RESUMEN
Hypertrophy of ligamentum flavum (LF) is a significant contributing factor to lumbar spinal canal stenosis (LSCS). lncRNA plays a vital role in organ fibrosis, but its role in LF fibrosis remains unclear. Our previous findings have demonstrated that Hedgehog-Gli1 signaling is a critical driver leading to LF hypertrophy. Through the RIP experiment, our group found lnc-RMRP was physically associated with Gli1 and exhibited enrichment in Gli1-activated LF cells. Histological studies revealed elevated expression of RMRP in hypertrophic LF. In vitro experiments further confirmed that RMRP promoted Gli1 SUMO modification and nucleus transfer. Mechanistically, RMRP induced GSDMD-mediated pyroptosis, proinflammatory activation, and collagen expression through the Hedgehog pathway. Notably, the mechanical stress-induced hypertrophy of LF in rabbit exhibited analogous pathological changes of LF fibrosis occurred in human and showed enhanced levels of collagen and α-SMA. Knockdown of RMRP resulted in the decreased expression of fibrosis and pyroptosis-related proteins, ultimately ameliorating fibrosis. The above data concluded that RMRP exerts a crucial role in regulating GSDMD-mediated pyroptosis of LF cells via Gli1 SUMOylation, thus indicating that targeting RMRP could serve as a potential and effective therapeutic strategy for LF hypertrophy and fibrosis.
Asunto(s)
Hipertrofia , Ligamento Amarillo , Piroptosis , Sumoilación , Proteína con Dedos de Zinc GLI1 , Humanos , Animales , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Ligamento Amarillo/metabolismo , Ligamento Amarillo/patología , Conejos , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Fibrosis , Modelos Animales de Enfermedad , GasderminasRESUMEN
To compared the effectiveness and safety of single standard mini percutaneous nephrolithotripsy (SM-PCNL) combined with retrograde intrarenal surgery (RIRS) and multiple standard mini percutaneous nephrolithotomy (MSM-PCNL) in the treatment of octopus stone of 2 to 4 cm. The clinical data of SM-PCNL combined with RIRS and MSM-PCNL for octopus stone with a 2 to 4 cm diameter from October 2019 to December 2022 were analyzed retrospectively, and propensity score matching was used to screen patients. The matched patients were paired, and the operation time, complications, postoperative pain, tubeless rate, stone-free rate (SFR), and postoperative hospital stay were further compared between the 2 groups. 88 patients underwent SM-PCNL combined with RIRS (combined group), and 143 patients underwent MSM-PCNL (multiple channel group). After matching analysis, there were 49 patients in each group, and there was no significant difference in the general preoperative data between the 2 groups. The perioperative complications and stone-free rate were no statistical difference. In postoperative pain (4.00â ±â 0.74 vs 5.00â ±â 0.74, Pâ =â .00), tubeless rate (44.90% vs 20.41%, Pâ =â .01), hemoglobin drop (9.38â ±â 7.48 vs 14.22â ±â 7.69, Pâ =â .01), postoperative hospital stay (3.37â ±â 1.09 vs 5.08â ±â 1.29, Pâ =â .00), the combined group was significantly better than the multiple channel group. Regarding operation time, the combined group was more than the multiple channel group (103.27â ±â 27.61 vs 78.39â ±â 19.31, Pâ =â .000). For octopus stone with a diameter of 2 to 4 cm, the effectiveness and safety of SM-PCNL combined with RIRS were similar to those of MSM-PCNL The surgeon should carefully evaluate the patient's physical condition, stone characteristics, and expectations before the operation and assist the patient in choosing an appropriate plan.
Asunto(s)
Cálculos Renales , Puntaje de Propensión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cálculos Renales/cirugía , Estudios Retrospectivos , Adulto , Tiempo de Internación/estadística & datos numéricos , Tempo Operativo , Nefrolitotomía Percutánea/métodos , Nefrolitotomía Percutánea/efectos adversos , Resultado del Tratamiento , Litotricia/métodos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
To compare the safety and effectiveness of the combination of intelligent intrarenal pressure control platforms (IPCP) and flexible ureteral access sheath (FUAS) combined with retrograde intrarenal surgery (RIRS) for the treatment of renal stones less than 2 cm. We retrospectively collected 383 patients with renal stones who underwent RIRS in our department from June 2022 to October 2023. Inclusion criteria: stone length or the sum of multiple stone lengths ≤ 2 cm. Finally, 99 cases were included and divided into an IPCP group (n = 40) and FUAS group (n = 59) based on surgical methods. The main endpoint was the stone-free rate (SFR) at third months after surgery, with no residual stones or stone fragments less than 2 mm defined as stone clearance. The secondary endpoints were surgical time and perioperative complications, including fever, sepsis, septic shock, and perirenal hematoma. There was no statistically significant difference in general information between the two groups, including age, gender, body mass index, comorbidities, stone side, stone location, stone length, urine bacterial culture, and hydronephrosis. The operation time for IPCP group and FUAS group was 56.83 ± 21.33 vs 55.47 ± 19.69 min (p = 0.747). The SFR of IPCP group and FUAS group on the first postoperative day was 75.00% vs 91.50% (p = 0.024). The SFR was 90.00% vs 94.90% in the third month (p = 0.349).In IPCP group, there were 11 cases with stones located in the lower renal calyces and 17 cases in FUAS group. The SFR of the two groups on the first day and third months after surgery were 45.50% vs 88.20% (p = 0.014) and 63.60% vs 94.10% (p = 0.040), respectively, with statistical differences. For kidney stones ≤ 2 cm, there was no difference in SFR and the incidence of infection-related complications between IPCP and FUAS combined with RIRS, both of which were superior to T-RIRS. For lower renal caliceal stones, FUAS has a higher SFR compared to IPCP.
Asunto(s)
Difosfonatos , Cálculos Renales , Ureteroscopía , Humanos , Ureteroscopía/efectos adversos , Ureteroscopía/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Renales/cirugíaRESUMEN
Ongoing chronic fibrosis and hypertrophy of the ligamentum flavum (LF) is an important cause of lumbar spinal canal stenosis (LSCS). Our previous work showed that WNT1-inducible signaling pathway protein 1 (WISP-1) is a critical driver of LF fibrosis. However, the potential mechanism has not been explored. Here, we found that Gli1 was upregulated in hypertrophic LF tissues and required for fibrogenesis in fibroblasts. Moreover, mechanical stretching increased the expression of WISP-1 in LF fibroblasts. Furthermore, WISP-1 induced fibrogenesis in vitro through the Hedgehog-Gli1 pathway. This conclusion was supported by the fact that WISP-1 activated the Hedgehog-Gli1 pathway in LF fibroblasts and that cyclopamine attenuated the effect of WISP-1-induced fibrogenesis. WISP-1 also promoted the transition of fibroblasts into myofibroblasts via the Hedgehog pathway. Importantly, a hypertrophic LF rabbit model induced by mechanical stress also showed pathological changes in fibrosis and elevated expression of WISP-1, Gli1, and α-SMA. Therapeutic administration of cyclopamine reduced collagen expression, fibroblast proliferation, and myofibroblast differentiation and ameliorated fibrosis in the mechanical stress-induced rabbit model. Collectively, our findings show mechanical stress/WISP-1/Hedgehog signaling as a new fibrotic axis contributing to LF hypertrophy and identify Hedgehog signaling as a therapeutic target for the prevention and treatment of LF fibrosis.
Asunto(s)
Proteínas Hedgehog , Ligamento Amarillo , Animales , Fibrosis , Proteínas Hedgehog/metabolismo , Hipertrofia/metabolismo , Ligamento Amarillo/metabolismo , Ligamento Amarillo/patología , Vértebras Lumbares/metabolismo , Vértebras Lumbares/patología , Conejos , Transducción de Señal , Estrés MecánicoRESUMEN
Mycoplasma hyorhinis (M. hyorhinis) is a swine pathogen that is associated with various human cancers and contamination in cell cultures. However, no studies on the adhesion molecules of this pathogen have yet been reported. The variable lipoprotein (Vlp) family is an important surface component of M. hyorhinis. Herein, we performed several experiments to identify the function of the Vlp family in adherence to host cells. Seven recombinant Vlp (rVlp) proteins were expressed in Escherichia coli and purified by affinity chromatography. The potential role of rVlp adherence to pig kidney (PK-15) and swine tracheal epithelial (STEC) cells was then studied by indirect immunofluorescence assay and microtiter plate adherence assay. Adhesion of M. hyorhinis to PK-15 and STEC cells was specifically inhibited by the addition of a cocktail of rVlp proteins. The rVlp protein mixture was shown to bind to both PK-15 and STEC cells. The binding increased in a dose-dependent manner and could be blocked by antisera against the rVlp proteins. Most of the rVlp proteins could bind individually to both PK-15 and STEC cells except for rVlpD and rVlpF, which bound only to STEC cells. Because Vlp members vary in size among different strains and generations, they may vary in their cytoadhesion capabilities in various strains. In summary, the present results indicate that the Vlp family functions as adhesins of M. hyorhinis.