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1.
Lung Cancer ; 150: 44-52, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33065462

RESUMO

OBJECTIVES: To investigate the potential of 2-deoxy-2(18F)fluoro-d-glucose (18F-FDG) combined positron emission tomography and computed tomography (PET/CT) in predicting programmed cell death ligand-1 (PDL1) expression status in pulmonary lesions of advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective study includes 133 untreated stage IIIB-IV NSCLC patients who underwent pulmonary lesion biopsy for PDL1 immunochemistry 1-4 weeks after 18F-FDG PET/CT scanning, randomly assigned to cohorts for modelling and validation of PDL1 expression predictors. Mean and maximum standard uptake values (pSUVmean and pSUVmax), metabolic tumour volume (pMTV), and total lesion glycolysis (pTLG) of primary lesions were determined. PDL1 expression in pulmonary lesions (pPDL1) was determined using tumour proportion score (TPS), and pPDL1 TPS < 1%, 1-49 %, and ≥ 50 % were considered as pPDL1-negative, pPDL1-moderate, and pPDL1-strong, respectively. RESULTS: pSUVmean and pSUVmax values were increased with the increase of pPDL1 levels, whereas pMTV and pTLG values were not associated with pPDL1 levels. In the modelling cohort, we found that pSUVmax rather than pSUVmean was an independent predictor for pPDL1-negative, pPDL1-moderate, and pPDL1-strong, whereas pSUVmax < 14.4, 14.4-17.5, and > 17.5 were suggested as predictors for pPDL1-negative, pPDL1-moderate, and pPDL1-strong, respectively (odds ratio: 4.82, 3.92, and 4.45, respectively; P = 0.002, 0.021, and 0.020, respectively). In the validation cohort, pSUVmax < 14.4, 14.4-17.5, and > 17.5 showed significantly high probabilities of being pPDL1-negative, pPDL1-moderate, and pPDL1-strong, respectively (P = 0.006). The accuracies of pSUVmax < 14.4, 14.4-17.5, and > 17.5 predicting pPDL1-negative, pPDL1-moderate, and pPDL1-strong, respectively, in validation cohort, were 66.7 %, 75.8 %, and 84.8 %, respectively. CONCLUSION: pSUVmax on 18F-FDG PET/CT is a potential biomarker for pPDL1 TPS < 1%, 1-49 %, and ≥ 50 % in untreated stage IIIB-IV NSCLC, and therefore may be helpful for determining immunotherapeutic strategy for advanced NSCLC.

2.
PeerJ ; 8: e10077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083135

RESUMO

Protoplasts are commonly used in genetic and breeding research. In this study, the isolation of sorghum protoplasts was optimized and applied to transient gene expression and editing by CRISPR/Cas9. The protoplast was most viable in 0.5 M mannitol, which was the highest of three concentrations after 48- and 72-hours treatments. Using this method we can derive an average of 1.6×106 cells which vary from 5 to 22 nm in size. The average transfection of the protoplasts was 68.5% using the PEG-mediated method. The subcellular assays located Sobic.002G279100-GFP and GFP proteins in the cell compartments as predicted bioinformatically. Two CRISPR/Cas9 plasmids were transfected into sorghum protoplasts to screen for an appropriate sgRNA for gene editing. One plasmid can correctly edit the target region using a single protoplast cell as template DNA. Our results indicated that the protoplast assays as optimized are suitable for transient gene expression and sgRNA screening in CRISPR/Cas9 gene editing procedures.

3.
Science ; 370(6514)2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33060330

RESUMO

Brains encode behaviors using neurons amenable to systematic classification by gene expression. The contribution of molecular identity to neural coding is not understood because of the challenges involved with measuring neural dynamics and molecular information from the same cells. We developed CaRMA (calcium and RNA multiplexed activity) imaging based on recording in vivo single-neuron calcium dynamics followed by gene expression analysis. We simultaneously monitored activity in hundreds of neurons in mouse paraventricular hypothalamus (PVH). Combinations of cell-type marker genes had predictive power for neuronal responses across 11 behavioral states. The PVH uses combinatorial assemblies of molecularly defined neuron populations for grouped-ensemble coding of survival behaviors. The neuropeptide receptor neuropeptide Y receptor type 1 (Npy1r) amalgamated multiple cell types with similar responses. Our results show that molecularly defined neurons are important processing units for brain function.

4.
Nat Chem ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895523

RESUMO

DNA origami has emerged as a highly programmable method to construct customized objects and functional devices in the 10-100 nm scale. Scaling up the size of the DNA origami would enable many potential applications, which include metamaterial construction and surface-based biophysical assays. Here we demonstrate that a six-helix bundle DNA origami nanostructure in the submicrometre scale (meta-DNA) could be used as a magnified analogue of single-stranded DNA, and that two meta-DNAs that contain complementary 'meta-base pairs' can form double helices with programmed handedness and helical pitches. By mimicking the molecular behaviours of DNA strands and their assembly strategies, we used meta-DNA building blocks to form diverse and complex structures on the micrometre scale. Using meta-DNA building blocks, we constructed a series of DNA architectures on a submicrometre-to-micrometre scale, which include meta-multi-arm junctions, three-dimensional (3D) polyhedrons, and various 2D/3D lattices. We also demonstrated a hierarchical strand-displacement reaction on meta-DNA to transfer the dynamic features of DNA into the meta-DNA. This meta-DNA self-assembly concept may transform the microscopic world of structural DNA nanotechnology.

5.
J Cell Mol Med ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990414

RESUMO

Microglia are rapidly activated following ischaemic stroke and participate in the induction of neuroinflammation, which exacerbates the injury of ischaemic stroke. However, the mechanisms regulating ischaemic microglia remain unclear. In the present study, middle cerebral artery occlusion and oxygen and glucose deprivation models were established for in vivo and vitro monitoring of experimental stroke. We applied recombinant human thioredoxin-1 (rhTrx-1) and Necrostatin-1 (Nec-1, inhibitor of RIPK1) to examine the role of receptor-interacting protein kinase 1 (RIPK1) in the development of inflammation in ischaemic microglia via explored the inflammatory responses and the associated mechanisms. Molecular docking results indicated that rhTrx-1 could directly bind to RIPK1. In vivo and vitro data revealed that rhTrx-1 reduced necroptosis, mitochondrial membrane potential damage, reactive oxygen species accumulation and NLR Family, pyrin domain-containing 3 protein (NLRP3) inflammasome activation and regulated the microglial M1/M2 phenotypic changes by inhibiting RIPK1 expression in ischaemic microglia. Consistent with these findings, further in vivo experiments revealed that rhTrx-1 treatment attenuated cerebral ischaemic injury by inhibiting the inflammatory response. Our data demonstrated the role of RIPK1 in microglia-induced neuroinflammation following cerebral ischaemia. Administration of rhTrx-1 provides neuroprotection in ischaemic stroke-induced microglial neuroinflammation by inhibiting RIPK1 expression.

6.
Int J Colorectal Dis ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32965529

RESUMO

PURPOSE: This study aimed to investigate the prevalence, risk, and prognostic factors for synchronous liver metastasis (LM) in colorectal cancer (CRC) and to construct nomogram for predicting occurrence and prognosis of synchronous LM. METHODS: A total of 203,998 CRC patients who were registered in the SEER database between 2010 and 2016 were included. Logistic regression was used to analyze risk factors and Kaplan-Meier was used to estimate the overall survival of CRC patients with LM. Potential prognostic factors were identified by multivariable Cox regression. For predicting the risk for development and prognosis in CRC patients with LM, we constructed nomogram and the predictive performance was estimated by the receiver operating characteristics cure, the concordance index, and calibration curve. RESULTS: In total, 15.3% of the CRC patients (N = 31,288) had synchronous LM. Male gender, black, uninsured status, left colon, T4/T1, and bone and lung metastases were positively associated with synchronous LM risk. The 1-year, 3-year, and 5-year overall survival rate was 49.1%, 18.4%, and 9.2%, respectively. Older age, male gender, black, uninsured status, poor histological differentiation, lymphatic metastasis, T4/T1, positive carcinoembryonic antigen, and lung, bone, and brain metastases were associated with the overall survival. Nomogram was constructed to predict the development and prognosis of synchronous LM and both of them were proved to have good calibration and discrimination. CONCLUSION: LM is highly prevalent in CRC patients. Nomogram basing on the risk and prognostic factors for synchronous LM was proved to have good performance for predicting the probability of LM occurrence and prognosis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32867663

RESUMO

BACKGROUND: Mammalian target of rapamycin (mTOR) has been evidenced as a multimodal therapy in the path-ophysiological process of acute ischemic stroke (AIS). However, the pathway that minocycline targets mTOR signaling is not fully defined in the AIS pathogenesis. This study is to aim at the effects of minocycline on the mTOR signaling in the AIS process and further discover the underlying mechanisms of minocycline involved in the following change of mTOR signaling-autophagy. METHODS: Cerebral ischemia/reperfusion (CIR) rat animal models were established with the transient suture occlusion into middle cerebral artery. Minocycline (50mg/kg) was given by intragastric administration. The Morris water maze was used to test the cognitive function of animals. Immunohisto chemistry and immuno fluorescence were introduced for testing the lev-els of synaptophysin and PSD-95. Western blot was conducted for investigating the levels of mTOR, p-mTOR (Ser2448), p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366), p-eIF4B (Ser406), LC3, p62, synaptophysin and PSD-95. RESULTS: Minocycline prevents cognitive decline of the MCAO stroke rats. Minocycline limits the expression of p-mTOR (Ser2448) and the downstream targets of mTOR [p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366) and p-eIF4B (Ser406)] (P<0.01), while minocycline has no influence on mTOR. LC3-II abundance and the LC3-II/I ratio were upregu-lated in the hippocampus of the MCAO stroke rats by the minocycline therapy (P<0.01). p62 was downregulated in the hip-pocampus from the MCAO stroke rats administrated with minocycline therapy(P<0.01). The levels of SYP and PSD-95 were up-regulated in the brain of the MCAO stroke rats administrated with minocycline therapy. CONCLUSION: Minocycline prevents cognitive deficits via inhibiting mTOR signaling and enhancing autophagy process, and promoting the expression of pre-and postsynaptic proteins (synaptophysin and PSD-95) in the brain of the MCAO stroke rats. The potential neuroprotective role of minocycline in the process of cerebral ischemia may be related to mitigating is-chemia-induced synapse injury via inhibiting activation of mTOR signaling.

8.
Elife ; 92020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869744

RESUMO

The basolateral amygdala complex (BLA), extensively connected with both local amygdalar nuclei as well as long-range circuits, is involved in a diverse array of functional roles. Understanding the mechanisms of such functional diversity will be greatly informed by understanding the cell-type-specific landscape of the BLA. Here, beginning with single-cell RNA sequencing, we identified both discrete and graded continuous gene-expression differences within the mouse BLA. Via in situ hybridization, we next mapped this discrete transcriptomic heterogeneity onto a sharp spatial border between the basal and lateral amygdala nuclei, and identified continuous spatial gene-expression gradients within each of these regions. These discrete and continuous spatial transformations of transcriptomic cell-type identity were recapitulated by local morphology as well as long-range connectivity. Thus, BLA excitatory neurons are a highly heterogenous collection of neurons that spatially covary in molecular, cellular, and circuit properties. This heterogeneity likely drives pronounced spatial variation in BLA computation and function.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32946221

RESUMO

NiCo-layered double hydroxide (LDH) has attracted increasing attention in recent years for application in supercapacitors (SCs) owing to its high redox activity and intercalating capability. However, the pristine NiCo-LDH is unable to reach theoretical specific capacitance and satisfying rate capability due to the limited electroactive species and a low ion diffusion rate. Here, we demonstrate novel vertically aligned nanosheet arrays of cobalt metal-organic framework (Co-MOF)@CoNiO2 core-shell composites constructed by the in situ grown Co-MOF shell with a uniform and controlled thickness on the CoNiO2 core via a vapor-phase approach. Owing to the intimate contact and synergistic effect between the Co-MOF shell and the CoNiO2 core, the as-synthesized Co-MOF@CoNiO2 displays a high specific capacitance of about 571 F g-1, which is significantly higher than the pristine NiCo-LDH electrode (380 F g-1). Moreover, the capacitive properties of Co-MOF@CoNiO2 can be further boosted to 757.2 F g-1 after cyclic voltammetry oxidation. The easy preparation and high electrochemical performance of the Co-MOF@CoNiO2 composite make it a potential material for SC application. These findings may inspire the exploration and construction of other MOF shell coating metal oxide from various nanostructured LDHs for varied applications. In addition, the as-assembled EO-Co-MOF@CoNiO2/carbon cloth (CC)//activated carbon (AC) device can achieve a high capacitance of 87.67 F g-1. Meanwhile, the asymmetric supercapacitor (ASC) device exhibits a high energy density of 27.4 Wh kg-1 at a power density of 750 W kg-1.

10.
Life Sci ; 261: 118479, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32966840

RESUMO

AIMS: This study was designed to investigate the molecular mechanisms underlying the anti-inflammatory and anti-fibrosis effects of Berberine hydrochloride (BBR) following canalicular laceration (CL) surgical repair. MAIN METHODS: We used a rabbit CL model in this study. BBR and the control medicine were administered during and after the surgical operation. The degree of fibrosis in the canaliculi was evaluated using hematoxylin and eosin and Masson's trichrome staining 7 days after the operation. Inflammation inside the canaliculi was observed using a transcanalicular endoscope. Expression levels of inflammatory cell cytokines [tumor growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), intracellular adhesion molecule-I (ICAM-1), and interleukin-ß1 (IL-1ß)] were detected using immunohistochemistry. P38 and ERK1 phosphorylation and activation were determined using western blot analysis. KEY FINDINGS: The degree of inflammation and fibrosis were less in the BBR groups compared to Surgery group. The anti-inflammatory and anti-fibrosis effects of BBR were concentration-dependent. The levels of TGF-ß1, CTGF, ICAM-1, and IL-1ß were significantly lower in the BBR groups compared to Surgery group. BBR reduced the phosphorylation of P38 compared to Surgery group. SIGNIFICANCE: In conclusion, this study shows that BBR can reduce local fibrosis after CL surgical repair via its anti-inflammatory and anti-fibrosis effects.

11.
Pathogens ; 9(8)2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32824178

RESUMO

Classical swine fever (CSF) is a highly contagious viral disease of pigs, including wild boar. It is regarded as one of the major problems in the pig industry as it is still endemic in many regions of the world and has the potential to cause devastating epidemics, particularly in countries free of the disease. Rapid and reliable diagnosis is of utmost importance in the control of CSF. Since clinical presentations of CSF are highly variable and may be confused with other viral diseases in pigs, laboratory diagnosis is indispensable for an unambiguous diagnosis. On an international level, well-established diagnostic tests of CSF such as virus isolation, fluorescent antibody test (FAT), antigen capture antibody enzyme-linked immunosorbent assay (ELISA), reverse-transcription polymerase chain reaction (RT-PCR), virus neutralization test (VNT), and antibody ELISA have been described in detail in the OIE Terrestrial Manual. However, improved CSF diagnostic methods or alternatives based on modern technologies have been developed in recent years. This review thus presents recent advances in the diagnosis of CSF and future perspectives.

12.
J Vasc Access ; : 1129729820951047, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32830606

RESUMO

BACKGROUND AND OBJECTIVES: For patients who rely on a tunneled cuffed catheter, the internal jugular vein is the preferred site of insertion. A few studies have suggested that the posterior approach for central lines is equivalent or better in comparison to the conventional central approach. However, there have been fewer studies examining tunneled cuffed catheter insertion using the posterior approach. We have performed many posterior insertions of tunneled cuffed catheters in our practice, and because the technique has not yet been comprehensively studied for long-term use, we performed a retrospective study to evaluate the safety and efficacy of posterior approach for tunneled cuffed catheter in maintained hemodialysis patients. METHODS: A retrospective review was conducted of 200 hemodialysis patients who were treated with tunneled cuffed catheters over a period of 3 years. There were 104 patients in the study group, as well as a 96-patient control group, who underwent catheter insertion by central approach. The clinical follow-up data were collected and analyzed. RESULTS: All catheters were successfully placed. The mean primary patency days per catheter were 712 catheter days for the study group and 585 catheter days for the control group. The episode of catheter infection was similar in both groups (p = 0.874), but the case of total catheter dysfunction was significantly lower in the study group compared to the control group (p = 0.006). The cumulative patency of catheters was higher in the study group than that in the control group (p = 0.02), while patient survival was the same in the two groups (p = 0.325). CONCLUSION: The posterior approach is safe, and similar infection rates were observed with lower dysfunction rates compared to tunneled catheter insertion by the conventional central approach.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32744433

RESUMO

The widespread application of CRISPR-Cas9 has transformed genome engineering. Nevertheless, the precision to control the targeting activity of Cas9 requires further improvement. We report a toehold-switch-based approach to engineer the conformation of single guide RNA (sgRNA) for programmable activation of Cas9. This activation circuit is responsive to multiple inputs and can regulate the conformation of the sgRNA through toehold-switch-mediated strand displacement. We demonstrate the orthogonal suppression and activation of Cas9 with orthogonal DNA inputs. Combination of toehold switches leads to a variety of intracellular Cas9 activation programs with simultaneous and orthogonal responses, through which multiple genome loci are displayed in different colors in a controllable manner. This approach provides a new route for programing CRISPR in living cells for genome imaging and engineering.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32787185

RESUMO

The bottom-up DNA-templated nanoelectronics exploits the unparalleled self-assembly properties of DNA molecules and their amenability with various types of nanomaterials. In principle, nanoelectronic devices can be bottom-up assembled with near-atomic precision, which compares favorably with well-established top-down fabrication process with nanometer precision. Over the past decade, intensive effort has been made to develop DNA-based nanoassemblies including DNA-metal, DNA-polymer, and DNA-carbon nanotube complexes. This review introduces the history of DNA-based fabrication for nanoelectronics briefly and summarizes the state-of-art advances of DNA-based nanoelectronics. In particular, the most widely applied characterization techniques to explore their unique electronic properties at the nanoscale are described and discussed, including scanning tunneling microscopy, conductive atomic force microscopy, and Kelvin probe force microscopy. We also provide a perspective on potential applications of DNA-based nanoelectronics.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32794717

RESUMO

Plasma membrane-derived extracellular vesicles (PEVs) are carriers of biological molecules that perform special cell-cell communications. Nevertheless, the characterization of complicated PEV biology is hampered by the failure of current methods, mainly due to lack of specific labels and insufficient resolution. Here, we employed atomic force microscopy and scanning ion conductance microscopy, both capable of three-dimensional nanoscale resolution, for the label-free visualization of the PEV morphology, release, and uptake at the single-vesicle level. Except for classical microvesicles, we observed a cluster-like PEVs subtype in tumor cells. Moreover, both PEV subtype release times positively correlated with size. Through three-dimensional nanoscale imaging, we visualized the multiform PEV-cell interaction behaviors of individual vesicles, which was challenged in conventional PEV imaging. Finally, we developed single-cell manipulation strategies to induce micrometer-sized PEV generation. Collectively, these results revealed the heterogeneous morphology and dynamics of PEVs at the single vesicle level, which provided new insight into the PEV biology.

16.
Oncol Lett ; 20(4): 51, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32788938

RESUMO

The application of additive manufacturing (AM) technology has been widely used in various medical fields, including craniomaxillofacial surgery. The aim of the present study was to examine the surgical efficiency and post-operative outcomes of patient-specific titanium mandibular reconstruction using AM. Major steps in directly designing and manufacturing 3D customized titanium implants are discussed. Furthermore, pre-operative preparations, surgical procedures and post-operative treatment outcomes were compared among patients who received mandibular reconstruction using a customized 3D titanium implant, titanium reconstruction plates or vascularized autologous fibular grafting. Use of a customized titanium implant significantly improved surgical efficiency and precision. When compared with mandibular reconstruction using the two conventional approaches, patients who received the customized implant were significantly more satisfied with their facial appearance, and exhibited minimal post-operative complications in the 12-month follow-up period. Patients who underwent mandibular reconstruction using a customized titanium implant displayed improved mandibular contour symmetry, restored occlusal function, normal range of mouth opening and no temporomandibular joint related pain; all complications frequently experienced by patients who undergo conventional approaches of mandibular reconstruction.

17.
J Bioinform Comput Biol ; : 2050027, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32757807

RESUMO

Background: Tumor purity is of great significance for the study of tumor genotyping and the prediction of recurrence, which is significantly affected by tumor heterogeneity. Tumor heterogeneity is the basis of drug resistance in various cancer treatments, and DNA methylation plays a core role in the generation of tumor heterogeneity. Almost all types of cancer cells are associated with abnormal DNA methylation in certain regions of the genome. The selection of tumor-related differential methylation sites, which can be used as an indicator of tumor purity, has important implications for purity assessment. At present, the selection of information sites mostly focuses on inter-tumor heterogeneity and ignores the heterogeneity of tumor growth space that is sample specificity. Results: Considering the specificity of tumor samples and the information gain of individual tumor sample relative to the normal samples, we present an approach, PESM, to evaluate the tumor purity through the specificity difference methylation sites of tumor samples. Applied to more than 200 tumor samples of Prostate adenocarcinoma (PRAD) and Kidney renal clear cell carcinoma (KIRC), it shows that the tumor purity estimated by PESM is highly consistent with other existing methods. In addition, PESM performs better than the method that uses the integrated signal of methylation sites to estimate purity. Therefore, different information sites selection methods have an important impact on the estimation of tumor purity, and the selection of sample specific information sites has a certain significance for accurate identification of tumor purity of samples.

18.
Free Radic Biol Med ; 160: 208-218, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32791187

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) leads to progressive lung injury, which significantly impacts patient morbidity and mortality but may differ clinically between the sexes. Cytochrome P450 (CYP) 1A enzymes are protective against hyperoxic lung injury and may contribute to sex-dependent pathology. NRF2 is a critical transcriptional regulator of antioxidants and loss of NRF2 leads to severe hyperoxic lung injury and mortality in mice. NRF2 deficiencies and polymorphisms have been observed in patients with pulmonary diseases such as chronic obstructive pulmonary disease and severe asthma. No prior studies have evaluated whether there are sex-specific differences in oxygen-mediated lung injury in Nrf2-/- mice and there are few rescue studies. OBJECTIVE: To test the hypothesis that hyperoxia induces greater lung injury and inflammation in Nrf2-/- mice compared to wild type (WT) that differs between sexes, and that this phenotype will be rescued by the administration of the cytochrome P450 (CYP) 1A inducer beta-naphthoflavone (BNF). DESIGN/METHODS: Male and female 8-10-week-old WT or Nrf2-/- C57BL/6 mice were pre-treated with BNF (40 mg/kg) or corn oil control and exposed to hyperoxia (95% O2) for 68 h. Survival, pulmonary edema, neutrophil recruitment, and lung injury scores were evaluated. Gene expression of phase II detoxification enzymes, pulmonary cytokines, and Cyp1a1/2 was quantified. CYP1A1/2 protein expression and catalytic activities were also measured. RESULTS: Hyperoxia exposure greatly reduced survival in Nrf2-/- mice, particularly in females. BNF treatment improved survival by 182.8% in Nrf2-/- females and by 41.4% in Nrf2-/- males as well as in WT females by 85.7%. Females had greater pulmonary edema as measured by lung weight to body weight ratios but was attenuated in all groups except Nrf2-/- females by BNF. Neutrophils doubled in Nrf2-/- lungs compared to WT in hyperoxia but were decreased in BNF-treated females of both genotypes. Pulmonary cytokine gene expression including Il-6 and Tnf-α increased in hyperoxia especially in Nrf2-/- mice and was unaffected by BNF. Pulmonary and hepatic Nqo1 gene expression w-as decreased in Nrf2-/- mice and was largely unaffected by BNF; however pulmonary Ho-1 did not vary significantly between the genotypes and was decreased in WT animals treated with BNF. Activities and protein expression of pulmonary and hepatic CYP1A1/2 were induced via BNF across all groups. Although hepatic Cyp1a2 gene expression was higher in Nrf2-/- males, the catalytic activity was higher in Nrf2-/- females. CONCLUSIONS: Hyperoxia augmented lung injury in Nrf2-/- mice, and pre-treatment with BNF was protective against mortality and injury, eliminating the sex-dependent survival difference in both genotypes. Our results support the hypothesis that NRF2 protects mice against lung injury, and the fact that BNF rescues the lung injury phenotype in Nrf2-/- mice suggests that augmented CYP1A expression by BNF may contribute to the beneficial effects. Further studies could lead to the development of BNF and other flavonoids for the prevention/treatment of hyperoxic lung injury, particularly in vulnerable patients with relative NRF2 deficiency, regardless of sex.

19.
Food Sci Nutr ; 8(7): 3626-3637, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32724625

RESUMO

Black chokeberries (Aronia melanocarpa), deciduous shrubs of the Rosaceae family, are native to northeastern North America. Chokeberry fruits are cultivated to make jellies, juices, and wines. Black chokeberry pulp is rich in phenolics and other antioxidants and exhibits potential for health and food packaging benefits. Chokeberries' in vitro antioxidant activity is among the highest values of all berries, though chokeberry extraction techniques frequently employ environmentally unfavorable solvents or are time-inefficient. Batch extraction of antioxidants from chokeberry pomace using supercritical carbon dioxide with an ethanol modifier was used to examine the effects of plant loading, pressure, temperature, and percent ethanol by weight. Effects on total phenolic content (TPC) and the optimal conditions for extractions within these ranges are reported. Multivariate analyses reveal the following relationships of extraction conditions upon TPC: Temperature is directly proportional, percent ethanol by weight is inversely proportional, and chokeberry loads can be increased to enhance antioxidant activity, though not through a linear relationship. In studies involving 0.5 g plant load, the conditions 24.9MPa, 68°C, 90wt-% CO2, and 10wt-% ethanol generated the highest TPC value, 3.42 ± 0.20 mg gallic acid equivalents/gram chokeberry. Chokeberry extracts displayed antiproliferative effects on the SKBr3 breast cancer line and the 52KO MEF line, although TPC was not predictive of cellular responses. HPLC-MS data suggest cyanidin hexose and cyanidin pentose compounds as well as quercetin deoxyhexose-hexose as components of the more favorable extraction product that reflected a significant decrease in viability for the extract in comparison with ethanol control in the SKBr3 breast cancer line.

20.
J Int Med Res ; 48(7): 300060520936414, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32644864

RESUMO

Aggressive angiomyxoma is an interstitial tumour that is often misdiagnosed and is likely to recur. There have been few reported cases of angiomyxoma in pregnant women. We report a case of a woman who was previously diagnosed with a tumour in her vulva that increased in size during both of her pregnancies and spontaneously decreased postpartum. Local excision was performed and a gonadotropin-releasing hormone agonist was administered. According to a literature review, aggressive angiomyxoma is associated with good maternal and child outcomes. Caesarean section is not the delivery method of choice, but it is indicated if the tumour is preventing vaginal birth. Treatment for angiomyxoma is mainly postpartum local resection supplemented by hormone therapy. This tumour frequently recurs and patients should undergo long-term follow-up.

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