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1.
Colloids Surf B Biointerfaces ; 241: 114031, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38878661

RESUMEN

The therapy of the clear cell renal cell carcinoma (ccRCC) is crucial for the human healthcare due to its easy metastasis and recurrence, as well as resistance to radiotherapy and chemotherapy. In this work, we propose the synthesis of MoS2@red phosphorus (MoS2@RP) heterojunction to induce synergistic photodynamic and photothermal therapy (PDT/PTT) of ccRCC. The MoS2@RP heterojunction exhibits enhanced spectra absorption in the NIR range and produce local heat-increasing under the NIR laser irradiation compared with pure MoS2 and RP. The high photocatalytic activity of the MoS2@RP heterojunction contributes to effective transferring of the photo-excited electrons from the RP to MoS2, which promotes the production of various types of radical oxygen species (ROS) to kill the ccRCC cells. After the NIR irradiation, the MoS2@RP can effectively induce the apoptosis in the ccRCC cells through localized hyperthermia and the generation of ROS, while exhibiting low cytotoxicity towards normal kidney cells. In comparison to MoS2, the MoS2@RP heterojunction shows an approximate increase of 22 % in the lethality rate of the ccRCC cells and no significant change in toxicity towards normal cells. Furthermore, the PDT/PTT treatment using the MoS2@RP heterojunction effectively eradicates a substantial number of deep-tissue ccRCC cells in vivo without causing significant damage to major organs. This study presents promising effect of the MoS2@RP heterojunction-based photo-responsive therapy for effective ccRCC treatment.

2.
Eur J Med Res ; 29(1): 341, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902792

RESUMEN

BACKGROUND: Research into the acute kidney disease (AKD) after acute ischemic stroke (AIS) is rare, and how clinical features influence its prognosis remain unknown. We aim to employ interpretable machine learning (ML) models to study AIS and clarify its decision-making process in identifying the risk of mortality. METHODS: We conducted a retrospective cohort study involving AIS patients from January 2020 to June 2021. Patient data were randomly divided into training and test sets. Eight ML algorithms were employed to construct predictive models for mortality. The performance of the best model was evaluated using various metrics. Furthermore, we created an artificial intelligence (AI)-driven web application that leveraged the top ten most crucial features for mortality prediction. RESULTS: The study cohort consisted of 1633 AIS patients, among whom 257 (15.74%) developed subacute AKD, 173 (10.59%) experienced AKI recovery, and 65 (3.98%) met criteria for both AKI and AKD. The mortality rate stood at 4.84%. The LightGBM model displayed superior performance, boasting an AUROC of 0.96 for mortality prediction. The top five features linked to mortality were ACEI/ARE, renal function trajectories, neutrophil count, diuretics, and serum creatinine. Moreover, we designed a web application using the LightGBM model to estimate mortality risk. CONCLUSIONS: Complete renal function trajectories, including AKI and AKD, are vital for fitting mortality in AIS patients. An interpretable ML model effectively clarified its decision-making process for identifying AIS patients at risk of mortality. The AI-driven web application has the potential to contribute to the development of personalized early mortality prevention.


Asunto(s)
Inteligencia Artificial , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Anciano , Accidente Cerebrovascular Isquémico/mortalidad , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Lesión Renal Aguda/mortalidad , Aprendizaje Automático , Medicina de Precisión/métodos , Algoritmos
3.
J Mater Chem B ; 12(16): 4039-4052, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38591157

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Nanocompuestos , Fósforo , Fotoquimioterapia , Terapia Fototérmica , Titanio , Titanio/química , Titanio/farmacología , Fósforo/química , Humanos , Animales , Nanocompuestos/química , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/terapia , Ratones , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Ratones Endogámicos BALB C , Ensayos de Selección de Medicamentos Antitumorales , Tamaño de la Partícula , Línea Celular Tumoral
4.
Small ; 20(13): e2308767, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37949814

RESUMEN

Dual single-atom catalysts (DSACs) are promising for breaking the scaling relationships and ensuring synergistic effects compared with conventional single-atom catalysts (SACs). Nevertheless, precise synthesis and optimization of DSACs with specific locations and functions remain challenging. Herein, dual single-atoms are specifically incorporated into the layer-stacked bulk-like carbon nitride, featuring in-plane three-coordinated Pd and interplanar four-coordinated Cu (Pd1-Cu1/b-CN) atomic sites, from both experimental results and DFT simulations. Using femtosecond time-resolved transient absorption (fs-TA) spectroscopy, it is found that the in-plane Pd features a charge decay lifetime of 95.6 ps which is much longer than that of the interplanar Cu (3.07 ps). This finding indicates that the in-plane Pd can provide electrons for the reaction as the catalytically active site in both structurally and dynamically favorable manners. Such a well-defined bi-functional cascade system ensures a 3.47-fold increase in CO yield compared to that of bulk-like CN (b-CN), while also exceeding the effects of single Pd1/b-CN and Cu1/b-CN sites. Furthermore, DFT calculations reveal that the inherent transformation from s-p coupling to d-p hybridization between the Pd site and CO2 molecule occurs during the initial CO2 adsorption and hydrogenation processes and stimulates the preferred CO2-to-CO reaction pathway.

5.
Materials (Basel) ; 16(21)2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37959641

RESUMEN

Acoustic metasurfaces, as two-dimensional acoustic metamaterials, are a current research topic for their sub-wavelength thickness and excellent acoustic wave manipulation. They hold significant promise in noise reduction and isolation, cloaking, camouflage, acoustic imaging, and focusing. Resonant structural units are utilized to construct acoustic metasurfaces with the unique advantage of controlling large wavelengths within a small size. In this paper, the recent research progresses of the resonant metasurfaces are reviewed, covering the design mechanisms and advances of structural units, the classification and application of the resonant metasurfaces, and the tunable metasurfaces. Finally, research interest in this field is predicted in future.

7.
J Org Chem ; 88(18): 13142-13148, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37654092

RESUMEN

With the increasing relevance of organophosphorus fluorine compounds in the pharmaceutical industry, their synthesis has attracted great attention. Herein, we report an efficient fluorination strategy for P(O)-H and P(O)-OH compounds using sulfuryl fluoride as the fluorination reagent. Avoiding the use of expensive or complex prepreparation reagents for fluoridation, this strategy could conveniently construct a variety of fluorophosphonates and phosphonofluoridates under mild conditions and without additional oxidants.

8.
Eur J Med Res ; 28(1): 312, 2023 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-37660080

RESUMEN

PURPOSE: Furosemide, a frequently prescribed diuretic for managing congestive heart failure and edema, remains a topic of debate regarding its potential risk of inducing acute kidney injury (AKI) in patients. Consequently, this study aims to examine the occurrence of hospital-acquired AKI (HA-AKI) in hospitalized patients who are administered furosemide and to investigate potential risk factors associated with this outcome. METHODS: This study encompassed a cohort of 22374 hospitalized patients who either received furosemide treatment or not from June 1, 2012, to December 31, 2017. Propensity score matching was employed to establish comparability between the two groups regarding covariates. Subsequently, a nomogram was constructed to predict the probability of AKI occurrence among patients who underwent furosemide treatment. RESULTS: The regression analysis identified the single-day total dose of furosemide as the most significant factor for AKI, followed by ICU administration, estimated glomerular filtration rate, antibiotic, statin, NSAIDs, ß-blockers, proton pump inhibitor, chronic kidney disease, and 7 other indicators. Subgroup analysis revealed a synergistic effect of furosemide with surgical operation, previous treatment with ß-blockers, ACEI/ARB and antibiotics, leading to an increased risk of AKI when used in combination. Subsequently, a visually represented prognostic nomogram was developed to predict AKI occurrence in furosemide users. The predictive accuracy of the nomogram was assessed through calibration analyses, demonstrating an excellent agreement between the nomogram predictions and the actual likelihood of AKI, with a probability of 77.40%. CONCLUSIONS: Careful consideration of factors such as dosage, concurrent medication use, and renal function of the patient is necessary for clinical practice when using furosemide. Our practical prognostic model for HA-AKI associated with furosemide use can be utilized to assist clinicians in making informed decisions about patient care and treatment.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Cardíaca , Humanos , Furosemida/efectos adversos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Lesión Renal Aguda/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Antibacterianos
9.
Eur J Med Res ; 28(1): 344, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37710348

RESUMEN

INTRODUCTION: Hexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms. METHODS: We assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 µg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin. RESULTS: In this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments. CONCLUSION: Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.


Asunto(s)
Lesión Renal Aguda , Daño por Reperfusión , Animales , Ratas , Proteína p53 Supresora de Tumor/genética , Simulación del Acoplamiento Molecular , Lesión Renal Aguda/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Isquemia
10.
Artículo en Inglés | MEDLINE | ID: mdl-37632677

RESUMEN

It is important to explore whether there are antagonistic and synergistic effects between different strains of Lactobacillus when developing mixed Lactobacillus strain products. In this study, we investigated the antagonistic and symbiotic effects of co-cultured Lactobacillus strains, as well as their amelioratory effects on lipopolysaccharide (LPS)-induced inflammation and oxidative stress in RAW264.7 cells. The Lactobacillus strains tested in this paper showed no antagonism. Co-culture of Lactiplantibacillus plantarum Y44 and L. plantarum AKS-WS9 was found to show inhibiting effects on the growth of Escherichia coli and Staphylococcus aureus. Additionally, the co-cultured Lactiplantibacillus plantarum Y44 and L. plantarum AKS-WS9 relieved inflammation in RAW264.7 cells induced by LPS by inhibiting the activation of NF-κB and P38 signaling pathways and down-regulating the expression of pro-inflammatory cytokines NO, ROS, iNOs and TNF-α. And the co-cultured Lactobacillus strains activated the Nrf2 signaling pathway in the LPS-induced RAW264.7 cells to promote the expression of antioxidant enzymes in response to oxidative stress. There was a difference in intracellular and extracellular metabolites between single or co-cultured Lactobacillus strains, and the co-cultured Lactobacillus strains significantly increased extracellular metabolites 4-chlorobenzaldehyde, psoromic acid, and 2-dodecylbenzenesulfonic acid and intracellular metabolites 9(S)-HODE, pyocyanin, and LysoPA. We inferred that the better antibacterial and anti-inflammatory ability of the co-cultured Lactobacillus strains were related to the changes in the metabolites of the co-cultured Lactobacillus strains. The co-cultured L. plantarum Y44 and L. plantarum AKS-WS9 strains exhibited better anti-inflammatory abilities and had the potential to alleviate the symptoms of inflammatory diseases as mixed probiotics.

11.
Ren Fail ; 45(1): 2212800, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37199267

RESUMEN

BACKGROUND: Patients with end-stage renal disease (ESRD) especially those undergoing dialysis have a high prevalence of hyperkalemia, which must be detected and treated immediately. But the initial symptoms of hyperkalemia are insidious, and traditional laboratory serum potassium concentration testing takes time. Therefore, rapid and real-time measurement of serum potassium is urgently needed. In this study, different machine learning methods were used to make rapid predictions of different degrees of hyperkalemia by analyzing the ECG. METHODS: A total of 1024 datasets of ECG and serum potassium concentrations were analyzed from December 2020 to December 2021. The data were scaled into training and test sets. Different machine learning models (LR, SVM, CNN, XGB, Adaboost) were built for dichotomous prediction of hyperkalemia by analyzing 48 features of chest leads V2-V5. The performance of the models was also evaluated and compared using sensitivity, specificity, accuracy, accuracy, F1 score and AUC. RESULTS: We constructed different machine models to predict hyperkalemia using LR and four other common machine-learning methods. The AUCs of the different models ranged from 0.740 (0.661, 0.810) to 0.931 (0.912,0.953) when different serum potassium concentrations were used as the diagnostic threshold for hyperkalemia, respectively. As the diagnostic threshold of hyperkalemia was raised, the sensitivity, specificity, accuracy and precision of the model decreased to various degrees. And AUC also performed less well than when predicting mild hyperkalemia. CONCLUSION: Noninvasive and rapid prediction of hyperkalemia can be achieved by analyzing specific waveforms on the ECG by machine learning methods. But overall, XGB had a higher AUC in mild hyperkalemia, but SVM performed better in predicting more severe hyperkalemia.


Asunto(s)
Hiperpotasemia , Fallo Renal Crónico , Humanos , Hiperpotasemia/diagnóstico , Hiperpotasemia/etiología , Potasio , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Aprendizaje Automático , Electrocardiografía/métodos
12.
Front Vet Sci ; 10: 1134193, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36950537

RESUMEN

Following the discovery of Eimeria kongi, we investigated the pathogenicity, immunogenicity, endogenous development and drug sensitivity of this coccidian. Coccidia-free rabbits were inoculated with 1 × 102 to 5 × 104 sporulated oocysts of E. kongi before challenge 14 days post inoculation. E. kongi was moderately pathogenic and induced good immunity against re-infection. All inoculated doses results in reduced food intake and body weight gain, and an inoculation oocyst dose of 1 × 103 or higher caused various degrees of diarrhea. Except for one death of the highest dose group, all rabbits recovered 12 days post inoculation. An inoculation dose of 1 × 103 or 1 × 104 oocysts conferred the most effective protection from re-infection, which reduced oocyst output by approximately 99% and maintained body weight gain. Four generations of schizogony were observed, and the endogenous development mainly occurred in the jejunum and ileum of rabbits. E. kongi was most sensitive to sulfachloropyrazine sodium, followed by decoquinate; it is resistant to diclazuril. Both decoquinate and sulfachloropyrazine sodium may be effective in the control of E. kongi infection.

13.
Food Chem ; 410: 135433, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36640658

RESUMEN

Homogeneous and secondary nuclei (HN and SN) are aggregates formed at different stages of whey protein isolate (WPI) self-assembly. More fibrils can form when HN/SN are added as nuclei than when WPI self-assembles. We evaluated the effect of hydrolysis treatment on fibril-induction ability of nuclei derived from WPI, and investigated the relationship between induction ability and nuclear structure. Hydrolyzed SN-induced 9.47% more WPI fibrils than unhydrolyzed SN-induced. Infrared spectroscopy, X-ray diffraction analysis, and atomic force microscopy were used to examine the structural changes in hydrolyzed nuclei and the fibrils induced using these nuclei. We concluded that hydrolysis treatment led to a looser inter-ß-sheet packaging in nuclei by increasing the inter-ß-sheet distance. The inter-ß-sheet distance of cross-ß structure was a key determinant of fibril-induction ability of nuclei, which could be enhanced when inter-ß-sheet structure was moderately loose. This research may provide a theoretical basis for the mechanism of nuclei-induced WPI fibrillation.


Asunto(s)
Amiloide , Proteína de Suero de Leche/química , Hidrólisis , Amiloide/química , Microscopía de Fuerza Atómica
14.
Appl Environ Microbiol ; 89(1): e0181522, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36533927

RESUMEN

Unravelling the structure-function variation of phycospheric microorganisms and its ecological correlation with harmful macroalgal blooms (HMBs) is a challenging research topic that remains unclear in the natural dynamic process of HMBs. During the world's largest green tide bloom, causative macroalgae Ulva prolifera experienced dramatic changes in growth state and environmental conditions, providing ideal scenarios for this investment. Here, we assess the phycospheric physicochemical characteristics, the algal host's biology, the phycospheric bacterial constitutive patterns, and the functional potential during the U. prolifera green tide. Our results indicated that (i) variation in the phycosphere nutrient structure was closely related to the growth state of U. prolifera; (ii) stochastic processes govern phycospheric bacterial assembly, and the contribution of deterministic processes to assembly varied among phycospheric seawater bacteria and epiphytic bacteria; (iii) phycospheric seawater bacteria and epiphytic bacteria exhibited significant heterogeneity variation patterns in community composition, structure, and metabolic potential; and (iv) phycospheric bacteria with carbon or nitrogen metabolic functions potentially influenced the nutrient utilization of U. prolifera. Furthermore, the keystone genera play a decisive role in the structure-function covariation of phycospheric bacterial communities. Our study reveals complex interactions and linkages among environment-algae-bacterial communities which existed in the macroalgal phycosphere and highlights the fact that phycospheric microorganisms are closely related to the fate of the HMBs represented by the green tide. IMPORTANCE Harmful macroalgal blooms represented by green tides have become a worldwide marine ecological problem. Unraveling the structure-function variation of phycospheric microorganisms and their ecological correlation with HMBs is challenging. This issue is still unclear in the natural dynamics of HMBs. Here, we revealed the complex interactions and linkages among environment-algae-bacterial communities in the phycosphere of the green macroalgae Ulva prolifera, which causes the world's largest green tides. Our study provides new ideas to increase our understanding of the variation patterns of macroalgal phycospheric bacterial communities and the formation mechanisms and ecological effects of green tides and highlights the importance of phycospheric microorganisms as a robust tool to help understand the fate of HMBs.


Asunto(s)
Algas Marinas , Ulva , Eutrofización , Agua de Mar/química , Bacterias/genética , China
15.
Carbohydr Polym ; 300: 120290, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36372497

RESUMEN

In this paper, amphiphilic chitosan and carboxymethyl modified gellan gum were synthesized to develop an active edible fresh-keeping material. The optimal weight ratio of CMCS-g-CA/CMGG was determined as 5:2 through the characterization of Fourier transform infrared (FT-IR), Thermogravimetric analysis (TGA), mechanical and barrier properties of the composite films. In addition, the water vapor permeability and oxygen permeability of CMCS-g-CA/CMGG composite films incorporated with mustard essential oil were all declined, and the antibacterial property of the composite film solutions against E. coli, S. aureus and Bacillus anthracis was distinctly improved with the increase of mustard essential oil (MEO) dosage. Furthermore, the CMCS-g-CA/CMGG + 2.0 µL/mL MEO composite film exhibited an effective preservation on mango fruits during 20 days of storage based on the characterization of surface appearance and quality indexes of fruits. Hence, the multifunctional CMCA-g-CA/CMGG/MEO composite films can be served as a prospective eco-friendly packaging material for fruit preservation.


Asunto(s)
Quitosano , Mangifera , Aceites Volátiles , Aceites Volátiles/farmacología , Staphylococcus aureus , Escherichia coli , Espectroscopía Infrarroja por Transformada de Fourier , Planta de la Mostaza , Estudios Prospectivos , Antibacterianos/farmacología , Permeabilidad , Embalaje de Alimentos
16.
Front Pharmacol ; 13: 970616, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36278223

RESUMEN

Renal ischemia reperfusion injury (IRI) is a leading and common cause of acute kidney injury (AKI), and inflammation is a critical factor in ischemic AKI progression. Calycosin (CAL), a major active component of Radix astragali, has been reported to have anti-inflammatory effect in multiple organs. However, whether CAL can alleviate renal IRI and its mechanism remain uncertain. In the present study, a renal IRI model is established by bilateral renal pedicles occlusion for 35 min in male C57BL/6 mice, and the effect of CAL on renal IRI is measured by serum creatinine and pathohistological assay. Hypoxia/reoxygenation (H/R) stimulated human renal tubular epithelial cells HK-2 were applied to explore the regulatory mechanisms of CAL. Luciferase reporter assay and molecular docking were applied to identify the CAL's target protein and pathway. In the mice with renal IRI, CAL dose dependently alleviated the renal injury and decreased nuclear factor kappa B (NF-κB) mediated inflammatory response. Bioinformatics analysis and experiments showed that early growth response 1 (EGR1) increased in mice with renal IRI and promoted NF-κB mediated inflammatory processes, and CAL dose-dependably reduced EGR1. Through JASPAR database and luciferase reporter assay, peroxisome proliferator-activated receptor γ (PPARγ) was predicted to be a transcription factor of EGR1 and repressed the expression of EGR1 in renal tubular epithelial cells. CAL could increase PPARγ in a dose dependent manner in mice with renal IRI and molecular docking predicted CAL could bind stably to PPARγ. In HK-2 cells after H/R, CAL increased PPARγ, decreased EGR1, and inhibited NF-κB mediated inflammatory response. However, PPARγ knockdown by siRNA transfection abrogated the anti-inflammation therapeutic effect of CAL. CAL produced a protective effect on renal IRI by attenuating NF-κB mediated inflammatory response via PPARγ/EGR1 pathway.

17.
Sci Rep ; 12(1): 13813, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35970918

RESUMEN

At present, there are few clinical studies on the application of high-concentration sodium chloride solutions in intracavitary ECG-guided catheter tip localization during the arm infusion port implantation. This study observed the effects of sodium chloride solutions with different concentrations on intracavitary ECG-guided arm infusion port implantation in the patients with cancer. The 657 patients receiving arm infusion port implantation in our hospital between January 2020 and August 2021 were randomly divided into 0.9% sodium chloride solution conduction group (group A), 5.45% sodium chloride solution conduction group (group B) and 10% sodium chloride solution conduction group (group C). The derived rate of stable intracavitary ECG, the occurrence rate of characteristic P wave, the time used for catheter tip localization and the optimal position rate of catheter tip were compared between the three groups. The derived rate of stable intracavitary ECG was significantly higher in the group B (97.78%) and group C (98.63%) than in the group A (93.90%) (all P < 0.05). The occurrence rate of characteristic P wave was also significantly higher in the group B (96.89%) and group C (97.72%) than in the group A (88.73%) (all P < 0.001). The time used for catheter tip localization was significantly shorter in the group B [(49.73 ± 8.15) s] and group C [(48.27 ± 8.61) s] than in the group A [(69.37 ± 19.99) s] (all P < 0.001). There was no significant difference in the optimal position rate of catheter tip among the three groups (P > 0.05). The 5.45% and 10% sodium chloride solutions are significantly superior comparing with 0.9% sodium chloride solution in the derived rate of stable intracavitary ECG, occurrence rate of characteristic P wave and time used for catheter tip localization, but there were no significant differences between 5.45 and 10% sodium chloride solutions. Moreover, the 5.45% sodium chloride solution is closer to physiological state comparing with 10% sodium chloride solution, so the 5.45% sodium chloride solution may be recommended for the intracavitary ECG-guided arm infusion port implantation.


Asunto(s)
Neoplasias , Cloruro de Sodio , Brazo , Electrocardiografía , Frecuencia Cardíaca , Humanos
18.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(4): 400-406, 2022 Apr.
Artículo en Chino | MEDLINE | ID: mdl-35692206

RESUMEN

OBJECTIVE: To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI). METHODS: (1) In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). (2) In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 µmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. RESULTS: (1) The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. (2) The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1ß mRNA (2-ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2-ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2-ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1ß mRNA (2-ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2-ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1ß mRNA(2-ΔΔCT): 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2-ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2-ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1ß mRNA (2-ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2-ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2-ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. CONCLUSIONS: Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.


Asunto(s)
Lesión Renal Aguda , Sepsis , Tumor de Wilms , Lesión Renal Aguda/inducido químicamente , Animales , Apigenina , Factor de Crecimiento del Tejido Conjuntivo , Proteína 61 Rica en Cisteína/genética , Glucuronatos , Riñón/metabolismo , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , ARN Mensajero , ARN Interferente Pequeño , Sepsis/patología , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Tumor de Wilms/patología
19.
Front Pharmacol ; 13: 862584, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35721209

RESUMEN

Background: Acute kidney injury (AKI) is a common syndrome impacting about 13.3 million patients per year. Tilianin has been reported to alleviate myocardial ischemia/reperfusion (I/R) injury, while its effect on AKI is unknown; thus, this study aimed to explore if tilianin protects I/R-induced AKI and the underlying mechanisms. Methods: The microarray dataset GSE52004 was downloaded from GEO DataSets (Gene Expression Omnibus). Differential expression analysis and gene-set enrichment analysis (GSEA) were performed by R software to identify apoptosis pathway-related genes. Then, RcisTarget was applied to identify the transcription factor (TF) related to apoptosis. The STRING database was used to construct a protein-protein interaction (PPI) network. Cytoscape software visualized PPI networks, and hub TFs were selected via cytoHubba. AutoDock was used for molecular docking of tilianin and hub gene-encoded proteins. The expression levels of hub genes were assayed and visualized by quantitative real-time PCR, Western blotting, and immunohistochemistry by establishing I/R-induced AKI mouse models. Results: Bioinformatics analysis showed that 34 genes, including FOS, ATF4, and Gadd45g, were involved in the apoptosis pathway. In total, seven hub TFs might play important roles in tilianin-regulating apoptosis pathways. In in vivo, tilianin improved kidney function and reduced the number of TUNEL-positive renal tubular epithelial cells (RTECs) after I/R-induced AKI. Tilianin reduced the activation of the ERK pathway and then downregulated the expression of EGR1. This further ameliorated the expression of anti-apoptotic genes such as BCL2L1 and BCL2, reduced pro-apoptotic genes such as BAD, BAX, and caspase-3, and reduced the release of cytochrome c. Conclusion: Tilianin reduced apoptosis after I/R-induced AKI by the ERK/EGR1/BCL2L1 pathway. Our findings provided novel insights for the first time into the protective effect and underlying molecular mechanisms of tilianin on I/R-induced AKI.

20.
Nephrology (Carlton) ; 27(8): 690-700, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35638402

RESUMEN

BACKGROUND: Acute kidney injury (AKI) results in high morbidity and mortality among inpatients, while effective treatment and intervention are still absent. Therefore, this study aims to explore the effects of Scutellarin (Scu) in experimental models in vivo and in vitro. METHODS: In vivo experiment, we employed a total of 30 Wistar rats, which further were modelled by a bilateral renal pedicle clip for 45 min, then received 50 mg/kg/day Scu. In vitro, HK-2 cells were administered with 20µΜ Scu and then incubated in hypoxia/reoxygenation (H/R) conditions for 24 h. The knockdown of Nrf2 expression was conducted by small interfering RNA (siRNA) transfection. RESULTS: As a result, the AKI model was well established with an increased SCr, BUN, KIM-1 level, and histological injury score, while Scu treatment reduced the levels above and increased the antioxidative enzyme HO-1. H/R induced an increase of ROS in HK-2 cells, while Scu decreased the ROS level. Bioinformatics results showed the transcription factor Nrf2 was a hub protein during the AKI, which also bound to Scu with low binding energy, indicating that the downstream effect of Scu might be mediated by Nrf2. To verify the suppose above, we employed siRNA against Nrf2, which shows a significant increase in ROS after Nrf2 was blocked. Meanwhile, the HO-1 showed similar expression compared with the 'H/R + Nrf2 siRNA' and 'H/R + Nrf2 siRNA + Scu' group, implying the protective effect of Scu was mediated by the Nrf2/HO-1 pathway. CONCLUSION: Scu led to up-regulation of HO-1 through activating the Nrf2 signalling pathway, protecting the kidneys from ischemia/reperfusion (I/R)-induced oxidative damage.


Asunto(s)
Lesión Renal Aguda , Daño por Reperfusión , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/prevención & control , Animales , Apigenina , Apoptosis , Glucuronatos , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Riñón/patología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/farmacología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/patología
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