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Insects · 2022 ·Vol. 13 ·期 12 ·1091 · IF 3.139

Subcellular-Level Mitochondrial Energy Metabolism Response in the Fat Body of the German Cockroach Fed Abamectin

Lin-Yu Yang,Xiao-Jie Yang,Zi-Shun Zhao,Qi-Lin Zhang

Simple SummaryTo date, it is rare to study the effects of environmental toxicants (e.g., abamectin, a widely used pesticide) on mitochondrial energy metabolism in vitro from a subcellular level in insects, especially from an omics perspective (e.g., metabolomics) due to insufficient samples of mitochondria. The fat body of the German cockroach (Blattella germanica) plays an important role for detoxification, with responses of critical subcellular components (e.g., mitochondria) to abamectin. WhenB. germanicawere fed abamectin, their in vitro mitochondrial morphology was affected, with changes in activity of key enzymes involved in energy metabolism. Furthermore, metabonomic analysis of in vitro mitochondria ofB. germanicauncovered a set of metabolites and their pathways related to mitochondrial energy metabolism in response to abamectin feeding/stress. These molecules and pathways were primarily involved in ATP production and energy consumption including oxidative phosphorylation, TCA cycle, and pentose phosphate pathway. The current work is a good example of investigations on subcellular toxicology from multiple perspectives (morphology, physiology, and metabolomics).AbstractMitochondria are the leading organelle for energy metabolism. The toxic effects of environmental toxicants on mitochondrial morphology, energy metabolism, and their determination of cell fate have already been broadly studied. However, minimal research exists on effects of environmental toxicants such as pesticides on mitochondrial energy metabolism at in vitro subcellular level, particularly from an omics perspectives (e.g., metabolomics). Here, German cockroach (Blattella germanica) was fed diets with (0.01 and 0.001 mg/mL) and without abamectin, and highly purified fat body mitochondria were isolated. Swelling measurement confirmed abnormal mitochondrial swelling caused by abamectin stress. The activity of two key mitochondrial energy metabolism-related enzymes, namely succinic dehydrogenase and isocitrate dehydrogenase, was significantly affected. The metabolomic responses of the isolated mitochondria to abamectin were analyzed via untargeted liquid chromatography/mass spectrometry metabolomics technology. Fifty-two differential metabolites (DMs) were identified in the mitochondria between the 0.001 mg/mL abamectin-fed and the control groups. Many of these DMs were significantly enriched in pathways involved in ATP production and energy consumption (e.g., oxidative phosphorylation, TCA cycle, and pentose phosphate pathway). Nineteen of the DMs were typically related to energy metabolism. This study is valuable for further understanding mitochondrial toxicology under environmental toxicants, particularly its subcellular level.Keywords:fat body mitochondria;Blattella germanica;abamectin feeding;energy metabolism;toxic response

CAS / MDL: 71751-41-2
研究领域: 毒理学 · 代谢组学 · 昆虫生理学
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RSC Advances · 2020 ·Vol. 10 ·期 25 ·14915-14927 · IF 3.119

Double-edged effects and mechanisms of Zn2+ microenvironments on osteogenic activity of BMSCs: osteogenic differentiation or apoptosis

Yiqiang Yu,Kai Liu,Zhuo Wen,Weicai Liu,Lei Zhang,Jiansheng Su

Zinc-incorporated biomaterials show promoting effects on osteogenesis; however, excessive zinc ions lead to cytotoxic reactions and also have other adverse effects. Therefore, the double-edged effects of Zn2+ microenvironments on osteogenesis may become critical issues for new material development. This study systematically investigated the bidirectional influences of diverse Zn2+ microenvironments on the cell adhesion, proliferation, osteogenic differentiation and apoptosis of rBMSCs. Furthermore, the mechanisms of zinc-induced osteogenic differentiation of rBMSCs and of cell apoptosis induced by high concentration of Zn2+ were both discussed in detail. The results indicated that the Zn2+ microenvironments of 2 μg mL−1 and 5 μg mL−1 effectively improved the initial adhesion and proliferation of rBMSCs, while that of 15 μg mL−1 had exactly the opposite effect. More importantly, the suitable Zn2+ microenvironments (2 μg mL−1 and 5 μg mL−1) moderately increased the intracellular Zn2+ concentration by regulating zinc transportation, and then activated the MAPK/ERK signaling pathway to induce the osteogenic differentiation of rBMSCs. In contrast, the high Zn2+ concentration (15 μg mL−1) not only inhibited the osteogenic differentiation of rBMSCs by damaging intracellular zinc homeostasis, but also induced rBMSC apoptosis by enhancing intracellular ROS generation. The current study clarified the double-edged effects of Zn2+ microenvironments on the osteogenic properties of rBMSCs and the related mechanisms, and may provide valuable guidance for optimizing the design of zinc-doped biomaterials and zinc-based alloys.

CAS / MDL: 7446-20-0
研究领域: 生物材料 · 细胞生物学 · 组织工程 · 生物医学工程
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Journal of Fungi · 2023 ·Vol. 9 ·期 1 ·94 · IF 4.7

The SUMOylation Pathway Components Are Required for Vegetative Growth, Asexual Development, Cytotoxic Responses, and Programmed Cell Death Events in Fusarium oxysporum f. sp. niveum

Azizullah,Muhammad Noman,Yizhou Gao,Hui Wang,Xiaohui Xiong,Jiajing Wang,Dayong Li,Fengming Song

SUMOylation is an essential protein modification process that regulates numerous crucial cellular and biochemical processes in phytopathogenic fungi, and thus plays important roles in multiple biological functions. The present study characterizes the SUMOylation pathway components, including SMT3 (SUMO), AOS1 (an E1 enzyme), UBC9 (an E2 enzyme), and MMS21 (an E3 ligase), inFusarium oxysporumf. sp.niveum(Fon), the causative agent of watermelon Fusarium wilt, in terms of the phylogenetic relationship, gene/protein structures, and basic biological functions. The SUMOylation components FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are predominantly located in the nucleus.FonSMT3,FonAOS1,FonUBC9, andFonMMS21are highly expressed in the germinating macroconidia, but their expression is downregulated gradually in infected watermelon roots with the disease progression. The disruption ofFonUBA2andFonSIZ1seems to be lethal inFon. The deletion mutant strains forFonSMT3,FonAOS1,FonUBC9, andFonMMS21are viable, but exhibit significant defects in vegetative growth, asexual reproduction, conidial morphology, spore germination, responses to metal ions and DNA-damaging agents, and apoptosis. The disruption ofFonSMT3,FonAOS1,FonUBC9, andFonMMS21enhances sensitivity to cell wall-perturbing agents, but confers tolerance to digestion by cell wall-degrading enzymes. Furthermore, the disruption ofFonSMT3,FonAOS1, andFonUBC9negatively regulates autophagy inFon. Overall, these results demonstrate that the SUMOylation pathway plays vital roles in regulating multiple basic biological processes inFon, and, thus, can serve as a potential target for developing a disease management approach to control Fusarium wilt in watermelon.Keywords:asexual reproduction;cell death;cell wall integrity;Fusarium oxysporumf. sp.niveum;mycelial growth;stress response;SUMOylation pathway;watermelon

CAS / MDL: 4602-84-0
研究领域: 植物病理学 · 分子生物学 · 真菌遗传学
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Applied Materials Today · 2024 · IF 7.2

An innovative approach to overcoming PD-1 resistance: Combined TIGIT blockade with nanophotothermal therapy

Xi Wang,Yu Wang,Qihang Zhao,Zhenchu Feng,Qingyi Liu,Gang Wang,Jiakui Zheng,Lin Tao,Jianguo Zhang,Xi Chen

Photothermal immunotherapy, especially combined with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1), marks a breakthrough in cancer treatment. However, therapy often triggers compensatory upregulation of other immune checkpoints. This study introduces an advanced strategy to enhance the efficacy of photothermal immunotherapy by utilizing a novel nanocarrier that targets both PD-1 and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) immune checkpoints. The dual blockade could counteract the compensatory upregulation of immune checkpoints triggered by PD-1 targeted therapies alone. The nanocarrier of this work is composed of a ZrB 2 photothermal core and a mesoporous silica layer, and finally coated with biocompatible polydopamine. This design could effectively deliver both TIGIT and PD-1 inhibitors directly to tumor sites, minimizing systemic side effects such as cytokine release syndrome. We demonstrate that this approach not only enhances cytotoxic responses of T and NK cells, but also promotes macrophage polarization towards a tumor-suppressing M1 phenotype dendritic cell maturation and immunogenic cell death. Our findings provide a promising avenue for cancer immunotherapy.

CAS / MDL: 57-09-0
研究领域: 癌症免疫治疗 · 纳米技术 · 免疫学 · 肿瘤学
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