Enriched oxygen improves age-related cognitive impairment through enhancing autophagy

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Feb. 14, 2024

Age-related cognitive impairment represents a significant health concern, with the understanding of its underlying mechanisms and potential interventions being paramount importance. This study aimed to investigate effects hyperbaric oxygen therapy (HBOT) on function neuronal integrity in aged (22-month-old) C57BL/6 mice. Male mice were exposed HBOT for 2 weeks, spatial learning memory abilities assessed using Morris water maze. We employed transcriptome sequencing Gene Ontology (GO) term enrichment analysis examine gene expression profiles, particular attention given synapse-related genes. Our data indicated upregulation postsynapse organization, synapse axonogenesis GO terms, likely contributing improved performance. Moreover, hyperphosphorylation tau, hallmark many neurodegenerative diseases, was significantly reduced HBO-treated group, both vivo vitro . Transmission electron microscopy revealed ultrastructural alterations hippocampus including an increase number synapses size active zone, reduction demyelinated lesions, decreased “PANTHOS.” Furthermore, Western blot analyses confirmed PSD95, BDNF, Syn proteins, suggesting enhanced synaptic plasticity neurotrophic support. increased autophagy, as evidenced by elevated levels Beclin-1 LC3 proteins level p62 protein. Finally, we demonstrated that activated AMPK-mTOR signaling pathway, critical regulator autophagy. Notably, our findings provide novel insights into which ameliorates age-related impairment, therapeutic value this approach.

Language: Английский

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COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway.

PubMed, Journal Year: 2025, Volume and Issue: 28(3), P. 240 - 246

Published: Jan. 1, 2025

COTI-2, an innovative oral homocysteine, has shown promising antitumor results on multiple types of cancer. However, its effects in treating bladder cancer (BCa) and the underlying molecular mechanisms have not been elucidated. The present study aimed to explore COTI-2 BCa potential mechanisms. cell lines, including 5637 T24 were treated with at concentrations 0.5 1 μM, respectively. Cell Counting Kit (CCK)-8 assay, colony formation apoptosis transwell migration invasion assay conducted evaluate cells. Western blotting, H&E, immunohistochemical staining, immunofluorescence analysis performed investigate Moreover, a xenograft model nude mice using cells was generated determine activities vivo. highly inhibited proliferation cells, induced their apoptosis. it efficiently suppressed Additionally, subcutaneous showed that treatment tumor growth by inducing We also found promoted presumably through activating AMPK/mTOR pathway. Our data suggest effectively reduces malignancy BCa, probably via signaling These highlight as therapeutic agent for BCa.

Language: Английский

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Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 372 - 372

Published: March 5, 2025

Translation regulation is essential to the survival of hosts. Most translation initiation falls under control mTOR pathway, which regulates protein production from mono-methyl-guanosine (m7G) cap mRNAs. However, does not regulate all translation; hosts and viruses alike employ alternative pathways, factors, internal ribosome entry sites bypass mTOR. Trimethylguanosine (TMG)-caps arise hypermethylation pre-existing m7G-caps by enzyme TGS1 are modifications known for snoRNA, snRNA, telomerase RNA. New findings originating HIV-1 research reveal that TMG-caps present on mRNA license via an mTOR-independent pathway. Research has identified TMG-capping selenoprotein mRNAs, junD, TGS1, DHX9, retroviral transcripts. TMG-mediated may be a missing piece understanding synthesis in cells with little activity, including HIV-infected resting T nonproliferating cancer cells. Viruses display nuanced interface have developed strategies take advantage delicate interplay between these pathways. This review covers current knowledge TMG-translation We discuss intimate relationship metabolism explore how this exploited context CD4+ postulate co-opting both pathways provides winning strategy dictate sequential its proteins balance viral host cell survival.

Language: Английский

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Heat Stress in Growing–Finishing Pigs: Effects of Low Protein with Increased Crystalline Amino Acids on Growth, Gut Health, Antioxidant Status and Microbiome

Animals, Journal Year: 2025, Volume and Issue: 15(6), P. 848 - 848

Published: March 15, 2025

A total of sixty crossbred ([Landrace × Yorkshire] Duroc) pigs with an initial body weight 46.34 ± 0.13 kg were randomly assigned to four treatments under thermoneutral (TN, 22 °C) or heat-stress (HS, 31 conditions for 54 d trial (Phase 1: 0–26 d; Phase 2: 27–54 d): a control diet (16% CP in phase 1, 14% 2) TN (PC), HS (NC), low crude protein (LCP) (14% 12% and LCP increased crystalline AA (an increase 5% Lys, Met, Thr Trp based on calculated SID AA) (LCP5) HS. Experimental consisted five replicate pens, three per pen. The results showed that reduced (p < 0.05) growth performance nutrient digestibility compared TN. However, LCP5 improved other groups. Heat stress adversely affected intestinal morphology, gut integrity serum oxidative markers, but these effects alleviated by supplementation. Notably, the production butyric acids among short-chain fatty acid decreased proteobacteria Spirochaetota phylum feces. These findings highlight potential diets supplemented as effective nutritional strategy mitigate negative pigs, enhancing their performance, health overall welfare high-temperature environments.

Language: Английский

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DDR1 Targeting HOXA6 Facilitates Bladder Cancer Progression via Inhibiting Ferroptosis

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(6)

Published: March 1, 2025

ABSTRACT Ferroptosis is an important factor affecting the progression of bladder cancer (BC). Previous studies have confirmed that discoidin domain receptor 1 (DDR1) promotes BC progression. However, regulatory mechanisms ferroptosis are largely unknown. Therefore, this study aimed to investigate effects DDR1 on cell ferroptosis. Ferroptosis‐sensitive and ‐resistant cells were screened, reverse‐transcription quantitative PCR western blotting used determine expression in cells. In vitro vivo assays performed analyse The inducer erastin inhibited TCCSUP inhibitor ferrostatin‐1 death caused by knockdown. increased glutathione, glutathione peroxidase 4 solute carrier family 7 member 11 expression, while decreasing malondialdehyde Fe 2+ levels acyl‐CoA synthetase long‐chain inhibiting epithelial mesenchymal transition neurofibromin 2‐yes‐associated protein. These abrogated knockdown homeobox A6 (HOXA6). targeting HOXA6 facilitated growth vivo. HOXA6. Thus, may serve as a potential therapeutic target for BC.

Language: Английский

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Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 16, 2025

Radiodermatitis (RD) is the primary acute adverse effect experienced by patients receiving radiotherapy (RT) for head and neck cancer (HNC). This study aimed to investigate correlation between triglyceride (TG) levels severity of RD, as well underlying mechanisms involved. Data were collected from 248 with locally advanced HNC treated intensity-modulated radiation therapy (IMRT). Clinical characteristics blood profiles prior RT collected. After RT, RD was assessed. A binary logistic regression analysis used determine risk factors. Mouse models established administering radiating at a dose 9 Gy over two consecutive days. TG in mice cells quantified using an automatic biochemical analyzer assay kit, respectively. Cell viability detected Counting Kit-8 (CCK-8) assay, while apoptotic cell percentages measured via flow cytometry. Western blotting analyze protein interest. The level sole independent factor grade 3 or higher (grade 3+) RD. Radiation found increase content both mouse skin cells. Skin high contents presented more severe radiation-induced damage when administered administration 200 µmol/L palmitic acid (PA) 2 independently did not affect HaCaT proliferation apoptosis rates. Their combination shown induce injury. Mechanistically, autophagy excessively activated. Furthermore, concentrations phospho-PI3K, phospho-Akt, phospho-mTOR notably decreased. TGs are crucially involved development Increased after treatment suppress PI3K/Akt/mTOR pathway, autophagy, exacerbate

Language: Английский

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Bromodomain and extraterminal protein inhibitor JQ1 induces maturation arrest and disrupts the cytoplasmic organization in mouse oocytes under in vitro conditions

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 18, 2025

Abstract JQ1, a small cell-permeable molecule is known for its potent inhibitory action on bromodomain and extraterminal (BET) proteins. Although earlier studies have shown effect male gametogenesis, limited information available about influence oocyte development. Since BET genes are to exhibit regulatory functions development maturation, the present study aimed investigate of JQ1 developmental competence under in vitro conditions . Germinal vesicle (GV) stage oocytes were collected from adult Swiss albino mice subjected maturation (IVM) presence various concentrations (25, 50, 100 μM). The metaphase II (MII) assessed cytoplasmic organization functional at 24 h after IVM. A significant decrease nuclear (at 50 μM), symmetric cytokinesis, altered distribution mitochondria cortical granules, poorly organized actin meiotic spindle, misaligned chromosomes, elevated endoplasmic reticulum (ER) stress oxidative was observed JQ1-exposed oocytes. Presence N-acetyl cysteine (NAC), IVM medium resulted reduction JQ1-induced cytokinesis. Administration (50 mg/kg, intra peritoneal) primed with pregnant mare serum gonadotrophin (PMSG) human chorionic (hCG) did not affect ovulation. However, high degree degeneration, intracellular reactive oxygen species (ROS), GRP78 expression JQ1-administered mice. In conclusion, our reveals that inhibitor has detrimental effects function

Language: Английский

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Substituents introduction of methyl and methoxy functional groups on resveratrol stabilizes mTOR binding for autophagic cell death induction

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 26, 2025

Abstract The regulation of the mammalian target rapamycin (mTOR) protein by cancer cells can lead to uncontrol cell growth and therapy resistance. drug discovery anticancer agent 5-(3-hydroxy-4-methoxyphenethyl)-2-methoxy-3-methylphenol (SM-3), a derivative resveratrol substituting methyl group at hydroxy ring A adding methoxy para position B, shows promising potential for targeting autophagy induce death suppress stem (CSCs) through inhibition mTOR protein. In human lung cells, SM-3 showed greater efficacy, with lower IC 50 values 72.74 ± 0.13, 67.66 0.10, 43.24 0.11 µM in A549, H292, H460 respectively, compared parent compound, Resveratrol (Res). Moreover, selectivity index (SI) BEAS2B tumor treated were 10.99, 11.81, 18.49 lines, respectively. Therefore, treatment led reduced proliferation rates colony formation cells. our study, spheroids higher proportion dead those Res. Additionally, resulted decreased expression markers (CD133, CD44, ALDH1A1) transcription factors (OCT4, NANOG, SOX2) organoids from inhibiting mTOR/pAkt pathway. was also found autophagic death, as indicated Monodansylcadaverine staining, acidic vesicle formation, conversion LC3BI LC3BII. Using MM/GBSA calculations, exhibited stronger binding affinity (-25.09 kcal/mol) Res (-18.85 kcal/mol). displayed stability during entire simulation, maintaining RMSD 2–3 Å even after 80 ns. summary, introduction functional groups on create effectively suppressed upstream

Language: Английский

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Sinapic Acid Ameliorates Cadmium-Induced Hepatotoxicity: Modulation of Oxidative Stress, Inflammation, and Apoptosis

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1065 - 1065

Published: April 28, 2025

Background/Objectives: Cadmium (Cd) is a harmful metal commonly used in industry. Numerous clinical diseases, including osteomalacia, testicular damage, renal and hepatic failure, pulmonary edema, are associated with Cd exposure. The current study evaluated the protective effect of Sinapic acid (SA) against Cd-induced hepatotoxicity by investigating different mechanistic pathways interfering Cd-related liver injury. Methods: Forty rats were randomly assigned to four groups as follows; group 1 served negative control received saline, 2 saline for 14 days CdCl2 (3.5 mg/kg IP) single dose on day 14, 3 4 treated SA (20, 40 PO), respectively, injected 14. Serum was collected evaluate function. Liver samples histopathological examination assessment markers related oxidative stress, inflammation, apoptosis. Results: Acute administration elevated enzymes induced pathological changes specimens, concurrent release inflammatory reduced antioxidant capabilities. Pretreatment improved function activities enzymes. ameliorated evidenced decreased expression NF-κB, TNF-α, TLR-4, COX-2, iNOS, IL-1β levels along suppression mTOR, JNK, ERK, BAX, Bcl-2. Conclusions: present data suggest that represents promising agent injury attenuating

Language: Английский

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Spexin peptide ameliorates renal injury in diabetic nephropathy rat model via modulation of metabolic, oxidative, inflammatory, and apoptotic dysregulations

Journal of Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 24, 2025

Language: Английский

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