RATIONALE AND OBJECTIVESThis study investigates the potential of quantitative Contrast-Enhanced Ultrasound (CEUS) parameters to distinguish between graft dysfunction due to rejection and non-rejection in kidney transplant recipients.METHODSIn this retrospective study, 50 kidney transplant patients who presented elevated serum creatinine or proteinuria were analyzed. They were categorized as rejection or non-rejection based on biopsy outcomes. These classifications were applied in both derivation (n = 33) and validation cohorts (n = 17). Prior to the biopsy, all patients underwent a CEUS. Quantitative parameters derived from the CEUS were further analyzed for their consistency and reliability. Additionally, the relationship between the Banff scores, a standard for diagnosing transplant rejections, and these CEUS parameters was explored.RESULTSSignificant differences between rejection and non-rejection groups were observed in the CEUS parameters of derivation cohorts. Specifically, Peak Intensity (PI), 1/2 Descending Time (DT/2), Area Under Curve (AUC), and Mean Transit Time (MTT) stood out. Sensitivity and specificity for these parameters were 76.5% and 87.5% for PI, 76.5% and 81.2% for DT/2, 76.5% and 87.5% for AUC, and 68.8% and 94.1% for MTT, respectively. DT/2 and MTT showed superior interobserver agreement compared to PI and AUC. When extrapolating the cutoff values from the derivation cohort to the validation group, DT/2 and AUC exhibited optimal diagnostic precision with positive and negative predictive values being 91.7% vs. 100% and 100% vs. 85.7%, respectively. Additionally, DT/2 effectively differentiated between mild and moderate to severe microvascular inflammation, pivotal in diagnosing antibody-mediated renal transplant rejection.CONCLUSIONDT/2 from CEUS parameters presents as a reliable tool to differentiate rejection from non-rejection causes in renal transplant dysfunction. Yet, large-scale, multi-center studies are essential for further validation.

2023-11-01·The ISME Journal

Two-tiered mutualism improves survival and competitiveness of cross-feeding soil bacteria

Article

作者: Dai, Jun ; Xie, Wan-Ying ; Zhao, Fang-Jie ; Huang, Ke ; Johnson, David R ; Ge, Zhan-Biao ; Wang, Peng ; Zhai, Zhi-Qiang

AbstractMetabolic cross-feeding is a pervasive microbial interaction type that affects community stability and functioning and directs carbon and energy flows. The mechanisms that underlie these interactions and their association with metal/metalloid biogeochemistry, however, remain poorly understood. Here, we identified two soil bacteria, Bacillus sp. BP-3 and Delftia sp. DT-2, that engage in a two-tiered mutualism. Strain BP-3 has low utilization ability of pyruvic acid while strain DT-2 lacks hexokinase, lacks a phosphotransferase system, and is defective in glucose utilization. When strain BP-3 is grown in isolation with glucose, it releases pyruvic acid to the environment resulting in acidification and eventual self-killing. However, when strain BP-3 is grown together with strain DT-2, strain DT-2 utilizes the released pyruvic acid to meet its energy requirements, consequently rescuing strain BP-3 from pyruvic acid-induced growth inhibition. The two bacteria further enhance their collective competitiveness against other microbes by using arsenic as a weapon. Strain DT-2 reduces relatively non-toxic methylarsenate [MAs(V)] to highly toxic methylarsenite [MAs(III)], which kills or suppresses competitors, while strain BP-3 detoxifies MAs(III) by methylation to non-toxic dimethylarsenate [DMAs(V)]. These two arsenic transformations are enhanced when strains DT-2 and BP-3 are grown together. The two strains, along with their close relatives, widely co-occur in soils and their abundances increase with the soil arsenic concentration. Our results reveal that these bacterial types employ a two-tiered mutualism to ensure their collective metabolic activity and maintain their ecological competitive against other soil microbes. These findings shed light on the intricateness of bacterial interactions and their roles in ecosystem functioning.

2020-03-01·Cardiovascular Research1区 · 医学

Levosimendan prevents doxorubicin-induced cardiotoxicity in time- and dose-dependent manner: implications for inotropy

1区 · 医学

Article

作者: Sigala, Fragiska ; Efentakis, Panagiotis ; Papapetropoulos, Andreas ; Iliodromitis, Efstathios K ; Klinakis, Apostolos ; Davos, Costantinos H ; Suter, Thomas ; Wenzel, Philip ; Farmakis, Dimitrios ; Cokkinos, Dennis V ; Chavdoula, Evangelia ; Kostomitsopoulos, Nikolaos ; Tasouli, Androniki ; Gioti, Katerina ; Andreadou, Ioanna ; Sanoudou, Despina ; Tenta, Roxane ; Varela, Aimilia

AbstractAimsLevosimendan (LEVO) a clinically-used inodilator, exerts multifaceted cardioprotective effects. Case-studies indicate protection against doxorubicin (DXR)-induced cardiotoxicity, but this effect remains obscure. We investigated the effect and mechanism of different regimens of levosimendan on sub-chronic and chronic doxorubicin cardiotoxicity.Methods and resultsBased on preliminary in vivo experiments, rats serving as a sub-chronic model of doxorubicin-cardiotoxicity and were divided into: Control (N/S-0.9%), DXR (18 mg/kg-cumulative), DXR+LEVO (LEVO, 24 μg/kg-cumulative), and DXR+LEVO (acute) (LEVO, 24 μg/kg-bolus) for 14 days. Protein kinase-B (Akt), endothelial nitric oxide synthase (eNOS), and protein kinase-A and G (PKA/PKG) pathways emerged as contributors to the cardioprotection, converging onto phospholamban (PLN). To verify the contribution of PLN, phospholamban knockout (PLN−/−) mice were assigned to PLN−/−/Control (N/S-0.9%), PLN−/−/DXR (18 mg/kg), and PLN−/−/DXR+LEVO (ac) for 14 days. Furthermore, female breast cancer-bearing (BC) mice were divided into: Control (normal saline 0.9%, N/S 0.9%), DXR (18 mg/kg), LEVO, and DXR+LEVO (LEVO, 24 μg/kg-bolus) for 28 days. Echocardiography was performed in all protocols. To elucidate levosimendan’s cardioprotective mechanism, primary cardiomyocytes were treated with doxorubicin or/and levosimendan and with N omega-nitro-L-arginine methyl ester (L-NAME), DT-2, and H-89 (eNOS, PKG, and PKA inhibitors, respectively); cardiomyocyte-toxicity was assessed. Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN−/− mice. Levosimendan’s cardioprotection was also evident in the BC model. Finally, in vitro PKA inhibition abrogated levosimendan-mediated cardioprotection, indicating that its cardioprotection is cAMP-PKA dependent, while levosimendan preponderated over milrinone and dobutamine, by ameliorating calcium overload.ConclusionSingle dose levosimendan prevented doxorubicin cardiotoxicity through a cAMP-PKA-PLN pathway, highlighting the role of inotropy in doxorubicin cardiotoxicity.

100 项与 DT-02 相关的药物交易

登录后查看更多信息