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1.
Plant Divers ; 43(4): 317-323, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34485774

RESUMO

Zingiber cassumunar is an important plant used in traditional medicine and as a natural mosquito repellent. However, the compounds responsible for the repellent activity of the plant are still unknown. The aim of the study is to identify the components of Z. cassumunar essential oil that show repellent activity against Aedes albopictus. We also evaluated the larvicidal and adulticidal activities of Z. cassumunar essential oil against Ae. albopictus. In-cage mosquito repellent experiments showed that Z. cassumunar essential oil possessed moderate repellent activity with a minimum effective dose (MED) of 0.16 ± 0.01 mg/cm2, compared to reference standard N,N-diethyl-3-methylbenzamide (DEET, 0.03 ± 0.01 mg/cm2). Bioassay-guided fractionation identified the major active compound of Z. cassumunar essential oil as (-)-terpinen-4-ol (1) (MED: 0.19 ± 0 mg/cm2). We also found that Z. cassumunar essential oil showed moderate larvicidal activity against first instar larvae of Ae. albopictus with a LC50 (50% lethal concentration) of 44.9 µg/L after 24 h. Fumigation bioassays showed that Z. cassumunar essential oil exhibits moderate adulticidal activity against Ae. albopictus with a LC50 of 5.44%, while (-)-terpinen-4-ol showed significant adulticidal activity with a LC50 of 2.10% after 24 h. This study verifies that the Z. cassumunar essential oil has mosquito repellent activity, and that (-)-terpinen-4-ol is mainly responsible for this activity. Furthermore, this study provides scientific support for the folk usage of Z. cassumunar essential oil as mosquito repellent and indicates that Z. cassumunar essential oil and (-)-terpinen-4-ol can be used as plant-derived repellents and insecticides for mosquito control.

2.
J Plant Physiol ; 266: 153510, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34521019

RESUMO

Source sink balance is one of the major determinants of carbon partitioning in plants. However, its effects on photosynthesis in fruit trees are largely unknown. In this work, the effects of low sink demand on net photosynthetic rate (Pn) and chlorophyll fluorescence after fruit removal (-fruit) in peach (Prunus persica (L.) Batsch cv. 'Zaojiubao') trees were investigated. The stepwise energy flow through photosystem II (PSII) at the reaction center (RC) was analyzed with quantitative analyses of fluorescence transient, also called JIP-test. We found that Pn was significantly lower and closely correlated to the leaf stomatal conductance (Gs) of -fruit trees than that of fruit retained (+fruit) trees. Leaf temperature (Tleaf) of -fruit trees was remarkably higher than that of +fruit trees. Day-time-period assays of chlorophyll (Chl) fluorescence revealed that, in the leaves of -fruit trees, the fluorescence parameters, such as NPQ (non-photochemical quenching coefficient) and ΦD0 (maximum quantum yield of non-photochemical de-excitation), decreased in the morning and recovered to the normal level in the afternoon, whereas other parameters, such as ΦE0 (quantum yield for electron transport at t = 0), Ψ0 (probability that a trapped exciton moves an electron to QA pool), F0 (minimum fluorescence, when all PSII RCs are open) and Wk (relative variable fluorescence at 300 µs of the chlorophyll fluorescence transient), did not. These results suggest that OEC complex and QA pool were irreversibly affected by low sink demand, whereas light harvest antenna and PSII potential efficiency retained a strong ability to recover.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34427555

RESUMO

Currently, Lactococcus garvieae contains two subspecies: L. garvieae subsp. bovis and L. garvieae subsp. garvieae. In a study by Varsha and Nampoothiri, high pheS (99.7 %) and rpoA (99.6 %) sequence similarities indicated that L. garvieae subsp. bovis and Lactococcus formosensis probably have a close taxonomic relationship; low pheS (92.2 %) and rpoA (97.8 %) sequence similarities and relatively low DNA-DNA hybridization value (75.8 %) indicated that L. garvieae subsp. bovis and L. garvieae subsp. garvieae probably represent two different species. In the present study, the taxonomic relationships between L. garvieae subsp. bovis, L. garvieae subsp. garvieae and L. formosensis were re-examined based on sequence analyses of 16S rRNA, pheS, recA, rpoA and rpoB genes, average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) values, average amino acid identity (AAI), fatty acid methyl ester analysis and phenotypic characterization. L. garvieae subsp. bovis LMG 30663T exhibited 97.3 % ANI, 78.3 % dDDH and 96.4 % AAI values to L. formosensis NBRC 109475T, higher than the threshold for species demarcation (95-96, 70 and 95-96 %, respectively), indicating that L. garvieae subsp. bovis LMG 30663T and L. formosensis NBRC 109475T belong to the same species. L. garvieae subsp. bovis LMG 30663T had 91.2 % ANI, 43.3 % dDDH and 92.9-93.0% AAI values with the type strain of L. garvieae subsp. garvieae, indicating that they represent two different species. Because L. formosensis has been proposed and validated before L. garvieae subsp. bovis, L. garvieae subsp. bovis is transferred to L. formosensis as L. formosensis subsp. bovis comb. nov. The type strain of L. formosensis subsp. bovis is BSN307T (=DSM 100577T=MCC 2824T=KCTC 21083T=LMG 30663T). The type strain of L. formosensis subsp. formosensis is 516T (=NBRC 109475T=BCRC 80576T).


Assuntos
Lactococcus/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Genes Bacterianos , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
4.
Biomed Res Int ; 2021: 9983858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239939

RESUMO

Argonaute (AGO) proteins play a pivotal role in plant growth and development as the core components of RNA-induced silencing complex (RISC). However, no systematic characterization of AGO genes in wheat has been reported to date. In this study, a total number of 69 TaAGO genes in the hexaploid bread wheat (Triticum aestivum cv. Chinese Spring) genome, divided into 10 subfamilies, were identified. Compared to all wheat genes, TaAGOs showed a significantly lower evolutionary rate, which is consistent with their high conservation in eukaryotes. However, the homoeolog retention was remarkably higher than the average, implying the nonredundant biological importance of TaAGO genes in bread wheat. Further homoeologous gene expression bias analyses revealed that TaAGOs may have undergone neofunctionalization after polyploidization and duplication through the divergent expression of homoeologous gene copies, to provide new opportunities for the generation of adaptive traits. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) analyses indicated that TaAGO gene expression was involved in response to heat, drought, and salt stresses. Our results would provide a theoretical basis for future studies on the biological functions of TaAGO genes in wheat and other gramineous species.


Assuntos
Proteínas Argonauta/genética , Cromossomos de Plantas , Genoma de Planta , Poliploidia , Triticum/genética , Pão , Secas , Éxons , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Filogenia , Proteínas de Plantas/genética
5.
J Magn Reson Imaging ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296813

RESUMO

BACKGROUND: Intravoxel incoherent motion (IVIM) tensor imaging is a promising technique for diagnosis and monitoring of cardiovascular diseases. Knowledge about measurement repeatability, however, remains limited. PURPOSE: To evaluate short-term repeatability of IVIM tensor imaging in normal in vivo human hearts. STUDY TYPE: Prospective. POPULATION: Ten healthy subjects without history of heart diseases. FIELD STRENGTH/SEQUENCE: Balanced steady-state free-precession cine sequence and single-shot spin-echo echo planar IVIM tensor imaging sequence (9 b-values, 0-400 seconds/mm2 and six diffusion-encoding directions) at 3.0 T. ASSESSMENT: Subjects were scanned twice with an interval of 15 minutes, leaving the scanner between studies. The signal-to-noise ratio (SNR) was evaluated in anterior, lateral, septal, and inferior segments of the left ventricle wall. Fractional anisotropy (FA), mean diffusivity (MD), mean fraction (MF), and helix angle (HA) in the four segments were independently measured by five radiologists. STATISTICAL TESTS: IVIM tensor indexes were compared between observers using a one-way analysis of variance or between scans using a paired t-test (normal data) or a Wilcoxon rank-sum test (non-normal data). Interobserver agreement and test-retest repeatability were assessed using the intraclass correlation coefficient (ICC), within-subject coefficient of variation (WCV), and Bland-Altman limits of agreements. RESULTS: SNR of inferior segment was significantly lower than the other three segments, and inferior segment was therefore excluded from repeatability analysis. Interobserver repeatability was excellent for all IVIM tensor indexes (ICC: 0.886-0.972; WCV: 0.62%-4.22%). Test-retest repeatability was excellent for MD of the self-diffusion tensor (D) and MF of the perfusion fraction tensor (fp ) (ICC: 0.803-0.888; WCV: 1.42%-9.51%) and moderate for FA and MD of the pseudo-diffusion tensor (D* ) (ICC: 0.487-0.532; WCV: 6.98%-10.89%). FA of D and fp and HA of D presented good test-retest repeatability (ICC: 0.732-0.788; WCV: 3.28%-8.71%). DATA CONCLUSION: The D and fp indexes exhibited satisfactory repeatability, but further efforts were needed to improve repeatability of D* indexes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

6.
ACS Appl Mater Interfaces ; 13(29): 33905-33914, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34278780

RESUMO

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.

7.
Int J Gen Med ; 14: 1239-1249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859492

RESUMO

Background: Pulmonary thromboembolism (PTE) is a common disease which may be a serious condition and has high mortality. Recently, it has been shown that circRNAs play an important role in the development of various diseases, including thromboembolic disease. However, circRNAs expression profiling is not clear in PTE, this study aims to identify the circRNAs expressed in PTE and to elucidate their possible role in pathophysiology of PTE. Methods: A total of 5 patients with CTPA-confirmed PTE and 5 healthy controls were recruited for the present study. The circRNAs expression profile was analyzed by microarray. Results: In total, 256 differentially expressed circRNAs (up 142, down114) and 1162 mRNA (up 446, down 716) were summarized by analyzing the circRNAs microarray data. The top 3 up-regulated and 3 down-regulated circRNAs were validated by Real-Time Polymerase Chain Reaction (qRT-PCR). Two differentially expressed circRNAs (hsa_circ_0000891, hsa_circ_0043506) were selected for further analysis. Finally, we construct a circRNA-miRNA-mRNA ceRNA network with a bioinformatic prediction tool. Pathway analysis shows that the enriched mRNAs targets take part in Protein processing in endoplasmic reticulum, Systemic lupus erythematosus, Endocytosis, Spliceosome, HTLV-I infection and Ubiquitin mediated proteolysis. Conclusion: Our findings indicated that aberrantly expressed circRNAs (hsa_circ_0000891, hsa_circ_0043506) may be involved in the development of PTE.

8.
Eur J Med Chem ; 215: 113251, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33611187

RESUMO

Development of the drug with high therapeutic efficacy and low toxicity is crucial to cancer ablation. In this study, we have demonstrated a red light-responsive prodrug BDP-TK-CPT by connecting the chemotherapeutic agent camptothecin with a boron dipyrromethene (BDP)-based photosensitizer via a reactive oxygen species (ROS)-labile thioketal chain. Since camptothecin is modified by a BDP-based macrocycle at the active site, the formed prodrug displays an extremely low toxicity in dark. However, upon illumination by red light, it can efficiently generate ROS leading to cell death by photodynamic therapy. Meanwhile, the ROS generated can destroy thioketal group to release free camptothecin which further results in local cell death by chemotherapy. The combined antitumor effects of the prodrug have been verified in HepG2, EC109, and HeLa cancer cells and mice bearing H22 tumors. This study may provide an alternative strategy for stimuli-responsive combination treatment of tumors by conjugation of ROS-activatable prodrugs with photosensitizing agents.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Pró-Fármacos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Terapia Combinada , Tratamento Farmacológico , Feminino , Humanos , Luz , Camundongos , Necrose/induzido quimicamente , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Pró-Fármacos/síntese química , Pró-Fármacos/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
9.
Chin Med J (Engl) ; 134(4): 415-424, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33617184

RESUMO

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION: Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Área Sob a Curva , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , China , Humanos , Curva ROC , Sensibilidade e Especificidade
10.
Hortic Res ; 8(1): 32, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33518702

RESUMO

The aroma of peach fruit is predominantly determined by the accumulation of γ-decalactone and ester compounds. A previous study showed that the biosynthesis of these aroma compounds in peach fruit is catalyzed by PpAAT1, an alcohol acyltransferase. In this work, we investigated the key active site residues responsible for γ-decalactone and ester biosynthesis. A total of 14 candidate amino acid residues possibly involved in internal esterification and 9 candidate amino acid residues possibly involved in esterification of PpAAT1 were assessed via site-directed mutagenesis. Analyses of the in vitro enzyme activities of PpAAT1 and its site-directed mutant proteins (PpAAT1-SMs) with different amino acid residue mutations as well as the contents of γ-decalactone in transgenic tobacco leaves and peach fruits transiently expressing PpAAT1 and PpAAT1-SMs revealed that site-directed mutation of H165 in the conserved HxxxD motif led to lost enzymatic activity of PpAAT1 in both internal esterification and its reactions, whereas mutation of the key amino acid residue D376 led to the total loss of γ-decalactone biosynthesis activity of PpAAT1. Mutations of 9 and 7 other amino acid residues also dramatically affected the enzymatic activity of PpAAT1 in the internal esterification and esterification reactions, respectively. Our findings provide a biochemical foundation for the mechanical biosynthesis of γ-decalactone and ester compounds catalyzed by PpAAT1 in peach fruits, which could be used to guide the molecular breeding of new peach species with more favorable aromas for consumers.

11.
Magn Reson Med ; 85(3): 1414-1426, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32989786

RESUMO

PURPOSE: To investigate intravoxel incoherent motion (IVIM) tensor imaging of the in vivo human heart and elucidate whether the estimation of IVIM tensors is affected by the complexity of pseudo-diffusion components in myocardium. METHODS: The cardiac IVIM data of 10 healthy subjects were acquired using a diffusion weighted spin-echo echo-planar imaging sequence along 6 gradient directions with 10 b values (0~400 s/mm2 ). The IVIM data of left ventricle myocardium were fitted to the IVIM tensor model. The complexity of myocardial pseudo-diffusion components was reduced through exclusion of low b values (0 and 5 s/mm2 ) from the IVIM curve-fitting analysis. The fractional anisotropy, mean fraction/mean diffusivity, and Westin measurements of pseudo-diffusion tensors (fp and D*) and self-diffusion tensor (D), as well as the angle between the main eigenvector of fp (or D*) and that of D, were computed and compared before and after excluding low b values. RESULTS: The fractional anisotropy values of fp and D* without low b value participation were significantly higher (P < .001) than those with low b value participation, but an opposite trend was found for the mean fraction/diffusivity values. Besides, after removing low b values, the angle between the main eigenvector of fp (or D*) and that of D became small, and both fp and D* tensors presented significant decrease of spherical components and significant increase of linear components. CONCLUSION: The presence of multiple pseudo-diffusion components in myocardium indeed influences the estimation of IVIM tensors. The IVIM tensor model needs to be further improved to account for the complexity of myocardial microcirculatory network and blood flow.


Assuntos
Testes Diagnósticos de Rotina , Coração , Imagem de Difusão por Ressonância Magnética , Coração/diagnóstico por imagem , Humanos , Microcirculação , Movimento (Física) , Miocárdio
12.
World J Gastrointest Oncol ; 12(4): 394-404, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32368318

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignancies, with a high incidence and poor prognosis worldwide. Recently, accumulating evidence has illustrated that long noncoding RNAs (lncRNAs) play pivotal roles in many cancers. It has been reported that LINC00511 contributes to tumorigenesis in various diseases. However, the role of LINC00511 in GC cell growth remains mostly unknown. AIM: To determine whether the lncRNA LINC00511 exerted its carcinogenic function in GC via the miR-124-3p/PDK4 axis. METHODS: Cell culture and transfection, RNA extraction and quantitative real-time PCR, CCK-8 assay, Colony formation assay, Luciferase reporter assay, RIP assay, RNA pull-down assay, and Western blot analysis were used to show expression and mechanisms of LINC00511 in GC progression and apoptosis. Rescue assays were performed to verify the relationships among LINC00511, miR-124-3p and PDK4 further. RESULTS: The expression of LINC00511 was remarkably upregulated in GC cells compared to that in corresponding normal cell lines. Compared to the controls, cell proliferation was inhibited, and cell apoptosis was increased upon LINC00511 knockdown, demonstrating that LINC00511 influenced GC cell growth. An exploration of the molecular mechanism revealed that LINC00511 functioned as a molecular sponge of miR-124-3p and that PDK4 was a downstream target of miR-124-3p in GC. Rescue assays showed that the overexpression of PDK4 could partly restore the inhibitory function of si-LINC00511 in GC. CONCLUSION: These data demonstrate that LINC00511 promotes gastric cancer cell growth by acting as a ceRNA to regulate the miR-124-3p/PDK4 axis, which may be a promising therapeutic target for GC.

13.
Asian J Androl ; 22(4): 396-400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31571639

RESUMO

Testosterone (T) plays a crucial role in spermatogenesis because extremely low levels of intratesticular T lead to correspondingly low serum levels of total T (tT), severe disorders of spermatogenesis, and male sterility. However, there is little consensus on the lower limits of serum tT in proven fertile men undergoing assisted reproductive technology treatments in Chinese or other Asian populations. We aimed to establish the reference range of serum tT based on a population of 868 fertile Chinese men undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatments. We defined a fertile man as having had a live baby with his partner as recorded in our IVF registration system. The lower limits of serum tT were established using a Siemens IMMULITE 2000 chemiluminescent system. The 1st, 2.5th, and 5th percentiles and their 95% confidence intervals (CIs) were 3.6 (95% CI: 2.7-4.1) nmol l-1, 4.3 (95% CI: 4.1-5.0) nmol l-1, and 5.6 (95% CI: 4.8-5.8) nmol l-1, respectively. Using the linear correlation of serum tT between the Siemens platform and a liquid chromatography-tandem mass spectrometry platform, the calculated lower limits of serum tT were also established for fertile Chinese men undergoing IVF/ICSI-ET treatments, which will benefit the clinical diagnosis and treatment of male infertility during such procedures.


Assuntos
Grupo com Ancestrais do Continente Asiático , Fertilidade , Nascido Vivo , Testosterona/sangue , Adulto , China , Cromatografia Líquida , Transferência Embrionária , Fertilização In Vitro , Humanos , Medições Luminescentes , Masculino , Valores de Referência , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Espectrometria de Massas em Tandem , Tempo para Engravidar
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 351-354, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701721

RESUMO

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 µl at the concentration of 200 µg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-ß and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-ß and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05). CONCLUSION: Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Assuntos
Carthamus tinctorius/química , Extratos Vegetais/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bleomicina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Hidroxiprolina/análise , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
15.
Clin Chem Lab Med ; 57(12): 1915-1922, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31377732

RESUMO

Background α-Dicarbonyl compounds (α-DCs) have been detected in body fluids including plasma and urine and elevation of this sort of compounds in vivo has been associated with the development of many kinds of chronic diseases. However whether α-DCs are present in human saliva, and if their presence/absence can be related with various chronic diseases is yet to be determined. Methods In this study, a pre-column derivatization HPLC-UV method was developed to measure 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane-2,3-dione (PD) in human saliva employing 4-(2,3-dimethyl-6-quinoxalinyl)-1,2-benzenediamine (DQB) as a derivatizing reagent. The derivatization of the α-DCs is fast and the conditions are facile. The method was evaluated and the results show that it is suitable for the quantification of α-DCs in human saliva. Results In the measurements of these α-DCs in the saliva of 15 healthy subjects and 23 type 2 diabetes mellitus (T2DM) patients, we found that the concentrations of GO and MGO in the saliva of the diabetic patients were significantly higher than those in healthy subjects. As far as we know, this is the first time that salivary α-DC concentrations have been determined and associated with T2DM. Conclusions The developed method would be useful for the measurement of the salivary α-DC levels and the data acquired could be informative in the early screening for diabetes.


Assuntos
Desoxiglucose/análogos & derivados , Glioxal/análise , Aldeído Pirúvico/análise , Adulto , Cromatografia Líquida de Alta Pressão/métodos , Desoxiglucose/análise , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/química
16.
Cancer Imaging ; 19(1): 39, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217036

RESUMO

BACKGROUND: Preoperative chemotherapy is becoming standard therapy for liver metastasis from colorectal cancer, so early assessment of treatment response is crucial to make a reasonable therapeutic regimen and avoid overtreatment, especially for patients with severe side effects. The role of three non-mono-exponential diffusion models, such as the kurtosis model, the stretched exponential model and the statistical model, were explored in this study to early assess the response to chemotherapy in patients with liver metastasis from colorectal cancer. METHODS: Thirty-three patients diagnosed as colorectal liver metastasis were evaluated in this study. Diffusion-weighted images with b values (0, 200, 500, 1000, 1500, 2000 s/mm2) were acquired at 3.0 T. The parameters (ADCk, K, DDC,α, Ds and σ) were derived from three non-mono-exponential models (the kurtosis, stretched exponential and statistical models) as well as their corresponding percentage changes before and after chemotherapy. The difference in above parameters between the response and non-response groups were analyzed with independent-samples T-test (normality) and Mann-Whitney U-test (non-normality). Meanwhile, receiver operating characteristic curve (ROC) analyses were performed to assess the response to chemotherapy. RESULTS: Significantly lower values of K (the kurtosis coefficient derived from the kurtosis model) and σ (the width of diffusion coefficient distribution in the statistical model) (P < 0.05) were observed in the respond group before treatment, as well as higher ΔK and Δσ values (P < 0.05) after the first cycle of chemotherapy were also found compared with the non-respond group. ROC analyses showed the K value acquired before treatment had the highest diagnostic performance (0.746) in distinguishing responders from non-responders. Furthermore, the high sensitivity (100%) and accuracy (76.3%) from the K value before treatment was found in assessing the response of colorectal liver metastasis to chemotherapy. CONCLUSIONS: The non-mono-exponential diffusion models may be able to predict early response to chemotherapy in patients with colorectal liver metastasis.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
17.
J Xray Sci Technol ; 27(3): 485-492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31081797

RESUMO

PURPOSE: To explore the radiomics features of triple negative breast cancer (TNBC) and non-triple negative breast cancer (non-TNBC) based on X-ray mammography, and to differentiate the two groups of cases. MATERIALS AND METHODS: Preoperative mammograms of 120 patients with breast ductal carcinoma confirmed by surgical pathology were retrospectively analyzed, which include 30 TNBC and 90 non-TNBC patients. The manual segmentation of breast lesions was performed by ITK-SNAP software and 12 radiomics features were extracted by Omni-Kinetics software. The differences of these radiomics features between TNBC and non-TNBC groups were compared, and the receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of each radiomics parameter for differentiating TNBC from non-TNBC, and the corresponding area under the curve (AUC), sensitivity and specificity were obtained. RESULTS: There were statistically significant differences for 4 radiomics features between TNBC and non-TNBC datasets (P < 0.05). They were the roundness, concavity, gray average and skewness of breast lesions. Compared with non-TNBC, TNBC cases have following characteristics of (1) more round with the roundness of 0.621 vs. 0.413 (P < 0.001), (2) more regular with the concavity of 0.087 vs. 0.141 (P < 0.01), (3) higher density or gray average (67.261 vs. 56.842, P < 0.05), and (4) lower skewness (- 0.837 vs.- 0.671, P = 0.034). AUCs of ROC curves computed using features of the roundness and concavity were both larger than 0.70. CONCLUSION: Radiomics features based on X-ray mammography may be helpful to distinguish between TNBC and non-TNBC, which were associated with breast tumor histology.


Assuntos
Mamografia , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Proc Natl Acad Sci U S A ; 116(21): 10447-10452, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31061131

RESUMO

STAT3 is a transcription factor that plays central roles in various physiological processes, including differentiation of Th cells. Its deregulation results in serious diseases, including inflammatory diseases and cancer. The mechanisms related to how STAT3 activity is regulated remain enigmatic. Here we show that overexpression of FAM64A potentiates IL-6-induced activation of STAT3 and expression of downstream target genes, whereas deficiency of FAM64A has the opposite effects. FAM64A interacts with STAT3 in the nucleus and regulates binding of STAT3 to the promoters of its target genes. Deficiency of Fam64a significantly impairs differentiation of Th17 but not Th1 or induced regulatory T cells (iTreg). In addition, Fam64a deficiency attenuates experimental autoimmune encephalomyelitis (EAE) and dextran sulfate sodium (DSS)-induced colitis, which is correlated with decreased differentiation of Th17 cells and production of proinflammatory cytokines. Furthermore, Fam64a deficiency suppresses azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) in mice. These findings suggest that FAM64A regulates Th17 differentiation and colitis and inflammation-associated cancer by modulating transcriptional activity of STAT3.


Assuntos
Carcinogênese/metabolismo , Colite/metabolismo , Fator de Transcrição STAT3/metabolismo , Células Th17 , Animais , Diferenciação Celular , Colite/complicações , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Camundongos
19.
Pulm Pharmacol Ther ; 57: 101803, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085231

RESUMO

Pulmonary fibrosis is a progressive fibrotic lung disease with a paucity of therapeutic options. Here we investigated the potential roles of probucol, a cholesterol-lowering drug with potent anti-oxidation properties, on pulmonary epithelial-mesenchymal transition (EMT) and fibrosis. We found that bleomycin-induced lung fibrosis was associated with increased transforming growth factor (TGF)-ß1, α-smooth muscle actin (α-SMA) and decreased E-cadherin expression in lung tissues, indicating EMT formation. Bleomycin treatment resulted in an induction of oxidative stress in lung tissues. Probucol treatment attenuated bleomycin-induced TGF-ß1 production, EMT and pulmonary fibrosis, meanwhile it suppressed bleomycin-induced oxidative stress. Bleomycin treatment resulted in decreases in protein expressions of Sirtuin 3 (SIRT3) in the lung, which were restored by ROS scavenger NAC and probucol treatment, suggesting that probucol might restore SIRT3 expression by suppressing bleomycin-induced oxidative stress. In the mouse alveolar type II epithelial cell line MLE-12, probucol treatment leads to an increase in SIRT3 expression in bleomycin-treated AT-II cells, which might contribute to the inhibitory effect of probucol on EMT through suppressing hypoxia inducible factor (HIF)-1α/TGF-ß1 pathway. In addition, probucol inhibited bleomycin-induced macrophage infiltration in the lung. Bleomycin decreased SIRT3 protein expression, whereas increased HIF-1α activation and TGF-ß1 release in the mouse macrophage cell line RAW264.7, which were attenuated by probucol treatment. Taken together, the present study suggests that probucol may ameliorate EMT and lung fibrosis through restoration of SIRT3 expression. The data obtained in this study provides proof for the idea that probucol may be a potential therapeutic option for the treatment of pulmonary fibrosis.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Probucol/farmacologia , Fibrose Pulmonar/tratamento farmacológico , Sirtuína 3/metabolismo , Actinas/metabolismo , Células Epiteliais Alveolares , Animais , Bleomicina/farmacologia , Caderinas/metabolismo , Técnicas de Cultura de Células , Colágeno Tipo I/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Sirtuína 3/biossíntese , Fator de Crescimento Transformador beta1/metabolismo
20.
Exp Ther Med ; 17(5): 3335-3342, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30988709

RESUMO

ß-patchoulene (ß-PAE), an active constituent of the Pogostemon cablin, is well known for its anti-inflammatory and antioxidative functions in various diseases. However, little is known about the impact of ß-PAE on the cerebral ischemia-reperfusion (I/R) injury. The current study aimed to determine the neuroprotective effect of ß-PAE and the underlying mechanisms on cerebral I/R injury. Following pretreatment with ß-PAE (10 mg/kg body weight) by tail intravenous injection for 1 h, Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 h and reperfusion for 24 h. The results indicated that pretreatment with ß-PAE could diminish the infarct volume, decrease the brain water content, reduce the neurological deficit score and restore the mitochondrial membrane potential, compared with the untreated I/R injury group. Furthermore, cell apoptosis was markedly suppressed by ß-PAE, and this effect was associated with the decreased apoptosis regulator BAX/apoptosis regulator Bcl-2 expression ratio and caspase-3 activity. In addition, ß-PAE significantly inhibited the release of proinflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß and IL-6. Superoxide generation and malondialdehyde levels were reduced while the levels of glutathione peroxidase and superoxide dismutase were elevated following treatment with ß-PAE, indicating the antioxidative role of ß-PAE in cerebral I/R injury. Furthermore, the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was inhibited by ß-PAE, as demonstrated by the decreased TLR4 expression and nuclear translocation of p65, and increased IκBα level. Taken together, the results suggested that ß-PAE may exhibit a neuroprotective effect on cerebral I/R injury in rats through inactivating the TLR4/NF-κB signaling pathway.

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