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1.
Plant Mol Biol ; 114(4): 77, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38909327

ABSTRACT

As self-incompatibility is a major issue in pummelo breeding and production, its mechanism in citrus was analyzed to improve breeding efficiency and reduce production costs. Rutaceae belongs to S-RNase type of gametophytic self-incompatibility. While the function of S-RNase/SLF and the mechanism of self-incompatibility have been studied extensively, the transcriptional regulation of S-RNase has been less studied. We performed transcriptome sequencing with the styles of 'Shatian' pummelo on the day of anthesis and 1-5 days before anthesis, and found that the transcript level of S-RNase gradually decreased with flower development. By analyzing differentially expressed genes and correlation with the expression trend of S-RNase, we identified a candidate gene, CgHSFB1, and utilized biochemical experiments such as yeast one-hybrid assay, electrophoretic mobility shift assay and dual-luciferase assay, as well as transient transformation of citrus calli and Citrus microcarpa and demonstrated that CgHSFB1 could directly bind to the S1-RNase promoter and repress the expression of S1-RNase, which is involved in the pummelo self-incompatibility response. In contrast, CgHSFB1 did not bind to the promoter of S2-RNase, and there was specificity in the regulation of S-RNase.


Subject(s)
Citrus , Flowers , Gene Expression Regulation, Plant , Plant Proteins , Ribonucleases , Self-Incompatibility in Flowering Plants , Citrus/genetics , Citrus/physiology , Citrus/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Flowers/genetics , Flowers/physiology , Flowers/growth & development , Self-Incompatibility in Flowering Plants/genetics , Ribonucleases/genetics , Ribonucleases/metabolism , Promoter Regions, Genetic/genetics , Transcriptome , Gene Expression Profiling
2.
Food Chem ; 443: 138616, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38306907

ABSTRACT

Guangchenpi (GCP), which is the peel of Citrus reticulata 'Chachiensis', is widely used as an herbal medicine, tea and food ingredient in southeast Asia. Prolonging its aging process results in a more pleasant flavor and increases its profitability. Through the integration of sensory evaluation with flavoromic analysis approaches, we evaluated the correlation between the flavor attributes and the profiles of the volatiles and flavonoids of GCP with various aging years. Notably, d-limonene, γ-terpinene, dimethyl anthranilate and α-phellandrene were the characteristic aroma compounds of GCP. Besides, α-phellandrene and nonanal were decisive for consumers' perception of GCP aging time due to changes of their odor activity values (OAVs). The flavor attributes of GCP tea liquid enhanced with the extension of aging time, and limonene-1,2-diol was identified as an important flavor enhancer. Combined with machine learning models, key flavor-related metabolites could be developed as efficient biomarkers for aging years to prevent GCP adulteration.


Subject(s)
Citrus , Cyclohexane Monoterpenes , Limonene , Tea
5.
Huan Jing Ke Xue ; 44(8): 4387-4396, 2023 Aug 08.
Article in Chinese | MEDLINE | ID: mdl-37694633

ABSTRACT

PAHs (polycyclic aromatic hydrocarbons) accumulated in arable soils have significant impacts on farmland quality and human health, which has attracted wide attention from scientists and the public. A total of 22 arable soil samples were collected from Taiyuan, an old industrial city, including three districts (industrial zones, hilly areas, and sewage irrigation area), and the contents of 21 PAHs were detected using the GC-MS method. The sources of PAHs in soils were analyzed using the diagnostic ratios (DRs) method and positive matrix factorization (PMF) model, and the soil health risks were analyzed using the incremental lifetime cancer risk (ILCR) model. The results indicated that the average concentrations of Σ21PAHs and Σ16PAHs in arable soils of Taiyuan were 934.6 ng·g-1 and 787.7 ng·g-1, respectively, which were lower than the soil pollution risk screening value of agricultural land stipulated in GB 15168-2018. 3-5 rings PAHs were the dominant components, accounting for~90% of the Σ21PAHs. Approximately 60% of sites in industrial zones, 13% in hilly areas, and 33% in the sewage irrigation area had high PAHs contents larger than 1000 ng·g-1. The spatial distribution of PAHs showed that more severe PAHs pollution in the soil occurred in industrial areas than that in the other two districts. The DRs suggested that the combustion of coals, bio-masses, and traffic emissions were the dominant sources for PAHs pollution in arable soils in Taiyuan. The simulation results of the PMF model indicated that the sources and contribution rates of PAHs in cultivated soils were coal and biomass burning sources (59%), traffic sources (22%), and coking sources (19%). The risk assessment confirmed that the arable soils in Taiyuan had high potential carcinogenic risks; thus, more attention should be paid to the PAHs pollutions in arable soils.

6.
Plants (Basel) ; 11(21)2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36365397

ABSTRACT

The effects of the increased soil copper (Cu) on fruit quality due to the overuse of Cu agents have been a hot social issue. Seven representative citrus orchards in Guangxi province, China, were investigated to explore the fruit quality characteristics under different soil Cu levels and the relationship between soil-tree Cu and fruit quality. These results showed that pericarp color a value, titratable acid (TA), and vitamin C (Vc) were higher by 90.0, 166.6, and 22.4% in high Cu orchards and by 50.5, 204.2, and 55.3% in excess Cu orchards, compared with optimum Cu orchards. However, the ratio of total soluble solids (TSS)/TA was lower by 68.7% in high Cu orchards and by 61.6% in excess Cu orchards. With the increase of soil Cu concentrations, pericarp color a value and Vc were improved, TA with a trend of rising first then falling, and TSS/TA with a trend of falling first then rising were recorded. As fruit Cu increased, pericarp color a value and TSS reduced and as leaf Cu increased, TSS/TA decreased while Vc was improved. Moreover, a rise in soil Cu enhanced leaf Cu accumulation, and a rise in leaf Cu improved fruit Cu accumulation. Fruit Cu accumulation reduced fruit quality by direct effects, leaf Cu improved fruit quality by direct and indirect effects. Soil Cu affected fruit quality by indirect effects by regulating leaf Cu and fruit Cu. Therefore, reasonable regulation and control of soil Cu concentrations can effectively increase pericarp color, sugar, and acid accumulation in citrus fruit.

7.
Int J Biol Sci ; 18(9): 3621-3635, 2022.
Article in English | MEDLINE | ID: mdl-35813477

ABSTRACT

The poor sensitivity of clear cell renal cell carcinoma (ccRCC) to conventional chemotherapy and radiotherapy makes its treatment challenging. The Ndc80 kinetochore complex component (NUF2) is involved in the development and progression of several cancers. However, its role in ccRCC remains unclear. In this study, we investigated the biological functions and underlying mechanism of NUF2 in ccRCC. We found that NUF2 expression was increased in ccRCC and associated with poor prognosis. Altering NUF2 level affected cell proliferation, migration, and invasion. Moreover, NUF2 acted as a potential oncogene to promote the progression of ccRCC through epigenetic activation of high-mobility group AT-hook 2 (HMGA2) transcription by suppressing lysine demethylase 2A expression and affecting its occupancy on the HMGA2 promoter region to regulate histone H3 lysine 36 di-methylation modification. In addition, Kaplan-Meier and multivariate analysis revealed that patients whose NUF2 and HMGA2 were both elevated showed the shortest survival; and the number of upregulated markers acted as an independent predictor to evaluate survival probability. Thus, our results demonstrate that NUF2 promotes ccRCC progression, at least partly by epigenetically regulating HMGA2 transcription, and that the NUF2-HMGA2 axis could be an ideal therapeutic target and a promising prognostic indicator for ccRCC.


Subject(s)
Carcinoma, Renal Cell , Cell Cycle Proteins/metabolism , F-Box Proteins , Kidney Neoplasms , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation , Demethylation , F-Box Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Kidney Neoplasms/metabolism , Lysine/metabolism
8.
Environ Technol ; : 1-12, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35815364

ABSTRACT

ABSTRACTPlant leaves can retain atmospheric particulate matter (PM) and thus alleviate air pollution. Herein, four plant species (Cerasus. serrulata, H. syriacus, H. tuberosus, and E. japonicus) from the central part of Shanxi Province, China, were investigated to analyse the dynamic changes in their PM retention capacity and grain size over five periods. The relationship between leaf morphological characteristics (leaf size and leaf surface microstructure) and dynamic changes were discussed in PM retention, revealing the influence of leaf morphological characteristics on the amount of PM retention and its composition. The results showed that amount and grain sizes of the retained PM differed significantly among the various studied species; however, the trends in PM retention of different species in the time series were the same. The grain size distributions of PM from the four species displayed a bimodal distribution, in which the main peak distribution range was 5-60 µm and the secondary peak distribution range was 0.4-1 µm. Leaves of smaller sizes and those with rough surfaces had a high PM retention capacity. Leaves with deep grooves are conductive to retaining PM2.5 and PM2.5-10, while leaves with hair are conductive to retaining PM>10. Therefore, the morphological characteristics of leaves should be considered when selecting the use of plant species to alleviate air pollution.Highlights Dynamics of PM retention capacity and grain size distributions of four plant species were analysed.Grain size distributions of PM retained on leaves had a bimodal distribution.Small leaves with grooves or hair are conductive to PM retention.Grooves are conductive to fine PM retention while hairs are conductive to coarse PM retention.

9.
J Virol Methods ; 309: 114593, 2022 11.
Article in English | MEDLINE | ID: mdl-35908735

ABSTRACT

The citrus tatter leaf virus (CTLV) is one of the most destructive citrus viral diseases worldwide. In this study, reverse transcription-recombinase polymerase amplification combined with a lateral flow dipstick (RT-RPA-LFD) assay for rapid visual detection of CTLV was established. The assay was performed at 35 â„ƒ in 27 min without specialised equipment. The RT-RPA-LFD assay showed high specificity to CTLV, and the sensitivity to CTLV was the same as that of quantitative RT-PCR at 3 × 103 copies/µL CTLV RNA transcripts. A total of 45 field tangor samples were tested using RT-RPA-LFD, RT-PCR, and RT-qPCR, and the results were consistent. The results demonstrated that the RT-RPA-LFD assay is a promising tool for rapid on-site CTLV detection.


Subject(s)
RNA , Recombinases , Flexiviridae , Immunoassay , Nucleic Acid Amplification Techniques/methods , Sensitivity and Specificity
10.
Plast Reconstr Surg ; 150(3): 550-557, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35759630

ABSTRACT

BACKGROUND: Lower blepharoplasty techniques continue to improve over time. With discovery of the numerous fat compartments of the face, surgeons noticed that the appearance of the lower eyelid area through aging could be improved through midface lifting. This article introduces a vertical V-Y advancement lifting technique using the concept of fat compartments for lower lid and midcheek rejuvenation. METHODS: Eighty female patients were categorized into four age groups at 20 patients each from 20 to 59 years old. The average measurement for the lower lid length in each group was recorded. An additional 318 patients who underwent lower eyelid blepharoplasty combined with fat compartments advancement lifting for lid-cheek junction rejuvenation from April of 2015 to May of 2018 were included in this study. The postoperative effect was evaluated based on preoperative and postoperative photographs, lower lid length measurements, and three-dimensional facial analyses. RESULTS: Lower lid lengths gradually increased with age, with the greatest increase occurring in the 30- to 39-year-old group. A total of 318 Asian female patients (age range, 35 to 58 years) underwent the surgical procedure. Measurements of lower lid length showed an average reduction of 0.31 cm 6 months after surgery. Three-dimensional facial analysis indicated that midcheek volume increased at varying degrees after surgery. CONCLUSIONS: Lower eyelid blepharoplasty combined with vertical V-Y advancement lifting makes it possible to restore facial fat compartments. This procedure improves projection in the midcheek without fillers, thus achieving a more youthful appearance of the lower lid and lid-cheek contour in middle-aged women. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Blepharoplasty , Skin Aging , Adult , Blepharoplasty/methods , Cheek/surgery , Eyelids/surgery , Female , Humans , Middle Aged , Rejuvenation , Young Adult
11.
Front Microbiol ; 13: 812771, 2022.
Article in English | MEDLINE | ID: mdl-35369462

ABSTRACT

Hepatocellular carcinoma (HCC), a primary liver cancer, is closely associated with the gut microbiota. However, the role of gut fungi in the development of HCC remains unclear. The aim of this study was to explore the influence of intestinal Candida albicans on HCC. Here, We found that patients with HCC showed significantly decreased diversity of the gut mycobiome and increased abundance of C. albicans, compared to the patients with liver cirrhosis. The gavage of C. albicans in the WT models increased the tumor size and weight and influenced the plasma metabolome, which was indicated by alterations in 117 metabolites, such as L-carnitine and L-acetylcarnitine, and several KEGG enriched pathways, such as phenylalanine metabolism and citrate cycle. Moreover, the expression of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in the intestinal tissues and primary intestinal epithelial cells of the WT mice interacted with C. albicans increased. Notably, the colonization of C. albicans had no effect on tumor growth in Nlrp6 -/- mice. In conclusion, the abnormal colonization of C. albicans reprogrammed HCC metabolism and contributed to the progression of HCC dependent on NLRP6, which provided new targets for the treatment of HCC.

12.
Am J Cancer Res ; 12(2): 549-561, 2022.
Article in English | MEDLINE | ID: mdl-35261786

ABSTRACT

The anti-HER2 monoclonal antibody trastuzumab is the mainstay of treatment for HER2-positive breast and gastric cancer, and its combination with multiple chemotherapeutic agents has represented an effective and rational strategy in the clinic. In this study, we report that trastuzumab in combination with PEGylated interferon-α1b (IFN-α1b), a polyethylene glycol (PEG)-conjugated form of a subtype of interferon alpha (IFN-α), synergistically inhibited the proliferation of HER2-positive cells, including BT-474 and SK-BR-3 breast cancer cells and NCI-N87 gastric cancer cells, and also induced their apoptosis, but had no effect on HER2-negative MDA-MB-231 breast cancer cells. Trastuzumab inhibited phosphorylation of HER2, AKT and ERK, an effect that was enhanced by PEGylated IFN-α1b, likely owing to PEGylated IFN-α1b-mediated downregulation of HER2 through the lysosomal degradation pathway. Moreover, PEGylated IFN-α1b significantly enhanced trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) in HER2-positive cells. Importantly, trastuzumab combined with PEGylated IFN-α1b exhibited significant synergistic antitumor activity in HER2-positive BT-474 xenografts, an effect that was associated with enhanced inhibition of HER2 expression and AKT and ERK phosphorylation. Strikingly, depletion of natural killer cells with anti-Asialo GM1 antibody abrogated the synergistic antitumor activity, indicating that augmented ADCC is essential for this synergy. Taken together, our findings indicate that both enhanced inhibition of HER2 downstream signaling and augmented ADCC contribute to the synergistic antitumor activity of trastuzumab with PEGylated IFN-α1b, and imply that combining trastuzumab with PEGylated IFN-α1b could be a promising strategy for HER2-positive cancers.

13.
Investig Clin Urol ; 63(1): 107-117, 2022 01.
Article in English | MEDLINE | ID: mdl-34983129

ABSTRACT

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is a highly aggressive disease, and approximately 30% of patients are diagnosed at the metastatic stage. Even with targeted therapies, the prognosis of advanced ccRCC is poor. The aim of this study was to investigate clinical prognosis signatures by analyzing the ccRCC datasets in The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the function of thrombospondin 3 (THBS3) in ccRCC. MATERIALS AND METHODS: We analyzed the ccRCC datasets in TCGA and CPTAC to search for extracellular matrix (ECM)-related and adhesion-associated genes, and conducted overall survival, Cox, and receiver operating characteristic analyses. We also performed CCK8, colony formation, and transwell assays to compared the proliferation and migration ability of THBS3 knockout cells with those of cells without THBS3 knockout. RESULTS: Comprehensive bioinformatics analysis revealed that THBS3 is a novel candidate oncogene that is overexpressed in ccRCC tumor tissue and that its elevated expression indicates poor prognosis. Our study also showed that knockdown of THBS3 inhibits proliferation, colony formation, and migration of ccRCC cells. CONCLUSIONS: In summary, our data have revealed that THBS3 is upregulated in cancer tissues and could be used as a novel prognostic marker for ccRCC. Our findings thus offer theoretical support with bioinformatics analyses to the study of ECM and adhesion proteins in ccRCC, which may provide a new perspective for the clinical management of ccRCC.


Subject(s)
Carcinoma, Renal Cell/chemistry , Carcinoma, Renal Cell/etiology , Kidney Neoplasms/chemistry , Kidney Neoplasms/etiology , Thrombospondins/analysis , Thrombospondins/physiology , Carcinoma, Renal Cell/genetics , Extracellular Matrix , Female , Humans , Kidney Neoplasms/genetics , Male , Prognosis , Thrombospondins/isolation & purification , Tumor Cells, Cultured
14.
Neoplasma ; 69(1): 174-182, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34846160

ABSTRACT

Isochorismatase domain-containing 1 (ISOC1) plays a carcinogenic role in various tumors. However, its expression and role in hepatocellular carcinoma (HCC) have not been elucidated. This is the first study to investigate the involvement of ISOC1 in HCC growth and migration. ISOC1 expression was analyzed using public databases and clinical samples, and clinical specimens were analyzed by real-time quantitative polymerase chain reaction, western blotting, and immunohistochemistry. ISOC1 was also overexpressed in two HCC cell lines (Huh7 and HepG2) to explore how ISOC1 affects HCC cells. Finally, a nude mouse xenograft tumor model was used to investigate the role of ISOC1 in HCC cell tumorigenicity. ISOC1 was downregulated in HCC tissues compared to that in matched paracancerous tissues, and low ISOC1 expression was associated with a poor prognosis. The proliferation and single-cell colony-forming ability of the ISOC1-overexpressing cell lines Huh7 and HepG2 were significantly inhibited. Moreover, ISOC1 overexpression suppressed the migration and invasion abilities of HCC cells in vitro, and ISOC1 upregulation hindered tumor growth in the xenograft tumor model in vivo. Therefore, ISOC1 is a potential HCC suppressor protein.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Hydrolases , Liver Neoplasms/genetics , Mice
15.
Front Genet ; 12: 720979, 2021.
Article in English | MEDLINE | ID: mdl-34539751

ABSTRACT

Metastasis is the main cause of clear cell renal cell carcinoma (ccRCC) treatment failure, and the key genes involved in ccRCC metastasis remain largely unknown. We analyzed the ccRCC datasets in The Cancer Genome Atlas database, comparing primary and metastatic ccRCC tumor records in search of tumor metastasis-associated genes, and then carried out overall survival, Cox regression, and receiver operating characteristic (ROC) analyses to obtain potential prognostic markers. Comprehensive bioinformatics analysis was performed to verify that the checkpoint with forkhead associated and ring finger domains (CHFR) gene is a reliable candidate oncogene, which is overexpressed in ccRCC metastatic tumor tissue, and that high expression levels of CHFR indicate a poor prognosis. A detailed analysis of the methylation of CHFR in ccRCC tumors showed that three sites within 200 bp of the transcription initiation site were significantly associated with prognosis and that hypomethylation was associated with increased CHFR gene expression levels. Knockdown of CHFR in ccRCC cells inhibited cell proliferation, colony formation, and migration ability. In summary, our findings suggest that the epigenetic signature on CHFR gene is a novel prognostic feature; furthermore, our findings offer theoretical support for the study of metastasis-related genes in ccRCC and provided new insights for the clinical treatment of the disease.

16.
Hortic Res ; 8(1): 199, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34465762

ABSTRACT

Self-incompatibility (SI) substantially restricts the yield and quality of citrus. Therefore, breeding and analyzing self-compatible germplasm is of great theoretical and practical significance for citrus. Here, we focus on the mechanism of a self-compatibility mutation in 'Guiyou No. 1' pummelo (Citrus maxima), which is a spontaneous mutant of 'Shatian' pummelo (Citrus maxima, self-incompatibility). The rate of fruit set and the growth of pollen tubes in the pistil confirmed that a spontaneous mutation in the pistil is responsible for the self-compatibility of 'Guiyou No. 1'. Segregation ratios of the S genotype in F1 progeny, expression analysis, and western blotting validated that the reduced levels of S2-RNase mRNA contribute to the loss of SI in 'Guiyou No. 1'. Furthermore, we report a phased assembly of the 'Guiyou No. 1' pummelo genome and obtained two complete and well-annotated S haplotypes. Coupled with an analysis of SV variations, methylation levels, and gene expression, we identified a candidate gene (CgHB40), that may influence the regulation of the S2-RNase promoter. Our data provide evidence that a mutation that affects the pistil led to the loss of SI in 'Guiyou No. 1' by influencing a poorly understood mechanism that affects transcriptional regulation. This work significantly advances our understanding of the genetic basis of the SI system in citrus and provides information on the regulation of S-RNase genes.

17.
Oncol Rep ; 46(5)2021 Nov.
Article in English | MEDLINE | ID: mdl-34498718

ABSTRACT

Pancreatic cancer (PC) is a lethal malignancy. Its prevalence rate remains low but continues to grow each year. Among all stages of PC, metastatic PC is defined as late­stage (stage IV) PC and has an even higher fatality rate. Patients with PC do not have any specific clinical manifestations. Most cases are inoperable at the time­point of diagnosis. Prognosis is also poor even with curative­intent surgery. Complications during surgery, postoperative pancreatic fistula and recurrence with metastatic foci make the management of metastatic PC difficult. While extensive efforts were made to improve survival outcomes, further elucidation of the molecular mechanisms of metastasis poses a formidable challenge. The present review provided an overview of the mechanisms of metastatic PC, summarizing currently known signaling pathways (e.g. epithelial­mesenchymal transition, NF­κB and KRAS), imaging that may be utilized for early detection and biomarkers (e.g. carbohydrate antigen 19­9, prostate cancer­associated transcript­1, F­box/LRR­repeat protein 7 and tumor stroma), giving insight into promising therapeutic targets.


Subject(s)
Early Detection of Cancer/methods , Neoplasm Metastasis/diagnostic imaging , Neoplasm Metastasis/pathology , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Biomarkers, Tumor , Humans , Magnetic Resonance Imaging , Tomography, X-Ray Computed
18.
Appl Opt ; 60(15): C47-C54, 2021 May 20.
Article in English | MEDLINE | ID: mdl-34143105

ABSTRACT

A compact fiber-coupled hyperspectral imaging sensor (HSIS) operating within the range of ultraviolet to near-infrared (UV-NIR) wavelengths is designed and developed for the remote recording of two-dimensional (2D) spectrally resolved thermal radiation and chemiluminescent emission from ultra-high-temperature ceramics (UHTCs). Using simulations, the entire system is optimized to improve the collection efficiency and minimize aberrations. The design, construction, and characterization of the HSIS sensor are discussed in detail. We present the 2D spectrally resolved measurements of the simultaneous thermal radiation and BO2∗ chemiluminescent emission from a commonly used UHTC (HfB2-SiC) material under high-heat-flux conditions. Our results show that BO2∗ chemiluminescence corresponds directly to material ablation and can be used to track the formation of the protective heat-resistant glass/oxide layer. Furthermore, the temperature measurements demonstrate the heat distribution properties of the sample and indicate the locations at which BO2∗ chemiluminescence is possible. These results highlight the application prospects of the compact fiber-coupled HSIS for high-temperature material characterization in practical arc-jet facilities with limited optical access.

19.
Cell Death Dis ; 12(2): 201, 2021 02 19.
Article in English | MEDLINE | ID: mdl-33608495

ABSTRACT

Because of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan-Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.


Subject(s)
Carcinoma, Renal Cell/genetics , Cell Cycle Proteins/genetics , Epigenesis, Genetic , Kidney Neoplasms/genetics , RNA Stability , RNA, Long Noncoding/genetics , RNA-Binding Proteins/genetics , Transcriptional Activation , Animals , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , DNA Methylation , Databases, Genetic , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Male , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolism , Signal Transduction , Tumor Burden
20.
Parkinsons Dis ; 2021: 3366870, 2021.
Article in English | MEDLINE | ID: mdl-35070257

ABSTRACT

BACKGROUND: Speech changes occur in the early stages of Parkinson's disease (PD) and cause communication difficulties, leading to social isolation. Lee Silverman voice treatment (LSVT) is a speech therapy approach designed to improve patients' language and voice capabilities. OBJECTIVE: The effectiveness of the LSVT was compared with that of other speech interventions or no treatment to evaluate PD patients with dysarthria. DESIGN: Systematic review with meta-analysis of randomized trials. Data Sources: PubMed, Embase, Cochrane Library, CNKI, and SinoMed library were searched from inception to December 2021 related to PD and LSVT. METHOD: Abstracts were screened and reviewed against the eligibility criteria (intervention group participants were PD assessed based on LSVT (LSVT Loud) and randomized control). RESULT: Ten randomized controlled trials were identified on speech symptoms in patients with PD. Compared with the respiratory therapy (RET) exercise, or no training group, a significant improvement was detected in the sound press level (SPL) after immediate treatment during the reading of vowel and rainbow passages and an increase in semitone standard deviation (STSD). Furthermore, the LSVT training significantly increased the participants' scores on unified Parkinson's disease rating scale (UPDRS-III) and speech intelligibility. CONCLUSION: This meta-analysis demonstrated the efficacy of LSVT in increasing vocal loudness and functional communication among individuals with PD. However, most studies included participants with mild-moderate PD. Thus, additional randomized controlled trials (RCTs) with large sample sizes are needed to validate the efficacy of LSVT in patients with different progressions of PD, including severe PD.

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