Investigating causal relationships of blood and urine biomarkers with urological cancer risks: a mendelian randomization study and colocalization analyses DOI Creative Commons
Jian Li, Bing Yang, Lei Guo

et al.

Journal of Cancer, Journal Year: 2024, Volume and Issue: 16(3), P. 1020 - 1031

Published: Dec. 31, 2024

Background: Establishing the causal links between biomarkers and cancer enhances understanding of risk factors facilitates discovery therapeutic targets.To this end, we used Mendelian randomization (MR) colocalization analysis to explore relationship blood urinary (BUBs) with urological cancers (UCs).Methods: First, a two-sample MR study 33 BUBs 4 UCs, while performed reverse randomization.After Bonferroni correction, for BUB UC significant causality confirmed direct by multivariate adjusting relevant factors.We also applied two-step further possible mediators causality, was BUB, mediators.Sensitivity were assess robustness results.Results: A found that there 8 CA, IGF-1, LPA, TP, CRE, BILD, TBIL NAP potential some UCs (p<0.05), but after correction only IGF-1 had PCa (OR = 1.14, 95% CI: 1.06-1.23;p=0.0006<0.05/33).Moreover, remained (P<0.05) in study.The SHBG be mediator PCa, common variant (nearby gene TNS3) (PPH4=93.21%),which mediating effect SHBG. Conclusion:Strong evidence from our suggests increases decreasing levels, addition have UCs.

Language: Английский

Addition of metformin to anti-PD-1/PD-L1 drugs activates anti-tumor immune response in peripheral immune cells of NSCLC patients DOI Creative Commons
Luisa Amato, Caterina De Rosa,

Gaetano Di Guida

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 13, 2025

Immunotherapy has transformed the treatment landscape for non-small cell lung cancer (NSCLC), yet achieving lasting benefits remains a challenge. The resistance mechanisms to immunotherapy are complex, involving interactions between tumor cells and immune that not fully understood. Metformin, an FDA-approved diabetes medication, shows promise in enhancing efficacy by boosting anti-tumor responses, although underlying molecular pathways still being investigated. This study utilized co-culture models of explore effects combining metformin with anti-PD-1/PD-L1 therapies on response LKB1 mutant (LKB1mut) versus wild-type (LKB1wt) NSCLC cells, alongside peripheral blood from patients. transcriptomic profiles LKB1mut LKB1wt were characterized via bulk RNA sequencing understand gene expression changes induced metformin. Patients advanced-stage provided mononuclear (PBMCs) analysis. assessed metformin's impact both alone combination agents innate pathways. Results indicated activated cGAS-STING pathway interferons PBMCs, their capabilities. Notably, treated exhibited synergistic effects, significantly reducing colony formation cells. Additionally, monocytes patients showed decreased viability co-culture, independent status, shifted towards M1 phenotype combined treatment. These findings supported 3D spheroids patient-derived organoids, highlighting novel biological rationale using immunotherapeutic boost activity across various subsets derived

Language: Английский

Citations

0
Self-assembled Gold@silver-ZIF structure-induced dual-enhancement luminescence synergized with interpretable machine learning empower precise monitoring of inflammatory homeostasis DOI
Gaoxiang Xu, Mengke Wang, Qing Li

et al.

Nano Today, Journal Year: 2025, Volume and Issue: 64, P. 102776 - 102776

Published: April 26, 2025

Language: Английский

Citations

0
Food-grade Lactococcus lactis expressing LEK peptide ameliorates hypertension and hyperlipidemia via ACE inhibition and lipid metabolism regulation DOI
Fei Gao, Yan Pan, Tao Han

et al.

Journal of Functional Foods, Journal Year: 2025, Volume and Issue: 129, P. 106830 - 106830

Published: April 29, 2025

Language: Английский

Citations

0
TRPC3 inhibition induces myofibroblast differentiation in diabetic dermal fibroblasts DOI Creative Commons
Giles J. Toogood, Robin J. Evans, Liping Zhang

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Diabetic wounds present a significant healthcare challenge due to impaired healing mechanisms, with dermal fibroblasts playing crucial role in tissue repair. This study investigates the of transient receptor potential canonical-3 (TRPC3) dysfunction diabetic and explores therapeutic TRPC3 inhibition. Findings reveal that expression is significantly elevated fibroblasts, which correlates suppressed transforming growth factor-beta (TGF-β) signaling differentiation into myofibroblasts. Inhibiting effectively restores fibroblast functionality by upregulating TGF-β1 its downstream effector, SMAD4. restoration enhances key myofibroblast markers, such as α-smooth muscle actin (ACTA2) type I collagen (COL1a1), are essential for wound contraction extracellular matrix remodeling. These results establish critical regulator activity inhibition promising strategy improving patients.

Language: Английский

Citations

0
Gene Expression of Thermosensitive TRP Ion Channels in the Spleen of Normotensive and Hypertensive Rats: Effect of Cold and Peripheral TRPM8 Channel Activation DOI
A. A. Evtushenko, I. P. Voronova,

Т. В. Козырева

et al.

Journal of Evolutionary Biochemistry and Physiology, Journal Year: 2025, Volume and Issue: 61(2), P. 411 - 424

Published: March 1, 2025

Language: Английский

Citations

0
Navigating the Controversies: Role of TRPM Channels in Pain States DOI Open Access
María A. Gandini, Gerald W. Zamponi

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10284 - 10284

Published: Sept. 24, 2024

Chronic pain is a debilitating condition that affects up to 1.5 billion people worldwide and bears tremendous socioeconomic burden. The success of medicine relies on our understanding the type experienced by patients mechanisms give rise it. Ion channels are among key targets for pharmacological intervention in chronic conditions. Therefore, it important understand how changes channel properties, trafficking, molecular interactions contribute sensation. In this review, we discuss studies have demonstrated involvement transient receptor potential M2, M3, M8 generation transduction, as well controversies surrounding these findings.

Language: Английский

Citations

2
Underneath the Gut–Brain Axis in IBD—Evidence of the Non-Obvious DOI Open Access
Lidiya V. Boldyreva, A. A. Evtushenko, Maria Lvova

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12125 - 12125

Published: Nov. 12, 2024

The gut–brain axis (GBA) plays a pivotal role in human health and wellness by orchestrating complex bidirectional regulation influencing numerous critical processes within the body. Over past decade, research has increasingly focused on GBA context of inflammatory bowel disease (IBD). Beyond its well-documented effects GBA–enteric nervous system vagus nerve dysregulation, gut microbiota misbalance—IBD also leads to impairments metabolic cellular functions: mitochondrial dysfunction, cationic transport, cytoskeleton dysregulation. These systemic are currently underexplored relation GBA; however, they crucial for cells’ functioning. This review summarizes studies particular mechanisms IBD. Understanding involvement these may help find new therapeutic targets develop approaches improve quality life IBD patients.

Language: Английский

Citations

1
Interplay of Glucose Metabolism and Hippo Pathway in Chondrocytes: Pathophysiology and Therapeutic Targets DOI Creative Commons
Jacob Jahn,

Quinn T. Ehlen,

Lee D. Kaplan

et al.

Bioengineering, Journal Year: 2024, Volume and Issue: 11(10), P. 972 - 972

Published: Sept. 27, 2024

In this review, we explore the intricate relationship between glucose metabolism and mechanotransduction pathways, with a specific focus on role of Hippo signaling pathway in chondrocyte pathophysiology. Glucose is vital element maintaining proper function, but it has also been implicated pathogenesis osteoarthritis (OA) via induction pro-inflammatory pathways establishment an intracellular environment conducive to OA. Alternatively, such as possess capacity respond mechanical stimuli have integral homeostasis. However, these can be dysregulated potentially contribute progression We discussed how alterations levels may modulate components variety mechanisms. Characterizing interaction highlights necessity balancing both metabolic maintain health optimal functionality. Furthermore, review demonstrates scarcity literature provides summary current research dedicated area study. Ultimately, increased into topic elucidate novel mechanisms relationships integrating metabolism. Through hope inspire future develop innovative treatments for addressing clinical challenges

Language: Английский

Citations

0
Analysis of key pathways and genes in nodal structure on rat skin surface using gene ontology and KEGG pathway DOI
Joonyoung Shin,

A Yeong Park,

Suk Ju

et al.

Genes & Genomics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Language: Английский

Citations

0
Investigating causal relationships of blood and urine biomarkers with urological cancer risks: a mendelian randomization study and colocalization analyses DOI Creative Commons
Jian Li, Bing Yang, Lei Guo

et al.

Journal of Cancer, Journal Year: 2024, Volume and Issue: 16(3), P. 1020 - 1031

Published: Dec. 31, 2024

Background: Establishing the causal links between biomarkers and cancer enhances understanding of risk factors facilitates discovery therapeutic targets.To this end, we used Mendelian randomization (MR) colocalization analysis to explore relationship blood urinary (BUBs) with urological cancers (UCs).Methods: First, a two-sample MR study 33 BUBs 4 UCs, while performed reverse randomization.After Bonferroni correction, for BUB UC significant causality confirmed direct by multivariate adjusting relevant factors.We also applied two-step further possible mediators causality, was BUB, mediators.Sensitivity were assess robustness results.Results: A found that there 8 CA, IGF-1, LPA, TP, CRE, BILD, TBIL NAP potential some UCs (p<0.05), but after correction only IGF-1 had PCa (OR = 1.14, 95% CI: 1.06-1.23;p=0.0006<0.05/33).Moreover, remained (P<0.05) in study.The SHBG be mediator PCa, common variant (nearby gene TNS3) (PPH4=93.21%),which mediating effect SHBG. Conclusion:Strong evidence from our suggests increases decreasing levels, addition have UCs.

Language: Английский

Citations

0