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CRISPR-Cas9 mediated mutation inside Materials WIDTH as well as WEIGHT2 (GW2) locus boosts aleurone coating and also grain nutritional quality throughout hemp.
s andin maintenance of hypoxic conditions, thereby suggesting the existence of an indirect miR-196a/HIF positive feedback loop under hypoxia.

Overall, our work identifies a novel association between hypoxia/HIF signalling and miR-196a in GBM and suggests its therapeutic significance.
Overall, our work identifies a novel association between hypoxia/HIF signalling and miR-196a in GBM and suggests its therapeutic significance.
Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. Firsocostat mouse It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors.

BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion.
BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion.
Immune responses have long been an area of interest in cancer research. In this study, the effects of programmedcell death-1 (PD-1) and its ligand (PD-L2)on the prognosis of colorectal cancer (CRC) were investigated.

Primary tumour specimens of stage III CRC patients operated between 2002 and 2013 were assessed for PD-1 and PD-L2 expression and various clinicopathological and prognostic factors.

We observed a significant relationship between poor prognostic factors and PD-1/PD-L2 expression. These biomarkers were also found to serve as independent risk factors for LIR and MSI. In univariate analysis, relapse-free survival (RFS) and overall survival (OS) rates were found to be poor in PD-1 and PD-L2positive patients. In multivariate analysis, these biomarkers were found to serve as independent poor prognostic factors for RFS and OS.

Our data indicate that PD-1 and PD-L2may serve as independent prognostic survival parameters for CRC patients and may be employed for the design of targeted therapies.
Our data indicate that PD-1 and PD-L2 may serve as independent prognostic survival parameters for CRC patients and may be employed for the design of targeted therapies.
PRMT5 is a type II protein arginine methyltransferase that methylates histone or non-histone proteins. Arginine methylation by PRMT5 has been implicated in gene transcription, ribosome biogenesis, RNA transport, pre-mRNA splicing and signal transduction. High expression of PRMT5 has been observed in various cancers and PRMT5 overexpression has been reported to improve cancer cell survival, proliferation, migration and metabolism and to inhibit cancer cell apoptosis. In addition, PRMT5 has been found to be required for cancer stem cell survival, self-renewal and differentiation. Several microRNAs have been shown to regulate PRMT5 expression. As PRMT5 has oncogene-like properties, several PRMT5 inhibitors have been used to explore their efficacy as potential drugs for different types of cancer, and three of them are now being tested in clinical trials.

In this review, we summarize current knowledge on the role of PRMT5 in cancer development and progression, including its functions andunderlying mechanisms. In addition, we highlight the rapid development of PRMT5 inhibitors and summarize ongoing clinical trials for cancer therapy. By affecting both tumor cells and the tumor microenvironment, PRMT5 inhibitors mayserve as effectiveanti-cancer agents, especially when combined with immune therapies.
In this review, we summarize current knowledge on the role of PRMT5 in cancer development and progression, including its functions and underlying mechanisms. In addition, we highlight the rapid development of PRMT5 inhibitors and summarize ongoing clinical trials for cancer therapy. By affecting both tumor cells and the tumor microenvironment, PRMT5 inhibitors may serve as effective anti-cancer agents, especially when combined with immune therapies.
Cervical cancer remains a major cause of cancer-related death in women, especially in developing countries. Previously, we found that the acetylation levels of chloride intracellular channel 1 (CLIC1) at lysine 131 were increased in cervical cancer tissues using a label-free proteomics approach. The aim of this study was to further determine the role of CLIC1 expression and its acetylation in cervical cancer.

CLIC1 expression and its implications for the prognosis of cervical cancer were analyzed using primary patient samples and cells, and the Gene Expression Profiling Interactive Analysis (GEPIA) database (gepia.cancer-pku.cn). The effect of CLIC1 on cervical cancer cells was evaluated using Cell Counting Kit (CCK)-8, flow cytometry, scratch wound healing, transwell, Western blotting and co-immunoprecipitation (Co-IP) assays. In vivo tumor growth was assessed using mouse xenograft models.

We found that CLIC1 expression was increased in cervical cancer tissues and cells and that patients with a high CLndicate that CLIC1 acts as a tumor promoter in cervical cancer, suggesting a potential treatment strategy for cervical cancer by regulating CLIC1 expression and/or acetylation.
Integrins, transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions, have been linked to several cancer-associated features. A less explored function of integrins in cancer is their role in leukocyte homing and activation. Understanding their relationship with immune cell infiltrates and immune checkpoints is an area of interest in cancer research.

The expression of 33 different integrins was evaluated in relation with breast cancer patient outcome using transcriptomic data (Affymetrix dataset, exploratory cohort) and the METABRIC study (validation cohort). The TIMER online tool was used to assess theassociation of the identified integrin genes with immune cell infiltration, and the TCGA and METABRIC studies to assess correlations between integrin gene expression and genomic signatures of immune activation.

We identified 7 genes coding for integrin α and β subunits, i.e., ITGA4, ITGB2, ITGAX, ITGB7, ITGAM, ITGAL and ITGA8, which predict a favorable prognosis in Basal-like and HER2+ breast cancers. Their expression positively correlated with the presence of immune cell infiltrates within the tumor (dendritic cells, CD4+ T-cells, neutrophils, CD8+ T-cells and B-cells), with markers of T-cell activation and antigen presentation, and with gene signatures of immune surveillance (cytotoxic T lymphocyte activation and IFN gamma signature). By contrast, we found that genes coding for integrins that predicted a detrimental outcome (IBSP, ITGB3BP, ITGB6, ITGB1 and ITGAV) were not associated with any of these parameters.

We identified an integrin signature composed of 7 genes with potential to recognize immune infiltrated and activated Basal-like and HER2+ breast cancers with a favorable prognosis.
We identified an integrin signature composed of 7 genes with potential to recognize immune infiltrated and activated Basal-like and HER2+ breast cancers with a favorable prognosis.Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3 ± 61.6., n = 111, 20.6 ± 13.4, n = 540, and 16.1 ± 7.4 mU/L, n = 46, respectively). Patients with severe AS were older than patients with hypertension (80 ± 6 years vs. 60 ± 15 years, P  less then  0.05). Serum ACE2 activity correlated negatively with the left ventricular ejection fraction, aortic root area, TAPSE, and positively with the right ventricular systolic pressure, cardiac diameters in patients with AS. In contrast, circulating ACE2 activity was independent of the blood pressure, peak flow velocity at the aortic root, kidney function (GFR), and inflammatory state (CRP). We found no effect of RAAS inhibitory drugs on the serum ACE2 activity in this group of patients. Our results illustrate circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 susceptibility. Elderly patients with AS have markedly elevated ACE2 levels together with altered left and right ventricular functions, which may pose higher risks during COVID-19. Our clinical data do not support a role for RAAS inhibitors in regulating circulating ACE2 levels.It is well established from previous cross-sectional studies that telomeres shorten with age. However, due to a considerable inter-individual variation in telomere length (TL), its relationship with biological aging is difficult to unpick. Longitudinal repeated assessments of TL changes within individuals should augment our understanding of TL dynamics in aging. This study disentangles within- and inter-individual effects of age on leukocyte telomere length (LTL) dynamics in a large population-based cohort of older adults. A total of 4053 subjects aged 50 and older from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Relative LTL (T/S ratio) was measured at baseline (2009-2010) and follow-up (2017-2018) by quantitative real-time polymerase chain reaction. We used linear random slope models to analyze LTL dynamics in relation to age and sex and within-subject centering method to distinguish within- versus between-subject effects. We observed LTL shortening in 66.32%, maintenance in 11.23%, and elongation in 22.45% of the study participants. LTL declined significantly with age both cross-sectionally and longitudinally. More importantly, the longitudinal decline in LTL was much greater than the cross-sectional decline (- 0.017 (p less then 0.001) versus - 0.002 (p less then 0.001) per year). Furthermore, women had a lower within-subject LTL shortening rate than men (- 0.014 versus - 0.020 per year, p less then 0.001). The within-individual longitudinal decline in LTL was much greater than the inter-individual cross-sectional decline, indicating that chronological age might impose a greater impact on LTL shortening than other influencing factors combined. Moreover, women showed a lower within-individual LTL shortening rate than men.
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