Analysis of endoplasmic reticulum stress-related gene signature for the prognosis and pattern in diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. This study aimed to determine the prognostic significance of endoplasmic reticulum (ER) stress-related genes in DLBCL. ER stress-related genes were obtained from the molecular signatures database. Gene expression data and clinical outcomes from the gene expression omnibus and TCGA datasets were collected, and differentially expressed genes (DEGs) were screened out. Gene ontology enrichment analysis, the kyoto encyclopaedia of genes and genomes pathway analysis, and geneset enrichment analysis were used to analyse the possible biological function of ER stress-related DEGs in DLBCL. Protein-protein interaction network construction using the STRING online and hub genes were identified by cytoHubba on Cytoscape software. The significant prognosis-related genes were screened, and the differential expression was validated. The immune microenvironment assessment of significant genes were evaluated. Next, the nomogram was built using univariate and multivariate Cox regression analysis. 26 ER stress-related DEGs were screened. Functional enrichment analysis showed them to be involved in the regulation of the endoplasmic reticulum mainly. NUPR1 and TRIB3 were identified as the most significant prognostic-related genes by comparison with the GSE10846, GSE11318, and TCGA datasets. NUPR1 was correlated with a good prognosis and immune infiltration in DLBCL; on the other hand, high expression of TRIB3 significantly correlated with a poor prognosis, which was an independent prognostic factor for DLBCL. In summary, we identified NUPR1 and TRIB3 as critical ER stress-related genes in DLBCL. NUPR1 might be involved in immune infiltration in DLBCL, and TRIB3 might serve as a potential therapeutic target and prognostic factor in DLBCL.

Doxorubicin nanomedicine based on ginsenoside Rg1 with alleviated cardiotoxicity and enhanced antitumor activity.

Aim: The authors aimed to develop Dox@Rg1 nanoparticles with decreased cardiotoxicity to expand their application in cancer. Materials & methods: Dox@Rg1 nanoparticles were developed by encapsulating doxorubicin (Dox) in a self-assembled Rg1. The antitumor effect of the nanoparticles was estimated using 4T1 tumor-bearing mice and the protective effect on the heart was investigated in vitro and in vivo. Results: Different from Dox, the Dox@Rg1 nanoparticles induced increased cytotoxicity to tumor cells, which was decreased in cardiomyocytes by the inhibition of apoptosis. The study in vivo revealed that the Dox@Rg1 nanoparticles presented a perfect tumor-targeting ability and improved antitumor effects. Conclusion: Dox@Rg1 nanoparticles could enhance the antitumor effects and decrease the cardiotoxicity of Dox.

Lay abstract Doxorubicin (Dox) is a drug used to treat cancer; however, it can be toxic to the heart. In this study, researchers made nanoparticles containing Dox and a component of ginseng, a root similar to ginger. They tested the nanoparticles in mice with tumors. The nanoparticles appeared to gather at the tumor site in greater amounts than free Dox. In healthy mice, the nanoparticles gathered less in the heart than free Dox. This means that putting Dox into nanoparticles such as these could improve their anticancer effect and decrease harm to the heart.

A dendritic polyamidoamine supramolecular system composed of pillar[5]arene and azobenzene for targeting drug-resistant colon cancer.

Fusobacterium nucleatum caused drug-resistant around tumor sites often leads to the failure of chemotherapy during colorectal cancer (CRC) treatment. Multifunctional cationic quaternary ammonium materials have been widely used as broad-spectrum antibacterial agents in antibacterial and anticancer fields. Herein, we design a smart supramolecular quaternary ammonium nanoparticle, namely quaternary ammonium PAMAM-AZO@CP[5]A (Q-P-A@CP[5]A), consisting of azobenzene (AZO)-conjugated dendritic cationic quaternary ammonium polyamidoamine (PAMAM) as the core and carboxylatopillar[5]arene (CP[5]A)-based switch, for antibacterial and anti-CRC therapies. The quaternary ammonium-PAMAM-AZO (Q-P-A) core endows the supramolecular system with enhanced antibacterial and anticancer properties. -N+CH3 groups on the surface of Q-P-A are accommodated in the CP[5]A cavity under normal conditions, which significantly improves the biocompatibility of Q-P-A@CP[5]A. Meanwhile, the CP[5]A host can be detached from -N+CH3 groups under pathological conditions, achieving efficient antibacterial and antitumor therapies. Furthermore, azoreductase in the tumor site can break the -NN- bonds of AZO in Q-P-A@CP[5]A, leading to the morphology recovery of supramolecular nanoparticles and CRC therapy through inducing cell membrane rupture. Both in vitro and in vivo experiments demonstrate that Q-P-A@CP[5]A possesses good biocompatibility, excellent antibacterial effect, and CRC treatment capability with negligible side effects. This supramolecular quaternary ammonium system provides an effective treatment method to overcome chemotherapy-resistant cancer caused by bacteria.

Specific protein kinase C isoform exerts chronic inhibition on the slowly activating delayed-rectifier potassium current by affecting channel trafficking.

The slowly activating delayed rectifier K+ current (IKs) plays a key role in the repolarization of ventricular action potential in the human heart and is formed by the pore-forming α-subunit encoded by KCNQ1 (Kv7.1) and ß-subunit encoded by KCNE1. Evidence suggested that IKs was regulated through protein kinase C (PKC) pathway, but the mechanism is controversial. This study was designed to identify the specific PKC isoform involved in the long-term regulation of IKs current. The IKs current was recorded using whole-cell patch-clamp technique in human embryonic kidney (HEK) 293B cell co-transfected with human KCNQ1/KCNE1 genes. The results revealed that both chronic activation of Ang II and PMA reduced the IKs current in a long-term regulation (about 24 hours). Further evidence showed that PKCε knockdown by siRNA antagonized the AngII-induced chronic inhibition on the IKs current, whereas knockdown of cPKC (PKCα and PKCß) attenuated the inhibition effect of PMA on the current. Moreover, the forward transport inhibition of the channel with brefeldin A alleviated the Ang II-induced chronic inhibition on IKs current, while the channel endocytosis inhibition with dynasore alleviated both Ang II and PMA-induced chronic inhibition on IKs current. The above results showed that PKCε activation promoted the channel endocytosis and inhibited the channel forward transport to the plasma membrane, while cPKC activation only promoted the channel endocytosis, which both down regulated the channel current.

One step assembly of ginsenoside Rb1-based nanovehicles with fast cellular transport in photothermal-chemical combined cancer therapy.

Nowadays, the research of photothermal-chemical co-therapy provides new ideas for the treatment of cancer. However, the harsh photothermal temperature hinders the clinical development of photothermal therapy. To ensure low-temperature photothermal-chemical combined therapy, a safe and feasible drug delivery system is highly desirable. Herein, through one step co-precipitation method, ginsenoside Rb1-based nanovehicles composed of the hydrophobic drug doxorubicin, the photochemical reagent Cypate and the heat shock protein inhibitor gambogic acid was prepared, resulting from the amphiphilicity and membrane permeability of Rb1. Encouragingly, this platform exhibited excellent biocompatibility and rapid cellular uptake, both of which led to significant and irreversible death of breast cancer cells under the trigger of short-term near-infrared light.