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1.
Phytomedicine ; 91: 153706, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34517264

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cause of cancer-related death worldwide. Curcumin (C) has been extensively investigated in different types of malignancies, including hepatocellular carcinoma, but its physicochemical properties have significantly influenced its clinical use. Several approaches are being explored to enhance curcumin's therapeutic response, including its combination with various drugs. PURPOSE: This study aimed to evaluate the anti-tumor effect of curcumin (C) in combination with F2 (N-n-butyl haloperidol iodide) on hepatocellular carcinoma and its potential underlying mechanism in vitro and in vivo. METHODS: Cell proliferation was evaluated by CCK-8 and colony formation assays, and apoptosis was measured by flow cytometry. The migratory and invasive abilities of Hep3B and SMMC-7721 cells were measured by wound-healing and matrigel transwell assays. In order to investigate the molecular pathways, various experiments such as western blotting, qPCR, RNA-seq, immunostaining and transfection were performed. To evaluate the anti-HCC effects in vivo, a xenograft tumor model was used. RESULTS: Our findings showed that the combination of curcumin (C) & F2 (F2C) strongly inhibited malignant proliferation and migration in SMMC-7721 and Hep3B cells. The F2C treatment downregulates enhancer of zeste homolog 2 (EZH2) transcription and protein expression, which is key epigenetic regulator responsible for HCC development. Moreover, the inhibition of EZH2 by F2C led to Wnt/ß-catenin signaling inhibition by decreasing tri-methylation of histone H3 at lysine 27 (H3K27me3) and long non-coding RNA H19 expression. The inhibition of F2C was associated with the suppression of tumorigenicity in xenograft HCC models. CONCLUSION: These findings suggested that, F2C inhibited HCC formation, migration and its modulatory mechanism seemed to be associated with downregulation of EZH2, silencing Wnt/ß-catenin signaling by interacting with H19, suggesting that F2C may be a promising drug in the clinical treatment of HCC.

2.
Rev Esp Enferm Dig ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34538057

RESUMO

A 26-year-old lactating mother presented with a 3-week history of abdominal pain, constipation and vomiting. She denied a history of alcohol abuse or other gastrointestinal problem. Contrast-enhanced CT revealed a small bowel obstruction caused by caecum cancer. Therefore, she underwent a right hemicolectomy and ileocolic anastomosis. Post-operatively, she gradually developed drowsiness, fainting and a rapid heart rate of 130. But blood tests were all normal. On the fourteenth postoperative day, she experienced two episodes of generalized tonic-clonic seizure. Neurologic examination revealed nystagmus, ophthalmoplegia and gait ataxia. She complained of impaired memory and blurred vision. Brain magnetic resonance image (MRI) showed bilaterally symmetric hyperintensities in paramedial thalami surrounding the third ventricle, dorsal brainstem and periaqueductal region in the axial T2-FLAIR images . Wernicke's encephalopathy (WE) was suspected and the patient was treated with Vitamin B1 immediately. Her symptoms improved rapidly, and a brain MRI two weeks later demonstrated marked resolution of the hyperintensities.

3.
J Org Chem ; 86(17): 11442-11455, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479405

RESUMO

A novel approach to 2-substituted-2-(dimethoxyphosphoryl)-pyrrolidines 7a-7o and 9a-9r has been developed, which features a TMSOTf-mediated one-pot intramolecular cyclization and phosphonylation of substituted tert-butyl 4-oxobutylcarbamates. The major advantages of this method include simple operation under mild reaction conditions, the use of cheap Lewis acid, and good to excellent yields with high diastereoselectivities (dr up to 99:1).

4.
Eur Respir J ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503987

RESUMO

RATIONALE: Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health. METHODS: We performed an individual participant meta-analysis among 18 326 mother-child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diet were estimated by energy-adjusted Dietary Inflammatory Index (E-DIITM) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured by questionnaires and lung function by spirometry. RESULTS: After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower FVC in children (Z-score difference (95% confidence interval (CI)): -0.05 (-0.08, -0.02), per IQR increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. When exploratively examining the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low FEV1/FVC (z-score <-1.64) (OR (95% CI) 1.20 (1.06, 1.36), 1.40 (1.06, 1.85), compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%. CONCLUSION: Main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

5.
Gynecol Oncol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509297

RESUMO

OBJECTIVE: The objective of this study was to evaluate medical adherence for patients with ovarian cancer who initiated treatment with a PARP inhibitor therapy, and to identify factors associated with nonadherence. METHODS: We used the MarketScan Database to identify ovarian cancer patients who initiated PARP inhibitor therapy between January 1, 2008 and December 31, 2017. The primary outcome was adherence defined as ≥ 80% proportion of days covered (PDC). A secondary outcome included adherence assessed using the medication possession ratio (MPR). Multivariable logistic regression analysis was performed to assess relation between PDC and explanatory variables. Sensitivity analysis was performed to evaluate impact of dose-adjustments and toxicity-related delays on adherence. RESULTS: Among 170,976 patients diagnosed with ovarian cancer, 151 patients met inclusion criteria. The median time from diagnosis to initiating therapy was 33 months. Overall, 40 (26.5%) were non-adherent based on a PDC less than 80%. Non-adherent patients were more likely to receive niraparib and have a longer duration of therapy (p < 0.05). We found no significant impact of age, comorbidities, insurance plan, or year of PARP inhibitor initiation on non-adherence. In a sensitivity analysis to assess different definition of adherence, non-adherence ranged from 11.3% to 41.1%. When accounting for possible dose-adjustments, 21.2% of patients were non-adherent. CONCLUSION: This population based study of ovarian cancer patients found that a quarter of patients may be sub-optimally adherent to PARP inhibitor therapy. Future research should focus on identification of patients at risk for nonadherence and interventions to lower nonadherence among these patients.

6.
Small ; : e2103127, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510742

RESUMO

Conjugated polymers (CPs) are capable of coordinating the electron coupling phenomenon to bestow powerful optoelectronic features. The light-harvesting and light-amplifying properties of CPs are extensively used in figuring out the biomedical issues with special emphasis on accurate diagnosis, effective treatment, and precise theranostics. This review summarizes the recent progress of CP materials in bioimaging, cancer therapeutics, and introduces the design strategies by rationally tuning the optical properties. The recent advances of CPs in bioimaging applications are first summarized and the challenges to clear the future directions of CPs in the respective area are discussed. In the following sections, the focus is on the burgeoning applications of CPs in phototherapy of the tumor, and illustrates the underlying photo-transforming mechanism for further molecular designing. Besides, the recent progress in the CPs-assistant drug therapy, mainly including drug delivery, gene therapeutic, the optical-activated reversion of tumor resistance, and synergistic therapy has also been discussed elaborately. In the end, the potential challenges and future developments of CPs on cancer diagnosis and therapy are also illuminated for the improvement of optical functionalization and the promotion of clinical translation.

7.
Sci Rep ; 11(1): 18023, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504296

RESUMO

Similar to global trends, the incidence rate of tuberculosis (TB) in China declined from 2000 to 2018. In this study, we aimed to evaluate TB trends in northern Guizhou Province and identify risk factors associated with rifampicin-resistant (RR) and concurrent extrapulmonary TB (EPTB). We analyzed data of TB patients hospitalized in Affiliated Hospital of Zunyi Medical University from 2011 to 2018, and assessed correlations between demographic characteristics of patients and RR-TB as well as concurrent EPTB. Our results showed that numbers of new, retreated, RR-TB and concurrent EPTB cases increased gradually from 2011 to 2018. Retreated patients had the highest odds of RR-TB but a lower likelihood of concurrent EPTB compared to new patients. Patients between 21 and 40 years of age had a higher likelihood of RR-TB compared to those 20 years and younger. Female patients and patients from Bijie city as well as the Miao ethnic minority had higher odds of concurrent EPTB. In summary, our data demonstrate upward trends in new, rifampicin-resistant and concurrent extrapulmonary TB cases in northern Guizhou Province of China, which should not be overlooked especially during and post the COVID-19 pandemic because TB is a greater long-term global health threat than COVID-19.

8.
Chem Commun (Camb) ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523655

RESUMO

A visible-light-driven direct carbonylative coupling of simple alkanes and alkenes via the combination of a hydrogen atom transfer process and photoredox catalysis has been demonstrated. Employing the N-alkoxyazinium salt as the oxidant and the precursor of an oxygen radical, a variety of α,ß-unsaturated ketones could be obtained in a metal-free fashion.

9.
Eur J Pharmacol ; : 174461, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34469757

RESUMO

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high disability and mortality, and no effective treatment is available. Previous research on intracerebral hemorrhage secondary brain injury drugs mainly targeted at cell apoptosis, inflammation and oxidative stress, but did not achieve good effects. In recent years, ferroptosis has become a focus concern in neurological diseases. Ferroptosis is a new type of programmed cell death caused by iron-dependent accumulation of lipid peroxides, in which glutathione peroxidase 4 (GPX4) is a key protein affecting ferroptosis. In this study, we used the STRING protein database to predict the proteins that may be co-expressed with GPX4, and studied the ability of Dauricine(Dau) to up-regulate the expression of GPX4 against ferroptosis and neuroprotection after intracerebral hemorrhage in normal cells in vitro, glutathione peroxidase 4 (GPX4) knockdown cells and collagenase injection in vivo in mouse models of intracerebral hemorrhage. The results showed that glutathione reductase (GSR) was a possible co-expression protein with GPX4. Dau could up-regulate the expression of glutathione peroxidase 4 (GPX4) in intracerebral hemorrhage(ICH) model, normal cells and GPX4 knockdown cells in vitro, and simultaneously up-regulate the expression of GSR in ICH mice. Dau could also reduce the levels of iron and lipid peroxidation, and have a neuroprotective effect on intracerebral hemorrhage(ICH) mice. It was tesified that Dauricine(Dau) could inhibit ferroptosis of nerve cells and alleviate brain injury after intracerebral hemorrhage by upregulating glutathione peroxidase 4 (GPX4) and glutathione reductase (GSR) co-expression. Therefore, Dau may be an effective drug for inhibiting ferroptosis and treating intracerebral hemorrhage.

11.
Cell Rep ; 36(11): 109718, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34525361

RESUMO

Scant understanding of the glioblastoma microenvironment and molecular bases hampers development of efficient treatment strategies. Analyses of gene signatures of human gliomas demonstrate that the SETD2 mutation is correlated with poor prognosis of IDH1/2 wild-type (IDH-WT) adult glioblastoma patients. To better understand the crosstalk between SETD2 mutant (SETD2-mut) glioblastoma cells and the tumor microenvironment, we leverage single-cell transcriptomics to comprehensively map cellular populations in glioblastoma. In this study, we identify a specific subtype of high-grade glioma-associated microglia (HGG-AM). Further analysis shows that transforming growth factor (TGF)-ß1 derived from SETD2-mut/IDH-WT tumor cells activates HGG-AM, exhibiting pro-inflammation and proliferation signatures. Particularly, HGG-AM secretes interleukin (IL)-1ß via the apolipoprotein E (ApoE)-mediated NLRP1 inflammasome, thereby promoting tumor progression. HGG-AM present extensive proliferation and infiltration to supplement the activated microglia pool. Notably, TGF-ß1/TßRI depletion dramatically reduces HGG-AM density and suppresses tumor growth. Altogether, our studies identify a specific microglia subpopulation and establish the cellular basis of interactions between HGG-AM and glioblastoma cells.

12.
RNA ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526358

RESUMO

Although long noncoding RNAs (lncRNAs) are generally expressed at low levels, emerging evidence has revealed that many play important roles in gene regulation by a variety of mechanisms as they engage with proteins. Given that the abundance of proteins often greatly exceeds that of their interacting lncRNAs, quantification of the relative abundance, or even the exact stoichiometry in some cases, within lncRNA-protein complexes is helpful for understanding of the mechanism(s) of action of lncRNAs. We discuss methods used to examine lncRNA and protein expression at the single cell, sub-cellular and sub-organelle levels, the average and local lncRNA concentration in cells, as well as how lncRNAs can modulate the functions of their interacting proteins even at a low stoichiometric concentration.

13.
Lupus ; : 9612033211045284, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528847

RESUMO

Background: Patients with skin of color (P-SOC) are disproportionately burdened by lupus and often have worse disease outcomes than white patients. This is partly because educational materials underrepresent P-SOC, thereby promoting unconscious bias and clinical deficiencies among practitioners.Purpose: We sought to measure providers' confidence in diagnosing the cutaneous manifestations of lupus (i.e., lupus-related rashes) in P-SOC and to assess which factors influenced their confidence.Research Design: We created and distributed a survey that gathered information about participants' personal characteristics, clinical specialty, training, and current practice as well as measuring their confidence assessing lupus-related rashes in various skin tones.Study Sample: Practitioners from the fields of rheumatology, dermatology, and internal medicine in the greater St. Louis area (Missouri, USA) participated in the survey.Analysis: We compared practitioners' mean confidence levels assessing lupus-related rashes in patients with fair skin and P-SOC with a linear mixed effects model and used univariate and multivariate linear regression models to determine if the aforementioned factors correlated with confidence.Results: Participants' mean confidence in diagnosing lupus-related rashes in P-SOC was significantly lower than assessing such findings in patients with fair skin (p = .009). Several factors correlated with confidence level at a univariate level; however, the multivariate model revealed experience as the only factor significantly associated with confidence (p = .001). Conclusions: Providers report significantly less confidence assessing lupus-related rashes in P-SOC than in patients with fair skin. Our analysis demonstrates that experience positively correlates with confidence and suggests that interventions which enhance practitioners' exposure to and experience with these rashes in P-SOC can improve clinical confidence as well as patient outcomes.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34532933

RESUMO

Current nonlinear optical materials face a conventional limitation in the trade-off between the band gap and birefringence, especially in the deep UV spectral region. To circumvent this dilemma, we propose a general principle, π-conjugated confinement, to partially decouple the interunit π-conjugated interactions by the separation of non-π-conjugated units. The goal is to further enlarge the band gap to a value larger than that of the singular π-conjugated counterpart and to maintain a suitable density of π-conjugated units to gain a large optical anisotropy. We reveal that π-conjugated confinement is a shared structural feature for all DUV NLO materials known to date, and thus, it provides a novel and essential design criterion for future design synthesis. Guided by this principle, the carbonophosphates are predicted to be a new promising DUV candidate system. Sr3Y[PO4][CO3]3 (1) and Na3X[PO4][CO3] (X = Ba, Sr, Ca, Mg, 2-5) exhibit not only greatly enhanced birefringence that is 3-24 times larger than that of singular phosphates but also enhanced band gaps that are 0.2-1.7 eV wider than those of singular carbonates.

15.
Food Funct ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533153

RESUMO

Three shell materials, lecithin (ZNP-L), chitosan (ZNP-CH) and sodium caseinate (ZNP-SC), were used to prepare core-shell zein nanoparticles. Astilbin was encapsulated as a model flavonoid to compare the influence of the shell materials on zein nanoparticles both in vitro and in vivo. The particle size was moderately increased by lecithin and sodium caseinate, but notably increased by chitosan. All the shell materials provided good redispersibility for the nanoparticles and significantly improved the colloidal stability. Chitosan and sodium caseinate significantly delayed and decreased the feces excretion of astilbin in rats, while lecithin exhibited a very weak effect. The results may be attributed to the difference in mucoadhesive properties between the shell materials. As a consequence, the bioavailability values of astilbin in rats were 18.2, 9.3 and 1.89 times increased through ZNP-CH, ZNP-SC and ZNP-L compared with that of free astilbin, respectively.

16.
Diagn Cytopathol ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506642

RESUMO

BACKGROUND: High-grade serous carcinoma (HGSC) is the most common epithelial carcinoma of the tubo-ovarian region, with a poor prognosis, which presents with an advanced stage at the time of diagnosis. This study summarizes the cytological features of cervical liquid-based cytological examination in order to diagnose ovarian or tubal HGSC at an early stage by cervical cytology smear. METHODS: A total of 12 patients who were diagnosed with atypical glandular cell (AGC) and above lesions by cervical cytological examination and ovarian or tubal HGSC by histopathology were enrolled in this study. The cytological characteristics, including the arrangement and shape of the neoplastic cells, nuclear and cytoplasmic features, and the presence of tumor diathesis were reviewed. RESULTS: Nine cases were determined to be AGC, and three cases were determined to be AGC favor neoplastic (AGC-FN) in the 12 cervical cytological diagnoses. The glandular cells showed significant atypia and proliferated actively with a three-dimensional structure. Increased nuclear-to-cytoplasmic ratios, prominent nucleoli, and hyperchromasia were common. Vacuole-like changes were observed in the cytoplasm. Tumor diathesis was observed in only one case (1/12, 8.30%). CONCLUSION: Ovarian or tubal HGSC can occasionally be detected using cervical liquid-based cytology. It has distinct cytological characteristics. Primary ovarian or tubal HGSC with positive cervical cytology was accompanied by tumor cells in ascites, which suggested that the patient had progressed to an advanced stage.

17.
Biosens Bioelectron ; 194: 113633, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34543825

RESUMO

Reliable discrimination of specific epidermal growth factor receptor (EGFR) gene mutations plays a critical role in guiding lung cancer therapeutics. Until now, convenient and accurate recognition of the specific deletion of EGFR exons has remained particularly challenging. Herein, we propose a palindromic-assisted self-annealing transcription amplification (PASTA) strategy for the reliable detection of circulating EGFR exon mutations. We designed a palindromic DNA hairpin nanorobot consisting of a palindromic tail, a T7 promoter, a target recognition region, and a transcription template. The nanorobot enabled prompt self-assembly into a target-hairpin/hairpin-target dimer in the presence of single-stranded DNA target and further triggered in vitro transcription. In a proof-of-concept experiment for detecting circulating 15n-del EGFR mutation, a detection limit of 0.8 fM and a linear detection range of 1 fM to 100 pM was achieved, and an accuracy of 100% was reached in clinical validation by analyzing 20 samples from clinical lung cancer patients. Empowered by the intrinsic sensitivity and selectivity, the proposed PASTA approach will lead to the development of a universal platform for reliable molecular subtyping.

18.
Stem Cell Res ; 56: 102516, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34469777

RESUMO

The homozygous autosomal recessive truncating mutations of LDL receptor related protein associated protein 1 (LRPAP1) is a possible reason for Nonsyndromic Extreme Myopia, patients with which show typical chorioretinal degeneration. We generated an LRPAP1 knockout FDCHDPe009-B embryonic stem cell line to study mechanisms of retinal degeneration underlying LRPAP1 deficiency with the help of the CRISPR/Cas9 system. Two distinct biallelic deletions in the cell line have been confirmed, which causing a frameshift and premature stop codons thus influence the translation of LRPAP1. FDCHDPe009-B has maintained normal stem cell morphology, pluripotent gene expression, parental karyotype, and ability to differentiate into three germ layers.

19.
Leg Med (Tokyo) ; 53: 101957, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34481193

RESUMO

The Microreader™ 19X Direct ID System was a newly developed multiplex PCR kit, which could detect 19 X-chromosomal STR loci (DXS6795, DXS9907, DXS6803, GATA172D05, DXS6807, GATA31E08, DXS7423, DXS6810, DXS101, DXS9902, DXS7133, DXS6800, DXS981, DXS10162, DXS6809, DXS10135, HPRTB, GATA165B12, DXS10079) and the sex determination locus of AMEL simultaneously. Different from other X-STR multiplex PCR kits, no linkage groups are included in this system, so the likelihood ratios could be calculated without the consideration of linkage groups. In this study, PCR conditions, sensitivity, species specificity, stability, DNA mixtures, concordance, stutter, sizing precision and population studies were conducted according to the SWGDAM developmental validation guidelines. The results indicated that this new X-STRs multiplex system was an efficient and reliable detection system, which could facilitate human kinship analysis and identification testing, as a powerful supplementary to autosomal STR kits.

20.
BMJ Open ; 11(8): e048629, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426464

RESUMO

INTRODUCTION: Dynapenia is a new term that is used to describe the age-related loss of muscle strength. Flexi-bar training is a safe and feasible device for older people with dynapenia. This study will investigate the effects of a 12-week flexi-bar training programme on muscle strength and physical function in older people with dynapenia. METHODS AND ANALYSIS: A total of 114 participants (aged more than 65 years) with age-related muscle loss will participate in a 12-week flexi-bar training programme. The participants will be randomly divided into three groups, namely, flexi-bar, placebo and control, with equal number of participants in each group. The assessments will be conducted at preintervention, postintervention and 12 weeks after training completion. The primary outcome is timed-up-and-go test. The secondary outcomes are five-repetition sit-to-stand test, 10-metre walking test, handgrip strength, as well as the serum albumin and haemoglobin levels. ETHICS AND DISSEMINATION: The procedures of this study were reviewed and approved by the Human Ethics Review Board of Wuhan Brain Hospital (General Hospital of the Yangtze River Shipping) on 29 September 2020 (#L20200013). The findings of this study will be published in peer-reviewed journals and presented at conferences. The trial was registered on 6 November 2020. TRIAL REGISTRATION NUMBER: ISRCTN14316668.


Assuntos
Força da Mão , Equilíbrio Postural , Idoso , Humanos , Força Muscular , Desempenho Físico Funcional , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Tempo e Movimento
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