Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 3, 2024

Abstract Zinc metabolism at the cellular level is critical for many biological processes in body. A key observation disruption of homeostasis, often coinciding with disease progression. As an essential factor maintaining equilibrium, zinc has been increasingly spotlighted context development. Extensive research suggests zinc’s involvement promoting malignancy and invasion cancer cells, despite its low tissue concentration. This led to a growing body literature investigating metabolism, particularly functions transporters storage mechanisms during transportation under control two major transporter families: SLC30 (ZnT) excretion SLC39 (ZIP) intake. Additionally, this element predominantly mediated by metallothioneins (MTs). review consolidates knowledge on signaling underscores potential molecular pathways linking progression, special focus cancer. We also compile summary clinical trials involving ions. Given main localization cell membrane, targeted therapies, including small molecules monoclonal antibodies, offers promising avenues future exploration.

Language: Английский

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Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction?

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 939 - 939

Published: April 23, 2024

Methylglyoxal (MGO) is a highly reactive α-dicarbonyl compound formed endogenously from 3-carbon glycolytic intermediates. accumulated in plasma and urine of hyperglycemic diabetic individuals acts as potent peptide glycation molecule, giving rise to advanced end products (AGEs) like arginine-derived hydroimidazolone (MG-H1) carboxyethyl-lysine (CEL). Methylglyoxal-derived AGEs exert their effects mostly via activation RAGE, cell surface receptor that initiates multiple intracellular signaling pathways, favoring pro-oxidant environment through NADPH oxidase generation high levels oxygen species (ROS). Diabetic bladder dysfunction bothersome urological complication patients with poorly controlled diabetes mellitus may comprise overactive bladder, urge incontinence, poor emptying, dribbling, incomplete emptying the urinary retention. Preclinical models type 1 2 have further confirmed relationship between voiding dysfunction. Interestingly, healthy mice supplemented MGO for prolonged periods exhibit vivo vitro dysfunction, which accompanied by increased AGE formation RAGE expression, well ROS overproduction tissues. Drugs reported scavenge inactivate metformin, polyphenols, alagebrium (ALT-711) shown favorable outcomes on obese leptin-deficient MGO-exposed mice. Therefore, MGO, AGEs, be critically involved pathogenesis individuals. However, there are no clinical trials designed test drugs selectively inhibit MGO–AGEs–RAGE signaling, aiming reduce manifestations diabetes-associated This review summarizes current literature role MGO–AGEs–RAGE–ROS axis directly ameliorate also reviewed here.

Language: Английский

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Underactive Bladder and Detrusor Underactivity: New Advances and Prospectives

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15517 - 15517

Published: Oct. 24, 2023

Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU urodynamic diagnosis which the International Continence Society (ICS) defines as "a contraction of reduced strength and/or duration, resulting in prolonged emptying failure to achieve complete within normal time span". Despite widespread prevalence UAB/DU, there are significant gaps our understanding its pathophysiological mechanisms, diagnosis, and treatment compared with overactive (OAB) overactivity (DO). These such clinicians regard UAB/DU an incurable condition. In recent years, UAB has increased. The definition been clarified, diagnostic criteria for have considered more comprehensively. Meanwhile, number non-invasive methods also reported. Clinical trials involving novel drugs, electrical stimulation, stem cell therapy shown promising results. Therefore, this review summarizes reports on highlights latest advances their treatment.

Language: Английский

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Diabetes and the risk of bladder cancer subtypes in men and women: results from the Netherlands Cohort Study

European Journal of Epidemiology, Journal Year: 2024, Volume and Issue: 39(4), P. 379 - 391

Published: March 16, 2024

Abstract Meta-analyses have shown modest positive associations between diabetes mellitus (DM) and bladder cancer risk, but results are heterogeneous. This might be due to lack of distinction subtypes, sexes, possibly Type 2 1 DM (T2DM T1DM). The relationship T2DM (and secondarily T1DM) characteristics with risk subtypes (invasive versus noninvasive) was investigated in the Netherlands Cohort Study. In 1986, 120,852 men women aged 55–69 years provided information on lifestyle data. After 20.3 follow-up, multivariable case-cohort analyses were based 1020 invasive 1088 noninvasive cases, 4267 subcohort members complete data confounders. While not associated cancer, it statistically significantly risk: multivariable-adjusted HR = 1.57 (95% CI 1.04–2.37), comparing participants without DM. association only significant women, showed a stronger [HR 2.19 1.10–4.34)] than 1.42 0.88–2.30)]; interaction by sex nonsignificant. Associations those whose age at diagnosis 55+ years, diagnosed less five before baseline. using antidiabetic medication had higher Exploratory age-sex-adjusted suggested T1DM this few cases. These findings suggest that positively risk.

Language: Английский

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NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 7, 2023

Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of inflammation and accelerate destruction. The chronic high glucose condition a hallmark diabetes-related pathogenesis, has been demonstrated to impair osteogenic differentiation ligament stem cells (PDLSCs), leading delayed recovery defects in diabetic patients. Reactive oxygen species (ROS) are small molecules influence cell fate determination direction differentiation. Although excessive accumulation ROS found be associated with glucose-induced damage, underlying mechanisms remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) important electron donor functions as critical scavenger antioxidant systems. It identified key mediator various biological processes, including energy metabolism However, whether NADPH involved dysregulation further compromise PDLSC under conditions still not known. In present study, we PDLSCs incubated showed impaired differentiation, increased production. Furthermore, after inhibiting synthesis NADPH, was significantly enhanced, accompanied by reduced cellular accumulation. Our findings crucial role regulating suggested new target rescuing dysfunction promoting tissue regeneration future.

Language: Английский

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Ratiometric SERS imaging for indication of peroxynitrite fluctuations in diabetic wound healing process

Chemical Engineering Journal, Journal Year: 2023, Volume and Issue: 470, P. 144024 - 144024

Published: June 9, 2023

Language: Английский

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Microencapsulation of anthocyanins extracted from black soybean peels by whey protein/fructo‐oligosaccharide contributes to improved stability, bioavailability, and ability to regulate glycolipid metabolism

Food Frontiers, Journal Year: 2024, Volume and Issue: 5(2), P. 570 - 583

Published: Jan. 10, 2024

Abstract Black soybean peels (BSPs) are rich in anthocyanins (ANCs), a naturally active substance added to manufactured foods. However, the instability of ANC structure limits its application food industry. In present study, an efficient and simple microencapsulation method improve stability was successfully established. BSP ANCs were encapsulated microencapsulated complex with fructo‐oligosaccharide (FOS) whey protein (WP) associated high encapsulation rate (65.41%) drug‐loading capacity (6.13%). The particle size polydispersity index anthocyanin‐loaded (ALM) 4.648 ± 0.350 µm 0.405 0.107, respectively. test showed that ALM performed enhanced thermostability, pH stability, storage light stability. Meanwhile, vitro release experiments indicated dramatically delayed contact time environment reduced degradation. Moreover, animal demonstrated better improved blood glucose homeostasis lipid high‐fat‐ high‐fructose‐treated mice liver accumulation damage. Additionally, vivo bioactivity could be attributed extended bioavailability proved by pharmacokinetics test. These results suggested employed WP‐FOS complexes as wall materials great potential health‐promoting properties ANC, providing promising solution dietary supplementation.

Language: Английский

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Astragalus Polysaccharides Ameliorate Diabetic Bladder Dysfunction via Normalization of Neuromuscular Conduction

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

Published: March 3, 2025

Neuromuscular conduction dysfunction-induced underactive bladder (UAB) is a major urological complication associated with diabetes mellitus (DM), and there remain deficiencies in reliable pharmacological treatment options. Astragalus polysaccharides (APS), as an edible active substance membranaceus, have therapeutic effect on its complications. We investigated the effects mechanism of APS high-fat-diet-induced (HFD) diabetic UAB mice. significantly reduced fasting plasma glucose, insulin, HOMA-IR index. Furthermore, decreased maximum capacity, residual volume, compliance, contraction intervals, empty full resting pressure, increased voiding volume voided efficiency. In addition, ameliorated hyporesponsiveness purinergic cholinergic-mediated neuromuscular detrusor improved dysregulation inhibitory excitatory neurotransmission by downregulating levels nNOS VIP, upregulating ChAT SP HFD This study revealed that ameliorates via normalization conduction.

Language: Английский

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Mitochondrial Fusion Protein 2‐Modified Bone Marrow Mesenchymal Stem Cells Improved Hyperglycemia‐Induced Schwann Cell Injury via Regulating Mitochondria‐Associated Endoplasmic Reticulum Membranes

Neurourology and Urodynamics, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

ABSTRACT Objective High glucose damages rat Schwann cells (SCs), which is closely related to the dysfunction of mitochondria‐associated endoplasmic reticulum membranes (MAMs). Therefore, present study aimed investigate protective effects and mechanisms modified bone marrow mesenchymal stem (BMSCs) mitochondrial fusion protein 2 (Mfn2) BMSCs against SCs injury. Methods The Mfn2‐modified were constructed after culturing with neural‐induced differentiation solution. MAP‐2 (microtubule‐associated protein‐2, neuron marker) GFAP (glial fibrillary acidic protein, astrocytes immunofluorescence staining was used observe changes in potential neural‐like BMSCs. (RSC96) cultured under high conditions cocultured Changes functional expression MAMs detected by Western Blot. Transmission electron microscopy (TEM) microscopic morphology MAMs, mitochondria reticulum. Results level Mfn2 significantly increased transfected Mfn2. fluorescence densities upregulated Mfn2‐BMSCs induction neural inducible When RSC96 incubated Mfn2‐modified/non‐modified BMSCs, increased, while PERK, IP3R Drp1 expressions reduced. And showed more significant comparing Mfn2‐non‐modified TEM structural integrity clear structure cristae obvious structurally intact extension Mfn2‐BMSC group. Conclusions transfection promoted cell modulated homeostasis regulating levels proteins.

Language: Английский

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6PPD impairs growth performance by inducing intestinal oxidative stress and ferroptosis in zebrafish

Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology, Journal Year: 2025, Volume and Issue: 293, P. 110161 - 110161

Published: Feb. 21, 2025

Language: Английский

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