Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, although AKI has been recognized as a disease with long-term sequelae, partly because of the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including the transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively, by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2950 phosphosites through multi-proteomics analyses. Among them, we identified an array of highly promising candidate marker proteins indicative of disease onset and progression accompanied by immunoblot validations, and further denoted the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.

Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for primary cultured glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

Jake Arrieta on Thursday offered an unexpected explanation for his second-half struggles in 2018: he pitched much of last season with an injured left knee.

The Oilers look to claw themselves up above .500 against the team that started their memorable turnaround last season.

Buffalo’s leading scorer did not return for the third period of the 7-5 loss to Montreal

Tennessee won easily over Mississippi State. Indiana and BYU won nail-biters. So why did they jump over the Vols? We asked the CFP committee chair.

Early in the second half, Ohio State freshman Jaloni Cambridge went down with an apparent lower-back injury.

Sharon G. Kujawa
Nov 11, 2009; 29:14077-14085
BehavioralSystemsCognitive

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function.

Canadian swingman RJ Barrett was upgraded to day-to-day and engaged in non-contact practise on Monday, two days before Toronto hosts the Cleveland Cavaliers at Scotiabank Arena.

In a survey of educators in an urban Midwest district, 4 in 5 said the witnessed other staff doing things that were morally wrong, while almost half said they themselves had acted in a way that betrayed their values.

Broken bones, head injuries and temporary or permanent disabilities can result from falls. The Delaware Coalition for Injury Prevention’s Falls Prevention Team encourages Delawareans to prevent such mishaps. Governor John Carney and Lieutenant Governor Bethany Hall-Long proclaimed September 18-22, 2023 as Falls Prevention Awareness Week in accordance with the nationally recognized observance. “It’s important that we […]

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Category: Health News
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BACKGROUD:Lung volume measurements are important for monitoring functional aeration and recruitment and may help guide adjustments in ventilator settings. The expiratory phase of airway pressure release ventilation (APRV) may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (expiratory time [TE]). We hypothesized that expiratory flow would correlate with estimated lung volume (ELV) as measured using a modified nitrogen washout/washin technique in a large-animal lung injury model.METHODS:Eight pigs (35.2 ± 1.0 kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration, which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15 mm Hg in normal and injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC INview tool. The expiratory flow-time slope and TE were measured from the expiratory flow profile.RESULTS:Lung elastance increased with induced lung injury from 29.3 ± 7.3 cm H2O/L to 39.9 ± 15.1cm H2O/L, and chest wall elastance increased with increasing intra-abdominal pressures (IAPs) from 15.3 ± 4.1 cm H2O/L to 25.7 ± 10.0 cm H2O/L in the normal lung and 15.8 ± 6.0 cm H2O/L to 33.0 ± 6.2 cm H2O/L in the injured lung (P = .39). ELV decreased from 1.90 ± 0.83 L in the injured lung to 0.67 ± 0.10 L by increasing IAP to 15 mm Hg. This had a significant correlation with a TE decrease from 2.3 ± 0.8 s to 1.0 ± 0.1 s in the injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29 ± 0.06 L/s2 to 0.63 ± 0.05 L/s2 (ρ = 0.78).CONCLUSIONS:Changes in ELV over time, and the TE and flow-time slope, could be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.

In the first quarter of Monday's Dolphins-Rams game, ESPN reported that Tyreek Hill said a torn ligament in his wrist became worst after he was detained by police.

Bollywood star Suniel Shetty sustained a minor injury on the sets of the web series ‘Hunter 2’

Researchers at the Wyss Institute at Harvard University have developed a microfluidic chip that can recreate some of the features of radiation-induced lung injury. The lungs are very sensitive to radiation, and this can limit the application of radiotherapy to treat cancer. Accurately modeling radiation-induced lung injury could assist in developing new methods to prevent […]

Curious about Tim Hardaway Jr.‘s condition following his recent on-court injury? As fans discuss the Detroit Pistons’ nail-biting NBA Cup opener against the Miami Heat, many are also concerned about Hardaway’s recovery and when he might return to the lineup. Here’s a quick look at Tim Hardaway’s injury, recovery, and its impact on the Pistons. […]

The post Pistons’ Tim Hardaway Avoids Serious Injury After Head Collision appeared first on ComingSoon.net - Movie Trailers, TV & Streaming News, and More.

Light therapy administered through the skull was found to accelerate tissue recovery following mild traumatic brain injury (mTBI) (!--ref1--). Their

Stem cell therapy emerges as a viable and safe choice for individuals grappling with challenging traumatic medlinkspinal cord injuries/medlink, said experts (!--ref1--).

The eagerly anticipated cage match between Elon Musk and Mark Zuckerberg might face delays, as the Meta founder sustained an injury during his training and recently underwent surgery.

Growing pains are common in developing medlinkchildren/medlink, but irregular growth can sometimes lead to injuries. A new study highlights that a

The incident involving Rashid Khan and Rahmanullah Gurbaz occurred during the third ODI between Afghanistan and Bangladesh at Sharjah Cricket Stadium on Monday, November 11.

Trauma surgeon Annie Onishi is back with WIRED, this time to go over the Home Alone films (you know, the ones that MATTER). Annie breaks down every injury from the first two films, explaining what would happen if Harry and Marv actually experienced the physical trauma that they sustain in the films.

Dr. J. Mack Slaughter takes to Twitter to answer the internet's burning questions about injuries. What happens if you break a bone and don't set it? How can you tell if you've dislocated your shoulder? Why do shin splints hurt so much? Is it OK to treat a dog bite at home? Is an Achilles tendon tear the worst injury in sports? Dr. Slaughter answers all these questions and much more! Director: Justin Wolfson Director of Photography: Barry Bowden Editor: Richard Trammell Expert: Dr. J. Mack Slaughter Line Producer: Joseph Buscemi Associate Producer: Brandon White Production Manager: Eric Martinez Casting Producer: Nicole Ford Assistant Camera: Dayton Thomason Audio: Marcos Garcia Post Production Supervisor: Nicholas Ascanio Post Production Coordinator: Ian Bryant Supervising Editor: Doug Larsen Assistant Editor: Andy Morell

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