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1.
Artigo em Inglês | MEDLINE | ID: mdl-36700644

RESUMO

Better understanding of important roles of metabolic reprogramming in therapeutic resistance provides insights into advancing cancer treatment. Herein, we present a photoactive metabolic reprogramming strategy (termed as photometabolism therapy, PMT), in which photoregulation of mitochondria leads to cancer cell metabolic crisis, and consequently overcomes therapeutic resistance while improving treatment efficacy. In specific, a stimuli-responsive metabolism NanoValve is developed for improving cascade cancer therapy through blocking mitochondrial energy supply. NanoValve is composed of an onion-like architecture with a gold nanorod core, a mesoporous silica shell encapsulating photosensitizer chlorin e6 and oxygen-saturated perfluorocarbon, and cationic liposomal coating with MMP2-cleavable polyethylene glycol corona, which together initiate mitochondria-specific PMT. NanoValve selectively responds to tumor-overexpressed MMP2 and achieves size decrease and charge reversal, which consequently enhances tumor penetration, cancer cell uptake, endosome escape, and most critically, mitochondrial accumulation. Importantly, NanoValve-mediated phototherapy can strongly destruct mitochondrial energy metabolism, thereby minimizing therapy resistance. Particularly, perfluorocarbon supplies oxygen to further overcome the tumor hypoxia-associated therapeutic barrier and maximizes synergistic anticancer effects. In vivo studies show that NanoValve can effectively eliminate tumors without side effects, thereby dramatically prolonging the survival of tumor-bearing mice. Thus, NanoValve provides a modular PMT approach and has the potential of advancing the treatment of malignancy.

2.
Eur J Intern Med ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36710136

RESUMO

BACKGROUND: Deep-sedated colonoscopy with propofol is widely used in China. However, its impact on quality metrics remains controversial. We aimed to investigate the effects of deep-sedated colonoscopy on missed adenomas, specifically in each colorectal segment. METHODS: Data of 3710 individuals from seven hospitals in China who underwent an initial colonoscopy with or without propofol sedation and a second colonoscopy without sedation within six months for surveillance or polypectomy by endoscopist of the same level between October 2020 and September 2021 were retrospectively analyzed. RESULTS: A total of 1113 missed adenomas in 3710 patients were evaluated. The adenoma miss rate (AMR) was significantly higher in deep-sedated colonoscopy than in unsedated colonoscop [19.14% (578/3020) vs. 16.15% (535/3313), P < 0.05]. The risk of missing adenomas in deep-sedated colonoscopy was 1.229 times higher than in unsedated colonoscopy (OR, 1.229; 95% CI: 1.080-1.399). AMRs of the splenic flexure (26.02% [96/369] vs. 16.04% [47/293], P < 0.05) and descending colon (20.86% [102/489] vs. 13.37% [54/404], P < 0.05) were significantly higher in deep-sedated colonoscopy than in unsedated colonoscopy when performed by middle-level endoscopists rather than high-level endoscopists (P < 0.05). CONCLUSIONS: AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy. Furthermore, adenomas in the splenic flexure and descending colon were more frequently missed in deep-sedated colonoscopy than in unsedated colonoscopy, particularly when performed by less experienced endoscopists.

3.
Biomed Res Int ; 2023: 7407772, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36714023

RESUMO

Iris bulleyana Dykes (Southwest iris) is an extensively distributed Iridaceae species with blue or white flowers. Hereby, we performed a systematic study, employing metabolomics and transcriptomics to uncover the subtle color differentiation from blue to white in Southwest iris. Fresh flower buds from both cultivars were subjected to flavonoid/anthocyanin and carotenoid-targeted metabolomics along with transcriptomic sequencing. Among 297 flavonoids, 24 anthocyanins were identified, and 13 showed a strong down-accumulation pattern in the white flowers compared to the blue flowers. Significant downregulation of 3GT and 5GT genes involved in the glycosylation of anthocyanins was predicted to hinder the accumulation of anthocyanins, resulting in white coloration. Besides, no significant altered accumulation of carotenoids and expression of their biosynthetic genes was observed between the two cultivars. Our study systematically addressed the color differentiation in I. bulleyana flowers, which can aid future breeding programs.


Assuntos
Iris (Planta) , Iris (Planta)/genética , Iris (Planta)/metabolismo , Antocianinas/genética , Melhoramento Vegetal , Perfilação da Expressão Gênica , Flavonoides/metabolismo , Carotenoides/metabolismo , Flores/genética , Flores/metabolismo , Cor , Pigmentação/genética , Transcriptoma/genética , Regulação da Expressão Gênica de Plantas/genética
4.
J Thorac Oncol ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36646210

RESUMO

INTRODUCTION: In CameL phase 3 study (ClinicalTrials.gov, NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stage IIIB-IV non-squamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization. METHODS: Eligible patients were randomized 1:1 to 4-6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n=205 and 207, respectively). Total camrelizumab exposure was up to 2 years. RESULTS: As of January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio, 0.72 [95% CI, 0.57-0.92]). In the chemotherapy alone group, 95 (45.9%) patients crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio, 0.55 [95% CI, 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%); and 93.9% (31/33) of patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab. CONCLUSIONS: Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity, as well as remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced non-squamous NSCLC.

5.
Cell Metab ; 35(1): 101-117.e11, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36525963

RESUMO

sn-1,2-diacylglycerol (sn-1,2-DAG)-mediated activation of protein kinase Cε (PKCε) is a key pathway that is responsible for obesity-related lipid metabolism disorders, which induces hepatic insulin resistance and type 2 diabetes. No small molecules have been previously reported to ameliorate these diseases through this pathway. Here, we screened and identified the phytochemical atractylenolide II (AT II) that reduces the hepatic sn-1,2-DAG levels, deactivates PKCε activity, and improves obesity-induced hyperlipidemia, hepatosteatosis, and insulin resistance. Furthermore, using the ABPP strategy, the diacylglycerol kinase family member DGKQ was identified as a direct target of AT II. AT II may act on a novel drug-binding pocket in the CRD and PH domains of DGKQ to thereby allosterically regulate its kinase activity. Moreover, AT II also increases weight loss by activating DGKQ-AMPK-PGC1α-UCP-1 signaling in adipose tissue. These findings suggest that AT II is a promising lead compound to improve obesity-induced insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Proteína Quinase C-épsilon/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diglicerídeos/metabolismo , Obesidade/tratamento farmacológico
6.
BMC Ophthalmol ; 22(1): 519, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585663

RESUMO

BACKGROUND: The aim of this study is to investigate the prevalence of myopia and high myopia and the associated risk factors in key schools in Xi'an, China. METHODS: This cross-sectional study started in September 2021 and was conducted for one month. A total of 11,011 students from 10 key primary schools, five key junior high schools and five key high schools in Xi'an were randomly selected to undergo visual acuity measurement and non-cycloplegic autorefraction. The questionnaire was completed by the students and their parents together. RESULTS: The prevalence of myopia and high myopia in key schools were 75.7% and 9.7%, respectively. The prevalence of myopia and high myopia rose significantly as grade or age increased (all P < 0.001), and the prevalence of myopia and high myopia in females was higher than that in males (P < 0.001, P < 0.5). According to the multivariable logistic regression analysis, older age (OR=1.42), female compared with male (OR=1.43), having one myopic parent (OR=1.64), having two myopic parent (OR=2.30) and often taking extracurricular tuition (OR=1.35) were more likely to be associated with develop myopia (P < 0.001). Older age (OR=1.39), having one myopic parent (OR=2.29), having two myopic parent (OR= 3.69), and often taking extracurricular tuition (OR=1.48) were more likely to be associated with high myopia (P < 0.001). CONCLUSIONS: The overall rate of myopia and high myopia in key schools in Xi'an, China, is extremely high. Myopia and high myopia are associated with increasing age, parents' myopia, few outdoor exercises, and extracurricular tuition. Myopia is also associated with female and not having the habit of "one punch, one foot, one inch (when reading and writing, 10 cm from the chest to the table, 33 cm from the eye to the book and 3.3 cm from the tip of the pen to the finger)".


Assuntos
Miopia , Humanos , Masculino , Feminino , Prevalência , Estudos Transversais , Miopia/epidemiologia , China/epidemiologia , Inquéritos e Questionários , Fatores de Risco , Instituições Acadêmicas , Refração Ocular
8.
Neural Netw ; 157: 240-256, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36399979

RESUMO

Time series forecasting models that use the past information of exogenous or endogenous sequences to forecast future series play an important role in the real world because most real-world time series datasets are rich in time-dependent information. Most conventional prediction models for time series datasets are time-consuming and fraught with complex limitations because they usually fail to adequately exploit the latent spatial dependence between pairs of variables. As a successful variant of recurrent neural networks, the long short-term memory network (LSTM) has been demonstrated to have stronger nonlinear dynamics to store sequential data than traditional machine learning models. Nevertheless, the common shallow LSTM architecture has limited capacity to fully extract the transient characteristics of long interval sequential datasets. In this study, a novel deep autoregression feature augmented bidirectional LSTM network (DAFA-BiLSTM) is proposed as a new deep BiLSTM architecture for time series prediction. Initially, the input vectors are fed into a vector autoregression (VA) transformation module to represent the time-delayed linear and nonlinear properties of the input signals in an unsupervised way. Then, the learned nonlinear combination vectors of VA are progressively fed into different layers of BiLSTM and the output of the previous BiLSTM module is also concatenated with the time-delayed linear vectors of the VA as an augmented feature to form new additional input signals for the next adjacent BiLSTM layer. Extensive real-world time series applications are addressed to demonstrate the superiority and robustness of the proposed DAFA-BiLSTM. Comparative experimental results and statistical analysis show that the proposed DAFA-BiLSTM has good adaptive performance as well as robustness even in noisy environment.

9.
Int J Biol Macromol ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36395943

RESUMO

Novel resources of very small granular starch are of great interests to food scientists. We previously found Chlorella sp. MBFJNU-17 contained small granular starch but whether the MBFJNU-17 was a novel resource of very small granular starch remained unresolved. This study isolated and characterized the starch from MBFJNU-17 in comparison with quinoa starch (a typical very small granular starch), and discussed whether the MBFJNU-17 could be a resource of very small granular starch. Results showed that chlorella starch displayed a smaller size (1024 nm) than quinoa starch did (1107 nm), suggesting MBFJNU-17 was a good resource of very small granular starch. Additionally, chlorella starch had less amylose, higher proportion of long amylopectin branches, more ordered structures, thinner amorphous lamellae, better paste thermostability, and slower enzymatic digestion than quinoa starch did. These findings indicated that Chlorella sp. MBFJNU-17 was a novel resource of very small granular starch with desirable thermostability and nutritional attributes.

10.
Cancer Commun (Lond) ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36331328

RESUMO

BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy. METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group. CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

11.
Mar Drugs ; 20(11)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36421987

RESUMO

A novel approach to producing high-purity fucoxanthinol (FXOH) was exploited as a sustainable method to maximize fucoxanthin (FX) utilization. Through fusing the genes of cholesterol esterase and SpyTag and then expressing them in Escherichia coli, the fusion chimera was self-assembled into insoluble active aggregates by SpyTag, which could be regarded as carrier-free immobilization. The immobilization yield of the active cholesterol esterase aggregates could reach 60%. They have expressed good activity retention at 92.48% and 60.13% after 3 and 12 cycles, respectively, which is an exciting finding. The conversion ratio of FX to FXOH is 95.02%, which is remarkably higher than those realized via the conventional chemical reduction method (55.86%) and the enzymatic hydrolysis method by free cholesterol esterases (84.51%). The purity of FXOH obtained by this method is as high as 98%, which is much higher than those obtained by other methods. Thus, a promising method for simultaneously purifying and immobilizing active cholesterol esterase aggregates is demonstrated in this study by SpyTag tailoring. In addition, this study provides an eco-friendly method for producing high-purity FXOH from FX in a highly efficient manner.


Assuntos
Esterol Esterase , beta Caroteno , Esterol Esterase/genética , Xantofilas
12.
Sci Rep ; 12(1): 16637, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198714

RESUMO

Palmitoleic acid, a monounsaturated fatty acid which could affect glucose and lipid metabolism and reduce insulin resistance has two isomers, i.e. cis-palmitoleic acid (cPOA) and trans-palmitoleic acid (tPOA). However, the pharmacokinetic, metabolic transformation and structure-activity relationship of the two isomers have not been reported. A precise and accurate ultra performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed to determine cPOA and tPOA simultaneously. Both the cPOA and tPOA were administered i.g. (intragastric gavage) to rats at 75 mg/kg. Serum samples were collected and analyzed for the two isomers by UPLC-MS/MS on a reverse-phase BDS C18 column equilibrated and eluted with water (A) and acetonitrile (B) at a flow rate of 0.3 mL/min. The calibration curves for cPOA and tPOA were linear over the range 0.1-12 µg/mL. Analytes were monitored by selected-reaction monitoring in negative electrospray ionization mode. The Tmax of cPOA was 0.94 ± 0.44 h and the Cmax 8.17 ± 1.97 µg/L, and the Tmax and Cmax of tPOA were 1.50 ± 0.98 h and 14.77 ± 11.91 µg/L, respectively. AUC0-24 h of cPOA and tPOA were 59.45 ± 29.83 and 113.88 ± 72.25 mg/L·h. The method was applied in pharmacokinetic study of cPOA and tPOA in rat serum successfully. Besides, the concentrations of cPOA and tPOA in rat serums were observed fluctuating with a consistent trend, which may be due to reciprocal bio-convert in the body.


Assuntos
Ácidos Graxos Monoinsaturados , Espectrometria de Massas em Tandem , Acetonitrilas , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Glucose , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Água
13.
Sci Rep ; 12(1): 15356, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097050

RESUMO

To investigate if deep-sedated colonoscopy affects adenoma detection in certain colorectal segment. Review of colonoscopy reports, electronic images and medical records of individuals underwent screening colonoscopy with or without propofol sedation between October 2020 and March 2021 from seven hospitals in China. A total of 4500 individuals were analyzed. There was no significant difference in ADR between deep-sedated colonoscopy and unsedated colonoscopy [45.4% vs. 46.3%, P > 0.05]. The APP of deep-sedated colonoscopy was lower than unsedated colonoscopy (1.76 ± 0.81 vs. 2.00 ± 1.30, P < 0.05). Both average number of adenomas and luminal distention score of splenic flexure and descending colon were lower in deep-sedated colonoscopy (P < 0.05), and average number of adenomas was positively correlated with an improved distension score in splenic flexure and descending colon (splenic flexure r = 0.031, P < 0.05; descending colon r = 0.312, P < 0.05). Linear regression model showed deep-sedated colonoscopy significantly affected luminal distention of splenic flexure and descending colon as well as average number of adenomas detected in splenic flexure (P < 0.05). Deep-sedated colonoscopy decreased adenoma detection in splenic flexure and the luminal distention of splenic flexure and descending colon compared with unsedated colonoscopy.


Assuntos
Adenoma , Neoplasias Colorretais , Propofol , Adenoma/diagnóstico por imagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Programas de Rastreamento/métodos
14.
Front Microbiol ; 13: 913465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147851

RESUMO

Many studies demonstrated that Zhenwu decoction (ZWD) is effective in the treatment of kidney fibrosis, whereas the mechanism remains unclear. In this work, a microbiomics-based strategy was used to investigate the mechanism of protective effects of ZWD on kidney fibrosis. Unilateral ureteral obstruction was used to replicate a rat model of renal fibrosis, and rats were divided into prophylactic, early, and progression stages according to the timing of administration. Feces was collected to perform microbiota evaluation by high-throughput 16S DNA sequencing. The results indicated that Corynebacterium, Alistipes, Dorea, and Lactonifactor were highlighted as key targeted flora of ZWD in the treatment of renal fibrosis, and their biological functions were related to inflammation, immunity, and renal excretion. Especially, Corynebacterium presented a significant positive correlation with the concentration of Cys-C, Scr, and BUN. The studies on the changes in inflammatory cytokines (INF-γ, IL-1ß, IL-4, and TNF-α) and immunoglobulin (IgA, IgM, and IgG) confirmed the beneficial effects of ZWD on kidney fibrosis. Therefore, this study confirmed the protective effect of ZWD against renal fibrosis at various disease stages, and its mechanism was associated with re-establishing dysbiosis of the intestinal microbiota, reducing inflammation, as well as regulating immune functions. In particular, Corynebacterium may be a key flora in the treatment of renal fibrosis.

15.
Front Genet ; 13: 926546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072667

RESUMO

This study comprehensively explored the clinical function of Aurora kinase A (AURKA) gene in nasopharyngeal carcinoma (NPC) and analyzed its potential as a therapeutic target in cancer. Data were downloaded from GEO, STRING, GTEx, and CellMiner databases, and subjected to multiple bioinformatic analyses, including differential expression analysis, WCGNA, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), miRNA-hub gene regulatory network analysis, immune cell infiltration, and drug sensitivity analysis. In-depth analysis of AURKA gene expression in NPC and its corresponding clinicopathological features was performed to explore its potential as a therapeutic target. Moreover, AURKA gene expression in NPC was validated by qRT-PCR in 21 NPC tissues and 17 normal nasopharyngeal epithelial tissues. AURKA was highly expressed in NPC tissues. Enrichment analysis of AURKA and its co-expressed hub genes indicated their oncogenic role in NPC and their potential involvement in cancer-promoting processes through histone kinase activity and microtubule motility activity, cell cycle, and p53 signaling pathways. AURKA high expression group had greater infiltration of neutrophils, macrophages M2, and dendritic cells resting and less infiltration of T cells CD4+ naïve and T cells γδ. Drug susceptibility analysis found that dacarbazine, R-306465, vorinostat, and other antitumor drugs that act on the cell cycle were closely related to AURKA. qRT-PCR verified the high expression of AURKA in NPC tissues (p < 0.05). We confirmed upregulation of AURKA in NPC tissues. Our results support an oncogenic role of AURKA in the context of NPC, and indicate its potential role as a novel therapeutic target.

16.
Front Endocrinol (Lausanne) ; 13: 953305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060932

RESUMO

Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats.


Assuntos
Curcumina , Diabetes Mellitus , Angiopatias Diabéticas , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Flavanonas , Peróxido de Hidrogênio , Ratos , Ratos Wistar
17.
Front Immunol ; 13: 950365, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159855

RESUMO

Background: Esophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA. Methods: RNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: In ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias Esofágicas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/genética , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Humanos , Metilação , Prognóstico , RNA/metabolismo , Microambiente Tumoral
18.
Front Pharmacol ; 13: 960375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160416

RESUMO

Metastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore, we believe that interrupting CTCs adhesion to endothelium and transendothelial migration may efficiently prevent cancer metastasis. Fucoxanthin (Fx) is an algal carotenoid widely distributed in brown algae, macroalgae, and diatoms. Previous studies have found that Fx has various pharmacological activities, including antidiabetic, antioxidant, anti-inflammatory, anti-obesity, antimalarial, anticancer, and so on. However, it remains unclear whether Fx has a preventive effect on cancer metastasis. Here, we found that Fx interrupts breast cancer cells MCF-7 adhesion to endothelium and transendothelial migration, thus inhibiting CTCs-based pulmonary metastasis in vivo. The hetero-adhesion assay showed that Fx significantly inhibited the expression of inflammatory factor-induced cell adhesion molecules (CAMs) and the resulting adhesion between MCF-7 cells and endothelial cells. The wound-healing and transwell assays showed that Fx significantly inhibited the motility, invasion, and transendothelial migration abilities of MCF-7 cells. However, the same concentration of Fx did not significantly alter the cell viability, cell cycle, apoptosis, and ROS of breast cancer cells, thus excluding the possibility that Fx inhibits MCF-7 cell adhesion and transendothelial migration through cytotoxicity. Mechanistically, Fx inhibits the expression of CAMs on endothelial cells by inhibiting the NF-кB signaling pathway by down-regulating the phosphorylation level of IKK-α/ß, IкB-α, and NF-кB p65. Fx inhibits transendothelial migration of MCF-7 cells by inhibiting Epithelial-to-mesenchymal transition (EMT), PI3K/AKT, and FAK/Paxillin signaling pathways. Moreover, we demonstrated that Fx significantly inhibits the formation of lung micrometastatic foci in immunocompetent syngeneic mouse breast cancer metastasis models. We also showed that Fx enhances antitumor immune responses by substantially increasing the subsets of cytotoxic T lymphocytes in the peripheral immune system. This new finding provides a basis for the application of Fx in cancer metastatic chemoprevention and suggests that interruption of the CTCs adhesion to endothelium and transendothelial migration may serve as a new avenue for cancer metastatic chemoprevention.

19.
Int J Food Microbiol ; 381: 109910, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36063683

RESUMO

Listeria monocytogenes, as a food-associated pathogen, is able to develop biofilms on different surfaces of food contact, which seriously threatens food safety. Phenyllactic acid (PLA) exhibits excellent inhibitory effects on many bacterial strains including L. monocytogenes. Our study aimed to investigate effects of PLA on L. monocytogenes biofilms and its growth in milk and on spiced beef. Biofilm biomass was measured by the microplate method and biofilm structure was observed by electron microscopy. Growth of L. monocytogenes in food samples was determined by colony counting. Results from the agar dilution method demonstrated that L. monocytogenes 10403S had a PLA minimum inhibitory concentration (MIC) value of 6 mg/ml. Sub-inhibitory concentrations of PLA could inhibit biofilm formation by reducing the secretion of exopolysaccharides and extracellular proteins in L. monocytogenes. PLA at concentrations above 1/2MIC could destroy mature biofilms of L. monocytogenes by decreasing the exopolysaccharides and extracellular proteins in the biofilm framework. Both swimming and swarming motilities of L. monocytogenes were inhibited by PLA. The hemolytic activity of L. monocytogenes was inactivated by PLA. However, the capacity to attach and invade Caco-2 cells was not affected by PLA. The results displayed that PLA had no effect on the expression of genes associated with motility, but reduced the expression level of the hly gene encoding Listeria hemolysin. When added to ultra-high temperature (UHT) whole and pasteurized milk, PLA at 3 mg/ml inhibited L. monocytogenes growth through 14 days of storage at 4 °C. PLA at concentrations ≥3 mg/ml significantly reduced L. monocytogenes counts on spiced beef samples during storage. PLA has potential as an alternative antimicrobial to control L. monocytogenes contamination and its biofilms in food industry.


Assuntos
Listeria monocytogenes , Ágar/metabolismo , Animais , Biofilmes , Células CACO-2 , Bovinos , Proteínas Hemolisinas , Humanos , Lactatos , Leite/microbiologia , Poliésteres/farmacologia
20.
Front Endocrinol (Lausanne) ; 13: 913207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909561

RESUMO

Objective: Studies have shown that sex differences in lean mass, concentrations of sex hormones, and lifestyles influence cle health and glucose metabolism. We evaluated the sex-specific association between low muscle mass and glucose fluctuations in hospitalized patients with type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) therapy. Methods: A total of 1084 participants were included. Body composition was determined by dual-energy X-ray absorptiometry. Intraday blood glucose fluctuation was estimated by the Largest amplitude of glycemic excursions (LAGE) and standard deviation of blood glucose (SDBG). Results: The prevalence of low muscle mass was higher in males than in females (p<0.001). There was a significant sex-specific interaction between the status of low muscle mass and glucose fluctuations (LAGE and SDBG) (p for interaction=0.025 and 0.036 for SDBG and LAGE, respectively). Among males, low muscle mass was significantly associated with a higher LAGE and SDBG (difference in LAGE: 2.26 [95% CI: 1.01 to 3.51], p < 0.001; difference in SDBG: 0.45 [95% CI: 0.25 to 0.65], p < 0.001) after adjustment for HbA1c, diabetes duration, hyperlipidemia, diabetic peripheral neuropathy, diabetic nephropathy, and cardiovascular disease. These associations remained significant after further adjustment for age and C-peptide. Among females, low muscle mass was not associated with LAGE or SDBG after adjustment for all covariates. Conclusion: The prevalence of low muscle mass was higher in males than in females. Low muscle mass was significantly associated with higher LAGE and SDBG among males, but not females.


Assuntos
Diabetes Mellitus Tipo 2 , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Glucose , Humanos , Insulina , Masculino , Músculos
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