Phage-assisted evolution of compact Cas9 variants targeting a simple NNG PAM.

Compact Cas9 nucleases hold great promise for therapeutic applications. Although several compact Cas9 nucleases have been developed, many genomic loci still could not be edited due to a lack of protospacer adjacent motifs (PAMs). We previously developed a compact SlugCas9 recognizing an NNGG PAM.

Bispecific GPC3/PD‑1 CAR‑T cells for the treatment of HCC.

Constantly stimulated by the tumor microenvironment (TME), programmed death 1 (PD‑1) is elevated, and it interacts with PD ligand 1 (PD‑L1), rendering chimeric antigen receptor (CAR)‑T cells dysfunctional. Hence, CAR‑T cells immune to PD‑1‑induced immunosuppression were constructed to improve the function of CAR‑T cells in hepatocellular carcinoma (HCC). Double‑target CAR‑T cells, targeting glypican‑3 (GPC3) [a tumour-associated antigen (TAA)] and hindering PD‑1‑PD‑L1 binding, were established.

Nucleos(t)ide analogues altered quasispecies composition of hepatitis B virus (HBV)-resistant mutations in serum HBV DNA and serum HBV RNA.

Serum hepatitis B virus (HBV) RNA is a new serological indicator reflecting viral replication with good clinical application prospects. This study aimed to clarify the dynamic changes of serum HBV RNA levels and the quasispecies of HBV RNA virus-like particles in nucleos(t)ide analogues (NAs)-experienced chronic hepatitis B (CHB) patients harboring NAs-resistant mutations and their identifiable effects on NAs resistance. We included CHB patients who were on long-term NAs treatment and with HBV DNA rebound.

LMP1 mediates tumorigenesis through persistent epigenetic modifications and PGC1β upregulation.

Latent membrane protein 1 (LMP1), which is encoded by the Epstein‑Barr virus (EBV), has been considered as an oncogene, although the detailed mechanism behind its function remains unclear. It has been previously reported that LMP1 promotes tumorigenesis by upregulation of peroxisome proliferator‑activated receptor‑γ coactivator‑1β (PGC1β). The present study aimed to investigate the potential mechanism for transient EBV/LMP1 exposure‑mediated persistent PGC1β expression and subsequent tumorigenesis through modification of mitochondrial function.

Silencing of TMED5 inhibits proliferation, migration and invasion, and enhances apoptosis of hepatocellular carcinoma cells.

Background: Transmembrane P24 trafficking protein 5 (TMED5) is highly expressed in cervical and bladder cancer cell lines. Moreover, TMED5 promotes nuclear autophagy and the malignant behavior of cervical cancer cells. However, the role of TMED5 in hepatocellular carcinoma (HCC) has not been extensively reported.

Anti-aging effect of β-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process.

Background: Research on aging is growing as the elderly make up a greater share of the population, focusing on reversing and inhibiting the aging process. The exhaustion and senescence of stem cells are the fundamental drivers behind aging. β-Carotene has been depicted to have many biological functions, and we speculate that it may have an anti-aging effect.

Characteristics of HBV Novel Serum Markers across Distinct Phases in Treatment-Naïve Chronic HBV-Infected Patients.

Methods: A total of 111 patients in total from different disease phases were recruited, including 21 in immune-tolerant (IT) phase, 49 in immune-clearance (IC) phases, 29 in immune-control or low replicative (LR) phase, and 12 in reactivation phases. Serum HBV RNA, anti-HBc, HBcrAg, and intrahepatic covalently closed circular DNA (cccDNA) were quantified and each of these indicator's correlation with liver inflammation was analyzed.

Results: HBeAg-positive individuals had significant higher serum levels of HBV RNA and HBcrAg than those who were HBeAg negative, similar to that of serum HBV DNA.

MicroRNA-139-5p negatively regulates NME1 expression in hepatocellular carcinoma cells.

Background: High expression of NME1 is associated with hepatocellular carcinoma (HCC) progression and poor prognosis. However, there are few reports on the association between NME1 and microRNAs (miRNAs) in HCC progression.

Objectives: To explore miRNAs that regulate NME1 expression in HCC.

Exosomes derived from NGF-overexpressing bone marrow mesenchymal stem cell sheet promote spinal cord injury repair in a mouse model.

Cell transplantation has been an appealing way to improve the recovery of motor, sensory, and autonomic functions following spinal cord injury (SCI). Herein, we sought to elucidate the function of bone marrow mesenchymal stem cells (BMSCs) sheet in the progression of SCI and its underlying mechanism. BMSCs were extracted from bone marrow of femur and tibia collected from C57BL/6 mice, and the BMSC sheet was prepared when cells grew to 100% confluence after approximately 14 days.

Different isoforms of growth hormone (20 kD-GH and 22 kD-GH) shows different biological activities in mesenchymal stem cell (MSC).

There are two main types of growth hormone (GH) in the circulatory system. One is 22 kD-GH, which is the predominant isoform in the circulating system, 90% GH is present as a 22 kD protein, and 10% of GH is present as a 20 kD protein. Amino acid sequences are identical between 20 kD-GH and 22 kD-GH protein, except that 20 kD-GH lacks 15 amino acid residues 32 to 46.

microRNA-378a-3p regulates the progression of hepatocellular carcinoma by regulating PD-L1 and STAT3.

Programmed death ligand 1 (PD-L1) plays an essential role in the development or progression of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression during normal and pathophysiological events. Here, we explored the functions and detailed mechanisms of and PD-L1 in HCC progression.

METTL3 facilitates the progression of hepatocellular carcinoma by modulating the m6A level of USP7.

Objective: To explore whether METTL3 was involved in the pathogenesis of hepatocellular carcinoma (HCC) by modulating the m6A level of USP7.

Methods: We performed qRT-PCR and western blot assays to detect the expression level of METTL3 in HCC tissues and paired adjacent normal tissues, as well as HCC cell lines. The level of m6A in HCC tissues and cells was quantitatively analyzed by m6A RNA Methylation Quantitative Kit.

Objective to identify and verify the regulatory mechanism of DTNBP1 as a prognostic marker for hepatocellular carcinoma.

Although the overall survival of hepatocellular carcinoma (HCC) patients has been significantly improved, prognostic clinical evaluation remains a substantial problem owing to the heterogeneity and complexity of tumor. A reliable and accurate predictive biomarker may assist physicians in better monitoring of patient treatment outcomes and follow the overall survival of patients. Accumulating evidence has revealed that DTNBP1 plays functional roles in cancer prognosis.

attenuates hepatocellular carcinoma progression through the / axis.

Hepatocellular carcinoma (HCC) is one of the most death-related cancers worldwide. Identifying cancer-associated genes and uncovering the vital molecular mechanisms of HCC progression contribute greatly to the prognosis and novel therapeutic strategies for HCC patients. Although lncRNAs have been proved to be critical modulators of various cellular processes, the functions of lncRNAs in HCC progression are just emerging.

Uridine alleviates carbon tetrachloride-induced liver fibrosis by regulating the activity of liver-related cells.

At present, liver fibrosis is a major challenge of global health. When hepatocyte regeneration cannot compensate for hepatocyte death, it will develop into liver fibrosis in chronic liver disease. Initially, collagen produced by myofibroblasts plays a role in maintaining liver integrity, but excessive collagen accumulation can inhibit the residual liver function, leading to liver failure.

A Highly Sensitive GFP Activation Assay for Detection of DNA Cleavage in Cells.

CRISPR/Cas9 nucleases hold great potential for gene therapy, but they frequently induce unwanted off-target cleavage. We previously developed a GFP activation assay for detection of DNA cleavage in cells. Here, we demonstrate two novel applications of this assay.

22-kD growth hormone-induced nuclear GHR/STAT5/CyclinD1 signaling pathway plays an important role in promoting mesenchymal stem cell proliferation.

Growth hormone (GH) exhibited the important biological activities in the mesenchymal stem cell (MSCs). However, the cellular behavior and properties of GH/GHR in MSCs remain unclear. A series of experiments (such as confocal laser scanning microscope [CLSM] and Western-blot) were performed to systematically investigate the cellular behavior of GH/GHR in MSCs, and the results showed that GH/GHR not only internalized into the cytoplasm, but also transported into the cell nuclei of MSCs.

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy.

Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated.