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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

SAA1 is transcriptionally activated by STAT3 and accelerates renal interstitial fibrosis by inducing endoplasmic reticulum stress

Renal interstitial fibrosis (RIF) is the common irreversible pathway by which chronic kidney disease (CKD) progresses to the end stage. The transforming growth factor-β (TGF-β)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a common factor leading to inflammation-mediated RIF, but its downstream regulatory mechanism is still unclear. Bioinformatics analysis predicted that serum amyloid A protein 1 (SAA1) was one of the target genes for transcriptional activation of STAT3 signaling. As an acute phase reaction protein, SAA1 plays an important role in many inflammatory reactions, and research has suggested that SAA1 is significantly elevated in the serum of patients with CKD. In this research, multiple experiments were performed to investigate the role of SAA1 in the process of RIF. SAA1 was abnormally highly expressed in kidney tissue from individuals who underwent unilateral ureteral obstruction (UUO) and TGF-β-induced HK2 cells, and the abnormal expression was directly related to the transcriptional activation of STAT3. Additionally, SAA1 can directly target and bind valosin-containing protein (VCP)-interacting membrane selenoprotein (VIMP) to inhibit the function of the Derlin-1/VCP/VIMP complex, preventing the transportation and degradation of the misfolded protein, resulting in endoplasmic reticulum (ER) stress characterized by an increase in glucose-regulated protein 78 (GRP78) levels and ultimately promoting the occurrence and development of RIF.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further.

36 MATERIALS SCIENCE↗
DOE OSTI2023

High flux novel polymeric membrane for renal applications

Biocompatibility and the ability to mediate the appropriate flux of ions, urea, and uremic toxins between blood and dialysate components are key parameters for membranes used in dialysis. Oxone-mediated TEMPO-oxidized cellulose nanomaterials have been demonstrated to be excellent additives in the production and tunability of ultrafiltration and dialysis membranes. In the present study, nanocellulose ionic liquid membranes (NC-ILMs) were tested in vitro and ex vivo. An increase in flux of up to two orders of magnitude was observed with increased rejection (about 99.6%) of key proteins compared to that of polysulfone (PSf) and other commercial membranes. NC-ILMs have a sharper molecular weight cut-off than other phase inversion polymeric membranes, allowing for high throughput of urea and a uremic toxin surrogate and limited passage of proteins in dialysis applications. Superior anti-fouling properties were also observed for the NC-ILMs, including a > 5-h operation time with no systemic anticoagulation in blood samples. Finally, NC-ILMs were found to be biocompatible in rat ultrafiltration and dialysis experiments, indicating their potential clinical utility in dialysis and other blood filtration applications. These superior properties may allow for a new class of membranes for use in a wide variety of industrial applications, including the treatment of patients suffering from renal disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivity in vitro

Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing two human ccRCC cell lines resistant to sunitinib. Consistent with the literature, sunitinib-resistant ccRCC cell lines presented an aberrant overexpression of Axl and PD-L1, as well as a metabolic rewiring characterized by enhanced OXPHOS and glutamine metabolism. Therapeutic challenges of sunitinib-resistant ccRCC cell lines in vitro using small molecule inhibitors targeting Axl, AMPK and p38, as well as using PD-L1 blocking therapeutic antibodies, showed limited CTL-mediated cytotoxicity in a co-culture model. However, the AMPK activator metformin appears to sensitize the effect of PD-L1 blocking therapeutic antibodies and to enhance CTLs’ cytotoxic effects on ccRCC cells. These effects were not broadly observed with the Axl and the p38 inhibitors. Taken together, these data suggest that targeting certain pathways aberrantly activated by sunitinib resistance such as the AMPK/PDL1 axis might sensitize ccRCC to immunotherapies as a second-line therapeutic approach.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

High levels of exfoliated fragments following glycocalyx destruction in hemorrhagic fever with the renal syndrome are associated with mortality risk

Background The glycocalyx is a gel-like structure that covers the luminal side of vascular endothelial cells. It plays an important role in maintaining the integrity of the vascular endothelial barrier structure. However, the presence or absence of glycocalyx destruction in hemorrhagic fever with renal syndrome (HFRS) and its specific mechanism and role is still unclear. Methods In this study, we detected the levels of exfoliated glycocalyx fragments, namely, heparan sulfate (HS), hyaluronic acid (HA), and chondroitin sulfate (CS), in HFRS patients and investigated their clinical application value on the evaluation of disease severity and prognosis prediction. Results The expression of exfoliated glycocalyx fragments in plasma was significantly increased during the acute stage of HFRS. The levels of HS, HA, and CS in HFRS patients during the acute stage were significantly higher than in healthy controls and convalescent stages of the same type. HS and CS during the acute stage gradually increased with the aggravation of HFRS, and both fragments showed a significant association with disease severity. In addition, exfoliated glycocalyx fragments (especially HS and CS) showed a significant correlation with conventional laboratory parameters and hospitalization days. High levels of HS and CS during the acute phase were significantly associated with patient mortality and demonstrated an obvious predictive value for the mortality risk of HFRS. Conclusion Glycocalyx destruction and shedding may be closely associated with endothelial hyperpermeability and microvascular leakage in HFRS. The dynamic detection of the exfoliated glycocalyx fragments may be beneficial for the evaluation of disease severity and prognosis prediction in HFRS.

Du, Hong↗
NASA NTRS1971

Hypothalamic stimulation and baroceptor reflex interaction on renal nerve activity.

The basal level of mean renal nerve activity (MRNA-0) measured in anesthetized cats was found to be modified by the additive interaction of hypothalamic and baroceptor reflex influences. Data were collected with the four major baroceptor nerves either intact or cut, and with mean aortic pressure (MAP) either clamped with a reservoir or raised with l-epinephrine. With intact baroceptor nerves, MRNA stayed essentially constant at level MRNA-0 for MAP below an initial pressure P1, and fell approximately linearly to zero as MAP was raised to P2. Cutting the baroceptor nerves kept MRNA at MRNA-0 (assumed to represent basal central neural output) independent of MAP. The addition of hypothalamic stimulation produced nearly constant increments in MRNA for all pressure levels up to P2, with complete inhibition at some level above P2. The increments in MRNA depended on frequency and location of the stimulus. A piecewise linear model describes MRNA as a linear combination of hypothalamic, basal central neural, and baroceptor reflex activity.

Wilson, M. F.↗
NASA NTRS1974

Ultrasonic Doppler measurement of renal artery blood flow

Implantable pulsed Doppler ultrasonic flowmeter development has resulted in designs for application to the aortas of dogs and humans, and to human renal and coronary arteries. A figure of merit was derived for each design, indicating the degree of its precision. An H-array design for transcutaneous observation of blood flow was developed and tested in vitro. Two other simplified designs for the same purpose obviate the need to determine vessel orientation. One of these will be developed in the next time period. Techniques for intraoperative use and for implantation have had mixed success. While satisfactory on large vessels, higher ultrasonic frequencies and alteration of transducer design are required for satisfactory operation of pulsed Doppler flowmeters with small vessels.

Source record↗
NASA NTRS1974

Effects of an anti-G suit on the hemodynamic and renal responses to positive /+Gz/ acceleration

The effects of the currently used U.S. Air Force (CSU-12/P) anti-G suit on renal function during positive radial acceleration (+Gz) were assessed in seven normal male subjects in balance on a 200 meq sodium diet. Following suit inflation in the seated position, +2.0 Gz for 30 min resulted in a decrease in the rate of sodium excretion from 125 plus or minus 19 to 60 plus or minus 14 microeq/min, which persisted during a 25-min recovery period. Fractional excretion of sodium also decreased significantly during +Gz. The magnitude of the antinatriuresis was indistinguishable from that observed during +Gz without suit inflation. In contrast to the antinatriuresis observed during centrifugation without suit, however, the antinatriuresis with suit was mediated primarily by an enhanced tubular reabsorption of sodium.

Shubrooks, S. J., Jr.↗
NASA NTRS1974

Changes in mesenteric, renal, and aortic flows with +Gx acceleration

Previous studies in man and dogs have indicated that the splanchnic bed might contribute to the maintenance of arterial pressure during +Gx acceleration. Eight mongrel dogs were chronically instrumented with Doppler flow probes around the superior mesenteric (SMA) and renal arteries (RA) as well as the terminal aorta (TA). A solid-state pressure transducer was placed in the aorta distal to the flow probe. Using alpha-chloralose anesthesia following a 2-4 week recovery period, the animals were subjected to 120 sec at levels of 5, 10 and 15 +Gx acceleration on a 7.6-m radius centrifuge. The results indicate that both an active component and a mechanical component contribute to the maintenance of arterial pressure during +Gx acceleration.

Stone, H. L.↗
NASA NTRS1975

Ultrasonic Doppler measurement of renal artery blood flow

An extensive evaluation of the practical and theoretical limitations encountered in the use of totally implantable CW Doppler flowmeters is provided. Theoretical analyses, computer models, in-vitro and in-vivo calibration studies describe the sources and magnitudes of potential errors in the measurement of blood flow through the renal artery, as well as larger vessels in the circulatory system. The evaluation of new flowmeter/transducer systems and their use in physiological investigations is reported.

Freund, W. R.↗