Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics

Clinical Science, Journal Year: 2025, Volume and Issue: 139(02), P. 171 - 198

Published: Jan. 1, 2025

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, global T2DM is anticipated double by 2050 compared with 2021. Prior studies indicate that oxidative stress inflammation are instrumental causing instigating metabolic diseases. Numerous methods drugs been designed combat resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), dipeptidyl peptidase 4 (DPP4i). Bilirubin an antioxidant fat-burning actions binding PPARα nuclear transcription factor, improving sensitivity, reducing inflammation, reversing dysfunction. Potential treatment antioxidants like bilirubin increasing enzyme produces it, heme oxygenase (HMOX), has also gained attention. This review discusses relationships between bilirubin, HMOX, how medications affect HMOX levels activity, potentially using nanoparticles treat resistance. We explore sex differences these treatments system affected. discuss emerging concept bioconversion urobilin may a role comprehensive summarizes our understanding functioning hormone, isoforms their beneficial mechanisms, analyzes might cause dichotomy responses, examines potential use nanoparticle therapies treating

Language: Английский

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Unmasking primary aldosteronism: Transforming disease management with advanced steroid profiling

Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: unknown, P. 120186 - 120186

Published: Feb. 1, 2025

Language: Английский

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Ultrasound-mediated nanomaterials for the treatment of inflammatory diseases

Ultrasonics Sonochemistry, Journal Year: 2025, Volume and Issue: 114, P. 107270 - 107270

Published: Feb. 13, 2025

Sterile and infection-associated inflammatory diseases are becoming increasingly prevalent worldwide. Conventional drug therapies often entail significant drawbacks, such as the risk of overdose, development resistance in pathogens, systemic adverse reactions, all which can undermine effectiveness treatments for these conditions. Nanomaterials (NMs) have emerged a promising tool treatment due to their precise targeting capabilities, tunable characteristics, responsiveness external stimuli. Ultrasound (US), non-invasive effective method, has been explored combination with NMs achieve enhanced therapeutic outcomes. This review provides comprehensive overview recent advances use US-mediated treating diseases. A introduction application classification US was first presented, emphasizing advantages mechanisms through interact enhance anti-inflammatory therapy. Subsequently, specific applications sterile inflammation were summarized. Finally, challenges prospects clinical translation discussed, along an outline future research directions. aims provide insights guide improvement more interventions

Language: Английский

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One-Pot Synthesis of Novel Tetrasubstituted α-Aminophosphonates Derived from α-Methylphosphoserine and In Vivo Evaluation as Anti-Inflammatory Agents

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

A series of new tetrasubstituted α-aminophosphonate derivatives with a methylphosphoserine fragment were described. These compounds synthesized by three-component (3-CR) "Kabachnik-Fields reaction." The novel α-aminophosphonates screened for in vivo anti-inflammatory activity through topical and oral administration routes. All decreased TPA-induced ear edema dose-dependent fashion. In this test, 2, 5, 7 showed the same efficacy (≈ 90%) higher potency than indomethacin inflammatory marker neutrophil-to-lymphocyte ratio (NLR). Moreover, pretreatment post-treatment 2-7 reduced CFA-induced paw edema, as did or (S)-naproxen. Based on promising results, we investigated their physicochemical pharmacokinetics profiles silico. analysis also revealed that not break Lipinski's rule five had drug-likeness favorable ADME properties transdermal administration.

Language: Английский

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Glucocorticoid receptor

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

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Tanshinone IIA Reverses Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells Impaired by Glucocorticoids via the ERK1/2‐CREB Signaling Pathway

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(3)

Published: March 1, 2025

Glucocorticoids-induced osteoporosis poses a critical health issue due to its detrimental impact on bone marrow mesenchymal stem cells (BMSCs); Tanshinone IIA (TSA) emerges as promising therapeutic intervention, demonstrating capacity reverse osteogenic differentiation impairment. The aim is determine whether TSA enhances the of BMSCs damaged by dexamethasone (DEX) through ERK1/2 -CREB signaling pathway. were treated with varying concentrations DEX (0.1-30 μM) and (0.04-5 for 18 or 36 h. Cell viability was assessed using MTT assay. Osteogenic evaluated Alizarin Red S staining quantified qRT-PCR markers such Runx2 ALP. Apoptosis measured Annexin V-FITC/PI TUNEL/DAPI co-staining. ERK1/2-CREB pathway examined Western blot immunofluorescence. at 5 μM significantly bolstered differentiation, reversing deleterious effects 30 DEX. pre-treatment decreased apoptosis ROS levels, importantly, it enhanced pathway, evidenced increased phosphorylation CREB. inhibitor PD98059 siCREB abrogated TSA's protective effects, highlighting pathway's significance. These findings indicate that TSA, axis, provides strategy against DEX-induced impairment in BMSCs. modulation reverses inhibition BMSCs, suggesting efficacy glucocorticoid-induced disorders.

Language: Английский

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Sexual Dimorphisms in Endocrinopathies: Their Impact on the Evolution of Metabolic Diseases

Molecular and Cellular Endocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 112521 - 112521

Published: March 1, 2025

Language: Английский

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Identification of angiotensin II-responsive circadian clock gene expression in adrenal zona glomerulosa cells and human adrenocortical H295R cells

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

Published: March 26, 2025

The mammalian circadian timing system is organized in a hierarchy, with the master clock residing suprachiasmatic nucleus (SCN) of hypothalamus and subsidiary peripheral clocks tissues. Because diversity tissues cell-types body, existence autonomous identification its potential entrainment signals need to be empirically defined on cell type-by-cell type basis. In this study, we characterized basic properties adrenal zona glomerulosa cells, or ZG cells. Using isolated explants from Per2 Luc mice, dissociated cells Per2-dluc rats, related human adrenocortical line H295R, showed that possess genetically-encoded, self-sustained cell-autonomous clock. As signals, angiotensin II (Ang II) caused phase-dependent phase-shifts cultured slices. Ang treatment also drove initiation (or reset) gene expression H295R associated immediate up-regulation PER1 E4BP4 mRNA expression. We found I receptor blocker CV11974, one most widely used clinical drugs for hypertensive diseases, attenuation phase resetting Our vitro data provide basis understand argue gland as component entrainable clocks.

Language: Английский

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Lycium barbarum polysaccharide ameliorates corticosterone-induced cognition decline with modulation of CRHR1

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111346 - 111346

Published: April 1, 2025

Lycium barbarum polysaccharide (LBP) has anti-inflammatory, anti-oxidation and anti-aging properties, but the mechanism of LBP on stress-induced cognitive dysfunction caused by elevated GC level is still unclear. Therefore, present study aimed to investigate corticosterone-injected（CORT-injected） impairment. The rat model was induced corticosterone in vivo. Water maze test HE staining were used observe effect function brain morphology CORT-injected rats. RT-qPCR, Western blot, immunofluorescence detect expression proteins. SH-SY5Y cells treated with CORT D-gal vitro, respectively. cell proliferation observed, western blotting detected protein expressions. In this study, treatment ameliorated CORT-induced learning protected hypothalamic hippocampal neurons from injury addition, reduced plasma concentrations results also indicated that enhanced synapsis-related proteins PSD95 SYN up-regulating CRHR1 RGS2 hippocampus hypothalamus group. Meanwhile, we confirmed - D-Gal-induced further verified changes CRHR1, RGS2, synapse-related This demonstrates cognition decline regulating CRHR1. may represent a potential drug for prevention patients increased GCs.

Language: Английский

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TRPV4 subserves physiological and pathological elevations in intraocular pressure

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Ocular hypertension (OHT) caused by mechanical stress and chronic glucocorticoid exposure reduces the hydraulic permeability of conventional outflow pathway. It increases risk for irreversible vision loss, yet healthy individuals experience nightly intraocular pressure (IOP) elevations without adverse lifetime effects. is not known which sensors regulate physiological vs. pathological OHT nor how they impact principal drainage pathway through trabecular meshwork (TM). We report that induced circadian rhythm, occlusion iridocorneal angle glucocorticoids requires activation TRPV4, a stretch-activated cation channel. Wild-type mice responded to nocturnal topical administration agonist GSK1016790A with IOP lowering, while intracameral injection elevated diurnal IOP. Microinjection TRPV4 antagonists HC067047 GSK2193874 lowered during phase in hypertensive eyes treated steroids or polystyrene microbeads. Conventional outflow-specific Trpv4 knockdown partial lowering occluded protected retinal neurons from injury. Indicating central role TRPV4-dependent mechanosensing outflow, doubled facility TM-populated steroid-treated 3D nanoscaffolds. Tonic signaling thus represents fundamental property TM biology as driver increased in vitroand vivo resistance. The TRPV4-dependence under conditions mimic primary secondary glaucomas could be explored novel target glaucoma treatments.

Language: Английский

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