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1.
Food Funct ; 12(9): 4142-4151, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977961

RESUMO

Irritable bowel syndrome (IBS) is a common chronic functional bowel disease, associated with a high risk of depression and anxiety. The brain-gut axis plays an important role in the pathophysiological changes involved in IBS; however, an effective treatment for the same is lacking. The natural compound costunolide (COS) has been shown to exert gastroprotective, enteroprotective, and neuroprotective effects, but its therapeutic effects in IBS are unclear. Our study explored the effect of COS on intestinal dysfunction and depressive behaviour in stress-induced IBS mice. Mice were subjected to chronic unpredictable mild stress to trigger IBS, and some were administered COS. Behavioural tests, histochemical assays, western blotting, and measurement of 5-hydroxytryptamine (5-HT) levels in the colon and hippocampus were applied to monitor the physiological and molecular consequences of COS treatment in IBS mice. COS administration relieved intestinal dysfunction and depression-like behaviours in IBS mice. Improvements in low-grade colon inflammation and intestinal mucosal permeability, inhibition of the activation of mast cells, upregulation of colonic Occludin expression, and downregulation of Claudin 2 expression were also observed. COS was also found to upregulate GluN2A, BDNF, p-ERK1/2, and p-CREB expression and 5-HT levels in hippocampal cells but inhibited 5-HT metabolism. Molecular docking showed that COS could form hydrogen bonds with the serotonin transporter (SERT) to affect the reuptake of 5-HT in the intercellular space. In conclusion, COS alleviates intestinal dysfunction and depressive behaviour in stress-induced IBS mice by inhibiting mast cell activation in the colon and regulating 5-HT metabolism in the central nervous system.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33954334

RESUMO

Pre-mRNA processing factor 19 (PRPF19) is a multifaceted protein and participates in DNA damage response and pre-mRNA processing. The role of PRPF19 in cancer is unclear. Here, we report that the expression of PRPF19 in human tongue cancer is associated with unfavorable prognosis. Overexpression of PRPF19 promotes while knockdown of PRPF19 inhibits tongue cancer cell migration, proliferation, and tumor growth. Overexpression of PRPF19 increases the resistance of tongue cancer cells to radiation and cisplatin treatment. Furthermore, PRPF19 regulates the expression of solute carrier family 40 member 1 (SLC40A1) and mono-ADP ribosylhydrolase 2 (MACROD2), knockdown of SLC40A1 or MACROD2 decreases the sensitivity of tongue cancer cells to radiation and cisplatin treatment. Thus, our results establish a key role of PRPF19 in tongue cancer growth and chemoradiotherapy resistance, targeting PRPF19 would be an effective therapeutic strategy for tongue cancer, especially for those resistant to chemoradiotherapy.

3.
BMC Med Genomics ; 14(1): 124, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964903

RESUMO

BACKGROUND: Osteosarcoma is a highly malignant and common bone tumour with an aggressive disease course and a poor prognosis. Previous studies have demonstrated the relationship between long noncoding RNAs (lncRNAs) and tumorigenesis, metastasis, and progression. METHODS: We utilized a large cohort from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database osteosarcoma project to identify potential lncRNAs related to the overall survival of patients with osteosarcoma by using univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves were generated to evaluate the overall survival difference between patients in the high-risk group and the low-risk group. A time-dependent receiver operating characteristic curve (ROC) was employed, and the area under the curve (AUC) of ROC was measured to assess the sensitivity and specificity of the multi-lncRNA signature. RESULTS: Five lncRNAs (RP11-128N14.5, RP11-231|13.2, RP5-894D12.4, LAMA5-AS1, RP11-346L1.2) were identified, and a five-lncRNA signature was constructed. The AUC for predicting 5-year survival was 0.745, which suggested good performance of the five-lncRNA signature. In addition, functional enrichment analysis of the five-lncRNA-correlated protein-coding genes (PCGs) was performed to show the biological function of the five lncRNAs. Additionally, PPI network suggested RTP1 is a potential biomarker that regulates the prognosis of osteosarcoma. CONCLUSIONS: We developed a five-lncRNA signature as a potential prognostic indicator for osteosarcoma.

4.
Phytother Res ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33856723

RESUMO

Anxiety disorders are a common frequently psychiatric symptom in patients that lead to disruption of daily life. Scutellarin (Scu) is the main component of Erigeron breviscapus, which has been used as a neuroprotective agent against glutamate-induced excitotoxicity. However, the potential effect of Scu on the stress-related neuropsychological disorders has not been clarified. In this study, Anxiety-like behavior was induced by acute restraint stress in mice. Scu were injected intraperitoneally (twice daily, 3 days). Results showed that Scu exhibited good protective activity on mice by decreasing transmitter release levels. Restraint stress caused significant anxiety like behavior in mice. Treatment of Scu could significantly improve the moving time of open arms in Elevated Plus Maze and central time on open field test. Scu treatment suppressed action potential firing frequency, restored excessive presynaptic quantal release, and down-regulated glutamatergic receptor expression levels in the prefrontal cortex (PFC) of stressed mice. GABAA Rα1 and GABAA γ2 expression in the brain PFC tissues of mice were nearly abrogated by Scu treatment. In stress-induced anxiety mice, stress can increase the frequency of mini excitatory postsynaptic currents (mEPSC), which can be reversed by Scu treatment. Therefore, Scu has a potent anxiolytic activity and may be valuable for the treatment of stress-induced anxiety disorders.

5.
Neuropsychologia ; 157: 107864, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33891956

RESUMO

A growing body of research has largely confirmed and supported the idea that experimental sleep loss, such as sleep deprivation or sleep restriction, could affect individuals' risk-taking behavior and brain activity. However, whether self-reported sleep quality resulting from daily life modulates how feedback is evaluated during decision-making is still unclear. In this study, we used event-related potentials (ERPs) with a Balloon Analogue Risk Task (BART) to investigate how self-reported daily sleep quality modulates the brain's response to feedback from decision-making in the gain and loss frames. Behavioral data showed an increased aversion to uncertainty in the gain frame relative to the loss frame for individuals with higher sleep quality. However, this was not true for individuals with lower voluntary sleep quality. Similarly, the ERP data demonstrated that individuals with lower self-reported daily sleep quality displayed no changes in feedback-related negativity (FRN) in response to outcomes from decision-making in the gain and loss frames; however, individuals with higher self-reported daily sleep quality showed a greater FRN in response to decision-making in the gain frame than that in the loss frame. A Pearson correlation analysis showed that self-reported daily sleep quality was positively related to the variance of the FRN amplitude in response to the gain and loss frames. These findings suggest that framing effects on decision-making under uncertainty may depend on self-reported daily sleep quality and that the effects disappear when the sleep quality declines.

6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(3): 328-332, 2021 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33927082

RESUMO

A patient with thymoma associated immunodeficiency syndrome (Good's syndrome) and bronchiectasis was retrospectively analyzed. Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. It is important to bear in mind that Good's syndrome should be included in the differential diagnosis When patients repeatedly visited for bronchiectasis or infection, we should alert to their immune state and history of thymoma. Early screening of immunological status and aggressive correction of immune deficiency are beneficial to improving the prognosis to patients with Good's syndrome.


Assuntos
Agamaglobulinemia , Bronquiectasia , Timoma , Neoplasias do Timo , Agamaglobulinemia/complicações , Bronquiectasia/complicações , Humanos , Estudos Retrospectivos , Timoma/complicações , Neoplasias do Timo/complicações
7.
Environ Sci Technol ; 55(6): 3836-3844, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33667084

RESUMO

Arsenolipids are a class of lipid-soluble arsenic species. They are present in seafoods and show high potentials of cytotoxicity and neurotoxicity. Hindered by traditional low-throughput analytical techniques, the characterization of arsenolipids is far from complete. Here, we report on a sensitive and high-throughput screening method for arsenolipids in krill oil, tuna fillets, hairtail heads, and kelp. We demonstrate the detection and identification of 23 arsenolipids, including novel arsenic-containing fatty acids (AsFAs), hydroxylated AsFAs, arsenic-containing hydrocarbons (AsHCs), hydroxylated AsHCs, thiolated trimethylarsinic acids, and arsenic-containing lysophosphatidylcholines not previously reported. The new method incorporated precursor ion scan (PIS) into data-independent acquisition. High-performance liquid chromatography (HPLC) electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-qToF-MS) was used to perform the sequential window acquisition of all theoretical spectra (SWATH). Comprehensive HPLC-MS and MS/MS data were further processed using a fragment-guided chromatographic computational program Precursorfinder developed here. Precursorfinder achieved efficient peak-picking, retention time comparison, hierarchical clustering, and wavelet coherence calculations to assemble fragment features with their target precursors. The identification of arsenolipids was supported by coeluting the HPLC-MS peaks detected with the characteristic fragments of arsenolipids. Method validation using available arsenic standards and the successful identification of previously unknown arsenolipids in seafood samples demonstrated the applicability of the method for environmental research.


Assuntos
Arsênico , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Ácidos Graxos , Lipídeos , Espectrometria de Massas por Ionização por Electrospray
8.
Epigenomics ; 13(6): 411-422, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33641342

RESUMO

Aim: To explore the roles of lncRNA NONHSAT177112.1 in the inflammatory injury of human cardiomyocytes (HCMs) induced by lipopolysaccharide (LPS). Materials & methods: The sublocalization of NONHSAT177112.1 was detected by FISH. HCMs were stimulated with LPS to induce inflammatory injury. NONHSAT177112.1 expression was detected by quantitative real-time PCR. Cell apoptosis and viability were detected by flow cytometry and CCK-8 assays. The expression of inflammatory cytokines and myocardial enzymes were detected by PCR and ELISA. Results: NONHSAT177112.1 is expressed in the nucleus and cytoplasm. NONHSAT177112.1 showed dynamic expression that first increased and then decreased during LPS stimulation. NONHSAT177112.1 knockdown reversed the promotion effect of LPS on inflammatory injury. Conversely, NONHSAT177112.1 overexpression exerted the opposite effects. Conclusion: NONHSAT177112.1 aggravates inflammatory injury in LPS-treated HCMs.

9.
Neurosci Bull ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33788145

RESUMO

Key requirements of successful animal behavior research in the laboratory are robustness, objectivity, and high throughput, which apply to both the recording and analysis of behavior. Many automatic methods of monitoring animal behavior meet these requirements. However, they usually depend on high-performing hardware and sophisticated software, which may be expensive. Here, we describe an automatic infrared behavior-monitor (AIBM) system based on an infrared touchscreen frame. Using this, animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events. This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms. The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient, unbiased, and low-cost manner.

10.
Invest New Drugs ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666785

RESUMO

Neuroblastoma (NB) is a common tumor in children, usually in the retroperitoneum. After various treatments, low- and intermediate-risk patients have achieved good results, but the prognosis of high-risk patients is still very poor. Therefore, it is necessary to find new effective targets for the treatment of high-risk patients. In this study, comprehensive bioinformatics analysis was used to identify the differentially expressed genes (DEG and DEM) between high-risk patients and non-high-risk patients, and it was identified that ADRB2 may affect the survival status of high-risk patients due to miR -30a-5p regulation. The GSE49710, GSE73517, and GSE121513 datasets were downloaded from the Gene Expression Synthesis (GEO) database, and DEG and DEM were selected. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to the selected DEGs. The STRING database and Cytoscape software were used to construct protein-protein interaction (PPI) networks and perform modular analysis of the DEGs. The TARGET data set containing information on overall survival days were used for the prognostic analysis of central genes. We identified a total of 255 DEGs from GSE49710 and GSE73517, and 193 DEMs from GSE121513. We identified the 5 most important central genes from the PPI network, performed a prognostic analysis in the target data set, and verified their expression using RT-qPCR to select the most important ADRB2 gene to predict miRNA. Integrating the differential miRNA predicted by miRDB and miRSystem and GSE121513 between the targeted miRNA and the prognosis, miR-30a-5p was finally identified as the targeted miRNA of ADRB2.

11.
J Med Chem ; 64(3): 1701-1712, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33529017

RESUMO

Glutathione transferase (GST P1-1) is a potential target for anticancer drugs. In this work, a series of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) derivatives as GST P1-1 inhibitors were designed, synthesized, and evaluated for their biological activity. Among the target compounds, 4n showed more selective inhibition toward GST P1-1 and GST M2-2, better water solubility, and more potent anticancer activities toward all the tested cancer cells (except for HOS) than its parent molecule. Detailed biological studies on the effect of 4n toward 143b cells revealed that 4n could arrest the cell cycle at the G2 phase and induced cell apoptosis in a dose-dependent manner. Like NBDHEX, 4n displayed good pharmacokinetic characteristics. An in vivo study on 143b xenograft models demonstrated that 4n could significantly reduce tumor growth in a dose-dependent manner, showing stronger antitumor activity than NBDHEX. Thus, 4n deserves to be further investigated as a potential antitumor agent for cancer therapy.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glutationa Transferase/antagonistas & inibidores , Oxidiazóis/química , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Descoberta de Drogas , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/toxicidade , Fase G2/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley , Solubilidade , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Eur J Med Chem ; 216: 113300, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33640672

RESUMO

Multi-target, especially dual-target, drug design has become a popular research field for cancer treatment. Development of small molecule dual-target inhibitors through hybridization strategy can provide highly potent and selective anticancer agents. In this study, three series of quinazoline derivatives bearing a benzene-sulfonamide moiety were designed and synthesized as dual EGFR/CAIX inhibitors. All the synthesized compounds were evaluated against epidermoid carcinoma (A431) and non-small cell lung cancer (A549 and H1975) cell lines, which displayed weak to potent anticancer activity. In particular, compound 8v emerged as the most potent derivative against mutant-type H1975 cells, which exhibited comparable activity to osimertinib. Importantly, 8v exhibited stronger anti-proliferative activity than osimertinib against H1975 cells under hypoxic condition. Kinase inhibition studies indicated that 8v showed excellent inhibitory effect on EGFRT790M enzyme, which was 41 times more effective than gefitinib and almost equal to osimertinib. Mechanism studies revealed that 8v exhibited remarkable CAIX inhibitory effect comparable to acetazolamide and significantly inhibited the expression of p-EGFR as well as its downstream p-AKT and p-ERK in H1975 cells. Notably, 8v was found to inhibit the expression of CAIX and its upstream HIF-1α in H1975 cells under hypoxic condition. Molecular docking was also performed to gain insights into the ligand-binding interactions of 8v inside EGFRWT, EGFRT790M and CAIX binding sites.


Assuntos
Anidrase Carbônica IX/antagonistas & inibidores , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Receptores ErbB/antagonistas & inibidores , Quinazolinas/química , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação , Anidrase Carbônica IX/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Inibidores Enzimáticos/metabolismo , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Relação Estrutura-Atividade
13.
J Crohns Colitis ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33319236

RESUMO

BACKGROUND AND AIMS: Current consensus recommendations define small bowel strictures (SBS) in Crohn's disease (CD) on imaging as luminal narrowing with unequivocal upstream bowel dilation. The aim of this study was to 1) evaluate the performance of cross-sectional imaging for SBS diagnosis in CD using luminal narrowing with upstream SB dilation and luminal narrowing with or without upstream dilation, and 2) compare the diagnostic performance of CT and MR enterography (MRE) for SBS diagnosis. METHODS: One hundred and eleven CD patients (81 with pathologically confirmed SBS, 30 controls) who underwent CT and/or MRE were assessed. Two radiologists (R1, R2) blinded to pathology findings independently assessed the presence of luminal narrowing and upstream SB dilation. Statistical analysis was performed for a) luminal narrowing with or without SB upstream dilation ("possible SBS"), b) luminal narrowing with upstream SB dilation ≥3cm ("definite SBS"). RESULTS: Sensitivity for detecting SBS was significantly higher using "possible SBS" (R1, 82.1%; R2, 77.9%) compared to "definite SBS" (R1, 62.1%; R2, 65.3%; p<0.0001) with equivalent specificity (R1, 96.7%; R2, 93.3%; p>0.9). Using criterion "possible SBS", sensitivity/specificity were equivalent between CT (R1, 87.3%/93.3%; R2, 83.6%/86.7%) and MRE (R1, 75.0%/100%; R2: 70.0%/100%). Using criterion "definite SBS", CT showed significantly higher sensitivity (78.2%) compared to MRE (40.0%) for R1 but not R2 with similar specificities (CT, 86.7%-93.3%; MRE, 100%). CONCLUSION: SBS can be diagnosed using luminal narrowing alone without the need for upstream dilation. CT and MRE show similar diagnostic performance for SBS diagnosis using luminal narrowing with or without upstream dilation.

14.
Medicine (Baltimore) ; 99(51): e23759, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371138

RESUMO

BACKGROUND: Xinyin Tablet (XYT) has been widely used in the treatment of CHF, Which helping to improve the clinical symptoms, enhance exercise, and even may improve the long-term prognosis of patients. However, the exact effectiveness and safety of XYT for CHF has not be comprehensively researched, so we want to generalize the effectiveness and safety of XYT for CHF through the meta-analysis, which may benefit the design of future clinical trials and provide valuable references. METHODS: This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. From the inception until September 2020, a systematic and comprehensive electronic search about Relevant randomized controlled trials will be conducted in 4 English literature databases and 4 Chinese literature databases. The registration number: INPLASY2020100015. 2 investigators will be arranged to deal with the study selection and data extraction independently. The New York Heart Function Classification, traditional Chinese medicine (TCM) symptom scores, the scores of quality of life, 6-min walk distance (6MWD), etc. will be systematically measured as outcomes. At last, the data will be handled by Review Manager 5.3 and Stata 15.0. RESULTS AND CONCLUSION: This study is hoping to provide a high-level evidence to prove the therapeutic effect of XYT on CHF, which may enhance the application of Chinese medicine.


Assuntos
Protocolos Clínicos , Insuficiência Cardíaca/tratamento farmacológico , Medicina Tradicional Chinesa/normas , Insuficiência Cardíaca/fisiopatologia , Humanos , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/tendências , Metanálise como Assunto , Peptídeo Natriurético Encefálico/análise , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Revisões Sistemáticas como Assunto , Ultrassonografia/métodos
15.
Reprod Sci ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33171515

RESUMO

GALNT2 is a GalNAc transferase that regulates insulin signaling, lipogenesis, and serum lipid fractions. The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of polycystic ovary syndrome (PCOS) and related traits. The two SNPs were genotyped in 616 PCOS patients and 482 control subjects. Genetic associations with related traits were also analyzed. The genotype distributions of the two SNPs in PCOS patients were similar to those of normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables. In the PCOS group, subjects with genotype AA at the rs4846914 SNP exhibited an increased fasting serum insulin and homeostasis model insulin resistance (HOMA-IR) index compared with that of corresponding GG or GA genotype carriers (all P < 0.05). When PCOS patients were further separated into obese and non-obese subgroups, the genotype-related effects on insulin and HOMA-IR were more obvious, and variations in BMI and FSH levels were exclusively observed in obese PCOS subjects (all P < 0.05). In addition, fasting plasma glucose levels were affected by the genotypes of the rs2144300 SNP in normal control women (P < 0.05). rs4846914 and rs2144300 polymorphisms in the GALNT2 gene are associated with insulin and HOMA-IR, BMI, and FSH levels in obese PCOS patients and glucose levels in normal control women, respectively, but not with PCOS. GALNT2 rs4846914 AA carrier status may be associated with insulin resistance and related traits in obese patients.

16.
Eur J Clin Invest ; : e13438, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33091151

RESUMO

BACKGROUND: Oxidative stress plays a pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in myeloperoxidase (MPO; G-463A) and NADPH oxidase p22phox subunit (CYBA; C242T) cause inter-individual variability in enzyme activities. Here, we investigated the associations between MPO activity and the MPO G-463A and CYBA C242T polymorphisms in Chinese women with PCOS. METHODS: This case-control study included 1003 patients with PCOS and 810 controls. The G-463A and C242T polymorphisms were detected by polymerase chain reaction and restriction analysis, and clinical, hormonal, metabolic and oxidative stress parameters and MPO activity were analysed. RESULTS: The frequencies of the GA + AA genotype and A allele frequency of the MPO G-463A polymorphism were significantly higher in the PCOS group than in the control group. Logistic regression analysis showed that the MPO-463A allele is a risk factor for PCOS (OR = 1.261, 95% CI: 1.042-1.526, P = .017). Patients with the AA genotype tended to have higher plasma MPO activity than those with the GG genotype. No statistical significance was found in the genotype and allele frequencies of the CYBA C242T polymorphism between the PCOS and control groups. However, we demonstrated that the coexistence of the MPO A allele (GA + AA genotypes) and the CYBA CC genotype was associated with an increased risk of PCOS when compared with the wild-type GG/CC genotypes (OR = 1.302, 95% CI: 1.030-1.646, P = .027). CONCLUSION: The MPO G-463A variant, but not CYBA C242T variant, is associated with a risk of PCOS in Chinese women.

17.
Sleep Med Rev ; 55: 101376, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32987319

RESUMO

Insomnia is highly prevalent among patients with breast cancer (BC). Although cognitive behavioral therapy for insomnia (CBT-I) is available in integrative oncology settings, it poses unique challenges for BC survivors. Our review aimed to assess the evidence for the therapeutic effects of CBT-I on insomnia in BC. Randomized controlled trials (RCTs) that included patients/survivors with BC and insomnia, and at least one validated self-report measure of sleep quality were included in the review. Of the 14 included RCTs (total N = 1363), the most common components incorporated in CBT-I interventions were sleep hygiene, stimulus control and sleep restriction. Pooled effect sizes favored CBT-I at post-intervention (Hedges' g = -0.779, 95% CI = -0.949, -0.609), short-term follow-up (within six months, Hedges' g = -0.653, 95% CI = -0.808, -0.498), and long-term follow-up (12 mo, Hedges' g = -0.335, 95% CI = -0.532, -0.139). In sub-analyses, CBT-I had similar effect sizes regardless of potential modifiers (comparison design, delivery formats, etc.). As an integrative oncology intervention, CBT-I is efficacious for reducing insomnia and improving sleep quality in women treated for BC, with medium-to-large effect sizes that persist after intervention delivery ends. Given the variability in the CBT-I components tested in RCTs, future studies should investigate the optimal integration of CBT-I components for managing insomnia during BC survivorship.

18.
J Biol Chem ; 295(49): 16743-16753, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-32978261

RESUMO

Mitochondrial dysfunction is associated with a variety of human diseases including neurodegeneration, diabetes, nonalcohol fatty liver disease (NAFLD), and cancer, but its underlying causes are incompletely understood. Using the human hepatic cell line HepG2 as a model, we show here that endoplasmic reticulum-associated degradation (ERAD), an ER protein quality control process, is critically required for mitochondrial function in mammalian cells. Pharmacological inhibition or genetic ablation of key proteins involved in ERAD increased cell death under both basal conditions and in response to proinflammatory cytokines, a situation frequently found in NAFLD. Decreased viability of ERAD-deficient HepG2 cells was traced to impaired mitochondrial functions including reduced ATP production, enhanced reactive oxygen species (ROS) accumulation, and increased mitochondrial outer membrane permeability. Transcriptome profiling revealed widespread down-regulation of genes underpinning mitochondrial functions, and up-regulation of genes associated with tumor growth and aggression. These results highlight a critical role for ERAD in maintaining mitochondrial functional and structural integrity and raise the possibility of improving cellular and organismal mitochondrial function via enhancing cellular ERAD capacity.

19.
Biotechnol Lett ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32989662

RESUMO

OBJECTIVES: The capsid protein (VP1) of the foot-and-mouth (FMD) AKT-III strain was expressed on the surface of the T7 phage capsid (AKT-T7 strain) and the potential of AKT-T7 strain as an FMD vaccine was evaluated. RESULTS: The AKT-T7 strain was successfully constructed and was not cytotoxic to BHK-21, MDBK, or sheep kidney cells. The AKT-T7 strain was well phagocytosed by mouse macrophages. Immunization of BALB/c mice revealed that animals were quickly induced and produced high levels of FMDV antibodies. Monitoring data indicated that FMDV antibody levels could be maintained at higher levels for longer periods of time. The AKT-T7 strain induced high levels of IFN-γ levels in mice with little effect on IL-4. CONCLUSIONS: The AKT-T7 induced the mice to produce FMDV antibodies, which has the advantage of phage and FMDV, and is a potential candidate for an FMD vaccine.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32840656

RESUMO

As TDO inhibitors can improve the efficacy of tumor chemotherapeutics, two TDO-targeted conjugates consisting of irinotecan (Ir) and a TDO inhibitor unit were designed and prepared to reverse tumor immune suppression, which could remarkably enhance antitumor activity of Ir by boosting cellular uptakes against TDO overexpressed HepG2 cancer cells. In vitro mechanistic studies demonstrated that compound PVIS-Ir and PVIG-Ir could arrest cell cycle at G2 phase and induce cell apoptosis by mitochondrial apoptotic pathway. Furthermore, compound PVIS-Ir could effectively inhibit TDO protein expression via releasing a TDO inhibitor derivative, which could also completely embed in TDO protein pocket. Further mechanism study indicated that PVIS-Ir could block kynurenine production and deactivate aryl hydrocarbon receptor (AHR), resulting in T-cell activation and proliferation. In vivo studies confirmed that PVIS-Ir could improve tumor immune microenvironment in a murine model. This combinational strategy of chemotherapy and immunotherapy can be a promising way in the treatment of hepatocellular carcinoma. Conjugates obtained by combining an immune checkpoint TDO inhibitor with irinotecan via different linkers could improve tumor immune microenvironment by inhibiting the TDO enzyme expression to block kynurenine production and induce HepG2 cancer cell apoptosis via DNA damage through releasing a TDO inhibitor and irinotecan in cancer cells.

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