Biomarkers Of Injury Research Articles

Walnut kernel against liver damage induced by salt processed Psoraleae Fructus through regulating bile acid metabolism in ovariectomized rats

Walnut kernel (WK) is a globally popular health food known for its potent antioxidant properties. WK shows a promising prospect in protecting against liver damage induced by salt processed psoraleae fructus (SPF). This study explored the impact of WK in mitigating liver damage induced by SPF in an ovariectomized (OVX) rat model. Serum metabolomics was employed to explore potential detoxification mechanisms. The levels of Farnesoid X receptor (FXR), Bile salt export pump (BSEP), and Cholesterol 7α-hydroxylase (CYP7A1) proteins were determined through western blot analysis. The results demonstrated that WK exhibits a noteworthy protective effect against liver damage induced by SPF. The WK normalized the metabolic disorder and reversed sixteen liver injury biomarkers and five metabolic pathways induced by SPF. These results demonstrated that WK exhibits a protective effect against SPF-induced liver damage in OVX rats by regulating bile acid metabolism.

Blood-based biomarkers of neuronal and glial injury in active major neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE. This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected. Thirteen patients with active major NPSLE, 13age/sex/kidney function matched SLE controls without active major NPSLE, and 13age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3pg/ml (p = .42) and 1.2pg/ml higher (p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy. Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting.

The role of puff volume in vaping emissions, inhalation risks, and metabolic perturbations: a pilot study

Secondhand vaping exposure is an emerging public health concern that remains understudied. In this study, saliva and exhaled emissions from ENDS users (secondhand) and non-ENDS users (baseline) were collected, firsthand emissions were generated using an automated ENDS aerosol generation system programmed to simulate puffing topography profiles collected from ENDS users. Particulate concentrations and sizes along with volatile organic compounds were characterized. We revealed puffing topography metrics as potential mediators of firsthand and secondhand particle and chemical exposures, as well as metabolic and respiratory health outcomes. Particle deposition modeling revealed that while secondhand emissions displayed smaller deposited mass, total and pulmonary particle deposition fractions were higher than firsthand deposition levels, possibly due to smaller secondhand emission particle diameters. Lastly, untargeted metabolomic profiling of salivary biomarkers of lung injury due to firsthand ENDS exposures revealed potential early indicators of respiratory distress that may also be relevant in bystanders exposed to secondhand vaping scenarios. By leveraging system toxicology, we identified 10 metabolites, including leukotriene D4, that could potentially serve as biomarkers for ENDS use, exposure estimation, and the prediction of vaping-related disease. This study highlights characterization of vaping behavior is an important exposure component in advancing our understanding of potential health effects in ENDS users and bystanders.

Urine glyphosate predicts changes in kidney injury biomarkers and estimated glomerular filtration rate in Mesoamerican Nephropathy Occupational Study (MANOS)

Urine glyphosate predicts changes in kidney injury biomarkers and estimated glomerular filtration rate in Mesoamerican Nephropathy Occupational Study (MANOS)

Perspective for Donor-Derived Cell-Free DNA in Antibody-Mediated Rejection After Kidney Transplantation: Defining Context of Use and Clinical Implications.

Antibody-mediated rejection (AMR) is a major cause of graft failure limiting long-term graft survival after kidney transplantation. Current diagnostic strategy to detect AMR is suboptimal and requires further improvement. Previously suggested treatment regimens for AMR could not demonstrate efficacy, however novel therapeutic agents are currently under investigation. Donor-derived cell-free DNA (dd-cfDNA) is a novel non-invasive biomarker for allograft injury, that has been mainly studied in the context of rejection. Its short-half-life in circulation and injury-dependent release are its key advantages that contribute to its superior diagnostic accuracy, compared to traditional biomarkers. Moreover, previous studies showed that dd-cfDNA-release is well-linked to histological and molecular features of AMR, and thus able to reflect real-time injury. Further observations suggest that dd-cfDNA can be used as a suitable screening tool for early detection of AMR in patients with donor-specific-anti-HLA-antibodies (DSA), as well as for monitoring AMR activity after anti-rejection treatment. The weight of evidence suggests that the integration of dd-cfDNA in the graft surveillance of patients with AMR, or those suspicious of AMR (e.g., due to the presence of donor-specific anti-HLA-antibodies) has an added value and might have a positive impact on outcomes in this specific cohort.

A Highly Sensitive Lateral-Flow Strip Using Latex Microspheres to Detect NGAL in Urine Samples.

The incidence of kidney disease is increasing worldwide. Rapid and cost-effective approaches for early detection help prevent this disease. Neutrophil gelatinase-associated lipocalin protein (NGAL) is a novel biomarker for acute kidney injury (AKI) and chronic kidney disease (CKD). We aimed to develop a lateral flow strip (LFS) based on a lateral flow immunoassay method (LFIA), using latex microspheres (LMs) as a color labeling to detect NGAL in urine. The performance and potential of the developed LMs-LFS at a point-of-care (POC) testing were evaluated. The results showed that LMs-LFS successfully detected urinary NGAL within 15 min with high specificity without cross-reactivity to or interference from other endogenous substances in urine. The visual limit of detection (vLOD) was 18.75 ng/mL, and the limit of detection (LOD) was 1.65 ng/mL under the optimum condition. The LMs-LFS developed in this study showed a high correlation with the enzyme-linked immunosorbent assay (ELISA) method (R 2 = 0.973, n = 60 urine specimens) for detecting NGAL in urine. The LMs-LFS remained stable for at least six months at room temperature. The LMs-LFS can be a rapid, sensitive, and specific tool for the diagnosis and follow-up of renal disorders at the POC.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Assessed the Liver Injury Biomarker Following Candida Infection in Female Diabetic Rats

Assessed the Liver Injury Biomarker Following Candida Infection in Female Diabetic Rats

Assessing the predictive value of elevated postoperative syndecan-1 levels for progressive acute kidney injury and kidney replacement therapy necessity in adult cardiac surgery patients

BackgroundThe development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression.MethodsIn this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2–3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints.ResultsIn the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (β = 0.014, p = 0.022) and ICU stays (β = 0.013, p < 0.001).ConclusionElevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study’s findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.

Serum and urinary biomarkers of vancomycin-induced acute kidney injury: A prospective, observational analysis.

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (μg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Biomarkers of lung congestion and injury in acute heart failure.

Acute heart failure (AHF) classification and management are primarily based on lung congestion and/or hypoperfusion. The quantification of the vascular and tissue lung damage is not standard practice though biomarkers of lung injury may play a relevant role in this context. Haemodynamic stress promotes alveolar and vascular derangement with loss of functional units, impaired lung capillary permeability and fluid swelling. This culminates in a remodelling process with activation of inflammatory and cytokines pathways. Four families of lung surfactant proteins (i.e., SP-A, SP-B, SP-C, and SP-D), essential for the membrane biology and integrity are released by alveolar type II pneumocites. With deregulation of fluid handling and gas exchange pathways, SPs become sensitive markers of lung injury. We report the pathobiology of lung damage; the pathophysiological and clinical implications of alveolar SPs along with the newest evidence for some classical HF biomarkers that have also shown to reflect a vascular and/or a tissue lung-related activity.

Clinical aspects of the applicability of biomarkers of acute kidney injury in ischemia-reperfusion in operative urology

The development of acute kidney injury during surgical renal-preserving interventions characterizes the nature of the clinical course and prognosis for the development of chronic kidney disease. The use of standard indicators of disease progression (serum creatinine and urea nitrogen) in clinical practice can lead to unfavorable outcomes of acute kidney injury due to their low sensitivity and high specificity against the background of damage to more than 50% of the renal parenchyma). Other biomarkers of acute kidney injury (cystatin C, IL-18, KIM-1, NGAL, L-FABP, NAG and others) are superior to creatinine in sensitivity and specificity, but require additional research to identify the most optimal ones for clinical practice.

Association of Acute Systemic Inflammation with Patient-Centric Postoperative Pulmonary Complications After Elective Cardiac Surgery.

Postoperative pulmonary complications (PPCs) occur frequently after cardiac surgery. Absolute postoperative values of biomarkers of inflammation (interleukin [IL]-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) and alveolar epithelial injury (soluble receptor for advanced glycation end-products [sRAGE]) have been associated with hypoxia and prolonged ventilation. However, relationships between these biomarkers and PPCs, contextualized to preoperative inflammation and perioperative lung injury risk factors, are uncertain. We aimed to determine associations between perioperative increases in biomarkers of inflammation and alveolar epithelial injury with a patient-centric PPC definition in adult cardiac surgical patients, accounting for the influence of intraoperative risk factors for lung injury. Adults undergoing elective cardiac surgery were eligible for this observational cohort study. Blood concentrations of IL-6, IL-8, TNF-α, and sRAGE were collected after anesthesia induction (baseline) and on postoperative day 1 (POD 1). The primary outcome was the occurrence of moderate or severe PPCs, graded using a validated scale, in POD 0 to 7. We estimated the association between POD 1 IL-6, IL-8, TNF-α, and sRAGE concentrations and moderate/severe PPC presence using separate logistic regression models for each biomarker, adjusted for baseline biomarker values and risk factors for postoperative lung injury (age, baseline PaO2/FiO2, left ventricle ejection fraction [LVEF], procedural type, cardiopulmonary bypass duration, and transfusions). Covariables were chosen based on relevance to lung injury and unadjusted between-group differences among patients with versus without PPCs. The secondary outcome was postoperative ventilation duration, which was log-transformed and analyzed using linear regression, adjusted using the same variables as the primary outcome. We enrolled 204 patients from 2016 to 2018. Biomarkers were analyzed in 2023 among 175 patients with complete data. In adjusted analyses, POD 1 IL-8 and IL-6 were significantly associated with moderate/severe PPCs. The odds ratio (OR) for developing a PPC for every 50 pg/mL increase in POD 1 IL-8 was 7.19 (95% confidence interval [CI], 2.13-28.53, P = .003) and 1.42 (95% CI, 1.13-1.93, P = .01) for every 50 pg/mL increase in POD 1 IL-6. In adjusted analyses, postoperative ventilation duration was significantly associated with POD 1 sRAGE; each 50 pg/mL increase in sRAGE was associated with a 25% (95% CI, 2%-52%, P = .03) multiplicative increase in hours of ventilation. TNF-α was not significantly associated with PPCs or ventilation duration. Acute systemic inflammation is significantly associated with PPCs after elective cardiac surgery in adults when taking into consideration preoperative inflammatory burden and perioperative factors that may influence postoperative lung injury.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol

IntroductionPoststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality...

Allicin and L-carnitine as Preventive Agents Against Doxorubicin-induced Cardiac Damage in Rats

Background: Doxorubicin (DOX) is a potent anthracycline chemotherapy agent widely employed to treat various malignancies, such as cancers and this study sought to determine how allicin (ALC) and or L-carnitine (LC) affect DOX-induced cardiotoxicity in rats.Methods: In this study, the possible alleviative role of ALC (20 mg/kg/day orally (PO)) or LC (100 mg/kg/day PO) or the combined treatment of both ALC and LC (with the previously mentioned dosages) was evaluated against the cardiotoxic effect of a widely used chemotherapeutic agent, DOX (20 mg DOX /kg intraperitoneal injection (IP) as a single dose) in rats in 30 days experiment. Results: The results revealed that ALC and LC significantly suppressed the DOX-induced increment in serum levels of cardiac damage biomarkers, such as lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-megabyte (CK-MB). Moreover, DOX-associated oxidative stress, including the elevation in malondialdehyde (MDA) level and reduced activity of antioxidant enzymes, such as catalase (CAT) and superoxide dismutase (SOD) and the level of reduced glutathione (GSH) was corrected in ALC and or LC treated groups. Furthermore, DOX-induced cardiomyopathy showed significant pathological changes, including myocyte degeneration, vacuolization, interstitial edema, and focal necrosis. Nevertheless, the histopathological lesions were corrected in the treated groups mostly in the combined treatment with ALC plus LC. Compared to ALC and LC, ALC plus LC was more effective at restoring the cardiac injury biomarkers, inhibiting cardiac oxidative damage and preserving the cardiac architecture. Conclusions: Conclusively, the study results evidenced the beneficial role of the combined treatment with ALC plus LC in mitigating DOX-induced cardiotoxicity.

Blood biomarkers for neuroaxonal injury and astrocytic activation in chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer. Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) every 3 weeks × 3, followed by weekly paclitaxel 80 mg/m² × 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20. Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN. NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.

Clinical utility of plasma percent donor-derived cell-free DNA for lung allograft surveillance: A real-world single-center experience

BackgroundPlasma percent donor-derived cell-free DNA (%dd-cfDNA) has been investigated as a biomarker of allograft injury after lung transplantation (LT). We sought to determine the clinical utility of plasma percent donor-derived cell-free DNA (%dd-cfDNA) as a screening tool for acute cellular rejection (ACR) and respiratory infections (RIs) among LT recipients (LTRs). MethodsWe retrospectively analyzed %dd-cfDNA results from 95 plasma samples collected from 81 bilateral LTRs at our center with a paired transbronchial biopsy within 24 hours after sample collection. We calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of %dd-cfDNA to detect ACR and RIs and used a generalized estimating equation model to compare %dd-cfDNA between groups. ResultsA dd-cfDNA threshold of 0.5% had low sensitivity to detect ACR among LTRs >45 days after LT (41.67%), as did a 70% increase in %dd-cfDNA (50.00%). The NPV was high (88.89% and 87.50%, respectively) but driven by the low prevalence of ACR (12/95 [12.6%]). The area under the receiver operating characteristic curve (AUC) was 0.499 (95%CI [0.326-0.672]) and 0.360 (95%CI [0.132-0.588]) for the detection of ACR and ACR grade ≥A2, respectively. The adjusted mean %dd-cfDNA trended higher in LTRs with a definite or possible RI (1.218, 95%CI [0.671-2.212]) than in LTRs without microbial isolation (0.731, 95%CI [0.525-1.017], p=0.059), but was not significantly different from those with microbial colonization (0.873, 95%CI [0.538-1.415], p=0.390). There was no significant difference in the adjusted mean %dd-cfDNA between patients with microbial colonization and those without microbial isolation (p=0.464). %dd-cfDNA testing had an AUC of 0.573 (95%CI [0.431-0.716]) for the detection of lung allograft dysfunction due to ACR and/or infection. Conclusions%dd-cfDNA may have limited utility as a screening tool to detect ACR among LTRs.

Abstract Mo048: Cereblon as a potential biomarker for early detection of diabetic cardiomyopathy

Type 2 diabetes mellitus (T2DM) patients have a higher risk of heart failure and cause cardiomyopathy without other cardiac disease. There is no specific biomarker for discriminating patients with diabetic cardiomyopathy (DCM). In this study, we investigated the cereblon (CRBN) level in mice and human samples to determine its potential as a biomarker for early detection of diabetic cardiomyopathy (DCM). C57BL/db/db male mice at 6 and 8 weeks of age, as the early DCM model with obesity and T2DM were investigated. We confirmed that mitochondrial function was decreased in the 8 weeks old db/db mice without alterations of cardiac function and structures. Compared to the control mice, CRBN protein level was significantly increased and phosphorylation of AMPK, a negative regulator by CRBN, was significantly decreased in the heart tissue of 8 weeks old db/db mice. Blood CRBN level was also significantly increased in both 6 and 8 weeks old db/db mice compared with control mice. In blood of diabetic patients, CRBN level was significantly correlated with IL-6, IL-1b, TNF-a, IGFBP-7, and adiponectin, which are previously reported biomarkers of DCM. However, CRBN level was not correlated with cardiac troponin I, NT-proBNP, and ST2, which are biomarkers of myocardial injury and heart failure. Furthermore, the CRBN level showed a higher tendency in patients with diastolic dysfunction without systolic dysfunction compared to patients with normal function and systolic dysfunction, although the difference was not statistically significant. In conclusion, cardiac mitochondrial dysfunction occured and CRBN levels of heart and blood increased prior to cardiac functional and structural changes in the early DCM mouse model, and CRBN might serve as a potential biomarker for the early detection of DCM in T2DM patients.

EFFECT OF ARTESUNATE TREATMENT ON INTESTINAL INJURY AFTER CARDIOPULMONARY RESUSCITATION IN SWINE.

Intestinal injury is often caused by systemic ischemia-reperfusion injury early after cardiac arrest (CA) and resuscitation. Artesunate (Art) has been confirmed to protect vital organs against diverse of regional I/R injury. This study aimed to investigate the effect of Art on intestinal injury after CA and cardiopulmonary resuscitation (CPR) in swine. Twenty-two swine were randomly divided into three groups: sham (n = 6), CA/CPR (n = 8), and CA/CPR + Art (n = 8). The CA/CPR swine model was established by inducing 9 minutes of untreated ventricular fibrillation (VF) followed by 6 minutes of CPR. Five minutes after resuscitation, 4.8 mg/kg of Art was intravenously administered for 2 hours in the CA/CPR + Art group. Intestinal fatty acid-binding protein (iFABP) and diamine oxidase (DAO) concentrations were compared among the three groups before CA and at 1, 2, 4, and 24 hours after resuscitation. At 24 hours post-resuscitation, intestinal zonula occluden-1(ZO-1), occludin, apoptosis, caspase-3/gasdermin E (GSDME)-mediated pyroptosis proteins concentrations, and proinflammatory cytokine concentrations were examined to evaluate intestinal injury. During CPR, spontaneous circulation was achieved in 7 and 6 swine in the CA/CPR and CA/CPR + Art groups, respectively. Serum iFABP and DAO concentrations were significantly higher and intestinal tissue ZO-1 and occludin concentrations were significantly lower in the CA/CPR and CA/CPR + Art groups than in the sham group. However, Art treatment resulted in markedly improved levels of intestinal injury biomarkers compared with those in the CA/CPR group. Additionally, intestinal apoptosis and concentrations of caspase-3/GSDME-mediated pyroptosis proteins and proinflammatory cytokines were significantly higher in the CA/CPR and CA/CPR + Art groups than in the sham group. However, these variables were significantly lower in the CA/CPR + Art group than in the CA/CPR group. Art treatment effectively alleviates post-resuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.

Screening for Early Biomarkers of Cisplatin-Induced Acute Kidney Injury in Rats Through Serum Metabolomics Technology.

To systematically identify early biomarkers of cisplatin-induced acute kidney injury (AKI) in rats. An experimental study. Place and Duration of the Study: Experimental Animal Laboratory of Lanzhou University, Gansu, China, and the Department of Pharmacy, The First Hospital of Lanzhou University, Gansu, China, from July 2022 to October 2023. In this study, an AKI model was established by continuously injecting cisplatin into rats at a dose of 1 mg/kg once a day for control group and for 2, 3, 4, and 5 days to other four groups, respectively. Subsequently, rat plasma samples were collected for metabolomics analysis to identify early differentiated metabolites in the plasma prior to creatinine elevation. Furthermore, accurate HPLC-MS/MS methods were developed to validate the biomarker variation in other AKI models. The occurrence of time-dependent renal cortical injury and significant alterations of creatinine (Cr) concentration were observed on day-4 and 5, which demonstrated successful model construction. Sixty-six compounds changed on Day-2 while 61 compounds changed on Day-3. Eleven compounds with variable importance in projection (VIP) >1.5 and false discover rate (FDR) <0.2 were selected and identified by HPLC-MS/MS. Among these, N-acetylglutamine and citramalic acid changed earlier than serum creatinine (sCr) in the AKI model. N-acetylglutamine and citramalic acid may serve as early biomarker of cisplatin-induced AKI. Acute kidney injury, Biomarker, Cisplatin, Metabolomics, LC-MS/MS, Rats.