Optimal use of ß-lactams in neonates: machine learning-based clinical decision support system.

BACKGROUND: Accurate prediction of the optimal dose for ß-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections. METHODS: Five ß-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses. FINDINGS: For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses. INTERPRETATION: An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal ß-lactam antibiotic doses. FUNDING: This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.

Population pharmacokinetics and dose optimization of levofloxacin in elderly patients with pneumonia.

AIMS: Levofloxacin is a quinolone antibiotic with a broad antibacterial spectrum. It is frequently used in elderly patients with pneumonia. The pharmacokinetic profile of elderly patients changes with age, but data on the pharmacokinetics of levofloxacin in these patients are limited. The aim of this study was to establish a population pharmacokinetic model of levofloxacin in elderly patients with pneumonia and to optimize individualized dosing regimens based on this newly developed model. METHODS: This is a prospective, open-label pharmacokinetic study in elderly patients with pneumonia. Blood samples were collected using an opportunistic approach. The plasma concentrations of levofloxacin were determined by high-performance liquid chromatography. A population pharmacokinetic model was established using nonlinear mixed-effect model software. Monte Carlo simulations were used for dose simulation and dose optimization. RESULTS: Data from 51 elderly patients with pneumonia were used for the population pharmacokinetic analysis. A one-compartment model with first-order elimination was most suitable for describing the data, and the estimated glomerular filtration rate was the only covariate that had a significant impact on the model. The final model estimated that the mean clearance of levofloxacin in elderly patients with pneumonia was 5.26 L/h. Monte Carlo simulation results showed that the optimal dosing regimen for levofloxacin was 750 mg once a day in elderly patients with pneumonia, with a minimum inhibitory concentration of 2 mg/L. CONCLUSIONS: The population pharmacokinetic model of levofloxacin in elderly patients with pneumonia was established, and the dose optimization of levofloxacin was completed through Monte Carlo simulation.

The STING inhibitor C-176 attenuates MPTP-induced neuroinflammation and neurodegeneration in mouse parkinsonian models.

Recent emerging evidence reveals that cGAS-STING-mediated Type I interferon (IFN) signaling axis takes part in the microglial-associated neuroinflammation. However, the potential role of pharmacological inhibition of STING on neuroinflammation and dopaminergic neurodegeneration remains unknown. In the present study, we investigated whether pharmacological inhibition of STING attenuates neuroinflammation and neurodegeneration in experimental models of Parkinson's disease. We report that therapeutic inhibition of STING with C-176 significantly inhibited the activation of downstream signaling pathway, suppressed neuroinflammation, and ameliorated MPTP-induced dopaminergic neurotoxicity and motor deficit. Furthermore, pharmacological inhibition of STING with C-176 attenuated proinflammatory response in BV2 microglial cells exposed to LPS/MPP+. More importantly, C-176 also reduced NLRP3 inflammasome activation both in vitro and in vivo. The results of our study suggest that pharmacologic inhibition of STING protects against dopaminergic neurodegeneration and neuroinflammation that may act at least in part through suppressing NLRP3 inflammasome activation. STING signaling may hold great promise for the development of new treatment strategy for PD.

[Emergency Management of Medical Equipment in Designated Hospitals for Public Health Emergencies].

Medical supply is a key resource for responding to public health emergencies and maintaining people's lives and health. As the medical equipment management department, the medical devices department is mainly responsible for the procurement, supply, technical support, management and coordination of medical equipment and medical consumables, playing an important role in epidemic prevention and control. Through the analysis of the expansion cases of designated hospitals, the experience of emergency management of medical equipment has been accumulated, which has strong practicability and replicability.

Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model.

Microglia-mediated neuroinflammation and mitochondrial dysfunction play critical role in the pathogenic process of Parkinson's disease (PD). Mitophagy plays central role in mitochondrial quality control. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia-mediated neurodegeneration and neuroinflammation. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA). Several preclinical studies have reported the beneficial effects of UA on age-related conditions by increasing mitophagy and blunting excessive inflammatory responses. However, the specific role of UA in pathology of PD remains unknown. In this study, we showed that treatment with UA reduced the loss of dopaminergic neurons, ameliorated behavioral deficits and neuroinflammation in MPTP mouse model of PD. Further study revealed that UA promotes mitophagy, restores mitochondrial function and attenuate proinflammatory response in BV2 microglial cells exposed to LPS. Moreover, UA also reduced NLRP3 inflammasome activation both in vitro and in vivo. Importantly, disruption of microglial mitophagy with pharmacological or genetic approach partly blunted the neuroprotective effects of UA in MPTP mouse model of PD. Collectively, these results provide strong evidence that UA protects against dopaminergic neurodegeneration and neuroinflammation. The mechanism may be related with its inhibition of NLRP3 inflammasome activation via promoting mitophagy in microglia.

Design, synthesis and biological evaluation of dual HDAC and VEGFR inhibitors as multitargeted anticancer agents.

Herein, a novel series of dual histone deacetylase (HDAC) and vascular endothelial growth factor receptor (VEGFR) inhibitors were designed, synthesized and biologically evaluated based on previously reported pazopanib-based HDAC and VEGFR dual inhibitors. Most target compounds showed significant HDAC1, HDAC6 and VEGFR2 inhibition, which contributed to their potent antiproliferative activities against multiple cancer cell lines and significant antiangiogenic potencies in both human umbilical vein endothelial cell (HUVEC) tube formation assays and rat thoracic aorta ring assays. Further HDAC selectivity evaluations indicated that hydroxamic acids 5 and 9e possessed HDAC isoform selectivity profiles similar to that of the approved HDAC inhibitor suberoylanilide hydroxamic acid(SAHA), while hydrazide12 presented an HDAC isoform selectivity profilesimilar to that of the clinical HDAC inhibitor MS-275. The VEGFR inhibition profiles of 5, 9e and 12 were similar to that of the approved VEGFR inhibitor pazopanib. The intracellular target engagements of Compounds 5 and 12 were confirmed by western blot analysis. The metabolic stabilities of 5, 9e and 12 in mouse liver microsomes were inferior to that of pazopanib. These dual HDAC and VEGFR inhibitors provide lead compounds for further structural optimization to obtainpolypharmacological anticancer agents.

Urolithin A protects dopaminergic neurons in experimental models of Parkinson's disease by promoting mitochondrial biogenesis through the SIRT1/PGC-1α signaling pathway.

Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Therapeutic strategies targeting mitochondrial dysfunction hold considerable promise for the treatment of PD. Recent reports have highlighted the protective role of urolithin A (UA), a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries and walnuts, in several neurological disorders including Alzheimer's disease and ischemic stroke. However, the potential role of UA in PD has not been characterized. In this study, we investigated the underlying mechanisms for role of UA in 6-OHDA-induced neurotoxicity in cell cultures and mice model of PD. Our results revealed that UA protected against 6-OHDA cytotoxicity and apoptosis in PC12 cells. Meanwhile, administration of UA to 6-OHDA lesioned mice ameliorated both motor deficits and nigral-striatal dopaminergic neurotoxicity. More important, UA treatment significantly attenuated 6-OHDA-induced mitochondrial dysfunction in PC12 cells accompanied by enhanced mitochondrial biogenesis. Mechanistically, we demonstrated that UA exerts neuroprotective effects by promoting mitochondrial biogenesis via SIRT1-PGC-1α signaling pathway. Taken together, these data provide new insights into the novel role of UA in regulating mitochondrial dysfunction and suggest that UA may have potential therapeutic applications for PD.

In vitro and in vivo anti-inflammatory effect of Zaluzanin D isolated from Achillea acuminate.

The present study was investigated to verify anti-inflammatory and immune regulation effect of Zaluzanin D on LPS-induced macrophages and acute lung injury. NR8383 macrophages were pre-treated with Zaluzanin D and stimulated by LPS. Zaluzanin D reduced the production of nitric oxide in NR8383 macrophages and decreased the secretions of inflammatory cytokines. In addition, intravenous of Zaluzanin D to LPS-induced rats reduced the infiltrations of macrophages into BALF and the histological inflammatory changes in lung tissues. Furthermore, Z.D inhibited lipid peroxidation and effectively recruit the anti-oxidative defense system, regulated the levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in the lungs by inhibitory expression of nuclear factor-kappa B pathway. These findings suggested that Zaluzanin D attenuated pulmonary inflammatory responses by inhibiting the expression of diverse inflammatory mediators in vitro and in vivo.

Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance.

BACKGROUND: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo. MATERIALS AND METHODS: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs. RESULTS: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg-1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells. CONCLUSION: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.

Purification, structural characterization and in vivo immunoregulatory activity of a novel polysaccharide from Polygonatum sibiricum.

The purpose of this study was to study polysaccharides isolated from Polygonatum sibiricum to establish the structure-activity relationships of the active substances and to discover the optimal fraction for further development and application. Four polysaccharides fractions (PSP1, PSP2, PSP3 and PSP4) from P. sibiricum were obtained by DEAE-Sepharose Fast Flow ion-exchange chromatography. Acid hydrolysis and FT-IR spectral and NMR spectral analyses were employed for structural analysis. Our results illustrated that PSP with different chemical structure and monosaccharide composition showed different abilities to activate phagocytic activity in vitro. According to the preliminary screening results in vitro, the newly identified water-soluble polysaccharides of PSP3 were selected for further evaluation in vivo. The results demonstrated that PSP3 possessed an immunomodulatory function and could be regarded as a promising candidate as an immunomodulator.

Models Matter, So Does Training: An Empirical Study of CNNs for Optical Flow Estimation.

We investigate two crucial and closely-related aspects of CNNs for optical flow estimation: models and training. First, we design a compact but effective CNN model, called PWC-Net, according to simple and well-established principles: pyramidal processing, warping, and cost volume processing. PWC-Net is 17 times smaller in size, 2 times faster in inference, and 11 percent more accurate on Sintel final than the recent FlowNet2 model. It is the winning entry in the optical flow competition of the robust vision challenge. Next, we experimentally analyze the sources of our performance gains. In particular, we use the same training procedure for PWC-Net to retrain FlowNetC, a sub-network of FlowNet2. The retrained FlowNetC is 56 percent more accurate on Sintel final than the previously trained one and even 5 percent more accurate than the FlowNet2 model. We further improve the training procedure and increase the accuracy of PWC-Net on Sintel by 10 percent and on KITTI 2012 and 2015 by 20 percent. Our newly trained model parameters and training protocols are available on https://github.com/NVlabs/PWC-Net.

Polysaccharides from Polygonatum sibiricum Delar. ex Redoute induce an immune response in the RAW264.7 cell line via an NF-κB/MAPK pathway.

The aim of this study was to examine the effect of polysaccharides from Polygonatum sibiricum (PSP) on RAW 264.7 cells together with the underlying signaling pathways. Water-soluble polysaccharides were extracted from Polygonatum sibiricum and the immunological activity/mechanism was explored in depth in RAW 264.7 cells. Our results demonstrated that PSP induced dendritic-like morphological changes in RAW 264.7 cells, and increased the production of nitric oxide, TNF-α and IL-6 in a dose-dependent manner. Mechanistic studies revealed that PSP promoted the accumulation of TNF-α and IL-6 mRNA and caused IκB-α degradation and NF-κB p65 translocation into the nucleus at both the transcriptional and translational levels. The expression of iNOS, COX-2, NF-κB and phosphorylated p38 MAPK was upregulated in PSP-treated RAW 264.7 cells. Water-soluble polysaccharides possess immunological activity and the immunostimulatory mechanism may be attributed to the NF-κB and p38 MAPK pathways similar to the mechanism of lipopolysaccharides.

Qualitative and quantitative analysis of Yifei Tongluo granules to identify main bioactive components using LC-DAD/MS and pharmacokinetic studies.

A standard fingerprint containing twelve common peaks was constructed from ten batches of Yifei Tongluo granules to evaluate batch-to-batch consistency by using HPLC-DAD. Additionally, the corresponding medicinal material attributes of these chemical constituents were analyzed according to the data acquired from the HPLC method and the identification was further carried out using the LC-MS/MS method. Comparing the retention time or accurate mass with previous studies or standards, the common components were tentatively identified in 50 min for ten batches of samples. At the same time, a reliable LC-MS/MS method was established to quantify marker substances simultaneously in 25 min, and the linear relationship of the standard curves was good in the experimental range. The validations of the method were successfully applied to the quality control and pharmacokinetic study. The results obtained from this study suggest that militarine was most abundant and the components in the granules caused pharmacokinetic herb-drug interactions in rats. This study provides a meaningful basis for evaluating the viability of Yifei Tongluo granules for clinical applications.

Acetyl-11-keto-ß-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties.

Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms. We showed that AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells; its IC50 value in anti-proliferation was ∼17 µM. Furthermore, AKBA dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by significant decrease in the ability of mammosphere formation and down-regulated expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. AKBA (10-30 µM) dose-dependently suppressed the activation of Akt and Stat3 signaling pathways in PC3/Doc cells. In contrast, overexpression of Akt and Stat3 significantly attenuated the inhibition of AKBA on PC3/Doc cell proliferation. In docetaxel-resistant PCa homograft mice, treatment with AKBA significantly suppresses the growth of homograft RM-1/Doc, equivalent to its human PC3/Doc, but did not decrease their body weight. In summary, we demonstrate that AKBA inhibits the growth inhibition of docetaxel-resistant PCa cells in vitro and in vivo via blocking Akt and Stat3 signaling, thus suppressing their cancer stem cell-like properties.

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells.

Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP-based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins. Notably, Excision repair cross-complementing 1, a critical gene in the nucleotide excision repair pathway, exhibited the most significant decrease. When combined with CDDP, RAB-mediated impairment of DNA repair resulted in prolonged DNA damage, as demonstrated by the long-lasting appearance of phosphorylation of histone H2AX at Ser139, which potentially enhanced the chemosensitivity to CDDP. Concurrently, the proapoptotic protein death receptor 5 (DR5) was activated by RAB, which also enhanced the chemotherapeutic response of CDDP. Knockdown of DR5 partially blocked RAB-CDDP synergism, suggesting the crucial involvement of DR5 in this event. The results of the present study identified that RAB functioned synergistically with CDDP to increase the efficacy of CDDP by inhibiting DNA damage repair and activating DR5, suggesting the mechanistic basis for the antitumor effect of RAB in combination with current chemotherapeutics.

Acetylpuerarin protects against OGD-induced cell injury in BV2 microglia by inhibiting HMGB1 release.

High mobility group box 1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic injury, initiates inflammatory response and aggravates brain tissue damage. Acetylpuerarin (AP), an acetylated derivative of puerarin, was reported to protect against cerebrovascular ischemia-reperfusion injury in rats through anti-inflammation. In the present study, we aim to investigate whether AP inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated BV2 microglia. BV2 microglia viability after OGD with or without AP was measured by CCK-8 assay, apoptosis of BV2 microglia was determined by Hoechst 33258 staining and FITC-Annexin V/7-AAD staining. HMGB1 protein level and release was detected by western blotting and immunofluorescent FITC-staining. The results demonstrated that AP significantly rescued OGD-induced cell death and apoptosis in a dose-dependent manner. AP inhibited OGD-induced HMGB1secretion at the level of nuclear to cytoplasmic translocation, decreased cytoplasmic HMGB1 at protein level, and the effects showed dose-dependent. The findings suggest that AP can protect against OGD-induced cellular injury in BV2 microglia by inhibition of HMGB1 release.

Suppression of the NF­κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute.

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)­κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a novel macrocyclicbis (bibenzyl) compound, was isolated from the Chinese liverwort plant. Previous studies have suggested that Riccardin D exerted chemo­preventative effects against the intestinal malignancy formation. In the present study, cell counting kit­8, Hochest 33258 staining, mitochondria membrane permeability assay, western blotting analysis, reverse transcription­polymerase chain reaction, luciferase reporter gene assay and molecular modeling analysis were performed to detect the effect and mechanisms of Riccardin D on human colon cancer cells. The results demonstrated that Riccardin D significantly inhibited the growth of HT­29 cells. In addition, the cDNA expression of cyclooxygenase­2, and the protein expression and activity of NF­κB and tumor necrosis factor­α were downregulated; however, the protein expression of cleaved caspase­3 and ­9, and cleaved poly (adenosine diphosphate­ribose) polymerase, and the B­cell lymphoma (Bcl)­2: Bcl­2­associated X protein ratio were upregulated. Furthermore, Auto Dock analysis identified binding sites between Riccardin D and NF­κB. These results indicated that Riccardin D may inhibit cell proliferation and induce apoptosis in HT­29 cells, which may be associated with the blocking of the NF­κB signaling pathway. Thus, Riccardin D should be investigated as an NF­κB inhibitor in cancer therapy.

Deblurring Images via Dark Channel Prior.

We present an effective blind image deblurring algorithm based on the dark channel prior. The motivation of this work is an interesting observation that the dark channel of blurred images is less sparse. While most patches in a clean image contain some dark pixels, this is not the case when they are averaged with neighboring ones by motion blur. This change in sparsity of the dark channel pixels is an inherent property of the motion blur process, which we prove mathematically and validate using image data. Enforcing sparsity of the dark channel thus helps blind deblurring in various scenarios such as natural, face, text, and low-illumination images. However, imposing sparsity of the dark channel introduces a non-convex non-linear optimization problem. In this work, we introduce a linear approximation to address this issue. Extensive experiments demonstrate that the proposed deblurring algorithm achieves the state-of-the-art results on natural images and performs favorably against methods designed for specific scenarios. In addition, we show that the proposed method can be applied to image dehazing.

Strategies to release doxorubicin from doxorubicin delivery vehicles.

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli. This article focuses on various strategies that serve as potential tools to release DOX from DOX-loaded vehicles efficiently to achieve a higher DOX concentration in tumour tissue and a lower concentration in normal tissue. With a deeper understanding of the differences between normal and tumour tissues, it might be possible to design ever more promising prodrug systems for DOX delivery and cancer therapy in the near future.

Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways.

Renal injury is a dose-dependent side effect of epirubicin that limits its clinical application in the field of tumor chemotherapy. Paeonol is an active ingredient with a variety of biological activities, including the prevention of multiple antineoplastic-induced toxicities. In the present study, we assessed the renoprotective effect of paeonol on epirubicin-induced nephrotoxicity and investigated the underlying mechanism. Renal function, kidney histology, oxidative stress, nitrative stress, inflammation, apoptotic proteins and the effects on signaling pathways were investigated. Paeonol lowered the levels of biomarkers of renal injury, relieved histopathological alterations, alleviated oxidative stress and nitrative stress, and ameliorated inflammation. Moreover, paeonol inhibited epirubicin-induced apoptosis by suppressing the activation of caspase-9 and caspase-3, the Bax/Bcl-2 imbalance and cytochrome c release. Further studies suggest that paeonol up-regulates the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1 and down-regulates the NF-κB pathway by reducing IκBα degradation and blocking the p-NF-κB nuclear translocation. In conclusion, paeonol alleviates epirubicin-induced renal injury in mice by regulating the Nrf2 and NF-κB signaling pathways.