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1.
Talanta ; 226: 122160, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33676705

RESUMO

Immunoglobulin G (IgG) is related to the occurrence of many diseases, such as measles and inflammatory. In this paper, IgG imprinted polymers (IgGIPs) were fabricated on the surface of nano Au/nano Ni modified Au electrode (IgGIPs/AuNCs/NiNCs/Au) via metal-free visible-light-induced atom transfer radical polymerization (MVL ATRP). The IgGIPs were prepared by IgG conjugated with fluorescein isothiocyanate (FITC-IgG) as both a template and a photocatalyst. After the templates were removed, the photocatalysts (FITC) would not remain in the polymer and avoided all the effect of catalysts on the electrode. The fabricated electrodes were examined by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Under the optimized conditions, IgGIPs/AuNCs/NiNCs/Au was prepared and used as an electrochemical biosensor. The biosensor could be successfully applied for the determination of IgG by differential pulse voltammetry (DPV) measurement. The results showed that the proposed biosensor displayed a broader linear range and a lower detection limit for IgG determination when it was compared to those similar IgG sensors. The linear range from 1.0 × 10-6 mg L-1 to 1.0 × 101 mg L-1 was obtained with a low detection limit (LOD) of 2.0 × 10-8 mg L-1 (S/N = 3). Briefly, the biosensor in this study introduced an easy and non-toxic method for IgG determination and also provided a progressive approach for designing protein imprinted polymers.

2.
Plant Cell ; 33(1): 44-65, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33710280

RESUMO

Leaf morphogenesis involves cell division, expansion, and differentiation in the developing leaf, which take place at different rates and at different positions along the medio-lateral and proximal-distal leaf axes. The gene expression changes that control cell fate along these axes remain elusive due to difficulties in precisely isolating tissues. Here, we combined rigorous early leaf characterization, laser capture microdissection, and transcriptomic sequencing to ask how gene expression patterns regulate early leaf morphogenesis in wild-type tomato (Solanum lycopersicum) and the leaf morphogenesis mutant trifoliate. We observed transcriptional regulation of cell differentiation along the proximal-distal axis and identified molecular signatures delineating the classically defined marginal meristem/blastozone region during early leaf development. We describe the role of endoreduplication during leaf development, when and where leaf cells first achieve photosynthetic competency, and the regulation of auxin transport and signaling along the leaf axes. Knockout mutants of BLADE-ON-PETIOLE2 exhibited ectopic shoot apical meristem formation on leaves, highlighting the role of this gene in regulating margin tissue identity. We mapped gene expression signatures in specific leaf domains and evaluated the role of each domain in conferring indeterminacy and permitting blade outgrowth. Finally, we generated a global gene expression atlas of the early developing compound leaf.

3.
Proc Natl Acad Sci U S A ; 118(10)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33649242

RESUMO

Patterns and morphology develop in living systems such as embryos in response to chemical signals. To understand and exploit the interplay of chemical reactions with mechanical transformations, chemomechanical polymer systems have been synthesized by attaching chemicals into hydrogels. In this work, we design autonomous responsive elastic shells that undergo morphological changes induced by chemical reactions. We couple the local mechanical response of the gel with the chemical processes on the shell. This causes swelling and deswelling of the gel, generating diverse morphological changes, including periodic oscillations. We further introduce a mechanical instability and observe buckling-unbuckling dynamics with a response time delay. Moreover, we investigate the mechanical feedback on the chemical reaction and demonstrate the dynamic patterns triggered by an initial deformation. We show the chemical characteristics that account for the shell morphology and discuss the future designs for autonomous responsive materials.

4.
Lancet ; 397(10274): 592-604, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33581821

RESUMO

BACKGROUND: We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%. METHODS: In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing. FINDINGS: Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9-not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2-17·5) with chemotherapy (n=280; hazard ratio [HR] 0·57 [0·42-0·77]; p=0·0002). Median progression-free survival was 8·2 months (6·1-8·8) with cemiplimab versus 5·7 months (4·5-6·2) with chemotherapy (HR 0·54 [0·43-0·68]; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy. INTERPRETATION: Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population. FUNDING: Regeneron Pharmaceuticals and Sanofi.

5.
Sensors (Basel) ; 21(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33401444

RESUMO

With the popularity of portable positioning devices, crowd-sourced trajectory data have attracted widespread attention, and led to many research breakthroughs in the field of road network extraction. However, it is still a challenging task to detect the road networks of old downtown areas with complex network layouts from high noise, low frequency, and uneven distribution trajectories. Therefore, this paper focuses on the old downtown area and provides a novel intersection-first approach to generate road networks based on low quality, crowd-sourced vehicle trajectories. For intersection detection, virtual representative points with distance constraints are detected, and the clustering by fast search and find of density peaks (CFDP) algorithm is introduced to overcome low frequency features of trajectories, and improve the positioning accuracy of intersections. For link extraction, an identification strategy based on the Delaunay triangulation network is developed to quickly filter out false links between large-scale intersections. In order to alleviate the curse of sparse and uneven data distribution, an adaptive link-fitting scheme, considering feature differences, is further designed to derive link centerlines. The experiment results show that the method proposed in this paper preforms remarkably better in both intersection detection and road network generation for old downtown areas.

6.
FASEB J ; 35(2): e21316, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33433947

RESUMO

Maintaining ovarian steroidogenesis is of critical importance, considering that steroid hormones are required for successful establishment and maintenance of pregnancy and proper development of embryos and fetuses. Investigating the mechanism that butyrate modulates the ovarian steroidogenesis is beneficial for understanding the impact of lipid nutrition on steroidogenesis. Herein, we identified that butyrate improved estradiol and progesterone synthesis in rat primary ovarian granulosa cells and human granulosa KGN cells and discovered the related mechanism. Our data indicated that butyrate was sensed by GPR41 and GPR43 in ovarian granulosa cells. Butyrate primarily upregulated the acetylation of histone H3K9 (H3K9ac). Chromatin immune-precipitation and sequencing (ChIP-seq) data of H3K9ac revealed the influenced pathways involving in the mitochondrial function (including cellular metabolism and steroidogenesis) and cellular antioxidant capacity. Additionally, increasing H3K9ac by butyrate further stimulated the PPARγ/CD36/StAR pathways to increase ovarian steroidogenesis and activated PGC1α to enhance mitochondrial dynamics and alleviate oxidative damage. The improvement in antioxidant capacity and mitochondrial dynamics by butyrate enhanced ovarian steroidogenesis. Collectively, butyrate triggers histone H3K9ac to activate steroidogenesis through PPARγ and PGC1α pathways in ovarian granulosa cells.

7.
Vet Microbiol ; 253: 108970, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421685

RESUMO

H3N2 canine influenza virus (CIV) has been circulating in many countries since 2008. The epidemic spread of CIV could be a concern for public health because of the close contact between humans and companion animals. In this study, we used Madin-Darby canine kidney (MDCK) cells as a coinfection model of H3N2 CIV and the pandemic (2009) H1N1 influenza virus to investigate the possibility of genetic mutation or recombination. One of the resultant progeny viruses, designated as CP15, was identified with a significantly increased replication ability. For this viral strain all segments exhibit a homology close to 100 % with its parental strain A/Canine/Jiangsu/06/2010 (JS/10), except for two site mutations K156E and R201 K which occur in the receptor-binding sites of hemagglutinin (HA) and antigen binding sites of neuraminidase (NA), respectively. Virus growth in MDCK cells showed that CP15 had a higher virus titer (more than 10 times) than JS/10. Consistent with this, CP15 exhibited extensive tissue tropism and higher viral RNA loads in the spleen, kidney and lung of mice challenged with this virus compared to JS/10. However, body weight loss and lung injure score due to CP15 infection were greatly reduced. Importantly, anti-CP15 serum antibodies could confer a high neutralization activity against JS/10. These findings indicated that the CP15 strain of high replication ability represents a promising candidate to develop an efficient CIV vaccine.

8.
Ecotoxicol Environ Saf ; 207: 111501, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254389

RESUMO

Deltamethrin (DLM) is widely used in agriculture and the prevention of human insect-borne diseases. However, the molecular mechanism of DLM induced liver injury remains unclear to date. This study investigated the potential molecular mechanism that DLM induced liver fibrosis in quails. Japanese quails received resveratrol (500 mg/kg) daily with or without DLM (45 mg/kg) exposure for 12 weeks. Histopathology, transmission electron microscopy, biochemical indexes, TUNEL, quantitative real-time PCR, and western blot analysis were performed. DLM exposure induced hepatic steatosis, oxidative stress, inflammation, and apoptosis. Most importantly, the Nrf2/TGF-ß1/Smad3 signaling pathway played an important role on DLM-induced liver fibrosis in quails. Interestingly, the addition of resveratrol, an Nrf2 activator, alleviates oxidative stress and inflammation response by activating Nrf2, thereby inhibits the liver fibrosis induced by DLM in quails. Collectively, these findings demonstrate that chronic exposure to DLM induces oxidative stress via the Nrf2 expression inhibition and apoptosis, and then results in liver fibrosis in quails by the activation of NF-κB/TNF-α and TGF-ß1/Smad3 signaling pathway.


Assuntos
Inseticidas/toxicidade , Cirrose Hepática/induzido quimicamente , Nitrilos/toxicidade , Substâncias Protetoras/farmacologia , Piretrinas/toxicidade , Codorniz/fisiologia , Resveratrol/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Fator 2 Relacionado a NF-E2 , NF-kappa B/metabolismo , Estresse Oxidativo , Codorniz/metabolismo , Transdução de Sinais , Proteína Smad3 , Fator de Crescimento Transformador beta1/metabolismo
9.
Environ Pollut ; 267: 115564, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254669

RESUMO

Dibutyl phthalate (DBP), an important plastic contaminant in the environment, is known to cause organ toxicity. Although current research has shown that DBP-induced organ toxicity is associated with oxidative stress, the toxic effect of DBP on the lungs have not been fully elucidated. Therefore, we investigated the potential mechanism by which DBP induces pulmonary toxicity using a model of DBP-induced allergic airway inflammation in rats. The results showed that chronic exposure to DBP induced histopathological damage, inflammation, oxidative stress, apoptosis, and increased the protein levels of thymic stromal lymphopoietin (TSLP) and its downstream protein Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6). Moreover, DBP exposure inhibited nuclear factor-erythroid-2-related factor 2 (Nrf2) and levels of its target genes NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Additionally, using in vitro experiments, we found that DBP induced oxidative stress, reduced cell viability, and inhibited the Nrf2/HO-1/NQO1 pathway in mouse alveolar type II epithelial cell line. Overall, these data demonstrate that DBP induces allergic airway inflammation in rats via inhibition of the Nrf2/TSLP/JAK1 pathway.

10.
Microorganisms ; 8(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256164

RESUMO

A newly isolated phosphate-solubilizing fungus from the topsoil of Spartina alterniflora habitats in Yancheng coastal salt marsh was cultivated. Scanning electron microscopy observation revealed that the sporangia are nearly spherical, peach-shaped, and the spores formed on the top of sporangia. The spores are ellipsoidal with raised white nubbins on the surface. Based on a polyphasic study and the genetic distance analysis referring to the sequence analysis of ITS (ITS1 + 5.8S + ITS2) and 28S rDNA (D1/D2 domains) genes, the novel species belongs to the genus Apophysomyces and is named as A. jiangsuensis. The optimum growth temperature and salinity of the new species were 28 °C and 1.15% NaCl, respectively. A study of its phosphate-solubilizing ability revealed that the fungus had an obvious decomposition effect on lecithin, Ca3(PO4)2, and AlPO3, respectively. The pH of the fermented liquid progressively decreased from 6.85 to 2.27 after 7 days of incubation, indicating that the low molecular weight organic acids excreted into the culture liquor were oxalic, succinic, and malic acids and a trace amount of citric acid. Among these, oxalic acid was the major organic acid, and its amount reached 652.5 mg/L. These results indicated that the main mechanism underlying the dissolved phosphorus was related to the secretion of large amounts of organic acids.

11.
Phys Rev Lett ; 125(23): 236102, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33337177

RESUMO

The interplay between interlayer van der Waals interaction and intralayer lattice distortion can lead to structural reconstruction in slightly twisted bilayer graphene (TBG) with the twist angle being smaller than a characteristic angle θ_{c}. Experimentally, the θ_{c} is demonstrated to be very close to the magic angle (θ≈1.08°). Here we address the transition between reconstructed and unreconstructed structures of the TBG across the magic angle by using scanning tunneling microscopy (STM). Our experiment demonstrates that both structures are stable in the TBG around the magic angle. By using a STM tip, we show that the two structures can be changed to each other and a triangular network of chiral one-dimensional states hosted by domain boundaries can be switched on and off. Consequently, the bandwidth of the flat band, which plays a vital role in the emergent strongly correlated states in the magic angle TBG, is tuned. This provides an extra control knob to manipulate the exotic electronic states of the TBG near the magic angle.

12.
Biomed Chromatogr ; : e5034, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226666

RESUMO

Marsdenia tenacissima (Roxb.) Wight et Arn. (M. tenacissima) is considered as an anti-cancer medicine in the traditional Chinese medicine (TCM), which is extensively adopted in clinical application since it has great therapeutic effects. Currently, although a number of articles have examined M. tenacissima in terms of its pharmacology and quality control, few of them investigated the in vivo process of the M. tenacissima active ingredients. Previously, we have studied the pharmacokinetics of 8 active ingredients after oral administration of M. tenacissima extracts in rats plasma. This study constructed a new scientific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach to simultaneously quantify the contents of Tenacissosides B, G, H, I, cryptochlorogenic acid, chlorogenic acid, neochlorogenic acid and caffeic acid in rats administered with M. tenacissima extract orally. Thereafter, the proposed approach was used successfully for investigating the distributions of those 8 analytes in rat tissues, with digoxin being used as an internal control. The Eclipse Plus C18 RRHD column was used for determination at the 30°C column temperature. The mobile phase system consisted of acetonitrile and water (supplemented with 0.1% formic acid) at optimal gradient elution conditions. Afterwards, this approach was validated according to the requirements for the analysis of biological samples developed by the US Food and Drug Administration (FDA), including precision, accuracy, stability and matrix effects. Based on tissue distribution analysis, those eight analytes showed rapid distribution within all the tested tissues. With regard to organic acid distribution, it followed the order below, stomach> liver> kidney> small intestine >lung> spleen > heart, whereas for the four steroids, they followed the order below, stomach >lung> spleen> small intestine > liver > kidney > heart. Moreover, the present study can lay theoretical foundation for the use and development of M. tenacissima in clinical practice.

13.
Metallomics ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159781

RESUMO

Hexavalent chromium (Cr(vi)), the most toxic valence state of chromium, is widely present in industrial effluents and wastes. Sulforaphane (SFN), rich in Brassica genus plants, bears multiple biological activity. Wistar rats were used to explore the protective role of SFN against the cardiotoxicity of chronic potassium dichromate (K2Cr2O7) exposure and reveal the potential molecular mechanism. The data showed that SFN alleviated hematological variations, oxidative stress, heart dysfunction and structure disorder, and cardiomyocyte apoptosis induced by K2Cr2O7. Moreover, SFN reduced p53, cleaved caspase-3, Bcl2-associated X protein, nuclear factor kappa-B, and interleukin-1ß levels, and increased Sesn2, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) levels. This study demonstrates that SFN ameliorates Cr(vi)-induced cardiotoxicity via activation of the Sesn2/AMPK/Nrf2 signaling pathway. SFN may be a protector against Cr(vi)-induced heart injury and a novel therapy for chronic Cr(vi) exposure.

14.
Biosci Rep ; 40(12)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33146718

RESUMO

MicroRNAs (miRNAs) regulate the progression of human malignancy by targeting oncogenes or tumor suppressors, which are 12 promising targets for cancer treatment. Increasing evidence has suggested the aberrant expression and tumor-suppressive function of miR-1298 in cancers, however, the regulatory mechanism of miR-1298 in breast cancer (BC) remains unclear. Here, our findings showed that miR-1298 was down-regulated in BC tissues and cell lines. Lower level of miR-1298 was significantly correlated with the advanced progression of BC patients. Experimental study showed that overexpression of miR-1298 inhibited the proliferation, induced apoptosis and cell cycle arrest in BC cells. The in vivo xenograft mice model showed that highly expressed miR-1298 significantly reduced the tumor growth and metastasis. Further mechanism analysis revealed that miR-1298 bound the 3'-untranslated region (UTR) of a disintegrin and metalloproteinase 9 domain (ADAM9) and suppressed the expression of ADAM9 in BC cells. ADAM9 was overexpressed in BC tissues and inversely correlated with miR-1298. Down-regulation of ADAM9 induced apoptosis and cell cycle arrest of BC cells. Moreover, ectopic expression of ADAM9 by transiently transfecting with vector encoding the full coding sequence of ADAM9 attenuated the inhibitory effects of miR-1298 on the proliferation and cell cycle progression of BC cells. Collectively, our results illustrated that miR-1298 played a suppressive role in regulating the phenotype of BC cells through directly repressing ADAM9, suggesting the potential application of miR-1298 in the therapy of BC.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33146741

RESUMO

PURPOSE: Part 1 of this two-part, open-label, Phase 1 study (NCT03233139) assessed the safety, tolerability, pharmacokinetics, immunogenicity, and clinical activity of cemiplimab in Japanese patients with advanced malignancies. METHODS: Patients received cemiplimab 250 mg (n = 6) or 350 mg (n = 7) every 3 weeks intravenously for up to 108 weeks in Part 1. Tumor responses were assessed by investigators every 9 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Of 13 patients enrolled, median age was 62 years (range 33-75) and eight patients were female. Median duration of cemiplimab exposure was 13.1 weeks (range 3.0‒113.6). At the time of data cut-off, 11 patients (84.6%) had discontinued treatment (majority due to disease progression: n = 8, 61.5%). The most common treatment-emergent adverse events (TEAEs) of any grade were contact dermatitis, rash, and viral upper respiratory tract infection (each n = 3, 23.1%). Five grade ≥ 3 TEAEs were reported in four patients: autoimmune colitis, dehydration, hyponatremia, hypophosphatemia, and muscular weakness. No dose-limiting toxicities were reported and no TEAEs led to death. Cemiplimab concentrations in serum were consistent with previously reported pharmacokinetic characteristics of cemiplimab. No anti-drug antibodies were detected in serum. Objective response rate [ORR; complete response + partial response (PR)] was 30.8% (four PR) and disease control rate [ORR + stable disease (SD)] was 46.2% (6/13; two SD). CONCLUSION: Cemiplimab exhibited antitumor activity in Japanese patients with advanced malignancies. The safety profile was comparable to those previously reported for cemiplimab and other PD-1 inhibitors. TRIAL REGISTRATION: NCT03233139 at ClinicalTrials.gov.

16.
Sci Rep ; 10(1): 16239, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004887

RESUMO

High myopia (HM) is associated with impaired long-distance vision. accumulating evidences reported that abnormal visual experience leads to dysfunction in brain activity in HM even corrected. However, whether the long-term of abnormal visual experience lead to neuroanatomical changes remain unknown, the aim at this study is to investigate the alternation of cortical surface thickness in HM patients. 82 patients with HM (HM groups), 57 healthy controls (HC groups) were recruited. All participants underwent high-resolution T1 and resting-state functional magnetic resonance imaging (MRI) scans. The cortical thickness analysis was preformed to investigate the neuroanatomical changes in HM patients using computational anatomy toolbox (CAT 12) toolbox. Compare with HCs, HM patients showed decreased the cortical surface thickness in the left middle occipital gyrus (MOG), left inferior parietal lobule (IPL), right inferior temporal gyrus (ITG), right precuneus, right primary visual area 1 (V1), right superior temporal gyrus (STG), right superior parietal lobule (SPL), right occipital pole, and right the primary motor cortex (M1), and increased to the parietal operculum (OP4) (P < 0.01, FWE-corrected), the mean cortical thickness of right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC) and right subcallosal cortex showed negatively correlation between clinical variables (axis length (ALM), the average macular thickness (AMT), keratometer (KER) 1, KER2, the mean KER, the mean macular fovea thickness (MFK), the refractive diopter) in HM patients. Our result mainly provided an evidence of cortical thickness reduction and disconnection in visual center and visual processing area, and cortical thickness increase in left multimodal integration region in HM patients. This may provide important significance of the study of the neural mechanism of HM.

17.
Trials ; 21(1): 844, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046128

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has a long history of use in breast cancer, but lacking systematic evidence to support its clinical benefits. In this study, we evaluated the prophylactic and therapeutic effects of moxibustion combined with decoctions for treating chemotherapy-induced myelosuppression (CIM) in early-stage breast cancer patients. METHODS: This is a randomized controlled clinical trial single-blinded for TCM decoction but not moxibustion. Patients are equally divided into the control group without decoction and moxibustion treatment (control), the decoction+moxibustion group (MD), and the placebo+moxibustion group (MP), according to the following stratification factors: age (below 40s, 40s, 50s, and 60s or above), chemotherapy regimen (anthracyclines, taxanes, anthracyclines+taxane, and others), and chemotherapy strategy (adjuvant and neoadjuvant). The TCM decoction is Wenshen Shengbai Decoction. The anticipated sample size is 462 cases (154 cases in each group). All participants are expected to treat with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). The primary outcomes include the proportion of patients with relief of leukopenia and/or neutropenia, the myelosuppression-associated serious adverse event including grade 3-4 leukopenia and/or neutropenia, and febrile neutropenia, and the dose of rhG-CSF. The secondary outcomes include chemotherapy adherence, stratified analysis, adverse reactions, quality of life by EORTC Breast-Cancer-Specific Quality of Life Questionnaire including EORTC QLQ-C30 (V3.0) and QLQ-BR23, TCM Constitution, and 3-year disease-free survival and overall survival. Baseline information including age, surgical approach, chemotherapy regimen and strategy, pathological stage, and molecular subtype will be recorded. DISCUSSION: This will be the first randomized controlled trial to evaluate the efficacy of moxibustion combined with TCM decoction in treating CIM in early-stage breast cancer patients, aiming to standardize the TCM decoction and moxibustion method, thus providing evidence for its clinical benefit. TRIAL REGISTRATION: chictr.org.cn ChiCTR-INR-16009557 . Registered on 23 October 2016.

18.
Chemosphere ; 264(Pt 2): 128547, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33049514

RESUMO

Hexavalent chromium (Cr(VI)), the most toxic valence state of chromium, is widely present in industrial effluents and wastes. Although previous study has reported that Cr(VI) can cause cytomembrane structure impairment by aggravating lipid peroxidation in the heart, the detailed mechanism of Cr(VI)-induced heart dysfunction is still unclear. Sesn2, a novel antioxidant and stress-inducible molecule, is evidenced to protect against various cardiometabolic diseases such as atherosclerosis and cardiomyopathy. To define the potential mechanism of heart dysfunction induced by chronic Cr(VI) exposure, Wistar rats were intraperitoneal injected with potassium dichromate (K2Cr2O7) for 35 d in the present study. The data showed that chronic K2Cr2O7 exposure caused dose-dependently hematological variations, oxidative stress, dysfunction, and disorganized structure of heart, cardiomyocyte apoptosis, ATP depletion, and mitochondria impairment in rats. In addition, the expressions of Drp1 and Bax were increased by K2Cr2O7. However, the suppression of Mfn2, PGC-1α, Sesn2, nuclear Nrf2, HO-1, and NQO1 protein levels was observed in K2Cr2O7-treated rat hearts. In conclusion, these results demonstrate that chronic K2Cr2O7 exposure dose-dependently causes heart dysfunction, and the molecular mechanism of this event is associated with the loss of Sesn2 mediated mitochondrial function and energy supply impairment.

19.
ACS Nano ; 14(10): 13081-13090, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33052664

RESUMO

In the magic-angle twisted bilayer graphene (MA-TBG), strong electron-electron (e-e) correlations caused by the band-flattening lead to many exotic quantum phases such as superconductivity, correlated insulator, ferromagnetism, and quantum anomalous Hall effects, when its low-energy van Hove singularities (VHSs) are partially filled. Here our high-resolution scanning tunneling microscope and spectroscopy measurements demonstrate that the e-e correlation in a nonmagic-angle TBG with a twist angle θ = 1.49° still plays an important role in determining its electronic properties. Our most interesting observation on that sample is when one of its VHSs is partially filled, the one associated peak in the spectrum splits into four peaks. Simultaneously, the spatial symmetry of electronic states around the split VHSs is broken by the e-e correlation. Our analysis based on the continuum model suggests that such a one-to-four split of the VHS originates from the formation of an interaction-driven spin-valley-polarized metallic state near the VHS, which is a symmetry-breaking phase that has not been identified in the MA-TBG or in other systems.

20.
Food Funct ; 11(10): 9252-9262, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33047770

RESUMO

Ongoing groundwater arsenic contamination throughout China was first recognized in the 1960s. Groundwater arsenic contamination is a high risk for human and animal health worldwide. Apart from drinking water, diet is the second pathway for arsenic to enter the human body and eventually cause liver injury. Natural astaxanthin extracted from the green algae Haematococcus pluvialis has dominated the nutraceutical market for potential health benefits. Nevertheless, the molecular mechanism underlying the protective effect post astaxanthin against arsenic-induced hepatotoxicity remains largely obscure. In this study, we investigate the effect of natural astaxanthin (derived from Haemotococcus pluvialis) on oxidative stress and liver inflammatory response in rats after the cessation of chronic arsenic exposure. Wistar rats were given astaxanthin (250 mg kg-1) daily for 2 weeks after the cessation of exposure to sodium arsenite (300 µg L-1, drinking water, 24 weeks) by intragastric administration. The results showed that post treatment with astaxanthin attenuated liver injury induced by long-term exposure to arsenic in rats. Most importantly, post treatment with astaxanthin decreased the increasing of inflammatory cytokine NF-κB, tumor necrosis factor-α, interleukin-1ß, oxidative stress level, and total arsenic content in livers of rats exposed to arsenic. In addition, post treatment with astaxanthin reversed the increasing of protein levels of alpha-smooth muscle actin and collagen Iα1, which are the activation markers of hepatic stellate cells (HSCs). Collectively, these data demonstrate that post astaxanthin treatment attenuates inflammation response in the liver after the cessation of chronic arsenic exposure via inhibition of cytokine-mediated cell-cell interactions. Daily ingestion of natural astaxanthin might be a potential and beneficial candidate for the treatment of liver damage after the cessation of chronic exposure to sodium arsenite.

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