Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Recent studies have shown that the formation of the primary cilium is associated with a specific cellular organelle known as the midbody remnant(MBR),which is a point-like organelle formed by shedding of the midbody at the end of mitosis.MBRs move along the cell surface close to the center body and regulate it to form primary cilia at the top of the centriole.Primary cilia can act as an organelle to inhibit tumorigenesis,and it is lost in a variety of tumors.Studies have shown that the accumulation of MBRs in tumor cells affects ciliogenesis;in addition,both MBRs and primary cilia are degraded in tumor cells through the autophagy pathway,and MBRs can also transfer tumor signaling pathway factors to primary cilia affecting tumorigenesis.In this article,the basic structure and the formation process of MBR and primary cilia are reviewed and the mechanism of MBRs regulating ciliogenesis is elaborated.The significance of MBR-mediated ciliogenesis in tumorigenesis and its potential as a target for cancer treatment are discussed.

Ubiquitination is an important post-translational modification of proteins,which plays an important regulatory role in pathological processes such as cancer and immune diseases.Ubiquitination and deubiquitination are not only involved in the process of activation,proliferation and differentiation of immune cells,but also can regulate immune checkpoints and change the response rate of tumor to immunotherapy.Based on this,targeting the process of ubiquitination and deubiquitination can improve the inhibitory tumor microenvironment,increase the activity and infiltration number of immune cells,and downregulate immune checkpoints,which can enhance the anti-tumor effect when further combined with immune checkpoint inhibitors and chemotherapy drugs.Therefore,this review focuses on the roles of ubiquitination and deubiquitination enzymes in tumor-infiltrating immune cells and immune check-points,and summarizes the latest discoveries and applications of their small molecule inhibitors in tumor therapy.It provides a new idea to target the immune microenvironment by ubiquitination and deubiquitination,and improve the responsiveness of tumors to immunotherapy.

The liver's remarkable regenerative capacity is crucial to restore its function, which can be compromised in cases of severe or chronic liver injury. Thus, the search of new methods to promote liver regeneration is of great clinical importance. In recent years, the gut microbiota is an emerging field of research that attracts the scientific community. The gut microbiota not only affects the integrity of digestive system but also exerts a significant impact on liver function via the so-called " gut-liver axis". Increasing evidence suggests that an imbalance in gut microbiota is associated with the development of various liver diseases, and modulation of gut microbiota might be a potential cure for liver diseases. Research into the role of gut microbiota in liver regeneration not only help us understand the pathogenesis of liver diseases but also facilitate the development of new therapeutic strategies.

The liver is a highly proliferative organ. As the liver injured, the hepatocytes can quickly enter the cell cycle to restore the volume and function of liver. Liver regeneration involves complex processes that depend on the interaction of many different cell types. As limited by the average cell change level in tissues, traditional sequencing methods can only acquire the average genetic information reflecting dominant cell subpopulations, but ignore the secondary cell subpopu-lations, which leads to the loss of cellular heterogeneity information. Single-cell sequencing tech-nology can analyze the biological behavior of single cell, which helps to better understand the distri-bution, interaction and cell heterogeneity of different cells during liver regeneration. The authors review the application of single cell sequencing technology in liver regeneration.

The uPA-uPAR system is highly expressed in various tumor tissues. This system can promote the degradation of extracellular matrix proteins, as well as combine with vitronectin and integrin to transmit intracellular signal transduction. Subsequently, it mediates the occurrence and development of tumors. In recent years, a series of therapeutic programs that target this system has achieved notable results in tumor treatment, and some of them have been under the clinical trial stage, thus providing new ideas for tumor targeted therapy. Therefore, this paper intends to provide a review of research progress on the gene therapy, drug therapy, and immunotherapy targeting uPA-uPAR system.

[Abstract] Objective: To investigate the expression of tight junction protein claudin-7 (CLDN-7) in pancreatic cancer and its correlation with the clinicopathological features and prognosis of pancreatic cancer patients. Methods: Oncomine, GEPIA and GEO databases were used to comprehensively analyze the mRNA expression level of CLDN-7 in pancreatic cancer, and Kaplan-Meier Plotter database was used to analyze the relationship between the expression of CLDN-7 and the survival prognosis of pancreatic cancer patients. Immunohistochemical staining was used to detect the protein level of CLDN-7 in 44 cases of pancreatic cancer tissues and 31 cases of para-cancerous tissues resected in the Department of General Surgery of the Second Hospital of Lanzhou University from 2015 to 2018, and the relationship between CLDN-7 expression and clinicopathological characteristics and prognosis of patients was also analyzed. GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis were conducted to analyze the possible signaling pathways that CLDN-7 may involve in and their main functions, which were further verified in TCGA and GEPIA databases. Results: Analysis of both the databases and the clinical samples showed that CLDN-7 was significantly over-expressed in pancreatic cancer tissues, and its high expression was correlated with clinical prognosis of pancreatic cancer patients; moreover, CLDN-7 expression was an independent factor affecting the overall survival time of pancreatic cancer patients (all P<0.05). GO analysis and KEGG pathway enrichment analysis confirmed that CLDN-7 was involved in DNA damage repair and glucose metabolism in pancreatic cancer patients. TCGA and GEPIA database validation showed that CLDN-7 expression in pancreatic cancer was significantly and positively correlated with the expression of DNA damage repair related genes (POLD4, SMUG1, NTHL1) and glucose metabolism related genes (ALDOA, TALDO1, PGLS) (all P<0.01). Conclusion: CLDN-7 is highly expressed in pancreatic cancer and indicates a worse clinical prognosis; moreover, CLDN-7 is associated with DNA damage repair and intratumoral glucose metabolism in pancreatic cancer.

With the deepening research of comprehensive treatment for gastric cancer, the FLOT regimen has begun to be used for the treatment of gastric cancer patients. FLOT neoadjuvant regimen can significantly improve the R 0 resection rate and prolong the overall survival time of locally advanced gastric cancer patients. FLOT regimen combined with immune-checkpoint inhibi-tors, targeted therapy and hyperthermic intraperitoneal chemotherapy have great potential in neo-adjuvant therapy for gastric cancer. The authors systematically analyse the development history and latest clinical research progress of FLOT neoadjuvant regimen for gastric cancer based on their clinical practice experience.

Theaflavins are a class of natural products extracted from black tea or green tea, with significant anti-tumor effects on gastric cancer, liver cancer, breast cancer and other tumors. Theaflavins were once considered as the new products for anticancer therapy. However, the anti-tumor mechanism of theaflavins involves a variety of biological processes, and the regulation is complex. Therefore, this article summarizes the role of theaflavins in promoting tumor cell apoptosis, inducing tumor cell mitotic arrest and regulating tumor immunity, and reviews the inhibition of tumorigenesis and growth through MAPK, PI3K/AKT, Hedgehog, NF-κB, JAK/STAT and Wnt/β-Catenin signal pathways, in order to provide new ideas for cancer treatment and anti-cancer drug development.

Changes in nuclear morphology are common in malignant tumors, but the underlying molecular mechanisms remain poorly understood. Lamins is involved in supporting nuclear structure, and the expression of Lamins is the molecular basis for nuclear morphological changes during tumor progression. In recent years, the research on the relationship between Lamins and malignant tumors has made great progress. Lamins is of great value in the diagnosis, treatment, and prognosis of various malignant tumors.
Cell Nucleus ; Humans ; Lamins/genetics* ; Neoplasms/genetics* ; Prognosis