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Abstract We aimed to compare the efficacy and safety of ultra-mini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) for the management of lower calyceal stones. A group of 136 patients with a single lower calyceal stone (2-3 cm in diameter) was divided into the UMP or RIRS groups. The average operation time in the RIRS group was significantly longer than that in the UMP group, and the intraoperative blood loss in the former was markedly less than that in the latter. Besides, in the RIRS group, the decreased value of postoperative Hb was obviously lower, the postoperative hospital stay was evidently shorter, and the total hospitalization expenses were markedly less than those in UMP group were. Moreover, the success rate of the first-stage lithotripsy in the UMP group was notably higher than that in RIRS group. The RIRS group had an obviously lower VAS score but a markedly higher BCS score than the UMP group six hours after surgery. At 24 h after operation, the levels of serum CRP, TNF-α and IL -6 in patients in both groups were remarkably increased, and they were evidently lower in the RIRS group than those in the UMP group were. Three days after surgery, the levels of serum CRP, TNF-α and IL -6 were notably lower in the UMP group than those in RIRS group were. RIRS and UMP are safe and effective in the treatment of 2-3 cm lower calyceal stones. The first-stage UMP is characterized by a high stone-free rate (SFR), short operation time and low postoperative infection risk, while RIRS is associated with less blood loss and low total expenses.
Resumen Nuestro objetivo fue comparar la eficacia y seguridad de la nefrolitotomía percutánea ultramini (UMP) y la cirugía intrarrenal retrógrada (CRIR) en el manejo quirúrgico de los cálculos caliceales inferiores. Un grupo de 136 pacientes con un solo cálculo calicial inferior (2-3 cm de diámetro) se dividió en un grupo UMP o un grupo CRIR. El tiempo de operación promedio en el grupo CRIR fue significativamente más largo que en el grupo UMP, y la pérdida de sangre intraoperatoria en el primero fue marcadamente menor que en el segundo. Además, en el grupo CRIR, el valor disminuido de la Hb postoperatoria fue obviamente menor, la estancia hospitalaria postoperatoria fue evidentemente más corta y los gastos totales de hospitalización fueron notablemente menores que los del grupo UMP. Además, la tasa de éxito de la litotricia de primera etapa en el grupo UMP fue notablemente más alta que en el grupo CRIR. El grupo CRIR tuvo una puntuación VAS obviamente más baja pero una puntuación BCS marcadamente más alta que el grupo UMP a seos horas después de la operación. A las 24 h después de la operación, los niveles séricos de PCR, TNF-α e IL -6 en los pacientes de ambos grupos aumentaron notablemente y fueron evidentemente más bajos en el grupo CRIR que en el grupo UMP. Tres días después de la operación, los niveles séricos de PCR, TNF-α e IL -6 fueron notablemente más bajos en el grupo UMP que en el grupo CRIR. Los procedimientos CRIR y el UMP son seguros y eficaces en el tratamiento de cálculos caliciales inferiores de 2-3 cm. El UMP de primera etapa se caracteriza por tener una tasa libre de cálculo (SFR) alta, un tiempo de operación corto y un riesgo de infección posoperatorio bajo, y el RIRS se caracteriza por una menor pérdida de sangre y gastos totales bajos.
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BACKGROUND/AIMS: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-κB signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. METHODS: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1ß and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. RESULTS: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-α, IL-1ß and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-κB, IL-6, TNF-α and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-κB signaling pathway. CONCLUSION: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-κB signaling pathway in rats with renal I/R injury.
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Apoptosis , Citocinas/metabolismo , Células Epiteliales/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Animales , Proliferación Celular , Silenciador del Gen , Inflamación , Riñón/lesiones , Túbulos Renales/patología , Lentivirus , FN-kappa B/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/farmacología , Ratas , Daño por Reperfusión , Transducción de Señal , Receptor Toll-Like 4/metabolismoRESUMEN
Krüppel-like factor 4 (KLF4) is a transcription factor involved in both tumor suppression and oncogenesis as a transcriptional activator or repressor in a context-dependent manner. KLF4 acts as a regulator of p53 depending on p21 status in breast cancer. However, the mechanisms underlying the distinct role of KLF4 remain poorly understood. Here, we revealed that p21 depletion converted KLF4 from a cell cycle inhibitor to a promoter of bladder cancer cell proliferation. Additionally, KLF4 was acetylated in a p21-dependent manner to inhibit bladder cancer cell growth as a tumor suppressor. However, deacetylated KLF4 functioned as an oncogene promoting bladder cancer cell proliferation. Mechanistically, p21 and CK2 interaction, but not CK2 alone, enhanced HDAC2 phosphorylation and restricted KLF4 deacetylation and subsequent tumor promotion. Furthermore, we observed that KLF4 was acetylated by CBP/p300 and that overexpression of CBP resulted in KLF4 acetylation and tumor suppression even in p21-depleted bladder cancer cells. Moreover, we discovered that Notch-1 knockdown-induced KLF4 is acetylated form of KLF4, which may mediate Notch-1 function in bladder cancer cell proliferation. Our data demonstrate that KLF4 acts as a tumor suppressor or oncogene to activate or repress target gene transcription depending on its acetylation status, which is regulated by p21 and CK2 interaction-mediated HDAC2 phosphorylation. Targeting KLF4 at the post-transcriptional levels may provide novel insight for bladder cancer therapy.
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Quinasa de la Caseína II/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Histona Desacetilasa 2/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Acetilación , Western Blotting , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , Inmunoprecipitación , Factor 4 Similar a Kruppel , Fosforilación , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
The aim of the present study was to elucidate the molecular mechanisms of fibroblast growth factor receptor 3 (FGFR3) activation via overexpression or mutation of the FGFR3 target gene in bladder cancer (BC). The transcription profile data GSE41035, which included 18 BC samples, containing 3 independent FGFR3 short hairpin (sh)RNA, and 6 control samples, containing enhanced green fluorescent protein (EGFP) shRNA, were obtained from the National Center of Biotechnology Information Gene Expression Omnibus database. The Limma package with multiple testing correction was used to identify differentially expressed genes (DEGs) between FGFR3 knockdown and control samples. Gene ontology (GO) and pathway enrichment analysis were conducted in order to investigate the DEGs at the functional level. In addition, differential co-expression analysis was employed to construct a gene co-expression network. A total of 196 DEGs were acquired, of which 101 were downregulated and 95 were upregulated. In addition, a gene signature was identified linking FGFR3 signaling with de novo sterol biosynthesis and metabolism using GO and pathway enrichment analysis. Furthermore, the present study demonstrated that the genes NME2, CCNB1 and H2AFZ were significantly associated with BC, as determined by the protein-protein interaction network of DEGs and co-expressed genes. In conclusion, the present study revealed the involvement of FGFR3 in the regulation of sterol biosynthesis and metabolism in the maintenance of BC; in addition, the present study provided a novel insight into the molecular mechanisms of FGFR3 in BC. These results may therefore contribute to the theoretical guidance into the detection and therapy of BC.