Recent advances in chemical protein synthesis: method developments and biological applications

Steroidal saponins are a group of glycosides widely distributed among monocotyledonous families. They exert a wide spectrum of biological effects including cytotoxic and antitumor properties which are the most studied. This review is an update of our previous paper—Saponins as cytotoxic agents (Podolak et al. in Phytochem Rev 9:425–474, 2010) and covers studies that were since published (2010–2018). In this paper we refer to steroidal saponins presenting results of cytotoxicity studies, mechanisms of action and structure–activity relationships.

/pdf/saponins-as-cytotoxic-agents-an-update-2010-2018-part-i-3vse5gcjj3.pdf

Saponins as cytotoxic agents: an update (2010-2018). Part I-steroidal saponins

Background Breast cancer remains a great threat to females worldwide. As a recently defined programmed cell death pathway that associates with immune activation, RIP1/RIP3/MLKL necroptosis signaling has been implicated in a variety of diseases. The present study aimed to investigate the role of RIP1/RIP3/MLKL signaling in breast cancer cell proliferation and metastasis in vivo and in vitro. Methods Western blot and quantitative real-time PCR were performed to evaluate the activation of necroptosis signaling in clinical human breast cancer tissues. Correlation of necroptosis signaling markers with clinicopathological parameters was statistically assessed. Cell viability assay, colony formation assay, wound healing assay, and transwell migration and invasion assays were performed to investigate the effects of necroptosis inhibition on breast cancer cell proliferation and metastasis. Results Clinical breast cancer tissues showed significantly higher levels of tumor necrosis factor alpha (TNFα), RIP1, RIP3 and MLKL at both mRNA and protein levels as compared with their paired non-cancerous tissues. Phosphorylation of RIP3 and MLKL was also remarkably provoked. Statistics showed that both RIP1 and MLKL positively correlated with cancer parameters such as N-cadherin (p=0.002 for RIP1 and p=0.021 for MLKL) and Ki67 (p=0.031 for RIP1 and p=0.05 for MLKL). The MLKL expression level significantly correlated with tumor size (p=0.001) and the proliferation indicator Ki67 (p=0.018). In addition, pharmacological inhibition of the necroptosis signaling using necrostatin-1 promoted breast cancer cell proliferation and colony formation by approximately 50%. Blockade of necroptosis signaling also accelerated wound healing process and cell transmigration in breast cancer cells. Conclusion Our results suggested that pharmacological inhibition of necroptosis promoted breast cancer cell proliferation and metastasis. Modulation of tumor cell necroptosis might represent a novel strategy as to breast cancer treatment.

/pdf/pharmacological-inhibition-of-necroptosis-promotes-human-59es9w2orf.pdf

Pharmacological Inhibition of Necroptosis Promotes Human Breast Cancer Cell Proliferation and Metastasis.

Tsinling lenok trout (Brachymystax lenok tsinlingensis) is a typical cold water fish. High temperature has been shown to damage the liver of fish. However, few studies have investigated the liver apoptosis induced by high temperature stress in fish from the perspective of gene expression and metabolic function. Therefore, we investigated the changes caused by high temperature stress (24 °C) on the liver tissue structure, antioxidant capacity, liver gene expression, and the metabolome of tsinling lenok trout. The transcriptomic results showed that genes associated with apoptosis, such as CASP8, CASP3, PERK, Bcl-6 and TRAIL, were upregulated under high temperature stress. Metabolomic analysis showed that the metabolic pathway of nucleotide synthesis was significantly downregulated, while that of oxygen radical synthesis was significantly upregulated. Integrated analysis showed that after high temperature stress, immune-related signaling pathways in trout were activated and their apoptosis level increased, which might be related to hepatopancreas injury. In addition, abnormalities in the tricarboxylic acid cycle and mitochondrial function were observed, suggesting that functional hypoxia caused by high temperature might be involved fish cell apoptosis. These results provide new insights into the process of cell apoptosis in fish under high temperature stress. 

FoxO signaling and mitochondria-related apoptosis pathways mediate tsinling lenok trout (Brachymystax lenok tsinlingensis) liver injury under high temperature stress.

Tannic acid repair of zearalenone-induced damage by regulating the death receptor and mitochondrial apoptosis signaling pathway in mice.

Polyphyllin has been reported to exhibit anticancer effects against various types of cancer via the proapoptotic signaling pathway. The aim of the present study was to investigate the role of the endoplasmic reticulum stress and death receptor signaling pathways in PPI-induced apoptosis of human hepatocellular carcinoma HepG2 cells. Analysis demonstrated that PPI could significantly inhibit the proliferation and induce apoptosis of HepG2 cells in a dose- and time-dependent manner. Investigation into the molecular mechanism of PPI indicated that PPI notably mediated ER stress activation via IRE-1 overexpression and activation of the caspase-12 to protect HepG2 cells against apoptosis. In addition, PPI markedly induced the expression of death receptors signaling pathways-associated factors, including tumor necrosis factor (TNF) receptor 1/TNF-α and FAS/FASL. Additionally, suppression of the death receptor signaling pathways with a caspase-8 inhibitor, Z-IETD-FMK, revealed an increase in the death rate and apoptotic rate of HepG2 cells. Collectively, the findings of the present study suggested that the ER stress and death receptor signaling pathways were associated with PPI-induced HepG2 cell apoptosis; however, endoplasmic reticulum stress may serve a protective role in this process. The combination of PPI and Z-IETD-FMK may activate necroptosis, which enhances apoptosis. Therefore, the results of the present study may improve understanding regarding the roles of signaling pathways in PPI regulated apoptosis and contribute to the development of novel therapies for the treatment of HCC.

/pdf/role-of-the-death-receptor-and-endoplasmic-reticulum-stress-1w6y5m8vj2.pdf

Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells.

The VQ motif-containing proteins play a vital role in various processes such as growth, resistance to biotic and abiotic stresses and development. However, there is currently no report on the VQ genes in sugarcane (Saccharum spp.). Herein, 78 VQ genes in Saccharum spontaneum were identified and classified into nine subgroups (I-IX) by comparative genomic analyses. Each subgroup had a similar structural and conservative motif. These VQ genes expanded mainly through whole-genome segmental duplication. The cis-regulatory elements (CREs) of the VQ genes were widely involved in stress responses, phytohormone responses and physiological regulation. The RNA-seq data showed that SsVQ gene expression patterns in 10 different samples, including different developmental stages, revealed distinct temporal and spatial patterns. A total of 23 SsVQ genes were expressed in all tissues, whereas 13 SsVQ genes were not expressed in any tissues. Sequence Read Archive (SRA) data showed that the majority of SsVQs responded to cold and drought stress. In addition, quantitative real-time PCR analysis showed that the SsVQs were variously expressed under salicylic acid (SA), jasmonic acid (JA), abscisic acid (ABA) and cold treatment. This study conducted a full-scale analysis of the VQ gene family in sugarcane, which could be beneficial for the functional characterization of sugarcane VQ genes and provide candidate genes for molecular resistance breeding in cultivated sugarcane in the future.

https://www.mdpi.com/1422-0067/23/11/6334/pdf?version=1654590854

A Comprehensive Identification and Expression Analysis of VQ Motif-Containing Proteins in Sugarcane (Saccharum spontaneum L.) under Phytohormone Treatment and Cold Stress

Bcl10 phosphorylation-dependent droplet-like condensation positively regulates DNA virus-induced innate immune signaling

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Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells.

A Comprehensive Identification and Expression Analysis of VQ Motif-Containing Proteins in Sugarcane (Saccharum spontaneum L.) under Phytohormone Treatment and Cold Stress

Bcl10 phosphorylation-dependent droplet-like condensation positively regulates DNA virus-induced innate immune signaling