Molecular Biology Reports最新文献

Background: Exosomes derived from mesenchymal stem cells (MSCs) have been reported to improve the prognosis in septic mice. Additionally, we have confirmed that TGF-β1 plays a critical role in MSC-mediated protection against sepsis. In this study, we aimed to investigate whether exosomes derived from TGF-β1-overexpressing MSCs (TGF-β1-Exo) offer protective effects in sepsis.

Methods: MSCs were collected from mouse MSCs stably transfected with TGF-β1 using a lentiviral vector. Exosomes were isolated and purified from MSCs (Exo), GFP-MSCs (GFP-Exo), and TGF-β1-MSCs (TGF-β1-Exo). A sepsis model was induced in mice via cecal ligation and perforation (CLP). After 6 h, exosomes from different sources were intravenously administered into septic mice. Mice were euthanised 24 h later, and histopathological changes were assessed using hematoxylin and eosin (H&E) staining. Inflammatory cytokine levels were measured using ELISA and RT-PCR. Flow cytometry was employed to evaluate macrophage phenotypes in lung tissues and in vitro macrophages. Additionally, we co-cultured fluorescently labeled exosomes with macrophages in vitro.

Results: TGF-β1-Exo significantly ameliorated histopathological damage and improved survival rates in septic mice. ELISA and RT-PCR analyses revealed that several pro-inflammatory cytokines were notably suppressed in the TGF-β1-Exo group. Furthermore, TGF-β1-Exo promoted the polarization of M1 macrophages to M2 macrophages both in vivo. In vitro, TGF-β1-Exo were internalized by LPS-pretreated macrophages, promoting the shift from the M1 to M2 phenotype, reducing the expression of pro-inflammatory cytokines, and enhancing the production of anti-inflammatory factors.

Conclusions: Our findings suggest that TGF-β1-Exo exert therapeutic effects in septic mice by modulating macrophage polarization and inhibiting macrophage-mediated inflammation.

Background: Mitochondrial biogenesis is an adaptive reaction that restores metabolic equilibrium following mitochondrial malfunction. Lutein has been studied for its ability to inhibit hepatotoxicity caused by sodium fluoride (NaF) or irradiation by inducing mitochondrial biogenesis through AMPK-PGC1α signaling.

Methods and results: Animals were randomized to six groups: Group I (vehicle) received sunflower oil; group II (Lutein) received Lutein (40 mg/kg) for two weeks; group III (NaF) received sodium fluoride (48 mg/kg) for two weeks; group IV (NaF + Lutein) received NaF and 1 h later received Lutein; group V (IRR) was exposed to 7 Gy single dose of gamma rays, and group VI (IRR + Lutein) was provided Lutein for two weeks together with a single irradiation dose. Hepatotoxicity was reported following NaF or irradiation exposure, as increased serum ALT, AST, MDA, and 3-nitrotyrosine levels were detected, paired with decrease in albumin, total protein, GSH and Nrf2 expression. Both NaF and irradiation caused a decline in the mitochondrial biogenesis pathway PGC1α/TFAM, as well as a significant decrease in AMPK, ATP, complex I, and complex II levels as compared to control. In contrast, lutein improved the levels of these biomarkers, implying that it helped lessen hepatotoxicity caused by irradiation or NaF, by enhancing mitochondrial biogenesis and conserving energy metabolism.

Conclusion: The findings suggests that lutein plays a preventive role against NaF or gamma-radiation by activating AMPK-PGC1α mitochondrial biogenesis.

Background: Chemotherapy resistance, particularly resistance to oxaliplatin, remains a major clinical challenge in the treatment of colorectal cancer (CRC). Ferroptosis, a newly characterized form of regulated cell death, has emerged as a potential mechanism for overcoming chemotherapy resistance. The transcription factor FOSL1 has been implicated in CRC progression and chemoresistance; however, its role in ferroptosis is not well defined.

Methods: Gene and protein expression levels were assessed by quantitative real-time PCR (qRT-PCR) and western blotting, respectively. Malondialdehyde (MDA), glutathione (GSH), and intracellular iron levels were measured using ELISA. Lipid peroxidation was evaluated using the C11-BODIPY 581/591 probe. Cell viability and cell death were determined by the CCK-8 assay and Calcein-AM/propidium iodide (PI) double staining, respectively. The interaction between FOSL1 and the SRSF2 promoter was examined using dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays.

Results: FOSL1 was significantly overexpressed in CRC tissues and oxaliplatin-resistant CRC cells and was negatively correlated with the ferroptosis-related proteins GPX4, SLC7A11, and FTH1. Silencing of FOSL1 reduced oxaliplatin resistance in CRC cells by promoting ferroptosis. Mechanistically, FOSL1 transcriptionally activated SRSF2 expression. Overexpression of SRSF2 reversed the ferroptosis-promoting and oxaliplatin resistance-suppressing effects induced by FOSL1 knockdown.

Conclusion: FOSL1 promotes oxaliplatin resistance in CRC by suppressing ferroptosis through the upregulation of SRSF2. Targeting FOSL1 may represent a novel therapeutic strategy to overcome oxaliplatin resistance in colorectal cancer.

Background: Species of Trissolcus Ashmead (Hymenoptera: Scelionidae) are minute egg parasitoids of economic importance in biological control. Trissolcus elasmuchae (Watanabe) parasitizes several stink bugs, including Niphe elongata (Dallas) (Hemiptera: Pentatomidae), a serious pest in East Asia and the Oriental Region. Mitochondrial genomic data for Indian scelionids remain unavailable, limiting evolutionary and phylogenetic insights.

Methods and results: The complete mitochondrial genome of T. elasmuchae was sequenced and annotated. The circular genome is 16,290 bp long and contains 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and two putative control regions. It exhibits strong A + T bias (84.5%), with positive AT skew (+ 0.0470) and negative GC skew (- 0.2392). All PCGs use standard ATN start codons and predominantly terminate with TAA. Codon usage is biased toward Leu, Ile, Phe, and Met. Most tRNAs show typical cloverleaf structures except trnS1 and trnR. Five conserved ancestral gene blocks were identified. Platygastrinae retains more ancestral gene order features than Scelionidae, which shows derived rearrangements. The cox1 gene was most conserved, whereas nad6 was most variable. Selection analyses indicated strong purifying selection across 11 PCGs and positive selection on two. Phylogenetic analyses supported the monophyly of Telenominae and Platygastrinae and the paraphyly of Scelioninae.

Conclusions: The high A + T content, strong purifying selection on cox1, and conserved gene rearrangements, including ancestral gene blocks and hotspot regions, underscore key evolutionary patterns within Scelionidae. These findings advance our understanding of mitogenome evolution and functional genomics in Platygastroidea and provide a foundation for future phylogenomic and comparative studies.