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1.
J Clin Invest ; 130(3): 1073-1083, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32118585

RESUMO

The functional state of the preexisting T cells in the tumor microenvironment is a key determinant for effective antitumor immunity and immunotherapy. Increasing evidence suggests that immunosenescence is an important state of T cell dysfunction that is distinct from exhaustion, a key strategy used by malignant tumors to evade immune surveillance and sustain the suppressive tumor microenvironment. Here, we discuss the phenotypic and functional characteristics of senescent T cells and their role in human cancers. We also explore the possible mechanisms and signaling pathways responsible for induction of T cell senescence by malignant tumors, and then discuss potential strategies to prevent and/or reverse senescence in tumor-specific T cells. A better understanding of these critical issues should provide novel strategies to enhance cancer immunotherapy.

3.
Front Immunol ; 11: 235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32153570

RESUMO

Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 balance. We previously reported that nicotine protects against mouse DSS colitis (similar to UC) by enhancing microRNA-124 (miR-124) expression. Intriguingly, elevation of miR-124 in CD is reported to aggravate the disease. Here we investigate the dual regulation of miR-124 in inflammatory bowel diseases (IBDs), which may explain the similar bidirectional regulation of tobacco. We found that overexpressed miR-124 protected against mouse DSS-induced colitis with a Th1 polarization in peripheral blood lymphocytes and colon tissues, which was also found in human peripheral blood lymphocytes. Conversely, miR-124 knockdown worsened DSS murine colitis with a Th2 polarization. Moreover, knockdown of miR-124 could eliminate the polarization toward Th1 after nicotine treatment, suggesting that miR-124 mediates the effect of nicotine on the Th1/Th2 balance. In addition, interference of IL-6R, which is a downstream target of miR-124, could remarkably weaken the Th1 polarization induced by miR-124. Taken together, these results suggest that nicotine shifts the balance of Th1/Th2 toward Th1 via a miR-124-mediated IL-6R pathway, which might explain its dual role in IBDs.

4.
J Vasc Access ; : 1129729820908088, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32141365

RESUMO

PURPOSE: To evaluate the effects of passive music therapy on anxiety and vital signs among lung cancer patients at their first peripherally inserted central catheter placement procedure in China. METHODS: A randomized controlled clinical trial was conducted in the cancer center of a hospital in Chengdu from May to December 2017. A total of 304 lung cancer patients who met the inclusion and exclusion criteria were recruited and randomly assigned to experimental (n = 152) and control (n = 152) group, respectively. The control group only received standard care, while the experimental group received standard care and passive music therapy during peripherally inserted central catheter placement (30-45 min) and after catheterization, until discharged from the hospital (twice a day, 30 min once). Measures include anxiety and vital signs (blood pressure, heart rate, and respiratory rate). RESULTS: Repetitive measurement and analysis of variance showed that the patients in experimental group had a statistically significant decrease in anxiety, diastolic blood pressure, and heart rate over time compared to the control group, but no significant difference was identified in systolic blood pressure and respiratory rate. CONCLUSION: Passive music therapy can efficiently relieve the anxiety of lung cancer patients during peripherally inserted central catheter placement. It also can lower the patient's diastolic blood pressure and slow down the heart rate. So, music therapy benefits patients with peripherally inserted central catheter.

5.
Int J Biol Sci ; 16(6): 935-946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32140063

RESUMO

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL.

6.
J Stroke Cerebrovasc Dis ; : 104743, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32127256

RESUMO

BACKGROUND: Bone marrow stromal cell (BMSC) transplantation is a promising therapeutic approach for cerebral ischemia, as it elicits multiple neuroprotective effects. However, it remains unclear how BMSC transplantation modulates the ubiquitin-proteasome system (UPS) and autophagy under cerebral ischemia. METHODS: In the present study, an intermediate level of cerebral ischemia (30 minutes) was chosen to examine the effect of BMSC transplantation on the molecular switch regulating UPS and autophagy. BMSC or vehicle was stereotactically injected into the penumbra 15 minutes after sham operation or transient middle cerebral artery occlusion (tMCAO). RESULTS: Thirty minutes of tMCAO artery occlusion significantly increased TUNEL-, ubiquitin-, and p62-positive cells (which peaked at 72 hours, 2 hours, and 2 hours after reperfusion, respectively) and ratios of both BAG3/BAG1 and LC3-II/LC3-I at 24 hours after reperfusion. However, intracerebral injection of BMSCs significantly reduced infarct volume and numbers of TUNEL- and p62-positive cells, and improved BAG3/BAG1 and LC3-II/LC3-I ratios. In addition, observed increases in ubiquitin-positive cells 2 hours after reperfusion were slightly suppressed by BMSC transplantation. CONCLUSIONS: These data suggest a protective role of BMSC transplantation, which drove the molecular switch from autophagy to UPS in a murine model of ischemic stroke.

7.
J Sch Health ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32141621

RESUMO

BACKGROUND: This study examined implementation of district sun safety policy in schools and tested correlates of implementation in California public school districts. METHODS: Principals (N = 118) and teachers (N = 113) in California public elementary schools (N = 118) were recruited and completed a survey on sun protection policies and practices. The sample contained schools whose districts subscribed to the California School Boards Association and adopted Board Policy 5141.7 for sun safety. Principals and teachers reported on implementation of 10 school practices related to BP 5141.7 indicating which practices were implemented in the school. RESULTS: Years in public education (Exponentiated Score (ES) = 0.51, p < .001), years worked in the current district (ES = 0.49, p < .001), perception that parents should take action to protect children from the sun (ES = 0.43, p < .01), and personal skin phenotype (Low Risk ES = 0.55; High Risk ES = 0.09, p < .05) were associated with number of practices implemented in the school using multiple Poisson regression. CONCLUSIONS: Policy implementation is more likely among schools with experienced faculty, when parents are seen as important partners in student skin cancer prevention, and when school principals and teachers have a lower personal risk phenotype.

8.
Sensors (Basel) ; 20(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178312

RESUMO

Citri Reticulatae Pericarpium (CRP), has been used in China for hundreds of years as a functional food and medicine. However, some short-age CRPs are disguised as long-age CRPs by unscrupulous businessmen in order to obtain higher profits. In this paper, a rapid and nondestructive method for the classification of different-age CRPs was established using portable near infrared spectroscopy (NIRS) in diffuse reflectance mode combination with appropriate chemometric methods. The spectra of outer skin and inner capsule of CRPs at different storage ages were obtained directly without destroying the samples. Principal component analysis (PCA) with single and combined spectral pretreatment methods was used for the classification of different-age CRPs. Furthermore, the data were pretreated with the PCA method, and Fisher linear discriminant analysis (FLD) with optimized pretreatment methods was discussed for improving the accuracy of classification. Data pretreatment methods can be used to eliminate the noise and background interference. The classification accuracy of inner capsule is better than that of outer skin data. Furthermore, the best results with 100% prediction accuracy can be obtained with FLD method, even without pretreatment.

9.
J Colloid Interface Sci ; 571: 297-306, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32208200

RESUMO

Solution of the increasingly important problem of aquatic pollution requires the use of an economical, energy-efficient, highly effective and environmentally-friendly catalyst. Polymeric carbon nitride (C3N4) has shown to be a promising metal-free photocatalyst that however suffers from strong charge recombination and poor conductivity, while MXenes have shown to be perfect co-catalysts for the photocatalytic process but show poor stability. In this study, we successfully constructed a robust heterostructure photocatalyst in which few-layer Ti3C2Tx was embedded into alkalized C3N4 without being oxidized. The photocatalyst showed stable and effective photocatalytic performance for the removal of tetracycline hydrochloride and other organic compounds under visible light irradiation. Different characterization methods were used to elucidate the morphology and structure of the as-prepared photocatalyst. The robust heterostructure and the intimate interaction between the two constituents of the composite were verified. Based on the van der Waals heterostructure, Ti3C2Tx acts as the electron acceptor and helps to form Schottky junction, preventing charge recombination of the photocatalyst. And in the meantime, the electrons from C3N4 protect Ti3C2Tx from oxidation. SEM and XRD results demonstrated that the Ti3C2Tx structure remains unchanged after calcination and after photodegradation experiments. Furthermore, a possible mechanism for photocatalytic tetracycline hydrochloride degradation was proposed based on the results of radical scavenging experiments. This work provides a strategy to strengthen heterostructure between 2D materials, and shows that carbon nitride and Mxenes could be promising materials for photocatalytic wastewater pre-treatment applications.

10.
Biomed Pharmacother ; 126: 110012, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32213428

RESUMO

Heart failure (HF) has become a worldwide public health problem that seriously threatens human's health. Due to "multi-target" effect, traditional Chinese medicine (TCM) has unique advantages in this field. Chinese herb-derived active components would provide valuable candidate compounds for new drug development. Astragaloside IV(AS-IV) is a main effective ingredient of Astragalus membranaceus, a commonly used Chinese patent medicine for the patients with chronic heart failure(CHF). Our aim is to review the recent progresses of AS-IV in HF, and provide potential evidence for its clinical application. Data showed that AS-IV could protect myocardial ischemia, regulate sarcoplasmic reticulum Ca2+ pump, promote angiogenesis, improve energy metabolism, inhibit cardiac hypertrophy and fibrosis, reduce myocardial cell apoptosis, etc, which are direct or indirect involved in the beneficial effects of AS-IV in rodents or cellular models of HF. AS-IV or its derivatives may act as a potential therapeutic drug in the clinical treatment of HF.

11.
Mycopathologia ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32185617

RESUMO

PURPOSES: To investigate the role of 17ß-estrogen in Candida albicans (C. albicans) adhesion on human vaginal epithelial cells in vulvovaginal candidiasis (VVC). METHODS: The vaginal epithelial cell line, VK2/E6E7, was used to study the estrogen-induced molecular events between C. albicans and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation in cell adhesion. The phosphorylation status of FAK and estrogen receptor α (ERα) upon estrogen challenge was assessed by western blotting. Specific inhibitors for ERα were used to validate the involvement of ERα-FAK signaling cascade. RESULTS: A transient activation of ERα and FAK was observed following the stimulation with 1000 nM estrogen for 48 h, as well as the increased average number of C. albicans adhering to each vaginal epithelial cell. Estrogen-induced activation of ERa and FAK was inhibited by the specific inhibitor of ERα, especially when the inhibitor reached a 10 µM concentration and allowed to act for 12 h. Simultaneously, a decrease in the number of adherent C. albicans was observed. However, this inhibitory effect diminished as the concentration of estrogen increased. CONCLUSION: FAK and ERα signaling cascades were involved in the early interaction between the vaginal epithelial cells and C. albicans, which appeared to be linked with the enhanced cell adhesion leading to VVC and promoted by a certain concentration of estrogen.

12.
Biochem Pharmacol ; 175: 113890, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32119837

RESUMO

Triterpenoids are a powerful group of phytochemicals derived from plant foods and herbs. Many reports have shown that they possess chemopreventive and chemotherapeutic effects not only in cell lines and animal models but also in clinical trials. Because epigenetic changes could potentially occur in the early stages of carcinogenesis preceding genetic mutations, epigenetics are considered promising targets in early interventions against cancer using epigenetic bioactive substances. The biological properties of triterpenoids in cancer prevention and in health have multiple mechanisms, including antioxidant and anti-inflammatory activities, cell cycle regulation, as well as epigenetic/epigenomic regulation. In this review, we will discuss and summarize the latest advances in the study of the pharmacological effects of triterpenoids in cancer chemoprevention and in health, including the epigenetic machinery.

13.
Nat Prod Bioprospect ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016770

RESUMO

A series of dearomatized isoprenylated acylphloroglucinols derivatives, hyperhenols A-E (1-5), as well as seven known analogues (6-12), were characterized from Hypericum henryi. Their structures were determined by combination of NMR, ECD spectroscopy, and X-ray diffraction analysis. Compounds 1 and 6-8 were tested to exhibit potential antitumor properties, of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest. In addition, these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines, as well as suppress lung cancer A549 cells metastasis in vitro.

14.
Psych J ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040980

RESUMO

Previous studies have shown that perceived discrimination is negatively correlated with children's psychological development. However, how perceived group discrimination (PGD) leads to negative adjustment is not known. For 692 Chinese rural-to-urban migrant children, we examined the relations between PGD and both behavioral and emotional adaptation (antisocial behavior and positive affect), as mediated by collective self-esteem (CSE) and personal self-esteem (PSE). Children (50.7% boys; Mage = 13.37 years) completed questionnaires on PGD, antisocial behavior, positive affect, CSE, and PSE. PGD was positively associated with antisocial behavior and negatively associated with positive affect according to structural equation modeling. CSE and PSE accounted for some of the PGD related to antisocial behavior and fully accounted for PGD effects on positive affect. These findings suggested that the combination of CSE and PSE is a potential mechanism that underlies PGD associated with both antisocial behavior and positive affect.

15.
Cell Death Differ ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001780

RESUMO

The metabolism-controlled differentiation of αß T cells has been well documented; however, the role of a metabolism program in γδ T cell differentiation and function has not been clarified. Here, using CD2-cre; mTORC1 Raptor-f/f, and mTORC2 Rictor-f/f mice (KO mice), we found that mTORC1, but not mTORC2, was required for the proliferation and survival of peripheral γδ T cells, especially Vγ4 γδ T cells. Moreover, mTORC1 was essential for both γδ T1 and γδ Τ17 differentiation, whereas mTORC2 was required for γδ T17, but not for γδ Τ1, differentiation. We further studied the underlying molecular mechanisms and found that depletion of mTORC1 resulted in the increased expression of SOCS1, which in turn suppressed the key transcription factor Eomes, consequentially reducing IFN-γ production. Whereas the reduced glycolysis resulted in impaired γδ Τ17 differentiation in Raptor KO γδ T cells. In contrast, mTORC2 potentiated γδ Τ17 induction by suppressing mitochondrial ROS (mitoROS) production. Consistent with their cytokine production profiles, the Raptor KO γδ T cells lost their anti-tumor function both in vitro and in vivo, whereas both Raptor and Rictor KO mice were resistant to imiquimod (IMQ)-induced psoriasis-like skin pathogenesis. In summary, we identified previously unknown functions of mTORC1 and mTORC2 in γδ T cell differentiation and clarified their divergent roles in mediating the activity of γδ T cells in tumors and autoimmunity.

16.
Cancer Lett ; 475: 22-33, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32014457

RESUMO

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality. Artemisinin (ART) and SOMCL-14-221 (221), a spirobicyclic analogue of ART, have been reported to inhibit the proliferation of A549 cells with unclear underlying mechanism. In the present study, we validated that both ART and 221 inhibited the proliferation and migration of NSCLC cells and the growth of A549 xenograft tumors without appreciable toxicity. The proteomic data revealed proteins upregulated in ART and 221 groups were involved in "response to endoplasmic reticulum stress" and "amino acid metabolism". Asparagine synthetase (ASNS) was identified as a key node protein in these processes. Interestingly, knockdown of ASNS improved the antitumor potency of ART and 221 in vitro and in vivo, and treatments with ART and 221 disordered the amino acid metabolism of A549 cells. Moreover, ART and 221 activated ER stress, and inhibition of ER stress abolished the anti-proliferative effects of ART and 221. In conclusion, this study demonstrates that ART and 221 suppress tumor growth by triggering ER stress, and the inhibition of ASNS enhances the antitumor activity of ART and 221, which provides new strategy for drug combination therapy.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32081430

RESUMO

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro, but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment.

18.
J Clin Oncol ; : JCO1902314, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083995

RESUMO

Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM), including MYD88 (95%-97%), CXCR4 (30%-40%), ARID1A (17%), and CD79B (8%-15%). Deletions involving chromosome 6q are common in patients with mutated MYD88 and include genes that modulate NFKB, BCL2, Bruton tyrosine kinase (BTK), and apoptosis. Patients with wild-type MYD88 WM show an increased risk of transformation and death and exhibit many mutations found in diffuse large B-cell lymphoma. The discovery of MYD88 and CXCR4 mutations in WM has facilitated rational drug development, including the development of BTK and CXCR4 inhibitors. Responses to many agents commonly used to treat WM, including the BTK inhibitor ibrutinib, are affected by MYD88 and/or CXCR4 mutation status. The mutation status of both MYD88 and CXCR4 can be used for a precision-guided treatment approach to WM.

19.
Mol Psychiatry ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32086435

RESUMO

Parkinson's disease (PD) is characterized by dopaminergic neuronal loss and the presence of intra-neuronal Lewy body (LB) inclusions with aggregated α-synuclein (α-Syn) as the major component. MAOB, a crucial monoamine oxidase for dopamine metabolism, triggers oxidative stress in dopaminergic neurons and α-Syn aggregation. However, the key molecular mechanism that mediates PD pathogenesis remains elusive. Here we show that C/EBPß acts as an age-dependent transcription factor for both α-Syn and MAOB, and initiates the PD pathologies by upregulating these two pivotal players, in addition to escalating δ-secretase activity to cleave α-Syn and promotes its neurotoxicity. Overexpression of C/EBPß in human wild-type α-Syn transgenic mice facilitates PD pathologies and elicits motor disorders associated with augmentation of δ-secretase, α-Syn, and MAOB. In contrast, depletion of C/EBPß from human α-Syn Tg mice abolishes rotenone-elicited PD pathologies and motor impairments via downregulating the expression of these key factors. Hence, our study supports that C/EBPß/δ-secretase signaling mediates PD pathogenesis via regulating the expression and cleavage of α-Syn and MAOB.

20.
Cardiovasc Diabetol ; 19(1): 22, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075646

RESUMO

BACKGROUND: Little is known about whether mitochondria 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of mitochondrial DNA (mtDNA) oxidative damage, contributes to the development of coronary artery disease (CAD) in diabetic patients. Here, we explored the associations of mtDNA 8-OHdG in leukocytes with obstructive CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year adverse outcomes after coronary revascularization in patients with type 2 diabetes mellitus (T2DM). METHODS: In a total of 1920 consecutive patients with T2DM who underwent coronary angiography due to symptoms of angina or angina equivalents, the presence of obstructive CAD, the number of diseased vessels with ≥ 50% stenosis, and modified Gensini score were cross-sectionally evaluated; the level of mtDNA 8-OHdG was quantified by quantitative PCR. Then, 701 of 1920 diabetic patients who further received coronary revascularization completed 1-year prospective follow-up to document major adverse cardiovascular and cerebral events (MACCEs). In vitro experiments were also performed to observe the effects of mtDNA oxidative damage in high glucose-cultured human umbilical vein endothelial cells (HUVECs). RESULTS: Cross-sectionally, greater mtDNA 8-OHdG was associated with increased odds of obstructive CAD (odds ratio [OR] 1.38, 95% CI confidence interval 1.24-1.52), higher degree of coronary stenosis (number of diseased vessels: OR 1.29, 95% CI 1.19-1.41; modified Gensini scores: OR 1.28, 95% CI 1.18-1.39), and higher levels of C-reactive protein (ß 0.18, 95% CI 0.06-0.31) after adjusting for confounders. Sensitivity analyses using propensity score matching yielded similar results. Stratification by smoking status showed that the association between mtDNA 8-OHdG and obstructive CAD was most evident in current smokers (Pinteration < 0.01). Prospectively, the adjusted hazards ratio per 1-SD increase in mtDNA 8-OHdG was 1.59 (95% CI 1.33-1.90) for predicting 1-year MACCEs after revascularization. In HUVECs, exposure to antimycin A, an inducer for mtDNA oxidative damage, led to adverse alterations in markers of mitochondrial and endothelia function. CONCLUSION: Greater mtDNA 8-OHdG in leukocytes may serve as an independent risk factor for CAD in patients with T2DM.

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