RESUMEN
Kidney fibrosis is an inevitable result of various chronic kidney diseases (CKDs) and significantly contributes to end-stage renal failure. Currently, there is no specific treatment available for renal fibrosis. ELA13 (amino acid sequence: RRCMPLHSRVPFP) is a conserved region of ELABELA in all vertebrates; however, its biological activity has been very little studied. In the present study, we evaluated the therapeutic effect of ELA13 on transforming growth factor-ß1 (TGF-ß1)-treated NRK-52E cells and unilateral ureteral occlusion (UUO) mice. Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum, and reduce the expression of fibrosis biomarkers confirmed by Masson staining, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot. Inflammation biomarkers were increased after UUO and decreased by administration of ELA13. Furthermore, we found that the levels of essential molecules in the mothers against decapentaplegic (Smad) and extracellular signal-regulated kinase (ERK) pathways were reduced by ELA13 treatment in vivo and in vitro. In conclusion, ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.
Asunto(s)
Enfermedades Renales , Obstrucción Ureteral , Ratones , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Transducción de Señal , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/metabolismo , Factor de Crecimiento Transformador beta1 , Riñón/metabolismo , Fibrosis , Biomarcadores/metabolismoRESUMEN
Recently, the substance P (SP)/neurokinin-1 receptor (NK-1R) system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019 (COVID-19). Besides, studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis. These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy. This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers, as well as the underlying mechanisms. Furthermore, the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized, such as solid dispersion systems, nanonization, and nanoencapsulation. As a radiopharmaceutical therapeutic, the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors. However, combining NK-1R antagonists with other drugs can produce a synergistic effect, thereby enhancing the therapeutic effect, alleviating the symptoms, and improving patients quality of life in several diseases and cancers.
Asunto(s)
Neoplasias , Antagonistas del Receptor de Neuroquinina-1 , Humanos , Antagonistas del Receptor de Neuroquinina-1/farmacología , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Calidad de Vida , Sustancia P , Receptores de Neuroquinina-1 , Neoplasias/tratamiento farmacológicoRESUMEN
In chronic wound management, efficacious handling of exudate and bacterial infections stands as a paramount challenge. Here a novel biomimetic fabric, inspired by the natural transpiration mechanisms in plants, is introduced. Uniquely, the fabric combines a commercial polyethylene terephthalate (PET) fabric with asymmetrically grown 1D rutile titanium dioxide (TiO2) micro/nanostructures, emulating critical plant features: hierarchically porous networks and hydrophilic water conduction channels. This structure endows the fabric with exceptional antigravity wicking-evaporation performance, evidenced by a 780% one-way transport capability and a 0.75 g h-1 water evaporation rate, which significantly surpasses that of conventional moisture-wicking textiles. Moreover, the incorporated 1D rutile TiO2 micro/nanostructures present solar-light induced antibacterial activity, crucial for disrupting and eradicating wound biofilms. The biomimetic transpiration fabric is employed to drain exudate and eradicate biofilms in Staphylococcus aureus (S. aureus)-infected wounds, demonstrating a much faster infection eradication capability compared to clinically common ciprofloxacin irrigation. These findings illuminate the path for developing high-performance, textile-based wound dressings, offering efficient clinical platforms to combat biofilms associated with chronic wounds.