CRISPR-HOLMES-based NAD detection.

Studies have indicated that the intracellular nicotinamide adenine dinucleotide (NAD) level is associated with the occurrence and development of many diseases. However, traditional nicotinamide adenine dinucleotide (NAD) detection techniques are time-consuming and may require large and expensive instruments. We recently found that the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a protein can be inactivated by AcrVA5-mediated acetylation and reactivated by CobB, using NAD as the co-factor.

Corrigendum: Ribosomal protein L23 drives the metastasis of hepatocellular carcinoma upregulating MMP9.

[This corrects the article DOI: 10.3389/fonc.2021.

meHOLMES: A CRISPR-cas12a-based method for rapid detection of DNA methylation in a sequence-independent manner.

Aberrant DNA methylation is closely associated with various diseases, particularly cancer, and its precise detection plays an essential role in disease diagnosis and monitoring. In this study, we present a novel DNA methylation detection method (namely meHOLMES), which integrates both the TET2/APOBEC-mediated cytosine deamination step and the CRISPR-Cas12a-based signal readout step. TET2/APOBEC efficiently converts unmethylated cytosine to uracil, which is subsequently changed to thymine after PCR amplification.

Intracellular hydrogelation of macrophage conjugated probiotics for hitchhiking delivery and combined treatment of colitis.

Immune cell membrane coated nanomedicine was developed to neutralize cytokines via receptor-ligand interaction, which showed potential for the treatment of inflammatory bowel disease (IBD). However, cell membrane isolation and re-assembly process involved protein loss and spatial disorder, which reduced the sequestration efficiency towards cytokines. In addition, oral administration of probiotics was accepted for IBD treatment via gut microbiota modulation, but most probiotics showed weak adhesion to intestine mucosa and were quickly expelled from gastrointestinal tract.

Prognostic subtypes of thyroid cancer was constructed based on single cell and bulk-RNA sequencing data and verified its authenticity.

There has been an increase in the mortality rate of thyroid cancer (THCA), which is the most common endocrine malignancy. We identified six distinct cell types in the THAC microenvironment by analyzing single-cell RNA sequencing (Sc-RNAseq) data from 23 THCA tumor samples, indicating high intratumoral heterogeneity. Through re-dimensional clustering of immune subset cells, myeloid cells, cancer-associated fibroblasts, and thyroid cell subsets, we deeply reveal differences in the tumor microenvironment of thyroid cancer.

Human liver cancer organoids: Biological applications, current challenges, and prospects in hepatoma therapy.

Liver cancer and disease are among the most socially challenging global health concerns. Although organ transplantation, surgical resection and anticancer drugs are the main methods for the treatment of liver cancer, there are still no proven cures owing to the lack of donor livers and tumor heterogeneity. Recently, advances in tumor organoid technology have attracted considerable attention as they can simulate the spatial constructs and pathophysiological characteristics of tumorigenesis and metastasis in a more realistic manner.

DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling.

: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver that is the leading cause of cancer-related mortality worldwide. However, genetic alterations and mechanisms underlying HCC development remain unclear. Tissue specimens were used to evaluate the expression of DEAD-Box 56 (DDX56) to determine its prognostic value.

[Retracted] Upregulation of microRNA‑25‑3p inhibits proliferation, migration and invasion of osteosarcoma cells by directly targeting SOX4.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Figs. 3B and 5C were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal.

Protein corona-driven nanovaccines improve antigen intracellular release and immunotherapy efficacy.

During vaccine delivery in vivo, the vaccine carrier dynamically adsorbs the surrounding proteins or biomacromolecules to form a protein corona layer, which determines the physiological and therapeutic responses of the vaccine. Although the importance of the protein corona effect in drug delivery is widely accepted, understanding of the rational use of the protein corona to improve antigen controlled release is still sparse. Here, we constructed a protein corona-driven nanovaccine (PCNV), which has the dual effects of resisting the protein corona-induced antigen extracellular release and promoting protein corona-triggered antigen cytosolic release under reductive conditions.

KAT2A Promotes Hepatitis B Virus Transcription and Replication Through Epigenetic Regulation of cccDNA Minichromosome.

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Sufficient maintenance of the HBV covalently closed circular DNA (cccDNA), which serves as a template for HBV transcription, is responsible for the failure of antiviral therapies. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation and methylation of cccDNA-bound histone 3 (H3) and histone 4 (H4), the potential contributions of histone succinylation and related host factors remain obscured.

Hepatocellular Carcinoma Differentiation: Research Progress in Mechanism and Treatment.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Although progress has been made in diagnosis and treatment, morbidity and mortality continue to rise. Chronic liver disease and liver cirrhosis are still the most important risk factors for liver cancer.

Ribosomal Protein L23 Drives the Metastasis of Hepatocellular Carcinoma Upregulating MMP9.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Tumor metastasis is one of the major causes of high mortality of HCC. Identifying underlying key factors contributing to invasion and metastasis is critical to understand the molecular mechanisms of HCC metastasis.

DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis.

Background And Aims: The mechanism underlying HCC metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro-metastatic HCC is poorly understood.

Approach And Results: By performing RNA sequencing on nine pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and nine pairs of metastasis-free HCC (MFH) tissues, we depicted the AS landscape in HCC and found a higher frequency of AS events in EHMH compared with MFH.

Overexpression of ubiquitin-conjugating enzyme E2 L3 in hepatocellular carcinoma potentiates apoptosis evasion by inhibiting the GSK3β/p65 pathway.

UBE2L3 is a ubiquitin-conjugating protein belonging to the E2 family that consists of 153 amino acid residues. In this study, we found that UBE2L3 was generally upregulated in clinical HCC samples compared to non-tumour samples and that there was a strong association between high UBE2L3 expression and tumour size, clinical grade and prognosis in HCC patients. UBE2L3 depletion inhibited the proliferation and induced the apoptosis of HCC cells.

NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma.

Background: Our previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated.

Methods: Expression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry.

Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortalities worldwide. The role of ornithine transcarbamylase (OTC) in HCC remains unclear. In the present study, the expression of OTC in HCC was analyzed based on datasets from the Gene Expression Omnibus database of the National Center for Biotechnology Information and further confirmed by immunohistochemistry, western blotting analysis and reverse transcription-quantitative polymerase chain reaction assays on clinical samples and cell lines.

PBK overexpression promotes metastasis of hepatocellular carcinoma via activating ETV4-uPAR signaling pathway.

Invasion and metastasis are the predominant causes of lethal outcomes in patients with hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the invasive or metastatic process are still insufficiently understood. Here, we first integrated several public databases and identified a novel protein kinase, PDZ-binding kinase (PBK) that was frequently upregulated and correlated with poor prognosis in patients with HCC.