Interplay of Ferroptosis, Cuproptosis, Autophagy and Pyroptosis in Male Infertility: Molecular Crossroads and Therapeutic Opportunities DOI Open Access

Dong-Zhen Cai,

Junda Li, Peng Zhang

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3496 - 3496

Опубликована: Апрель 8, 2025

Male infertility is intricately linked to dysregulated cell death pathways, including ferroptosis, cuproptosis, pyroptosis, and autophagy. Ferroptosis, driven by iron-dependent lipid peroxidation through the Fenton reaction inactivation of GPX4/Nrf2/SLC7A11 axis, disrupts spermatogenesis under conditions oxidative stress, environmental toxin exposure, or metabolic disorders. Similarly, cuproptosis-characterized mitochondrial dysfunction disulfide stress due copper overload-exacerbates germ apoptosis via FDX1 activation NADPH depletion. Pyroptosis, mediated NLRP3 inflammasome gasdermin D, amplifies testicular inflammation loss IL-1β/IL-18 release, particularly in response insults. Autophagy maintains homeostasis clearing damaged organelles proteins; however, its dysregulation impairs sperm maturation compromises blood-testis barrier integrity. These pathways intersect shared regulators; reactive oxygen species mTOR modulate autophagy-pyroptosis balance, while Nrf2 bridge ferroptosis-cuproptosis crosstalk. Therapeutic interventions targeting these mechanisms have shown promise preclinical models. However, challenges persist, tissue-specific roles isoforms, off-target effects pharmacological inhibitors, transgenerational epigenetic impacts toxins. This review synthesizes current molecular insights into implicated male infertility, emphasizing their interplay translational potential for restoring spermatogenic function.

Язык: Английский

Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation DOI Creative Commons
Zhen Yang,

Xingyu Kao,

Lin Zhang

и другие.

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 349 - 368

Опубликована: Янв. 1, 2025

Dachaihu decoction (DCHD) is a common Chinese medicine formula against sepsis-induced acute lung injury (SALI). PANoptosis novel type of programmed cell death. Nevertheless, The mechanisms DCHD SALI via anti-PANoptosis remains unknown. First, we identified the intersecting targets among DCHD, SALI, and using relevant databases published literature. Then, protein-protein interaction (PPI) network, molecular docking, functional enrichment analysis were conducted. In vivo, cecal ligation puncture (CLP) was used to construct sepsis mouse model, therapeutic effects on evaluated hematoxylin eosin (H&E) staining, quantitative real-time PCR (qRT-PCR), ELISA. Finally, qRT-PCR, immunofluorescence Western blotting verify effect DCHD-containing serum (DCHD-DS) LPS-induced RAW 264.7 macrophages in vitro. 82 by mapping PANoptosis. Enrichment showed that modulating tumor necrosis factor (TNF), AGE-RAGE, phosphoinositide 3-kinase (PI3K)-AKT, Toll-like receptor signaling pathways targeting Casp3, cellular antigen p53 (TP53), B-cell lymphoma 2 (Bcl2), toll-like receptor-4 (TLR4), STAT3, STAT1, RELA, NF-κB1, myeloid leukemia-1 (MCL1), JUN, IL-1β, HSP90AA1, Casp9, Casp8, Bcl2l1. Molecular docking revealed key components have high binding affinity core targets. improved histopathological injury, reduced inflammatory expression, alleviated oxidative stress tissues. vitro, DCHD-DS morphology changes, release pro-inflammatory factors, p65 nucleus aggregation. Furthermore, verified inhibited downregulating PI3K/AKT/NF-κB signalling pathway. attenuates inhibiting control Our study provides solid foundation for investigating its clinical application treatment SALI.

Язык: Английский

Процитировано

1
Wilson’s Disease—Crossroads of Genetics, Inflammation and Immunity/Autoimmunity: Clinical and Molecular Issues DOI Open Access
Grażyna Gromadzka,

Julia Czerwińska,

Elżbieta Krzemińska

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9034 - 9034

Опубликована: Авг. 20, 2024

Wilson's disease (WD) is a rare, autosomal recessive disorder of copper metabolism caused by pathogenic mutations in the

Язык: Английский

Процитировано

7
Exosomes derived from FN14-overexpressing BMSCs activate the NF-κB signaling pathway to induce PANoptosis in osteosarcoma DOI Creative Commons
Liangming Wang, Yanbin Huang, Xiaolu Zhang

и другие.

APOPTOSIS, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

0
Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria DOI Creative Commons

Luying Yang,

Leiyu Xie,

Min Li

и другие.

Frontiers in Physiology, Год журнала: 2025, Номер 16

Опубликована: Март 20, 2025

Sepsis is defined as a life-threatening organ dysfunction caused by dysregulated host response to infection. Skeletal muscle atrophy due critical illness common phenomenon in the intensive care unit (ICU) and referred ICU-acquired weakness (ICU-AW). The occurrence of ICU-AW patients with sepsis known sepsis-acquired (SAW). Furthermore, it well that maintaining normal function closely relates mitochondrial homeostasis. Once impaired, both quality are affected. Copper plays key role homeostasis transition metal regulates stability various enzymes. also involved oxidation-reduction reactions, intracellular copper overload causes oxidative stress induces cell death. Previous studies have shown excess death targeting lipid-acylated proteins regulate tricarboxylic acid (TCA) cycle, which differs from canonical mechanisms regulated inhibitors death, such apoptosis, necroptosis, pyroptosis ferroptosis, not effective preventing copper-induced This new form has been termed “Cuproptosis”; however, mechanism SAW remains unclear. In this paper, we review possible relationship between cuproptosis SAW. Cuproptosis may be regulating pathological through mitochondria-related signaling pathways, ferroptosis mechanisms, genes, provide ideas for further investigations into

Язык: Английский

Процитировано

0
Unravelling the Role of PANoptosis in Liver Diseases: Mechanisms and Therapeutic Implications DOI Open Access
Wanyuan Xiong, Junfeng Li, Aiping Tian

и другие.

Liver International, Год журнала: 2025, Номер 45(4)

Опубликована: Март 21, 2025

PANoptosis is a multimodal form of cell death that involves inflammatory, apoptotic, and necroptotic pathways, playing key role in the development liver diseases. This article first outlines definition characteristics PANoptosis, then explores its mechanisms action different types diseases, including acute injury, failure, metabolic dysfunction-associated fatty disease, hepatocellular carcinoma. Furthermore, this analyses molecular regulatory network potential therapeutic targets. Finally, summarises current research on diseases future directions, it reviews emerging mechanism

Язык: Английский

Процитировано

0
Integrating cuproptosis and immunosenescence: A novel therapeutic strategy in cancer treatment DOI
Ali Ahmadizad Firouzjaei, Seyed Hamid Aghaee‐Bakhtiari

Biochemistry and Biophysics Reports, Год журнала: 2025, Номер 42, С. 101983 - 101983

Опубликована: Март 29, 2025

Язык: Английский

Процитировано

0
Associations between serum trace elements and biological age acceleration in the Chinese elderly: A community-based study investigating the mediating role of inflammatory markers and the moderating effect of physical activity DOI
Yan Wang,

Wenyuan Zhu,

Tao� Zhang

и другие.

Journal of Hazardous Materials, Год журнала: 2025, Номер unknown, С. 138273 - 138273

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer DOI Creative Commons
Ziyu Guo,

Danyao Chen,

Lei Yao

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Май 8, 2025

Abstract Copper, an essential micronutrient, plays significant roles in numerous biological functions. Recent studies have identified imbalances copper homeostasis across various cancers, along with the emergence of cuproptosis, a novel copper-dependent form cell death that is crucial for tumor suppression and therapeutic resistance. As result, manipulating levels has garnered increasing interest as innovative approach to cancer therapy. In this review, we first delineate at both cellular systemic levels, clarifying copper’s protumorigenic antitumorigenic functions cancer. We then outline key milestones molecular mechanisms including mitochondria-dependent independent pathways. Next, explore cuproptosis biology, well interactions mediated by between cells immune system. also summarize emerging opportunities targeting discuss clinical associations cuproptosis-related genes. Finally, examine potential biomarkers put forward existing challenges future prospects leveraging Overall, review enhances our understanding landscape cancer, highlighting copper- or cuproptosis-based therapies treatment.

Язык: Английский

Процитировано

0
The Effect of Cuproptosis-Related Proteins on Macrophage Polarization in Mesothelioma is Revealed by scRNA-seq DOI Creative Commons
Jiaxin Xu, Lijing Ma,

Li-Ying Tu

и другие.

Biological Trace Element Research, Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

High invasiveness mesothelioma is a malignant tumor of the peritoneum or pleura. The effect cuproptosis on (MESO) still unknown, though. Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify differential genes linked in mesothelioma. Multigene features then created assess course disease. Use single-cell data vitro validation uncover crucial gene regulation mechanisms. In MESO, we found nine differentially expressed cuproptosis. Using univariate Cox LASSO regression techniques, 3-gene feature (P < 0.05) was created, showing good predictive potential for survival time. According risk score, patients low-risk subset had considerably greater rate than those high-risk = 0). similar pattern prediction performance are also seen queue. findings drug sensitivity research indicate that patients, vinblastine, paclitaxel, gefitinib, erlotinib sensitive medications 0.05). Classical monocytes identified as core cells connected by CellChat results. SLC31A1 implicated positive M2 macrophage polarization, according cell subtype analysis confirmation. Genes have major influence immunity can predict how MESO will progress.

Язык: Английский

Процитировано

3
Interplay of Ferroptosis, Cuproptosis, Autophagy and Pyroptosis in Male Infertility: Molecular Crossroads and Therapeutic Opportunities DOI Open Access

Dong-Zhen Cai,

Junda Li, Peng Zhang

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3496 - 3496

Опубликована: Апрель 8, 2025

Male infertility is intricately linked to dysregulated cell death pathways, including ferroptosis, cuproptosis, pyroptosis, and autophagy. Ferroptosis, driven by iron-dependent lipid peroxidation through the Fenton reaction inactivation of GPX4/Nrf2/SLC7A11 axis, disrupts spermatogenesis under conditions oxidative stress, environmental toxin exposure, or metabolic disorders. Similarly, cuproptosis-characterized mitochondrial dysfunction disulfide stress due copper overload-exacerbates germ apoptosis via FDX1 activation NADPH depletion. Pyroptosis, mediated NLRP3 inflammasome gasdermin D, amplifies testicular inflammation loss IL-1β/IL-18 release, particularly in response insults. Autophagy maintains homeostasis clearing damaged organelles proteins; however, its dysregulation impairs sperm maturation compromises blood-testis barrier integrity. These pathways intersect shared regulators; reactive oxygen species mTOR modulate autophagy-pyroptosis balance, while Nrf2 bridge ferroptosis-cuproptosis crosstalk. Therapeutic interventions targeting these mechanisms have shown promise preclinical models. However, challenges persist, tissue-specific roles isoforms, off-target effects pharmacological inhibitors, transgenerational epigenetic impacts toxins. This review synthesizes current molecular insights into implicated male infertility, emphasizing their interplay translational potential for restoring spermatogenic function.

Язык: Английский

Процитировано

0