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1.
Chemosphere ; : 142616, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906194

RESUMO

The water accommodated fraction (WAF) of spilled crude oil is a severe threat to the health of marine fish. This study was conducted to investigate the effects of short-term embryonic exposure to the WAF on the ovarian development and reproductive capability of F0 adult female marine medaka (Oryzias melastigma). Following embryonic exposure to the WAF with nominal total petroleum hydrocarbon concentrations of 0.5, 5, 50, and 500 µg/L for 7 days, the number of spawned eggs and gonadosomatic indices of F0 adult females were significantly reduced at 130 days postfertilization. In these F0 adult females, the proportion of mature oocytes was significantly lower, the level of 17ß-estradiol was lower, and the level of testosterone was greater than those in control group. The mRNA levels of the follicle-stimulating hormone ß subunit, luteinizing hormone ß subunit, cytochrome P450 aromatase 19b, estrogen receptor α and ß, and androgen receptor α and ß genes were upregulated, while the mRNA level of the salmon-type gonadotropin-releasing hormone was downregulated in F0 adult females exposed to the WAF during the embryonic stage. Additionally, the methylation level of vitellogenin (vtg) in F0 adult females was significantly elevated, this might have, in turn, downregulated the mRNA level of vtg. The mortality rate of the unexposed F1 embryos was significantly increased and the hatching success was significantly reduced. These results collectively indicated the necessity of incorporating and evaluating the effects of short-term early-life exposure to crude oil in the assessment of risks to the reproductive health of marine fish.

2.
Chemosphere ; 359: 142297, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729443

RESUMO

The large use and emission of p-nitrophenol (p-NP) seriously pollute the environment and endanger human health. In this work, a hydrazone-linked fluorescent covalent organic framework (BATHz-COF) was simply synthesized at room temperature and covalently linked N-acetyl-L-cysteine (NALC) via the "thiol-ene" click reaction, where carboxyl groups were introduced to improve dispersion and fluorescence intensity. As a rapid, good selectivity and reusability fluorescence sensor, the obtained COF-NALC has been used for quantitative analysis of p-NP predicated on the internal filtering effect (IFE). Under optimal conditions, COF-NALC enabled quantitative detection of p-NP with a linear range of 5-50 µM and the detection limit was 1.46 µM. The application of COF-NALC to the detection of p-NP in river water samples was successful, and the satisfactory recoveries were 98.0%-109.3%. Furthermore, the fluorescent COF paper chips constructed by in situ growth were combined with a smartphone to build a visual platform for the quick and real-time detection of p-NP, providing an excellent illustration for the development of intelligent fluorescence sensing in environmental analysis.


Assuntos
Hidrazonas , Nitrofenóis , Poluentes Químicos da Água , Nitrofenóis/análise , Nitrofenóis/química , Hidrazonas/química , Poluentes Químicos da Água/análise , Cisteína/análise , Cisteína/química , Limite de Detecção , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Papel , Fluorescência , Monitoramento Ambiental/métodos , Espectrometria de Fluorescência , Rios/química
3.
Mater Today Bio ; 26: 101064, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38698883

RESUMO

Autologous nerve transplantation (ANT) is currently considered the gold standard for treating long-distance peripheral nerve defects. However, several challenges associated with ANT, such as limited availability of donors, donor site injury, mismatched nerve diameters, and local neuroma formation, remain unresolved. To address these issues comprehensively, we have developed porous poly(lactic-co-glycolic acid) (PLGA) electrospinning fiber nerve guide conduits (NGCs) that are optimized in terms of alignment and conductive coating to facilitate peripheral nerve regeneration (PNR) under electrical stimulation (ES). The physicochemical and biological properties of aligned porous PLGA fibers and poly(3,4-ethylenedioxythiophene):polystyrene sodium sulfonate (PEDOT:PSS) coatings were characterized through assessments of electrical conductivity, surface morphology, mechanical properties, hydrophilicity, and cell proliferation. Material degradation experiments demonstrated the biocompatibility in vivo of electrospinning fiber films with conductive coatings. The conductive NGCs combined with ES effectively facilitated nerve regeneration. The designed porous aligned NGCs with conductive coatings exhibited suitable physicochemical properties and excellent biocompatibility, thereby significantly enhancing PNR when combined with ES. This combination of porous aligned NGCs with conductive coatings and ES holds great promise for applications in the field of PNR.

4.
Adv Sci (Weinh) ; : e2400426, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666466

RESUMO

Adaptive metabolic responses and innate metabolites hold promising therapeutic potential for stroke, while targeted interventions require a thorough understanding of underlying mechanisms. Adiposity is a noted modifiable metabolic risk factor for stroke, and recent research suggests that it benefits neurological rehabilitation. During the early phase of experimental stroke, the lipidomic results showed that fat depots underwent pronounced lipolysis and released fatty acids (FAs) that feed into consequent hepatic FA oxidation and ketogenesis. Systemic supplementation with the predominant ketone beta-hydroxybutyrate (BHB) is found to exert discernible effects on preserving blood-brain barrier (BBB) integrity and facilitating neuroinflammation resolution. Meanwhile, blocking FAO-ketogenesis processes by administration of CPT1α antagonist or shRNA targeting HMGCS2 exacerbated endothelial damage and aggravated stroke severity, whereas BHB supplementation blunted these injuries. Mechanistically, it is unveiled that BHB infusion is taken up by monocarboxylic acid transporter 1 (MCT1) specifically expressed in cerebral endothelium and upregulated the expression of tight junction protein ZO-1 by enhancing local ß-hydroxybutyrylation of H3K9 at the promoter of TJP1 gene. Conclusively, an adaptive metabolic mechanism is elucidated by which acute lipolysis stimulates FAO-ketogenesis processes to restore BBB integrity after stroke. Ketogenesis functions as an early metabolic responder to restrain stroke progression, providing novel prospectives for clinical translation.

5.
Cancer Manag Res ; 16: 73-86, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318097

RESUMO

Objective: Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and tolerability of anlotinib plus PD-1 blockades in patients with treatment-refractory metastatic CRC retrospectively. Methods: A total of 68 patients with previously treated metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in this study retrospectively. Demographic and clinical characteristics of the patients, therapeutic outcomes and safety profile during administration were collected and briefly analyzed. All subjects were followed up regularly. Therapeutic outcomes, including drug response and prognosis, were presented, and a safety profile was depicted to illustrate the adverse reactions. Results: A total of 68 patients with treatment-refractory metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in the final analysis. Best therapeutic response during treatment indicated that partial response was observed in 11 patients, stable disease was noted in 41 patients, and progressive disease was found in 16 patients, producing an objective response rate of 16.2% (95% CI: 8.4%-27.1%) and a disease control rate of 76.5% (95% CI: 64.6%-85.9%). Prognostic analysis suggested that the median progression-free survival (PFS) of the 68 patients was 5.3 months (95% CI: 3.01-7.59), and the median overall survival (OS) was 12.5 months (95% CI: 9.40-15.60). Of the 11 patients who responded, the median duration of response was 6.7 months (95% CI: 2.89-10.53). Safety profile during treatment showed that patients experienced adverse reactions regardless of grade, and grade ≥3 adverse reactions were found in 61 patients (89.7%) and 41 patients (60.3%), respectively. Common adverse reactions were hypertension, myelosuppression (including leukopenia, neutropenia, thrombocytopenia, and anemia), fatigue, and hand-foot syndrome. Conclusion: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and acceptable safety profile in patients with treatment-refractory metastatic CRC preliminarily in clinical practice. This conclusion should be confirmed in prospective clinical trials.

7.
J Cancer ; 15(6): 1642-1656, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370372

RESUMO

Fragments derived from tRNA, called tRNA-derived small RNAs (tsRNAs), have attracted widespread attention in the past decade. tsRNAs are widespread in prokaryotic and eukaryotic transcriptome, which contains two main types, tRNA-derived fragments (tRFs) and tRNA-derived stress-inducing RNA (tiRNAs), derived from the precursor tRNAs or mature tRNAs. According to differences in the cleavage position, tRFs can be divided into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF, whereas tiRNAs can be divided into 5'-tiRNA and 3'-tiRNA. Studies have found that tRFs and tiRNAs are abnormally expressed in a variety of human malignant tumors, promote or inhibit the proliferation and apoptosis of cancer cells by regulating the expression of oncogene, and play an important role in the aggressive metastasis and progression of tumors. This article reviews the biological origins of various tsRNAs, introduces their functions and new concepts of related mechanisms, and focuses on the molecular mechanisms of tsRNAs in cancer, including breast cancer, prostate cancer, colorectal cancer, lung cancer, b-cell lymphoma, and chronic lymphoma cell leukemia. Lastly, this article puts forward some unresolved problems and future research prospects.

8.
Chemistry ; 30(15): e202303827, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38183168

RESUMO

The stable Pepsin@covalent organic framework (Pepsin@COF) were constructed base on matching COF pore diameter to pepsin dimension. It exhibits excellent chiral recognition capabilities (e. e. % up to 62.63 %) and potential for enantioseparation. Furthermore, a positive correlation between the immobilized enzyme activity and chiral recognition was revealed, offering insights for the design of biocatalytic nanosystems in chiral separation.

9.
Bioorg Med Chem Lett ; 97: 129564, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38000482

RESUMO

The aggregation of α-Syn is a pivotal mechanism in Parkinson's disease (PD). Effectively maintaining α-Syn proteostasis involves both inhibiting its aggregation and promoting disaggregation. In this study, we developed a series of aromatic amide derivatives based on Rhein. Two of these compounds, 4,5-dihydroxy-N-(3-hydroxyphenyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (a5) and 4,5-dihydroxy-N-(2-hydroxy-4-chlorophenyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (a8), exhibited good binding affinities to α-Syn residues, demonstrating promising inhibitory activity against α-Syn aggregation in vitro, with low IC50 values (1.35 and 1.08 µM, respectivly). These inhibitors acted throughout the entire aggregation process by stabilizing α-Syn's conformation and preventing the formation of ß-sheet aggregates. They also effectively disassembled preformed α-Syn oligomers and fibrils. Preliminary mechanistic insights indicated that they bound to the specific domain within fibrils, inducing fibril instability, collapse, and the formation of smaller aggregates and monomeric α-Syn units. This research underscores the therapeutic potential of Rhein's aromatic amides in targeting α-Syn aggregation for PD treatment and suggests broader applications in managing and preventing neurodegenerative diseases.


Assuntos
Antracenos , Doença de Parkinson , Humanos , alfa-Sinucleína , Antraquinonas/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Doença de Parkinson/metabolismo , Antracenos/química , Antracenos/farmacologia
10.
Insect Sci ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37969037

RESUMO

Sex pheromones are considered to play critical roles in partner communication of most parasitic Hymenoptera. However, the identification of sex pheromone components remains limited to a few families of parasitoid wasps. In this study, we functionally characterized a candidate sex pheromone component in Microplitis mediator (Hymenoptera: Braconidae), a solitary parasitoid of Noctuidae insects. We found that the body surface extract from female wasps could significantly stimulate courtship behavior of males. Gas chromatography-electroantennographic detection (GC-EAD) analysis revealed that a candidate semiochemical from extract triggered significant electrophysiological response of antennae of males. By performing gas chromatography-mass spectrometer (GC-MS) measurement, GC-EAD active compound was identified as n-octyl acrylate, a candidate sex pheromone component in female M. mediator. In electroantennogram (EAG) tests, antennae of male wasps showed significantly higher electrophysiological responses to n-octyl acrylate than those of females. Y-tube olfactometer assays indicated that male wasps significantly chose n-octyl acrylate compared with the control. Furthermore, male wasps showed a remarkable preference for n-octyl acrylate in a simulated field condition behavioral trial; simultaneously, n-octyl acrylate standard could also trigger significant courtship behavior in males. We propose that n-octyl acrylate, as a candidate vital sex pheromone component, could be utilized to design behavioral regulators of M. mediator to implement the protection and utilization of natural enemies.

11.
Bioorg Med Chem ; 96: 117529, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37976808

RESUMO

This study focuses on the misfolding and aggregation of α-Syn as a central mechanism linking various pathological processes in PD. Maintaining α-Syn proteostasis through suitable inhibitors emerges as an effective approach to prevent PD. A more efficient strategy for PD treatment involves disintegrating neurotoxic oligomers and fibrils into normal functional α-Syn using inhibitors. To this end, a series of 4-arylidene curcumin derivatives were synthesized with a sheet-like conjugated skeleton and higher binding energies with α-Syn residues. Among these derivatives, three candidate compounds exhibited promising α-Syn aggregation inhibitory activities in vitro, with IC50 values as low as 0.61 µM. The inhibitory action extended throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation and preventing ß-sheets aggregation. Furthermore, the candidate compounds demonstrated effective disintegration capabilities against preformed α-Syn oligomers and fibrils. Initial mechanistic investigations indicated that the inhibitors may bind to a specific domain within the fibril, inducing fibril instability and subsequent collapse. This process resulted in the formation of a complex system of aggregates with smaller sizes and monomers. Overall, these findings provide valuable insights into the potential of 4-arylidene curcumin derivatives as therapeutic agents for targeting α-Syn aggregation in PD treatment.


Assuntos
Curcumina , alfa-Sinucleína , alfa-Sinucleína/metabolismo , Curcumina/farmacologia , Ligação Proteica , Amiloide/metabolismo , Agregados Proteicos
12.
Rev Sci Instrum ; 94(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37862524

RESUMO

A resonant screw-driven piezoelectric motor operating in single-mode vibrations is proposed, designed, manufactured, and studied. The motor is constructed with a stator and a threaded rotor. The stator consists of a hollow parallelogram metal elastomer and two piezoelectric ceramic plates. The motor is excited by a single-phase signal to produce two separate vibration modes: the first expansion mode (B1 mode) and the second expansion mode (B2 mode). Each mode drives the threaded rotor in one direction, and the bidirectional motion is achieved by switching the two modes. The construction is designed, and modal simulation is performed using finite element software to determine the structural parameters. A frequency-domain analysis is performed to obtain the frequency response characteristics, and the motion trajectories of the stator are obtained using transient analysis. Finally, a prototype is produced, and experiments are conducted. Experimental results indicate that the no-load speeds of the motor under the 200 Vp-p voltage excitation are 1.67 and 1.04 mm/s in the two modes, which correspond to maximum loads of 35 and 20 mN, respectively.

13.
Artigo em Inglês | MEDLINE | ID: mdl-37883193

RESUMO

The development of a self-calibrating ratio fluorescence probe without the need for additional substrates is a major advancement in biosensing. In this study, at room temperature, a self-calibrating infinite coordination polymer (SSA-Tb-ATP ICPs) has been proposed by self-assembling adenosine triphosphate (ATP) with 5-sulfosalicylic acid (SSA) and Tb3+. Due to the antenna effect, SSA-Tb-ATP ICPs exhibited strong green fluorescence emission of Tb3+ (at 547 nm) and blue fluorescence emission of SSA (at 407 nm). This material offers several advantages over existing detection methods, including simplicity of synthesis and exceptional sensitivity. Our self-calibrating SSA-Tb-ATP ICPs demonstrated excellent performance in detecting alkaline phosphatase (ALP) and phosphate (Pi) in both serum and environmental samples with detection limits of 0.076 U/L and 0.025 µM, respectively. Moreover, we successfully employed the SSA-Tb-ATP ICPs to perform cellular imaging of ALP in both hepatocellular carcinoma cells (HepG2) and normal liver cells (LO2), representing a significant advancement in ALP detection and imaging. The simplicity of the synthesis and high sensitivity make this probe a promising tool for early diagnosis of hepatocellular carcinoma in clinical settings and environment analysis.

14.
Rev Sci Instrum ; 94(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37737702

RESUMO

Uncertainty evaluation for unknown distribution data is a key problem to be solved in uncertainty evaluation theory. To evaluate the measurement uncertainty of data with unknown distributions, a novel uncertainty evaluation method based on the particle filter (PF) and beta distribution is proposed in this paper. A beta distribution with wide adaptability was adopted as the distribution type of measurement results, the parameters of the beta distribution were taken as the parameters to be estimated, and a state-space model was established. The PF method, suitable for non-Gaussian data, was utilized to obtain the estimates of the parameters of the beta distribution according to the measurement results. Finally, the best estimates of the measurement results and their uncertainty were calculated using the beta distribution parameters. Simulation results show that the proposed method is adaptive to accurately evaluate the measurement uncertainties of data, especially for non-Gaussian distribution data or asymmetrically distributed data. Multiple evaluation results show that the method has good robustness. The experimental results for the drift errors of a laser interferometer show that the uncertainty result of the proposed method is consistent with the Monte Carlo method. This method is suitable for a variety of distribution types that can be characterized through beta distribution and can solve the optimal estimation and uncertainty evaluation of most measurement results with unknown distribution types.

15.
BMC Cardiovasc Disord ; 23(1): 423, 2023 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-37635204

RESUMO

BACKGROUND: It has been reported that there are sex differences in plaque composition and hemodynamically significant stenosis. This study aimed to explore the impact of sex on cardiovascular risk factors for specific plaque compositions and hemodynamically significant stenosis. METHODS: Data regarding demographics and cardiovascular risk factors were collected. Hemodynamically significant stenosis was identified by a computed tomography-derived fractional flow reserve of ≤ 0.8. Associations among cardiovascular risk factors, plaque composition, and hemodynamically significant stenosis were assessed using a multivariate binary logistic regression analysis across sexes. The discriminating capacity of diverse plaque components for hemodynamically significant stenosis was assessed by area under the receiver-operating characteristics curve with 95% confidence intervals. RESULTS: A total of 1164 patients (489 men and 675 women) were included. For men, hyperlipidemia and cigarette smoking were risk factors for each plaque component (all P < 0.05), and diabetes mellitus also predicted fibrotic components (P < 0.05). For women, risk factors for each plaque component were hypertension and diabetes mellitus (all P < 0.01). Nonetheless, hyperlipidemia (P < 0.05) was a specific risk factor for non-calcified components. Calcified components combined with fibrotic components showed superior discrimination of hemodynamically significant stenosis in men and calcified components alone in women (all P < 0.01). Hypertension (P < 0.01) was a risk factor for hemodynamically significant stenosis in women. In contrast, diabetes, hyperlipidemia, and cigarette smoking were risk factors for hemodynamically significant stenosis in men (all P < 0.05). CONCLUSIONS: In men, hemodynamically significant stenosis was predicted by a combination of calcified and fibrotic components with multiple risk factors. In women, hemodynamically significant stenosis was predicted by calcified components caused by a single risk factor. It might be a key point to improve prognosis by more precise risk management between men and women, which needs to be proved by further prospective trials.


Assuntos
Doenças Cardiovasculares , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Hipertensão , Feminino , Humanos , Masculino , Angiografia por Tomografia Computadorizada , Constrição Patológica , Fatores de Risco , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologia , Fatores de Risco de Doenças Cardíacas , Hipertensão/complicações , Hipertensão/epidemiologia
16.
Nutrients ; 15(15)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37571425

RESUMO

This study focused on the development and validation of a nutrition literacy assessment instrument for Chinese lactating women (NLAI-L). A comprehensive literature review and group discussion by experts in relevant fields were adopted to determine the dimension, topics and questions of NLAI-L. Content validity was evaluated by a panel of experts. The exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were used to evaluate the construct validity. Cronbach's α and split-half reliability were applied to examine the reliability of NLAI-L. The final NLAI-L consisted of 38 questions covering three dimensions: knowledge, behavior and skill. The EFA revealed four sub-domains for knowledge, one sub-domain for behavior and four sub-domains for skill. The results showed that NLAI-L had satisfactory content validity (CVI = 0.98, CVR = 0.96), good reliability (Cronbach's α coefficient = 0.84) and acceptable construct validity (χ2/df = 2.28, GFI = 2.81, AGFI = 0.79, RMSEA = 0.057). In the application part, the average NL score was 46.0 ± 9.3. In multivariate linear regression, education level, age, postnatal period and occupation were the potential influencing factors of NL for Chinese lactating women. The study established an effective and reliable assessment instrument for Chinese lactating women (NLAI-L) through qualitative and quantitative methods. The establishment of NLAI-L will provide an effective tool for exploring the role of NL in health or disease and provide a basis for the formulation of targeted nutrition interventions.


Assuntos
População do Leste Asiático , Letramento em Saúde , Inquéritos Nutricionais , Feminino , Humanos , Lactação , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários
17.
Biosens Bioelectron ; 238: 115576, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37557027

RESUMO

Compared with single signal readout, dual-signal readout commendably corrects the impact of systematic or background error, achieving more accurate results for the diagnosis of many diseases. This work aimed to design and prepare dual-emissive fluorescent probes for the construction of ratiometric fluorescence biosensors to detect liver disease biomarkers. Sodium alginate (SA) with numerous potential sub-fluorophores and active sites and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP) with macrocyclic conjugated structures were introduced to prepare the carbonized polymer dots (CPDs) with red/blue dual emission based on the cross-linking enhanced emission (CEE) effect and the luminescence of macrocyclic conjugated structures. The ratiometric fluorescence sensing systems were constructed by integrating the specific response of CPDs to Cu2+ and the affinity difference of Cu2+ to substrates or products of enzymes. The sensing systems, CPDs/Cu2+/PPi and CPDs/Cu2+/BTCh, were designed to detect liver disease biomarkers, alkaline phosphatase (ALP) and butyrylcholinesterase (BChE), respectively. The limit of detection for ALP and BChE was 0.35 U/L and 0.19 U/L, respectively. The proposed sensors were successfully applied to human serum samples from different health stages with satisfactory recoveries. These results demonstrate the successful design of a novel dual-emissive fluorescent probe and provide a feasible strategy for clinical detection.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Humanos , Butirilcolinesterase , Polímeros/química , Fosfatase Alcalina/química , Corantes Fluorescentes/química , Pontos Quânticos/química
18.
Cell Biol Int ; 47(11): 1854-1867, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37493437

RESUMO

Breast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being the leading cause of death. Tn antigen, a tumor-associated carbohydrate antigen, was frequently detected in breast cancer, but its exact role in breast cancer metastasis has not been well elucidated. Here we investigated the impact of Tn antigen expression on breast cancer metastasis and its underlying mechanisms. The expression of Tn antigen was induced in two breast cancer cell lines by deleting T-synthase or Cosmc, both of which are required for normal O-glycosylation. It showed that Tn-expressing cancer cells promoted epithelial-mesenchymal transition (EMT) and metastatic features as compared to Tn(-) control cells both in vitro and in vivo. Mechanistically, we found that cancer susceptibility candidate 4 (CASC4), a heavily O-glycosylated protein, was significantly downregulated in both Tn(+) cells. Overexpression of CASC4 suppressed Tn-induced activation of EMT and cancer metastasis via inhibition of Cdc42 signaling. Furthermore, we confirmed that O-glycosylation is essential for the functional role of CASC4 because defective O-glycosylated CASC4 (mutant CASC4, which lacks nine O-glycosylation sites) exerted marginal metastatic-suppressing effects in comparison with WT CASC4. Collectively, these data suggest that Tn-mediated aberrant O-glycosylation contributes to breast cancer metastasis via impairment of CASC4 expression and function.


Assuntos
Neoplasias da Mama , Chaperonas Moleculares , Feminino , Humanos , Antígenos Glicosídicos Associados a Tumores/metabolismo , Linhagem Celular Tumoral , Proteínas de Membrana/metabolismo , Melanoma Maligno Cutâneo
19.
Front Oncol ; 13: 1165437, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313468

RESUMO

Objective: Fondaparinux is a synthetic anticoagulant for the prevention of venous thromboembolism (VTE), and its administration in Chinese cancer patients is rarely reported. This study aimed to assess the efficacy and safety of fondaparinux in preventing VTE in Chinese cancer patients. Methods: A total of 224 cancer patients who received fondaparinux treatment were reviewed in this single-arm, multicenter, retrospective study. Meanwhile, VTE, bleeding, death, and adverse events of those patients in the hospital and at 1 month after treatment (M1) were retrieved, respectively. Results: The in-hospital VTE rate was 0.45% and there was no (0.00%) VTE occurrence at M1. The in-hospital bleeding rate was 2.68%, among which the major bleeding rate was 2.23% and the minor bleeding rate was 0.45%. Moreover, the bleeding rate at M1 was 0.90%, among which both the major and minor bleeding rates were 0.45%. The in-hospital death rate was 0.45% and the death rate at M1 was 0.90%. Furthermore, the total rate of adverse events was 14.73%, including nausea and vomiting (3.13%), gastrointestinal reactions (2.23%), and reduced white blood cells (1.34%). Conclusion: Fondaparinux could effectively prevent VTE with low bleeding risk and acceptable tolerance in cancer patients.

20.
ACS Appl Mater Interfaces ; 15(22): 27214-27222, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37236148

RESUMO

Chiral covalent organic frameworks (CCOFs) benefit from superior stability, abundant chiral environment, and homogeneous pore configuration. In its constructive tactics, only the post-modification method allows for the integration of supramolecular chiral selectors into achiral COFs. Here, the finding utilizes 6-deoxy-6-mercapto-ß-cyclodextrin (SH-ß-CD) as chiral subunits and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde (DVA) as the platform molecule to synthesize chiral functional monomers through thiol-ene click reactions and directly establish ternary "pendant-type" SH-ß-CD COFs. The chiral site density on SH-ß-CD COFs was regulated by changing the proportion of chiral monomers to obtain an optimal construction strategy and remarkably improve the ability of chiral separation. SH-ß-CD COFs were coated on the inner wall of the capillary in a covalently bound manner. The prepared open tubular capillary was achieved for the separation of six chiral drugs. By combining the outcomes of selective adsorption and chromatographic separation, we observed the higher density of chiral sites in the CCOFs, and poorer results were achieved. From the perspective of spatial conformational distribution, we interpret the variation in the performance of these chirality-controlled CCOFs for selective adsorption and chiral separation.

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