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• Necroptosis as a form of programmed necrotic cell death played a role in intervertebral disc degeneration(IVDD). • The core components of the necrosome are the RIPK1, RIPK3 and MLKL. • Necroptosis occurred in different types of cells in intervertebral disc. • Targeting necroptosis had potential therapeutic value for the treatment of in IVDD. Intervertebral disc degeneration (IVDD) is a complex pathological condition associated with the development of low back pain. Despite numerous studies, the specific molecular mechanisms underlying IVDD remain unclear. At the cellular level, IVDD involves a series of changes, including cell proliferation, cell death, and inflammation. Of these, cell death plays a critical role in the progression of the condition. In recent years, necroptosis has been identified as a new form of programmed cell death (PCD). Necroptosis can be activated by ligands of death receptors, which then interact with RIPK1, RIPK3 and MLKL and lead to necrosome formation.. According to various previous studies, the necroptosis related pathway is activated in IVDD, and plays a significant role in the pathogenesis of IVDD. Furthermore, necroptosis may serve as a target for the IVDD treatment. Recently, several studies have reported the role of necroptosis in IVDD, but few studies have summarized the association between IVDD and necroptosis. The review gives a brief summary of the research progress of necroptosis, and discusses strategies and mechanisms that target necroptosis in IVDD. Lastly, matters needing attention in the necroptosis targeted therapy of IVDD are put forward at last. To the best of our knowledge, the review paper is the first one that integrates current research about the impact of necroptosis on IVDD, and contributes to the future therapy of IVDD from new perspectives. [ABSTRACT FROM AUTHOR]

• Caspase-1-induced pyroptosis pathway of classical inflammatory vesicles. • Non-classical inflammatory vesicle scorch pathway. • Pyroptosis and digestive system malignancies. • Pyroptosis and non-small cell lung cancer. • The role and mechanism of cell scorching in antitumor therapy. Pyroptosis, also known as cellular inflammatory necrosis, is a programmed cell death mediated by the Gasdermin family of proteins. The mechanisms by which pyroptosis occurs are divided into the GSDMD-mediated Caspase-1 and Caspase-4/-5/-11-dependent classical inflammatory vesicle pathway and the GSDME-mediated Caspase-3 and granzyme-dependent non-classical inflammatory vesicle pathways, among others. Recent studies have shown that pyroptosis has both inhibitory and promotive effects on tumor development. Pyroptosis induction also plays a dual role in antitumor immunotherapy: on the one hand, it suppresses antitumor immunity by promoting the release of inflammatory factors, and on the other hand, it inhibits tumor cell proliferation by triggering antitumor inflammatory responses. In addition, cell scorching plays an essential role in chemotherapy. It has been found that natural drugs modulating the induction of cell scorch are necessary to treat tumors. Therefore, studying the specific mechanisms of cell pyroptosis in different tumors can provide more ideas for developing oncology drugs. In this paper, we review the molecular mechanisms of pyroptosis and the role of pyroptosis in tumor development and treatment to provide new targets for clinical tumor treatment, prognosis, and antitumor drug development. [ABSTRACT FROM AUTHOR]

α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating inflammatory reactions, as well as the cell viability. They are expressed in both the plasma membrane and mitochondria of eukaryotic cells. Previously we found that neuroinflammation resulted in the decrease of α7 nAChR density in the brain of mice and was accompanied by accumulation of amyloid-beta (Aβ) peptides and memory impairment. In the present paper, it is shown that inflammation induced by either regular bacterial lipopolysaccharide (LPS) injections or immunizations with α7 nAChR extracellular domain (1–208) affected also the brain cell mitochondria. Using various modifications of sandwich ELISA, we observed the decrease of α7 nAChRs and accumulation of Aβ(1–40) and Aβ(1–42) in mitochondria of immunized or LPS-treated mice compared to control ones. Mitochondria of treated mice responded with cytochrome c release to lower Ca 2 + concentrations than mitochondria of control mice and were less sensitive to its attenuation with α7 nAChR agonist PNU282987. It is concluded that inflammation decreases α7 nAChR expression in both mitochondria and cell plasma membrane and makes mitochondria more susceptible to apoptosis induction. [ABSTRACT FROM AUTHOR]

Abstract: Oridonin is a natural compound purified from Rabdosia rubescens that has remarkable anti-inflammatory and antitumor activities. Although oridonin has been used in traditional Chinese medicine for many years to treat inflammatory diseases, the underlying mechanisms of these activities are not well understood. In this paper, we explored whether oridonin could be used in transplantation and the mechanisms of its immunosuppression. Oridonin efficacy in transplantation is manifested by prolonged graft survival and decreased graft infiltration. Oridonin induces T cell apoptosis in a concentration- and time-dependent manner. In vivo, oridonin depleted large numbers of T cells from the spleen and peripheral blood. Decreased T cell numbers resulted from apoptosis, which was accompanied by increased phagocyte numbers in the periphery. Reduction in the number of thymocytes was observed in mice treated for 8days, and CD4+CD8+ cells were more sensitive to apoptosis induced by oridonin. Additionally, successive treatment with oridonin for 16days resulted in a considerable reduction in the total number of spleen cells and spleen volume. Thus, T cell depletion may play an essential role in prolonged graft survival and immunosuppression induced by oridonin. [Copyright &y& Elsevier]

• Circ-UQCRC2 directly targeted miR-326. • Circ-UQCRC2 regulated PDCD4 expression through miR-326. • Circ-UQCRC2 regulated LPS-induced cell injury by the miR-326/PDCD4/NF-κB pathway. Circular RNAs (circRNAs) have been shown as important modulators in the pathogenesis of pediatric pneumonia. In this paper, we focused on the molecular basis of circRNA ubiquinol-cytochrome c reductase core protein 2 (circ-UQCRC2, circ_0038467) in lipopolysaccharide (LPS)-induced cell injury. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to gauge the levels of circ-UQCRC2, microRNA (miR)-326 and programmed cell death 4 (PDCD4) mRNA. PDCD4 protein expression and the activation of the NF-κB signaling pathway were evaluated by western blot. Ribonuclease R (RNase R) assay was performed to assess the stability of circ-UQCRC2. Cell viability and apoptosis were detected by the Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 were measured by the enzyme-linked immunosorbent assay (ELISA). Targeted relationship between miR-326 and circ-UQCRC2 or PDCD4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data showed the up-regulation of circ-UQCRC2 level in pneumonia serum and LPS-treated MRC-5 cells. The silencing of circ-UQCRC2 attenuated LPS-induced MRC-5 cell injury. Mechanistically, circ-UQCRC2 directly targeted miR-326, and circ-UQCRC2 regulated PDCD4 expression through miR-326. MiR-326 was a downstream effector of circ-UQCRC2 function, and PDCD4 was a functional target of miR-326 in regulating LPS-induced MRC-5 cell injury. Additionally, circ-UQCRC2 knockdown inactivated the NF-κB signaling pathway by regulating the miR-326/PDCD4 axis. Our findings demonstrated a novel regulatory network, the miR-326/PDCD4/NF-κB pathway, for the function of circ-UQCRC2 in LPS-induced cell injury in MRC-5 cells. [ABSTRACT FROM AUTHOR]

Abstract: Contamination of water with arsenic is a problem affecting several regions of the world. Peripheral blood mononuclear cells (PBMC) from chronically exposed individuals show a lower replicating activity than non-exposed individuals when stimulated with phytohemagglutinin (PHA). We have previously reported that PBMC from healthy donors treated in vitro with 1 μM sodium arsenite (NaAsO2) and stimulated with PHA showed a reduction in proliferation by a delay in cell cycle entry and a decrease in the rounds of cell division. In this paper we tested the effect of 1–5 μM NaAsO2 on the proliferation, viability, blast transformation, expression of the CD4 and CD8 molecules, and during the activation and proliferation of both CD4+ and CD8+ T lymphocytes. We found a reduction in cell proliferation and an increase in non-dividing cells with higher concentrations of NaAsO2 (2–5 μM) when proliferation was studied by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution. The use of 7-aminoactinomycin D (7-AAD) in CFSE-labeled cells allowed us to detect an increase in percentage of non-dividing cells, and an increase in apoptotic/dead cells mainly in non-proliferating cells. Analysis of the expression of CD4 and CD8 molecules on these cells showed that concentrations ≥2 μM NaAsO2 reduced the expression of the CD8 molecule and induced apoptosis/death in CD4+ cells. Analysis of blast transformation by flow cytometry showed an accumulation of CD8+ resting cells in the presence of NaAsO2. Analysis of CD25 and CD69 expression in kinetics experiments in both subtypes showed a delay in the expression of CD25 and a delay in the downregulation of the CD69 molecule, in both CD4+ and CD8+ cells. However, in the case of CD8+ cells, we detected an accumulation of a CD25−CD69− population in the presence of increasing concentrations of NaAsO2. Altogether, our results show that NaAsO2 alters the expression kinetics of the early activation molecules CD25 and CD69 similarly in both subtypes. In addition, activated and non-activated CD4+ cells die by apoptotic mechanisms and although a percentage of CD8+ cells also die by apoptosis, a subpopulation of these cells is unable to activate and thus accumulates as resting cells. [Copyright &y& Elsevier]

Dehydroepiandrosterone (DHEA), the most plentiful steroid hormone, has been convincingly known to have many biological effects and diverse influence in various types of cells, tissues and organs. The effects of DHEA on the humoral and cellular immune response are widely tested, but it is unclear whether DHEA itself serves as an activator of immune function and the literature pertaining to the in vitro effects of DHEA remains contested. In the present paper, the effects of DHEA on the thymocytes in vitro were studied. The results showed that DHEA could enhance the expression of Fas and Fas-L and induce thymocyte apoptosis. This suggests that dehydroepiandrosterone may induce the apoptosis of thymocyte through Fas/Fas-L pathway. [Copyright &y& Elsevier]