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Ferroptosis is a predominant contributor to graft kidney ischemiaâreperfusion injury (IRI), resulting in delayed graft function (DGF). However, much less is known about the early predicting biomarkers and therapeutic targets of DGF, especially aiming at ferroptosis. Here, we propose a precise predicting model for DGF, relying on the Akirin1 level in extracellular vesicles (EVs) derived from recipient urine 48 h after kidney transplant. In addition, we decipher a new molecular mechanism whereby Akirin1 induces ferroptosis by strengthening TP53-mediated suppression of SLC7A11 during the graft kidney IRI process, that is, Akirin1 activates the EGR1/TP53 axis and inhibits MDM2-mediated TP53 ubiquitination, accordingly upregulating TP53 in two ways. Meanwhile, we present the first evidence that miR-136-5p enriched in EVs secreted by human umbilical cord mesenchymal stem cells (UM-EVs) confers robust protection against ferroptosis and graft kidney IRI by targeted inhibition of Akirin1 but knockout of miR-136-5p in UM sharply mitigates the protection of UM-EVs. The functional and mechanistic regulation of Akirin1 is further corroborated in an allograft kidney transplant model in wild-type and Akirin1-knockout mice. In summary, these findings suggest that Akirin1, which prominently induces ferroptosis, is a pivotal biomarker and target for early diagnosis and treatment of graft kidney IRI and DGF after kidney transplant.
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As an economical and environment-friendly material, hydrothermal carbonation carbon (HTCC) has been widely used in the field of adsorption and catalysis. Previous studies mainly used glucose as raw material to prepare HTCC. Cellulose in biomass can be further hydrolyzed into carbohydrate; however, there are few reports on the direct preparation of HTCC from biomass and the relevant synthesis mechanism is unclear. In this study, HTCC with efficient photocatalytic performance was prepared from reed straw using dilute acid etching under hydrothermal conditions and was used for the degradation of tetracycline (TC). The mechanism of photodegradation of TC by HTCC was systematically elucidated through various characterization techniques and density functional theory (DFT) calculations. This study provides a new perspective on the preparation of green photocatalysts and demonstrates their promising application in environmental remediation.
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Antibacterianos , Celulosa , Carbono , Tetraciclina , Carbohidratos , Catálisis , LuzRESUMEN
Hydrothermal carbonation carbon (HTCC) is a promising semiconductor material for the photocatalytic degradation of pollutants. However, the poor charge transfer capability of HTCC and the unclear mechanism of photocatalysis limit its practical application. In this study, a novel Z-type heterojunction photocatalyst of silver carbonate (Ag2CO3) and HTCC (Ag2CO3/HTCC) was developed for the degradation of methylene blue (MB) and tetracycline (TC) from wastewater using a hydrothermal- coprecipitation method. Compared to Ag2CO3 and HTCC, 40% Ag2CO3/HTCC had excellent photocatalytic activity and stability. The free radical scavenger experiments showed that â¢O2- and h+ were the main substances for the degradation of MB and TC. The intermediates formed during the photodegradation were identified by HPLC-MS, and a possible mechanism and pathway for the degradation of MB and TC by Ag2CO3/HTCC was proposed. This study provides a new idea for the synthesis of Z-type HTCC heterojunction with a high-photocatalytic efficiency and its photocatalytic mechanism.
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Carbono , Azul de Metileno , Tetraciclina , Antibacterianos , Fotólisis , CatálisisRESUMEN
PURPOSE: To share experience in managing ureteral strictures following ureteroscopic lithotripsy. METHODS: Ninety five patients diagnosed as ureteral strictures after ureteroscopic lithotripsy between January 2013 and January 2018 were included. 53 received endourological treatment, 34 underwent reconstruction, 6 underwent nephrectomy for severe renal impairment, and 2 chose routine ureteral stent replacement. Therapeutic success was defined as absence of clinical symptoms and radiologic relief of obstruction. RESULTS: The follow-up time ranged from 13 to 57 months, with a median time of 24. It lasted more than 13 months in all patients, exception for 2 nephrectomies. Two patient groups including 69 endourological procedures and 37 reconstructions were used to compare therapeutic effects and complications. The overall success rate was 60.9% (42/69) in endourological intervention vs. 97.3% (36/37) in reconstruction (p < 0.001), while 74.4% (29/39) patients with stricture less than 1 cm and 68.8% (33/48) patients with mild-to-moderate hydronephrosis achieved success in endourological group. All except 1 failure appeared within the first year postoperatively. Subgroup analyses for endourological procedures revealed significant differences in the success rate of different stricture lengths and hydronephrosis (p = 0.004 and p = 0.043). Multivariate Cox regression analysis indicated that reconstruction was significantly related to a more successful outcome, compared with endourological procedures (HR 0.052, 95% CI 0.007-0.394, p = 0.004). CONCLUSION: Reconstruction performs better than endourological procedures in surgical outcome. Endourological procedure provides an acceptable success rate in patients with stricture shorter than 1 cm and slight hydronephrosis. Most stricture recurrence appeared within the first year postoperatively.
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Complicaciones Posoperatorias/cirugía , Obstrucción Ureteral/cirugía , Ureteroscopía , Adulto , Anciano , Constricción Patológica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cálculos Ureterales/cirugía , Adulto JovenRESUMEN
Bladder cancer (BC) is the second most common malignant tumor of the urinary tract in the world. In this study, we found that ubiquitin-specific protease (USP21) was upregulated in BC and the ectopic expression of USP21 was closely associated with tumor size and metastasis. Moreover, patients with higher levels of USP21 had poorer survival rate. Multiple function analysis such as CCK-8, colony formation, wound healing, and transwell analysis indicated that USP21 regulated cell proliferation and metastasis in bladder carcinoma cell lines. We also found that USP21 could facilitate epithelial-mesenchymal transition. As EZH2 has been reported to promote cell metastasis in BC, our work identified that USP21 deubiquitinated EZH2 and stabilized it. Our data demonstrated that USP21 might play a crucial role in regulating BC progression and could provide a potential therapeutic strategy for BC.
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BACKGROUND: Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. RESULTS: The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E-binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. CONCLUSIONS: The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.
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Cistitis/complicaciones , Dolor/tratamiento farmacológico , Dolor/etiología , Sirolimus/farmacología , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Cromonas/farmacología , Ciclofosfamida/toxicidad , Cistitis/inducido químicamente , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Femenino , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/etiología , Inmunosupresores/toxicidad , Morfolinas/farmacología , Dolor/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Fosforilación/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Sirolimus/metabolismo , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/fisiopatologíaRESUMEN
Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.