing apoptosis; in vivo, the co‑administraion of sclareolide and gemcitabine effectively suppressed tumor growth. Sclareolide may be a novel agent in combination with gemcitabine for the treatment of gemcitabine‑resistant pancreatic cancer, which resensitizes GR‑HPCCs to gemcitabine through mediating NICD and Gli1.

Background: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics., Objective: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells., Materials and Methods: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system., Results: TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control., Conclusion: Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases., Summary: Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein., Competing Interests: There are no conflicts of interest.

Ethylmercury (EtHg) is derived from the degradation of thimerosal, the most widely used organomercury compound. In this study, EtHg-induced toxicity and autophagy in the mouse kidney was observed and then the mechanism of toxicity was explored in vitro in HK-2 cells. Low doses of EtHg induced autophagy without causing any histopathological changes in mouse kidneys. However, mice treated with high doses of EtHg exhibited severe focal tubular cell necrosis of the proximal tubules with autophagy. EtHg dose-dependently increased the production of reactive oxygen species, reduced the mitochondrial membrane potential, activated the unfolded protein response, and increased cytosolic Ca 2+  levels in HK-2 cells. Cell death induced by EtHg exposure was caused by autophagy and necrosis. N-acetyl cysteine and 4-phenylbutyric acid attenuated EtHg-induced stress and ameliorated the autophagic response in HK-2 cells. Furthermore, EtHg blocked autophagosome fusion with lysosomes, which was demonstrated via treatment with wortmannin and chloroquine. Low doses of EtHg and rapamycin, which resulted in minimal cytotoxicity, increased the levels of the autophagic SNARE complex STX17 (syntaxin 17)-VAMP8-SNAP29 without altering mRNA levels, but high dose of EtHg was cytotoxic. Inhibition of autophagic flux by chloroquin increased autophagosome formation and necrotic cell death in HK-2 cells. Collectively, our results show that EtHg induces autophagy via oxidative and ER stress and blockade of autophagic flux. Autophagy might play a dual role in EtHg-induced renal toxicity, being both protective following treatment with low doses of EtHg and detrimental following treatment with high doses., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Cimicifugae rhizoma has been widely used as a traditional herbal medicine to treat inflammation and menopausal symptoms. In this study, we found that some of the triterpenoidal saponins purified from the ethanol extract of Cimicifugae rhizoma dramatically induced histamine release. The structure-related induction of mast cell degranulation by them and the mechanism of action were determined. β-Hexosaminidase release in HMC-1 cells was increased in a concentration-dependent manner, with maximal 6.5- and 8.5-fold increases, by 200 μg/mL 24-epi-7,8-didehydrocimigenol-3-O-xyloside (comp 1) and cimigenol 3-O-beta-d-xyloside (comp 4) compared with those treated with phorbol 12-myristate 13-acetate and A23187 (PMACI), respectively. However, β-hexosaminidase release was not changed by 7,8-dihydrocimigenol (comp 3), or 23-OAc-shengmanol-3-O-xyloside (comp 7). These triterpenoidal saponins changed neither the intracellular Ca(2+ )level nor the activation of PKC, both of which play essential roles in histamine release. However, cromolyn and ketotifen, membrane stabilizers, effectively inhibited the β-hexosaminidase release induced by comp 1 or comp 4 by 39 and 45%, respectively. Collectively, xylose on the cimigenol-related backbone among triterpene glycosides isolated from Cimicifugae rhizoma may play an important role in activating mast cells and induction of degranulation partly via membrane destabilization of mast cells.

Background: Intervertebral disk degeneration (IDD) has a greater than 90% lifetime incidence and is one of the leading causes of chronic back pain in the United States. Despite the high societal cost of IDD, there is limited understanding of the biological effects of mechanical overloading on further degeneration. The transcription factor NF-κB (nuclear factor κB) has been implicated as a key mediator of disk cell response to inflammatory and mechanical stresses and represents a potential control point., Objective: The study objective was to measure the effect of NF-κB signaling pathway inhibition on annulus fibrosus (AF) cell matrix synthesis and gene expression under conditions of combined inflammatory and mechanical stimulation., Methods: Annulus fibrosus cells were harvested from rabbit intervertebral disks and grown in vitro on flexible plates. The cells were exposed to inflammatory and mechanical stimulation for 24 hours with and without NF-κB inhibition. Nuclear translocation of NF-κB was measured via immunofluorescent staining. Intervertebral disk cell homeostasis was assessed via inflammatory, anabolic, and catabolic gene expression and via matrix synthetic ability., Results: NF-κB nuclear translocation in response to interleukin-1 beta (IL-1β) was reversed with exposure to NF-κB inhibition. NF-κB inhibition decreased matrix metalloproteinase-3, inducible nitric oxide synthase, and cyclooxygenase-2 gene expression and prostaglandin E2 production response to combined inflammatory and mechanical stimulation. Proteoglycan and collagen synthesis were decreased by combined stimulation, but this effect was not reversed by NF-κB inhibition., Limitations: In vitro modeling of conditions within the disk may not fully reflect the response that AF cells have in native matrix., Conclusions: NF-κB signaling mediates catabolic and inflammatory responses to inflammatory and mechanical stimulation but does not mediate the decrease in matrix synthesis under combined harmful stimulation. Identification of key control points in the cellular responses to inflammatory and mechanical stimuli will facilitate rational design of exercise-based therapies and facilitate synergistic treatments of novel biochemical treatments with rehabilitation regimens., (© 2016 American Physical Therapy Association.)

The endocrine-disrupting effects of androgenic signaling play crucial roles in several androgen-related diseases. In attempting to develop an in vitro cell line to be used in androgen receptor (AR)-mediated reporter gene assays, we developed a stable 22Rv1/MMTV cell line, which is a human prostate cancer cell line that endogenously expresses functional AR, to evaluate AR-mediated transcriptional activation (TA). Using 22Rv1/MMTV cells, we established and optimized a test protocol for the AR-TA assay and validated the proposed assay using 20 compounds recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). All the performance parameters for agonist and antagonist assays were 91-100% comparable between the 22Rv1/MMTV assay and the ICCVAM report. In conclusion, the AR-TA assay using 22Rv1/MMTV cells might be a quick and relatively inexpensive method for screening large numbers of chemicals for their potential to activate or inhibit AR-mediated gene transcription., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this study was to develop a simultaneous method to quantify 10 bioactive compounds in Rhus verniciflua extracts using high-performance liquid chromatography-tandem mass spectrometry. The chromatographic separation was performed using a C18 column under gradient elution with 0.1% formic acid and acetonitrile as the mobile phase solvents. The analytes were detected in the negative-ion mode using multiple-reaction monitoring detection with an electrospray ionization interface. The calibration curves for all the analytes showed good linearity (r(2) >0.997) over the concentration range of 1-1,000 ng/mL. The recovery values were within 89.53-110.14%, and the intra- and interday coefficients of variation were <4.86% for all the tested compounds. The developed method was successfully applied to a quality assessment of the R. verniciflua extract samples., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Rhus verniciflua stokes (RVS) is a popular medicinal plant in oriental medicines which is commonly used to resolve extravasated blood. To elucidate the molecular mechanism of the role of RVS extracts on the regulation of lipid and cholesterol biosynthesis, we investigated whether RVS extract protect the hyperlipidemia in western diet-induced C57BL6/J mice. Mice fed a western diet and additionally RVS extracts was administered orally at a dose of 0.1 or 1 g/kg/day for 2 weeks respectively. Group with higher dose of RVS extract showed a significantly decreased body weight compared with western diet fed mice groups. And total cholesterol, LDL-cholesterol levels and fatty liver formation were also improved especially in group of mice fed western diet supplemented high dose RVS extracts. Next, synthesis of hepatic bile acids were significantly increased in RVS extract fed groups. Furthermore, RVS extracts significantly increase promoter activity of Cyp7a1 via up-regulate the transcriptional expression level of LXRα. Our data suggest that RVS extracts could be a potent therapeutic ingredient for prevent a hyperlipidemia via increase of bile acids biosynthesis.

We used a meta-analysis approach to investigate the association between proton pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to identify eligible studies. We included studies that compared cirrhotic patients who did or did not use PPIs. The primary outcome was SBP, and the secondary outcome was overall bacterial infection. Results were pooled using random-effect models. This process led to identification of 12 journal articles and 5 conference abstracts. The pooled data showed that PPI use in patients with cirrhosis and ascites was significantly associated with an increased risk of SBP [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I2 = 85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P < 0.05; I2 = 0). Subgroup analysis revealed that journal articles and studies reporting adjusted effect estimates demonstrated that PPI users had a significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I2 = 29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I2 = 67%, respectively). In conclusion, PPI use increased the risk of SBP and overall bacterial infection in patients with cirrhosis and ascites. PPIs should be administered after careful assessment of the indications in cirrhotic patients. Future well-designed prospective studies are warranted to clarify the dose relationships and to compare infection risks associated with different classes of PPIs.

Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Rhus verniciflua (Toxicodendron vernicifluum) is a medicinal tree popularly used in Asian countries such as China, Japan, and Korea as a food additive or herbal medicine because of its beneficial effects. R. verniciflua extract (RVE) contains diverse phenolic compounds, such as flavonoids, as its major biological active constituents. In this study, the pharmacokinetic profiles of eight phenolic compounds were investigated following oral administration of RVE to rats. The eight phenolic compounds were 2,4-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, fisetin, fustin, butin, sulfuretin, taxifolin, and garbanzol. The plasma concentrations of the eight compounds were determined by using a liquid chromatography-triple-quadrupole mass spectrometer before and after treatment with β-glucuronidase. When 1.5 g/kg RVE was administered, the eight compounds were all detected in plasma, mainly as conjugated forms. These pharmacokinetic data would be useful for understanding the pharmacological effects of RVE.

Rhus verniciflua stokes (RVS) is known to promote blood circulation by preventing blood stasis, although the active ingredients and the underlying mechanism are unclear. Platelets are the primary cells that regulate circulation and contribute to the development of diverse cardiovascular diseases by aggregation and thrombosis. The study assessed the antiplatelet activity of RVS and sought to identify the active constituents. Pretreatment of washed platelets with RVS heartwood extract blunted the aggregatory response of platelets to collagen. In the subfractions, fisetin, butein, and sulfuretin were identified as effective inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'-diphosphate. Antiplatelet activities of all three compounds were concentration dependent, and fisetin had longer in vitro duration of action compared with butein or sulfuretin. Extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase activation by collagen was prevented by fisetin, whereas butein and sulfuretin failed to inhibit ERK and p38 activation was not affected by any of the compounds. Rats orally administered 100 mg/(kg·day(-1)) fisetin for 7 days were resistant to arterial thrombosis, although total extract of RVS heartwood exhibited little effect at a dose of 1000 mg/(kg·day(-1)). RVS heartwood may have cardiovascular protective activity by inhibiting platelet aggregation. The active constituents are fisetin, butein, and sulfuretin, and fisetin is orally effective against thrombosis.

Background: Very few studies have evaluated the potential of using B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as surrogate markers to guide clinical interventional or conservative therapy decisions., Aim: : The aim of the current study was to evaluate the potential of using BNP and NT-proBNP as surrogate markers to guide clinical interventional or conservative therapy decisions., Methods: We identified randomized controlled trials that randomized patients with acute coronary syndrome (ACS) of unstable angina and myocardial infarction without ST-segment elevation ACS to early invasive therapy versus a more conservative approach by systematic search of articles and databases., Results: Five randomized controlled trials with a total of 8125 patients and with a mean duration of 11.2 months were included in the meta-analysis. At a mean follow-up of 11.2 months, the incidence of all-cause mortality was 5.9% in the early invasive group, compared with 6.8% in the conservative group (risk ratio = 0.74; 95% confidence interval, 0.59-0.86; P = 0.001)., Conclusions: In summary, BNP/NT-proBNP-guided management of ACS is significantly improved by early invasive therapy by improving long-term survival and reducing nonfatal myocardial infarction for unstable angina. However, there does not seem to be a clear benefit of using such a strategy over existing clinical recommendations.

Objective: The aim of this study was to evaluate the safety and efficacy of percutaneous transluminal angioplasty (PTA) for symptomatic pulmonary stenosis in Takayasu arteritis (TA)., Methods: From January 2009 to December 2012, clinical data of 14 patients [mean age 33.9 ± 9.3 yrs; 11 patients female (78.6%)] with symptomatic pulmonary stenosis in TA underwent PTA and were analyzed prospectively., Results: PTA was successfully performed in 22 lesions of 14 patients. Among those lesions, 18 were treated by PTA alone while the others were treated with stent implantation. Three patients (21.4%) had reperfusion pulmonary injury; 2 patients recovered completely while the other died of respiratory failure 3 days after the procedure. Mean pulmonary arterial pressure (PAP) decreased from 53.4 ± 15.8 mmHg to 38.4 ± 12.7 mmHg immediately after intervention (p < 0.001). After an average of 29 months of followup, the New York Heart Association functional class and 6-min walking distances improved while mean PAP measured by echocardiography decreased significantly (compared with baseline, all p < 0.01). One patient died of severe pulmonary infection and cardiac shock at 28 months after the procedure., Conclusion: The study showed that PTA improved subjective symptoms and objective variables of the patients with symptomatic pulmonary stenosis in TA, with an acceptable mortality. PTA may be a promising therapeutic strategy for symptomatic pulmonary stenosis in TA.

Aromatase (CYP 19A1) is a key steroidogenic enzyme that catalyzes the conversion of androgen to estrogen. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for aromatase inhibitor screening was developed and validated. The substrate androstenedione was incubated with human CYP 19A1 supersomes in the presence of NADPH for 30 min, and estrone formation was determined by LC-MS/MS analysis. Cortisone was used as internal standard. The incubation mixture was extracted using a liquid-liquid extraction method with ethyl acetate. Chromatographic separation was achieved using a C18 column (3.0 × 50 mm, 2.7 μm) with a mobile phase consisting of 0.1% formic acid/acetonitrile adopting gradient elution at a flow rate of 0.4 mL/min. The mass spectrometer was operated in positive electrospray ionization mode. The precursor-product ion pairs used for multiple reaction monitoring were m/z 287→97 (androstenedione), m/z 271 → 159 (estrone), and m/z 361 → 163 (IS, cortisone). The developed method met the required criteria for the validation of bioanalytical methods. The validated method was successfully applied to evaluate aromatase inhibitory activity of plants extracts of Simaroubaceae.

Rhus verniciflua Stokes has been used as a traditional herbal medicine in Asia. In this study, the effect of R. verniciflua extract on human aromatase (cytochrome P450 19, CYP19) activity was investigated to elucidate the mechanism for the effect of R. verniciflua extract on androgen hormone levels. Androstenedione was used as a substrate and incubated with R. verniciflua extract in cDNA-expressed CYP19 supersomes in the presence of NADPH, and estrone formation was measured using liquid chromatography-tandem mass spectrometry. R. verniciflua extract was assessed at concentrations of 10-1000 μg/mL. The resulting data showed that R. verniciflua extract inhibited CYP19-mediated estrone formation in a concentration-dependent manner with an IC50 value of 136 μg/mL. Subsequently, polyphenolic compounds from R. verniciflua extract were tested to identify the ingredients responsible for the aromatase inhibitory effects by R. verniciflua extract. As a result, butin showed aromatase inhibitory effect in a concentration-dependent manner with an IC50 value of 9.6 μM, whereas the inhibition by other compounds was negligible. These results suggest that R. verniciflua extract could modulate androgen hormone levels via the inhibition of CYP19 activity and butin is a major ingredient responsible for this activity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)