Cancer remains a great challenge for mankind. The complex and diverse phenotypes, mechanisms, as well as therapeutic responsiveness of cancer have gradually been understood since the second half of the 20th century, which was a representative of entering the molecular era of oncology research. In 2000, the groundbreaking review “Hallmarks of Cancer” came out and it had been updated to the third version with 14 characteristics of cancer in 2022. These series of reviews helped to distil the increasingly complicated concepts of oncology into a logical science, which contributed to a more comprehensive understanding of the mechanisms for cancer genesis and development and applying the knowledges to the diagnosis and treatment of tumors. Mastering, applying, and exploring the hallmarks of cancer will help us face the challenges of cancer more confidently in the future.
Cancer is a heterogeneous disease characterized by maladjustment of cell death. The types of cell death were mainly divided into two forms including accidental cell death and regulated cell death (RCD). In recent years, researchers have discovered dozens of RCD modes, among which apoptosis, pyroptosis, necroptosis, and ferroptosis are the most widely studied. Cuproptosis is a new cell death mechanism that first proposed on 17 March 2022. It is recognized as a unique and both copper and mitochondria dependent RCD. The research and development of targeted drugs for regulating different cell death pathways will be hots and difficulties in the treatment of refractory cancer in the future.
As one of the most breakthrough cutting-edge technologies in the biomedical field in recent years, organoid culture technology can use cells derived from, either (pluripotent) stem cells or tissue-derived differentiated/progenitor cells (foetal, neonatal, or adult) to form 3D multicellular structure organoids with self-organizing and recapitulating at least some features of the organ including tissue architecture or function abilities. Recently, organoids have been widely used in disease model construction, anti-cancer drug screening, gene or cell therapy, etc., providing an ideal model for basic biomedical research, drug development and clinical precision medicine, and has shown an important role in regenerative medicine.
The Human Cell Atlas project is an international collaboration following the Human Genome Project, which aims to establish a reference map for the characterization of all human cells. Recent years, the project has brought together various different types of cell atlas, mostly focusing on the cell types of individual tissues and organs. Science published the latest research results of the Pan-tissue Human Cell Atlas on 12 May 2022, which integrates cell atlas of multiple tissues and organs in the human. It contributes to a more comprehensive understanding of disease pathogenesis, vaccine development, cell engineering, tumor immunity, and regenerative drug development.
RNA can be labeled by more than 170 chemical modifications after transcription, and these chemical modifications are collectively referred to as RNA modifications. It opened a new chapter of epigenetic research and became a major research hotspot in recent years. RNA modification regulates the expression of genes from the transcriptome level by regulating the fate of RNA, thus participating in many biological processes and disease occurrence and development. With the deepening of research, the diversity and complexity of RNA modification, as well as its physiological significance and potential as a therapeutic target, can not be ignored.
Evidence from numerous animal models and clinical studies in recent years has demonstrated that macrophages play an important role in the regulation of liver fibrosis regression. The safety and efficacy of utilizing autologous macrophages for the treatment of liver fibrosis have been demonstrated in patients and shows promising application prospects, but the therapeutic effects need to be improved. Cirrhotic liver undergoes a process of marked extracellular matrix degradation after partial hepatectomy surgery, and single-cell sequencing identified multiple restorative macrophage subsets that express different matrix metalloproteinases (MMPs) at high levels. Future efforts to further characterize this population of macrophages and improve their enrichment in the liver may allow macrophage therapy to be a highly effective strategy to reverse liver fibrosis.
ObjectiveTo investigate changes of lipopolysaccharidebinding protein (LBP) and its clinical significance in activation of Kupffer cells (KCs) during endotoxemia.MethodsWistar rat endotoxemia model was established by injection of a dose of LPS (5 mg/kg, Escherichia coli O111∶B4) via the tail vein of rats, then sacrificed 1, 3, 6 and 12 hour respectively. Hepatic tissue was collected to measure LBP mRNA expression by reverse transcritasepolymerase chain reaction (RTPCR). The levels of plasma endotoxins, LBP, TNFα and IL6 were determined. The pathological changes of hepatic tissue were observed under electron microscope.ResultsWhen the levels of plasma LPS elevated, expression of LBP mRNA in hepatic tissue were ber than that in control rats. The levels of plasma LBP, TNFα and IL6 were increased markedly also in rat with endotoxemia when compared with that in control groups (P＜0.01). KCs were seen to be enlarged in size, their surface projections were increased in number, and their cytoplasm was full of phagocytic vacuoles or electron dense phagosomes which indicated active phagocytosis.ConclusionLPS can markedly upregulate LBP mRNA expression in hepatic tissue, the levels of plasma LBP also increased. LBP may be a critical factor of LPS which stimulates KCs to produce and release different proinflammary mediators.
ObjectiveTo determine the nuclear factor kappa B (NFkB) activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NFkB activation with severity of biliary tract infection and clinical outcome.MethodsTwenty patients with ACST were divided into survivor group (14 cases) and nonsurvivor group (6 cases). Other 10 patients undergoing elective gastrectomy or inguinal hernia repair were selected as control group. Peripheral blood samples were taken 24 hours after operation, PBMC was separated and nuclear proteins were isolated from PBMC, and NFkB was determined with electrophoretic mobility shift assay (EMSA). The levels of TNFα, IL6 and IL10 in plasma were determined by using an enzymelinked immunoassay (ELISA). ResultsThe NFkB activity was 5.02±1.03, 2.98±0.51 and 1.02±0.34 respectively in three groups. It was increased in all patients with ACST, versus the control group (P＜0.05), and the patients of nonsurvivor group had higher levels of NFkB activation than those of survivor group (P＜0.05). The levels of TNFα and IL6 were (496.28±52.35) ng/L and (578.13±67.72) ng/L in nonsurvivor group; (284.47±39.41) ng/L and (318.67±34.92) ng/L in survivor group; (89.43±10.39) ng/L and (101.27±13.47) ng/L in control group. All patients with ACST had increased levels of TNFα and IL6, which were many fold greater than that of control group, and there was an evidence of significantly higher levels in nonsurvivor group than in survivor group (P＜0.05). All patients had also increased levels of IL10 as compared to control group (P＜0.05), but the IL10 concentrations in plasma were not significantly higher in nonsurvivors than that of in those survivors (Pgt;0.05). ConclusionNFkB activation in PBMCs in patients with ACST