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Glioblastoma multiforme (GBM) is the most prevalent and lethal primary intracranial neoplasm in the adult population, with treatments of limited efficacy. Recently, bufotalin has been shown to have anti-cancer activity in a variety of cancers. This investigation aims to investigate the effect of bufotalin on GBM and elucidate its potential underlying mechanism. Our results show that bufotalin not only inhibits the proliferation and epithelial-mesenchymal transition (EMT) but also triggers apoptosis in GBM cells. The result of RNA-seq indicated that bufotalin could induce mitochondrial dysfunction. Moreover, our observations indicate that bufotalin induces an excessive accumulation of intracellular reactive oxygen species (ROS) in GBM cells, leading to mitochondrial dysfunction and the dephosphorylation of AKT. Moreover, bufotalin improved TMZ sensitivity of GBM cells in vitro and in vivo . In conclusion, bufotalin enhances apoptosis and TMZ chemosensitivity of glioblastoma cells by promoting mitochondrial dysfunction via AKT signaling pathway.

Background: The 4-hydroxysesamin (4-HS, a di-tetrahydrofuran lignin) is a modified sesamin that was prepared in the laboratory. This preclinical study was designed to preliminarily investigate the neuroprotective properties of 4-HS. Methods: In vitro, neuronal injury and inflammation were simulated by oxygen-glucose deprivation and lipopolysaccharide (LPS) exposure in mouse hippocampal neuronal HT22 cell line, and treated with 4-HS and/or metformin (MET, MAPK pathway activator for exploring mechanism). CCK-8, flow cytometry, and enzyme-linked immunosorbent assay were performed to evaluate cell viability, apoptosis, and inflammation. Apoptosis- and pathway-related proteins were detected by Western blotting. Middle cerebral artery occlusion (MCAO) was constructed as a stroke model and treated with 4-HS for in vivo confirmation. Histological staining was used for in vivo evaluation of 4-HS properties. Results: The 4-HS showed similar anti-inflammatory activity to sesamin but did not affect the cell viability of HT22 cells. In vitro, 4-HS improved the cell viability, ameliorated neuronal apoptosis, along with the reversion of apoptotic proteins (Bax, cleaved-caspase 3/9, Bcl-2) expression and inflammatory cytokines (IL-6, TNF-α, IL-10) in LPS-treated HT22 cells. The 4-HS suppressed the phosphorylation of ERK, JNK, and p38 but the addition of MET reversed 4-HS-induced changes of phenotype and protein expression in LPS-treated cells. In vivo, 4-HS showed apparent improvement in cerebral infarction, brain tissue morphology, neuronal architecture, apoptosis, and inflammation of MCAO mice, and also showed inhibiting effects on the phosphorylation of ERK, JNK, and p38, confirming in vivo results. Conclusion: In this first pre-clinical study on 4-HS, we preliminarily demonstrated the neuroprotective properties of 4-HS both in cell and animal models, and proposed that the underlying mechanism might be associated with the MAPK pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Protozoa that parasitize within host cells can avoid direct damage from the host immune system. In this review, we have revealed some key factors and signaling pathways that inhibit host cell apoptosis, regulate cell apoptosis signal transduction, and interfere with the molecular mechanisms of cell apoptosis. These findings provide important clues to further understand the infection mechanism and pathogenesis of Apicomplexan protozoa and a theoretical basis for the development of new therapeutic strategies and preventive measures. Apicomplexan protozoa, which are a group of specialized intracellular parasitic protozoa, infect humans and other animals and cause a variety of diseases. The lack of research on the interaction mechanism between Apicomplexan protozoa and their hosts is a key factor restricting the development of new drugs and vaccines. In the early stages of infection, cell apoptosis is inhibited by Apicomplexan protozoa through their interaction with the host cells; thereby, the survival and reproduction of Apicomplexan protozoa in host cells is promoted. In this review, the key virulence proteins and pathways are introduced regarding the inhibition of cell apoptosis by the interaction between the protozoa and their host during the early stage of Apicomplexan protozoa infection. It provides a theoretical basis for the development of drugs or vaccines for protozoal diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • GABA fails to induce significant colitis within colons of healthy mice. • GABA facilitates susceptibility to DSS-induced colitis and impairs the intestinal barrier. • GABA inhibits colonic epithelium proliferation and promotes its apoptosis. Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter. Recently, it is considered to be a bioactive molecule with various health benefits. Ulcerative colitis (UC) is a chronic inflammatory disorder. An intestinal barrier defect is considered as one of the key events in the pathogenesis of UC. However, the issue of whether GABA is involved with intestinal inflammation remains debatable. In the present study, we investigated the effects of GABA on intestinal barrier function in healthy mice and susceptibility to UC in a dextran sulphate sodium (DSS) mouse model. Our results indicate that GABA treatment fails to induce significant colitis in healthy mice, however, GABA treatment enhances susceptibility to DSS-induced colitis in mice. Further, our results revealed GABA induces an intestinal barrier defect by inhibiting colonic epithelium proliferation and promoting its apoptosis. Accordingly, use of GABA treatment as applied for human health requires careful consideration. [ABSTRACT FROM AUTHOR]

Aflatoxin B 1 (AFB 1), a mycotoxin contaminating food and feed, can trigger liver immune toxicity and threaten the poultry industry. Phillygenin (PHI) is a natural lignan derived primarily from Forsythia suspensa with hepatoprotective pharmacological and medicinal properties. This research aimed to investigate the preventive effects of PHI on the toxicity of AFB 1 in the liver of chickens. Chickens were administered with AFB 1 (2.8 mg/kg) and/or treated with PHI (24 mg/kg) for 33 days. The histopathological changes, serum biochemical indices, oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and Nrf2 signaling pathways were measured. Results revealed that dietary PHI ameliorated liver function indicators, reduced the malondialdehyde and inflammatory mediator production and the apoptotic cell number, and increased the antioxidant enzyme contents and Bcl-2 level. The quantitative realtime PCR and Western blot results revealed that PHI reduced p53, cytochrome c, Bax, caspase-9, and caspase-3 levels, normalized the NF-κB p65 phosphorylation, and upregulated the Nrf2 and its downstream genes expression in chicken liver. These results indicated that PHI has beneficial effects on AFB 1 -induced liver damage, oxidative damage, inflammatory response, apoptosis, and immunotoxicity by inhibiting NF-κB and activating the Nrf2 signaling pathway in chickens. This study provides new insight into the therapeutic uses of PHI. [Display omitted] • Phillygenin(PHI) ameliorates aflatoxin B 1 - induced liver damage in chicken. • PHI inhibits oxidative stress and inflammation in the AFB 1 -induced liver damage. • PHI reduces AFB 1 -induced hepatocytes apoptosis in the liver of chicken. • PHI alleviates AFB 1 toxicity by the NF-κB and Nrf2 signaling pathways. [ABSTRACT FROM AUTHOR]

Spermidine have been reported a role in antioxidative, antiaging, and antiinflammatory. Oxidative stress causes granulosa cell (GC) apoptosis, follicular atresia, and impairs poultry reproductive functions. Studies have found that autophagy is the protective mechanism against antioxidant stress and apoptosis in cells. However, the relationship between spermidine-induced autophagy, oxidative stress, and apoptosis in goose GCs remains unclear. In this study, we investigated the autophagy mechanism to mediate spermidine effects on the alleviation of oxidative stress and apoptosis in goose GCs. Follicular GCs were treated with spermidine combination with 3-Nitropropanoic acid (3-NPA), rapamycin (RAPA), and chloroquine (CQ) or with hydrogen peroxide, RAPA, and CQ. Spermidine upregulated the ratio of LC3-II/I, inhibited the accumulation of p62 protein, and induced autophagy. 3-NPA treatment significantly increased ROS production, MDA content, SOD activity, cleaved CASPASE-3 protein expression, and decreased BCL-2 protein expression in follicular GCs. Spermidine inhibited oxidative stress and apoptosis induced by 3-NPA. In addition, hydrogen peroxide-induced oxidative stress was inhibited by spermidine. However, the inhibitory effect of spermidine was eliminated under chloroquine. Our results demonstrated that spermidine relieved oxidative stress and apoptosis of GCs by inducing autophagy, indicating that spermidine has a great potential to maintain proteostasis and sustain granulosa cell viability in geese. [ABSTRACT FROM AUTHOR]

Oxidative stress is the major culprits responsible for ovarian dysfunction by damaging granulosa cells (GCs). Ferritin heavy chain (FHC) may participate in the regulation of ovarian function by mediating GCs apoptosis. However, the specific regulatory function of FHC in follicular GCs remains unclear. Here, 3-nitropropionic acid (3-NPA) was utilized to establish an oxidative stress model of follicular GCs of Sichuan white geese. To explore the regulatory effects of FHC on oxidative stress and apoptosis of primary GCs in geese by interfering or overexpressing FHC gene. After transfection of siRNA- FHC to GCs for 60 h, the expressions of FHC gene and protein decreased significantly (P < 0.05). After FHC overexpression for 72 h, the expressions of FHC mRNA and protein upregulated considerably (P < 0.05). The activity of GCs was impaired after interfering with FHC and 3-NPA coincubated (P < 0.05). When overexpression of FHC combined with 3-NPA treatment, the activity of GCs was remarkably enhanced (P < 0.05). After interference FHC and 3-NPA treatment, NF-κB and NRF2 gene expression decreased (P < 0.05), the intracellular reactive oxygen species (ROS) level increased greatly (P < 0.05), BCL-2 expression reduced, BAX/BCL-2 ratio intensified (P < 0.05), the mitochondrial membrane potential decreased notably (P < 0.05), and the apoptosis rate of GCs aggravated (P < 0.05). While overexpression of FHC combined with 3-NPA treatment could promote BCL-2 protein expression and reduce BAX/BCL-2 ratio, indicating that FHC regulated the mitochondrial membrane potential and apoptosis of GCs by mediating the expression of BCL-2. Taken together, our research manifested that FHC alleviated the inhibitory effect of 3-NPA on the activity of GCs. FHC knockdown could suppress the expression of NRF2 and NF-κB genes, reduce BCL-2 expression and augment BAX/BCL-2 ratio, contributing to the accumulation of ROS and jeopardizing mitochondrial membrane potential, as well as exacerbating GCs apoptosis. [ABSTRACT FROM AUTHOR]