scholarly journals Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun-zi Liu ◽  
Ming-yuan Xu ◽  
Xiao-yu Dai ◽  
Lang Yan ◽  
Lei Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Pyruvate Kinase ◽  
Egf Receptor ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Immune Cell Infiltration ◽  
Glycolytic Metabolism ◽  
Keratinocyte Proliferation ◽  
Rate Limiting

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Effects of ASCL1 expression on tumorigenesis and immune cell infiltration in a syngenic mouse model of lung adenocarcinoma

2019 ◽  
Author(s):  
Naoya Miyashita ◽  
Masafumi Horie ◽  
Yu Mikami ◽  
Hirokazu Urushiyama ◽  
Kensuke Fukuda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Opposite Roles of Tumor Cell Proliferation and Immune Cell Infiltration in Postoperative Liver Metastasis of PDAC

2021 ◽  
Vol 9 ◽  
Author(s):  
Guangfu Wang ◽  
Shangnan Dai ◽  
Hao Gao ◽  
Yong Gao ◽  
Lingdi Yin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
Cell Proliferation ◽  
T Cells ◽  
Liver Metastasis ◽  
Tumor Cell ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Tumor Cell Proliferation

BackgroundRecurrence of liver metastasis after pancreatectomy is often a predictor of poor prognosis. Comprehensive genomic analysis may contribute to a better understanding of the molecular mechanisms of postoperative liver metastasis and provide new therapeutic targets.MethodsA total of 67 patients from The Cancer Genome Atlas (TCGA) were included in this study. We analyzed differentially expressed genes (DEGs) by R package “DESeq2.” Weighted gene co-expression network analysis (WGCNA) was applied to investigate the key modules and hub genes. Immunohistochemistry was used to analyze tumor cell proliferation index and CD4+ T cells infiltration.ResultsFunctional analysis of DEGs between the liver metastatic and recurrence-free groups was mainly concentrated in the immune response. The liver metastasis group had lower immune and stroma scores and a higher TP53 mutation rate. WGCNA showed that the genes in key modules related to disease-free survival (DFS) and overall survival (OS) were mainly enriched in the cell proliferation process and tumor immune response. Immunohistochemical analysis showed that the pancreatic cancer cells of patients with early postoperative liver metastasis had higher proliferative activity, while the infiltration of CD4+ T cells in tumor specimens was less.ConclusionOur study suggested that increased immune cell infiltration (especially CD4+ T cells) and tumor cell proliferation may play an opposite role in liver metastasis recurrence after pancreatic cancer.

Construction of Hyaluronic Acid-CeO2 Conjugated Composite Nanoparticles and Their Activity Efficiency in Diabetic Retinopathy Alleviation

2021 ◽  
Vol 17 (11) ◽  
pp. 2219-2225
Author(s):  
Jingzhi Shao ◽  
Jingjing Wan ◽  
Fengyan Zhang ◽  
Lirong Zhang
Keyword(s):  
Diabetic Retinopathy ◽  
Hyaluronic Acid ◽  
Mouse Model ◽  
Clinical Efficacy ◽  
Structural Integrity ◽  
Foreign Body Reaction ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Retinal Structure

We developed an effective nanoparticle-biomaterial in alleviating diabetic retinopathy (DR), hyaluronic acid (HA)-CeO2, composed mainly of CeO2 and HA. To demonstrate its anti-DR capacity, retinal cells from a B6/J mouse model were used to compare the efficiency of PEI-CeO2 and HA-CeO2. We investigated the transport performance, histolysis, immune cell infiltration, angiogenesis, and hyperemia induced by the transport system. The structural integrity, microvascular apoptosis, and superoxide and peroxide concentrations in the retina were measured to evaluate the clinical efficacy of CeO2. The infiltration efficiency of HA-CeO2 was higher than that of PEI-CeO2. Lower levels of foreign body reaction were evident for HA-CeO2 with less histolysis, immune cell infiltration, angiogenesis, and hyperemia. The clinical efficacy of HA-CeO2 in terms of preservation of retinal structure and lowering of microvascular apoptosis and superoxide and peroxide concentrations was superior to those of PEI-CP. HA-CeO2 was shown to have significant antioxidation and anti-vascular injury capacity in a mouse model, and may be a potential compound nanodrug for DR treatment in the future.

scholarly journals Role of CXCL10 in the progression of in situ to invasive carcinoma of the breast

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Milim Kim ◽  
Hye Yeon Choi ◽  
Ji Won Woo ◽  
Yul Ri Chung ◽  
So Yeon Park
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Mrna Expression ◽  
Breast Cancer Cell ◽  
Invasive Carcinoma ◽  
Immune Cell ◽  
Immune Cell Infiltration ◽  
Carcinoma Of The Breast ◽  
Immune Profiling

AbstractTumor immune microenvironment plays a crucial role in tumor progression. We performed immune profiling to compare immune-related gene expression between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast using nCounter PanCancer immune Profiling Panel and found that CXCL10 was the most significant gene that had the highest difference in expression between them. Effect of CXCL10 on breast cancer cell proliferation and invasion was examined in vitro, and expression of CXCL10 and its relationship with immune cell infiltration was assessed in breast cancer samples. CXCL10 induced cell proliferation, migration and epithelial-mesenchymal transition in MCF-7 and MDA-MB-231 breast cancer cell lines. We confirmed that CXCL10 mRNA expression was significantly higher in invasive carcinoma than in DCIS, especially in hormone receptor (HR)-negative tumors using a validation set. CXCL10 mRNA expression showed a positive correlation with tumor infiltrating lymphocyte (TIL) density in both DCIS and invasive carcinoma; CXCL10-positive tumors generally showed higher infiltration of CD8+ and FOXP3+TILs as well as PD-L1+ immune cells compared to CXCL10-negative tumors, albeit with different patterns according to HR status. In conclusion, our study showed that CXCL10 promotes tumor cell proliferation, invasion, and immune cell infiltration, implying its contribution in the progression of DCIS to invasive carcinoma of the breast.

Hyperglycemia results in decreased immune cell infiltration and increased viral load in the lung in a mouse model of RSV infection

Cytokine ◽  
2021 ◽  
pp. 155539
Author(s):  
Farshad Khodakhah ◽  
Alireza Tahamtan ◽  
Mona Marzban ◽  
Azadeh Shadab ◽  
Masoumeh Tavakoli-Yaraki ◽  
...  
Keyword(s):  
Viral Load ◽  
Mouse Model ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Rsv Infection

scholarly journals miR-130-3p Promotes MTX-Induced Immune Killing of Hepatocellular Carcinoma Cells by Targeting EPHB4

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Liangtian Shao ◽  
Qing Ye ◽  
Moyang Jia
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Target Gene ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Block Type ◽  
Immunogenic Cell Death ◽  
Immune Cell Infiltration ◽  
Drug Induced ◽  
The Impact

The vast majority of primary hepatocellular cancer is hepatocellular carcinomas (HCCs). Currently, HCC is one of the more common cancers in humans, and it has a high mortality and disability rate. Mitoxantrone (MTX) is an antitumor drug that can block type II topoisomerase. It has been reported that immunogenic cell death evoked by MTX can induce the discharge of damage associated with molecular patterns (DAMPs) and subsequently influence immune cell infiltration in the tumor microenvironment. High mobilities aggregation box 1 (HMGB1) is the prototypical extracellular DAMP. Many cellular processes have been reported to involve EPHB4 receptor tyrosine kinases, but the relation of DAMP and EPHB4 is uncertain. In this research, we assessed the impact of miR-130-3p by Edu incorporation test on cell proliferation, and we have proven its impact on HCC cell migration through Transwell and wound healing tests. Flow cytometry was applied to study its influence on apoptosis. Luciferase report test was integrated in detecting the miR-130-3p target gene. The influence of miR-130-3p on the manifestation of classical DAMPs was studied, such as HMGB1, ATP, and Calreticulin. A coculture experiment was carried out to further confirm its effects on immune cell infiltration. The result displayed that miR-130-3p overexpression considerably facilitates apoptosis and suppresses the migration or proliferation of HCC cells. EPHB4 was confirmed as the target gene of miR-130-3p. Overexpression of this target gene promotes emission of Calreticulin, ATP, and HMGB1 and subsequently promotes DCs maturation and proliferation of CD4+ T cells. In summary, our results demonstrated that miR-130-3p inhibits HCC cell proliferation and migration by targeting EPHB4 and promotes drug-induced immunogenic cell death.

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