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Trends in Plant Science Jun 2024Brassinosteroids (BRs) play a vital role in plant growth and stress response, operating through a well-defined signaling pathway. Yet, the export of BRs through plasma...
Brassinosteroids (BRs) play a vital role in plant growth and stress response, operating through a well-defined signaling pathway. Yet, the export of BRs through plasma membranes poses significant challenges. Ying et al. recently identified the essential role of the ATPase activity of ABCB19 (Arabidopsis thaliana ATP-binding cassette transporter) in BR transport.
PubMed: 38944596
DOI: 10.1016/j.tplants.2024.06.005 -
Cancer Genomics & Proteomics 2024Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor...
BACKGROUND/AIM
Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations.
MATERIALS AND METHODS
Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells.
RESULTS
JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay.
CONCLUSION
Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.
Topics: Humans; Female; Ovarian Neoplasms; Transcription Factors; DNA-Binding Proteins; Adenocarcinoma, Clear Cell; T-Lymphocytes, Cytotoxic; Cell Line, Tumor; Antigens, Neoplasm; HLA-A2 Antigen; Membrane Proteins
PubMed: 38944423
DOI: 10.21873/cgp.20460 -
Bioorganic & Medicinal Chemistry Letters Jun 2024Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the...
Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.
PubMed: 38944398
DOI: 10.1016/j.bmcl.2024.129862 -
Chemosphere Jun 2024Adding heavy metals such as copper and zinc to animal feeds is common practice to promote growth, but meanwhile has side consequence of enhancing spread of antibiotic...
Adding heavy metals such as copper and zinc to animal feeds is common practice to promote growth, but meanwhile has side consequence of enhancing spread of antibiotic resistance genes (ARGs) in soil. This presents a global challenge to food security and human health. We in this study investigated the transmission of typical ARGs, i. e. β-lactamase genes (β-RGs), in dairy farm environments where dietary Cu and Zn were present in a wide range of concentration. The β-RGs were demonstrated to be highly prevalent across environmental media, with a relative abundance of 94.55%, dominated by mechanisms of antibiotic deactivation (93.75%) and cellular protection (6.25%). More importantly, we first found the transmission of ARGs to be highly dependent on the overlooked volcanic effect, i. e. low-concentration Cu (12-22 mg/kg) and Zn (45-80 mg/kg) acted as micronutrients necessary for microbial growth but facilitated ARGs transfer, whereas higher-concentration Cu (22-39 mg/kg) and Zn (80-153 mg/kg) became toxic to microbial communities and gene expression patterns. Notably, the specific microbial phyla Proteobacteria (2.28-82.94%), Bacteroidetes (0.02-56.48%) and Actinobacteria (1.62-12.92%) exhibited resistance at low concentration of Cu and Zn, which enhanced the transmission of β-RGs. However, this process was inhibited at higher concentration due to inactivation of microbes by Cu and Zn. The increase in resistance was first observed in class Gammaproteobacteria (2.02-88.51%) and Alphaproteobacteria (0.68-10.1%) with increased Cu and Zn concentration. This resulted in heightened transfer of ARGs by tnpA-07 (80.35%) due to protection of thicker cell membrane by chelation with Cu and Zn. This study not only offers mechanistic insights into the volcanic effect of dietary metals on dissemination of ARGs, but also has important implications for safe management of agricultural settings.
PubMed: 38944351
DOI: 10.1016/j.chemosphere.2024.142713 -
Bioresource Technology Jun 2024Microalgae extracellular polymeric substances (EPS) are complex high-molecular-weight polymers and the physicochemical properties of EPS strongly affect the core... (Review)
Review
Microalgae extracellular polymeric substances (EPS) are complex high-molecular-weight polymers and the physicochemical properties of EPS strongly affect the core features of microalgae cultivation and resource utilization. Revealing the key roles of EPS in microalgae life-cycle processes in an interesting and novelty topic to achieve energy-efficient practical application of microalgae. This review found that EPS showed positive effect in non-gas uptake, extracellular electron transfer, toxicity resistance and heterotrophic symbiosis, but negative impact in gas transfer and light utilization during microalgae cultivation. For biomass harvesting, EPS favored biomass flocculation and large-size cell self-flocculation, but unfavored small size microalgae self-flocculation, membrane filtration, charge neutralization and biomass dewatering. During bioproducts extraction, EPS exhibited positive impact in extractant uptake, but the opposite effect in cellular membrane permeability and cell rupture. Future research on microalgal EPS were also identified, which offer suggestions for comprehensive understanding of microalgal EPS roles in various scenarios.
PubMed: 38944317
DOI: 10.1016/j.biortech.2024.131054 -
Cellular Signalling Jun 2024Promyelocytic leukemia protein (PML), a tumor suppressor protein, plays a key role in cell cycle regulation, apoptosis, senescence and cellular metabolism. Here, we...
Promyelocytic leukemia protein (PML), a tumor suppressor protein, plays a key role in cell cycle regulation, apoptosis, senescence and cellular metabolism. Here, we report that PML promotes apoptosis and ferroptosis. Our data showed that PML over-expression inhibited cell proliferation and migration. PML over-expression increased apoptotic cells, nuclear condensation and the loss of mitochondrial membrane potential, accompanied by regulation of Bcl-2 family proteins and reactive oxygen species (ROS) level, suggesting that PML enhanced apoptosis. Meanwhile, PML over-expression not only increased lipid ROS accumulation and Malondialdehyde (MDA) content but also downregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, indicating that PML enhanced ferroptosis. Additionally, knockdown of p53 attenuated the effect of PML on SLC7A11 and GPX4, and inhibited the increase of lipid ROS and ROS by PML over-expression. Moreover, translocation of PML from nucleus to cytoplasm not only promoted apoptosis and ferroptosis, but also inhibited cell proliferation. Taken together, PML promotes apoptosis and ferroptosis, in which the mediation of p53 and the nuclear export of PML play important roles.
PubMed: 38944257
DOI: 10.1016/j.cellsig.2024.111278 -
Free Radical Biology & Medicine Jun 2024Phenol red (PR) is a commonly used compound in culture media as a pH indicator. However, it is unknown whether this compound can interfere with the pharmacological...
Phenol red (PR) is a commonly used compound in culture media as a pH indicator. However, it is unknown whether this compound can interfere with the pharmacological induction of ferroptosis. Here, using high-content live-cell imaging death analysis, we determined that the presence of PR in the culture medium preconditioned normal and tumor cells to ferroptosis induced by system x inhibition mediated by imidazole ketone erastin (IKE) or GPX4 blockade in response to RSL-3, but had no significant effects against treatment with the endoperoxide FINO. Mechanistically, we revealed that PR decreases the levels of the antiferroptotic genes Slc7a11, Slc3a2, and Gpx4, while promoting the overexpression de Acls4, a key inducer of ferroptosis. Additionally, through superresolution analysis, we determined that the presence of PR mislocalizes the system x from the plasma membrane. Thus, our results show that the presence of PR in the culture medium can be a problematic artifact for the accurate interpretation of cell sensitivity to IKE or RSL-3-mediated ferroptosis induction.
PubMed: 38944214
DOI: 10.1016/j.freeradbiomed.2024.06.023 -
Environmental Pollution (Barking, Essex... Jun 2024Oxidative stress is a universal interpretation for the toxicity mechanism of nanoplastics to microalgae. However, there is a lack of deeper insight into the regulation...
Oxidative stress is a universal interpretation for the toxicity mechanism of nanoplastics to microalgae. However, there is a lack of deeper insight into the regulation mechanism in microalgae response to oxidative stress, thus affecting the prevention and control for nanoplastics hazard. The integrated analysis of transcriptomics and metabolomics was employed to investigate the mechanism for the oxidative stress response of Chlorella pyrenoidosa to nanoplastics and subsequently lock the according core pathways and driver genes induced. Results indicated that the linoleic acid metabolism, glycine (Gly)-serine (Ser)-threonine (Thr) metabolism, and arginine and proline metabolism pathways of C. pyrenoidosa were collectively involved in oxidative stress. The analysis of linoleic acid metabolism suggested that nanoplastics prompted algal cells to secrete more allelochemicals, thereby leading to destroy the immune system of cells. Gly-Ser-Thr metabolism and arginine and proline metabolism pathways were core pathways involved in algal regulation of cell membrane function and antioxidant system. Key genes, such as LOX2.3, SHM1, TRPA1, and proC1, are drivers of regulating the oxidative stress of algae cells. This investigation lays the foundation for future applications of gene editing technology to limit the hazards of nanoplastics on aquatic organism.
PubMed: 38944181
DOI: 10.1016/j.envpol.2024.124466 -
Food and Chemical Toxicology : An... Jun 2024Alicyclobacillus bacteria are important contaminants in the beverage industry because their spores remain in the product after usual pasteurization. At the same time,...
Alicyclobacillus bacteria are important contaminants in the beverage industry because their spores remain in the product after usual pasteurization. At the same time, their impact on human health has yet to be characterized, as it is generally assumed to be low or non-existent. However, these bacteria are causing quality concerns mainly due to odor and taste changes of the product. Since potential health effects are not precisely known, an experimental assessment was performed, including a biosafety assessment of six viable and non-viable vegetative and spore forms of Alicyclobacillus spp. strains using cell cultures and rodent study. The monolayer of Caco-2 (Cancer coli-2) cells was investigated for its adsorption effect on the epithelium of the small intestine of mice. Lactate dehydrogenase leakage (LDH) and transepithelial electrical resistance (TEER) tests were used to ensure the integrity of the cell membrane and tight junctions. The methylthiazole tetrazolium bromide (MTT) assay examined in vitro cytotoxicity in Caco-2 and HepG2 cell lines. The hemolysis of erythrocytes was spectrophotometrically measured. The results showed negligible cytotoxicity or non-toxic response in mice. In conclusion, Alicyclobacillus spp. exhibited biocompatibility with negligible cytotoxicity and minimal safety concerns.
PubMed: 38944144
DOI: 10.1016/j.fct.2024.114840 -
The Journal of Biological Chemistry Jun 2024Mitochondria are the nexus of cellular energy metabolism and major signaling hubs that integrate information from within and without the cell to implement cell function.... (Review)
Review
Mitochondria are the nexus of cellular energy metabolism and major signaling hubs that integrate information from within and without the cell to implement cell function. Mitochondria harbor a distinct polyploid genome, mitochondrial DNA (mtDNA), that encodes respiratory chain components required for energy production. MtDNA mutation and depletion have been linked to obesity and metabolic syndrome in humans. At the cellular and subcellular levels, mtDNA synthesis is coordinated by membrane contact sites implicated in lipid transfer from the endoplasmic reticulum, tying genome maintenance to lipid storage and homeostasis. Here, we examine the relationship between mtDNA and lipid trafficking, the influence of lipotoxicity on mtDNA integrity, and how lipid metabolism may be disrupted in primary mtDNA disease.
PubMed: 38944117
DOI: 10.1016/j.jbc.2024.107498