Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity.

Isoxazoline is a novel structure with strong potential for controlling agricultural insect pests, but its high toxicity to honeybees limits its development in agriculture. Herein, a series of N-phenylamide isoxazoline derivatives with low honeybee toxicity were designed and synthesized using the intermediate derivatization method. Bioassay results showed that these compounds exhibited good insecticidal activity. Compounds 3b and 3f showed significant insecticidal effects against Plutella xylostella (P. xylostella) with median lethal concentrations (LC50) of 0.06 and 0.07 mg/L, respectively, comparable to that of fluralaner (LC50 = 0.02 mg/L) and exceeding that of commercial insecticide fluxametamide (LC50 = 0.52 mg/L). It is noteworthy that the acute honeybee toxicities of compounds 3b and 3f (LD50 = 1.43 and 1.63 µg/adult, respectively) were significantly reduced to 1/10 of that of fluralaner (LD50 = 0.14 µg/adult), and were adequate or lower than that of fluxametamide (LD50 = 1.14 µg/adult). Theoretical simulation using molecular docking indicates that compound 3b has similar binding modes with fluralaner and a similar optimal docking pose with fluxametamide when binding to the GABA receptor, which may contribute to its potent insecticidal activity and relatively low toxicity to honey bees. This study provides compounds 3b and 3f as potential new insecticide candidates and provides insights into the development of new isoxazoline insecticides exhibiting both high efficacy and environmental safety.

Influence of Spider Silk Protein Structure on Mechanical and Biological Properties for Energetic Material Detection.

Spider silk protein, renowned for its excellent mechanical properties, biodegradability, chemical stability, and low immune and inflammatory response activation, consists of a core domain with a repeat sequence and non-repeating sequences at the N-terminal and C-terminal. In this review, we focus on the relationship between the silk structure and its mechanical properties, exploring the potential applications of spider silk materials in the detection of energetic materials.

Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity.

Poor immunogenicity seriously hampers the broader implementation of antitumor immunotherapy. Enhanced immunogenicity capable of achieving greater antitumor immunity is urgently required. Here, a novel polymer that contains hydrophobic ferrocene (Fc) units and thioketal bonds in the main chain, which further delivered a prodrug of oxaliplatin and artesunate, i.e., Artoxplatin, to cancer cells is described. This polymer with Fc units in the nanoparticle can work as a polyigniter to spark the peroxide bonds in Artoxplatin and generate abundant reactive oxygen species (ROS) to kill cancers as nanobombig for cancer therapy. Moreover, ROS can trigger the breakdown of thioketal bonds in the polymer, resulting in the biodegradation of the polymer. Importantly, nanobombig can facilitate the maturation of dendritic cells and promote the activation of antitumor immunity, through the enhanced immunogenic cell death effect by ROS generated in situ. Furthermore, metabolomics analysis reveals a decrease in glutamine in nanobombig -treated cancer cells, resulting in the upregulation of programmed death ligand 1 (PD-L1). Consequently, it is further demonstrated enhanced tumor inhibitory effects when using nanobombig combined with anti-PD-L1 therapy. Overall, the nanosystem offers a rational design of an efficient chemo-immunotherapy regimen to promote antitumor immunity by improving tumor immunogenicity, addressing the key challenges cancer immunotherapy faced.

Combined analysis of cross-population healthy adult human microbiome reveals consistent differences in gut microbial characteristics between Western and non-Western countries.

Despite extensive research on the gut microbiome of healthy individuals from a single country, there are still a limited number of population-level comparative studies. Moreover, the sequencing approach used in most related studies involves 16 S ribosomal RNA (rRNA) sequencing with a limited resolution, which cannot provide detailed functional profiles. In the present study, we applied a combined analysis approach to analyze whole metagenomic shotgun sequencing data from 2035 healthy adult samples from six countries across four continents. Analysis of core species revealed that 13 species were present in more than 90 % of all investigated individuals, the majority of which produced short-chain fatty acids (SCFA)-producing bacteria. Our analysis revealed consistently significant differences in gut microbial species and pathways between Western and non-Western countries, such as Escherichia coli and the relation of MetaCyc pathways to the TCA cycle. Specific changes in microbial species and pathways are potentially related to lifestyle and diet. Furthermore, we identified several noteworthy microbial species and pathways that exhibit distinct characteristics specific to China. Interestingly, we observed that China (CHN) was more similar to the United States (USA) and United Kingdom (GBR) in terms of the taxonomic and functional composition of the gut microbiome than India (IND) and Madagascar (MDG), which were more similar to the China (CHN) diet. The current study identified consistent microbial features associated with population and geography, which will inspire further clinical translations that consider paying attention to differences in microbiota backgrounds and confounding factors.

Application of QSAR models for acute toxicity of tetrazole compounds administrated orally and intraperitoneally in rat and mouse.

Tetrazoles and their derivatives possess various biological activities, such as antibacterial, anti-fungal, and other activities. However, these compounds may induce specific cumulative and toxic effects in living organisms. Therefore, quantitative structure-activity relationship (QSAR) models were constructed to study the acute oral toxicity of tetrazoles in rats and mice. The toxicity data of 111 tetrazole compounds were collected using the ChemIDplus, ChEMBL and ECHA databases as response variables, while the PaDEL-descriptor generated the 2D descriptors as independent variables. The models were developed and validated following the OECD guidelines by the DTC-QSAR tool. Three QSAR models were successfully established for the oral routes of rat and mouse and the intraperitoneal route of mouse, respectively. The scatter plots showed high consistency between the training and test data sets. All the models successfully met the external and internal validation criteria. Most of the descriptors kept in the final models exhibited positive correlations with toxicity, whereas only 6 descriptors exhibited negative associations. Several chemicals were identified as response or structural outliers, based on the standardized residuals and leverage values. In conclusion, the findings of this investigation demonstrate that the proposed QSAR models hold promise in forecasting the acute toxicity of recently developed or synthesized tetrazole compounds, thereby mitigating potential risks to human health and the environment.

Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization.

Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder.

Dearomatization Silylation of Benzofurans and Furopyridines via Silyl Radical Addition and Endocyclic C-O Bond Scission.

Direct introduction of silyl radicals to forge C-Si bonds is of central importance in organic synthesis, owing to the formidable potential of silyl groups as coupling partners for further derivatization reactions to achieve more valuable compounds. Cleavage of heteroaromatic endocyclic carbon-heteroatom bonds to assemble C-Si bonds is scarce. Here, we demonstrate a dearomatization silylation of benzofurans and furopyridines via silyl radical addition and C(2)-O bond scission under metal-catalyst-free and mild conditions. Preliminary mechanistic experiments suggest that these transformations involve radical/single-electron transfer and [1,5]-Brook rearrangement processes. This protocol for the total synthesis of Doxepin and oxyresveratrol derivatives is carried out. The silylated products in several transformation reactions have proven to be useful as synthetic intermediates.

A survey of epidemic management data models.

The COVID-19 epidemic has demonstrated the important role that data plays in the response to and management of public health emergencies. It has also heightened awareness of the role that ontologies play in the design of semantically precise data models that improve data interoperability among stakeholders. This paper surveys vocabularies and ontologies relevant to the task of achieving epidemic-related data interoperability. The paper first reviews 16 vocabularies and ontologies with respect to the use cases. Next it identifies patterns of knowledge that are common across multiple vocabularies and ontologies, followed by an analysis of patterns that are missing, based on the use cases. Conclusions show that existing vocabularies and ontologies provide significant coverage of the concepts underlying epidemic use cases, but there remain gaps in the coverage. More work is required to cover missing but significant concepts.

Preparation and Characterization of Insecticide/Calix[4]arene Complexes and Their Enhanced Insecticidal Activities against Plutella xylostella.

Applications of supramolecular materials in plant protection have attracted significant interest in recent years. To develop a feasible method to improve the efficacy and reduce the usage of chemical pesticides, the effect of calix[4]arene (C4A) inclusion on enhancing the insecticidal activity of commercial insecticides was investigated. Results showed that all three tested insecticides (chlorfenapyr, indoxacarb, and abamectin) with distinct molecular sizes and modes of action were able to form stable 1:1 host-guest complexes with C4A through simple preparation steps. The insecticidal activities of the complexes against Plutella xylostella were effectively enhanced compared to the guest molecule, with the synergism ratio being up to 3.05 (for indoxacarb). An obvious correlation was found between the enhanced insecticidal activity and the high binding affinity between insecticide and C4A, while the improvement in water solubility may not be a determining factor. The work would provide hints for the further development of functional supramolecular hosts as synergists in pesticide formulations.

Salidroside protect Chinese hamster V79 cells from genotoxicity and oxidative stress induced by CL-20.

Hexanitrohexaazaisowurtzitane (CL-20) is a high-energy elemental explosive widely used in chemical and military fields. CL-20 harms environmental fate, biosafety, and occupational health. However, there is little known about the genotoxicity of CL-20, in particular its molecular mechanisms. Therefore, this study was framed to investigate the genotoxic mechanisms of CL-20 in V79 cells and evaluate whether the genotoxicity could be diminished by pretreating the cells with salidroside. The results showed that CL-20-induced genotoxicity in V79 cells primarily through oxidative damage to DNA and mitochondrial DNA (mtDNA) mutation. Salidroside could significantly reduce the inhibitory effect of CL-20 on the growth of V79 cells and reduce the levels of reactive oxygen species (ROS), 8-hydroxy-2 deoxyguanosine (8-OHdG), and malondialdehyde (MDA). Salidroside also restored CL-20-induced superoxide dismutase (SOD) and glutathione (GSH) in V79 cells. As a result, salidroside attenuated the DNA damage and mutations induced by CL-20. In conclusion, oxidative stress may be involved in CL-20-induced genotoxicity in V79 cells. Salidroside could protect V79 cells from oxidative damage induced by CL-20, mechanism of which may be related to scavenging intracellular ROS and increasing the expression of proteins that can promote the activity of intracellular antioxidant enzymes. The present study for the mechanisms and protection of CL-20-mediated genotoxicity will help further to understand the toxic effects of CL-20 and provide information on the therapeutic effect of salidroside in CL-20-induced genotoxicity.

Advance toward isolation, extraction, metabolism and health benefits of kaempferol, a major dietary flavonoid with future perspectives.

As a major ubiquitous secondary metabolite, flavonoids are widely distributed in planta. Among flavonoids, kaempferol is a typical natural flavonol in diets and medicinal plants with myriad bioactivities, such as anti-inflammatory activity, anti-cancer activity, antioxidant activity, and anti-diabetic activity. However, the natural sources, absorption and metabolism as well as the bioactivities of kaempferol have not been reviewed comprehensively and systematically. This review highlights the latest research progress and the effect of kaempferol in the prevention and treatment of various chronic diseases, as well as its protective health effects, and provides a theoretical basis for future research to be used in nutraceuticals. Further, comparison of the different extraction and analytical methods are presented to highlight the most optimum for PG recovery and its detection in plasma and body fluids. Such review aims at improving the value-added applications of this unique dietary bioactive flavonoids at commercial scale and to provide a reference for its needed further development.

Association of visit-to-visit HbA1c variability with cardiovascular diseases in type 2 diabetes within or outside the target range of HbA1c.

Background: Although a growing attention has been recently paid to the role of HbA1c variability in the risk of diabetic complications, the impact of HbA1c variability on cardiovascular diseases (CVD) in type 2 diabetes is still debated. The aim of the study is to investigate the association of HbA1c variability with CVD in individuals within or outside the target range of HbA1c. Methods: Using data from Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), we enrolled 855 patients with type 2 diabetes in China. The primary outcomes included major macrovascular events and major microvascular events. Visit-to-visit HbA1c variability was expressed as the coefficient of variation (CV) of five measurements of HbA1c taken 3-24 months after treatment. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). Results: Among 855 patients in the intensive glucose treatment group, 563 and 292 patients were assigned to the group of "within the target range of HbA1c" (WTH) (updated mean HbA1c ≤ 7.0%) and "outside the target range of HbA1c" (OTH) (updated mean HbA1c > 7.0%), respectively. HbA1c variability was positively associated with the risk of major microvascular events in all patients and both the subgroups during a median follow-up period of 4.8 years. Particularly, the risk related to HbA1c variability was higher in patients in WTH group for the new or worsening nephropathy [aHR: 3.35; 95% confidence interval (CI): 1.05-10.74; P = 0.042]. Conclusions: This retrospective cohort study confirmed the positive correlation between HbA1c variability and major microvascular events, especially in subjects in WTH or OTH.

Hydraulic constraints determine the distribution of heteromorphic leaves along plant vertical height.

As an interesting and important trait of some drought-tolerant species, heteromorphic leaves are distributed differentially along plant vertical heights. However, the underpinning mechanism for the formation of heteromorphic leaves remains unclear. We hypothesize that heteromorphic leaves are caused by the hydraulic constraints possibly due to the compensation of the changes in functional traits in response to water transport capacity or the reduction of ineffective water loss. In this study, differences in water transport capacity, morphological traits, anatomical structures, and cellular water relations among three typical types of heteromorphic leaves (i.e., lanceolate, ovate, and broad-ovate) of Populus euphratica Oliv. (a dominant species of desert riparian forest in Central and West Asia) and their relationships were analyzed in order to explore the forming mechanism of heteromorphic leaves. The results showed that the lanceolate, ovate, and broad-ovate leaves were growing in the lower, intermediate, and higher positions from the ground, respectively. Morphological traits, anatomical structures, cellular water relations, and water transport capacity significantly varied among the three types of heteromorphic leaves (P< 0.01). Drought stress in broad-ovate leaves was significantly higher than that in ovate and lanceolate leaves (P< 0.01). Water transport capacity has significant correlations with morphological traits, anatomical structures, and cellular water relations (R 2 ≥ 0.30; P< 0.01). Our results indicated that heteromorphic leaves were used as an important adaptive strategy for P. euphratica to alleviate the increase of hydraulic constraints along vertical heights.

Taurine ameliorates volatile organic compounds-induced cognitive impairment in young rats via suppressing oxidative stress, regulating neurotransmitter and activating NMDA receptor.

Long-term exposure to volatile organic compounds (VOCs) in children leads to intellectual and cognitive impairment. Taurine is an essential nutritional amino acid for children, which can improve neurological development in children. However, the neuroprotective effect of taurine on VOCs-induced cognitive impairment in children remains unclear. The aim of this study was to investigate the neuroprotective effects of taurine on VOCs-induced cognitive impairment in young rats. The rats were nose-only exposed to VOCs for a period of 4 weeks to create a model of cognitive impairment, and 0.5% and 1% taurine in tap water were administered throughout the trial period, respectively. Our results showed that young rats adjusted the recovery of their physiological functions by voluntarily increasing the intake of taurine in tap water when exposed to excessive VOCs by inhalation. In addition, taurine enhanced grasp, shortened the latency period of escape, and improved the learning and memory function of young rats. Moreover, taurine decreased malondialdehyde (MDA), γ-aminobutyric acid (GABA), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Urea, Creatinine (CREA) and injury biomarker level, enhanced superoxide dismutase (SOD), reduced glutathione (GSH) and glutamic acid (Glu) activities, up-regulated the protein expression of brain derived neurotrophic factor (BDNF) and N-Methyl-d-aspartate receptor 1 (NMDAR1) in model rats, and in most of cases 1% but not 0.5%, ameliorated the defects induced by VOCs. Collectively, these findings suggested that taurine protected against VOCs-induced cognitive-behavioral impairment in young rats through inhibiting oxidative stress and regulating neurotransmitter homeostasis. In addition, taurine were capable of restoring abilities of learning and memory in young rats exposed to VOCs by activating the N-Methyl-d-aspartate (NMDA) receptor. The findings suggest taurine as a potential novel drug for the treatment of cognitive behavioral disorders in children.

Toxicity prediction of 1,2,4-triazoles compounds by QSTR and interspecies QSTTR models.

1,2,4-triazole derivatives exhibit various biological activities, including antibacterial and antifungal properties. On the other hand, these chemicals may have unique cumulative and harmful effects on living organisms. The goal of this work is to use quantitative structure-toxicity relationship (QSTR) and interspecies quantitative toxicity-toxicity relationship (iQSTTR) models to predict the acute toxicity of 1,2,4-triazole derivatives. The QSTR models were generated by multiple linear regression (MLR) following the OECD recommendations for QSAR model development and validation. The iQSTTR models were constructed using data on acute oral toxicity in rats and mice, as well as the 2D descriptor. The application domain (AD) analysis was used to identify model outliers and determine if the forecast was credible. Six QSTR models were successfully constructed in rats and mice using various delivery methods, and the scatter plots demonstrated excellent consistency across training and test sets. According to external and internal validation criteria, all six QSTR models may be broadly accepted; however, the orally administered mice model was the optimum one among the six species. Several chemicals with leverage values above the requirements were identified as response or structural outliers in the training sets for six QSTR and two iQSTTR models. All outliers, however, fell slightly outside the threshold or had low prediction errors, which may have had little impact on the capacity to forecast and were therefore preserved in the final models. In fact, neither the QSTR nor the iQSTTR test sets contained any response outliers. Additionally, all external and internal validation results for the iQSTTR models were approved, with the iQSTTR models outperforming the comparable QSTR models, which are deemed more dependable. The QSTR and iQSTTR models performed well in predicting toxicity using test sets, which would be beneficial in evaluating and synthesizing newly discovered 1,2,4-triazoles derivatives with low toxicity and environmental hazard.

Development and Validation of a Predictive Nomogram with Age and Laboratory Findings for Severe COVID-19 in Hunan Province, China.

Purpose: To identify more objectively predictive factors of severe outcome among patients hospitalized for coronavirus disease 2019 (COVID-19). Patients and Methods: A retrospective cohort of 479 hospitalized patients diagnosed with COVID-19 in Hunan Province was selected. The prognostic effects of factors such as age and laboratory indicators were analyzed using the Kaplan-Meier method and Cox proportional hazards model. A prognostic nomogram model was established to predict the progression of patients with COVID-19. Results: A total of 524 patients in Hunan province with COVID-19 from December 2019 to October 2020 were retrospectively recruited. Among them, 479 eligible patients were randomly assigned into the training cohort (n = 383) and validation cohort (n = 96), at a ratio of 8:2. Sixty-eight (17.8%) and 15 (15.6%) patients developed severe COVID-19 after admission in the training cohort and validation cohort, respectively. The differences in baseline characteristics were not statistically significant between the two cohorts with regard to age, sex, and comorbidities (P > 0.05). Multivariable analyses included age, C-reactive protein, fibrinogen, lactic dehydrogenase, neutrophil-to-lymphocyte ratio, urea, albumin-to-globulin ratio, and eosinophil count as predictive factors for patients with progression to severe COVID-19. A nomogram was constructed with sufficient discriminatory power (C index = 0.81), and proper consistency between the prediction and observation, with an area under the ROC curve of 0.81 and 0.86 in the training and validation cohort, respectively. Conclusion: We proposed a simple nomogram for early detection of patients with non-severe COVID-19 but at high risk of progression to severe COVID-19, which could help optimize clinical care and personalized decision-making therapies.

The individual and combined effects of polystyrene and silver nanoparticles on nitrogen transformation and bacterial communities in an agricultural soil.

The effects of emerging contaminants micro/nanoplastics (MPs/NPs) and silver nanoparticles (Ag NPs) on health have attracted universal concern throughout the world. However, it is unclear on the combined effects of MPs/NPs and Ag NPs on the biogeochemistry cycle such as nitrogen transformation and functional microorganism in the soil. In the present study, we conducted a 45-day soil microcosm experiment with polystyrene (PS) MPs/NPs and Ag NPs to investigate their combined impact on nitrogen cycling and the bacterial community. The results showed that MPs or NPs exerted limited effects on nitrogen transformation in the soil. The combined effects of PS MPs/NPs and Ag NPs were mainly caused by the presence of Ag NPs. However, PS NPs alleviated the inhibition of anammox and denitrification induced by Ag NPs via upregulating anammox-related genes and elevating nitrate and nitrite reductase activities. PS MPs + Ag NPs treatment significantly reduced bacterial diversity. PS MPs/NPs + Ag NPs increased the relative abundances of denitrifying Cupriavidus by 0.32% and 0.06% but decreased nitrogen-fixing functional microorganisms of Microvirga (by 2.05% and 2.24%), Bacillus (by 0.16% and 0.22%), and Herbaspirillum (by 0.14% and 0.07%) at the genus level compared with Ag NPs alone. The significant downregulation of nitrogen-fixing genes (K02586, K02588, and K02591) was observed in PS MPs/NPs + Ag NPs treatment compared to Ag NPs in the nitrogen metabolism pathway. Moreover, g-Lysobacter and g-Aquimonas were identified as biomarkers in PS MPs + Ag NPs and PS NPs + Ag NPs by LEfSe analysis. Our study sheds the light that changes of functional microorganism abundances contributed to the alteration of nitrogen transformation. Taking the particle size of plastics into account will be helpful to accurately assess the combined ecological risks of plastics and nanomaterial contaminants.

Bacterial community profile of the crude oil-contaminated saline soil in the Yellow River Delta Natural Reserve, China.

Crude oil contamination greatly influence soil bacterial community. Proliferative microbes in the crude oil-contaminated soil are closely related to the living conditions. Oil wells in the Yellow River Delta Natural Reserve (YRDNR) region is an ideal site for investigating the bacterial community of crude oil-contaminated saline soil. In the present study, 18 soil samples were collected from the depths of 0-20 cm and 20-40 cm around the oil wells in the YRDNR. The bacterial community profile was analyzed through high-throughput sequencing to trace the oil-degrading aerobic and anaerobic bacteria. The results indicated that C15-C28 and C29-C38 were the main fractions of total petroleum hydrocarbon (TPH) in the sampled soil. These TPH fractions had a significant negative effect on bacterial biodiversity (Shannon, Simpson, and Chao1 indices), which led to the proliferation of hydrocarbon-degrading bacteria. A comprehensive analysis between the environmental factors and soil microbial community structure showed that Streptococcus, Bacillus, Sphingomonas, and Arthrobacter were the aerobic hydrocarbon-degrading bacteria; unidentified Rhodobacteraceae and Porticoccus were considered to be the possible facultative anaerobic bacteria with hydrocarbon biodegradation ability; Acidithiobacillus, SAR324 clade, and Nitrosarchaeum were predicted to be the anaerobic hydrocarbon-degrading bacteria in the sub-surface soil. Furthermore, large amount of carbon sources derived from TPH was found to cause depletion of bioavailable nitrogen in the soil. The bacteria associated with nitrogen transformation, such as Solirubrobacter, Candidatus Udaeobacter, Lysinibacillus, Bradyrhizobium, Sphingomonas, Mycobacterium, and Acidithiobacillus, were highly abundant; these bacteria may possess the ability to increase nitrogen availability in the crude oil-contaminated soil. The bacterial community functions were significantly different between the surface and the sub-surface soil, and the dissolved oxygen concentration in soil was considered to be potential influencing factor. Our results could provide useful information for the bioremediation of crude oil-contaminated saline soil.

Corrigendum: Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.

[This corrects the article DOI: 10.3389/fphys.2021.706359.].

Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.

Cisplatin (CDDP) is one of the most frequently prescribed chemotherapy medications. However, its nephrotoxicity which often leads to acute kidney injury (AKI), greatly limits its clinical application. Chrysophanol (CHR), a mainly active anthraquinone ingredient, possesses various biological and pharmacological activities. In this study, we aimed to investigate the underlying protective mechanisms of CHR against CDDP-induced AKI (CDDP-AKI) using C57BL/6 mouse and human proximal tubule epithelial cells. In vivo, we found that pre-treatment with CHR greatly relieved CDDP-AKI and improved the kidney function and morphology. The mechanistic studies indicated that it might alleviate CDDP-AKI by inhibiting oxidative stress, apoptosis, and IKKß/IκBα/p65/transcription factor nuclear kappa B (NF-κB) inflammation signaling pathway induced by CDDP. Moreover, we found that the cell viability of HK2 cells reduced by CDDP was partially rescued by CHR pre-incubation. Flow cytometry results further indicated that CHR pre-incubation suppressed CDDP induced cellular reactive oxygen species (ROS) generation and inhibited cell apoptosis in a dose-dependent manner. In summary, our results suggested that CHR might be a novel therapy for CDDP-induced AKI.