Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines

Biomedicines, Год журнала: 2025, Номер 13(1), С. 150 - 150

Опубликована: Янв. 9, 2025

Background: Chronic venous disease (CVD) comprises a set of vascular disorders that affect the system with important local and systemic repercussions. A growing body evidence displays relationship between suffering from CVD marked deregulation immune inflammatory system. In this sense, previous literature has reported some significant changes in level various circulating parameters these patients. However, more research is required to detail deepen complex relationship. Methods: work, we studied, using multiplex technique, levels cytokines chemokines detectable serum 40 patients compared it 38 healthy controls (HCs). parallel, performed Spearman's correlation analysis explore potential networks CVD. Results: study, measured assay. Results showed increased several pro-inflammatory mediators (IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-12, IL-17A, IL-23, TNF-α, IFN-γ, fractalkine, ITAC, GM-CSF) decrease IL-13, no IL-4, IL-10, IL-21, MIP-1α, MIP-1β, or MIP-3α. The Spearman revealed strong, positive correlations among HC, particularly TNF-alpha, IL-1β, forming highly interconnected cytokine network. contrast, fewer, weaker, distinct correlations, new associations such as IFN-γ IL-1β suggesting disrupted profile. Conclusions: profile patients, characterized by altered chemokine less coordinated network, underscores reconfiguration pathways condition. These findings highlight therapeutic targets aimed at restoring balance mitigating chronic inflammation

Язык: Английский

---

Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Март 27, 2025

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.

Язык: Английский

---

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1113 - 1113

Опубликована: Янв. 17, 2024

Mucopolysaccharidoses (MPSs) are a group of inborn errors the metabolism caused by deficiency in lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time various tissues and disrupt multiple biological systems, including catabolism other substances, autophagy, mitochondrial function. pathological changes ultimately increase oxidative stress activate innate immunity inflammation. We have described pathophysiology MPS activated inflammation this paper, starting with accumulating primary storage materials, GAGs. At initial stage GAG accumulation, affected tissues/cells reversibly but progress irreversibly to: (1) disruption substrate degradation pathogenic function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), inflammatory process, (3) progressive tissue/organ damage cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current future treatment, several potential treatments for that can penetrate blood–brain barrier bone been proposed and/or clinical trials, targeting peptides molecular Trojan horses monoclonal antibodies attached via receptor-mediated transport. Gene therapy trials AAV, ex vivo LV, Sleeping Beauty transposon system underway innovative therapeutic options. In addition, possible immunomodulatory reagents suppress symptoms summarized review.

Язык: Английский

---

The Interleukin-1 Family

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

---

Placentas from Women with Late-Onset Preeclampsia Exhibit Increased Expression of the NLRP3 Inflammasome Machinery

Biomolecules, Год журнала: 2023, Номер 13(11), С. 1644 - 1644

Опубликована: Ноя. 13, 2023

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension commonly accompanied proteinuria multiorgan affections. According to the time of diagnosis, it differentiated between early-onset (EO-PE) late-onset preeclampsia (LO-PE). Despite being less dangerous presenting distinct pathophysiological signatures, LO-PE has greater prevalence than EO-PE, both having significant consequences on placenta. Previous works have evidenced that exacerbated inflammation in this organ might play potential pathogenic role development pre-eclampsia, there some preliminary evidence hyperactivation inflammasomes can be related altered immunoinflammatory responses observed placentas these patients. However, precise women with remains fully understood. In work, we studied gene protein expression main components canonical non-canonical pathways inflammasome NLRP3 (NLRP3, ASC, caspase 1, 5, 8, interleukin 1β, 18) placental tissue LO-PE. Our results show marked increase all who undergone LO-PE, suggesting plays entity. Future should aim evaluate possible translational approaches dysregulation

Язык: Английский

---

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(5), С. 3839 - 3865

Опубликована: Апрель 25, 2024

Pancreatic cancer is a type of gastrointestinal tumor with growing incidence and mortality worldwide. ductal adenocarcinoma (PDAC) constitutes 90% cases, late-stage diagnosis common, leading to 5-year survival rate less than 10% in high-income countries. The use biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis identification potential therapeutic targets. Several studies have shown correlation between the tissue expression levels various molecules, measured through immunohistochemistry (IHC), rates PDAC. Following hallmarks cancer, epigenetic metabolic reprogramming, together immune evasion tumor-promoted inflammation, plays critical role initiation development. In this study, we aim explore via IHC Kaplan–Meier analyses prognostic value epigenetic-related markers (histones 3 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding 7 (RBBP7), importin (IPO4) IPO5), regulators (Phosphoglycerate mutase (PGAM)) inflammatory mediators (allograft factor (AIF-1), interleukin 10 (IL-10), IL-12A IL-18) patients Also, analysis, explored possible interconnections these molecules. Our results show that higher molecules are directly associated poorer PDAC patients, except case IL-10, which shows an inverse association mortality. HAT1 was molecule more clearly mortality, hazard risk 21.74. correlogram demonstrates important almost all studied (except IL-18), highlighting interactions Overall, our study relevance including from techniques order identify unexplored develop methods targeted therapies. Additionally, analysis reveals among markers, offering insights into PDAC’s pathogenesis paving way for therapies tailored individual patient profiles. Future should be conducted confirm components broader sample size, as well evaluate biological networks connecting them.

Язык: Английский

---

Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5528 - 5528

Опубликована: Май 18, 2024

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the system, approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting placenta. While systemic inflammation has been associated with pregnancy-related preliminary findings suggest potential link between this condition and exacerbated placental tissue. Inflammasomes are major orchestrators immune responses different organs systems. Notwithstanding relevance inflammasomes, specifically NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which demonstrated placentas obstetric complications, precise involvement component CVD remains to be explored. This study employs immunohistochemistry real-time PCR (RT-qPCR) examine gene protein expression key components both canonical non-canonical pathways inflammasome (NLRP3, ASC-apoptosis-associated speck-like containing C-terminal caspase recruitment domain-caspase 1, 5, 8, interleukin 1β) within tissue affected by CVD. Our reveal substantial upregulation these CVD-affected placentas, indicating pathophysiological role development condition. Subsequent investigations should focus on assessing translational interventions addressing dysregulation patient populations.

Язык: Английский

---

Improving understanding of ferroptosis: molecular mechanisms, connection with cellular senescence and implications for aging

Heliyon, Год журнала: 2024, Номер 10(21), С. e39684 - e39684

Опубликована: Окт. 24, 2024

Язык: Английский

---

Therapeutic potential of vitamin D3 in mitigating high glucose‑induced renal damage: Mechanistic insights into oxidative stress inhibition and TXNIP/NLRP3 signaling pathway blockade

Experimental and Therapeutic Medicine, Год журнала: 2024, Номер 28(1)

Опубликована: Май 9, 2024

In the development of diabetic nephropathy, pathological damage such as interstitial fibrosis and cell apoptosis often occur in renal tubules. present study, control group mice were randomly treated with vitamin D3 or vehicle for 6 months. addition, human tubular epithelial (HK‑2) cells cultured high‑glucose medium oxidative inhibitor NAC. Immunohistochemistry, western blotting, quantitative PCR), ELISA showed that decreased expression α‑smooth muscle actin E‑cadherin cells, improving fibrosis. It also downregulated ratio Bax/Bcl2 protein, alleviating cells. Furthermore, significantly inhibited stress response blocked (Thioredoxin Interacting Protein) TXNIP/NLRP3 inflammatory pathway. Therefore, can protect from by inhibiting blocking pathway nephropathy.

Язык: Английский

---

NLRP3 Inhibitor Alleviates Glycemic Variability-Induced Cognitive Impairment in Aged Rats with Type 2 Diabetes Mellitus

Molecular and Cellular Endocrinology, Год журнала: 2024, Номер 595, С. 112406 - 112406

Опубликована: Ноя. 1, 2024

Язык: Английский

---