Genipin,an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature

Genipin is a protein cross-linking agent extracted from Gardenia (Gardenia jasminoides Ellis) fruits. This fruit has conventionally been used as a Chinese herbal medicine for the treatment of inflammation and jaundice and as an edible colorant in oriental countries. Uncoupling protein (UCP)-2 is a member of the family of uncoupling proteins, which are anion transporters positioned in the mitochondrial inner membrane. Genipin has been shown to have hepatoprotective activity, acting as an effective antioxidant and inhibitor of mitochondrial UCP2, and is also reported to exert significant anticancer effects. In this review, the author presents the latest progress of genipin as an anticancer agent and concisely describes its various mechanisms of action. In brief, genipin inhibits UCP2 to attenuate generation of reactive oxygen species (ROS), leading to ROS/c-Jun N-terminal kinase-dependent apoptosis of cancer cells. Genipin also increases the tissue inhibitors of matrix metalloproteases (MMP)-2, a kind of tumor promoter in a variety of cancers, as well as induces caspase-dependent apoptosis in in vitro and in vivo models. These findings suggest that genipin can serve as a promising novel antitumor agent that could be applicable for chemotherapy and/or chemoprevention for cancers.     

Comprehensive Analysis of Oligo/Polysialylglycoconjugates in Cancer Cell Lines

In cancer cells, cell-surface sialylation is altered, including a change in oligo/polysialic acid (oligo/polySia) structures. Since they are unique and rarely expressed in normal cells, oligo/polySia structures may serve as promising novel biomarkers and targets for therapies. For the diagnosis and treatment of the disease, a precise understanding of the oligo/polySia structures in cancer cells is necessary. In this study, flow cytometric analysis and gene expression datasets were obtained from sixteen different cancer cell lines. These datasets demonstrated the ability to predict glycan structures and their sialylation status. Our results also revealed that sialylation patterns are unique to each cancer cell line. Thus, we can suggest promising combinations of antibody and cancer cell for glycan prediction. However, the precise prediction of minor glycans need to be further explored.     

Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer

The extracellular heat shock protein 90α (eHSP90α) has been reported to promote cancer cell motility. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α, as well as its underlying mechanism for PC progression, were still unclear. Our study demonstrated that the amounts of secreted HSP90α proteins were discrepant in multiple PC cells. In addition, highly invasive Capan-2 cells have a higher level of secreted HSP90α compared with those of less invasive PL45 cells. The conditioned medium of Capan-2 cells or recombinant HSP90α treatment stimulated the migration and invasion of PC cells, which could be prevented with a neutralizing anti-HSP90α antibody. Furthermore, secreted HSP90α promoted elements of epithelial–mesenchymal transition in PL45 cells, including increases in vimentin and Snail expressions, decreases in E-cadherin expression, and changes in cell shape towards a mesenchymal phenotype, but these phenomena were reversed by the anti-HSP90α antibody in Capan-2 cells. In addition, high levels of low-density lipoprotein receptor-related protein 1 (LRP1) were associated with worsened patient survival in pancreatic adenocarcinoma. We demonstrated LRP1 as a receptor of eHSP90α for its stimulatory role in metastasis, by activating the AKT pathway. In addition, silencing LRP1 enhanced the chemosensitivity to gemcitabine and doxorubicin in Capan-2 cells. Therefore, our study indicated that blocking secreted HSP90α underlies an aspect of metastasis and chemoresistance in PC.     

Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients’ samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-β, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs’ roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.     

The Anticancer Activity Conferred by the Mud Crab Antimicrobial Peptide Scyreprocin through Apoptosis and Membrane Disruption

Scyreprocin is an antimicrobial peptide first identified in the mud crab Scylla paramamosain. Herein, we showed that its recombinant product (rScyreprocin) could significantly inhibit the growth of human lung cancer NCI-H460 cells (H460), but showed no cytotoxicity to human lung fibroblasts (HFL1). rScyreprocin was a membrane-active peptide that firstly induced the generation of reactive oxygen species (ROS) in H460, and led to endoplasmic reticulum stress and Ca²⁺ release, which resulted in mitochondrial dysfunction and subsequently activation of caspase-3 cascades, and ultimately led to apoptosis. The comprehensive results indicated that rScyreprocin exerted anticancer activity by disrupting cell membrane and inducing apoptosis. The in vivo efficacy test demonstrated that intratumoral injection of rScyreprocin significantly inhibited the growth of H460 xenografts, which was close to that of the cisplatin (inhibition rate: 69.94% vs. 80.76%). Therefore, rScyreprocin is expected to become a promising candidate for the treatment of lung cancer.     

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients

Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between DNA damage formation, antioxidant status, and DNA repair capacity is responsible for the accumulation of genetic mutations and genomic instability. The lesion-specific DNA glycosylases, e.g., hOGG1 and MUTYH, initiate the repair of oxidative DNA damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline mutations causing a loss-of-function in base excision repair glycosylases, serve as straight forward evidence on the role of oxidative DNA damage and its repair. Altered or inhibited function of above glycosylases result in an accumulation of oxidative DNA damage and contribute to the adenoma-adenocarcinoma transition. Oxidative DNA damage, unless repaired, often gives rise G:C > T:A mutations in tumor suppressor genes and proto-oncogenes with subsequent occurrence of chromosomal copy-neutral loss of heterozygosity. For instance, G>T transversions in position c.34 of a KRAS gene serves as a pre-screening tool for MUTYH-associated polyposis diagnosis. Since sporadic colorectal cancer represents more complex and heterogenous disease, the situation is more complicated. In the present study we focused on the roles of base excision repair glycosylases (hOGG1, MUTYH) in colorectal cancer patients by investigating tumor and adjacent mucosa tissues. Although we found downregulation of both glycosylases and significantly lower expression of hOGG1 in tumor tissues, accompanied with G>T mutations in KRAS gene, oxidative DNA damage and its repair cannot solely explain the onset of sporadic colorectal cancer. In this respect, other factors (especially microenvironment) per se or in combination with oxidative DNA damage warrant further attention. Base excision repair characteristics determined in colorectal cancer tissues and their association with disease prognosis have been discussed as well.     

T型发射区单晶硅太阳电池的输出特性研究

利用TCAD半导体器件仿真软件对具有T型发射区结构的单晶硅太阳电池进行了仿真研究。全面系统地分析了在不同衬底少子寿命情况下,不同T型发射区深度对太阳电池外量子效率、短路电流密度、开路电压、填充因子及转换效率的影响。仿真结果表明:采用T型发射区结构可在一定程度上提高常规均匀发射区太阳电池的电学性能;T型发射区结构对700~1200nm长波段入射光的外量子效率具有明显的改善作用;当衬底少子寿命一定时,太阳电池短路电流密度、填充因子均随T型发射区深度的增大而增大,而开路电压随T型发射区深度的增大而减小;当T型发射区深度大于80μm时,对于低衬底少子寿命的单晶硅太阳电池,T型发射区结构对其转换效率的改善效果最为显著。     

Self-Renewal and Cancers of the Gastric Epithelium: An Update and the Role of the Lectin TFF1 as an Antral Tumor Suppressor

In 2020, gastric cancer was the fourth leading cause of cancer deaths globally. About 90% of gastric cancers are sporadic and the vast majority are correlated with Helicobacter pylori infection; whereas familial clustering is observed in about 10% of cases. Gastric cancer is now considered to be a disease originating from dysregulated self-renewal of the gastric glands in the setting of an inflammatory environment. The human stomach contains two types of gastric units, which show bi-directional self-renewal from a complex variety of stem cells. This review focuses on recent progress concerning the characterization of the different stem cell populations and the mainly mesenchymal signals triggering their stepwise differentiation as well as the genesis of pre-cancerous lesions and carcinogenesis. Furthermore, a model is presented (Lectin-triggered Receptor Blocking Hypothesis) explaining the role of the lectin TFF1 as an antral tumor suppressor possibly regulating Lgr5⁺ antral stem cells in a paracrine or maybe autocrine fashion, with neighboring antral gland cells having a role as niche cells.