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1.
Small ; : e2004557, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043568

RESUMO

Realizing near-infrared (NIR) driven photocatalytic reaction is one of the promising strategies to promote the solar energy utilization and photocatalytic efficiencies. However, effective reactive oxygen species (ROS) activation under NIR irradiation remains to be great challenge for nearly all previously reported photocatalysts. Herein, the cubic-phase tungsten nitride (WN) with strong plasmonic NIR absorption and low-work function (≈3.59 eV) is proved to be able to mediate direct ROS activation by both of experimental observation and theoretical simulation. The cubic WN nanocubes (NCs) are synthesized via the hydrothermal-ammonia nitridation process and its NIR-driven photocatalytic properties, including photocatalytic degradation, hydroxylation, and de-esterification, are reported for the first time in this work. The 3D finite element simulation results demonstrate the size dependent and wavelength tuned plasmonic NIR absorption of the WN NCs. The NIR-driven photocatalytic mechanism of WN NCs is proposed based on density functional theory (DFT) calculated electronic structure and facet dependent O2 (or H2 O) molecular activation, radicals scavenging test, spin trapped electron paramagnetic resonance measurements, and ultraviolet photoelectronic spectrum (UPS). Overall, the results in this work pave a way for the application of low-work-function materials as highly reactive NIR photocatalyst.

2.
Medicine (Baltimore) ; 99(42): e22681, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080713

RESUMO

Button batteries are the second most frequently-ingested foreign bodies and can lead to serious clinical complications within hours of ingestion. The purpose of this study was to analyze the outcomes of 14 children with button batteries lodged in the upper gastrointestinal tract.Totally 14 children with button batteries lodged in the upper gastrointestinal tract were included. The diagnosis was made primarily by the history of button battery ingestion, physical examination and chest-abdomen X-ray examination.The button batteries lodged in the esophagus were removed by esophagoscope, and those in the gastrointestinal tract were under observation. Among 10 children with batteries in the first esophageal stenosis, 9 were cured and 1 suffered from tracheoesophageal fistula. One case of battery in the second esophageal stenosis was dead due to intercurrent aortoesophageal fistula. Two cases of batteries in the third esophageal stenosis were cured after removal, and 1 case of the battery in the gastrointestinal tract discharged spontaneously.Ingested button batteries are mainly lodged in the esophageal stenoses and are easy to cause esophageal injury and severe complications. Early detection, prompt treatment, strengthening observation and regular follow-up after discharge may help to decrease the incidence of complications and improve the outcomes.

3.
J Clin Transl Hepatol ; 8(3): 267-276, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083249

RESUMO

Background and Aims: Glecaprevir/pibrentasvir is a pangenotypic regimen recently approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the present review was to summarize the findings from clinical trials to understand how patient-related factors influence glecaprevir/pibrentasvir efficacy (sustained virologic response rates at 12 weeks' after treatment [referred to as SVR12]) and safety. Methods: Data from 21 phase III clinical trials were analyzed. Results: The integrated efficacy analysis included 4,817 patients. Findings showed 97.5% of all included patients with chronic HCV achieved SVR12 in the intention-to-treat population. SVR12 rate was >95% across subgroups of interest. The integrated safety analysis included 4,015 patients. Findings showed that 64.1% of patients reported an adverse event, and <0.1% of patients reported a serious adverse event related to glecaprevir/pibrentasvir. Conclusions: These results indicate that the 8- or 12-week glecaprevir/pibrentasvir treatment is effective for patients infected with HCV genotypes 1-6 without or with compensated cirrhosis, with good safety profiles, irrespective of treatment-experience. Glecaprevir/pibrentasvir is a good option for patients with human immunodeficiency virus/HCV coinfection and comorbid HCV and severe renal impairment.

4.
J Cell Mol Med ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33085209

RESUMO

Pernicious placenta previa with placenta percreta (PP) is a catastrophic condition during pregnancy. However, the underlying pathogenesis remains unclear. In the present study, the placental tissues of normal cases and PP tissues of pernicious placenta previa cases were collected to determine the expression profile of protein-coding genes, miRNAs, and lncRNAs through sequencing. Weighted gene co-expression network analysis (WGCNA), accompanied by miRNA target prediction and correlation analysis, were employed to select potential hub protein-coding genes and lncRNAs. The expression levels of selected protein-coding genes, Wnt5A and MAPK13, were determined by quantitative PCR and immunohistochemical staining, and lncRNA PTCHD1-AS and PAPPA-AS1 expression levels were determined by quantitative PCR and fluorescence in situ hybridization. The results indicated that 790 protein-coding genes, 382 miRNAs, and 541 lncRNAs were dysregulated in PP tissues, compared with normal tissues. WGCNA identified coding genes in the module (ME) black and ME turquoise modules that may be involved in the pathogenesis of PP. The selected potential hub protein-coding genes, Wnt5A and MAPK13, were down-regulated in PP tissues, and their expression levels were positively correlated with the expression levels of PTCHD1-AS and PAPPA-AS1. Further analysis demonstrated that PTCHD1-AS and PAPPA-AS1 regulated Wnt5A and MAPK13 expression by interacting with specific miRNAs. Collectively, our results provided multi-omics data to better understand the pathogenesis of PP and help identify predictive biomarkers and therapeutic targets for PP.

5.
Redox Biol ; 37: 101731, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33002760

RESUMO

Matcha and green tea catechins such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) have long been studied for their antioxidant and health-promoting effects. Using specific fluorophores for H2S (AzMC) and polysulfides (SSP4) as well as IC-MS and UPLC-MS/MS-based techniques we here show that popular Japanese and Chinese green teas and select catechins all catalytically oxidize hydrogen sulfide (H2S) to polysulfides with the potency of EGC > EGCG >> EG. This reaction is accompanied by the formation of sulfite, thiosulfate and sulfate, consumes oxygen and is partially inhibited by the superoxide scavenger, tempol, and superoxide dismutase but not mannitol, trolox, DMPO, or the iron chelator, desferrioxamine. We propose that the reaction proceeds via a one-electron autoxidation process during which one of the OH-groups of the catechin B-ring is autooxidized to a semiquinone radical and oxygen is reduced to superoxide, either of which can then oxidize HS- to thiyl radicals (HS•) which react to form hydrogen persulfide (H2S2). H2S oxidation reduces the B-ring back to the hydroquinone for recycling while the superoxide is reduced to hydrogen peroxide (H2O2). Matcha and catechins also concentration-dependently and rapidly produce polysulfides in HEK293 cells with the potency order EGCG > EGC > EG, an EGCG threshold of ~300 nM, and an EC50 of ~3 µM, suggesting green tea also acts as powerful pro-oxidant in vivo. The resultant polysulfides formed are not only potent antioxidants, but elicit a cascade of secondary cytoprotective effects, and we propose that many of the health benefits of green tea are mediated through these reactions. Remarkably, all green tea leaves constitutively contain small amounts of H2S2.

6.
Zootaxa ; 4808(1): zootaxa.4808.1.6, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055992

RESUMO

A new species of Tullbergiidae, Paratullbergia chuana sp. nov. from Sichuan Province, southwest China is described. Paratullbergia chuana is characterised by the presence of one pair of pseudocelli on each segment from Th. I-Abd. V and a formula of 11/111/11111, postantennal organ composed by 34-50 vesicles arranged in two rows, seta px present on Abd. IV, setae a2 and a4 on Abd. V as macrosetae, p4 as mesoseta, and a less differentiated sensillum p3 on Abd. V. In addition, chaetotaxic variations on Abd. IV and V are discussed. An abnormal morphology of an antenna that was observed for the first time is reported.

7.
Medicine (Baltimore) ; 99(40): e22616, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019482

RESUMO

RATIONALE: Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory demyelinating disorders of the central nervous system; they are characterized by severe optic neuritis and transverse myelitis. Intravenous methylprednisolone pulse (IVMP) therapy is an effective treatment that is administered to patients in the acute phase of NMOSD; this therapy has achieved remarkable results in clinical practice. However, there are no reports on NMOSD patients who have experienced an acute bilateral cerebral infarction while undergoing IVMP treatment. PATIENT CONCERNS: We report on a 62-yr-old woman who was undergoing IVMP therapy for the primary diagnosis of NMOSD. Unexpectedly, the patient's existing limb weakness worsened, and she developed motor aphasia on the second day of IVMP treatment. Additionally, brain magnetic resonance imaging revealed acute bilateral cerebral infarction. DIAGNOSIS: The patient's clinical manifestations, medical imaging results, and laboratory test results were taken into consideration; the final diagnosis was acute bilateral cerebral infarction in the presence of NMOSD. INTERVENTIONS: Subsequent to the onset of acute cerebral infarction, the patient was immediately treated with oral aspirin, atorvastatin, and intravenous butylphthalide. The hormone dose was adjusted to an oral 60-mg/d dose for maintenance; this was followed by immunoadsorption plasmapheresis for 3 days, and double-filtration plasmapheresis for 2 days. OUTCOMES: Following treatment onset, the patient's ocular symptoms significantly improved, and her limb muscle strength gradually recovered. Two months after discharge, the patient's husband reported that she was able to walk with the help of others and take care of herself, and that there was no recurrence. LESSONS: Medical professionals must be aware of the possibility of NMOSD patients with cerebrovascular risk factors suffering an acute cerebral infarction while undergoing high-dose IVMP therapy, as this therapy can exacerbate existing problems.


Assuntos
Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Neuromielite Óptica/complicações , Neuromielite Óptica/tratamento farmacológico , Doença Aguda , Administração Intravenosa , Administração Oral , Anticolesterolemiantes/uso terapêutico , Afasia de Broca/induzido quimicamente , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Benzofuranos/administração & dosagem , Benzofuranos/uso terapêutico , Infarto Cerebral/tratamento farmacológico , Feminino , Humanos , Imagem por Ressonância Magnética , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Plasmaferese/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Resultado do Tratamento
8.
Nat Commun ; 11(1): 5131, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046699

RESUMO

As artificial intelligence (AI) is increasingly applied to biomedical research and clinical decisions, developing unbiased AI models that work equally well for all ethnic groups is of crucial importance to health disparity prevention and reduction. However, the biomedical data inequality between different ethnic groups is set to generate new health care disparities through data-driven, algorithm-based biomedical research and clinical decisions. Using an extensive set of machine learning experiments on cancer omics data, we find that current prevalent schemes of multiethnic machine learning are prone to generating significant model performance disparities between ethnic groups. We show that these performance disparities are caused by data inequality and data distribution discrepancies between ethnic groups. We also find that transfer learning can improve machine learning model performance for data-disadvantaged ethnic groups, and thus provides an effective approach to reduce health care disparities arising from data inequality among ethnic groups.

9.
J Mol Endocrinol ; 65(4): 135-148, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33048061

RESUMO

The pituitary gland functions as a prominent regulator of diverse physiologic processes by secreting multiple hormones. Circular RNAs (circRNAs) are an emerging novel type of endogenous noncoding RNA that have recently been recognized as powerful regulators participating in various biological processes. However, the physiological roles and molecular mechanisms of circRNAs in pituitary remain largely unclear. Herein, we concentrated on expounding the biological function and molecular mechanism of circRNA in rat pituitary. In this study, we identified a novel circRNA in pituitary tissue, circAkap17b, which was pituitary- and stage-specific. Then, we designed circAkap17b siRNA and constructed an overexpression plasmid to evaluate the effect of loss- and gain-of-circAkap17b function on FSH secretion. Interestingly, silencing circAkakp17b significantly inhibited FSH expression and secretion, while overexpression of circAkap17b enhanced FSH expression and secretion. Furthermore, dual luciferase reporter and RNA immunoprecipitation (RIP) assays confirmed that circAkap17b could serve as miR-7 sponge to regulate target genes. Additionally, miR-7b suppressed FSH expression and secretion by directly targeting Fshb through the dual luciferase reporter and RT-qPCR analysis. Additionally, rescue experiments showed that circAkap17b could regulate FSH secretion in pituitary cells through a circAkap17b-miR-7-Fshb axis. Collectively, we demonstrated that circAkap17b could act as a molecular sponge of miR-7 to upregulate expression of the target gene Fshb and facilitate FSH secretion. These findings provide evidence for a novel regulatory role of circRNAs in pituitary.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33034554

RESUMO

An aerobic, non-motile, Gram-stain-negative, pink, convex, coccobacilli-shaped, mesophilic bacterium, designated strain BU-1T, was isolated from an urban soil sample from Zibo city, Shandong province, PR China. The strain grew at 20-37 °C (optimum, 30 °C), pH 5-10 (optimum, pH 7) and growth occurred with 0-2 % (w/v) NaCl (optimally with 0.5 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that BU-1T was closely related to members of the genus Roseomonas and had highest 16S rRNA gene sequence similarities with Roseomonas frigidaquae JCM 15073T (97.8 %), Roseomonas tokyonensis JCM 14634T (96.9 %), Roseomonas stagni JCM 15034T (96.5 %), and Roseomonas riguiloci JCM 17520T (95.9 %). BU-1T also formed a subcluster with R. frigidaquae JCM 15073T and R. stagni JCM 15034T in phylogenetic trees based on genomic sequences. The genome size of BU-1T was 5.79 Mb and the DNA G+C content was 71.7 %. ANI, dDDH and AAI values between BU-1T and R. frigidaquae JCM 15073T were 84.0, 27.2 and 86.7 %, respectively. Furthermore, the genome of BU-1T contained 5446 predicted protein coding genes and 4945 (90.8%) of them had classifiable functions. BU-1T contained Q-10 as the main ubiquinone. The predominant fatty acids (>10 %) were summed feature 3, summed feature 8 and C16:0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and five unidentified aminolipids. Combined data from phenotypic, phylogenetic and chemotaxonomic studies indicated that strain BU-1T is a representative of a novel species of the genus Roseomonas. Since strain BU-1T can reduce highly toxic selenite [Se(IV)] to low toxicity elemental selenium [Se(0)], the name Roseomonas selenitidurans sp. nov. is proposed. The type strain is BU-1T (=KACC 21750T =GDMCC 1.1776T).

11.
Med Phys ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33012059

RESUMO

PURPOSE: To develop a biological dose prediction model considering tissue bio-reactions in addition to patient anatomy for achieving a more comprehensive evaluation of tumor control and promoting the automatic planning of bulky lung cancer. METHODS: A database containing images and partial stereotactic ablation boost radiotherapy (P-SABR) plans of 94 bulky lung cancer patients was studied. Patient-specific parameters of gross tumor boost (GTVb), planning gross target volume (PGTV), and identified organs at risk (OARs) were extracted via Numpy and simple ITK. The original dose and structure maps for P-SABR patients were resampled to have a voxel resolution of 3.9 × 3.9 × 3 mm3 . Biological equivalent dose (BED) distributions were reprogrammed based on physical dose volumes. A developed deep learning architecture, Nestnet, was adopted as the training framework. We utilized two approaches for data organization to correlate the structures and BED: (a) BED programming before training model (B-Nestnet); (b) BED programming after the training process (D-B Nestnet). The early-stop mechanism was adopted on the validation set to avoid overfitting. The evaluation criteria of predictive accuracy contains the minimum BED of GTVb and PGTV, the maximum and the mean BED of all targets, BED-volume metrics. For comparison, we also used the original Unet for BED prediction. The absolute differences were statistically analyzed with the paired-samples t-test. RESULTS: The statistical outcomes demonstrate that D-B Nestnet model predicts biological dose distributions accurately. The average absolute biases of [max, mean] BED for GTVb, PGTV are [2.1%, 3.3%] and [2.1%, 4.7%], respectively. Averaging across most of OARs, the D-B Nestnet model is capable of predicting the errors of the max and mean BED within 6.3% and 6.1%, respectively. While the compared models performed worse with averaged max and mean BED prediction errors surpassing 10% on some specific OARs. CONCLUSIONS: The study developed a D-B Nestnet model capable of predicting BED distribution accurately for bulky lung cancer patients in P-SABR. The predicted BED map enables a quick intuitive evaluation of tumor ablation, modification of the ablation range to improve BED of tumor targets, and quality assessment. It represents a major step forward towards automated P-SABR planning on bulky lung cancer in real clinical practice.

12.
J Integr Neurosci ; 19(3): 507-511, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070531

RESUMO

Transsynaptic degeneration in the cerebellum and brainstem may give rise to a rare neurological condition with various clinical manifestations, namely hypertrophic olivary degeneration. The classical manifestations of hypertrophic olivary degeneration comprise myoclonus, palatal tremor, ataxia, and ocular symptoms. Any lesions interrupting the dentate-rubro-olivary pathway, referred to as the anatomic Guillain-Mollaret triangle, contribute to the broad aetiologies of hypertrophic olivary degeneration. The clinical diagnosis depends primarily on the associated symptoms and the characteristic magnetic resonance imaging findings. Concerning treatment and prognosis, there are no widely accepted guidelines. Here, we identified 11 cases of hypertrophic olivary degeneration secondary to brainstem infarction from 1964 to the present. Combined with two of our cases, the clinical and imaging findings of 13 patients with hypertrophic olivary degeneration secondary to brainstem infarction were studied. A meta-analysis of case studies gives the correlation coefficient between infraction location and time to develop hypertrophic olivary degeneration as 0.217 (P = 0.393, P > 0.05). At the significance level of P < 0.05, there was no significant correlation between information location and time to develop hyperophic olivary degeneration. The χ2 between infraction location and magnetic resonance imaging findings of hypertrophic olivary degeneration was 8.750 (P = 0.364, P > 0.05). At the significance level of P < 0.05, there was no significant correlation between infraction location and magnetic resonance imaging findings of hypertrophic olivary degeneration. Conclusion based on the analysis of available data suggests that when newly developed or progressive worsening motor symptoms are presented in patients with previous brainstem infarction, a diagnosis of hypertrophic olivary degeneration should be investigated.

13.
Int J Pharm ; 591: 119986, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33069895

RESUMO

Ovarian cancer is the most common cause of death among gynecological malignancies globally. Ovarian cancer treatment integrates debulking surgery and systemic therapy. Genomic and proteomic analyses have shown that ovarian cancer is heterogeneous with unique molecular characteristics that may facilitate the development of systemic targeted chemotherapeutic and immunotherapeutic precision medicines. However, despite their advantages, these therapies have some limitations. Chemotherapy has drawbacks such as drug resistance and high toxicity due to nonspecific tumor targeting; the targeted versions have limited utility and off-target side effects. Immunotherapy has a low response rate due to the intrinsically immunosuppressive tumor microenvironment in ovarian cancer. Nanotechnology-based drug delivery systems have the potential to overcome such limitations. Various nanoparticles have been developed for controlled drug delivery to ovarian cancer. In this review, we summarize the application of nanotechnology in ovarian cancer systemic therapy including nanoformulations in the market and in clinical trials, as well as the recent nanoparticle research therapeutic strategies. The potential and challenges of nanoparticles in ovarian cancer treatment are also discussed.

14.
Chin J Integr Med ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037518

RESUMO

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

15.
Neurol Sci ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009963

RESUMO

After acute ischemic stroke (AIS), peripheral monocytes infiltrate into the lesion site within 24 h, peak at 3 to 7 days, and then differentiate into macrophages. Traditionally, monocytes/macrophages (MMs) are thought to play a deleterious role in AIS. Depletion of MMs in the acute phase can alleviate brain injury induced by ischemia. However, several studies have shown that MMs have anti-inflammatory functions, participate in angiogenesis, phagocytose necrotic neurons, and promote neurovascular repair. Therefore, MMs play dual roles in ischemic stroke, depending mainly upon the MM microenvironment and the window of time post-stroke. Because activated microglia and MMs are similar in morphology and function, previous studies have often investigated them together. However, recent studies have used special methods to distinguish MMs from microglia and have found that MMs have properties which differ from microglia. Here, we review the unique role of MMs and the interaction between MMs and neurovascular units, including neurons, astrocytes, microglia, and microvessels. Future therapeutics targeting MMs should regulate the polarization and subset transformation of the MMs at different stages of AIS rather than comprehensively suppressing MM infiltration and differentiation. In addition, more studies are needed to elucidate the cellular and molecular mechanisms of MM subsets and polarization during ischemic stroke.

16.
Prostate ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022812

RESUMO

BACKGROUND: Nerves are key factors in prostate cancer (PCa) progression. Here, we propose that neuropeptide Y (NPY) nerves are key regulators of cancer-nerve interaction. METHODS: We used in vitro models for NPY inhibition studies and subsequent metabolomics, apoptotic and migration assays, and nuclear transcription factor-κB (NF-κB) translocation studies. Human naïve and radiated PCa tissues were used for NPY nerve density biomarker studies. Tissues derived from a Botox denervation clinical trial were used to corroborate metabolomic changes in humans. RESULTS: Cancer cells increase NPY positive nerves in vitro and in preneoplastic human tissues. NPY-specific inhibition resulted in increased cancer apoptosis, decreased motility, and energetic metabolic pathway changes. A comparison of metabolomic response in NPY-inhibited cells with the transcriptome response in human PCa patients treated with Botox showed shared 13 pathways, including the tricarboxylic acid cycle. We identified that NF-κB is a potential NPY downstream mediator. Using in vitro models and tissues derived from a previous human chemical denervation study, we show that Botox specifically, but not exclusively, inhibits NPY in cancer. Quantification of NPY nerves is independently predictive of PCa-specific death. Finally, NPY nerves might be involved in radiation therapy (RT) resistance, as radiation-induced apoptosis is reduced when PCa cells are cocultured with dorsal root ganglia/nerves and NPY positive nerves are increased in prostates of patients that failed RT. CONCLUSION: These data suggest that targeting the NPY neural microenvironment may represent a therapeutic approach for the treatment of PCa and resistance through the regulation of multiple oncogenic mechanisms.

17.
Int J Pediatr Otorhinolaryngol ; 137: 110216, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896342

RESUMO

OBJECTIVES: To evaluate the effect of hypothermic saline application for pediatric coblation tonsillectomy on postoperative pain. METHODS: Forty-eight children with adenotonsillar hyperplasia underwent tonsillectomy ± adenoidectomy. 24 children were in the HTS group (which used hypothermic saline as the coblation medium in operation), the other 24 children with the same age were in the control NTS group (who use normothermic saline as the coblation medium). All children and their parents were asked to complete a daily questionnaire for 7 days following their surgery. RESULTS: Significant differences were observed when comparing the two outlet water temperatures of the coblation wand both at ablation power and at coagulation power (p = 0.000). Children in HTS group got lower scores than those in the NTS group (p < 0.05). No side effects were observed. CONCLUSIONS: Using hypothermic normal saline as the media of coblation wand is potential for reduce postoperative pain in pediatric patients while also having no detrimental financial or medical effects on said patients.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32870797

RESUMO

Identifying cancer drivers is a crucial challenge to explain the underlying mechanisms of cancer development. There are many methods to identify cancer drivers based on the single mutation site or the entire gene. But they ignore a large number of functional elements with medium in size. It is hypothesized that mutations occurring in different regions of the protein sequence have different effects on the progression of cancer. Here, we develop a novel functional region driver(frDriver) identification method based on Bayesian probability and multiple linear regression models to identify protein regions that can regulate gene expression levels and have high functional impact potential. Combining gene expression data and somatic mutation data, with functional impact scores(SIFT, PROVEAN) as a priori knowledge, we identified cancer driver regions that are most accurate in predicting gene expression levels. We evaluated the performance of frDriver on the BRCA and GBM datasets from TCGA. The results showed that frDriver identified known cancer drivers and outperformed the other three state-of-the-art methods(eDriver, ActiveDriver and OncodriveCLUST). In addition, we performed KEGG pathway and GO term enrichment analysis, and the results indicated that the cancer drivers predicted by frDriver were related to processes such as cancer formation and gene regulation.

19.
J Org Chem ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32872780

RESUMO

Herein, we report a metal-free and step-economic synthesis of phenanthridines from 2-biarylmethanamines under mild conditions. The reaction involves iodine-supported intramolecular C-H amination and oxidation of 5,6-dihydrophenanthridine under air and benign visible light. The mechanism study reveals that visible light plays a key role in both these steps.

20.
Sci Transl Med ; 12(560)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908002

RESUMO

Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene PTEN (encoding phosphatase and tensin homolog) and increased programmed cell death ligand 1 abundance through a pathway involving PI3K-AKT-S6K1, and (ii) activating Toll-like receptors 7 and 8 (TLR7/8) signaling pathways. Combination treatment increased T cell activation and expansion, CD103+ tumor-infiltrating dendritic cells, and tumor-associated M1 macrophages, ultimately enhancing the overall recruitment of activated CD8+ T cells to tumors. In patients with melanoma, a high KDM5A gene signature correlated with KDM5A expression and could potentially serve as a marker of response to anti-PD-1 immunotherapy. Furthermore, our results indicated that bifunctional agents that enhance both KDM5A and TLR activity warrant investigation as combination therapies with ICB agents.

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