Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying Chelidonium majus L. in the treatment of allergic asthma.

BACKGROUND: Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. METHODS: Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. RESULTS: After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. CONCLUSION: Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.

Factors influencing the thriving of emergency department nurses in China.

INTRODUCTION: Thriving is a positive feeling arising from nurses' work and is increasingly valued by managers. Given their demanding workloads and various duties, it is necessary to research the determinants of ED nurses' thriving. This study aimed to investigate the factors influencing thriving and the mechanisms of interaction between the factors among ED nurses. METHODS: 380 ED nurses from six tertiary hospitals in Shandong Province, China, participated in this cross-sectional study. The instruments used were the General Information Questionnaire, Challenge-Hindrance Stressors Scale, Psychological Detachment Scale, and Thriving at Work Scale. Data analysis methods included univariate analysis, Pearson correlation, PROCESS 4.0, and hierarchical multiple regression. RESULTS: Weekly working hours affected nurses' thriving. Challenge stressors and psychological detachment were positively related to thriving. Hindrance stressors had a negative link with thriving. Psychological detachment suppressed the relationship between challenge stressors and thriving; however, it mediated the relationship between hindrance stressors and thriving. CONCLUSION: Challenge-hindrance stressors and psychological detachment are significant elements influencing ED nurses' thriving. Nursing administrators should help ED nurses properly address stressors with different attributes and adopt appropriate strategies to improve nurses' thriving by enhancing psychological detachment.

Diffusion kurtosis imaging of brain white matter alteration in patients with coronary artery disease based on the TBSS method.

Object: The aim of our study was to examine the alterations in microstructure in patients with coronary artery disease (CAD) and cognitive impairment (CI) using diffusion kurtosis imaging (DKI). Additionally, we aimed to investigate the potential correlation between DKI parameters and cognitive function. Materials and methods: A total of 28 CAD patients and 30 healthy controls (HC) were prospectively enrolled in our study. All participants underwent routine and diffusion sequences of head imaging. DKE software was utilized to generate various diffusion kurtosis imaging parameters (DKI), including kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD). Nonparametric tests were conducted using tract-based spatial statistics (TBSS) to compare the parameter values between the two groups. The parameter values of the significantly different fiber tracts were extracted and correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Results: Compared to the HC group, patients with coronary artery disease exhibited significant reductions in FA values in the bilateral Superior corona radiata, bilateral Anterior corona radiata, bilateral Posterior corona radiata, corpus callosum, left Posterior thalamic radiation, right Posterior limb of internal capsule, Anterior limb of internal capsule, and Cerebral peduncle, as well as in the left Superior longitudinal fasciculus. Additionally, KFA values decreased in the bilateral Anterior corona radiata, bilateral Anterior limb of internal capsule, and Genu of the corpus callosum. The MK values decreased in the right Posterior corona radiata, Retrolenticular part of the internal capsule, Posterior thalamic radiation (including optic radiation), Superior longitudinal fasciculus, and left Posterior thalamic radiation (including optic radiation). Moreover, the RK values decreased in the bilateral Retrolenticular part of the internal capsule, right Posterior thalamic radiation (including optic radiation), and Superior longitudinal fasciculus, as well as in the left Superior longitudinal fasciculus and Posterior thalamic radiation (including optic radiation) (p < 0.01, TFCE corrected), while no significant differences were observed in other parameter values (p > 0.01, TFCE corrected). The FA values of the right posterior limb of the internal capsule (r = 0.610, p = 0.001) and the right cerebral peduncle (r = 0.622, p < 0.001) were positively correlated with MMSE scores. Additionally, a significant correlation between kurtosis and diffusion coefficient parameters (FA and KFA) was observed. Conclusion: CAD patients showed radial shrinkage and complexity of brain white matter microstructure. Whole-brain white matter analysis based on TBSS DKI can objectively reflect the characteristics of white matter damage in CAD patients, providing a basis for the auxiliary diagnosis of CAD with CI.

Classification of and individual treatment strategies for complex tethered cord syndrome.

Objective: To study the classification, diagnosis, and treatment strategies of complex tethered cord syndrome (C-TCS) on the basis of the patients' clinical symptoms, imaging findings, and therapeutic schedule. Methods: The clinical data of 126 patients with C-TCS admitted to our department from January 2015 to December 2020 were retrospectively analyzed. Classification criteria for C-TCS were established by analyzing the causes of C-TCS. Different surgical strategies were adopted for different types of C-TCS. The Kirollos grading, visual analogue scale (VAS), critical muscle strength, and Japanese Orthopaedic Association (JOA) scores were used to evaluate the surgical outcomes and explore individualized diagnosis and treatment strategies for C-TCS. Results: C-TCS was usually attributable to three or more types of tether-causing factors. The disease mechanisms could be categorized as pathological thickening and lipomatosis of the filum terminal (filum terminal type), arachnoid adhesion (arachnoid type), spina bifida with lipomyelomeningocele/meningocele (cele type), spinal lipoma (lipoma type), spinal deformity (bone type), and diastomyelia malformation (diastomyelia type). Patients with different subtypes showed complex and varied symptoms and required individualized treatment strategies. Conclusion: Since C-TCS is attributable to different tether-related factors, C-TCS classification can guide individualized surgical treatment strategies to ensure complete release of the tethered cord and reduce surgical complications.

Dexmedetomidine nasal administration improves perioperative sleep quality and neurocognitive deficits in elderly patients undergoing general anesthesia.

OBJECTIVE: To investigate the improvement of perioperative sleep quality and neurocognitive impairment in elderly patients under general anesthesia by nasal administration of dexmedetomidine. METHODS: One hundred and twenty patients admitted to our hospital for various laparoscopic elective gynecological surgeries lasting more than 1 h under general anesthesia from July 2021 to March 2023 were selected. All subjects were divided into 3 groups according to the random number table method. From 21:00 to 21:30 every night from one day before to 5 days after surgery, group A was given alprazolam 0.4 mg orally; group B was given dexmedetomidine 1.5ug/kg nasal drip; group C was given saline nasal drip. All subjects were observed for general information, sleep quality, postoperative cognitive function, anxiety status, sleep quality, adverse effects and complication occurrence. RESULTS: The difference in general information between the three groups was not statistically significant, P > 0.05; the sleep quality scores of the three groups on admission were not statistically significant, P > 0.05. At the Preoperative 1d, postoperative 1d, 3d and 5d, the RCSQ scores of the subjects in group A and group B were higher than those in groups C, and with the postoperative RCSQ scores of subjects in group B were higher as the time increased; the assessment of anxiety status in the three groups 1d before surgery was not statistically significant, P > 0.05. The cognitive function scores of subjects in the three groups were not statistically significant in the preoperative 1d, P > 0.05. The postoperative 1d (24.63 ± 2.23), 3d (25.83 ± 2.53), and 5d (26.15 ± 2.01) scores of the subjects in group B were higher than those in groups A and C (P < 0.05), and the subjects in group B had better recovery of postoperative cognitive function with increasing time; the occurrence of postoperative delirium (POD) in group B (12.5%) were lower on postoperative 5d than those in groups A (37.5%) and C (32.5%) (P < 0.05). There was no statistical significance in the evaluation of anxiety state of the three groups on the first day before operation (P > 0.05). The scores in group B were lower than those in group C on the postoperative 1d, 3d, 5 d (P < 0.05). The overall incidence of adverse reactions and complications in subjects in group B was 17.5% significantly lower than that in groups A and C (P < 0.05). CONCLUSION: Dexmedetomidine can effectively improve the sleep disorder of elderly general anesthesia patients, reduce the damage to their neurocognitive function and the occurrence of POD, effectively reduce the anxiety of patients and the occurrence of adverse reactions and complications, and has better sedative, improve postoperative cognitive function and anti-anxiety effects, with a high drug safety, worthy of clinical application and promotion.

Clinical and radiological differentiation between Trousseau syndrome and cardiogenic embolism: a retrospective case-control study.

Background: Trousseau syndrome (TS) is a thromboembolic event in cancer patients caused by abnormalities in coagulation and fibrinolytic mechanisms. Acute multiple cerebral infarction (AMCI) is a rare form of TS. This study aimed to discuss the differentiation of clinical and radiographic characteristics between TS and cardiogenic embolism (CE) with AMCI as the main manifestation. Methods: We retrospectively analyzed 69 patients with TS-AMCI and 105 patients with CE-AMCI who were treated at Shandong Provincial Hospital between August 2018 and October 2022. The clinical baseline data, laboratory indices, and imaging characteristics of the two groups were compared. A logistic regression was used to analyze the risk factors of TS-AMCI, and receiver operating characteristic (ROC) curves were used to analyze the predictive value of the risk factors. Results: In relation to the clinical data, there were statistically significant differences between the two groups of patients in terms of the lipid and coagulation indices. D-dimer [odds ratio (OR) =4.459, 95% confidence interval (CI): 1.871-10.625; P=0.001] and triglyceride (OR =6.001, 95% CI: 2.375-15.165; P<0.001) were independent risk factors for TS-AMCI. In relation to the radiographic characteristics, the infarctions in the TS-AMCI group were widely distributed in multiple arterial supply areas [23 (33.3%) vs. 10 (9.5%); P<0.001]. More importantly, bilateral anterior + posterior circulation was also an independent risk factor for TS-AMCI (OR =15.005, 95% CI: 1.757-128.17; P=0.013). Conclusions: Unexplained AMCI in the cancer-prone age group, abnormalities in the lipid and D-dimer levels, and infarction foci involving multiple arterial blood supply areas suggested a high probability of TS.

The prognostic value of CD8+ CTLs, CD163+ TAMs, and PDL1 expression in the tumor microenvironment of primary central nervous system lymphoma.

To explore immune cell infiltration and PDL1 expression in the tumor microenvironment (TME) of primary central nervous system lymphoma (PCNSL), we performed immunohistochemical staining on paraffin-embedded tumor tissues from 34 patients diagnosed with PCNSL. CD8 and CD163 positive cells were manually counted, and PDL1 expression was quantified by the H-score scoring method in the tumor center and around the tumor. The Kaplan-Meier method was used to analyze the prognostic value of the TME. We found obvious infiltration of CD8+ CTLs and CD163+ TAMs in the TME of PCNSL patients. And PDL1 was expressed in the tumor center as well as around the tumor. Survival analysis showed that high CD8+ CTLs levels and high intratumoral PDL1 expression were significantly correlated with longer OS. High CD8+ CTLs and CD163+ TAMs levels were associated with longer PFS.

Missed Nursing Care as a Mediator in the Relationship between Career Calling and Turnover Intention.

AIM: To explore the role of missed nursing care in mediating the relationship between career calling and intention to leave among nurses. INTRODUCTION: Increasing nurse turnover is still a major concern in the global healthcare system. The most reliable indicator of turnover is turnover intention. It is crucial to understand its affecting elements to suggest measures to lower nurses' turnover intention. BACKGROUND: Turnover intention has been linked to career calling and missed nursing care. Little empirical research has investigated the possibility that missed nursing care mediates between career calling and turnover intention. METHODS: A cross-sectional survey of 347 nurses was conducted. The survey instruments included the General Information Questionnaire, Calling Scale, Missed Nursing Care Scale and Turnover Intention Questionnaire. Structural equation models were used to build the model. This study made use of the STROBE checklist. RESULTS: For 43.8% of nurses, turnover intention was high or very high. Missed nursing care and turnover intention were negatively correlated with career calling. Missed nursing care and turnover intention were positively related. Missed nursing care mediated the relationship between career calling and turnover intention. DISCUSSION: Career calling and missed nursing care can both influence turnover intention. Career calling can reduce the likelihood of turnover by preventing missed nursing care. CONCLUSION: Missed nursing care mediated the relationship between career calling and intention to leave. IMPLICATIONS FOR NURSING AND NURSING POLICY: Nursing managers should improve nurses' career calling through professional education and minimize missed nursing care by using electronic nursing reminder devices to reduce turnover intention.

Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.

CD146-targeted nuclear medicine imaging in cancer: state of the art.

The transmembrane glycoprotein adhesion molecule CD146 is overexpressed in a wide variety of cancers. Through molecular imaging, a specific biomarker's expression and distribution can be viewed in vivo non-invasively. Radionuclide-labeled monoclonal antibodies or relevant fragments that target CD146 may find potential applications in cancer imaging, thereby offering tremendous value in cancer diagnosis, staging, prognosis evaluation, and prediction of drug resistance. This review discusses the recent developments of CD146-targeted molecular imaging via nuclear medicine, especially in malignant melanoma, brain tumor, lung cancer, liver cancer, breast cancer, and pancreatic cancer. Many studies have proved that CD146 targeting may present a promising strategy for cancer theranostics.

Gray matter asymmetry alterations in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder.

Despite the high coexistence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) (ASD + ADHD), the underlying neurobiological basis of this disorder remains unclear. Altered brain structural asymmetries have been verified in ASD and ADHD, respectively, making brain asymmetry a candidate for characterizing this coexisting disorder. Here, we measured the gray matter (GM) volume asymmetry in ASD + ADHD versus ASD without ADHD (ASD-only), ADHD without ASD (ADHD-only), and typically developing controls (TDc). High-resolution T1-weighted data from 48 ASD + ADHD, 63 ASD-only, 32 ADHD-only, and 211 matched TDc were included in our study. We also assessed brain-behavior relationships and the effects of age on GM asymmetry. We found that there were both shared and disorder-specific GM volume asymmetry alterations in ASD + ADHD, ASD-only, and ADHD-only compared with TDc. This finding demonstrates that ASD + ADHD is neither an endophenocopy nor an additive pathology of ASD and ADHD, but an entirely different neuroanatomical pathology. In addition, ASD + ADHD displayed altered GM volume asymmetries in the prefrontal regions responsible for executive function and theory of mind compared with ASD-only. We also found significant effects of age on GM asymmetry. The present study may provide structural insights into the neural basis of ASD + ADHD.

Investigating altered brain functional hubs and causal connectivity in coronary artery disease with cognitive impairment.

Background: Coronary artery disease (CAD) and cognitive impairment (CI) have become significant global disease and medical burdens. There have been several reports documenting the alterations in regional brain function and their correlation with CI in CAD patients. However, there is limited research on the changes in brain network connectivity in CAD patients. To investigate the resting-state connectivity and further understand the effective connectivity strength and directionality in patients with CAD, we utilized degree centrality (DC) and spectral dynamic causal modeling (spDCM) to detect functional hubs in the whole brain network, followed by an analysis of directional connections. Using the aforementioned approaches, it is possible to investigate the hub regions and aberrant connections underlying the altered brain function in CAD patients, providing neuroimaging evidence for the cognitive decline in patients with coronary artery disease. Materials and Methods: This study was prospectively conducted involving 24 patients diagnosed with CAD and 24 healthy controls (HC) who were matched in terms of age, gender, and education. Functional MRI (fMRI) scans were utilized to investigate brain activity in these individuals. Neuropsychological examinations were performed on all participants. DC analysis and spDCM were employed to investigate abnormal brain networks in patients with CAD. Additionally, the association between effective connectivity strength and cognitive function in patients with CAD was examined based on the aforementioned results. Results: By assessing cognitive functions, we discovered that patients with CAD exhibited notably lower cognitive function compared to the HC group. By utilizing DC analysis and spDCM, we observed significant reductions in DC values within the left parahippocampal cortex (PHC) and the left medial temporal gyrus (MTG) in CAD patients when compared to the control group. In terms of effective connectivity, we observed the absence of positive connectivity between the right superior frontal gyrus (SFG) and PHC in CAD patients. Moreover, there was an increase in negative connectivity from PHC and MTG to SFG, along with a decrease in the strength of positive connectivity between PHC and MTG. Furthermore, we identified a noteworthy positive correlation (r = 0.491, p = 0.015) between the strength of connectivity between the PHC and the MTG and cognitive function in CAD patients. Conclusions: These research findings suggest that alterations in the connectivity of the brain networks involving SFG, PHC, and MTG in CAD patients may mediate changes in cognitive function.

Nonlinear optical properties in chiral copper oxide nanosheets.

Chiral transition metal oxides (TMOs) are in the forefront of research as potential active materials in various optoelectronic applications. However, the nonlinear optical (NLO) properties of the chiral TMOs have not been fully understood. Here, several kinds of copper oxide nanosheets capped with different chiral amino acids are synthesized. Notably, we investigate the NLO activities of these materials, including broadband second harmonic generation and transformation of nonlinear optical properties from saturable absorption to reverse saturable absorption. This work will broaden the use of chiral TMO materials in nonlinear photonic devices.

Role and application of chemokine CXCL13 in central nervous system lymphoma.

Chemokine ligand 13 (CXCL13) and its chemokine receptor 5 (CXCR5) both play significant roles in the tumor microenvironment (TME). CXCL13 in cerebrospinal fluid (CSF) has recently been found to have significant diagnostic and prognostic value in primary and secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL), and the CXCL13-CXCR5 axis has been shown to play an important chemotactic role in the TME of CNS-DLBCL. In this review, we first describe the clinical value of CXCL13 in CSF as a prognostic and diagnostic biomarker for CNS-DLBCL. In addition, this review also discusses the specific mechanisms associated with the CXCL13-CXCR5 axis in tumor immunity of primary diffuse large B cell lymphoma of the central nervous system (PCNS-DLBCL) by reviewing the specific mechanisms of this axis in the immune microenvironment of DLBCL and CNS inflammation, as well as the prospects for the use of CXCL13-CXCR5 axis in immunotherapy in PCNS-DLBCL.

CD39 (ENTPD1) in tumors: a potential therapeutic target and prognostic biomarker.

As a regulator of the dynamic balance between immune-activated extracellular ATP and immunosuppressive adenosine, CD39 ectonucleotidase impairs the ability of immune cells to exert anticancer immunity and plays an important role in the immune escape of tumor cells within the tumor microenvironment. In addition, CD39 has been studied in cancer patients to evaluate the prognosis, the efficacy of immunotherapy (e.g., PD-1 blockade) and the prediction of recurrence. This article reviews the importance of CD39 in tumor immunology, summarizes the preclinical evidence on targeting CD39 to treat tumors and focuses on the potential of CD39 as a biomarker to evaluate the prognosis and the response to immune checkpoint inhibitors in tumors.

Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity.

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.

Endotoxin induced acute kidney injury modulates expression of AQP1, P53 and P21 in rat kidney, heart, lung and small intestine.

This study was designed to explore whether aquaporin 1(AQP1), P53 and P21 can be used as diagnostic biomarkers of lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and potential indicators of sepsis-induced multiple organ injury. Bioinformatics results demonstrated that AQP1, P53, P21 was dramatically elevated 6h after Cecal ligation and puncture (CLP)-AKI in rat renal tissue. The expression of AQP1, P53, P21, NGAL and KIM-1 in kidney were increased significantly at first and then decreased gradually in LPS-induced AKI rats. Histopathological sections showed swelling of tubular epithelial cells and destruction of basic structures as well as infiltration of numerous inflammatory cells in LPS-induced AKI. Moreover, the expressions of AQP1, P53 and P21 in heart were significantly increased in LPS treatment rats, while the AQP1 expressions in lung and small intestine were significantly decreased. The level of NGAL mRNA in heart, lung and small intestine was firstly increased and then decreased during LPS treatment rats, but the expression of KIM-1 mRNA was not affected. Therefore, our results suggest that AQP1, P53 and P21 is remarkably upregulated in LPS-induced AKI, which may be considered as a potential novel diagnostic biomarker of Septic AKI. NGAL may serve as a biomarker of sepsis-induced multiple organ damage during the process of LPS-induced AKI.

Combining network pharmacology and in vitro and in vivo experiments to study the mechanism of Keluoxin in the treatment of radiation nephropathy†.

Radiation nephropathy refers to kidney damage caused by radiation therapy for malignant tumours. Currently, the pathogenesis is unclear and there is a lack of effective treatment methods. With the development of traditional Chinese medicine, the role of traditional Chinese medicine in the protection of radiation nephropathy is receiving increasing attention. Therefore, in this study, we used X-ray intraperitoneal irradiation to construct a mouse model of radiation nephropathy and studied the protective effect of traditional Chinese medicine Keluoxin on radiation nephropathy. We first analysed the potential targets and pathways of Keluoxin in the treatment of radiation nephropathy using network pharmacology methods, combined with in vitro and in vivo experimental verification, to study its potential mechanism. By searching the database, 136 components of Keluoxin were identified. A total of 333 intersectional targets related to radiation nephropathy were obtained. Among them, key targets include IL-6, TNF-α, HIF-1α, STAT1, STAT3, JAK1, JAK2, etc. In in vivo and in vitro experiments, we found that as the irradiation dose increased and time prolonged, kidney damage in mice gradually worsened in a time-dependent and dose-dependent manner. As the irradiation dose increases, the expression of pro-inflammatory factors Il-6, TNF-α, TGF-ß increased. Compared with the irradiation group, the intervention of Keluoxin can reduce kidney damage caused by X-ray irradiation and reduce the expression of IL-6, TNF-α, TGF-ß, STAT1, STAT3, JAK1, JAK2, etc. These results indicated that Keluoxin can alleviate kidney damage caused by X-ray irradiation, possibly by regulating the JAK/STAT signalling pathway, reducing inflammation levels and oxidative stress damage.