Zebrafish in dermatology: a comprehensive review of their role in investigating abnormal skin pigmentation mechanisms.

Skin pigmentation abnormalities, ranging from aesthetic concerns to severe hyperpigmentation disease, have profound implications for individuals' psychological and economic wellbeing. The intricate etiology of hyperpigmentation and our evolving comprehension of its underlying mechanisms underscore the need for robust animal models. Zebrafish, renowned for their transparent embryos and genetic parallels to humans, have been spotlighted as a pivotal model for skin pigmentation studies. This review offers a concise overview of zebrafish skin attributes, highlighting the shared melanin production pathways with humans. We systematically dissect the diverse strategies to craft zebrafish models of abnormal skin pigmentation, spanning physical, chemical, and genetic interventions, while critically appraising the merits and constraints of each approach. Additionally, we elucidate the metrics employed to gauge the efficacy of these models. Concluding, we cast a visionary gaze on prospective breakthroughs in the domain, aiming to steer forthcoming efforts in refined zebrafish models for skin pigmentation research.

The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder predominantly affecting the elderly. While conventional pharmacological therapies remain the primary treatment for AD, their efficacy is limited effectiveness and often associated with significant side effects. This underscores the urgent need to explore alternative, non-pharmacological interventions. Oxidative stress has been identified as a central player in AD pathology, influencing various aspects including amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, mitochondrial dysfunction, and synaptic dysfunction. Among the emerging non-drug approaches, hydrogen therapy has garnered attention for its potential in mitigating these pathological conditions. This review provides a comprehensively overview of the therapeutic potential of hydrogen in AD. We delve into its mechanisms of action, administration routes, and discuss the current challenges and future prospects, with the aim of providing valuable insights to facilitate the clinical application of hydrogen-based therapies in AD management.

Study on the Mechanism of Treating Femoral Head Necrosis with Drynariae Rhizoma Based on Network Pharmacology.

Through the network pharmacology thought, the action target of the active ingredients of Drynariae Rhizoma was predicted, and the mapping was combined with the related targets of ONFH, and the key nodes of interaction were identified for enrichment analysis, so as to comprehensively explore the pharmacological mechanism of Drynariae Rhizoma against ONFH. The main active ingredients of Drynariae Rhizoma were screened based on pharmacokinetic characteristics in pharmacokinetic database and analysis platform of TCM system (TCMSP). We used the organic small molecule bioactivity database (PubChem) and Swiss target prediction database to predict related targets based on 2D or 3D structural similarity and then mined the known ONFH therapeutic targets through the Human Mendelian Genetic Database (OMIM) and Pubmed texts. Combined with the predicted targets, String database was imported to construct the OP target interaction network diagram of bone fracture therapy. CytoNCA software was used to topology the key nodes of interaction according to relevant node parameters, and String was imported again to construct the protein interaction network diagram. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. It was revealed that Drynariae Rhizoma may regulate stem cells, osteoblasts, osteoclasts, and immune cells through multiple pathways, including proliferation, differentiation, immunity, and oxidative stress. Conclusion: Pharmacological studies based on network indicate that Drynariae Rhizoma may participate in the regulation of several major signaling pathways through direct or indirect action targets and affect the proliferation and differentiation of multiple types of cells, thus playing an anti-ONFH role, which provides a scientific basis for explaining the material basis and mechanism of its anti- ONFH.

Interleukin-1ß augments the angiogenesis of endothelial progenitor cells in an NF-κB/CXCR7-dependent manner.

Endothelial progenitor cells (EPCs) are able to trigger angiogenesis, and pro-inflammatory cytokines have beneficial effects on angiogenesis under physiological and pathological conditions. C-X-C chemokine receptor type 7 (CXCR-7), receptor for stromal cell-derived factor-1, plays a critical role in enhancing EPC angiogenic function. Here, we examined whether CXCR7 mediates the pro-angiogenic effects of the inflammatory cytokine interleukin-1ß (IL-1ß) in EPCs. EPCs were isolated by density gradient centrifugation and angiogenic capability was evaluated in vitro by Matrigel capillary formation assay and fibrin gel bead assay. IL-1ß elevated CXCR7 expression at both the transcriptional and translational levels in a dose- and time-dependent manner, and blockade of the nuclear translocation of NF-κB dramatically attenuated the IL-1ß-mediated up-regulation of CXCR7 expression. IL-1ß stimulation significantly promoted EPCs tube formation and this effect was largely impaired by CXCR7-siRNA transfection. IL-1ß treatment stimulated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and inhibition of Erk1/2 phosphorylation partially impaired IL-1ß-induced tube formation of EPCs but without significant effects on CXCR7 expression. Moreover, blocking NF-κB had no significant effects on IL-1ß-stimulated Erk1/2 phosphorylation. These findings indicate that CXCR7 plays an important role in the IL-1ß-enhanced angiogenic capability of EPCs and antagonizing CXCR7 is a potential strategy for inhibiting angiogenesis under inflammatory conditions.

A Novel CXCR4 antagonist enhances angiogenesis via modifying the ischaemic tissue environment.

Endothelial progenitor cells (EPCs) play a capital role in angiogenesis via directly participating in neo-vessel formation and secreting pro-angiogenic factors. Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 play a critical role in the retention and quiescence of EPCs within its niche in the bone marrow. Disturbing the interaction between SDF-1 and CXCR4 is an effective strategy for EPC mobilization. We developed a novel CXCR4 antagonist P2G, a mutant protein of SDF-1ß with high antagonistic activity against CXCR4 and high potency in enhancing ischaemic angiogenesis and blood perfusion. However, its direct effects on ischaemic tissue remain largely unknown. In this study, P2G was found to possess a robust capability to promote EPC infiltration and incorporation in neo-vessels, enhance the expression and function of pro-angiogenic factors, such as SDF-1, vascular endothelial growth factor and matrix metalloprotein-9, and activate cell signals involved in angiogenesis, such as proliferating cell nuclear antigen, protein kinase B (Akt), extracellular regulated protein kinases and mammalian target of rapamycin, in ischaemic tissue. Moreover, P2G can attenuate fibrotic remodelling to facilitate the recovery of ischaemic tissue. The capability of P2G in direct augmenting ischaemic environment for angiogenesis suggests that it is a potential candidate for the therapy of ischaemia diseases.

Physiological and Pharmacological Roles of FGF21 in Cardiovascular Diseases.

Cardiovascular disease (CVD) is one of the most severe diseases in clinics. Fibroblast growth factor 21 (FGF21) is regarded as an important metabolic regulator playing a therapeutic role in diabetes and its complications. The heart is a key target as well as a source of FGF21 which is involved in heart development and also induces beneficial effects in CVDs. Our review is to clarify the roles of FGF21 in CVDs. Strong evidence showed that the development of CVDs including atherosclerosis, coronary heart disease, myocardial ischemia, cardiac hypertrophy, and diabetic cardiomyopathy is associated with serum FGF21 levels increase which was regarded as a compensatory response to induced cardiac protection. Furthermore, administration of FGF21 suppressed the above CVDs. Mechanistic studies revealed that FGF21 induced cardiac protection likely by preventing cardiac lipotoxicity and the associated oxidative stress, inflammation, and apoptosis. Normally, FGF21 induced therapeutic effects against CVDs via activation of the above kinases-mediated pathways by directly binding to the FGF receptors of the heart in the presence of ß-klotho. However, recently, growing evidence showed that FGF21 induced beneficial effects on peripheral organs through an indirect way mediated by adiponectin. Therefore whether adiponectin is also involved in FGF21-induced cardiac protection still needs further investigation.

Low-dose radiation prevents type 1 diabetes-induced cardiomyopathy via activation of AKT mediated anti-apoptotic and anti-oxidant effects.

We investigated whether low-dose radiation (LDR) can prevent late-stage diabetic cardiomyopathy and whether this protection is because of the induction of anti-apoptotic and anti-oxidant pathways. Streptozotocin-induced diabetic C57BL/6J mice were treated with/without whole-body LDR (12.5, 25, or 50 mGy) every 2 days. Twelve weeks after onset of diabetes, cardiomyopathy was diagnosed characterized by significant cardiac dysfunction, hypertrophy and histopathological abnormalities associated with increased oxidative stress and apoptosis, which was prevented by LDR (25 or 50 mGy only). Low-dose radiation-induced cardiac protection also associated with P53 inactivation, enhanced Nrf2 function and improved Akt activation. Next, for the mechanistic study, mouse primary cardiomyocytes were treated with high glucose (33 mmol/l) for 24 hrs and during the last 15 hrs bovine serum albumin-conjugated palmitate (62.5 µmol/l) was added into the medium to mimic diabetes, and cells were treated with LDR (25 mGy) every 6 hrs during the whole process of HG/Pal treatment. Data show that blocking Akt/MDM2/P53 or Akt/Nrf2 pathways with small interfering RNA of akt, mdm2 and nrf2 not only prevented LDR-induced anti-apoptotic and anti-oxidant effects but also prevented LDR-induced suppression on cardiomyocyte hypertrophy and fibrosis against HG/Pal. Low-dose radiation prevented diabetic cardiomyopathy by improving cardiac function and hypertrophic remodelling attributed to Akt/MDM2/P53-mediated anti-apoptotic and Akt/Nrf2-mediated anti-oxidant pathways simultaneously.

Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases.

Fibroblast growth factor (FGF)19 and FGF21 are hormones that regulate metabolic processes particularly during feeding or starvation, thus ultimately influencing energy production. FGF19 is secreted by the intestines during feeding and negatively regulates bile acid synthesis and secretion, whereas FGF21 is produced in the liver during fasting and plays a crucial role in regulating glucose and lipid metabolism, as well as maintaining energy homeostasis. FGF19 and FGF21 are regarded as late-acting hormones because their functions are only used after insulin and glucagon have completed their actions. Although FGF19 and FGF21 are activated under different conditions, they show extensively functional overlap in terms of improving glucose tolerance, insulin sensitivity, weight loss, and lipid, and energy metabolism, particularly in pathological conditions such as diabetes, obesity, metabolic syndrome, and cardiovascular and renal diseases. Most patients with these metabolic diseases exhibit reduced serum FGF19 levels, which might contribute to its etiology. In addition, the simultaneous increase in serum FGF21 levels is likely a compensatory response to reduced FGF19 levels, and the 2 proteins concertedly maintain metabolic homeostasis. Here, we review the physiological and pharmacological cross talk between FGF19 and FGF21 in relation to the regulation of endocrine metabolism and various chronic diseases.

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model.

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.