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1.
Food Chem ; 366: 130509, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34339923

RESUMO

In China, three Rosaceae fruits with distinctive flavours and functions have recently been transformed from edible plants into standardised juice or beverage products. To enhance the development of these fruit products, the results and conclusions from various investigations of the chemical and biological properties of fruits should be summarised. Based on industrial advances, there are still some limitation in the research and development of these fruit products that need to be addressed. Therefore, in this report, we provided a comprehensive and rigorous review to summarise critical data from phytochemical and biological investigations and from flavour profiles and industrial development of these fruit products. Our goal is to provide insights into recent research findings in order to advance studies and developments of products of these flavourful fruits from a reasonable perspective.


Assuntos
Rosa , Frutas , Compostos Fitoquímicos , Plantas Comestíveis , Pyracantha
2.
Neural Regen Res ; 17(1): 137-143, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100449

RESUMO

The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

3.
Adv Healthc Mater ; : e2101577, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34808031

RESUMO

Conductive biomaterials provide an important control for engineering neural tissues, where electrical stimulation can potentially direct neural stem/progenitor cell (NS/PC) maturation into functional neuronal networks. We anticipate that stem cell-based therapies to repair damaged central nervous system (CNS) tissues and ex vivo, "tissue chip" models of the CNS and its pathologies will each benefit from development of biocompatible, biodegradable, and conductive biomaterials. Here, we review technological advances in conductive biomaterials over the past two decades that may facilitate development of engineered tissues with integrated physiological and electrical functionalities. First, we briefly introduce NS/PCs of the CNS. Then, the significance of incorporating microenvironmental cues, to which NS/PCs are naturally programmed to respond, into biomaterial scaffolds is discussed with a focus on electrical cues. Next, practical design considerations for conductive biomaterials are discussed followed by a review of studies evaluating how conductive biomaterials can be engineered to control NS/PC behavior by mimicking specific functionalities in the CNS microenvironment. Finally, steps researchers can take to move NS/PC-interfacing, conductive materials closer to clinical translation are discussed. This article is protected by copyright. All rights reserved.

4.
Org Biomol Chem ; 19(44): 9746-9751, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34730165

RESUMO

The iridium/f-diaphos L1, L5 or L12 catalyzed asymmetric hydrogenation of 2-imidazolyl aryl/alkyl ketones to afford two enantiomers of the desired chiral alcohols with high conversions (up to 99% yield) and moderate to excellent enantioselectivities (61% - >99% ee) was realized for the first time. This protocol could be easily conducted on a gram-scale with a TON of 9700.

5.
J Magn Reson Imaging ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741576

RESUMO

BACKGROUND: Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) denoising through deep learning (DL) often faces insufficient training data from patients. One solution is to train DL models using healthy subjects' data which are more widely available and transfer them to patients' data. PURPOSE: To evaluate the transferability of a DL-based ASL MRI denoising method (DLASL). STUDY TYPE: Retrospective. SUBJECTS: Four hundred and twenty-eight subjects (189 females) from three cohorts. FIELD STRENGTH/SEQUENCE: 3 T two-dimensional (2D) echo-planar imaging (EPI)-based pseudo-continuous ASL (PCASL) and 2D EPI-based pulsed ASL (PASL) sequences. ASSESSMENT: DLASL was trained using young healthy adults' PCASL data (Dataset 1: 250/30 subjects as training/validation set) and was directly transferred (DTF) to PCASL data from Dataset 2 (45 subjects test set) of normal controls (NC) and Alzheimer's disease (AD) groups. DLASL was fine-tuned (DLASLFT) and tested on PASL data from Dataset 3 (103 subjects test set) of NC and AD. An existing non-DL method (NonDL) was used for comparison. Cerebral blood flow (CBF) images from ASL MRI were compared between NC and AD to assess characteristic hypoperfusion (lower CBF) patterns in AD. CBF image quality and CBF map sensitivity for detecting hypoperfusion using peak t-value and suprathreshold cluster size are outcome measures. STATISTICAL TESTS: Paired t-test, two-sample t-test, one-way analysis of variance, and Tukey honestly significant difference, and linear mixed-effects models were used. P < 0.05 was considered statistically significant. RESULTS: Mean contrast-to-noise ratio (CNR) of Dataset 2 showed that DTF outperformed NonDL (AD: 3.38 vs. 2.64, NC: 3.80 vs. 3.36). On Dataset 3, DLASLFT outperformed NonDL measured by mean CNR (AD: 2.45 vs. 1.87, NC: 2.54 vs. 2.17) and mean radiologic score (2.86 vs. 2.44). Image quality improvement was significant on both test sets. DTF and DLASLFT improved sensitivity for detecting AD-related hypoperfusion patterns compared with NonDL. DATA CONCLUSION: We demonstrated the DLASL's transferability across different ASL sequences and different populations. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

6.
Inorg Chem ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738796

RESUMO

Zero-dimensional (0D) metal halides with solid-state luminescence switching (SSLS) have attracted attention as sensors and luminescent anticounterfeiting. Herein, selective solvent molecule response and accordingly luminescence switching were discovered in 0D [EtPPh3]2[SbCl5] (1, EtPPh3 = ethyltriphenylphosphonium). More than a dozen kinds of solvent molecules have been tested to find out the selection rule for molecule absorption in 1, which is demonstrated to be the size effect of guest molecules. Confirmed by crystal structural analysis, only the solvents with molecular volume less than 22.3 Å3 could be accommodated in 1 leading to the solvatochromic photoluminescence (PL). The mechanism of solvatochromic PL was also deeply studied, which was found to be closely related to the supramolecular interactions between solvent molecules and the host material. Different functional groups of the solvent molecule can affect its strength of hydrogen bonding with [SbCl5]2-, which is crucial for the distortion level of [SbCl5]2- unit and thus results in not only distinct solvatochromic PL but also distinct thermochromic PL. In addition, they all show typical self-trapped exciton triplet emissions. The additional supramolecular interactions from guest molecules can enhance the photoluminescence quantum yield to be as high as 95%.

7.
Arch Biochem Biophys ; 715: 109094, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34813774

RESUMO

In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). Particularly, it damages the function of granulosa cells, and thus hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)-induced Granulosa-like tumor cell line (KGN), mediated via antioxidant mechanisms. The study assessed the positive effects of salidroside on DHT-induced apoptosis, reactive oxygen species (ROS) accumulation, damage of antioxidant capacity, and mitochondrial membrane potential depolarization. Interestingly, salidroside partly reversed DHT mediated effects, via stimulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the downstream antioxidant proteins heme oxygenase-1(HO-1) and quinine oxidoreductase 1(NQO1). Additionally, the knockdown of Nrf2 partly moderated the antioxidant and anti-apoptosis effects of salidroside in DHT-treated KGN cells. Mechanistically, AMP-activated protein kinase (AMPK) was identified to be the upstream signaling involved in salidroside-induced Nrf2 activation, as silencing of AMPK partly prevented the upregulation of Nrf2 and the downstream proteins HO-1 and NQO1. Altogether, the present study is the first to effectively demonstrate the inhibitory effect of salidroside on DHT-stimulated oxidative stress and apoptosis in KGN cells, which was dependent on Nrf2 activation that involved AMPK.

8.
Carbohydr Res ; 511: 108463, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34741878

RESUMO

The mechanism of the initial reactions in the acid-catalytic conversion of d-xylose/d-xylulose to furfural was studied with density functional theory. The reactions included mutual transformations among d-xylose, d-xylulose and the intermediate of 1,2-enediol. The catalytic performances of several acids including H2SO4, HNO3, HCl, HBr and HI, and the solvent effects of water and THF (tetrahydrofuran) were studied. A simplified kinetic model of the d-xylose/d-xylulose-to-furfural conversion in water solvent was built, with the assumption that the conversion from 1,2-enediol to furfural was the rate-limiting step and could be treated as one-step reaction. The simulation can well fit the experimental regulation, which verifies the rationality of the model simplification. The dominant reaction pathways from d-xylose/d-xylulose to furfural were deduced based on the calculated energy barriers and corresponding reaction rate constants, with different acid catalysis and reaction mediums.

9.
Small ; : e2104282, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623019

RESUMO

Ni-rich layered oxides are significantly promising cathode materials for commercial high-energy-density lithium-ion batteries. However, their major bottlenecks limiting their widespread applications are capacity fading and safety concerns caused by their inherently unstable crystal structure and highly reactive surface. Herein, surface structure and bulk charge regulation are concurrently achieved by introducing high-valence Ta5+ ions in Ni-rich cathodes, which exhibit superior electrochemical properties and thermal stability, especially a remarkable cyclic stability with a capacity retention of 80% for up to 768 cycles at a 1C rate versus Li/Li+ . Due to the partial Ta enrichment on surface, the regulated surface enables high reversibility of Li+ insertion/extraction by preventing surface Ni reduction in deep charging. Moreover, bulk charge regulation that boosts charge density and its localization on oxygen remarkably suppresses microcracks and oxygen loss, which in turn prevents the fragmentation of the regulated surface and structural degradation associated with oxygen skeleton. This study highlights the significance of an integrated optimization strategy for Ni-rich cathodes and, as a case study, provides a novel and deep insights into the underlying mechanisms of high-valence ions substitution of Ni-rich layered cathodes.

10.
J Dig Dis ; 22(11): 663-671, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34697888

RESUMO

OBJECTIVE: This study aimed to investigate the clinical features and potential pathogenesis of a rare nonhereditary polyposis syndrome, Cronkhite-Canada syndrome (CCS). METHODS: Medical records of eight patients with CCS who were admitted to our hospital from January 2005 to November 2019 were reviewed. Transcriptome profiling was performed in one patient to investigate its difference between gastric polyp tissue and normal mucosa. Differentially expressed genes (DEGs) were determined for functional analysis. The expression of inhibin beta A (INHBA) was further assessed by using immunohistochemistry. RESULTS: All patients presented with gastrointestinal polyposis, accompanied by diarrhea, skin hyperpigmentation, hair loss and nail dystrophy. Hyperplastic polyps were observed in seven patients, tubular adenoma in two, inflammatory polyps in one and hamartomatous polyps in one, respectively. All patients underwent comprehensive treatment and five achieved clinical remission. A total of 2107 DEGs, including 1265 upregulated and 842 downregulated, were found in the gastric polyp. Gene ontology analysis showed that upregulated genes were significantly enriched in the positive regulation of cell proliferation, epithelium development and angiogenesis. A protein-protein interaction analysis suggested that INHBA was at the center of the interaction network and might play an important role in CCS. Immunohistochemistry confirmed that INHBA expression was upregulated in CCS gastric polyps. CONCLUSIONS: CCS is a rare disease and its diagnosis mainly depends on typical clinical manifestations, endoscopic findings and histological features. INHBA upregulation may contribute to its pathogenesis.


Assuntos
Adenoma , Neoplasias Colorretais , Polipose Intestinal , Neoplasias Gástricas , Humanos , Imuno-Histoquímica , Polipose Intestinal/genética
11.
Bioorg Chem ; 116: 105387, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34628225

RESUMO

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an ß-amyloid (Aß) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Aß1-42 aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Aß1-42 pentamers. Moreover, 13a effectively attenuated Aß1-42 oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.

12.
iScience ; 24(10): 103097, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34622152

RESUMO

The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5 -/- ) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5 -/- mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development.

13.
Medicine (Baltimore) ; 100(37): e27234, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664866

RESUMO

ABSTRACT: Various studies have revealed an association between cigarette smoking and increased risk for multiple sclerosis (MS). However, its role in neuromyelitis optica spectrum disorder (NMOSD) remains elusive. Therefore, in the present case-control study, we aimed to assess the association of active and passive cigarette smoking with the risk of MS and NMOSD.Thirty-six patients with NMOSD, 46 patients with MS, and 122 healthy individuals were included in this study. Standardized questionnaires and telephone interviews were used to collect information regarding the active and passive cigarette smoking behaviors of the patients and normal controls.The risk of MS was significantly higher among smokers than among nonsmokers (odds ratio = 2.166, 95% confidence interval: 1.109-4.170; P = .027). Further analysis of the risk between active and passive smokers, male smokers and nonsmokers showed no statistical difference. However, neither smokers nor active smokers had a greater or lower risk of NMOSD than their nonsmoking counterparts.Our preliminary study showed no significant association between cigarette smoking and the risk of NMOSD, strongly suggesting that, unlike MS, cigarette smoking might not confer NMOSD susceptibility, at least in the Northern Han Chinese population.


Assuntos
Fumar Cigarros/efeitos adversos , Neuromielite Óptica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Criança , China/epidemiologia , Fumar Cigarros/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/epidemiologia , Razão de Chances , Fatores de Risco , Inquéritos e Questionários , Tabaco/efeitos adversos , Tabaco/fisiologia
14.
Ecotoxicol Environ Saf ; 227: 112898, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673416

RESUMO

In the hazard assessment of mixtures, the mixture predicted no-effect concentration (mPNEC) is always derived by the concentration addition (CA) model (mPNECCA) to assess the risk of mixtures combined with exposure assessment. However, the independent action (IA) model, which is also widely used as the CA model in the prediction and evaluation of mixture toxicity, is always used to calculate the population fraction showing a predefined effect, not mPNEC, and this limits the application of IA model in the mixture risk assessment. In this study, we explored the process of mPNEC derived by the IA method (mPNECIA) based on the species sensitivity distribution (SSD) and compared mPNECIA with mPNECCA. Taking two common pesticides, dimethoate (DIM) and dichlorvos (DIC), exposed in the actual water environment as an example, their SSD models were constructed separately using nine distribution functions after toxicity data screening and quality testing. For both DIC and DIM, all different nine models had passed the Kolmogorov-Smirnov test. Then, the PNECs of two pesticides were derived based on SSD models. Finally, mPNECIA with different concentration ratios was derived and compared to mPNECCA based on 81 combinations of nine SSD models. Most mPNEC values derived by IA model were more conservative than those by CA. It is worth noting that the mPNECIA is more conservative than mPNECCA for the commonly used log-logit distribution (function 7), log-normal distribution (8), and log-Weibull distribution (9). This study provides a new direction for the application of IA in the risk assessment and enriches the framework of mixture risk assessment.


Assuntos
Praguicidas , Diclorvós , Dimetoato , Praguicidas/toxicidade , Medição de Risco
15.
Microb Pathog ; 161(Pt A): 105240, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34655729

RESUMO

In this study, the differences in the phosphoproteomic landscape of sporulated oocysts between virulent and avirulent strains of Toxoplasma gondii were examined using a global phosphoproteomics approach. Phosphopeptides from sporulated oocysts of the virulent PYS strain (Chinese ToxoDB#9) and the avirulent PRU strain (type II) were enriched by titanium dioxide (TiO2) affinity chromatography and quantified using IBT approach. A total of 10,645 unique phosphopeptides, 8181 nonredundant phosphorylation sites and 2792 phosphoproteins were identified. We also detected 4129 differentially expressed phosphopeptides (DEPs) between sporulated oocysts of PYS strain and PRU strain (|log1.5 fold change| > 1 and p < 0.05), including 2485 upregulated and 1644 downregulated phosphopeptides. Motif analysis identified 24 motifs from the upregulated phosphorylated peptides including 22 serine motifs and two threonine motifs (TPE and TP), and 15 motifs from the downregulated phosphorylated peptides including 12 serine motifs and three threonine motifs (TP, RxxT and KxxT) in PYS strain when comparing PYS strain to PRU strain. Several kinases were consistent with motifs of overrepresented phosphopeptides, such as PKA, PKG, CKII, IKK, MAPK, EGFR, INSR, Jak, Syk, Src, Ab1. GO enrichment, KEGG pathway analysis and STRING analysis revealed DEPs significantly enriched in many biological processes and pathways. Kinase related network analysis showed that AGC kinase was the most connected kinase peptide. Our findings reveal significant difference in phosphopeptide profiles of sporulated oocysts between virulent and avirulent T. gondii strains, providing new resources for further elucidation of the mechanisms underpinning the virulence of T. gondii.

16.
Anal Bioanal Chem ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34693471

RESUMO

In this study, Lba Cas12a (Cpf1) as one of the CRISPR systems from Lachnospiraceae bacterium was coupled with a hybridization chain reaction (HCR) to develop an electrochemical biosensor for detecting the pathogenic bacterium, Salmonella typhimurium. Autonomous cross-opening of functional DNA hairpin structures of HCR yielded polymer double-stranded DNA wires consisting of numerous single-stranded DNAs, which initiated the trans-cleavage activity of CRISPR-Cas12a to indiscriminately cleave random single-stranded DNA labeling electrochemical tags on the surface of the electrode. It led to a variation in the electron transfer of electrochemical tags. The polymer double-stranded DNA of HCR was immobilized on dynabeads (DBs) via the S. typhimurium aptamer and released from DBs. The established method could selectively and sensitively quantify S. typhimurium in samples with detection limits of 20 CFU/mL. Our study provides a novel insight for exploring universal analytical methods for pathogenic bacteria based on CRISPR-Cas12a coupled with HCR.

17.
CNS Neurosci Ther ; 27(12): 1483-1492, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34605602

RESUMO

AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

18.
Curr Med Sci ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34669113

RESUMO

OBJECTIVE: The present study was designed to evaluate the effects of adjuvant chemotherapy (CT) vs. radiotherapy (RT, alone or combined with CT) on the prognosis of patients with high-risk, early-stage (stage I and stage II) endometrioid endometrial carcinoma. METHODS: This single-center retrospective clinical study was conducted in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between 2010 and 2019. In the present study, endometrioid endometrial carcinoma patients, who underwent total hysterectomy and bilateral salpingo-oophorectomy followed by postoperative adjuvant CT or RT (alone or combined with CT), and were diagnosed with stage IA grade 2/3 with lymph-vascular space invasion (LVSI), and stage IB with two or more uterine risks, including old age, histological grade 2 or 3, LVSI and stage II, were included. According to the postoperative adjuvant therapy, all eligible patients were divided into two groups: CT group and RT (RT±CT) group. The primary objective was to investigate overall survival (OS) and disease-free survival (DFS) between the CT and RT groups. Grade 3 or worse adverse events were also presented in the present study. RESULTS: A total of 145 eligible patients were included. Among these patients, 97 patients underwent adjuvant CT and 48 patients underwent adjuvant RT (RT±CT). The median follow-up was 47.2 months, and the five-year OS rate was 92.7% in the CT group and 88.6 % in the RT group [hazard ratio (HR): 0.81, 95% confidence interval (CI): 0.22-2.99). The 5-year DFS rate for the two groups was 85.7% and 80.2%, respectively (HR: 0.82, 95% CI: 0.33-2.05). The cumulative incidence of local-regional disease recurrence at 60 months of follow-up was 6.2% in the CT group and 6.3% in the RT group (HR=1.11; 95%CI: 0.28-4.35). The cumulative incidence of distant recurrence at 60 months of follow-up was 5.2% in the CT group and 10.4% in the RT group (HR=0.65; 95%CI: 0.19-2.24). Both groups of patients were well-tolerant, and the only grade 3 or worse adverse events were neutropenia and thrombocytopenia. CONCLUSION: There was no difference in efficacy for adjuvant CT or adjuvant RT (RT±CT) in high-risk, early-stage endometrioid endometrial carcinoma. CT exhibited a trend of reducing the distant relapse, although there was no significant difference, when compared with adjuvant RT (RT±CT).

19.
Toxicol Appl Pharmacol ; 432: 115753, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637808

RESUMO

T-2 toxin is a highly toxic trichothecene that can induce toxic effects in a variety of organs and tissues, but the pathogenesis of its nephrotoxicity has not been elucidated. In this study, we assessed the involvement of protein kinase RNA-like ER kinase (PERK)-mediated endoplasmic reticulum (ER) stress and apoptosis in PK-15 cells cultured at different concentrations of T-2 toxin. Cell viability, antioxidant capacity, intracellular calcium (Ca2+) content, apoptotic rate, levels of ER stress, and apoptosis-related proteins were studied. T-2 toxin inhibited cell proliferation; increased the apoptosis rate; and was accompanied by increased cleaved caspase-3 expression, altered intracellular oxidative stress marker levels, and intracellular Ca2+ overloading. The ER stress inhibitor 4-phenylbutyrate (4-PBA) and PERK selective inhibitor GSK2606414 prevented the decrease of cell activity and apoptosis caused by T-2 toxin. The altered expression of glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 proved that ER stress was involved in cell injury triggered by T-2 toxin. T-2 toxin activated the phosphorylation of PERK and the alpha subunit of eukaryotic initiation factor 2 (eIF2α) and upregulated the activating transcription factor 4 (ATF4), thereby triggering ER stress via the GRP78/PERK/CHOP signaling pathway. This study provides a new perspective for understanding the nephrotoxicity of T-2 toxin.

20.
Neurol Sci ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518934

RESUMO

OBJECTIVE: We investigated rate-dependent depression (RDD) of the Hoffman reflex (H-reflex) in patients with amyotrophic lateral sclerosis (ALS), a degenerative disease with ventral horn involvement. PATIENTS AND METHODS: In this case-control study, we enrolled 27 patients with ALS and 30 matched healthy control subjects. Clinical and electrophysiological assessments, as well as RDD in response to various stimulation frequencies (0.5 Hz, 1 Hz, 3 Hz and 5 Hz), were compared between groups. Multiple clinical and electrophysiological factors were also explored to determine any underlying associations with RDD. RESULTS: The ALS group showed a significant loss of RDD across all frequencies compared to the control group, most notably following 1 Hz stimulation (19.1 ± 20.3 vs. 34.0 ± 13.7%, p = 0.003). Among factors that might influence RDD, the enlargement of the motor unit potential (MUP) showed a significant relationship with RDD following multifactor analysis of variance (p = 0.007) and Pearson correlation analysis (ρ = - 0.70, p < 0.001), while various upper motor neuron manifestations were not correlated with RDD values (p > 0.05). CONCLUSION: We report a loss of RDD in patients with ALS. The strong correlation detected between the RDD deficit and increased MUP suggests that RDD is a sensitive indicator of underlying spinal disinhibition in ALS. TRIAL REGISTRATION: ChiCTR2000038848, 10/7/2020 (retrospectively registered), http://www.chictr.org.cn/ .

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