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1.
J Clin Oncol ; : JCO2101467, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990291

RESUMO

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

2.
Sci Rep ; 12(1): 394, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013471

RESUMO

Delayed luminescence (DL) is gradually used in various detection of biological systems as a rapid detection technique, however, its biological mechanism was still not clear. In this study, a new model of DL detection system for liquid biological samples is established to investigate the DL emission of Saccharomyces cerevisiae cells cultured in different glucose concentrations. We analyzed the relationship between the DL emission and cell growth, cell vitality, mitochondrial morphology, mitochondrial DNA (mtDNA) copy number, adenosine triphosphate (ATP), oxygen consumption rate (OCR), as well as mitochondria membrane potential (MMP) in S. cerevisiae cells cultured with 0.01, 0.05, 0.15, 3, 10 and 20 g/L glucose respectively. It was found that the DL emission had strong correlation with mitochondrial morphology, OCR, and MMP. The results suggested that DL is an indicator of mitochondria status under different glucose supply conditions, and may be an effective method to detect mitochondrial metabolism related disorders.

3.
Front Neurol ; 12: 745560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867727

RESUMO

The neutrophil-to-lymphocyte ratio (NLR), as an essential systemic inflammation factor, has been widely used as a prognostic indicator in various diseases, such as malignant tumors, cardiovascular disease, and intracranial hemorrhage. An increasing number of studies have believed that NLR is a valuable predictor of prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, these results remain controversial. In the current study, we planned to carry out a systematic review and meta-analysis to investigate the association between NLR and poor outcome, and the occurrence of delayed cerebral ischemia (DCI). We carried out a comprehensive search for published literatures on PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to April 1, 2021. We conducted an assessment of all included studies based on the principles proposed in the Newcastle-Ottawa Quality Assessment Scale (NOS). Poor outcome and the occurrence of DCI were considered as the main outcome measure. We calculated the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) to examine the strength of the association of NLR with poor outcome or the occurrence of DCI. We strictly selected a total of 10 studies comprising 4,989 patients. Nine studies reported the association between NLR and poor outcome, and five studies reported the association between NLR and the occurrence of DCI. The pooled results indicated higher NLR was significantly associated with both poorer outcomes (OR = 1.32, 95%CI 1.11-1.57; P = 0.002, I 2 = 87%), and the occurrence of DCI (OR = 1.72, 95%CI 1.22-2.41; P = 0.002, I 2 = 82%) in aSAH patients. The NLR is a valuable indicator of inflammation to independently predict poor outcome and occurrence of DCI after aSAH, where a higher NLR is significantly associated with poor outcomes and occurrence of DCI. These findings suggest that the NLR can help clinicians evaluate the prognosis and identify potentially severe patients early, which may contribute to better management and improve poor prognosis of aSAH patients.

4.
BMC Cancer ; 21(1): 1320, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886807

RESUMO

BACKGROUND: To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). RESULTS: A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants' ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC%high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p < 0.001) than those in the ΔADC%low group. Interestingly, ΔADC% was closely related to the response measured by RECIST 1.1 (p < 0.001) and plasma EBV DNA level (p = 0.037). The AUC significantly increased when post-IC plasma EBV DNA was added to ΔADC% to predict treatment failure. Thus, based on ΔADC% and plasma EBV DNA, we further divided the participants into three new prognostic response phenotypes (early response, intermediate response, and no response) that correlated with disparate risks of death (p = 0.001), disease progression (p < 0.001), distant metastasis (p < 0.001), and locoregional relapse (p < 0.001). CONCLUSION: The percentage change in ADC post-IC is indicative of treatment response and clinical outcome. ΔADC% and plasma EBV DNA-based response phenotypes may provide potential utility for early termination of treatment and allow guiding risk-adapted therapeutic strategies for LA-NPC.

5.
Alcohol Clin Exp Res ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862610

RESUMO

BACKGROUND: The impact of alcoholic hepatitis (AH) on health-related quality of life (HRQOL) remains inadequately described. We aimed to describe HRQOL in AH and heavy drinkers (HD), its associations with clinical variables and outcomes. METHODS: This is a post-hoc analysis of the TREAT001 study participants (NCT02172898). HRQOL was measured using Short Form Health Survey (SF-36). Mean SF-36 scores were compared in AH and HD with two sample t-test. Associations between clinical characteristics, 30-day mortality and SF-36 mental and physical component scores (MC, PC) were investigated with generalized linear and logistic multivariate regression models. Trends of MC and PC scores were analysed using one-way ANOVA. RESULTS: Those with AH (n=258) and HD (n=181) had similar demographics. AH cases had mean Model for End-stage Liver Disease score (MELD) of 23(7). AH cases had lower PC scores [37(10) vs. 48(11), p<0.001] but higher MC scores [37(13) vs. 32(13), p<0.001]. MC scores were independently associated with age, male gender and daily alcohol consumption; PC scores were independently associated with age, BMI, ALT, ALP, WBC and ascites. With each 5-point decrease in the baseline PC score, the adjusted odds of dying within 30 days increased by 26.7%(95% CI 1%-46%). Over time, HRQOL in AH improved(day 0-day 180 delta PC score: 4.5±1.7, p=0.008; delta MC score: 9.8±2.0, p<0.001). Those with MELD<15 by day 180 had greater increases in PC scores than those with MELD≥15 (delta PC score 7.1±1.8 vs. -0.7+2.3, p=0.009) while those abstinent by day 180 had greater increases in MC scores than those not abstinent (delta MC score 9.1±1.8 vs. 2.8±2.4, p=0.044). CONCLUSIONS: HRQOL is poor in AH and HD in a domain specific pattern. Independent of MELD, poorer baseline HRQOL is associated with higher 30-day mortality. Over time, HRQOL improved with greater gains seen in those with improvements in MELD and abstinence.

6.
Front Neurosci ; 15: 786513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955733

RESUMO

The use of adjuvant corticosteroids with surgery for chronic subdural hematoma (CSDH) has received considerable attention in recent years. However, there is no conclusive evidence regarding its effectiveness and safety for CSDH. Therefore, we performed a meta-analysis and systematic review to evaluate the effectiveness and safety of corticosteroids as an adjuvant treatment for the treatment of CSDH. We comprehensively searched electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) to identify relevant trials that investigated the efficacy and safety of adjuvant corticosteroids with surgery for CSDH, published from inception until May 2021. Outcome measures included recurrence rate, all-cause mortality, good functional outcome, length of hospitalization, and adverse events. We used the Cochrane risk of bias method to evaluate the quality of randomized controlled trials (RCTs), and the Newcastle Ottawa Scale to evaluate the quality of observational studies. We included nine studies, consisting of three RCTs and six observational studies, that compared corticosteroids as an adjuvant treatment to surgery with surgery alone. Pooled results revealed that the risk of recurrence was significantly reduced in patients who received adjuvant corticosteroids with surgery compared to those who underwent surgery alone (relative risk [RR] = 0.52, 95% confidence interval [CI] = 0.39-0.69, p < 0.00001). However, no statistically significant difference was observed between these groups in all-cause mortality (RR = 0.91, 95% CI = 0.37-2.23, p = 0.83), good functional outcome (RR = 1.03, 95% CI = 0.96-1.10, p = 0.47), length of hospitalization (MD = 0.35, 95% CI = -2.23 to 1.67, p = 0.83), and infection rates (RR = 0.99, 95% CI = 0.64-1.53, p = 0.95). Adjuvant corticosteroids with surgery reduce the risk of recurrence of CDSH, but do not improve the all-cause mortality or functional outcome, as compared to surgery alone. These findings support the use of adjuvant corticosteroids with surgery for CSDH patients. Further high-quality RCTs are required to confirm the efficacy and safety of adjuvant corticosteroids in the treatment of CSDH patients.

7.
Front Pharmacol ; 12: 753068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955827

RESUMO

Background: Radiation-induced skin injury is a major side-effect observed in cancer patients who received radiotherapy. Thus identifying new radioprotective drugs for prevention or treatment of post-irradiation skin injury should be prompted. A large number of clinical studies have confirmed that Compound Kushen injection (CKI) can enhance efficacy and reduce toxicity of radiotherapy. The aim of this study is to confirm the effect of CKI in alleviating radiotherapy injury in the skin and explore the exact mechanism. Methods: 60 patients who met the inclusion/exclusion criteria were allocated to treatment group (CKI before radiotherapy) or control group (normal saline before radiotherapy) randomly. MTT assay, flow cytometry, Western Blot, and transient transfection were performed to detect the cell viability, cell apoptosis and Bim expression after treatment with CKI or/and radiotherapy. Results: CKI had the effect of alleviating skin injury in cancer patients who received radiotherapy in clinic. CKI induced cancer cell apoptosis when combined with irradiation (IR), while it reversed the induction of cell apoptosis by IR in human skin fibroblast (HSF) cells. And Bim, as a tumor suppressor, was induced in cancer cells but had no change in HSF cells when treated with CKI. Moreover, the above effect could be attenuated when Bim was silenced by siRNA. Conclusion: We conclude that CKI represents a promising radio-protective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) and HSF cells (providing radio-protection via inhibiting IR-induced apoptosis), via regulating Bim. Our study uncovers a novel mechanism by which CKI inhibits human cancer cell while protects skin from radiotherapy, indicating CKI might be a promising radio-protective drug. Clinical Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn), identifier ChiCTR2100049164.

8.
J Dev Behav Pediatr ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34954761

RESUMO

OBJECTIVE: The objective of this study was to present clinician and caregiver perspectives regarding telehealth neurodevelopmental evaluation delivered at the onset of the coronavirus disease 2019 (COVID-19) pandemic. Specifically, we sought to describe telehealth neurodevelopmental evaluations, examine associations between child characteristics and diagnostic factors, determine the impact of technology and family barriers, and report on clinician and caregiver satisfaction with telehealth evaluation. METHODS: In response to the COVID-19 pandemic, in-person clinical services at a large children's hospital neurodevelopmental clinic were transitioned to telehealth. Data are presented for 254 remote evaluations of children (18-212 months; referral concern: 51% autism spectrum disorder [ASD], 24% developmental delay/intellectual disability, 25% other neurodevelopmental concern) conducted from May to July 2020. Data were gathered from electronic health records as well as clinician and caregiver surveys. RESULTS: A clinical diagnosis was provided in 72% of telehealth evaluations. Clinicians rated diagnostic certainty as "completely" or "somewhat" certain in 74% of evaluations. Certainty ratings were higher for evaluations in which a diagnosis of ASD was provided. Although technology and family challenges were reported, clinicians rarely identified these as disruptive to the evaluation process. Clinicians reported satisfaction with various aspects of delivering telehealth. Caregivers endorsed high satisfaction with receipt of telehealth and reduced travel burden. CONCLUSION: The COVID-19 pandemic has rapidly transformed service delivery for individuals with neurodevelopmental disabilities and provided an unprecedented opportunity to evaluate the deployment of telehealth evaluation to meet the need for ongoing diagnostic care. Our findings suggest that telehealth holds significant promise for neurodevelopmental assessment both within the context of a global pandemic and beyond.

9.
Front Physiol ; 12: 763478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916957

RESUMO

Aims: The aim was to describe the incidence of atrial fibrillation (AF) after cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL) without history of AF and to identify risk factors for new-onset AF after the procedure. Methods: A total of 191 patients with typical AFL undergoing successful CTI ablation were enrolled. Patients who had history of AF, structural heart disease, cardiac surgery, or ablation or who received antiarrhythmic drug after procedure were excluded. Clinical and electrophysiological data were collected. Results: There were 47 patients (24.6%) developing new AF during a follow-up of 3.3 ± 1.9 years after CTI ablation. Receiver operating characteristic (ROC) curves indicated that the cut-off values of left atrial diameter (LAD) and CHA2DS2-VASc score were 42 mm and 2, with area under the curve of 0.781 and 0.550, respectively. The multivariable Cox regression analysis revealed that obstructive sleep apnea (OSA) [hazard ratio (HR) 3.734, 95% confidence interval (CI) 1.470-9.484, P = 0.006], advanced interatrial block (aIAB) (HR 2.034, 95% CI 1.017-4.067, P = 0.045), LAD > 42 mm (HR 2.710, 95% CI 1.478-4.969, P = 0.001), and CHA2DS2-VASc score > 2 (HR 2.123, 95% CI 1.118-4.034, P = 0.021) were independent risk factors of new-onset AF. Conclusion: A combination of OSA, aIAB, LAD > 42 mm, and CHA2DS2-VASc > 2 was a strongly high risk for new-onset AF after ablation for typical AFL, and it had significance in postablation management in clinical practice.

10.
JAMA Netw Open ; 4(12): e2138470, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34928359

RESUMO

Importance: Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. Objective: To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. Design, Settings, and Participants: This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. Interventions: Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)- or cisplatin (100 mg/m2)-based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis-free survival, and locoregional relapse-free survival. Results: A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, -6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis-free survival (85.9% vs 90.4%, P = .17), and locoregional relapse-free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. Trial Registration: ClinicalTrials.gov Identifier: NCT01540136.

11.
ACS Omega ; 6(46): 31229-31235, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34841166

RESUMO

A "turn-off" supramolecular fluorescence array sensor based on the host-guest complexes between fluorescence dyes and cucurbit[n]urils for sensing metal ions was developed. Three fluorescent probes (RhB@Q[7], H33342@2Q[7], and BRE@Q[7]) were used as the sensing units to construct a supramolecular fluorescence array sensor. The binding ability of the metal ions and cucurbituril-dye probes varied; therefore, the probes and metal ions produced different fluorescence responses. When combined with linear discriminant analysis (LDA), the qualitative and quantitative detection of seven metal ions was achieved. In analytical samples, the supramolecular fluorescence array sensor recognized and distinguish seven metal ions. These results provided new research ideas for the rapid analysis and real-time monitoring of different heavy metal ions.

12.
Front Pediatr ; 9: 754623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796155

RESUMO

Background: Information regarding the localization of gastrointestinal perforation is crucial for the following surgical procedure. This study was to determine the key indicators and develop a prediction model for the localization in neonates with gastrointestinal perforation. Methods: A nomogram to predict the location of neonatal gastrointestinal perforation was developed using a cohort of patients who underwent surgery between July 2009 and May 2021. Baseline variables were analyzed using logistics regression and nomogram developed using significant predictors. The predictive performance of the nomogram was assessed by the concordance index (C-index), calibration curve, and area under the receiver operating characteristic (ROC) curve (AUC). The nomogram was further validated in an integrated external cohort. Results: We investigated the data of 201 patients, of which 65 (32.3%) were confirmed with upper gastrointestinal perforation by surgery. Multivariate logistic regression analysis identified the following as independent predictors: preterm [OR: 5.014 (1.492-18.922)], time of onset [OR: 0.705 (0.582-0.829)], preoperative hemoglobin [OR:1.017 (1.001-1.033)], bloody stool: No [OR: 4.860 (1.270-23.588)], shock [OR: 5.790 (1.683-22.455)] and sepsis: No [OR 3.044 (1.124-8.581)]. Furthermore, the nomogram was effective in predicting the perforation site, with an AUC of 0.876 [95% confidence interval (CI): 0.830-0.923]. Internal validation showed that the average AUC was 0.861. Additionally, the model achieved satisfactory discrimination (AUC, 0.900; 95% CI, 0.826-0.974) and calibration (Hosmer-Lemeshow test, P = 0.4802) in external validation. Conclusions: The nomogram based on the six factors revealed good discrimination and calibration, suggesting good clinical utility. The nomogram could help surgeons predict the location of gastrointestinal perforation before surgery to make a surgical plan.

13.
Nanoscale ; 13(45): 19133-19143, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34779473

RESUMO

Coordination engineering has recently emerged as a promising strategy to boost the activity of single atom catalysts (SACs) in electrocatalytic CO2 reduction reactions (CO2RR). Understanding the correlation between activity/selectivity and the coordination environment would enable the rational design of more advanced SACs for CO2 reduction. Herein, via density functional theory (DFT) computations, we systematically studied the effects of coordination environment regulation on the CO2RR activity of Ni SACs on C, N, or B co-doped graphene. The results reveal that the coordination environments can strongly affect the adsorption and reaction characteristics. In the C and/or N coordinated Ni-BXCYNZ (B-free, X = 0), only Ni acts as the active site. While in the B, C and/or N coordinated Ni-BXCYNZ (X ≠ 0), the B has transition-metal-like properties, where B and Ni function as dual-site active centers and concertedly tune the adsorption of CO2RR intermediates. The tunability in the adsorption modes and strengths also results in a weakened linear scaling relationship between *COOH and *CO and causes a significant activity difference. The CO2RR activity and the adsorption energy of *COOH/*CO are correlated to construct a volcano-type activity plot. Most of the B, C, and/or N-coordinated Ni-BXCYNZ (X ≠ 0) are located in the left region where *CO desorption is the most difficult step, while the C and/or N coordinated Ni-BXCYNZ (X = 0) are located in the right region where *COOH formation is the potential-determining step. Among all the possible Ni-BXCYNZ candidates, Ni-B0C3N1 and Ni-B1C1N2-N-oppo are predicted to be the most active and selective catalysts for the CO2RR. Our findings provide insightful guidance for developing highly effective CO2RR catalysts based on a codoped coordination environment.

14.
J Med Chem ; 64(23): 17221-17238, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34809430

RESUMO

Androgen receptor (AR) has proved to be a vital drug target for treating prostate cancer. Here, we reported the discovery of a novel AR antagonist 92 targeting the AR ligand-binding pocket, but distinct from the marketed drug enzalutamide (Enz), 92 demonstrated inhibition on the AR ligand-binding domain (LBD) dimerization, which is a novel mechanism reported for the first time. First, a novel hit (26, IC50 = 5.57 µM) was identified through virtual screening based on a theoretical AR LBD dimer bound with the Enz model. Then, guided by molecular modeling, 92 was discovered with 32.7-fold improved AR antagonistic activity (IC50 = 0.17 µM). Besides showing high bioactivity and safety, 92 can inhibit AR nuclear translocation. Furthermore, 92 inhibited the formation of the AR LBD dimer, possibly through attenuating the hydrogen-bonding network between the two monomers. This interesting finding would pave the way for the discovery of a new class of AR antagonists.

15.
Mol Nutr Food Res ; : e2100739, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811884

RESUMO

SCOPE: This study aims to investigate and compare the potentially neuroprotective effects and underlying mechanisms for brown seaweed polysaccharides (PS) of Alginate (Alg) and its two components, including Polymannuronic acid (PM) and Polyguluronic acid (PG), against Parkinson's disease (PD) pathogenesis. METHODS AND RESULTS: Model mice of PD were pretreated with Alg or PM or PG, separately via oral gavage once per day for four weeks. Our results found PM improved motor functions of PD mice, but Alg or PG did not. PM or PG, but not Alg, could prevent dopaminergic neuronal loss by increasing tyrosine hydroxylase expressions in midbrain of PD mice. The neuroprotective effects of PM relied on its anti-inflammation effects and its ability to improve striatal neurotransmitters (serotonin and 5-hydroxyindole acetic acid) levels in PD mice. PM inhibited inflammation, but PG or Alg induced inflammation in systemic circulation of PD mice. The neuroprotection provided by PG might be related to its ability to increase striatal neurotransmitter of 5-hydroxyindole acetic acid levels in PD mice. CONCLUSION: PM played better than PG to provide neuroprotection, but Alg did not show any neuroprotection against PD. Alg and its two components acted differently in preventing dopaminergic neuronal loss in PD mice. This article is protected by copyright. All rights reserved.

16.
Opt Express ; 29(20): 32006-32019, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615280

RESUMO

Quantum nonlinear interferometers (QNIs) can measure the infrared physical quantities of a sample by detecting visible photons. A QNI with Michelson geometry based on the spontaneous parametric down-conversion in a second-order nonlinear crystal is studied systematically. A simplified theoretical model of the QNI is presented. The interference visibility, coherence length, equal-inclination interference, and equal-thickness interference for the QNI are demonstrated theoretically and experimentally. As an application example of the QNI, the refractive index and the angle between two surfaces of a BBO crystal are measured using equal-inclination interference and equal-thickness interference.

17.
Biomed Chromatogr ; : e5254, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605575

RESUMO

Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.

18.
Front Chem ; 9: 733350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616713

RESUMO

Seven new clerodane diterpenoids, crassifolins Q-W (1-7), along with five known analogues (8-12), were isolated from the roots of Croton crassifolius. Their structures were identified by comprehensive spectroscopic analysis (UV, IR, NMR, and HR-ESI-MS), and their absolute configurations were determined by ECD spectra and X-ray crystallography. The activities of compounds 1-5 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, and compound 5 showed the most significant activity with the secretion levels of IL-6 and TNF-α at 32.78 and 12.53%, respectively. Moreover, compounds 1-5 were screened for their anti-angiogenesis using a human umbilical vein endothelial cells in vitro mode; the results showed all of them exhibited obvious anti-angiogenesis activities, in particular, compound 5 showed the strongest anti-angiogenesis effect in the range of 6.25-50 µM.

19.
World J Clin Cases ; 9(26): 7876-7885, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34621841

RESUMO

BACKGROUND: The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype. CASE SUMMARY: An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant's liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now. CONCLUSION: Based on the infant's clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.

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