Elevated Blood Urea Nitrogen Levels Research Articles

Juzentaihoto alleviates cisplatin‐induced renal injury in mice

AbstractAimCisplatin 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.MethodsFour 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.ResultsCisplatin 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.ConclusionOur 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.

HL156A, an AMP-Activated Protein Kinase Activator, Inhibits Cyst Growth in Autosomal Dominant Polycystic Kidney Disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder. While metformin has demonstrated the ability to inhibit cyst growth in animal models of ADPKD via activation of adenosine monophosphate-activated protein kinase (AMPK), its effectiveness in humans is limited due to its low potency. This study explored the impact of HL156A, a new and more potent AMPK activator, in a mouse model of ADPKD. Methods: To investigate whether HL156A inhibits the proliferation of renal cyst cells in ADPKD in vitro, exogenous human telomerase reverse transcriptase (hTERT)-immortalized renal cyst cells from ADPKD patients were treated with HL156A, and an MTT (dimethylthiazol-diphenyltetrazolium bromide) assay was performed. To assess the cyst-inhibitory effect of HL156A in vivo, we generated Pkd1 conditional knockout (KO) mice with aquaporin 2 (AQP2)-Cre, which selectively expresses Cre recombinase in the collecting duct. The effectiveness of HL156A in inhibiting cyst growth and improving renal function was confirmed by measuring the number of cysts and blood urea nitrogen (BUN) levels in the collecting duct-specific Pkd1 KO mice. Results: When cyst cells were treated with up to 20 µM of metformin or HL156A, HL156A reduced cell viability by 25% starting at a concentration of 5 µM, whereas metformin showed no effect. When AQP2-Cre male mice were crossed with Pkd1flox/flox female mice, and when AQP2-Cre female mice were crossed with Pkd1flox/flox male mice, the number of litters produced by both groups was comparable. In collecting duct-specific Pkd1 KO mice, HL156A was found to inhibit cyst growth, reducing both the number and size of cysts. Furthermore, it was confirmed that kidney function improved as HL156A treatment led to a reduction in elevated BUN levels. Lastly, it was observed that the increase in AMPK phosphorylation induced by HL156A decreased ERK phosphorylation and α-SMA expression. Conclusion: HL156A has potential as a drug that can restore kidney function in ADPKD patients by inhibiting cyst growth.

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

ObjectiveAlthough blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia.MethodsThis analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used.ResultsDuring the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis.ConclusionsThis study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis

Cisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that β-hydroxybutyrate (β-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therapeutic mechanisms of β-HB in acute kidney damage caused by chemotherapeutic drugs remain unclear. Our study developed a model of cisplatin-induced acute kidney injury (AKI), which involved the administration of a ketogenic diet or β-HB. We analyzed blood urea nitrogen (BUN) and creatinine (Cr) levels in serum, and used western blotting and immunohistochemical staining to assess ferroptosis and the calcium/calmodulin-dependent kinase kinase 2 (Camkk2)/AMPK pathway. The mitochondrial morphology and function were examined. Additionally, we conducted in vivo and in vitro experiments using selective Camkk2 inhibitor or activator to investigate the protective mechanism of β-HB on cisplatin-induced AKI. Exogenous or endogenous β-HB effectively alleviated cisplatin-induced abnormally elevated levels of BUN and Cr and renal tubular necrosis in vivo. Additionally, β-HB reduced ferroptosis biomarkers and increased the levels of anti-ferroptosis biomarkers in the kidney. β-HB also improved mitochondrial morphology and function. Moreover, β-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro. Furthermore, western blotting and immunohistochemical staining indicated that β-HB may prevent kidney injury by regulating the Camkk2-AMPK pathway. The use of the Camkk2 inhibitor or activator verified the involvement of Camkk2 in the renal protection by β-HB. This study provided evidence of the protective effects of β-HB against cisplatin-induced nephrotoxicity and identified inhibited ferroptosis and Camkk2 as potential molecular mechanisms.

Effect of verbascoside against acute kidney injury induced by rhabdomyolysis in rats.

Rhabdomyolysis is a pathological condition caused by muscle tissue degradation. In this condition, intracellular contents enter the bloodstream, and acute kidney injury (AKI) develops. Verbascoside (VB) is one of the most common phenylethanoid glycosides and has antioxidant and anti-inflammatory effects. This study investigated the effects of VB on AKI induced by rhabdomyolysis in rats. Male Wistar rats were divided into six groups (n = 6): (1) control group (normal saline), (2) 50% glycerol (10 ml/kg, IM, single injection, only on the first day), (3)-(5) 50% glycerol (same as group 2) + VB (30, 60, and 100 mg/kg, IP, 4 days), and (6) VB (100 mg/kg). Serum and kidney tissue samples were collected on day 5. Subsequently, serum creatinine (Cr), blood urea nitrogen (BUN), renal glutathione (GSH), malondialdehyde (MDA), lipocalin associated with neutrophil gelatinase (NGAL), tumor necrosis factor-alpha (TNF-α), and pathological changes were investigated. The injection of glycerol elevated levels of kidney damage markers, including Cr and BUN in serum, MDA, TNF-α, and NGAL, along with a reduction in GSH levels in the kidney tissue. The administration of VB (100 mg/kg) significantly lowered the levels of these markers, indicating the therapeutic effect of VB against AKI caused by rhabdomyolysis. Histopathological examinations revealed enhanced myoglobin cast formation and tubular necrosis in the glycerol group, which was reduced in rats that received VB, although this reduction did not reach statistical significance. VB can reduce rhabdomyolysis-induced AKI through its anti-inflammatory and antioxidant effects and decrease kidney damage severity.

Local antibiotic delivery via intra-articular catheter infusion for the treatment of periprosthetic joint infection: a systematic review.

There is an increasing interest in the use of intra-articular (IA) antibiotic infusion as a stand-alone or adjuvant therapy to standard revision surgery for periprosthetic joint infection (PJI). The objective of this systematic review is to evaluate the evidence with respect to this up-and-coming treatment modality. A systematic review of studies published until April 2023 was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Quality assessment was performed with the National Institute of Health quality assessment tool. Inclusion criteria were adult patients (≥ 18years) with a mean follow-up of ≥ 11months and a score ≥ 6 on the National Institute of Health quality assessment tool. Primary outcome was eradication of infection. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (12.2%), DAIR (debridement, antibiotics and implant retention) with adjuvant IA antibiotic infusion (5.7%) or two-stage revision with adjuvant IA antibiotic infusion (3.0%). Mean duration of IA antibiotic infusion was 19days (range 3-50). An overall failure rate of approximately 11% was found. In total 117 complications occurred, 71 were non-catheter-related and 46 were catheter-related. The most common catheter-related complications were premature loss of the catheter (18/46) and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. Based on the current evidence, we would advise against using it as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs and potential complications of this treatment modality.

Role of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways in the renoprotective effect of mirabegron against renal ischemia-reperfusion injury in rats

Acute kidney injury and other renal disorders are thought to be primarily caused by renal ischemia-reperfusion (RIR). Cyclic adenosine monophosphate (cAMP) has plenty of physiological pleiotropic effects and preserves tissue integrity and functions. This research aimed to examine the potential protective effects of the β3-adrenergic receptors agonist mirabegron in a rat model of RIR and its underlying mechanisms. Male rats enrolled in this work were given an oral dose of 30 mg/kg mirabegron for two days before surgical induction of RIR. Renal levels of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), cAMP, cAMP-responsive element binding protein (pCREB), and glycogen synthase kinase-3 beta (GSK-3β) were assessed along with blood urea nitrogen and serum creatinine. Additionally, caspase-3 and nuclear factor-kappa B (NF-κB) p65 were explored by immunohistochemical analysis. Renal specimens were inspected for histopathological changes. RIR led to renal tissue damage with elevated blood urea nitrogen and serum creatinine levels. The renal KIM-1, MCP-1, TNF-α, and GSK-3β were significantly increased, while IL-10, cAMP, and pCREB levels were reduced. Moreover, upregulation of caspase-3 and NF-κB p65 protein expression was seen in RIR rats. Mirabegron significantly reduced kidney dysfunction, histological abnormalities, inflammation, and apoptosis in the rat renal tissues. Mechanistically, mirabegron mediated these effects via modulation of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways. Mirabegron administration could protect renal tissue and maintain renal function against RIR.

Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.

Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report

BackgroundLetrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.Case presentationAn 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.ConclusionsAlthough TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.

Current status and clinical outcome of endoscopic hemostatic powder in gastrointestinal bleeding: a retrospective multicenter study.

Few multicenter studies have investigated the efficacy of hemostatic powders in gastrointestinal (GI) bleeding. We aimed to investigate the clinical outcomes of hemostatic powder therapy and the independent factors affecting rebleeding rates. We retrospectively recruited patients who underwent a new hemostatic adhesive powder (UI-EWD; Next-Biomedical) treatment for upper and lower GI bleeding between January 1, 2020 and March 1, 2023. We collected patients' medical records and bleeding lesions. The primary outcomes were clinical and technical success rates, and the secondary outcomes were early, delayed, and refractory bleeding, mortality, and factors affecting early rebleeding rates. This study enrolled 135 patients (age: 67.7±13.6 years, male: 74.1%) from five hospitals. Indications for UI-EWD were peptic ulcers (51.1%), post-procedure-related bleeding (23.0%), and tumor bleeding (19.3%). The clinical and technical success rates were both 97%. The early, delayed, and refractory rebleeding rates were 19.3%, 11.1%, and 12.8%, respectively. Initially elevated blood urea nitrogen (BUN) levels (p=0.014) and Forrest classification IA or IB compared with IIA or IIB (p=0.036) were factors affecting early rebleeding. UI-EWD showed high clinical and technical success rates; however, rebleeding after UI-EWD therapy in patients with initially high BUN levels and active bleeding, according to the Forrest classification, should be considered.

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota.

With the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs. Fifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed. After fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus. In conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

Protective effects and mechanisms of dapagliflozin on renal ischemia/reperfusion injury

BackgroundRenal diseases have a significant negative impact on human health and the quality of life. Renal ischemia/reperfusion (I/R) injury is considered as one of the leading causes of renal dysfunction and tissue damage. Oxidative stress and inflammation are responsible for cellular apoptosis playing critical roles in renal I/R injury. Recent studies suggested that dapagliflozin—a medication used to treat Type 2 Diabetes—may exert protective effects on I/R injury in kidneys by alleviating oxidative stress and inflammation. Our study evaluated the protective effects of dapagliflozinon in renal I/R injury. MethodsA group of 32 male Sprague-Dawley rats were divided into four groups: 1) control group without any manipulation; 2) sham-operated control group with surgery but without I/R injury; 3) experimental group with 30-min I/R injury; and 4) therapeutic group with 30-min IR injury and dapagliflozin therapy. The fourth therapeutic group received 1 mg/kg dapagliflozin delivered once daily by oral gavage. All rats were evaluated by measurements of neutrophil gelatinase-associated lipocalin (NGAL), creatinine kinase (CR), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1), myoglobin (MYO), creatinine kinase (CK), lactate dehydrogenase (LDH) LD, GSH, superoxide dismutase (SOD), MDA, interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a and glutathione peroxidase (GSH-Px) levels. TUNEL and flow cytometry assays evaluated apoptosis. ResultsOverall, the 30-min exposure to I/R injury significantly elevated levels of NGAL, CR, BUN, CK, LDH, KIM-1, and MYO (all p < 0.05). Inflammatory cytokine levels (IL-6 and TNF-a) were also increased after I/R injury (p > 0.05). At the same time, I/R injury decreased levels of SOD and GSH-Px (p > 0.05). In contrast, administration of dapagliflozin following I/R injury reduced renal damage, enhanced antioxidant capacity, and suppressed inflammatory responses (all p > 0.05), thus improving renal function, while reducing oxidative stress status and inflammatory responses. Further investigations revealed that dapagliflozin exerted its protective effects on renal tissues by activating the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, inhibiting cellular apoptosis, and promoting proliferation and autophagy through bone morphogenetic protein 4 (BMP4). ConclusionThese findings documented that dapagliflozin protected kidneys from I/R injury suggesting its therapeutic potential.

Logistic regression analysis of risk factors for hematoma after autologous arteriovenous fistula in hemodialysis patients.

To determine the risk factors and nursing countermeasures for post-operative hematoma in hemodialysis patients with autogenous arteriovenous fistula by logistic regression analysis. A retrospective analysis of 240 chronic hemodialysis patients admitted to our hospital from January 2019 to October 2022 was performed. Physical and vascular examinations of the patients were performed by surgeons. Continuous care measures were implemented for all patients. The patient serum creatinine (Scr) and blood urea nitrogen (BUN) were measured on the day of inclusion and after the implementation of care measures. Self-management scales were used to analyze patients' self-management. Fatigue symptoms were assessed using the Fatigue Scale 14. The WHO Quality of Life Scale (WHOQOL-BREF score) was used to assess patients' quality of life. Self-Rating Depression Scale and Self-Rating Anxiety Scale (SAS) were used to assess negative affect. Treatment compliance was assessed according to 3 levels: complete compliance, compliance, and noncompliance. In all, 240 patients underwent 240 initial and 48 repeat procedures; 18 of the 240 patients experienced fistula failure, with an overall success rate of 92.5% (222/240). There were no significant differences in renal function, self-management, General Self-Efficacy Scale, fatigue symptom scores, and WHOQOL-BREF scores between the postoperative hematoma group and no-hematoma group before the continuous care. After continuous care, renal function, self-management, General Self-Efficacy Scale, fatigue symptom scores, and WHOQOL-BREF scores were better in the postoperative no-hematoma group than in the hematoma group, and the difference was statistically significant (P < .05). Logistic regression analysis of risk factors for postoperative hematoma showed that elevated Scr and BUN levels, decreased self-management and SAS scores and poor treatment compliance were independent risk factors for postoperative hematoma in hemodialysis patients with autologous arteriovenous fistulas (P < .05). Elevated Scr levels, elevated BUN levels, decreased self-management scores, decreased SAS scores, and poor treatment compliance were independent risk factors for postoperative hematoma in hemodialysis patients with autogenous arteriovenous fistulas. By providing continuous care to hemodialysis patients based on timing theory, the negative emotions can be alleviated and the self-efficacy, quality of life, and treatment compliance of the patients can be improved.

Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI.

Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and binds to the interleukin-1 receptor R1 (IL-1R1) on leukocytes and kidney parenchymal cells. IL-1R1 on kidney tubular cells is known to amplify the immune response and exacerbate AKI. However, the specific role of IL-1R1 on myeloid cells during AKI is poorly understood. The objective of the present study was to elucidate the function of myeloid cell IL-1R1 during AKI. As IL-1R1 is known to signal through the pro-inflammatory Toll-like receptor (TLR)/MyD88 pathway, we hypothesized that myeloid cells expressing IL-1R1 would exacerbate AKI. Methods: IL-1R1 was selectively depleted in CD11c+-expressing myeloid cells with CD11cCre + /IL-1R1 fl/fl (Myel KO) mice. Myel KO and littermate controls (CD11cCre - /IL-1R1 fl/fl-Myel WT) were subjected to kidney ischemia/reperfusion (I/R) injury. Kidney injury was assessed by blood urea nitrogen (BUN), serum creatinine and injury marker neutrophil gelatinase-associated lipocalin (NGAL) protein expression. Renal tubular cells (RTC) were co-cultured with CD11c+ bone marrow-derived dendritic cells (BMDC) from Myel KO and Myel WT mice. Results: Surprisingly, compared to Myel WT mice, Myel KO mice displayed exaggerated I/R-induced kidney injury, as measured by elevated levels of serum creatinine and BUN, and kidney NGAL protein expression. In support of these findings, in vitro co-culture studies showed that RTC co-cultured with Myel KO BMDC (in the presence of IL-1β) exhibited higher mRNA levels of the kidney injury marker NGAL than those co-cultured with Myel WT BMDC. In addition, we observed that IL-1R1 on Myel WT BMDC preferentially augmented the expression of anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra/Il1rn), effects that were largely abrogated in Myel KO BMDC. Furthermore, recombinant IL-1Ra could rescue IL-1β-induced tubular cell injury. Discussion: Our findings suggest a novel function of IL-1R1 is to serve as a critical negative feedback regulator of IL-1 signaling in CD11c+ myeloid cells to dampen inflammation to limit AKI. Our results lend further support for cell-specific, as opposed to global, targeting of immunomodulatory agents.

Correlations of Serum Retinol-Binding Protein and Stromal Cell-Derived Factor-1 with Renal Function in Patients with Diabetic Kidney Disease.

The aim is to investigate the correlations of serum retinol-binding protein (RBP) and stromal cell-derived factor-1 (SDF-1) with renal function in patients with diabetic kidney disease (DKD). A total of 438 patients with type 2 diabetes mellitus (T2DM) treated from October 2017 to October 2020 were enrolled in this prospective study and divided into simple T2DM and DKD groups. According to urinary albumin-to-creatinine ratio (UACR), DKD patients were divided into moderate, severe, and nephrotic groups. They were assigned to one of the following categories of estimated glomerular filtration rate (eGFR): G1, G2, G3a, G3b, G4, and G5 stages. The correlations of RBP and SDF-1 with renal function were analyzed. The DKD group had a longer T2DM course and higher RBP, uric acid (UA), blood urea nitrogen (BUN), β2-microglobulin (β2-MG), serum creatinine (Scr) levels and UACR, and lower SDF-1 level and eGFR than those of simple T2DM group (p < 0.05). The areas under the receiver operating characteristic curves of RBP and SDF-1 for identifying DKD were 0.903 and 0.868, and the optimal cutoff values were 70.71 mg/L and 5.69 ng/mL, respectively. With increasing urinary albumin and clinical stage, RBP, UA, BUN, β2-MG and Scr levels and UACR significantly rose, while SDF-1 level and eGFR declined (p < 0.05). In patients with DKD, RBP was correlated positively with UACR, UA, BUN, β2-MG, and Scr (r = 0.764/0.787/0.693/0.577/0.801, p < 0.0001), and negatively with eGFR (r = -0.782, p < 0.0001). SDF-1 was correlated negatively with UACR, UA, BUN, β2-MG and Scr (r = -0.744/-0.794/-0.666/-0.605/-0.820, p < 0.0001), and positively with eGFR (r = 0.767, p < 0.0001). The multiple linear regression equation was RBP = 29.852 + 0.007 x UACR + 0.101 x UA + 0.497 x BUN + 0.034 x Scr-0.083 x eGFR (p < 0.001). RBP and SDF-1 can identify DKD in patients with T2DM, and the degree of renal function damage is correlated positively with RBP and negatively with SDF-1. Elevated levels of UA, BUN, Scr and UACR as well as reduced eGFR are risk factors for evaluating RBP.

The effect of neutrophil lymphocyte ratio and other biochemical parameters on mortality in cancer patients admitted to the emergency department

Aims: To investigate the effectiveness of the neutrophil/lymphocyte ratio and other biochemical parameters in predicting mortality in oncology patients with cancer admitted to the emergency department. Methods: This was a retrospective, observational, single-center study. The study period included a two-year period from January 2014 to December 2015. Demographic data, cancer history and blood tests, emergency department diagnoses, blood parameters evaluated in the emergency department, discharge, and mortality status of the patients were recorded in the data form. The APACHE 2 and SOFA scores of all patients were also calculated. Patients whose data could not be reached were excluded from the study. p&lt;0.05 was considered statistically significant. Results: A total of 180 patients were included in the study. The mean age of the survivor group was 66.4±10.752 years, while the mean age of the non-survivor group was 65.18±13 years. The mean neutrophil/lymphocyte (NLR) ratio of the non-survivor group was 1.0288±11.3, while the NLR of the survivor group was 4.400±3.563. (p&lt;0.05) The mean lactate ratio of the non-survivor group was 2.60±3.384, while the mean lactate ratio of the survivor group was 1.36±1. 090. (p&lt;0.05) When survivor and non-survivor patient groups were compared, a statistically significant difference was observed in mean white blood cell count, neutrophil count, hemoglobin, hematocrit, and blood urea nitrogen (BUN) values. (p&lt;0.05) Conclusion: According to the results of this study, NLR, elevated white blood cell and neutrophil values, decreased hemoglobin and hematocrit, and elevated BUN and lactate levels seem to be predictors of mortality during emergency admissions in cancer patients.

Risk Factors for 30-Day Mortality in Patients with Bacteremic Pneumonia Caused by Escherichia coli and Klebsiella pneumoniae: A Retrospective Study.

Escherichia coli and Klebsiella pneumoniae are prevalent Gram-negative microorganisms responsible for pneumonia, as well as the primary Enterobacteriaceae pathogens causing bacteremic pneumonia. The objective of this research is to analyze the risk factors associated with bacteremic pneumonia caused by these pathogens and develop a predictive model. This retrospective investigation encompassed a cohort of 252 patients diagnosed with Escherichia coli or Klebsiella pneumoniae-induced bacteremic pneumonia between 2018 and 2022. The primary endpoint was 30-day mortality, which was analyzed using multifactorial logistic regression, nomogram construction, and Bootstrap validation. Among the 252 patients diagnosed with Escherichia coli and Klebsiella pneumoniae, 65 succumbed to the disease while 187 survived. The overall 30-day mortality was found to be 25.8%. A multifactorial logistic regression analysis revealed that diastolic blood pressure, cerebrovascular diseases/transient ischemic attacks (TIA), immunosuppression, blood urea nitrogen, Pitt score, and CURB-65 score were statistically significant factors. The Nomogram model demonstrated an AUC of 0.954, which closely aligns with the Bootstrap-derived mean AUC of 0.953 (95% CI: 0.952-0.954). In patients with bacteremic pneumonia caused by Escherichia coli and Klebsiella pneumoniae, Low diastolic blood pressure (≤61 mmHg), pre-existing cerebrovascular disease/ transient ischemic attacks (TIA), immunosuppression status, elevated blood urea nitrogen levels (≥8.39 mmol/L), high Pitt score (≥3), and a high CURB-65 score (≥2) are all independent risk factors for Escherichia coli and Klebsiella pneumoniae bacteremic pneumonia, among which the first three warrant particular attention.

Impacts of dietary betaine on rectal temperature, laying performance, metabolism, intestinal morphology, and follicular development in heat-exposed laying hens

This experiment assessed the influences of betaine (BET; 2000 mg/kg) on rectal temperature (Tr), laying performance, metabolism, intestinal morphology, and follicular development in heat-stressed hens. One-hundred and twenty-eight Hisex white hens (42wks) were housed in 4 battery cages (8 pens/cage; 4 hens/pen) and divided into 4 treatments: 1) thermoneutral (TN) environments and a control diet (TNCON), 2) TN and a diet accompanied with BET (TNBET), 3) heat stress (HS) environments and a control diet (HSCON), or 4) HS and a diet accompanied with BET (HSBET). Following acclimation (15d), hens of TNCON and TNBET remained in TN, while HSCON and HSBET hens were subjected to cyclical HS (5d; 16.9–37.5 °C). Cyclical HS increased Tr compared with TN hens (1.6 °C; P < 0.01), but supplemental BET decreased Tr (0.4 °C; P < 0.01). Relative to TN treatments, HS declined egg production, weight, and mass (18, 4.2, and 26%, respectively; P < 0.01), but BET ameliorated the egg production and mass (13.1 and 16.2%, respectively; P < 0.01). Compared with HSCON, feed conversion ratio and survival rate were improved in HSBET hens (12.3 and 6.25%, respectively; P ≥ 0.03). Relative to TN hens, HS elevated glucose and blood urea nitrogen (BUN) levels (15 and 4%, respectively; P ≤ 0.04). Supplemental BET decreased BUN levels (6.6%; P < 0.01) relative to HSCON hens. Furthermore, HS diminished jejunal villus height and villus surface area (∼27 and 35%, respectively; P < 0.01) relative to TN hens but were unaltered by BET supplementation. Relative to TN hens, HS decreased oviduct's weight, ovary's length, and ovarian primordial and primary follicles count (18, 23, 34 and 44%, respectively; P < 0.01) and caused fibrosis in shell gland (3-fold; P = 0.05). Collectively, HS impaired productivity, metabolism, intestinal architecture, and reproductive efficiency. Feeding BET reduced Tr, improved laying performance, and slightly altered metabolism but did not affect intestinal and follicular measurements in heat-stressed hens.

COVID-19 in the intensive care unit: unmasking the critical factors impacting patient survival.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, intensive care units (ICUs) around the world have been pushed to their limits as they grapple with the effects of the severe acute respiratory syndrome coronavirus 2 virus. Identifying prognostic factors that influence mortality in COVID-19 patients admitted to the ICU could offer valuable insights for clinicians seeking to prevent disease progression. A retrospective analysis was conducted on COVID-19 patients admitted to the ICU between January and September 2020. The analysis considered patient demographics, comorbidities, neurological and non-neurological symptoms, as well as laboratory markers. The multivariate logistic regression analysis aims to uncover associations between these factors and patient outcomes. Of the 387 patients included in this study, nearly half (48.5%) of the ICU patients succumbed to COVID-19. Factors that contributed to increased mortality included being 60 years of age or older, impaired consciousness, lung disease, elevated international normalized ratio (INR), and elevated blood urea nitrogen (BUN) levels. Surprisingly, symptoms such as dizziness/lightheadedness, myalgia, and headache were associated with a higher likelihood of survival. In addition, elevated D-dimer and aspartate aminotransferase (AST) levels, as well as lymphopenia, were more commonly observed in deceased patients. The study concluded that those who died in the ICU tended to be older, white, and burdened with more comorbidities and impaired consciousness. With the intriguing link between specific symptoms and survival, further research is essential to uncover the underlying pathophysiological mechanisms that influence ICU patient outcomes in the context of COVID-19.