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1.
Bioengineered ; 12(1): 1369-1380, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33904373

RESUMO

Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major threat to human health without effective therapeutic drugs. Previous studies demonstrated the power of gene expression profiling to reveal pathological changes associated with sepsis-induced ARDS. However, there is still a lack of systematic data mining framework for identifying potential targets for treatment. In this study, we demonstrated the feasibility of druggable targets prediction based on gene expression data. Through the functional enrichment analysis of microarray-based expression profiles between sepsis-induced ARDS and non-sepsis ARDS samples, we revealed genes involved in anti-microbial infection immunity were significantly altered in sepsis-induced ARDS. Protein-protein interaction (PPI) network analysis highlighted TOP2A gene as the key regulator in the dysregulated gene network of sepsis-induced ARDS. We were also able to predict several therapeutic drug candidates for sepsis-induced ARDS using Connectivity Map (Cmap) database, among which doxorubicin was identified to interact with TOP2A with a high affinity similar to its endogenous ligand. Overall, our findings suggest that doxorubicin could be a potential therapeutic for sepsis-induced ARDS by targeting TOP2A, which requires further investigation and validation. The whole study relies on publicly available dataset and publicly accessible database or bioinformatic tools for data mining. Therefore, our study benchmarks a workflow for druggable target prediction which can be widely applicable in the search of targets in other pathological conditions.

2.
Biol Reprod ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33899080

RESUMO

Upon fertilization, extensive chromatin reprogramming occurs during preimplantation development. Growing evidence reveals species-dependent regulations of this process in mammals. ATP-dependent chromatin remodeling factor SMARCA5 (also known as SNF2H) is required for peri-implantation development in mice. However, the specific functional role of SMARCA5 in preimplantation development and if it is conserved among species remain unclear. Herein, comparative analysis of public RNA-seq datasets reveals that SMARCA5 is universally expressed during oocyte maturation and preimplantation development in mice, cattle, humans and pigs with species-specific patterns. Immunostaining analysis further describes the temporal and spatial changes of SMARCA5 in both mouse and bovine models. siRNA-mediated SMARCA5 depletion reduces the developmental capability and compromises the specification and differentiation of inner cell mass in mouse preimplantation embryos. Indeed, OCT4 is not restricted into the inner cell mass and the formation of epiblast and primitive endoderm disturbed with reduced NANOG and SOX17 in SMARCA5-deficient blastocysts. RNA-seq analysis shows SMARCA5 depletion causes limited effects on the transcriptomics at the morula stage, however, dysregulates 402 genes, including genes involved in transcription regulation and cell proliferation at the blastocyst stage in mice. By comparison, SMARCA5 depletion does not affect the development through the blastocyst stage but significantly compromises the blastocyst quality in cattle. Primitive endoderm formation is greatly disrupted with reduced GATA6 in bovine blastocysts. Overall, our studies demonstrate the importance of SMARCA5 in fostering the preimplantation development in mice and cattle while there are species-specific effects.

3.
Anal Chem ; 93(17): 6715-6722, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33887142

RESUMO

For intracellular molecular detection, the appropriate probes should include the abilities to enter target cells noninvasively, target specific sites, and then respond to the analytes reliably. Herein, a ratiometric fluorescent DNA nanostructure (RFDN) was designed for mitochondrial adenosine triphosphate (ATP) imaging in living cells. The DNA nanostructure was constructed by continuous hybridization of two hairpin DNA strands (HS1-Cy3 and HS2-Cy5) under the initiation of the trigger. HS1-Cy3 and HS2-Cy5 contained split aptamer fragments of ATP and are labeled with a fluorescent donor (Cy3) and acceptor (Cy5), respectively. The RFDN integrated multiple split aptamer fragments and increased the local concentration of sensing probes. The binding of ATP to aptamer fragments on the RFDN shortened the distance between Cy3 and Cy5, resulting in obvious ratiometric signals (fluorescence resonance energy transfer). The RFDN showed good biocompatibility and can be internalized into cells in a caveolin-dependent endocytosis pathway. The co-localization imaging results indicated that the DNA nanostructure could target the mitochondria via Cy3 and Cy5. Moreover, the confocal imaging results showed that the intracellular ATP changes stimulated by drugs in living cells could be indicated by the RFDN. In this way, the RFDN is expected to be a simple, flexible, and general platform for chemo/biosensing in living cells.

4.
Int J Biol Sci ; 17(3): 742-755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767585

RESUMO

Klotho expression abnormalities induces kidney injury and chronic kidney disease, however, the underlying mechanism remains unclear. Here, Klotho+/- mice and wild-type mice were treated with low-dose bovine serum albumin (BSA). Pathological examination demonstrated that the area of glomerular collagen deposition and fibrosis in BSA-Kl-/+ mice was significantly larger than that in BSA-WT mice. The serum levels of superoxide dismutase, malondialdehyde, creatinine, and urea in BSA-Kl-/+ mice were significantly increased. Sequencing of gut microbiota 16S rRNA v3-v4 region indicated that BSA-Kl-/+ mice showed a significantly higher relative abundance of the genera Dubosiella, Akkermansia, Alloprevotella, and Lachnospiraceae and a significantly lower relative abundance of the genera Allobaculum and Muribaculaceae than BSA-WT mice. KEGG analysis revealed that the metabolic pathways of signal transduction, xenobiotic biodegradation and metabolism, and lipid metabolism increased significantly in BSA-Kl-/+ mice. Flow cytometry showed that the proportion of CD68+/CD11b+ cells in the peripheral blood was significantly higher in BSA-KL-/+ mice than that in BSA-WT mice. qPCR and western blot suggested that Klotho and Nrf2 expression in MΦ1 cells of BSA-KL-/+ mice was significantly decreased. Thus, the findings suggest during the immune activation and chronic inflammation induced by the gut microbiota imbalance in Klotho-deficient mice treated to BSA, disrupted expression of proteins in the Nrf2/NF-κB signaling pathway in monocyte-derived macrophage M1 cells leads to the aggravation of inflammation and kidney injury.

5.
Biol Reprod ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763686

RESUMO

The NOTCH signaling pathway plays an important role in regulating various biological processes, including lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of the NOTCH pathway in early embryonic development is poorly understood, especially in large animals. Here, we show that the expression of genes encoding key transcripts of the NOTCH pathway is dynamic throughout early embryonic development. We also confirm the presence of active NOTCH1 and RBPJ. By using pharmacological and RNAi tools, we demonstrate that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator-RBPJ, whose deficiency also compromised the embryo quality. Indeed, both NOTCH1 and RBPJ knockdown cause a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres, suggesting a cell cycle arrest at mitosis. Importantly, RNA-seq analyses reveal that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.

6.
Scand J Immunol ; : e13038, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33665864

RESUMO

The inflammatory process in systemic lupus erythematosus (SLE) affects many organs including the lungs. Chemokines are suggested to play important roles in the pathogenesis of SLE with pulmonary fibrosis (PF). In the present study, our objective is to evaluate the correlation between chemokines and PF in SLE patients. Transcriptome sequencing analysis was used to find the different expressed genes between SLE patients with PF and without PF. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in SLE patients and healthy controls. Expression of CX3CR1 was measured by real-time polymerase chain reaction (PCR) and flow cytometer. Sixteen differentially chemokine genes were found to be associated to SLE with PF. Meanwhile, the upregulation of C-X3-C motif chemokine receptor 1 (CX3CR1) and its ligand, CX3C chemokine ligand 1 (CX3CL1) were observed in SLE patients with PF than that of SLE patients without PF and healthy control. Phenotypic analysis also showed that the surface expression of CX3CR1 increased in PBMCs from SLE patients with PF. Our observations indicated that CX3CL1/CX3CR1 axis is associated with PF in SLE. CX3CR1 might be a promising predictor of SLE with PF and the interactions between CX3CL1 and CX3CR1 might provide potential candidate target for the treatment of SLE with PF.

7.
Asia Pac J Clin Nutr ; 30(1): 130-139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787049

RESUMO

BACKGROUND AND OBJECTIVES: The correlation between chili pepper intake and gastric cancer (GC) risk has been controversial. We conducted a meta-analysis of 16 studies to provide updated evidence for this uncertainty. METHODS AND STUDY DESIGN: Medline, and China National Knowledge Infrastructure (CNKI) databases were searched to obtain all qualified literature related to pepper consumption and GC incidence before June 2020. Random effects models were adopted to integrate the relative risk of individual studies. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the literature of each included study. Dose response meta-analysis was implemented through the one-stage robust error meta-regression (REMR) approach. RESULTS: 16 studies (8337 cases) were included in quantitative meta-analysis. The pooled odds ratio (OR) of GC for the highest versus the lowest category of chili consumption were 1.51 (95% confidence interval [CI]=1.02-2.00) for all countries, 2.05 (95% CI=1.15-2.95) for Mexican, 2.03 (95% CI =0.71-3.34) for Colombian, 1.92 (95% CI=1.21-2.64) for Asian and 0.48 (95% CI=0.24-0.72) for other countries. Dose-response meta-analysis showed that there was a positive linear correlation between the risk of GC and the daily frequency of chili consumption. CONCLUSIONS: Significantly increased consumption of chili pepper or capsaicin has the potential to increase the risk of gastric cancer, however, inconsistencies still exist in subgroup analysis between different regions.

8.
J Hazard Mater ; 411: 125129, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33486229

RESUMO

Thermal treatment can not only efficiently remove volatile pollutants but also distinctly alter the speciation of organic carbon (C) and the behaviors of residual pollutants in contaminated soils. Here we examined the distribution and bioaccessibility of polycyclic aromatic hydrocarbons (PAHs) in industrially contaminated site soils affected by thermal treatment (temperature ranging of 105-650 â„ƒ) using synchrotron-based infrared microspectroscopy and n-butanol extraction (a mild solvent extractant). In the pristine soils, the sequestration and distribution of PAHs were simultaneously controlled by aromatic C, aliphatic C and clay minerals. Desorption efficiency of PAHs was substantially increased with increasing temperature, whereas the residual PAHs were strongly immobilized within their binding sites evidenced by their dramatically decreased bioaccessibility. Aliphatic and carboxylic C were gradually decomposed and/or carbonized with increasing temperature. In contrast, aromatic C remained relatively recalcitrant during the thermal treatment and was the key controlling factor for the desorption of residual PAHs in the soils with either thermal treatment or n-butanol extraction. This study is the first to visualize the changes in the binding sites and bioaccessibility of PAHs induced by thermal treatment, which have important implications for understanding the sequestration mechanisms of organic pollutants in soil and optimizing the remediation technique.

9.
Br J Pharmacol ; 178(7): 1669-1683, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33501656

RESUMO

BACKGROUND AND PURPOSE: Itching is the most frequent pathology in dermatology that has significant impacts on people's mental health and social life. Transient receptor potential vanilloid 3 (TRPV3) channel is a promising target for treating pruritus. However, few selecetive and potent antagonists have been reported. This study was designed to identify selective TRPV3 antagonist and elucidate its anti-pruritus pharmacology. EXPERIMENTAL APPROACH: FlexStation and calcium fluorescence imaging were conducted to track the functional compounds. Whole-cell patch clamp was used to record itch-related ion channel currents. Homologous recombination and site-directed mutagenesis were employed to construct TRPV3 channel chimeras and point mutations for exploring pharmacological mechanism. Mouse models were used for in vivo anti-pruritus assay. KEY RESULTS: An acridone alkaloid (citrusinine-II) was purified and characterized from Atalantia monophylla. It directly interacts with Y564 within S4 helix of TRPV3 to selectively inhibit the channel with a half maximal inhibitory concentration (IC50 ) of 12.43 µM. Citrusinine-II showed potential efficacy to attenuate both chronic and acute itch. Intradermal administration of citrusinine-II (143 ng/skin site) nearly completely inhibited itch behaviours. It also shows significant analgesic effects. Little side effects of the compound are observed. CONCLUSION AND IMPLICATIONS: By acting as a selective and potent inhibitor of TRPV3 channel, citrusinine-II shows valuable therapeutic effects in pruritus animal models and is a promising candidate drug and/or lead molecule for the development of anti-pruritus drugs.

10.
Waste Manag ; 121: 276-285, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33388650

RESUMO

Sulfur (S) is an abundant and redox-active element in urban wastewater systems and plays a critical role in both the wastewater and sludge treatment processes. This study comparatively characterized the transformation of S and several closely associated metals (Cu, Zn, and Fe) during pyrolysis (250 to 750 °C) and hydrothermal carbonization (HTC, 150 to 275 °C) treatments of sewage sludge. S, Fe, Zn, and Cu K-edge X-ray absorption spectroscopy was applied to quantitatively evaluate the fate of S and contribution of different S species in regulating metal speciation. During pyrolysis, aliphatic-S and sulfonate were preferentially degraded at low temperature (below 350 °C) and sulfate was thermochemically reduced at temperature above 450 °C, while metal sulfides (up to 27%) and thiophenes (up to 70%) were increasingly formed. Similar to the pyrolysis process, metal sulfides (up to 40% at temperature above 200 °C) and thiophenes were formed during HTC. The degradation of thiols and organic sulfide, as well as sulfate reduction, released sulfide and strongly affected metal speciation. For example, almost all Cu and half of Zn were transformed into Cu-Fe- or Zn-Fe-sulfides during HTC, whereas they were partially desulfidized during pyrolysis. High abundance of reduced S species (S-1 and S-2) in hydrochars may contribute to their strong reductive adsorption of Cr(VI). Results from this work reveal the thermochemical reactions driving the transformations of S and its associated metals during pyrolysis and HTC. The results provide fundamental knowledge for selecting thermochemical sludge treatment techniques for value-added applications of the products.


Assuntos
Metais Pesados , Esgotos , Pirólise , Enxofre , Águas Residuárias , Espectroscopia por Absorção de Raios X
11.
Spine (Phila Pa 1976) ; 46(11): E611-E617, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33428360

RESUMO

MINI: The anatomical relationship of the extrapedicular approach with the spinal nerve and its branches was researched in cadavers. Three types of extrapedicular paths were simulated: puncture inside the medial branch (MB), puncture outside the MB, and puncture outside the lateral branch (LB). At L1-L3, puncture outside the LB could avoid damage to these nerves.

12.
Sci Total Environ ; 753: 141872, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32906041

RESUMO

The phytotoxicities of TBECH diastereomers to plants at the biochemical and molecular levels were investigated in a hydroponic study by using maize as a model plant. The results showed that TBECH could induce the production of two species of reactive oxygen species (ROS), O2•- and H2O2, in maize tissues. The accumulation of ROS was the highest when maize was exposed to ß-TBECH. TBECH enhanced the phosphorylation of plant histone, and the contents of γ-H2AX in maize followed the order ß-TBECH > αß-TBECH > γδ-TBECH > γ-TBECH. Transcriptome profiling revealed that antioxidant enzyme genes (AEGs) were over-expressed in maize when stressed by technical grade TBECH. The RT-PCR detection further validated that three typical AEGs, including CAT, SOD, and POD genes, were time-dependent and selectively expressed under the influence of TBECH diastereomers. Molecular compositions of maize root exudates characterized by FT-ICR-MS were significantly different among the four groups of TBECH diastereomer treatments. TBECH diastereomers specifically affected the chemical diversity and abundance of root exudates. New insights into the biochemical effects of TBECH on plants are provided in this work, which is helpful to deepening the understanding of their stereo-selectivity.


Assuntos
Retardadores de Chama , Zea mays , Antioxidantes , Cicloexanos , Dano ao DNA , Peróxido de Hidrogênio , Estresse Oxidativo , Zea mays/genética
13.
Carbohydr Polym ; 252: 117138, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183597

RESUMO

Bacterial adhesion infection caused by medical materials in clinical application has become a serious threat, and it urgently needs new strategies to deal with these clinical challenges. In this work, LED209, a highly selective histidine sensor kinase inhibitor of Gram-negative bacteria, was covalently attached on cellulose membrane (CM) via click reaction. The data of contact angle measurements, ATR-FTIR and X-ray photoelectron spectroscopy confirmed the successful synthesis of LED-CM. In addition, the results of antibacterial activity of the membranes shown that LED-CM exhibited excellent anti-adhesion ability to Enterohemorrhagic Escherichia coli (EHEC), and significantly reduced the formation of bacterial biofilm. Importantly, LED-CM was able to repress the expression of virulence genes in EHEC. Furthermore, LED209-functionalized cellulose membrane indicated no cytotoxicity to mammalian cells. Hence, our present work demonstrated that CM modified with LED209 possessed markedly anti-adhesion activity against EHEC, which offered a potent antimicrobial material for combating bacterial infections.


Assuntos
Proteínas da Membrana Bacteriana Externa/antagonistas & inibidores , Enzimas Imobilizadas/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli O157/efeitos dos fármacos , Proteínas de Escherichia coli/antagonistas & inibidores , Complexos Multienzimáticos/antagonistas & inibidores , Sulfonamidas/farmacologia , Animais , Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Celulose/química , Membranas Artificiais , Camundongos , Células NIH 3T3
14.
Epilepsy Behav ; 115: 107687, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33360175

RESUMO

Arterial spin labeling (ASL) is an important tool for understanding cerebral perfusion in epilepsy patients. The aim of this study was to explore patterns of change in cerebral blood flow (CBF) and CBF connectivity in patients with focal to bilateral tonic-clonic seizures (FBTCS). High-resolution three-dimensional (3-D) T1-weighted and 3-D pseudo-continuous ASL magnetic resonance imaging (MRI) was collected from 32 patients with FBTCS and 16 healthy volunteers using a 3.0 T MRI scanner. Cerebral blood flow and its connectivity were compared between the FBTCS and control group. Correlation analysis was used to explore relationships of CBF and its connectivity changes with clinical parameters. Cerebral blood flow data of spatial standardization and normalization were used to improve statistical power. Patients with FBTCS exhibited increased CBF in the bilateral thalamus, caudate nucleus, olfactory cortex, and gyrus rectus, but decreased CBF in the bilateral supplementary motor areas (SMA) and middle cingulate cortex (MCC). Patients with FBTCS showed significant positive correlation between CBF and gray matter volume (GMV) in bilateral SMA and MCC. No significant correlations between CBF and clinical parameters were found among FBTCS patients. The anterior cingulate cortex (ACC) showed positive CBF connectivity with the bilateral SMA and MCC, and these CBF connectivity measures differed significantly between groups (cluster-level, FWE-corrected, P < 0.001). These findings suggest that patients with FBTCS have changes in cerebral CBF and CBF connectivity, which may relate to the underlying neuropathology of FBTCS.


Assuntos
Circulação Cerebrovascular , Imagem por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Substância Cinzenta , Humanos , Convulsões , Marcadores de Spin
15.
Adv Healthc Mater ; 10(7): e2001489, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33336561

RESUMO

Multi-photon photosensitizers (PSs) could significantly improve the efficacy of photodynamic therapy due to the long-wavelength favorability for deeper tissue penetration and lower biological damage. However, most studies are limited to single-photon or two-photon PSs at a relatively short-wave excitation window. To overcome this barrier, we rationally design a series of rigid plane compounds with efficient reactive oxygen species (ROS) production in vitro under laser irradiation. Furthermore, the studies show that one of the compounds (U-TsO) could induce rapid multi-types of cell death under three-photon exposure, suggesting a promising clinical outcome in ex vivo 3D multicellular tumor spheroid. This work offers a novel strategy to construct functional materials with competitive multi-photon photodynamic therapy (PDT) outcome.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33316578

RESUMO

Temperature is an important environmental factor in the living environment of crustaceans. Changes in temperature can affect their normal growth and metabolism and even cause bacterial disease. Currently, the potential anti-reverse molecular reaction mechanism of crustaceans during high-temperature conditions has not yet been fully understood. Therefore, in this study, we characterised the transcriptome of Procambarus clarkii using RNA sequencing and performed a comparison between super-high-temperature treated samples and controls. After assembly and annotation, 81,097 unigenes with an average length of 069 bp and 358 differentially expressed genes (DEGs) were identified. Among these DEGs, 264 were differentially upregulated and 94 were differentially downregulated. To obtain comprehensive gene function information, we queried seven databases, namely, Nr, Nt, Pfam, KOG, Swiss-Prot, KEGG, and GO to annotate gene functions. Transcriptome analysis revealed that the identified DEGs have significant effects on immune-related pathways, including lysosomal and phagosomal pathways, and that super-high-temperature conditions can cause disease in P. clarkii. Some significantly downregulated genes are involved in oxidative phosphorylation and the PPAR signalling pathway; this suggests a metabolic imbalance in P. clarkia during extreme temperature conditions. In addition, elevated temperature changed the expression patterns of key apoptosis genes XIAP, CASP2, CASP2, CASP8, and CYTC, thereby confirming that high-temperature conditions caused immune disorders, metabolic imbalance, and, finally, triggered apoptosis. Our results provide a useful foundation for understanding the molecular mechanisms underlying the responses of P. clarkii during high-temperature conditions.

17.
Biomed Res Int ; 2020: 3828249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274207

RESUMO

The occurrence of diarrhea-predominant irritable bowel syndrome (IBS-D) is the result of multiple factors, and its pathogenesis has not yet been clarified. Emerging evidence indicates abnormal changes in gut microbiota and bile acid (BA) metabolism have a close relationship with IBS-D. Gut microbiota is involved in the secondary BA production via deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, and esterification reactions respectively. Changes in the composition and quantity of gut microbiota have an important impact on the metabolism of BAs, which can lead to the occurrence of gastrointestinal diseases. BAs, synthesized in the hepatocytes, play an important role in maintaining the homeostasis of gut microbiota and the balance of glucose and lipid metabolism. In consideration of the complex biological functional connections among gut microbiota, BAs, and IBS-D, it is urgent to review the latest research progress in this field. In this review, we summarized the alterations of gut microbiota in IBS-D and discussed the mechanistic connections between gut microbiota and BA metabolism in IBS-D, which may be involved in activating two important bile acid receptors, G-protein coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR). We also highlight the strategies of prevention and treatment of IBS-D via regulating gut microbiota-bile acid axis, including probiotics, fecal microbiota transplantation (FMT), cholestyramine, and the cutting-edge technology about bacteria genetic engineering.

18.
Medicine (Baltimore) ; 99(50): e21789, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327221

RESUMO

X inactive specific transcript (XIST) is a novel long noncoding RNA (lncRNA) which has been reported to be frequently upregulated in various human cancer types and to function as an oncogene. It has been reported that the expression of lncRNA XIST was upregulated in non-small cell lung cancer (NSCLC). In the present study, we aimed to investigate the clinical significance and prognostic value of XIST in patients with NSCLC.A total of 156 pairs of NSCLC and corresponding adjacent normal lung tissue samples were obtained from NSCLC patients who had undergone surgery from July 2014 to March 2019. The Student's t test was used in different treated groups for statistical analysis. The association between XIST expression and clinicopathological features of NSCLC patients was evaluated using the chi-squared test. Survival curves were plotted using Kaplan-Meier method and compared by log-rank test.The expression of XIST was significantly higher in NSCLC samples compared to non-cancerous samples (P < .001). Statistically significant correlations were observed between high tissue XIST expression level and lymph node metastasis (P = .036) and high Tumor Node Metastasis (TNM) stage (P = .002). The log-rank test indicated that patients with increased XIST expression experienced poor overall survival (P = .006). Multivariate Cox regression analysis showed that XIST expression level (hazard ratio = 2.645, 95% confidence interval: 1.672-7.393, P = .029) was an independent factors in predicting the overall survival of NSCLC patients.The present study found that XIST expression level was significantly associated with advanced pathological stage and high TNM stage in NSCLC. Furthermore, upregulation of tissue lncRNA XIST predicts poor postoperative survival in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , China/epidemiologia , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Ativação Transcricional , Regulação para Cima/genética
19.
Sci Adv ; 6(48)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33246953

RESUMO

The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor-related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.

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