Histone Lactylation-Driven GPD2 Mediates M2 Macrophage Polarization to Promote Malignant Transformation of Cervical Cancer Progression

DNA and Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Cervical cancer (CC) is the most common in women. This study aims to explore molecular mechanism of lactate secreted by CC cells modulating macrophage polarization via histone lactylation. Normal cervical epithelium (NCE), low-grade squamous intraepithelial lesion (LSIL), high-grade (HSIL), and cell carcinoma (CESC) were collected assess H3K18la level infiltration. Macrophages incubated with SiHa cell-derived conditioned medium detect M1 M2 markers. NCE, HSIL, CESC samples used for ChIP-seq H3K18la. Histone lactylation-dirven

Language: Английский

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The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway

Molecules, Journal Year: 2025, Volume and Issue: 30(1), P. 139 - 139

Published: Jan. 1, 2025

Melanoma is among the most abundant malignancies in US and worldwide. Ligstroside aglycone (LA) a rare extra-virgin olive oil-derived monophenolic secoiridoid with diverse bioactivities. LA dose–response screening at NCI 60 cancer cells panel identified high sensitivity of Malme-3M cell line, which harbors BRAF V600E mutation. Daily oral 10 mg/kg exhibited potent vivo antitumor effects against xenograft nude mouse model by targeting signaling pathway. A human Clariom S microarray analysis collected Malme- 3M tumors 571 dysregulated genes, downregulation pathways critical for melanoma growth survival. Western blot animal further validated mutated BRAF–MAPK axis, as well GPD1 ELOVL6 expression levels. histopathological tumor sections showed extensive focal necrosis treated mice. An immunofluorescence study notable reductions proliferation marker ki67 vasculogenesis CD31 tumors. These findings promote potential nutraceutical lead control mutant melanoma.

Language: Английский

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Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108398 - 108398

Published: March 1, 2025

Language: Английский

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Candidate Biomarkers Associated With Circulating Tumor Cell Status in Metastatic Colorectal Cancer

Journal of Clinical Laboratory Analysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ABSTRACT Background Colorectal cancer (CRC) ranks as the third most prevalent worldwide. Recent studies suggest promising potential of microRNAs (miRNA) in predicting status circulating tumor cells (CTC), and their combined analyses could pave way for significant advancements assessing risk metastatic cancer. Here, we investigate miRNA signatures associated with CTC CRC (mCRC). Methods The mCRC patients was assessed using AdnaTest ColonCancer technology, which detects an immunomagnetic approach characterizes them based on colon‐specific surface markers. profiles were analyzed Agilent microarray 8 CTC‐positive, CTC‐negative, eight healthy individuals. functional implications dysregulated miRNAs interactions target mRNAs, TFs, lncRNAs determined through a comprehensive silico analysis. Candidate that differentially expressed CTC‐positive CTC‐negative groups, have prior evidence role biology, validated qPCR. Results We identified two groups multiple candidate biomarkers suggested regulatory networks. Three (hsa‐miR‐199a‐5p, hsa‐miR‐326, hsa‐miR‐500b‐5p), downregulated group compared to group, confirmed by qPCR prioritized predictors mCRC. Conclusion Our findings biomarker candidates can be used predict individuals This might also provide new insights into translational medicine applications management miRNA‐based CRC‐associated detection.

Language: Английский

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S-Adenosylmethionine Deficit Disrupts Very Low-Density Lipoprotein Metabolism Promoting Liver Lipid Accumulation in Mice

Journal of Lipid Research, Journal Year: 2025, Volume and Issue: unknown, P. 100794 - 100794

Published: April 1, 2025

Hepatic deletion of methionine adenosyltransferase-1a (Mat1a) in mice reduces S-adenosylmethionine (SAMe), a key methyl donor essential for many biological processes, which promotes the development and progression metabolic dysfunction-associated steatotic liver disease (MASLD). Hyperglycemia reduced MAT1A expression, along with low SAMe levels, are common MASLD patients. This study explores how Mat1a-knockout (KO) hepatocytes respond to prolonged high glucose conditions, focusing on metabolism lipid accumulation. Hepatocytes from Mat1a-KO were incubated conditions overnight, allowing analysis intermediates gene expression related glycolysis, gluconeogenesis, glyceroneogenesis, phospholipid synthesis, very low-density lipoprotein (VLDL) secretion. deficiency led protein methyltransferase-1 activity, resulting increased glycolytic enzymes (glucokinase, phosphofructokinase, pyruvate kinase) decreased gluconeogenic (phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase). These alterations reduction dihydroxyacetone phosphate (DHAP), subsequently inhibited mammalian target rapamycine complex 1 (mTORC1) activity. inhibition resulted phosphatidylcholine synthesis via CDP-choline pathway impaired VLDL secretion, ultimately causing Thus, under depletes DHAP, inhibits mTORC1 buildup.

Language: Английский

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Citrate oscillations during cell cycle are a targetable vulnerability in cancer cells

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189313 - 189313

Published: April 1, 2025

Cell cycle progression is timely interconnected with oscillations in cellular metabolism. Here, we first describe how these metabolic allow cycling cells to meet the bioenergetic needs specifically for each phase of cell cycle. In parallel, highlight cytosolic level citrate dynamically regulated during different phases, being low G1 phase, increasing S peaking G2/M, and decreasing mitosis. Of note, cancer cells, a dysregulation such oscillation can support by promoting deregulated Warburg effect (aerobic glycolysis), activating oncogenic signaling pathways (such as PI3K/AKT), acetyl-CoA production via alternative routes, overconsumption acetate. Then, review administration sodium (at high doses) arrests G0/G1 or inhibits glycolysis PI3K/AKT, induces apoptosis, significantly reduces tumor growth various vivo models. Last, reason on possibility implement reinforce effectiveness inhibitors better cure cancer.

Language: Английский

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Metabolic profile and disordered glycerophospholipid metabolism in recurrent vulvovaginal candidiasis

Microbes and Infection, Journal Year: 2025, Volume and Issue: unknown, P. 105504 - 105504

Published: April 1, 2025

Language: Английский

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Niclosamide extends health span and reduces frailty by ameliorating mTORC1 hyperactivation in aging models

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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A Piezoelectric and Suture‐Free Cardiac Patch Assembled by all FDA‐approved Materials Achieves a Minimally Invasive Gene Therapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Balancing biosafety with multifunctionality remains a critical challenge in biopatch development, impeding clinical translation. This study introduces minimally invasive myocardial patch fabricated entirely from FDA‐approved components, integrating piezoelectric property and sustained release of miRNA agomir. Briefly, the small intestinal submucosa (SIS) serves as matrix for situ growth β‐cyclodextrin metal‐organic framework (β‐CD‐MOF). Cholesterol‐modified miR‐210 Agomir is efficiently loaded into cyclodextrin cavities through host‐guest interactions. Flexibility water‐triggered adhesion properties, bestowed by poly (sodium thioctate) (PST) coating on rim, allow dry SIS‐Patch to fold catheter‐deliverable tube implantation. In rat infarction models, Ago‐Patch achieved release, effectively downregulating target gene expression. Simultaneously, SIS converts mechanical energy vivo electrical pulses, activating related signaling pathway. Synergistic gene‐electrical therapy improved cardiac function, increasing ejection fraction 14.0% fractional shortening 10.4%, while attenuating left ventricular remodeling fibrosis. The Ago‐Patch's dual‐action mechanism offers safe, multifunctional solution repair.

Language: Английский

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Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment

Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

ABSTRACT Cancer is a complex and heterogeneous disease characterised by uncontrolled cell growth proliferation. One hallmark of cancer cells their ability to undergo metabolic reprogramming, which allows them sustain rapid survival. This reprogramming creates an immunosuppressive microenvironment that facilitates tumour progression evasion the immune system. In this article, we review mechanisms underlying in discuss how these alterations contribute establishment microenvironment. We also explore potential therapeutic strategies targeting vulnerabilities enhance immune‐mediated anti‐tumour responses. Trial Registration ClinicalTrials.gov identifier: NCT02044861, NCT03163667, NCT04265534, NCT02071927, NCT02903914, NCT03314935, NCT03361228, NCT03048500, NCT03311308, NCT03800602, NCT04414540, NCT02771626, NCT03994744, NCT03229278, NCT04899921

Language: Английский

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