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1.
Cancer Control ; 31: 10732748241257142, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769028

RESUMO

OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.


Assuntos
Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Circular , Proteínas de Ligação a RNA , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , RNA Circular/genética , Regulação Neoplásica da Expressão Gênica , Masculino , Proliferação de Células/genética , Linhagem Celular Tumoral , Feminino , Camundongos , Animais , Movimento Celular/genética , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
2.
Br J Anaesth ; 132(1): 45-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007377

RESUMO

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Sugammadex/efeitos adversos , Rocurônio , Bloqueio Neuromuscular/métodos , gama-Ciclodextrinas/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Androstanóis/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia
3.
Fa Yi Xue Za Zhi ; 40(2): 172-178, 2024 Apr 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38847033

RESUMO

OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.


Assuntos
Apolipoproteínas E , Biomarcadores , Modelos Animais de Doenças , Hiperlipidemias , Restrição Física , Animais , Hiperlipidemias/metabolismo , Hiperlipidemias/complicações , Camundongos , Biomarcadores/metabolismo , Apolipoproteínas E/genética , Proteômica/métodos , Estresse Psicológico/complicações , MicroRNAs/metabolismo , MicroRNAs/genética , Ferroptose , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Camundongos Knockout , Proteína Desacopladora 1/metabolismo , Biologia Computacional
4.
Mar Drugs ; 21(12)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38132967

RESUMO

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.


Assuntos
Fungos , Metabolômica , Cromatografia Líquida de Alta Pressão , Fungos/metabolismo , Fermentação
5.
J Am Chem Soc ; 143(11): 4379-4386, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33705657

RESUMO

The curcusone natural products are complex diterpenes featuring a characteristic [6-7-5] tricyclic carbon skeleton similar to the daphnane and tigliane diterpenes. Among them, curcusones A-D demonstrated potent anticancer activity against a broad spectrum of human cancer cell lines. Prior to this study, no total synthesis of the curcusones was achieved and their anticancer mode of action remained unknown. Herein, we report our synthetic and chemoproteomics studies of the curcusone diterpenes which culminate in the first total synthesis of several curcusone natural products and identification of BRCA1-associated ATM activator 1 (BRAT1) as a cellular target. Our efficient synthesis is highly convergent, builds upon cheap and abundant starting materials, features a thermal [3,3]-sigmatropic rearrangement and a novel FeCl3-promoted cascade reaction to rapidly construct the critical cycloheptadienone core of the curcusones, and led us to complete the first total synthesis of curcusones A and B in only 9 steps, C and D in 10 steps, and dimericursone A in 12 steps. The chemical synthesis of dimericursone A from curcusones C and D provided direct evidence to support the proposed Diels-Alder dimerization and cheletropic elimination biosynthetic pathway. Using an alkyne-tagged probe molecule, BRAT1, an important but previously "undruggable" oncoprotein, was identified as a key cellular target via chemoproteomics. We further demonstrate for the first time that BRAT1 can be inhibited by curcusone D, resulting in impaired DNA damage response, reduced cancer cell migration, potentiated activity of the DNA damaging drug etoposide, and other phenotypes similar to BRAT1 knockdown.


Assuntos
Produtos Biológicos/química , Diterpenos/química , Proteínas Nucleares/análise , Produtos Biológicos/síntese química , Diterpenos/síntese química , Humanos , Conformação Molecular , Estereoisomerismo
6.
Cancer Immunol Immunother ; 70(4): 1101-1113, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33123754

RESUMO

Although immunotherapy has achieved impressive durable clinical responses, many cancers respond only temporarily or not at all to immunotherapy. To find novel, targetable mechanisms of resistance to immunotherapy, patient-derived melanoma cell lines were transduced with 576 open reading frames, or exposed to arrayed libraries of 850 bioactive compounds, prior to co-culture with autologous tumor-infiltrating lymphocytes (TILs). The synergy between the targets and TILs to induce apoptosis, and the mechanisms of inhibiting resistance to TILs were interrogated. Gene expression analyses were performed on tumor samples from patients undergoing immunotherapy for metastatic melanoma. Finally, the effect of inhibiting the top targets on the efficacy of immunotherapy was investigated in multiple preclinical models. Aurora kinase was identified as a mediator of melanoma cell resistance to T-cell-mediated cytotoxicity in both complementary screens. Aurora kinase inhibitors were validated to synergize with T-cell-mediated cytotoxicity in vitro. The Aurora kinase inhibition-mediated sensitivity to T-cell cytotoxicity was shown to be partially driven by p21-mediated induction of cellular senescence. The expression levels of Aurora kinase and related proteins were inversely correlated with immune infiltration, response to immunotherapy and survival in melanoma patients. Aurora kinase inhibition showed variable responses in combination with immunotherapy in vivo, suggesting its activity is modified by other factors in the tumor microenvironment. These data suggest that Aurora kinase inhibition enhances T-cell cytotoxicity in vitro and can potentiate antitumor immunity in vivo in some but not all settings. Further studies are required to determine the mechanism of primary resistance to this therapeutic intervention.


Assuntos
Aurora Quinase A/metabolismo , Aurora Quinase B/metabolismo , Resistencia a Medicamentos Antineoplásicos/imunologia , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Linfócitos T Citotóxicos/transplante , Animais , Apoptose , Aurora Quinase A/antagonistas & inibidores , Aurora Quinase A/genética , Aurora Quinase B/antagonistas & inibidores , Aurora Quinase B/genética , Proliferação de Células , Feminino , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/terapia , Camundongos , Prognóstico , Taxa de Sobrevida , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Neoplasma ; 68(4): 823-831, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34097427

RESUMO

Due to tumor heterogeneity, the consistency of programmed cell death-ligand 1 (PD-L1) expression between circulating tumor cells (CTCs) and tissue is controversial. This study aimed to establish a method for detecting CTC PD-L1 expression and exploring the impact of the same on the prognosis of lung cancer. In 32 patients with non-small cell lung cancer, lung cancer cells in the blood were enriched using CD326 immunomagnetic beads. Goat anti-mouse polyclonal CD326 antibody stained the epithelial lung cancer cells and anti-PD-L1 antibody was used to detect the expression of CTC PD-L1. The DAKO Link 48 automatic staining device detected the expression in lung cancer tissue. The consistency of PD-L1 expression was analyzed in lung cancer tissue and CTCs. The effect of plasma interferon gamma, tumor necrosis factor alpha, and interleukin-2 on PD-L1 expression and prognosis was analyzed. The number of CTCs detected in patients was 1-36, with a median of 2. There was no significant difference in PD-L1 expression fractions between CTCs and paired tumor tissue (p>0.05). The correlation coefficient was 0.20. Regardless of lung cancer tissue or CTCs, there was no statistically significant difference in the blood cytokine levels between the two groups with positive or negative PD-L1 expression (p>0.05). There was no correlation between CTCs and PD-L1 in 23 untreated patients. The expression of PD-L1 in CTCs and lung cancer tissue is heterogeneous and unaffected by the peripheral cytokines' levels. PD-L1 expression has no correlation between CTCs and tissues and is not related to prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Animais , Apoptose , Antígeno B7-H1 , Biomarcadores Tumorais , Humanos , Ligantes , Camundongos , Prognóstico
8.
BMC Pulm Med ; 21(1): 302, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34560863

RESUMO

BACKGROUND: Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates. METHODS: The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis. RESULTS: Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR < 30 L/min and 44.1% patients had a PIFR ≥ 60 L/min before technique training. After technique training, scarcely patient (1.5%) had a PIFR < 30 L/min, and 60.5% patients had a PIFR ≥ 60 L/min. The patient's average PIFR increased by 5.6L/min after training. The increase in PIFR before and after training was significant (p < 0.001) for most patients, but no significant variation was found in patients with acute exacerbation (p = 0.822). CONCLUSIONS: A considerable number of patients with COPD or asthma were not able to achieve the minimum or optimal PIFR for DPIs. Inhaler training can increase patients' PIFRs and improve their ability to use DPIs. Trail registration The study has registered in chictr.org.cn (ChiCTR1900024707) and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142).


Assuntos
Asma/tratamento farmacológico , Inaladores de Pó Seco , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Terapia Respiratória , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Estudos Prospectivos
9.
BMC Pediatr ; 21(1): 429, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592941

RESUMO

BACKGROUND: Z score utility is emphasized in classifying coronary artery lesions in Kawasaki disease patients. The present study is the largest such multicenter Chinese pediatric study about coronary artery diameter reference values and Z score regression equation to date. It is useful in Chinese pediatric echocardiography. METHODS: A multicenter cohort was assembled, which consisted of 852 healthy children between 1 month and 17 years of age, ten children were excluded because their ultrasound images were not clear, or lost in following up. Diameters of the right coronary artery, left coronary artery, and left anterior descending coronary artery were assessed using echocardiography. Data were body surface area (BSA)-corrected using BSA calculated via either the Stevenson BSA formula or the Haycock BSA formula. Coronary artery diameter reference values and Z score regression equations were established for use in the Chinese pediatric population. RESULTS: No difference was observed between coronary artery diameter data corrected using BSAste or BSAhay. Of the five assessed regression models, the exponential model exhibited the best fit and was therefore selected as the basis for derivation of the SZ method. When comparing Z scores, those produced by the SZ method conformed to the standard normal distribution, while those produced by the D method did not. In addition, there was a statistically significant difference between Z scores produced by the SZ and D methods (P < 0.05). CONCLUSIONS: Coronary artery diameter reference values for echocardiography were successfully established for use in the Chinese pediatric population, and a Z score regression equation more suitable for clinical use in this population was successfully developed.


Assuntos
Vasos Coronários , Ecocardiografia , Criança , China , Estudos de Coortes , Vasos Coronários/diagnóstico por imagem , Humanos , Lactente , Estudos Prospectivos , Valores de Referência
10.
Phytother Res ; 35(5): 2568-2578, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33350549

RESUMO

In China, the fruits of Physalis alkekengi L. var. franchetii, which are conventionally utilized as edible berry, have attracted wide attention due to its significant biological activities. In the present study, phytochemical studies on the fruits of Physalis plants afforded six compounds, including two new withanolides (1-2) and four known agnologues (3-6). The inhibitory effects of these compounds on the formation of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophages were evaluated. Physapubescin M (1), with IC50 value of 1.58 µM, was selected for further study. The protein expression of COX-2 and iNOS, and LPS-induced production of cytokines (IL-6, IL-1ß and TNF-α) were reduced by physapubescin M (1) in a dose-dependent way. In addition, transcriptomic analyses were conducted to profile gene expression alterations in LPS-induced RAW264.7 cells upon treatment of physapubescin M (1) and the potential antiinflammatory mechanism of withnolides was mentioned. These results provide broad view to the underlying antiinflammatory mechanism of withnolides, and give a theoretical basis for the utilization of the fruits of P. alkekengi L. var. franchetii.

11.
RNA Biol ; 17(12): 1727-1740, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32129701

RESUMO

Cancer is a complex process in which protein-coding and non-coding genes play essential roles. Long noncoding RNAs (lncRNAs), as a subclass of noncoding genes, are implicated in various cancer processes including growth, proliferation, metastasis, and angiogenesis. Due to presence in body fluids such as blood and urine, lncRNAs have become novel biomarkers in cancer detection, diagnosis, progression, and therapy response. Remarkably, increasing evidence has verified that lncRNAs play essential roles in chemoresistance by targeting different signalling pathways. Autophagy, a highly conserved process in response to environmental stresses such as starvation and hypoxia, plays a paradoxical role in inducing resistance or sensitivity to chemotherapy agents. In this regard, we reviewed chemoresistance, the role of lncRNAs in cancer, and the role of lncRNAs in chemoresistance by modulating autophagy.


Assuntos
Autofagia/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
12.
Molecules ; 25(20)2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33092283

RESUMO

Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells. This metabolic rewiring and crosstalk with the tumour microenvironment play a key role in cell proliferation, metastasis, and the development of treatment resistance. In this review, we will discuss therapeutic opportunities, which arise from dysregulated metabolism and metabolic crosstalk, highlighting strategies that may aid in the precision targeting of altered tumour metabolism with a focus on combinatorial therapeutic strategies.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Fibroblastos Associados a Câncer/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Neoplasias/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos
13.
Proc Natl Acad Sci U S A ; 113(48): 13576-13581, 2016 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-27856743

RESUMO

Improvements in thermoelectric material performance over the past two decades have largely been based on decreasing the phonon thermal conductivity. Enhancing the power factor has been less successful in comparison. In this work, a peak power factor of ∼106 µW⋅cm-1⋅K-2 is achieved by increasing the hot pressing temperature up to 1,373 K in the p-type half-Heusler Nb0.95Ti0.05FeSb. The high power factor subsequently yields a record output power density of ∼22 W⋅cm-2 based on a single-leg device operating at between 293 K and 868 K. Such a high-output power density can be beneficial for large-scale power generation applications.

14.
Molecules ; 24(12)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31200472

RESUMO

Due to the existence of Lingzhi adulteration, there is a growing demand for species classification of medicinal mushrooms by various techniques. The objective of this study was to explore a rapid and reliable way to distinguish between different Lingzhi species and compare the influence of data pretreatment methods on the recognition results. To this end, 120 fresh fruiting bodies of Lingzhi were collected, and all of them were analyzed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). Random forest (RF), support vector machine (SVM) and partial least squares discriminant analysis (PLS-DA) classification models were established for raw and pretreated second derivative (SD) spectral matrices to authenticate different Lingzhi species. The results of multivariate statistical analysis indicated that the SD preprocessing method displayed a higher classification ability, which may be attributed to the analysis of powder samples that requires removal of overlapping peaks and baseline shifts. Compared with RF, the results of the SVM and PLS-DA methods were more satisfying, and their accuracies for the test set were both 100%. Among SVM and PLS-DA, the training set and test set accuracy of PLS-DA were both 100%. In conclusion, ATR-FTIR spectroscopy data pretreated by SD combined with PLS-DA is a simple, rapid, non-destructive and relatively inexpensive method to discriminate between mushroom species and provide a good reference to quality assessment.


Assuntos
Reishi/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Discriminante , Análise dos Mínimos Quadrados , Análise Multivariada
15.
Molecules ; 24(6)2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30909473

RESUMO

Deregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/ß-catenin signaling pathway. Physalis peruviana-derived 4ßHWE showed a significant inhibitory activity with a calculated IC50 of 0.09 µΜ in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4ßHWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4ßHWE promoted the phosphorylation and degradation of ß-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4ßHWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4ßHWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4ßHWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/ß-catenin signaling pathway. In conclusion, our study suggested that 4ßHWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Physalis/química , Extratos Vegetais/farmacologia , Vitanolídeos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Relação Estrutura-Atividade , Vitanolídeos/química
16.
Zhonghua Nan Ke Xue ; 25(5): 420-423, 2019 May.
Artigo em Zh | MEDLINE | ID: mdl-32216227

RESUMO

OBJECTIVE: To investigate the necessity of medication for patients with type Ⅲ prostatitis-like symptoms for less than 3 months. METHODS: We enrolled in this study 171 outpatients with type Ⅲ prostatitis-like symptoms for less than 3 months in our hospital from November 2016 to October 2017, and randomly divided them into groups A (n = 57), B (n = 57) and C (n = 57). The patients of group A received tamsulosin, levofloxacin and health education, those of group B tamsulosin and health education, and those of group C health education only. Three months later, we evaluated the therapeutic effects according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores of the patients, 4-point reduction in the total score indicating effectiveness. RESULTS: After 3 months of treatment, the total NIH-CPSI scores of the patients in groups A, B and C were decreased by (9.0 ± 2.9), (8.2 ± 3.4) and (8.6 ± 3.2) points respectively, all indicating effectiveness, the pain scores (4.2 ± 1.8), (4.0 ± 1.9) and (4.2 ± 1.6) points, the urinary symptom scores decreased by decreased by (2.4 ± 1.2), (2.4 ± 1.4) and (2.2 ± 1.2) points, and quality of life scores decreased by (2.4 ± 1.4), (1.9 ± 1.4) and (2.2 ± 1.3) points, none with statistically significant difference among the three groups (P > 0.05). CONCLUSIONS: Health education is proved to have a therapeutic effect on type Ⅲ prostatitis-like symptoms similar to that of alpha receptor blockers.


Assuntos
Educação de Pacientes como Assunto , Prostatite/tratamento farmacológico , Prostatite/terapia , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Doença Crônica , Humanos , Levofloxacino/uso terapêutico , Masculino , Estudos Prospectivos , Qualidade de Vida , Tansulosina/uso terapêutico , Estados Unidos , Agentes Urológicos/uso terapêutico
17.
Org Biomol Chem ; 16(37): 8305-8310, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30225495

RESUMO

Dimericursones A and B (1 and 2), two unprecedented hexacyclic dimeric diterpenoids, were obtained from the root barks of Jatropha curcas. Their structures were elucidated by extensive spectroscopic analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Dimericursone B (2) showed significant inhibition on nitric oxide production of lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 5.65 µM.


Assuntos
Anti-Inflamatórios/química , Dimerização , Diterpenos/química , Jatropha/química , Raízes de Plantas/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Camundongos , Modelos Moleculares , Conformação Molecular , Células RAW 264.7
18.
Int J Clin Pract ; : e13279, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30269402

RESUMO

OBJECTIVE: The objective of this study was to investigate the association between metabolically healthy obese (MHO) phenotype and the risk of cardiovascular disease (CVD). METHODS: A total of 9393 subjects aged ≥40 years were enrolled in the cohort study (2011-2015). The participants were stratified by body mass index category and metabolic risk at baseline, and incidence of CVD was ascertained at follow-up. RESULTS: The MHO accounted for 6.7%. Compared with the metabolically healthy normal weight (MHNW) group, MHO subjects demonstrated increased risk of CVD events (HR = 1.91; 95% CI, 1.13-3.24). In people with obesity, there was no significant difference on increasing risk of incidence of CVD in the metabolically unhealthy individuals compared with metabolically healthy individuals (HR = 1.19; 95% CI, 0.74-1.91). Female (OR = 1.97; 95% CI, 1.06-3.64), smoking (OR = 2.09; 95% CI, 1.06-4.10), a larger waist circumference (OR = 1.07; 95% CI, 1.03-1.10) and higher LDL cholesterol levels (OR = 1.55; 95% CI, 1.20-2.00) were independent risk factors of the development of the MHO to the metabolically unhealthy obese (MUO) phenotype. CONCLUSIONS: The risk of CVD events of MHO phenotypes is similar to MUO phenotypes; both are higher than the MHNW phenotypes.

19.
Proc Natl Acad Sci U S A ; 112(11): 3269-74, 2015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25733845

RESUMO

Thermoelectric power generation is one of the most promising techniques to use the huge amount of waste heat and solar energy. Traditionally, high thermoelectric figure-of-merit, ZT, has been the only parameter pursued for high conversion efficiency. Here, we emphasize that a high power factor (PF) is equivalently important for high power generation, in addition to high efficiency. A new n-type Mg2Sn-based material, Mg2Sn0.75Ge0.25, is a good example to meet the dual requirements in efficiency and output power. It was found that Mg2Sn0.75Ge0.25 has an average ZT of 0.9 and PF of 52 µW⋅cm(-1)⋅K(-2) over the temperature range of 25-450 °C, a peak ZT of 1.4 at 450 °C, and peak PF of 55 µW⋅cm(-1)⋅K(-2) at 350 °C. By using the energy balance of one-dimensional heat flow equation, leg efficiency and output power were calculated with Th = 400 °C and Tc = 50 °C to be of 10.5% and 6.6 W⋅cm(-2) under a temperature gradient of 150 °C⋅mm(-1), respectively.

20.
Zhongguo Zhong Yao Za Zhi ; 43(15): 3171-3175, 2018 Aug.
Artigo em Zh | MEDLINE | ID: mdl-30200714

RESUMO

The aim of this paper is to investigate the effect of patchouli alcohol in enhancing Helicobater pylori's action in eradicating macrophages and its mechanism. H. pylori was co-cultured with macrophages at a ratio of MOI=100 in different concentrations of patchouli alcohol. The effect of patchouli alcohol in eradicating macrophages was detected by agar dilution method. The effect of patchouli alcohol on NO and myeloperoxidase (MPO) levels in macrophages were measured by H. pylori by biochemical methods. Patchouli alcohol effect on H. pylori-induced pro-inflammatory gene expression and protein secretion in macrophages were detected by RT-qPCR and ELISA method. The eradication of H. pylori has significantly enhanced, and the destabilization of lysosomes has been reversed. Meanwhile, patchouli alcohol has an effect in inhibiting pro-inflammation and oxidation. The mechanism of patchouli alcohol in eradicating H. pylori and resisting oxidative stress may be associated to the blocking of bacteria escape lysosome combination procedures.


Assuntos
Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Lisossomos/imunologia , Macrófagos/imunologia , Sesquiterpenos/farmacologia , Células Cultivadas , Humanos , Macrófagos/efeitos dos fármacos , Estresse Oxidativo
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