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1.
Carbohydr Polym ; 252: 117134, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183593

RESUMO

A series of lanthanide-based nanopaper (Nd-nanopaper) was synthesized via a neodymium organic framework (Nd-MOFs)-grafted TEMPO-oxidized cellulose nanofibrils (tCNF) using a solvothermal reaction. Not using the traditional down-conversion visible emissions of anti-counterfeiting techniques, this Nd-nanopaper achieved down-conversion near-infrared (NIR) and up-conversion visible emissions. The down-conversion luminescent property of these Nd-nanopapers exhibited characteristic NIR luminescence (λEm = 1080 nm) of Nd3+ ions with 311 nm excitation, undergoing an "antenna" effect. In contrast, the up-conversion visible light emission (λEm =450 nm) of Nd-nanopaper was detected under 580 nm excitation. The mechanism of up-conversion fluorescence was ascribed to excited-state absorption and energy transfer up-conversion. Interestingly, Nd-nanopaper induced both up and down-conversions for visible and NIR emissions that were completely devoid of the interference from fluorescent brighteners and background fluorescence. These switchable up and down-conversion fluorescent Nd-nanopapers with visible and NIR dual emissions or dual channels could be applied in high level anti-counterfeiting applications.

2.
J Appl Toxicol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33197057

RESUMO

Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4 ) and to further explore the biological functions of differentially expressed miRNAs. The profile of miRNAs in 16HBE cells was detected using the high-throughput sequencing between the control groups (n = 3) and the 150 µmol/L of BeSO4 -treated groups (n = 3). Bioinformatics analysis of differentially expressed miRNAs was performed, including the prediction of target genes, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify some damage-related miRNAs. We found that BeSO4 can increase the levels of some inflammatory cytokine such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). And BeSO4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 upregulated miRNAs and 91 downregulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. The qRT-PCR verification results were consistent with the sequencing results. miRNA expression profiling in 16HBE cells exposed to BeSO4 provides new insights into the toxicity mechanism of beryllium exposure.

3.
Clin Nutr ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33223117

RESUMO

BACKGROUND: Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer. METHODS: A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery. RESULTS: There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI <25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients. CONCLUSION: There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.

4.
Genome Med ; 12(1): 101, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225964

RESUMO

BACKGROUND: Heat shock proteins (HSPs), a representative family of chaperone genes, play crucial roles in malignant progression and are pursued as attractive anti-cancer therapeutic targets. Despite tremendous efforts to develop anti-cancer drugs based on HSPs, no HSP inhibitors have thus far reached the milestone of FDA approval. There remains an unmet need to further understand the functional roles of HSPs in cancer. METHODS: We constructed the network for HSPs across ~ 10,000 tumor samples from The Cancer Genome Atlas (TCGA) and ~ 10,000 normal samples from Genotype-Tissue Expression (GTEx), and compared the network disruption between tumor and normal samples. We then examined the associations between HSPs and cancer hallmarks and validated these associations from multiple independent high-throughput functional screens, including Project Achilles and DRIVE. Finally, we experimentally characterized the dual function effects of HSPs in tumor proliferation and metastasis. RESULTS: We comprehensively analyzed the HSP expression landscape across multiple human cancers and revealed a global disruption of the co-expression network for HSPs. Through analyzing HSP expression alteration and its association with tumor proliferation and metastasis, we revealed dual functional effects of HSPs, in that they can simultaneously influence proliferation and metastasis in opposite directions. We experimentally characterized the dual function of two genes, DNAJC9 and HSPA14, in lung cancer cells. We further demonstrated the generalization of this dual direction of associations between HSPs and cancer hallmarks, suggesting the necessity to more carefully evaluate HSPs as therapeutic targets and develop highly specific HSP inhibitors for cancer intervention. CONCLUSIONS: Our study furnishes a holistic view of functional associations of HSPs with cancer hallmarks to aid the development of HSP inhibitors as well as other drugs in cancer therapy.

5.
Biomed Res Int ; 2020: 8854245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204722

RESUMO

Cell division-related proteins are essential for the normal development and differentiation of cells and may be related to the occurrence of cancer and the drug resistance mechanism of cancer cells. The mitotic kinesin-like protein 1 (MKLP1) is a kinesin protein that has been involved in the assembly of the midzone/midbody during mitosis and cytokinesis. In this study, we found that the tail domain of MKLP1 exhibited an autoinhibitory effect on its motor activity. Overexpression of the tail domain in HEK293 cells blocked cytokinesis and caused bi-/multinucleation. It is possible that protein binding to the MKLP1 tail relieves this autoinhibition and induces the motility of MKLP1. We used the GST pull-down assay followed by the LC-MS/MS analysis and identified 54 MKLP1 tail domain-specific binding proteins. Further, we confirmed the MS result by coimmunoprecipitation and FRET that a serine/threonine kinase, p21-activated kinase 2 (PAK2), binding to MKLP1. Endogenous PAK2 expression was found to be identical to that of MKLP1 in HEK293 cells during cytokinesis. Finally, functional studies indicated that when PAK2 expression was downregulated by siRNA, MKLP1 underwent a change in its localization away from the midbody, and cell cytokinesis was subsequently impeded. This study presents a novel regulatory mechanism that PAK2 promotes the activation of MKLP1 and contributes to complete cell cytokinesis.

6.
Traffic Inj Prev ; : 1-6, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206565

RESUMO

OBJECTIVE: Few existing studies in the literature devoted efforts to examine the driver injury severity in left-turn crashes. To fill this research gap, this paper aims to provide a comprehensive study of the contributing factors of left-turn crashes and the corresponding injury severities. METHODS: The hierarchical ordered probit (HOPIT) model is first applied to study driver injury severity in left-turn crashes. The HOPIT model can overcome the limitations of traditional ordered probit models since its thresholds are always positive and ordered. It is a function of unique explanatory parameters that do not necessarily affect the ordered probability outcomes directly. Considering the driving condition during the wintertime could be significantly different from other seasons, this study divided the overall crash dataset into "winter" and "other-season" subsets based on the temperature, snowing condition, and other factors. RESULTS: With the "other-season" dataset, results demonstrated that contributing factors, such as young drivers, male drivers, clear, light, and ramp intersection with crossroad, are associated with a decrease in injury severity. On the contrary, factors like drug, alcohol, disregard traffic control device, high-speed limit, the protected left-turn signal, etc., are related to an increase in injury severity. In winter, results revealed that only nine contributing factors are significant to the left-turn crash. Alcohol, disregard traffic control device, nighttime, high-speed limit, head-on collision, and state road are associated with an increase in injury severity. Also, two-vehicle involved, snow, ramp intersection with crossroad are related to a decrease in injury severity. CONCLUSIONS: The HOPIT model is applied to examine contributing factors of left-turn crashes and the corresponding injury severity, based on left-turn crash records from 2010 to 2017 in Utah. Eighteen significant factors of left-turn crash injury severity are identified in the overall dataset. In seasons rather than winter, the significant factors are almost the same as that of the entire year. In the winter, less significant factors and different patterns are found compared with the overall crashes.

7.
J Hazard Mater ; : 124588, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33229264

RESUMO

Environmentally sound disposal of hyperaccumulator harvests is of critical importance to industrialization of phytoremediation. Herein, transformation behaviors and environmental risk of heavy metals were comprehensively examined during subcritical hydrothermal liquefaction of Sedum plumbizincicola. It is concluded that low temperature liquefaction favored resource recovery of heavy oil and hydrochars in terms of higher energy density, improved carbon sequestration and less energy consumption. Heavy metals were mainly distributed into hydrochars and water soluble phase with less than 10% in heavy oil. All metal elements except As could be accumulated in hydrochars by extending reaction time, whereas more than 96% of As was redistributed into water soluble phase. Prolonged liquefaction time facilitated immobilization of Cd, Cr and As in hydrochars, but fast liquefaction favored Pb stabilization. Liquefaction significantly reduced environmental risk level of Cd, Zn and As, but may mobilize Pb and Mn, especially for Mn to very high risk level at 240 ºC. High temperature with long reaction time tended to inhibit leaching rate of Mn, whereas low liquefaction temperature with short reaction time prevented the leaching of Zn and As from hydrochars. Overall, these findings are essential for downstream upgrading of heavy oil and metals recovery from hydrochars.

8.
BMC Plant Biol ; 20(1): 533, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228522

RESUMO

BACKGROUND: The AP2/ERFs belong to a large family of transcription factors in plants. The AP2/ERF gene family has been identified as a key player involved in both biotic and abiotic stress responses in plants, however, no comprehensive study has yet been carried out on the AP2/ERF gene family in rose (Rosa sp.), the most important ornamental crop worldwide. RESULTS: The present study comprises a genome-wide analysis of the AP2/ERF family genes (RcERFs) in the rose, involving their identification, gene structure, phylogenetic relationship, chromosome localization, collinearity analysis, as well as their expression patterns. Throughout the phylogenetic analysis, a total of 131 AP2/ERF genes in the rose genome were divided into 5 subgroups. The RcERFs are distributed over all the seven chromosomes of the rose, and genome duplication may have played a key role in their duplication. Furthermore, Ka/Ks analysis indicated that the duplicated RcERF genes often undergo purification selection with limited functional differentiation. Gene expression analysis revealed that 23 RcERFs were induced by infection of the necrotrophic fungal pathogen Botrytis cinerea. Presumably, these RcERFs are candidate genes which can react to the rose's resistance against Botrytis cinerea infection. By using virus-induced gene silencing, we confirmed that RcERF099 is an important regulator involved in the B.cinerea resistance in the rose petal. CONCLUSION: Overall, our results conclude the necessity for further study of the AP2/ERF gene family in rose, and promote their potential application in improving the rose when subjected to biological stress.

9.
World J Surg Oncol ; 18(1): 303, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228682

RESUMO

OBJECTIVE: Immunotherapy targeting the programmed cell death protein-1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) pathway has been observed to be efficient in several solid tumors. We aim to investigate the prognostic significance of PD-1/PD-L1 expression profile in intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: We investigated the expression of PD-1, PD-L1, CD8+ T cells, and CD68+ macrophages in paired tumor and adjacent normal tissues from 322 ICC patients using tyramide signal amplification (TSA)-based multiplexed immunohistochemistry. RESULTS: We found that high proportion of tumor-infiltrating CD8+ PD-1High within CD8+ PD-1+ T cells significantly correlated with advanced TNM stage (P = 0.035). ICC patients with high proportion of CD8+ PD-1High in CD8+ PD-1+ had worse postoperative survival than low proportion patients (P = 0.0037), which was an independently prognostic factor for OS (P = 0.025,). The density of CD68+ PD-L1+ significantly and positively correlated with the density of CD8+ PD-1High (P < 0.0001, r = 0.5927). The proportion of CD68+ PD-L1+ within CD68+ ICC was the risk factor for OS and TTR but not an independently factor for prognosis. The CD68+ PD-L1+ macrophages and CD8+ PD-1High T cells may cooperatively play a role in inhibiting anti-tumor immunity. CONCLUSION: CD68+ PD-L1+ macrophages and CD8+ PD-1High T cells predict unfavorable prognosis, which could also bring new progress about immune target therapy in ICC research.

10.
Biophys J ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189688

RESUMO

Terahertz waves have attracted great attention in biomolecule research due to the fact that they cover the range of energy levels of weak interactions, skeleton vibrations and dipole rotations during inter- and intramolecular interactions in biomacromolecules. In this study, we validated the feasibility of employing terahertz time-domain spectroscopy (THz-TDS) for the non-destructive and label-free monitoring of protein digestion. The acid protease, pepsin, was used at its optimal pH to hydrolyze bovine serum albumin (BSA). Correspondingly, the control group experiment was also conducted by adjusting the pH value to inactivate pepsin. The progress of these two experiments was tracked by a compact commercial THz-TDS for 1 hour. On one hand, the reaction time-dependent absorption coefficient was calculated and a direct absorption coefficient analysis was completed. The results indicate that protein hydrolysis can be easily monitored over time by focusing on the variation tendency of the absorption coefficient from a macroscopic perspective. On the other hand, we explored the use of the Debye model to analyze the dielectric properties of the solution during protein hydrolysis. The results of the Debye analysis prove that it's possible to investigate in detail the microscopic dynamics of biomacromolecule solutions at the molecular level by THz-TDS. Our research examined the process of protein hydrolysis by a combination of absorption spectra and Debye analysis, and demonstrated that terahertz spectroscopy is a powerful technology for the investigation of biomolecular reactions, with potential applications in variety of fields.

11.
Front Immunol ; 11: 560110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224134

RESUMO

HPS1, a BLOC-3 subunit that acts as a guanine nucleotide exchange factor of Rab32/38, may play a role in the removal of VAMP7 during the maturation of large dense core vesicles of Paneth cells. Loss of HPS1 impairs lysozyme secretion and alters the composition of intestinal microbiota, which may explain the susceptibility of HPS-associated inflammatory bowel disease. Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, bleeding tendency, and other chronic organ lesions due to defects in tissue-specific lysosome-related organelles (LROs). For some HPS subtypes, such as HPS-1, it is common to have symptoms of HPS-associated inflammatory bowel disease (IBD). However, its underlying mechanism is largely unknown. HPS1 is a subunit of the BLOC-3 complex which functions in the biogenesis of LROs. Large dense core vesicles (LDCVs) in Paneth cells of the intestine are a type of LROs. We here first report the abnormal LDCV morphology (increased number and enlarged size) in HPS1-deficient pale ear (ep) mice. Similar to its role in melanosome maturation, HPS1 plays an important function in the removal of VAMP7 from LDCVs to promote the maturation of LDCVs. The immature LDCVs in ep mice are defective in regulated secretion of lysozyme, a key anti-microbial peptide in the intestine. We observed changes in the composition of intestinal microbiota in both HPS-1 patients and ep mice. These findings provide insights into the underlying mechanism of HPS-associated IBD development, which may be implicated in possible therapeutic intervention of this devastating condition.

12.
Nat Cell Biol ; 22(11): 1332-1345, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33106653

RESUMO

Dystrophin proteomic regulation in muscular dystrophies (MDs) remains unclear. We report that a long noncoding RNA (lncRNA), H19, associates with dystrophin and inhibits E3-ligase-dependent polyubiquitination at Lys 3584 (referred to as Ub-DMD) and its subsequent protein degradation. In-frame deletions in BMD and a DMD non-silent mutation (C3340Y) resulted in defects in the ability of the protein to interact with H19, which caused elevated Ub-DMD levels and dystrophin degradation. Dmd C3333Y mice exhibited progressive MD, elevated serum creatine kinase, heart dilation, blood vessel irregularity and respiratory failure with concurrently reduced dystrophin and increased Ub-DMD status. H19 RNA oligonucleotides conjugated with agrin (AGR-H19) and nifenazone competed with or inhibited TRIM63. Dmd C3333Y animals, induced-pluripotent-stem-cell-derived skeletal muscle cells from patients with Becker MD and mdx mice subjected to exon skipping exhibited inhibited dystrophin degradation, preserved skeletal and cardiac muscle histology, and improved strength and heart function following AGR-H19 or nifenazone treatment. Our study paves the way for meaningful targeted therapeutics for Becker MD and for certain patients with Duchenne MD.

13.
Sci Rep ; 10(1): 16835, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033300

RESUMO

Marigold (Tagetes erecta L.) is an important ornamental plant with a wide variety of flower colors. Despite its economic value, few biochemical and molecular studies have explored the generation of flower color in this species. To study the mechanism underlying marigold petal color, we performed a metabolite analysis and de novo cDNA sequencing on the inbred line 'V-01' and its petal color mutant 'V-01M' at four flower developmental stages. A total of 49,217 unigenes were identified from 24 cDNA libraries. Based on our metabolites and transcriptomic analyses, we present an overview of carotenoid biosynthesis, degradation, and accumulation in marigold flowers. The carotenoid content of the yellow mutant 'V-01M' was higher than that of the orange inbred line 'V-01', and the abundances of the yellow compounds lutein, neoxanthin, violaxanthin, zeaxanthin, and antheraxanthin were significantly higher in the mutant. During flower development, the carotenoid biosynthesis genes were upregulated in both 'V-01' and 'V-01M', with no significant differences between the two lines. By contrast, the carotenoid degradation genes were dramatically downregulated in the yellow mutant 'V-01M'. We therefore speculate that the carotenoid degradation genes are the key factors regulating the carotenoid content of marigold flowers. Our research provides a large amount of transcriptomic data and insights into the marigold color metabolome.

14.
Biomed Environ Sci ; 33(9): 680-689, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33106213

RESUMO

Objective: To investigate the effect of c-fos gene silencing on differentially expressed proteins (DEPs) in human bronchial epithelial (HBE) cells after exposure to fine particulate matter (PM 2.5). Methods: HBE cells and c-fos-silenced HBE cells were exposed to 50 µg/mL PM 2.5, LC-MS/MS and tandem mass tag (TMT) labeling methods were combined with bioinformatics methods, and DEPs and interaction networks were identified. Results: In the HBE group, 414 DEPs were screened, of which 227 were up-regulated and 187 down-regulated. In the c-fos silenced HBE group, 480 DEPs were screened, including 240 up-regulated proteins and 240 down-regulated proteins. KEGG annotations showed that DEPs in the HBE group are mainly concentrated in the glycolysis/gluconeogenesis pathway and those in the c-fos silenced group are concentrated mainly in endoplasmic reticulum and the processing of proteins. Additionally, the abnormal expression of GPRC5C, DKK4, and UBE2C was identified in top 15 DEPs. After constructing the protein interaction network, 20 Hub proteins including HNRNPA2B1, HNRNPL, RPS15A, and RPS25 were screened from the HBE group and the c-fos silenced HBE group. Conclusion: c-fos gene affected the expression of cancer-related proteins. Our results provided a scientific basis for further study of PM 2.5-induced carcinogenesis mechanism.


Assuntos
Poluentes Atmosféricos/toxicidade , Brônquios/efeitos dos fármacos , Regulação da Expressão Gênica , Inativação Gênica , Genes fos/genética , Material Particulado/toxicidade , Mucosa Respiratória/efeitos dos fármacos , Brônquios/metabolismo , Células Cultivadas , Humanos , Proteômica , Mucosa Respiratória/metabolismo
15.
Inorg Chem ; 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103421

RESUMO

Three-dimensional (3D) bulk materials, such as metal-organic frameworks (MOFs) and inorganic phosphors, show the properties of large backscattering and stress concentration, which result in low mechanical and inferior transmittance when these materials are hydridized with a polymer matrix. Inspired by the "reinforcement" effects of two-dimensional (2D) materials, such as grapheme, C3N4, MoS2, and Mxene, it was interesting to examine a 2D lanthanide (Ln)-based MOF-grafted natural polymer (nanocellulose) with the goal of achieving light emission, transparency, and good mechanical properties. A series of near-infrared (NIR) luminescent cellulose nanopapers were prepared via 2D Ln-MOF-grafted (2,2,6,6-tetramethylpiperidin-1-yl)oxyl-oxidized cellulose nanofibrils (tCNFs; Ln = Nd, Yb, or Er). In addition to efficient NIR luminescence, these Ln nanopapers exhibited good flexibility, transparency (>90%), and mechanical properties (>28 MPa). Notably, the haze of these nanopapers was increased by 93-95% from 26% due to compositing with 2D Ln-MOFs, which prevented dense packing among the cellulose and formed air cavities in the nanopaper, inducing internal light scattering and improving optical haze. Moreover, these flexible Ln nanopapers exhibited efficient NIR luminescence, which, together with optical haze and transparency, offered an opportunity for utilization in paper-based anticounterfeiting, NIR-light-emitting diodes, or light softening devices.

16.
Mol Genet Genomic Med ; : e1534, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108070

RESUMO

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease with colorectal adenomatous polyps as the main clinical manifestations. The objective of this study was to analyze and compare the expression levels of tumor proliferation and angiogenesis-related genes in different tissue sections of FAP patients through qPCR, western blot, and immunohistochemistry (IHC) analysis. METHODS: Seventeen patients with FAP admitted to Tianjin Union Medical Center from January 2010 to June 2015 were selected, and then, normal intestinal mucosa, polyp tissue, or cancerous polyp tissue were collected. QPCR, western blot, and IHC were used to detect the expression level of genes or proteins correlated with tumor proliferation. RESULTS: The mRNA expression of CD31 in large polyp tissue was significantly higher than that in normal tissue and small polyp tissue. Compared with normal tissue and polyp tissue, the expression level of KI67 mRNA in cancer tissue was remarkably increased. The VEGFA mRNA and CDH5 mRNA expression in both polyp and cancer tissues were prominently lower than those in normal tissue. The expression of CD31 protein in cancer tissue was lower than that in normal tissue and polyp tissue, whereas the expression levels of VEGF, CDH5, and KI67 protein were widely higher than that in normal tissue and polyp tissue. CONCLUSION: Abnormal expressions of CD31, KI67, VEGF(A), and CDH5 were associated with the carcinogenesis of FAP.

17.
Front Immunol ; 11: 577869, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123161

RESUMO

Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

18.
Nucleic Acids Res ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119754

RESUMO

Enhancer RNA (eRNA) is a type of long non-coding RNA transcribed from DNA enhancer regions. Despite critical roles of eRNA in gene regulation, the expression landscape of eRNAs in normal human tissue remains unexplored. Using numerous samples from the Genotype-Tissue Expression project, we characterized 45 411 detectable eRNAs and identified tens of thousands of associations between eRNAs and traits, including gender, race, and age. We constructed a co-expression network to identify millions of putative eRNA regulators and target genes across different tissues. We further constructed a user-friendly data portal, Human enhancer RNA Atlas (HeRA, https://hanlab.uth.edu/HeRA/). In HeRA, users can search, browse, and download the eRNA expression profile, trait-related eRNAs, and eRNA co-expression network by searching the eRNA ID, gene symbol, and genomic region in one or multiple tissues. HeRA is the first data portal to characterize eRNAs from 9577 samples across 54 human tissues and facilitates functional and mechanistic investigations of eRNAs.

19.
J Stroke Cerebrovasc Dis ; 29(11): 105210, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066952

RESUMO

OBJECTIVE: We attempt to investigate the role of TNFRSF1A and its underlying mechanism in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in rat pheochromocytoma PC12 cells. METHODS: Public datasets GSE61616 and GSE106680 were downloaded from GEO database. PC12 cells were used to construct OGD/R models. QRT-PCR and western blot were implemented to test the relative mRNA and protein levels, respectively. The miRNA online prediction website TargetScan was used to predict TNFRSF1A upstream regulated miRNAs, which were then confirmed by luciferase reporter assay. The changes in cell viability and apoptosis were evaluated using cell counting kit 8 (CCK-8), lactose dehydrogenase (LDH), and flow cytometry assays. RESULTS: Bioinformatics analysis demonstrated that the expression of TNFRSF1A was upregulated in CI/RI and middle cerebral artery occlusion models compared with control, respectively. And a significant upregulation was also observed in OGD/R-damaged PC12 cells. Depletion of TNFRSF1A can notably enhance the cells proliferation after OGD/R treatment, while enlargement of TNFRSF1A presented the opposite outcomes. Moreover, miR-29a-3p was shown to be the upstream regulatory miRNA of TNFRSF1A. The levels of TNFRSF1A were inversely mediated by miR-29a-3p. Overexpression of miR-29a-3p can raise the cell viability, decrease the LDH activity, and reduce the apoptotic ratio in OGD/R-treated cells. Besides, TNFRSF1A can attenuate the protective effect of miR-29a-3p on OGD/R-treated cells. Furthermore, miR-29a-3p mimic inhibited, while overexpression of TNFRSF1A promoted the activation of NF-κB signaling pathway, and TNFRSF1A can attenuate the suppressive effect of miR-29a-3p on the NF-κB pathway. CONCLUSION: Our research illustrated that the potential regulatory role of miR-29a-3p/TNFRSF1A axis in neurons cells suffered from OGD/R, and their effects on NF-κB signaling pathway, providing a possible bio-target for protecting cells from OGD/R damage .

20.
J Integr Neurosci ; 19(3): 429-436, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070521

RESUMO

MicroRNAs are reportedly involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease and multiple system atrophy. We previously identified 7 differentially expressed microRNAs in Parkinson's disease patients and control sera (miR-30c, miR-31, miR-141, miR-146b-5p, miR-181c, miR-214, and miR-193a-3p). To investigate the expression levels of the 7 serum microRNAs in Parkinson's disease and multiple system atrophy, 23 early Parkinson's disease patients (who did not take any anti- Parkinson's disease drugs), 23 multiple system atrophy patients, and 24 normal controls were recruited at outpatient visits in this study. The expression levels of the 7 microRNAs in serum were detected using quantitative real-time polymerase chain reaction. A receiver operating characteristic curve was used to evaluate whether microRNAs can differentially diagnose Parkinson's disease and multiple system atrophy. Clinical scales were used to analyze the correlations between serum microRNAs and clinical features. The results indicated that miR-214 could distinguish Parkinson's disease from the controls, and another 3 microRNAs could differentiate multiple system atrophy from the controls (miR-141, miR-193a-3p, and miR-30c). The expression of miR-31, miR-141, miR-181c, miR-193a-3p, and miR-214 were lower in multiple system atrophy than in Parkinson's disease (all P < 0.05). Combinations of microRNAs accurately discriminated Parkinson's disease from multiple system atrophy (area under the receiver operating characteristic curve = 0.951). For the correlation analysis, negative correlations were discovered between the expression of miR-214 and the Hamilton Anxiety Scale and Parkinson's Disease Non-Motor Symptom scores (all P < 0.05). Our results demonstrate that the distinctive characteristics of microRNAs differentiate Parkinson's disease and multiple system atrophy patients from healthy controls and may be used for the early diagnosis of Parkinson's disease and multiple system atrophy.

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