Zhou Chen’s research while affiliated with Lanzhou University and other places

Gastric cancer, a prevalent malignancy globally, is influenced by various factors. The imbalance in the gut microbiome and the existence of particular intratumoural microbiota could have a strong connection with the onset and progression of gastric cancer. High-throughput sequencing technology and bioinformatics analysis have revealed a close correlation between abnormal abundance of specific microbial communities and the risk of gastric cancer. These microbial communities contribute to gastric cancer progression through mechanisms including increasing cellular genomic damage, inhibiting DNA repair, activating abnormal signaling pathways, exacerbating tumor hypoxia, and shaping a tumor immune-suppressive microenvironment. This significantly impacts the efficacy of gastric cancer treatments, including chemotherapy and immunotherapy. Probiotic, prebiotic, antibiotic, carrier-based, dietary interventions, fecal microbiota transplantation, and traditional Chinese medicine show potential applications in gastric cancer treatment. However, the molecular mechanisms regarding dysbiosis of microbiota, including gut microbiota, and intra-tumoral microbiota during the progression of gastric cancer, as well as the therapeutic efficacy of microbiota-related applications, still require extensive exploration through experiments.

Natural killer (NK) cells are critical regulators of immune processes during early pregnancy, playing a key role in maintaining maternal‐foetal immune tolerance and supporting successful implantation. In particular, uterine NK cells, a specialised subset of NK cells, facilitate trophoblast invasion, spiral artery remodelling and placental establishment. Dysregulation of NK cell activity, however, has been implicated in pregnancy complications, notably recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF). Aberrant NK cell functions, such as heightened cytotoxicity or defective immune signalling, can disrupt the balance between immune tolerance and response, leading to impaired placental development, reduced trophoblast activity and compromised uteroplacental blood flow. This review examines the role of NK cells in early pregnancy, emphasising their contributions to immune modulation and placentation. It also investigates the mechanisms by which NK cell dysfunction contributes to RSA and RIF, and explores therapeutic strategies aimed at restoring NK cell balance to improve pregnancy outcomes. A deeper understanding of NK cell interactions during early pregnancy may provide critical insights into the pathogenesis of pregnancy failure and facilitate targeted immunotherapeutic approaches.

Background Through bibliometric analysis, this paper summarizes the growing literature and analyses the development trends and hot spots in the research field of the association between intravenous anesthesia and tumors. Methods A literature overview was conducted using relevant articles retrieved from the Web of Science Core Collection published between 1991 and 2024. Bibliometric websites and tools (VOSviewer, CiteSpace, and bibliometric R package) are used to analyze the co-occurrence of keywords and reference citations, detailing countries, institutions, authors, references, journals, and keywords. Results A total of 1198 relevant articles were included in the study. The USA, China, and Germany have the largest number of publications, with the USA and China having the most interagency cooperation and Germany relatively less cooperation. The institution that publishes the most articles is the University of National Defense Medical Center, and the journal that publishes the most articles is Anesthesiology. The five most productive authors are Li J., Liu J., Zhang B., Yu X.J., and Xu J. “Surgery”, “anaesthesia”, and “propofol” are the most common keywords. In recent years, research has focused mainly on intravenous anesthesia and tumor survival. Conclusion Both Western countries and China have made outstanding contributions to intravenous anesthesia and tumors. In recent years, the number of publications in China has steadily increased, and the quality and influence of these articles deserve recognition. Future research should focus on the key areas of intravenous anesthesia, tumor recurrence, and survival.

Background Crosstalk between pancreatic cancer cells and tumor-associated macrophages (TAMs) is a critical driver of malignant progression, and plays an important role in the low response rate to immunotherapy in patients with for pancreatic cancer. Although it is known that cancer cells induce TAM infiltration and M2 polarization, the underlying mechanisms remain elusive. Herein, we identified matrix metalloproteinase 28 (MMP28), a highly expressed protein, as a key regulator of this process. Methods Immunohistochemical staining and qRT-PCR were used to validate MMP28 as a potential marker for the prognosis of patients with pancreatic cancer. We evaluated the tumor-promoting effect of MMP28 in vitro with CCK-8, Transwell, and EdU assay and Western blotting and explored the potential mechanism of MMP28-induced M2 polarization of TAMs with a coculture system, immunofluorescence staining and flow cytometry. A subcutaneous graft tumor model was constructed to assess the tumor-promoting effect of MMP28 and its ability to induce M2 TAM infiltration. Results The relevant results of this study revealed a strong correlation between MMP28 expression and TAM infiltration, with a predominance of M2-polarized TAMs in pancreatic cancer tissues. Mechanistic investigations demonstrated that MMP28 promotes the secretion of multiple cytokines, including IL-8 and VEGFA through the activation of the MAPK/JNK signaling pathway. These cytokines act as potent chemoattractants and polarizing factors for TAMs. Additionally, we discovered an interaction between MMP28 and ANXA2, which contributes to the regulation of TAM recruitment and polarization. In vivo studies confirmed the critical role of MMP28 in tumor growth and TAM infiltration. Depletion of macrophages, inhibition of JNK, or neutralization of IL-8 and VEGFA significantly suppressed tumor progression. Transcriptomic analysis suggested that IL-8 and VEGFA induce M2 TAM polarization by modulating TAM amino acid metabolism. Conclusions Collectively, our findings elucidate a novel mechanism by which pancreatic cancer cells manipulate the tumor microenvironment through MMP28-dependent cytokine secretion, promoting TAM infiltration and M2 polarization. These results highlight MMP28 as a promising therapeutic target for pancreatic cancer. Graphical Abstract Schematic overview of the mechanisms by which MMP28 promotes the migration and polarization of TAMs. High levels of MMP28 promote the secretion of IL-8 and VEGFA by cancer cells by mediating the phosphorylation of the MAPK/JNK signalling pathway and then recruiting TAMs. IL-8 and VEGFA subsequently induce amino acid metabolism alterations in TAMs by binding to relevant receptors on TAMs, which ultimately promote the polarization of TAMs to the M2 phenotype. In addition, ANXA2 increases MMP28-mediated M2 TAM infiltration by interacting with MMP28.

Pancreatic cancer (PC) is one of the most lethal types of cancer, as current treatments are largely ineffective. Our research uncovers that PPP2R2B is overexpressed in a majority of PC cases, playing a significant role in the growth and spread of PC tumors. Further analysis showed that reducing PPP2R2B levels in PC inactivates the MAPK pathways—ERK, JNK, and p38—impacting epithelial-mesenchymal transition (EMT) and apoptosis processes, ultimately promoting PC growth. Our experiments in live subjects demonstrate that removing PPP2R2B inhibits tumor growth in PC mouse models and alters the levels of proteins involved in EMT and cell death. Thus, our work highlights the crucial role of PPP2R2B as a new factor that promotes cancer progression by influencing EMT and cell death through the MAPK pathway in pancreatic cancer.

Pancreatic cancer (PC) is one of the most lethal types of cancer, as current treatments are largely ineffective. Our research uncovers that PPP2R2B is overexpressed in a majority of PC cases, playing a significant role in the growth and spread of PC tumors. Knockdown of PPP2R2B inhibits PC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting cell apoptosis. Conversely, overexpression of PPP2R2B enhances these processes, leading to increased proliferation, migration, invasion, and EMT, and reduced apoptosis. Further analysis showed that reducing PPP2R2B levels in PC inactivates the MAPK pathways—ERK, JNK, and p38, ultimately promoting PC growth. The addition of an ERK inhibitor reverses the effects of PPP2R2B knockdown, restoring cell proliferation, migration, and invasion. Our experiments in live subjects demonstrate that removing PPP2R2B inhibits tumor growth in PC mouse models and alters the levels of proteins involved in EMT and cell death. These findings demonstrate that PPP2R2B contributes to PC progression by modulating EMT and apoptosis through the ERK/MAPK pathway. Targeting PPP2R2B or its downstream signaling pathways may offer a promising therapeutic strategy for pancreatic cancer.

Pancreatic cancer (PC) has a really poor prognosis, and we urgently need to delve deeper into its molecular mechanisms. In this study, we found that KRT19 expression was significantly increased in PC tissues and cell lines and it was linked to unfavorable outcomes for patients. Overexpression of KRT19 boosted the proliferation, migration, and invasion of PC cells. Additionally, miR-374b-5p targets KRT19, inhibiting the activation of the Wnt/β-catenin pathway (WBC), which in turn suppresses epithelial-to-mesenchymal transition (EMT) and the progression of PC. Further experiments showed that under hypoxic conditions, HIF1α was positively correlated with KRT19, promoting its expression. The loss of miR-642a-5p and the upregulation of KRT19 induced by hypoxia can significantly favor PC progression. Plus, the increased expression of KRT19 might act as a predictive marker and potential target for PC treatment.

Background The recently identified carcinogenic long non-coding RNA (lncRNA) MIR4435-2HG has been validated to contribute to the initiation and progression of several malignancies. Nonetheless, its specific mechanistic function in pancreatic cancer (PC) is yet to be determined. This study aims to investigate the expression and functional role of MIR4435-2HG in PC and to elucidate its potential mechanism. Methods This study employed The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx)-Pancreas datasets for the analysis of MIR4435-2HG expression in PC and normal pancreatic tissues and its relations with prognosis in PC. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was employed for analyzing MIR4435-2HG, miR-128-3p, and ABHD17C expressions within cells and tissues. Cell proliferation and apoptosis were detected in vitro through Cell Counting Kit 8 (CCK-8) assay and flow cytometry while utilizing transwell and wound healing assays to assess cell migration and invasion. Predicting miR-128-3p binding sites with MIR4435-2HG or ABHD17C was conducted via the online tool starBase and validated through a dual-luciferase reporter (DLR), RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Herein, we deployed Western blot to assess protein expression levels. The in vivo role of MIR4435-2HG was studied using tumor xenografts. Results MIR4435-2HG overexpression exhibited a correlation with poor prognosis in PC. Knocking down MIR4435-2HG significantly hindered the proliferative, invading, and migrating PC cell abilities, accompanied by apoptosis induction, counteracted via a miR-128-3p inhibitor. Moreover, MIR4435-2HG could directly bind to miR-128-3p. Additionally, miR-128-3p directly targeted ABHD17C. Furthermore, in vitro as well as in vivo experiment results elucidated that knocking down MIR4435-2HG hindered PC progression by suppressing ABHD17C expression via miR-128-3p upregulation. Conclusions MIR4435-2HG can serve as a dependable target for PC diagnosis and treatment by modulating the miR-128-3p/ABHD17C axis to promote its progression.