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1.
Aust Health Rev ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33038937

RESUMO

ObjectivePeople detained in police custody are a vulnerable population with complex health needs, sometimes requiring emergency care. This study evaluated the effect of a 24/7 nursing presence in a police watch house on police presentations to the emergency department (ED).MethodsThis was a retrospective observational study conducted in a regional ED in Queensland. Equal time periods of 66 days before (T1), during (T2) and after (T3) the pilot service was trialled in 2013 were compared to determine changes in patient and service delivery outcomes. The time to see a doctor in the ED, ED length of stay, hospital admission rate, number of transfers from the watch house to the ED and associated costs were measured. The nature of health care delivered by nurses to detainees in the watch house during the pilot was also examined.ResultsFewer detainees were transferred from the police watch house to the ED during the pilot period (T1, n=40; T2, n=29; T3, n=34). Cost reductions associated with reduced police and ambulance attendance, as well as hospitalisations, outweighed the watch house nursing costs, with cost savings estimated at AUD7800 per week (60% benefiting police; 40% benefiting the health service). The most common health problems addressed during the 1313 healthcare delivery episodes provided to 351 detainees in the watch house during the pilot related to substance misuse, chronic disease and mental health problems.ConclusionFewer transfers from the police watch house to the ED were noted when there was a 24/7 nursing presence in the watch house. This model appears to be economically efficient, but further research is required.What is known about the topic?People detained in police custody are a vulnerable population with complex health needs, sometimes requiring emergency care.What does this paper add?Transfers from the police watch house to the ED were fewer when there was a 24/7 nursing presence in the police watch house (an economically efficient model). Nursing care provided to detainees in the watch house setting predominantly related to substance misuse, chronic disease and mental health problems.What are the implications for practitioners?With a 24/7 nursing presence in the police watch house, transfer to the ED was avoided for some detainees. Similar strategies that respond to coronial recommendations advocating for enhancements in police-health collaboration warrant evaluation.

2.
J Cell Biochem ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043480

RESUMO

Rapid detection and classification of cancer cells with label-free and non-destructive methods are helpful for rapid screening of cancer patients in clinical settings. Here, surface-enhanced Raman scattering (SERS) was used for rapid, unlabeled, and non-destructive detection of seven different cell types, including human cancer cells and non-tumorous cells. Au nanoparticles were used as enhanced substrates and directly added to cell surfaces. The single cellular SERS signals could be easily and stably collected in several minutes, and the cells maintained structural integrity over one hour. Different types of cells had unique Raman phenotypes. By applying multivariate statistical analysis to the Raman phenotypes, the cancer cells and non-tumorous cells were accurately identified. The high sensitivity enabled this method to discriminate subtle molecular changes in different cell types, and the accuracy reached 81.2% with principal components analysis and linear discriminant analysis. The technique provided a rapid, unlabeled, and non-destructive method for the detection and identification of various cancer types.

3.
BMC Med Genomics ; 13(1): 145, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023625

RESUMO

BACKGROUND: Identification of master regulators (MRs) using transcriptome data in cervical cancer (CC) could help us to develop biomarkers and find novel drug targets to fight this disease. METHODS: We performed differential expression (DE) analyses of public microarray and RNA-seq transcriptome data of CC and normal cervical tissues (N). Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER) was used to convert the DE outcomes to differential activity (DA) signature for MRs. Synergy analysis was conducted to study synergistic effect of MR-pairs. TCGA and microarray data were used to test the association of expression of a MR and a clinical feature or a molecular feature (e.g. somatic mutations). Various bioinformatic tools/websites (DAVID, GEPIA2, Oncomine, cBioPortal) were used to analyze the expression of the top MRs and their regulons. RESULTS: Ten DE and 10 DA signatures were generated for CC. Two MRs, DNA topoisomerase II alpha (TOP2A) and centromere protein F (CENPF) were found to be up-regulated, activated and synergistic in CC compared to N across the 10 datasets. The two MRs activate a common set of genes (regulons) with functions in cell cycle, chromosome, DNA damage etc. Higher expression of CENPF was associated with metastasis. High expression of both MRs is associated with somatic mutation of a set of genes including tumor suppressors (TP53, MSH2, RB1) and genes involved in cancer pathways, cell cycle, DNA damage and repair. The magnitude of up-regulation and the absolute expression level of both MRs in CC are significantly higher compared to many other cancer types. CONCLUSION: TOP2A and CENPF are a synergistic pair of MRs that are overexpressed and activated in CC. Their high expression is correlated with some prognosis features (e.g. metastasis) and molecular features (e.g. somatic mutations) and distinctly high in CC vs. many other cancer types. They may be good biomarkers and anticancer drug targets for CC.

4.
Nat Commun ; 11(1): 4913, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004813

RESUMO

Reprograming of proline metabolism is critical for tumor growth. Here we show that PINCH-1 is highly expressed in lung adenocarcinoma and promotes proline synthesis through regulation of mitochondrial dynamics. Knockout (KO) of PINCH-1 increases dynamin-related protein 1 (DRP1) expression and mitochondrial fragmentation, which suppresses kindlin-2 mitochondrial translocation and interaction with pyrroline-5-carboxylate reductase 1 (PYCR1), resulting in inhibition of proline synthesis and cell proliferation. Depletion of DRP1 reverses PINCH-1 deficiency-induced defects on mitochondrial dynamics, proline synthesis and cell proliferation. Furthermore, overexpression of PYCR1 in PINCH-1 KO cells restores proline synthesis and cell proliferation, and suppresses DRP1 expression and mitochondrial fragmentation. Finally, ablation of PINCH-1 from lung adenocarcinoma in mouse increases DRP1 expression and inhibits PYCR1 expression, proline synthesis, fibrosis and tumor growth. Our results identify a signaling axis consisting of PINCH-1, DRP1 and PYCR1 that regulates mitochondrial dynamics and proline synthesis, and suggest an attractive strategy for alleviation of tumor growth.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma de Pulmão/patologia , Proteínas com Domínio LIM/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Membrana/metabolismo , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Proliferação de Células/genética , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Dinaminas/metabolismo , Feminino , Técnicas de Inativação de Genes , Humanos , Proteínas com Domínio LIM/genética , Pulmão/citologia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Proteínas Musculares/metabolismo , Proteínas de Neoplasias/metabolismo , Prolina/biossíntese , Proteínas Proto-Oncogênicas p21(ras)/genética , Pirrolina Carboxilato Redutases/metabolismo , Análise de Sobrevida
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1545-1550, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067952

RESUMO

OBJECTIVE: To investigate the expression and mechanism of histone acetyltransferase 2A (KAT2A) and cyclin D1 dependent kinase 4/6 (CDK4/CDK6) in children with acute leukemia(AL). METHODS: Seventy-one children with leukemia were selected from June 2017 to November 2018 and were enrolled in AL children group. 59 persons of healthy physical examination were selected and enrolled in control group. Real-time fluorescent quantification PCR chip was used to determine the expression of histone-modified genes and the expression levels of CDK4, CDK6 and CDK4/CDK6 mRNA; Western blot was used to validated KAT2A-positive expression; SPSS Pearson correlation analysis software was used to analyze the correlation between KAT2A and CDK4/CDK6 expression in children with acute leukemia. RESULTS: By comprehensive analysis of the existing chip data, the positive expression of KAT2A in the AL children group was 78.87%, which was higher than that in the control group (8.47%) (P<0.05). The expression level of CDK4 and CDK6 mRNA in the AL children group was higher than that in the control group (P<0.05); the expression level of CDK4/CDK6 mRNA in the AL children group was lower than that in the control group (P<0.05). The results of Western blot showed that the expression levels of KAT2A, CDK4 and CDK6 in AL children were higher than those in the control group, while the CDK4/CDK6 expression level in AL children group was lower than that in control group. The results of SPSS Pearson correlation analysis showed that the positive expression rate of KAT2A in AL children group positively correlated with expression level of CDK4 and CDK6 mRNA(r=0.673, r=0.559), and negatively correlated with expression level of CDK4/CDK6 mRNA(r=-0.762). CONCLUSION: The KAT2A is highly expressed in AL children, while the CDK4/CDK6 is lowly expressed in AL children, there is a significant correlation between of them, which is expected to become a new target for the treatment of acute leukemia children.


Assuntos
Histonas , Leucemia Mieloide Aguda , Criança , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Histona Acetiltransferases , Humanos , RNA Mensageiro
6.
Diabetes Metab J ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-33081427

RESUMO

Background: Identification of modifiable dietary factors, which are involved in the development of gestational diabetes mellitus (GDM), could inform strategies to prevent GDM. Methods: We examined the dietary patterns in a Chinese population and evaluated their relationship with GDM risk using a case-control study including 1,464 cases and 8,092 control subjects. Propensity score matching was used to reduce the imbalance of covariates between cases and controls. Dietary patterns were identified using factor analysis while their associations with GDM risk were evaluated using logistic regression models. Results: A "vegetable" dietary pattern was characterized as the consumption of green leafy vegetables (Chinese little greens and bean seedling), other vegetables (cabbages, carrots, tomatoes, eggplants, potatoes, mushrooms, peppers, bamboo shoots, agarics, and garlic), and bean products (soybean milk, tofu, kidney beans, and cowpea). For every quartile increase in the vegetables factor score during 1 year prior to conception, the first trimester, and the second trimester of pregnancy, the GDM risk lowered by 6% (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89 to 0.99), 7% (OR, 0.94; 95% CI, 0.88 to 0.99), and 9% (OR, 0.91; 95% CI, 0.86 to 0.96). Conclusion: In conclusion, our study suggests that the vegetable dietary pattern is associated with lower GDM risk; however, the interpretation of the result should with caution due to the limitations in our study, and additional studies are necessary to explore the underlying mechanism of this relationship.

7.
Eur J Pharmacol ; 889: 173618, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010302

RESUMO

Pulmonary hypertension (PH) is a progressive and potentially serious lung disease, defined by an abnormal elevation of pulmonary arterial pressure. PH occurs for many reasons, and hypoxia is considered as an important stimulus for the disease. Proliferation and migration of pulmonary artery smooth muscular cells (PASMCs) in the small peripheral pulmonary arteries are common characteristic features in hypoxia-induced PH (HPH). However, the mechanisms involved in the hypoxia-induced cell proliferation and migration are not clear. The aim of the present study was to investigate the role of lncRNA Gas5 in the hypoxia-stimulated proliferation and migration of human PASMCs (hPASMCs). We found that the expression of Gas5 was down-regulated in a rat model with hypoxia and in cultured hypoxic hPASMCs, and silence of Gas5 significantly promoted hPASMCs proliferation and migration in both normal and hypoxia condition. Subsequent studies revealed that miR-23b-3p interacted with Gas5 by directly targeting the miRNA-binding site in the Gas5 sequence, and qRT-PCR results showed miR-23b-3p and Gas5 could affect each other's expression, respectively. Further study demonstrated that Gas5 acted as a competing endogenous RNA (ceRNA) for miR-23b-3p to modulate the KCNK3 expression, and these interactions led to promotion of hPASMCs proliferation and migration. This study identified that Gas5/miR-23b-3p/KCNK3 axis may be a mechanism that hypoxia-induced PASMCs proliferation and migration, providing a strategy for clinical treatment of HPH in the future.

8.
Theranostics ; 10(25): 11837-11861, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052249

RESUMO

Recently, the rapid development of biomaterials has induced great interest in the precisely targeted treatment of bone-related diseases, including bone cancers, infections, and inflammation. Realizing noninvasive therapeutic effects, as well as improving bone tissue regeneration, is essential for the success of bone­related disease therapies. In recent years, researchers have focused on the development of stimuli-responsive strategies to treat bone-related diseases and to realize bone regeneration. Among the various external stimuli for targeted therapy, near infrared (NIR) light has attracted considerable interests due to its high tissue penetration capacity, minimal damage toward normal tissues, and easy remote control properties. The main objective of this systematic review was to reveal the current applications of NIR light-assisted phototherapy for bone-related disease treatment and bone tissue regeneration. Database collection was completed by June 1, 2020, and a total of 81 relevant studies were finally included. We outlined the various therapeutic applications of photothermal, photodynamic and photobiomodulation effects under NIR light irradiation for bone­related disease treatment and bone regeneration, based on the retrieved literatures. In addition, the advantages and promising applications of NIR light-responsive drug delivery systems for spatiotemporal-controlled therapy were summarized. These findings have revealed that NIR light-assisted phototherapy plays an important role in bone-related disease treatment and bone tissue regeneration, with significant promise for further biomedical and clinical applications.

9.
J Ovarian Res ; 13(1): 122, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33069244

RESUMO

BACKGROUND: Long intergenic non-coding RNA 01094 (LINC01094) is probably a novel regulator in cancer biology. This study aimed to probe into the function and mechanism of LINC01094 in ovarian cancer (OC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was utilized to measure LINC01094 and miR-577 expressions in OC tissues and cell lines. Western blot was used to examine the expressions of epithelial-mesenchymal transition (EMT)-related proteins, ß-catenin, c-Myc and cyclin D1. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect the proliferation, migration and invasion of SKOV3 and 3AO cells, respectively. Eventually, dual-luciferase reporter gene assay was employed to detect the regulatory relationship between miR-577 and LINC01094. RESULTS: LINC01094 expression was elevated in OC tissues and cell lines. High LINC01094 expression was associated with higher FIGO stage, lymph node metastasis and the shorter overall survival rate in patients with OC. Meanwhile, LINC01094 knockdown inhibited OC cell proliferation, migration, invasion and EMT. In addition, miR-577 was demonstrated to be a direct downstream target of LINC01094 in OC and inhibition of miR-577 reversed the biological effects of LINC01094 knockdown on OC cells. Additionally, LINC01094 / miR-577 axis regulated the expressions of ß-catenin, c-Myc and cyclin D1 in OC cells. CONCLUSION: LINC01094 promotes the proliferation, migration, invasion and EMT of OC cells by adsorbing miR-577.

10.
Medicine (Baltimore) ; 99(42): e22285, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080673

RESUMO

The spatial distribution of lymph node (LN) metastasis was analyzed to provide data for an evidence-based approach to radiotherapy field design, particularly for guiding intensity-modulated radiation therapy. A total of 1886 postoperative patients were retrospectively reviewed. Pelvic LNs were classified as common iliac nodes, external iliac nodes, internal iliac nodes/obturator nodes, and deep inguinal nodes. The distribution of LN metastasis in these subgroups was calculated, and the distribution patterns of LN metastasis according to the pathologic types were investigated.We identified 392 eligible patients with LN metastasis. The frequency and number of external iliac node metastasis were higher in the left side in both single subgroup (P < .01) and cosubgroup (P = .04) analyses, whereas few differences were found in other subgroups. Among patients with squamous cell carcinoma, left external iliac node metastasis was observed in 102 (15.13%) patients, whereas right metastasis was observed in 65 (9.64%) patients, and the difference was significant (P < .01).The present results indicated uneven distribution of LN metastasis in the different subgroups, which could help surgeon focus on the dissection of the left subgroups, and help oncologists define margins, refine target volumes for radiation, and improve the accuracy of postoperative radiotherapy especially in patients with squamous cell carcinoma.

11.
Epidemiol Infect ; 148: e241, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32998791

RESUMO

A recently developed pneumonia caused by SARS-CoV-2 has quickly spread across the world. Unfortunately, a simplified risk score that could easily be used in primary care or general practice settings has not been developed. The objective of this study is to identify a simplified risk score that could easily be used to quickly triage severe COVID-19 patients. All severe and critical adult patients with laboratory-confirmed COVID-19 on the West campus of Union Hospital, Wuhan, China, from 28 January 2020 to 29 February 2020 were included in this study. Clinical data and laboratory results were obtained. CURB-65 pneumonia score was calculated. Univariate logistic regressions were applied to explore risk factors associated with in-hospital death. We used the receiver operating characteristic curve and multivariate COX-PH model to analyse risk factors for in-hospital death. A total of 74 patients (31 died, 43 survived) were finally included in the study. We observed that compared with survivors, non-survivors were older and illustrated higher respiratory rate, neutrophil-to-lymphocyte ratio, D-dimer and lactate dehydrogenase (LDH), but lower SpO2 as well as impaired liver function, especially synthesis function. CURB-65 showed good performance for predicting in-hospital death (area under curve 0.81, 95% confidence interval (CI) 0.71-0.91). CURB-65 ⩾ 2 may serve as a cut-off value for prediction of in-hospital death in severe patients with COVID-19 (sensitivity 68%, specificity 81%, F1 score 0.7). CURB-65 (hazard ratio (HR) 1.61; 95% CI 1.05-2.46), LDH (HR 1.003; 95% CI 1.001-1.004) and albumin (HR 0.9; 95% CI 0.81-1) were risk factors for in-hospital death in severe patients with COVID-19. Our study indicates CURB-65 may serve as a useful prognostic marker in COVID-19 patients, which could be used to quickly triage severe patients in primary care or general practice settings.

12.
Int Urol Nephrol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025405

RESUMO

The overlap syndromes of anti-neutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis (AACGN) and variants of immune complex medicated glomerulopathy (ICMGN) have been reported. But very few have compared AACGN alone with the overlap syndromes (AACGN plus ICMGN). The aim of this retrospective study was to make that comparison, following serum creatinine (sCr) to determine whether the two groups (AACGN-only group versus overlap group) would behave differently over time. We identified 14 cases with dual diagnoses of AACGN and various ICMGN in the overlap group. Data were collected and compared with 15 randomly selected AACGN-only cases over the similar period of time. The overlap syndrome represented 0.35% of our overall biopsies (14/4049). All 14 patients were ANCA positive and had crescentic formation. The percentage of crescents in the biopsies ranged from 10 to 78%. ICMGN included the following: membranoproliferative glomerulonephritis, post-infectious glomerulonephritis, membranous glomerulopathies, idiopathic mesangial proliferative glomerulonephritis, lupus nephritis, and IgA nephropathy. With the exception one biopsy revealing lupus nephritis class III, most of the ICMGN were mild. When compared to the AACGN-only group, there were no significant differences in clinical and histologic indices including age, percent of crescents, and sCr (on biopsy days, and over the follow-up periods), although the numbers of follow-up cases were limited over time. Our findings suggest that AACGN was the dominant disease process in the majority of overlap syndromes between AACGN and ICMGN, similar to the clinical processes of AACGN-only disease, therefore, the AACGN in overlap syndrome cases should be the main target for clinical management.

13.
Nat Commun ; 11(1): 4694, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020471

RESUMO

Tough hydrogels that are capable of efficient mechanical energy dissipation and withstanding large strains have potential applications in diverse areas. However, most reported fabrication strategies are performed in multiple steps with long-time UV irradiation or heating at high temperatures, limiting their biological and industrial applications. Hydrogels formed with a single pair of mechanisms are unstable in harsh conditions. Here we report a one-step, biocompatible, straightforward and general strategy to prepare tough soft hydrogels in a few tens of seconds under mild conditions. With a multimechanism design, the network structures remarkably improve the mechanical properties of hydrogels and maintain their high toughness in various environments. The broad compatibility of the proposed method with a spectrum of printing technologies makes it suitable for potential applications requiring high-resolution patterns/structures. This strategy opens horizons to inspire the design and application of high-performance hydrogels in fields of material chemistry, tissue engineering, and flexible electronics.

14.
Phys Chem Chem Phys ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016301

RESUMO

Wafer-scale growth of the unidirectional graphene monolayer on Ge surfaces has rejuvenated the intense study of the surfaces and interfaces of semiconductors underneath graphene. Recently, it was reported that the Ge atoms in the Ge(110) surface beneath a graphene monolayer underwent a rearrangement and formed an ordered (6 × 2) reconstruction. However, a plausible atomic model related to this (6 × 2) reconstruction is still lacking. Here, by using scanning tunnelling microscopy/spectroscopy (STM/S) and density functional theory (DFT) calculations, we deeply investigated the structural and electronic properties of the Ge(110) (6 × 2) surface encapsulated by a graphene monolayer. The (6 × 2) surface reconstruction was confirmed for the post-annealing-graphene-covered Ge(110) surface via STM, and was found to be quite air-stable, owing to the protection of the graphene monolayer against surface oxidation. Our study disclosed that the topographic features of the topmost graphene monolayer and the Ge(110) surface could be selectively imaged by utilizing suitable scanning biases. According to the STM results and DFT calculations, a rational ball-and-stick model of the (6 × 2) reconstruction was successfully provided, in which an elemental building block comprising two Ge triangles and two isolated Ge atoms adsorbed on the unreconstructed ideal Ge(110) surface. Local density of states of the graphene/Ge surface was explored via scanning tunneling spectroscopy (STS), presenting four well-defined differential conductance (dI/dV) peaks, protruding at energies of 0.2, 0.4, 0.6 and 0.8 eV, respectively. The four peaks predominantly originated from the surface states of the reconstructing adatoms and were well reproduced by our theoretical simulation. This result means that the Ge surface is very robust after being encapsulated by the epitaxial graphene, which could be advantageous for directly fabricating graphene/Ge-hybrid high-speed electronics and optoelectronics based on conventional microelectronics technology.

15.
Phys Rev Lett ; 125(12): 123201, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33016713

RESUMO

Rabi oscillation, originally proposed in nuclear magnetic resonance, is a well-known phenomenon associated with a driven two-level system. Although magnetic fields typically can bring about chirality into unusual phenomena such as chiral edge states in the quantum Hall effect, it is not clear if chirality exists in Rabi oscillations. Here we unveil the intrinsic chirality carried by the phase in a Rabi problem. For opposite detuning of the driving field, the phase evolution of the probability amplitude exhibits a mirror symmetry. Consequently, constructive or destructive interference of two off-resonant Rabi processes under different initial conditions is level dependent and symmetry protected. Experimentally, we demonstrate such features in a photonic setting with adjustable detuning, yet our results may prove pertinent to the study of similar phenomena in other driven two-level systems beyond photonics.

16.
J Cell Mol Med ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33090698

RESUMO

Retinoblastoma (RB) is a common intraocular malignancy in children. Due to the poor prognosis of RB, it is crucial to search for efficient diagnostic and therapeutic strategies. Studies have shown that methyltransferase-like 3 (METTL3), a major RNA N (6)-adenosine methyltransferase, is closely related to the initiation and development of cancers. Nevertheless, whether METTL3 is associated with RB remains unexplored. Therefore, we investigated the function and mechanisms of METTL3 in the regulation of RB progression. We manipulated METTL3 expression in RB cells. Then, cell proliferation, apoptosis, migration and invasion were analysed. We also analysed the expression of PI3K/AKT/mTOR pathway members. Finally, we incorporated subcutaneous xenograft mouse models into our studies. The results showed that METTL3 is highly expressed in RB patients and RB cells. We found that METTL3 knockdown decreases cell proliferation, migration and invasion of RB cells, while METTL3 overexpression promotes RB progression in vitro and in vivo. Moreover, two downstream members of the PI3K/AKT/mTOR pathway, P70S6K and 4EBP1, were affected by METTL3. Our study revealed that METTL3 promotes the progression of RB through PI3K/AKT/mTOR pathways in vitro and in vivo. Targeting the METTL3/PI3K/AKT/mTOR signalling axis could be a promising therapeutic strategy for the treatment of RB.

17.
PLoS Pathog ; 16(10): e1008994, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33049000

RESUMO

Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet+ CD4+ T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4+ T cells, but the underlying mechanisms of these immunoregulatory pathways are not clear. Here we studied the role of IL-27 signalling in experimental visceral leishmaniasis (VL) caused by infection of C57BL/6 mice with the human pathogen Leishmania donovani. We found IL-27 signalling was critical for the development of IL-10-producing Th1 (Tr1) cells during infection. Furthermore, in the absence of IL-27 signalling, there was improved control of parasite growth, but accelerated splenic pathology characterised by the loss of marginal zone macrophages. Critically, we discovered that IL-27 signalling limited glycolysis in Th1 cells during infection that in turn attenuated inflammation. Furthermore, the modulation of glycolysis in the absence of IL-27 signalling restricted tissue pathology without compromising anti-parasitic immunity. Together, these findings identify a novel mechanism by which IL-27 mediates immune regulation during disease by regulating cellular metabolism.

18.
Toxicol Appl Pharmacol ; 409: 115286, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068621

RESUMO

Postoperative cognitive dysfunction (POCD) is deemed to a severe surgical complication without effective treatment. Previous work has confirmed the important modulatory role of hydrogen sulfide (H2S) in cognitive function. This study was proposed to explore whether H2S relieves POCD and the possible mechanisms. We demonstrated that NaHS (a donor of H2S) reversed the inhibited endogenous H2S generation in the hippocampus of postoperative rats. NaHS attenuated the cognitive impairment of postoperative rats in the Y-maze, Novel object recognition, and Morris water maze tests. NaHS enhanced the expressions of synaptic plasticity-related proteins, synapsin-1 and PSD-95, increased the synaptic density, and decreased the destruction of synaptic structures in the hippocampus of postoperative rats. Moreover, NaHS promoted Warburg effect in the hippocampus of postoperative rats, as reflected by increases in the expressions of hexokinase 2, pyruvate kinase M2, lactate dehydrogenase A, and pyruvate dehydrogenase kinase 1, an enhancement in the content of lactate, and a reduction in the expression of pyruvate dehydrogenase. The inhibitor of Warburg effect, 2-Deoxy-D-glucose (2-DG), not only reversed NaHS-enhanced Warburg effect in the hippocampus of postoperative rats, but also significantly abolished NaHS-exerted protective effect on cognitive function. Furthermore, 2-DG reversed NaHS-exerted enhancement in the expressions of synapsin-1 and PSD-95, increase in the synaptic density, and decrease in the destruction of synaptic structures in the hippocampus of postoperative rats. Collectively, these results indicate that H2S alleviates POCD through enhancing hippocampal Warburg effect, which subsequently improves synaptic plasticity in the hippocampus.

20.
Molecules ; 25(20)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33076563

RESUMO

In order to explore highly efficient flame-retardant rigid polyurethane foam (RPUF), phosphorus/nitrogen compounds and expandable graphite (EG) were successfully incorporated into RPUF by a free one-spot method. The combustion results showed that the fire safety of the RPUF samples was remarkably improved by the addition of phosphoric/nitrogen compounds and EG. With the incorporation of 22.4 wt.% phosphorus/nitrogen compounds and 3.2 wt.% EG, the RPUF composites achieved UL-94 V-0 rating. Besides, the total heat release and total smoke release of RPUF composites were reduced by 29.6% and 32.4% respectively, compared to those of the pure RPUF sample. PO• and PO2• together with nonflammable gaseous products were evolved from phosphoric/nitrogen compounds in the gas phase, which quenched the flammable free radicals in the matrix and diluted the concentration of combustible gaseous products generated from PRUF during combustion. The compact char residues which acted as excellent physical barriers were formed by catalysis of EG and phosphoric/nitrogen compounds in the condense phase. The fire hazard of RPUF was significantly reduced by the synergistic effect of phosphorus-nitrogen compounds and EG. This work provides a promising strategy to enhance the fire safety of RPUF.

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