l-Glutamic Acid Alleviates Mastitis in Dairy Cows by Targeting the Sirt5/Nrf2/Prdx1 Signaling Axis and Mitochondrial Function

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Mastitis in dairy cows is an inflammatory disease that severely affects the health and lactation functions of cows. Mitochondrial damage closely related to response. How effectively alleviate mitochondrial key preventing treating mastitis In this study, we found elevated levels response accompanied by reduced expression Sirt5 (Sirtuin5) with compared healthy This suggests plays important role Subsequently, further analyzed mammary gland tissue from untargeted metabolomics (LC-MS/MS) screened for differential metabolite l-glutamic acid (l-Glu). To validate effect l-Glu on cows, conducted a study using MAC-T cells. The results showed was able ameliorate LPS-induced activating promoting fusion upregulation membrane potential (MMP) levels. contrast, unable protect function after knocking down Sirt5. Furthermore, upregulate nuclear factor E2-related (Nrf2) peroxiredoxin 1 (Prdx1) cells, promoted entry Nrf2 into nucleus, which reversed Next, explored whether alleviates through Nrf2/Prdx1 signaling axis inhibitor RA. use RA blocked protective function. conclusion, ameliorates targeting activate provides new target theoretical basis clinical control mastitis. could be added as dietary supplement diets maintain homeostasis, thereby protecting economic value

Language: Английский

---

Licoisoflavone a Inhibits Colorectal Cancer Cell Proliferation Through Targeting Cdk2-Cyclin E1 Axis-Mediated Cell Cycle Transition

Published: Jan. 1, 2025

Language: Английский

---

Licoisoflavone a Inhibits Colorectal Cancer Cell Proliferation Through Targeting Cdk2-Cyclin E1 Axis-Mediated Cell Cycle Transition

Published: Jan. 1, 2025

Language: Английский

---

PRDX1 knockdown promotes erastin-induced ferroptosis and impedes diffuse large B-cell lymphoma development by inhibiting the MAPK/ERK pathway

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 30, 2025

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and DLBCL cells are highly sensitive to ferroptosis. The purpose of this research was evaluate the role molecular mechanism peroxiredoxin 1 (PRDX1) on ferroptosis in DLBCL. expression PRDX1 tissues detected using bioinformatics analysis reverse transcription quantitative PCR. impacts cell proliferation, apoptosis, migration, invasion, were assessed through a series vitro experiments. A xenograft tumor model constructed verify roles vivo. Transcriptome sequencing conducted identify PRDX1-mediated signaling pathways. Anisomycin, agonist mitogen-activated protein kinase (MAPK), used explore modulation MAPK pathway. upregulated knockdown inhibited promoted suppressed growth. boosted erastin-induced by increasing levels iron MDA, while decreasing GSH. It also COX2 GPX4 SLC7A11 levels. reduced phosphorylation MEK ERK both under conditions with or without erastin induction. MAPK/ERK pathway anisomycin, significantly reversed inhibitory effects malignant behaviors promotion facilitates obstacles progression inhibiting pathway, offering potential treatment strategy for treatment.

Language: Английский

---

Diclofenac Enhances the Response of BRAF Inhibitor to Melanoma Through ROS/p38/p53 Signaling

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2025, Volume and Issue: 52(3)

Published: Jan. 9, 2025

ABSTRACT BRAF inhibitors (BRAFi) represent a cornerstone in melanoma therapy due to their high efficacy. However, the emergence of resistance causes significant challenge clinical utility. This study aims investigate potential diclofenac as sensitizer for BRAFi and elucidate its underlying mechanism. BRAFi‐acquired resistant cell lines SK‐MEL‐5R A375R were established treated with combination PLX4032. Cell viability was assessed using MTT assay, proliferation determined by crystal violet staining, apoptosis evaluated flow cytometry, intracellular ROS levels measured DCFH‐DA probe‐labeled cytometry. Mitochondrial membrane JC‐1 staining protein expression detected western blotting. Our results demonstrated that significantly augmented cytotoxicity PLX4032 enhanced ability induce cells. Diclofenac treatment led release reactive oxygen species (ROS), consequently reducing transmembrane potential, promoting mitochondrial apoptosis, activating downstream p38/p53 signaling pathway. Pretreatment N‐acetylcysteine reversed sensitizing effect on These findings suggested sensitized BRAFi‐resistant cells increasing might serve promising adjunct overcome treatment.

Language: Английский

---

Anti-Inflammatory and Anticancer Effects of Kaurenoic Acid in Overcoming Radioresistance in Breast Cancer Radiotherapy

Nutrients, Journal Year: 2024, Volume and Issue: 16(24), P. 4320 - 4320

Published: Dec. 14, 2024

Background/Objectives: Peroxisome proliferator–activated receptor γ (PPARγ) plays a key role in mediating anti-inflammatory and anticancer effects the tumor microenvironment. Kaurenoic acid (KA), diterpene compound isolated from Sphagneticola trilobata (L.) Pruski, has been demonstrated to exert anti-inflammatory, anticancer, antihuman immunodeficiency virus effects. Methods: In this study, we identified KA as novel activator of PPARγ with potent antitumor both vitro vivo. Given potential regulators overcoming radioresistance chemoresistance cancer therapies, hypothesized that may enhance efficacy breast radiotherapy. Results: lipopolysaccharide (LPS)-induced mouse inflammation model, treatment reduced levels pro-inflammatory cytokines, including COX-2, IL-6, IL-1β, TNFα. xenograft mode cancer, inhibited growth. Specifically, enhanced caspase-3 activity cytotoxicity against MDA-MB-231 MCF-7 cells. When was co-treated caspase inhibitor, Z-VAD-FMK, caspase-dependent apoptosis suppressed these found induce generation cytosolic calcium ions (Ca2+) reactive oxygen species (ROS), triggering endoplasmic reticulum (ER) stress via PERK-ATF4-CHOP axis. Hence, ER stressor thapsigargin (TG) synergized cells, while loss PERK or CHOP function phenomenon. shown oxidative NADPH oxidase 4 (NOX4) stimulate ROS production. NOX4 knockdown (KD) antioxidant (N-acetyl cysteine diphenyleneiodonium) such stress–mediated by inhibiting KA-enhanced activity, cytotoxicity, intracellular production treated radioresistant MDA-MB-231R MCF-7R combined 2 Gy radiation overcame upregulating modulating epithelial–mesenchymal transition (EMT) markers, E-cadherin, N-cadherin, vimentin. KD phenomenon due expression. Conclusions: conclusion, findings regulator promising

Language: Английский

---

Revolutionizing Cancer Treatment: ROS-Induced Apoptosis via Nanoformulated Alkaloids

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: unknown, P. 106556 - 106556

Published: Dec. 1, 2024

Language: Английский

---

An integrated machine learning framework for developing and validating a prognostic risk model of gastric cancer based on endoplasmic reticulum stress-associated genes

Biochemistry and Biophysics Reports, Journal Year: 2024, Volume and Issue: 41, P. 101891 - 101891

Published: Dec. 4, 2024

Language: Английский

---