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Background: Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed. Results: High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman's capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function. Conclusions: β-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury. [ABSTRACT FROM AUTHOR]

Aim: Cisplatin is a highly effective anti‐cancer agent, but its clinical use is restricted due to severe renal toxicity. This study aimed to investigate the alleviative effects of juzentaihoto (JTT) in a mouse model of cisplatin‐induced renal injury. Methods: Four groups of seven‐week‐old male C57BL/6J mice (control, JTT, cisplatin, and JTT + cisplatin groups) were used in the study. The JTT and JTT + cisplatin groups received oral JTT (500 mg/kg) once a day for three days. After 24 h, the cisplatin, and JTT + cisplatin groups were intraperitoneally injected with cisplatin (15 mg/kg). The mice in each group were euthanized 72 h after cisplatin administration, and blood and kidney samples were collected. Results: Cisplatin injection decreased body weight and elevated plasma blood urea nitrogen and creatinine levels, while also increasing renal oxidative stress, inflammation, and cell death. These changes were alleviated by JTT administration. We also found that platinum accumulation in the kidneys following cisplatin injection was attenuated by JTT treatment. Furthermore, Mate1 expression levels (a cisplatin efflux transporter) were upregulated by JTT injection. Conclusion: Our results demonstrated that JTT mitigated cisplatin‐induced renal injury in mice by alleviating oxidative stress, inflammation, and cell death, achieved through the upregulation of the cisplatin efflux transporter Mate1. [ABSTRACT FROM AUTHOR]

Drug-induced kidney injury (DIKI) is a frequently reported adverse event, associated with acute kidney injury, chronic kidney disease, and end-stage renal failure. Prospective cohort studies on acute injuries suggest a frequency of around 14%–26% in adult populations and a significant concern in pediatrics with a frequency of 16% being attributed to a drug. In drug discovery and development, renal injury accounts for 8 and 9% of preclinical and clinical failures, respectively, impacting multiple therapeutic areas. Currently, the standard biomarkers for identifying DIKI are serum creatinine and blood urea nitrogen. However, both markers lack the sensitivity and specificity to detect nephrotoxicity prior to a significant loss of renal function. Consequently, there is a pressing need for the development of alternative methods to reliably predict drug-induced kidney injury (DIKI) in early drug discovery. In this article, we discuss various aspects of DIKI and how it is assessed in preclinical models and in the clinical setting, including the challenges posed by translating animal data to humans. We then examine the urinary biomarkers accepted by both the US Food and Drug Administration (FDA) and the European Medicines Agency for monitoring DIKI in preclinical studies and on a case-by-case basis in clinical trials. We also review new approach methodologies (NAMs) and how they may assist in developing novel biomarkers for DIKI that can be used earlier in drug discovery and development. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective: To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods: Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results: All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion: The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy. Case presentation: We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient's renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable. Conclusions: This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency. [ABSTRACT FROM AUTHOR]

Objective To investigate the serum levels of homocysteine(HCY)and cystatin C(Cys-C)in patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)associated renal injury, and to explore the diagnostic value of combined detection of HCY and Cys-C in ANCA-associated renal injury. Methods We selected 70 ANCA-positive patients with renal injury admitted to the Department of Nephrology in our hospital from January 2016 to January 2019. Another 48 patients with ANCA-positive but not complicated with renal injury were in simple ANCA positive group while 50 patients with physical examination who came to the hospital during the same period were in control group. Healthy patients served as the control group. By comparing the differences in the test results of different groups, the area under the curve(AUC)of each test index for ANCA-positive renal injury was determined, and the correlation and diagnostic value of combined detection of HCY and Cys-C for ANCA-related renal injury were calculated. Results The levels of HCY and Cys-C in the ANCA positive combined with renal injury group, the pure ANCA positive group, and the control group differed significantly(P<0.05). The positive rates of HCY and Cys-C in the two groups were significantly different(P<0.05). The sensitivity and specificity of HCY and Cys-C in combination for the diagnosis of ANCA-positive related renal injury were significantly higher than those of the above indicators alone(P<0.05). ROC curve results showed that HCY combined with Cys-C had a better diagnosis for patients with positive ANCA and associated renal injury and a higher correlation. Conclusion HCY combined with Cys-C is closely correlated to ANCA-related renal injury, and the combined detection has a positive effect on the diagnosis of patients with ANCA-positive related renal injury, and has guiding value for the treatment of patients. [ABSTRACT FROM AUTHOR]

With recent advances in neonatal intensive care, preterm infants are surviving into adulthood. Nonetheless, epidemiological data on the health status of these preterm infants have begun to reveal a worrying theme; prematurity and the supplemental oxygen therapy these infants receive after birth appear to be risk factors for kidney disease in adulthood, affecting their quality of life. As the incidence of chronic kidney disease and the survival time of preterm infants both increase, the management of the hyperoxia-induced renal disease is becoming increasingly relevant to neonatologists. The mechanism of this increased risk is currently unknown, but prematurity itself and hyperoxia exposure after birth may predispose to disease by altering the normal trajectory of kidney maturation. This article reviews altered renal reactivity due to hyperoxia, the possible mechanisms of renal injury due to hyperoxia, and the role of resveratrol in renal injury. Key Points Premature infants commonly receive supplementary oxygen. Hyperoxia can cause kidney damage via signal pathways. We should reduce the occurrence of late sequelae. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) could lead to renal failure and its morbidity is increasing throughout the world. The activation of AMP-activated protein kinase (AMPK) has been proven to play a protective role in kidneys under diabetic conditions. Objective: The present study aimed to explore the protection of GSK621, an AMPK agonist, on high glucose (HG)-induced renal injury, and to establish the mechanisms underlying these effects. Results: Mouse podocytes (MPC5) were injured by HG stimulation, as revealed by decreased proliferation and increased apoptosis. The intervention of GSK621 significantly protected MPC5 cells from HG-induced damage. Mechanically, GSK621 effectively restored HG-impaired cellular autophagy in MPC5 cells. By using chloroquine (CQ), an autophagy inhibitor, the protection of GSK621 on the cell survival and apoptosis of HG-treated MPC5 cells was blocked. In the streptozotocin-induced DN mice model, GSK621 treatment effectively prevented renal injury as indicated by decreased extracellular matrix deposition and fibrotic lesions in the kidney. GSK621 also decreased urinary protein and albumin, fasting blood glucose, serum creatinine, as well as blood urea nitrogen levels. However, the administration of CQ could curtail these beneficial effects of GSK621. In addition, the autophagy was restored by GSK621 partly via regulating the AMPK/ULK1 pathway in the kidney of the DN mice model. Conclusion: Our findings revealed that GSK621 mitigates HG-induced renal injury by activating autophagy via the AMPK/ULK1 pathway in vitro and in vivo and, therefore, exerts a protective action on DN. GSK621 is a novel potential drug for DN. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed. Results High fructose diet fed rats had increased plasma KIM-1, NGAL (p

In this study, Lactobacillus paracasei FP02, a strain isolated from pickled Chinese cabbage, was tested for its capability to reduce uric acid in vitro, and its physiological and biochemical characteristics were characterized. Furthermore, the effect of this strain on the serum uric acid level of a hyperuricemic (HUA) rat model was explored. The in vitro results showed that L. paracasei FP02 degraded uric acid and its precursor substances, inosine and guanosine, by 29.10%, 67.09%, and 70.48%, respectively, and inhibited xanthine oxidase (XOD) activity by 64.20%. Simultaneously, this strain could ferment various sugars (alcohols) and exhibited good tolerance to gastric acid and bile salts. The 14-day continuous intragastric administration of freeze-dried L. paracasei FP02 powder reduced the serum uric acid concentration by 49.96% compared to the hyperuricemia model group (P < 0.001), which was established by intragastric administration of potassium oxonate combined with high dietary uric acid. After the treatment, the serum uric acid concentration approached the levels observed in the blank control group. Additionally, in the FP02 treatment group, uric acid excretion in the urine increased, and serum XOD activity was significantly inhibited (P < 0.001). Renal sections showed that renal injury was partially restored in the FP02 treatment group. This study will lay the foundation for the development of L. paracasei FP02 as a potential drug or functional food for preventing HUA.

Abstract Background Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Abstract Background Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy. Case presentation We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient’s renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable. Conclusions This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency.

Objective(s): Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways.Materials and Methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group.Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA’s preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism.Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones.

To investigate the preventive effect of aerobic exercise on renal damage caused by obesity. The mice in the Control (Con) and Control + Exercise (Con + Ex) groups received a standard chow diet for the 21-week duration of the study, while the High-fat diet (HFD) group and High-fat diet + Exercise (HFD + Ex) group were fed an HFD. Mice were acclimated to the laboratory for 1 week, given 12 weeks of being on their respective diets, and then the Con + Ex and HFD + Ex groups were subjected to moderate intensity aerobic treadmill running 45 min/day, 5 days/week for 8 weeks. We found that HFD-induced obesity mainly impacts kidney glycerin phospholipids, glycerides, and fatty acyls, and aerobic exercise mainly impacts kidney glycerides, amino acids and organic acids as well as their derivatives. We identified 18 metabolites with significantly altered levels that appear to be involved in aerobic exercise mediated prevention of HFD-induced obesity and renal damage, half of which were amino acids and organic acids and their derivatives. Aerobic exercise rewires kidney metabolites to reduce high-fat diet-induced obesity and renal injury. [ABSTRACT FROM AUTHOR]

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorlycontrolled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocytedamage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluatethe nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore theunderlying mechanism.Materials and Methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) toinduce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, andorgan weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levelswere determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the ratswere sacrificed and their renal tissues were removed for histopathological assessment.Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepaticweights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine(Cr) and, albumin. There was a decrease (P

Abstract Background The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. Results A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3−/−) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. Conclusion Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract Graphical Abstract

Congenital solitary functioning kidney (cSFK) is one of the major causes of chronic kidney disease (CKD) in children. Long-term renal hyperfiltration leads to kidney injury with hypertension, proteinuria and lower estimated glomerular filtration rate (eGFR). Early clinical manifestations of cSFK children are generally insignificant. They are more prone to develop kidney injury then progress to end-stage renal disease. Long-term managements and aggressive interventions should be implemented for better outcomes. The pathogenesis, pathophysiological rationales of renal injury, clinical manifestations and proper managements of cSFK were summarized.

BackgroundThe burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. ObjectiveTo preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. MethodsA mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. ResultsThe mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P0.05), but the renal histopathological injury scores were significantly increased (P0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P

We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of impaired renal function. Data were prospectively collected from patients who underwent PNL from December 2020 to December 2021. The patients were randomized into two groups according to access sheath diameter: Group 1 (22 Fr, n = 44) and Group 2 (28 Fr, n = 44). Relative renal function (RRF) was calculated by technetium-99 m dimercaptosuccinic acid scintigraphy, and glomerular filtration rate (GFR) was calculated by diethylenetriamine pentaacetic acid scintigraphy. A difference of 5% or more in RRF was considered a significant functional change. Preoperative and postoperative Kidney Injury Molecule-1 (KIM-1) levels were measured. Preoperative demographic data and stone characteristics were similar between the groups. There were also no statistically significant differences between the groups in terms of scar development, changes in RRF, GFR, or KIM-1/creatinine (Cr) (p > 0.05). Significant deterioration in RRF was detected in a total of six (6.8%) patients, three in each group. The factors predicting loss of function were analyzed by regrouping the patients without loss of function as Group A (n = 82) and those with loss as Group B (n = 6). Only stone volume was statistically significant in multivariate analysis (p = 0.002). Access sheath diameter had no significant effect on renal function after PNL. However, the stone volume was found to independently correlate to a loss of renal function after PNL. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease. [ABSTRACT FROM AUTHOR]

Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential renal failure. Renal injury and repair processes are accompanied by changes in cellular senescence phenotypes. However, the mechanism is poorly understood. The purpose of this study is to clarify the changes in senescence phenotype at different time points in renal disease caused by UUO and to further investigate whether eliminating senescent cells using the anti-senescence drug ABT263 could attenuate UUO-induced renal disease. Specifically, renal tissues were collected from established UUO rat models on days 1, 2, 7, and 14. The extent of renal tissue injury and fibrosis in rats was assessed using histological examination, serum creatinine, and blood urea nitrogen levels. The apoptotic and proliferative capacities of renal tissues and phenotypic changes in cellular senescence were evaluated. After the intervention of the anti-senescence drug ABT263, the cellular senescence as well as tissue damage changes were re-assessed. We found that before the drug intervention, the UUO rats showed significantly declined renal function, accompanied by renal tubular injury, increased inflammatory response, and oxidative stress, alongside aggravated cellular senescence. Meanwhile, after the treatment with ABT263, the rats had a significantly lower number of senescent cells, attenuated renal tubular injury and apoptosis, enhanced proliferation, reduced oxidative stress and inflammation, improved renal function, and markedly inhibited fibrosis. This suggests that the use of the anti-senescence drug ABT263 to eliminate senescent cells can effectively attenuate UUO-induced renal injury. This highlights the critical role of cellular senescence in the transformation of acute injury into chronic fibrosis. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds in managing CKD and its complications. By examining the existing research, we highlight their diverse biological activities and potential to combat CKD-related issues. We analyze the nutritional benefits, bioavailability, and safety profile of these compounds. While the clinical evidence is promising, preclinical studies offer valuable insights into underlying mechanisms, optimal dosages, and potential side effects. Further research is crucial to validate the therapeutic efficacy of phenolic compounds for CKD. We advocate for continued exploration of their innovative applications in food, pharmaceuticals, and nutraceuticals. This review aims to catalyze the scientific community's efforts to leverage phenolic compounds against CKD-related challenges. [ABSTRACT FROM AUTHOR]

High-fat diets (HFDs) and sedentary lifestyles are associated with obesity, a significant global health issue that affects over 30% of people in industrialized countries. It is associated with metabolic syndrome, type 2 diabetes, high cholesterol levels, and abnormal lipid metabolism. High-fructose diets can lead to type 2 diabetes, insulin resistance, and inflammation in fat tissue. Statins, particularly hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been used to treat obesity and diabetes, but their impact on kidney damage in obese rats is limited. This research aimed to investigate the impact of atorvastatin on renal damage resulting from a high-fat, high-fructose diet (HF-HFrD) in rats. This study involved 24 adult male Sprague Dawley rats, divided into four groups: the control group, the atorvastatin (Ator) group, the high-fat-high-fructose diet (HF-HFr) group, and the high-fat-high-fructose diet with atorvastatin (HF-HFr + Ator) group. Rats were anesthetized, weighed, and sacrificed, and blood was collected from the abdominal aorta and kidneys. Biochemical studies were performed to detect serum urea, creatinine, glucose, insulin, lipid profile, malondialdehyde (MDA) levels, and reduced glutathione (GSH) activity. The histopathological evaluation included H&E, Sirius red staining, NF-κB, and caspase-3 immunohistochemical staining. The HFHFrD group had elevated levels of serum glucose, insulin, HOMA-IR, creatinine, BUN, cholesterol, and triglycerides while showing a reduction in HDL. The renal tissue exhibited increased levels of MDA, decreased levels of GSH, higher collagen accumulation, and increased expression of NF-κB and caspase-3. Atorvastatin therapy effectively improved these alterations in comparison to the HF-HFrD group. In conclusion, atorvastatin improved HF-HFrD-induced renal injury by modulating lipotoxicity, oxidative stress, inflammation, and apoptosis. Atorvastatin may have therapeutic potential for obesity-related kidney damage. [ABSTRACT FROM AUTHOR]

Astaxanthin (ASX), a red pigment belonging to carotenoids, has antioxidant activity and anti-oxidative stress effect. Atrazine (ATZ), a frequently used herbicide, whose degradation products are the cause for nephrosis and other oxidative stress associated diseases. This study was aimed to reveal the potential protective mechanism of astaxanthin against atrazine-induced nephrosis. Atrazine was orally given (250 mg/kg bw) to the mice along with astaxanthin (100 mg/kg bw) for 28 days. Serum biochemical indicators, oxidative stress biomarkers, ATPase activities, ion concentration, histomorphology, and various renal genes expression linked with apoptosis, Nrf2 signaling pathway, and aquaporins (AQPs) were assessed. It was found that serum creatinine (SCr), blood urea nitrogen (BUN), and MDA levels were significantly increased after the treatment of atrazine, whereas serum renal oxidative stress indicators like CAT, GSH, T-AOC, SOD decreased. Renal histopathology showed that atrazine significantly damaged renal tissues. The activities of Ca 2+-Mg 2+-ATPase were increased whereas Na +-K +-ATPase decreased significantly (P  < 0.05). Moreover, results confirmed that the expression of AQPs , Nrf2 , and apoptosis genes were also altered after atrazine administration. Interestingly, astaxanthin supplementation significantly (P  < 0.05) improved atrazine-induced nephrotoxicity via decreasing SCr, BUN, oxidative stress, ionic homeostasis and reversing the changes in AQPs, Nrf2, and apoptosis gene expression. These findings collectively suggested that astaxanthin has strong potential ameliorative impact against atrazine induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

As a resistant hypertension, the pathogenesis of salt-sensitive hypertension is complex. Although mineralocorticoid receptor activation and renal injury play a key role in the development of salt-sensitive hypertension, the specific pathological mechanism is currently unclear. A model of Dahl SS hypertension was established by high-salt diet induction to explore the pathological mechanism of salt-sensitive hypertension and kidney injury. Compared with salt-insensitive SS-13BN rats, long-term high-salt diet caused local activation of sympathetic nerves and renin-angiotensin-aldosterone system (RAAS) in the kidney of Dahl SS rats, which eventually activated mineralocorticoid receptors (MR), resulting in the increased expression of epithelial sodium channels (ENaC), enhanced inflammatory response and oxidative stress, renal fibrosis, and triggered the increased expression of phosphorylated actin (P-Cofilin) and podocin in the kidney, resulting in podocyte damage and ultimately renal injury and hypertension. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) is the most commonly used diagnostic modality for blunt abdominal trauma (BAT), significantly influencing management approaches. Deep learning models (DLMs) have shown great promise in enhancing various aspects of clinical practice. There is limited literature available on the use of DLMs specifically for trauma image evaluation. In this study, we developed a DLM aimed at detecting solid organ injuries to assist medical professionals in rapidly identifying life-threatening injuries. The study enrolled patients from a single trauma center who received abdominal CT scans between 2008 and 2017. Patients with spleen, liver, or kidney injury were categorized as the solid organ injury group, while others were considered negative cases. Only images acquired from the trauma center were enrolled. A subset of images acquired in the last year was designated as the test set, and the remaining images were utilized to train and validate the detection models. The performance of each model was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value based on the best Youden index operating point. The study developed the models using 1302 (87%) scans for training and tested them on 194 (13%) scans. The spleen injury model demonstrated an accuracy of 0.938 and a specificity of 0.952. The accuracy and specificity of the liver injury model were reported as 0.820 and 0.847, respectively. The kidney injury model showed an accuracy of 0.959 and a specificity of 0.989. We developed a DLM that can automate the detection of solid organ injuries by abdominal CT scans with acceptable diagnostic accuracy. It cannot replace the role of clinicians, but we can expect it to be a potential tool to accelerate the process of therapeutic decisions for trauma care. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

OBJECTIVE: To investigate the clinical characteristics of anticoagulant-related nephropathy (ARN) induced by direct oral anticoagulants, so as to provide reference for clinical safe drug use. METHODS: Relevant literature databases at home and abroad (up to Sept. 30th, 2023) were retrieved, case report literature related to ARN induced by direct oral anticoagulants were collected. Patients’ gender, age, medication, comorbidities, occurrence of renal injury were recorded and statistically analyzed. RESULTS: A total of 36 patients were enrolled (3 domestic cases and 33 foreign cases), including 26 cases of dabigatran etexilate, 7 cases of rivaroxaban, and 3 cases of apixaban. There were 23 males and 13 females, the age ranged from 59 to 89 years, with an average age of 75. 75 years. Totally 22 cases had normal renal function and 14 cases had a history of chronic renal disease. Thirty-six patients had comorbidities/ past medical history; 22 cases had drug combination and 14 cases were not mentioned. The time from the use of anticoagulants to occurrence of renal injury was 2 d to 3 years, of which 30 cases had renal injury within 1 year. Renal biopsy was performed in 24 patients. Serum creatinine levels increased in 36 patients, mainly manifested as hematuria (16 cases of gross hematuria, 7 cases of microscopic hematuria), and a few patients showed oliguria (7 cases), anuria (1 case) or proteinuria (10 cases). After the diagnosis of renal injury, 36 patients stopped using direct oral anticoagulants and received different treatments. Among them, 6 patients received idarucizumab ( dabigatran etexilate reversal agent ), 14 patients underwent hemodialysis, 15 patients received glucocorticoid treatment, and 6 patients received intravenous fluid. After drug withdrawal and symptomatic treatment, the renal function of 24 patients was improved or returned to normal, but there were still 6 patients showed no improvement, 3 patients deteriorated, and 3 patients died ( died from other complications). CONCLUSIONS: Clinically, it is necessary to be alert to the occurrence of ARN induced by direct oral anticoagulants, pay close attention to patients’ renal function and clinical manifestations such as hematuria during medication, identify and diagnose as soon as possible, and perform renal biopsy if necessary. Once ARN occurs, symptomatic supportive treatment should be given according to the patients’ condition. [ABSTRACT FROM AUTHOR]

Background: The narrower focal zone (FZ) size of modern lithotripter was considered as one of the factors that resulted in suboptimal treatment result of extracorporeal shockwave lithotripsy (SWL). Therefore, we investigate the efficacy and safety of standard narrow or extended (FZ) sizes in SWL for patients with renal stones. Materials and Methods: In this prospective study conducted between April 2018 and October 2022, patients with renal stones were randomized to receive SWL with either standard or extended FZ. Treatment was delivered using a Modulith SLX-F2 lithotripter with a maximum of 3000 shocks at 1.5 Hz. The primary outcome was treatment success 12 weeks after a single SWL session, defined as the absence of a stone or stone fragment <4 mm on computed tomography. Secondary outcomes included the incidence of perinephric hematoma, stone-free rate (SFR), and changes in the urinary levels of acute renal injury markers. Results: A total of 320 patients were recruited, and 276 patients were randomized into the two groups. The two groups had similar baseline parameters. The treatment success rate was significantly better for standard FZ (74.3%) than the extended FZ group (59.3%) (p = 0.009). Standard FZ also had a significantly better SFR (Grade-A, 36.8% vs 23.0%, p = 0.013) and less pain after treatment. Both groups had similar perinephric hematoma formation rates, unplanned hospital admission rates, and changes in urinary acute renal injury markers. Conclusions: The standard narrow FZ has better treatment efficacy and similar safety compared with the extended FZ during SWL for renal stones. This clinical trial has been registered in the public domain (CCRBCTR) under trial number CUHK_CCRB00510. [ABSTRACT FROM AUTHOR]

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury. [ABSTRACT FROM AUTHOR]

Background: Gadolinium (Gd)‐based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined. Purpose: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs. Study Type: Animal study. Animal Model: Seventy‐two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 μL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group). Assessment: Inductively coupled plasma mass spectrometry (ICP‐MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis. Statistical Tests: Two‐way analysis of variances with post hoc Sidak's tests and independent‐samples t‐tests were performed. A P‐value <0.05 was considered statistically significant. Results: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group. Data Conclusion: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used. Level of Evidence: 1 Technical Efficacy: Stage 4 [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) is a metabolic disease and contributes to renal injury (RI). Vine grape tea polyphenols (VGTP) have been widely used to treat HUA and RI. However, the potential mechanism of VGTP activity remains unclear. To explore the underlying mechanism of VGTP treatment for HUA-induced RI based on network pharmacology that is confirmed by an in vivo study. All ingredients of VGTP were retrieved using a Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Comparative Toxicogenomics Database systems. The related targets of HUA and RI were obtained from GeneCards and National Center for Biotechnology Information (NCBI) databases. Some ingredients and targets were selected for molecular docking verification. One hour after administering potassium oxonate (300 mg/kg), VGTP (50, 100, and 200 mg/kg/d) was orally administered to HUA mice for 4 weeks. Histopathology and western blotting were performed in renal tissue. Our results showed that VGTP significantly reduced blood urea nitrogen, creatinine, uric acid, and significantly improved the RI and fibrosis of HUA mice. There were 54 active ingredients and 62 targets of HUA-induced RI. Further studies showed that VGTP decreased the expression of Bax, cleaved caspase 3, transforming growth factor-β (TGF-β1), CHOP, p-STAT3, and P53, and increased Bcl-2 expression in renal tissue. The related signaling pathways have apoptosis, TGF-β1, P53 and STAT, and endoplasmic reticulum stress (ERS). In this study, VGTP exerted antihyperuricemic and anti fibrosis effects by regulating the apoptosis and ERS signaling pathways. VGTP is expected to become a drug for combating HUA and RI. [ABSTRACT FROM AUTHOR]

Cardiac surgery–associated acute kidney injury (AKI) is associated with increased postoperative morbidity and mortality. Evidence suggests an association between perioperative acetaminophen administration and decreased incidence of postoperative AKI in pediatric cardiac surgery patients; however, an effect in adults is unknown. All patients (n = 6192) undergoing coronary and/or valve surgery with a recorded Society of Thoracic Surgeons (STS) risk score at our institution between 2010 and 2018 were stratified by acetaminophen exposure on the day of surgery using institutional pharmacy records. AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) staging criteria. Logistic regression was used to analyze the association between perioperative acetaminophen and postoperative kidney injury or STS major morbidity. A sensitivity analysis using propensity score matching on the STS predicted risk of renal failure and cardiopulmonary bypass time was performed to account for time bias. Perioperative acetaminophen exposure was associated with lower odds of stage 1 to 3 acute kidney injury (odds ratio [OR], 0.68; 95% CI, 0.56-0.83; P <.001) and decreased prolonged postoperative ventilation (OR, 0.53; 95% CI, 0.37-0.76; P <.001). A sensitivity analysis provided well-balanced (standard mean difference <0.10) groups of 401 pairs, in which acetaminophen was associated with a decreased incidence of postoperative AKI (OR, 0.7; 95% CI, 0.52-0.94; P =.016). Exposure to acetaminophen on the day of surgery was associated with a decreased incidence of AKI in our patients undergoing cardiac surgery. These data serve as a measure of effect size to further explore the therapeutic potential of acetaminophen to reduce postoperative AKI after cardiac surgery and to elucidate the mechanisms involved. [Display omitted] [ABSTRACT FROM AUTHOR]

Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI. [ABSTRACT FROM AUTHOR]

Because of their beneficial properties, natural products, especially medicinal plants, are becoming increasingly popular worldwide and play a significant role in research. This study was aimed to evaluate the nephroprotective effect of sinapic acid against mercuric chloride-induced renal toxicity in mice. The mice were allocated to four groups named a normal group (G1), model group (G2; received HgCl2, 1 mg/kg bw), treatments groups (G3 and G4: received 50 and 100 mg/kg bw of sinapic acid together with HgCl2). Mice received HgCl2 remarkably showed alteration in all examined biochemical biomarkers (urea, creatinine, and bilirubin), and induced alteration in blood cell picture and anemia. HgCl2 intoxication decreased both systemic and renal antioxidant activity and induced over all oxidative stress as indicated by alteration in inflammation and oxidative stress associated markers. HgCl2 affected renal histology with leukocytic and inflammatory cell infiltration, fibrosis and tubular necrosis. Administration of sinapic acid (50 and 100 mg/kg bw) markedly restored the HgCl2−induced oxidative stress (serum and renal: MDA, GSH, CAT, SOD, and T-AOC), proinflammatory cytokines (serum and renal: TNF-α, IL-6, IL-1β, and PGE2) and restored the changes on biochemical markers, and hematological parameters (hemoglobin, erythrocytes, platelets, and leukocytes). Taken together, the results of the present study disclose that sinapic acid has the potential to attenuate HgCl2-induced renal toxicity and may be an ideal choice against mercury poisoning. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to retrospectively evaluate the effect of plasmapheresis treatment concomitant with chemotherapy and the number of sessions on renal improvement and survival in patients with newly diagnosed multiple myeloma (MM) presenting with acute kidney injury (AKI). Material and methods: Retrospective analysis was performed on 55 newly diagnosed MM patients who were presented with AKI to the Hematology Clinic of University of the Health Sciences Antalya Training and Research Hospital between 2013 and 2021. Results: The study included 55 patients between 39 and 91 years of age and comprised 22 (40%) women and 33 (60%) men. Forty-eight (87.3%) patients were treated with plasmapheresis and chemotherapy. Based on the median number of plasmapheresis sessions, the patients were grouped as ≤ 3 and > 3. A significant difference was observed in both groups between the mean values of repeated measurements at the time of diagnosis, after completion of plasmapheresis treatment, and at 1 month of plasmapheresis, when statistics of differences were evaluated for urea, creatinine, estimated glomerular filtration rate (eGFR) (ml/min), total protein, albumin, and globulin (p < 0.05); however, there was no difference between these parameters and the number of plasmapheresis sessions. The 1.16 (0.56–2.38) fold higher risk of ex found in patients with ≤ 3 plasmapheresis sessions compared to those with > 3 was not statistically significant (p > 0.05). Conclusion: It was observed that plasmapheresis is beneficial in the short term for renal recovery in the treatment of MM with AKI and that > 3 plasmapheresis sessions have no superior effectiveness in renal improvement or survival. [ABSTRACT FROM AUTHOR]

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundIschemia-reperfusion injury (IRI) is unavoidable during kidney transplant and it is responsible for delayed or non-function after kidney transplantation. Cysteamine is the standard drug in the management of nephropathic cystinosis and its extra-renal complications. Thus, we designed this study to investigate its potential against renal reperfusion injury.ResultsSignificant elevation of H2O2, MDA, and nitrite and reduced GPx, GSH, and protein thiol in the Ischemia-reperfusion injury rats was reversed by cysteamine (50 and 100 mg/kg). Serum MPO, TNF-α, IL-1β, creatinine, and AOPP were significantly elevated in IRI while rats treated with cysteamine revealed a significant decrease (p < 0.05) in the activities of these pro-inflammatory and renal injury markers.ConclusionBased on its activity against inflammation, apoptosis, and free radical-induced stress, cysteamine has great potential to be used as a kidney transplant pre-operative drug to prevent renal reperfusion injury.

Podocytes maintain renal filtration integrity when the glomerular filtration barrier (GFB) is integrated. Impairment or attrition of podocytes, leading to compromised GFB permeability, constitutes the primary etiology of proteinuria and is a hallmark pathological feature of diabetic nephropathy (DN). This study centers on Heterogeneous Nuclear Ribonucleoprotein I (HNRNP I), an RNA-binding protein, delineating its role in facilitating DN-induced renal damage by modulating podocyte health. Comparative analyses in renal biopsy specimens from DN patients and high-glucose-challenged podocyte models in vitro revealed a marked downregulation of HNRNP I expression relative to normal renal tissues and podocytes. In vitro assays demonstrated that high-glucose conditions precipitated a significant reduction in podocyte viability and an escalation in markers indicative of apoptosis. Conversely, HNRNP I overexpression was found to restore podocyte viability and attenuate apoptotic indices. IRAK1, a gene encoding a protein integral to inflammatory signaling, was shown to interact with HNRNP I, which promotes IRAK1 degradation. This interaction culminates in suppressing the PI3K/AKT/mTOR signaling pathway, thereby diminishing podocyte apoptosis and mitigating renal damage in DN. This investigation unveils the mechanistic role of HNRNP I in DN for the first time, potentially informing novel therapeutic strategies for DN renal impairment.