Log odds of positive lymph nodes (LODDS)-based novel nomogram for survival estimation in patients with invasive micropapillary carcinoma of the breast.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high propensity for lymph node (LN) invasion. Inadequate LN dissection may compromise the precision of prognostic assessments. This study introduces a log odds of positive lymph nodes (LODDS) method to address this issue and develops a novel LODDS-based nomogram to provide accurate prognostic information. METHODS: The study analyzed data from 1,901 patients with breast IMPC from the Surveillance, Epidemiology, and End Results database. It assessed the relationships between LODDS and the number of excised LN (eLN), positive LN (pLN), and the pLN ratio (pLNR), identifying an optimal threshold value using a restricted cubic spline method. Predictive factors were identified by the Cox least absolute shrinkage and selection operator (Cox-LASSO) regression and validated through multivariate Cox regression to construct a nomogram. The model's accuracy, discrimination, and utility were assessed. The study also explored the consequences of excluding LODDS from the nomogram and compared its effectiveness with the tumor-node-metastasis (TNM) staging system. RESULTS: LODDS improved N status classification by identifying heterogeneity in patients with pLN ratios of 0% (pLN =0) or 100% (pLN =eLN) and setting -1.08 as the ideal cutoff. Five independent prognostic factors for breast cancer-specific survival (BCSS) were identified: tumor size, N status, LODDS, progesterone receptor status, and histological grade. The LODDS-based nomogram achieved a strong concordance index of 0.802 (95% CI: 0.741-0.863), surpassing both the version without LODDS and the conventional TNM staging in all tests. CONCLUSIONS: For breast IMPC, LODDS served as an independent prognostic factor, its effectiveness unaffected by the anatomical LN count, enhancing the accuracy of N staging. The LODDS-based nomogram showed promise in offering more personalized prognostic information.

Associations between the oxidative balance score and constipation: a cross-sectional study of the NHANES, 2005-2010.

OBJECTIVE: The oxidative balance score (OBS) reflects the overall burden of oxidative stress in an individual, with a higher OBS indicating greater antioxidant exposure. This study aimed to explore the association between constipation and OBS. METHODS: Variables were extracted from participants who completed a constipation questionnaire as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The OBS was developed based on dietary and lifestyle factors, encompassing 16 nutrients and 4 lifestyle variables. Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the association between OBS and constipation. RESULTS: After adjusting for all covariates, weighted multivariate logistic regression analysis revealed a 4% reduction in the incidence of constipation for each additional unit of OBS (OR: 0.96, 95% CI: 0.95-0.97, p < 0.001). In the OBS subgroup, the risk of constipation significantly decreased compared to that in the lowest quartile (Q2: 0.72, P = 0.024; Q3: 0.59, P < 0.001; Q4: 0.54, P < 0.001). CONCLUSIONS: The present study demonstrated a significant association between constipation and the oxidative balance score (OBS), particularly dietary OBS, and that an increase in OBS may reduce the risk of developing constipation, in which oxidative stress may play an important role. This finding suggested that dietary modification could be an important approach for preventing constipation.

Efficient conversion of rebaudioside C to steviol by Paenarthrobacter ilicis CR5301.

To improve the conversion efficiency of rebaudioside C, this study screened the Paenarthrobacter ilicis CR5301 from soil samples and identified it by 16S rRNA. The conversion experiment proved that P. ilicis CR5301 was capable of converting rebaudioside C. The effects of initial pH, temperature, inoculation amount, and substrate concentration on rebaudioside C conversion rate were investigated. The results showed that the conversion rate of rebaudioside C reached up to 100% when CR5301 was incubated in a conversion medium with an initial pH of 7.0 for 8 h at 28°C and 270 rpm. The conversion time was reduced by at least 16 h compared with previous studies. The conversion product was analyzed and identified as steviol by high performance liquid chromatography, ultra performance liquid chromatography-triple-time of flight mass spectrometer, and Fourier transform infrared spectroscopy methods. In addition, stevioside, rebaudioside A, dulcoside A, and some unknown components in steviol glycosides byproduct were all efficiently converted to steviol. These findings provide an efficient approach to the conversion of rebaudioside C and byproduct to steviol to simplify the subsequent industrial process and improve the reuse value of steviol glycosides.

Cdc14a has a role in spermatogenesis, sperm maturation and male fertility.

Cdc14a is an evolutionarily conserved dual-specific protein phosphatase, and it plays different roles in different organisms. Cdc14a mutations in human have been reported to cause male infertility, while the specific role of Cdc14a in regulation of the male reproductive system remains elusive. In the present study, we established a knockout mouse model to study the function of Cdc14a in male reproductive system. Cdc14a-/- male mice were subfertile and they could only produce very few offspring. The number of sperm was decreased, the sperm motility was impaired, and the proportion of sperm with abnormal morphology was elevated in Cdc14a-/- mice. When we mated Cdc14a-/- male mice with wild-type (WT) female mice, fertilized eggs could be found in female fallopian tubes, however, the majority of these embryos died during development. Some empty spaces were observed in seminiferous tubule of Cdc14a-/- testes. Compared with WT male mice, the proportions of pachytene spermatocytes were increased and germ cells stained with γH2ax were decreased in Cdc14a-/- male mice, indicating that knockout of Cdc14a inhibited meiotic initiation. Subsequently, we analyzed the expression levels of some substrate proteins of Cdc14a, including Cdc25a, Wee1, and PR-Set7, and compared those with WT testes, in which the expression levels of these proteins were significantly increased in Cdc14a-/- testes. Our results revealed that Cdc14a-/- male mice are highly subfertile, and Cdc14a is essential for normal spermatogenesis and sperm function.

Successful endoscopic treatment of an obstructing gastric antral web in a paediatric patient: A case report.

Gastric antral web (GAW) is a rare anomaly of the gastric antrum and can result in gastric outlet obstruction. Currently, endoscopic treatment of GAW is considered challenging due to high technical requirements and restenosis. Herein, we present a rare case of a paediatric patient with GAW cured by endoscopic transection and partial resection of the web. An 8-year-old boy was admitted because of a 9-month history of postprandial fullness and intermittent non-bilious vomiting of gastric contents. On performing upper gastrointestinal contrast and gastroscopy, the diagnosis of GAW was confirmed. Then, three electroincisions were performed in a radial fashion. Moreover, about a third of the web located in the larger curvature was resected. On follow-up for 6 months, the patient was completely relieved of the postprandial fullness and non-bilious vomiting. Hence, endoscopic treatment for GAW was considered safe and effective for this case. Furthermore, partial resection of the web contributed in avoiding restenosis.

Precise annotation of human, chimpanzee, rhesus macaque and mouse mitochondrial genomes leads to insight into mitochondrial transcription in mammals.

In the present study, we applied our 'precise annotation' to the mitochondrial (mt) genomes of human, chimpanzee, rhesus macaque and mouse using 5' and 3' end small RNAs. Our new annotations updated previous annotations. In particular, our new annotations led to two important novel findings: (1) the identification of five Conserved Sequence Blocks (CSB1, CSB2, CSB3, LSP and HSP) in the control regions; and (2) the annotation of Transcription Initiation and novel Transcription Termination Sites. Based on these annotations, we proposed a novel model of mt transcription which can account for the mt transcription and its regulation in mammals. According to our model, Transcription Termination Sites function as switches to regulate the production of short, long primary transcripts and uninterrupted transcription, rather than simply terminate the mt transcription. Moreover, the expression levels of mitochondrial transcription termination factors control the proportions of rRNAs, mRNAs and lncRNAs in total mt RNA. Our findings point to the existence of many other, as yet unidentified, Transcription Termination Sites in mammals.

Genome, transcriptome and fermentation analyses of Lactobacillus plantarum LY-78 provide new insights into the mechanism of phenyllactate biosynthesis in lactic acid bacteria.

Phenyllactate (PLA) is found in a variety of fermented foods and is a promising antibacterial agent, drug and plastic synthetic precursor. Previous studies have shown that PLA is a product of Phe catabolism in lactic acid bacteria (LAB), and PLA biosynthesis is mainly related to lactate dehydrogenases (LDHs). Here, the genome, transcriptome and fermentation characteristics of PLA-producing Lactobacillus plantarum LY-78 were studied. The fermentation experiments demonstrated that L. plantarum LY-78 possesses the ability to synthesize PLA de novo. Secondly, the genome and transcriptome analyses revealed candidate pathways, operons and key genes for PLA biosynthesis in the strain. Finally, genome-wide transcriptome analysis revealed significant changes in the expression profile of strain LY-78 in the absence and presence of PPA. Overall, this work demonstrates for the first time that PLA can be a by-product of Phe anabolism in LAB, provides new insights and evidence for elucidating the mechanism of PLA biosynthesis in LAB, and may provide new candidate genes and research strategies for future PLA biosynthesis applications.

A knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation.

SLC26A4 gene mutations lead to Pendred syndrome and non-syndromic hearing loss (DFNB4). The mouse model is well used to study the pathology of Pendred syndrome, however, mice with different Slc26a4 mutations exhibit different phenotypes, and these mice have severe deafness and inner ear malformations that are not imitated less severely Human phenotype. In this study, we generated a knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation to mimic the most common mutation found in human. Some L236P mice were observed to have significant vestibular dysfunction including torticollis and circling, the giant otoconia and destruction of the otoconial membrane was observed in L236P mice. Unlike other profoundly deafness in Slc26a4 mouse model, L236P mice present mild to profound hearing loss, consistent with the hearing threshold, inner ear hair cells also lost from slight to significant. Together, these data demonstrate that the L236P mouse phenotype is more similar to the human phenotype and should be used as a tool for further research into the human Pendred syndrome.

Vanillic acid mitigates the ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation.

Asthma is a chronic allergic ailment affecting a considerably large population of the world. The aim of this study is to evaluate the ameliorative effects of vanillic acid against ovalbumin (OVA)-induced asthma in rat model. Asthma was induced in Sprague Dawley rats and vanillic acid was orally administered at 25 and 50 mg/kg body weight for 28 days. Rats challenged with OVA showed heavy signs of airway inflammation and remodeling similar to chronic asthma, evidenced by the increased differential cell counts and presence of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), along with elevated serum immunoglobulin levels, and the histological results. However, vanillic acid dose-dependently attenuated the manifestation of OVA-induced asthma (p < 0.05) through suppression of inflammatory mediators and modulation of immunoglobulin levels in rats. The asthma mitigating properties of vanillic acid might be due to suppression of oxidative stress and prevention of lung airway inflammation.

Transcription factor E2F1 promotes EMT by regulating ZEB2 in small cell lung cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an early event in tumour invasion and metastasis, and widespread and distant metastasis at early stages is the typical biological behaviour in small cell lung cancer (SCLC). Our previous reports showed that high expression of the transcription factor E2F1 was involved in the invasion and metastasis of SCLC, but the role of E2F1 in the process of EMT in SCLC is unknown. METHODS: Immunohistochemistry was performed to evaluate the expressions of EMT related markers. Immunofluorescence was used to detect the expressions of cytoskeletal proteins and EMT related markers when E2F1 was silenced in SCLC cell lines. Adenovirus containing shRNA against E2F1 was used to knock down the E2F1 expression, and the dual luciferase reporter system was employed to clarify the regulatory relationship between E2F1 and ZEB2. RESULTS: In this study, we observed the remodelling of cytoskeletal proteins when E2F1 was silenced in SCLC cell lines, indicating that E2F1 was involved in the EMT in SCLC. Depletion of E2F1 promoted the expression of epithelial markers (CDH1 and CTNNB1) and inhibited the expression of mesenchymal markers (VIM and CDH2) in SCLC cell lines, verifying that E2F1 promotes EMT occurrence. Next, the mechanism by which E2F1 promoted EMT was explored. Among the CDH1 related inhibitory transcriptional regulators ZEB1, ZEB2, SNAI1 and SNAI2, the expression of ZEB2 was the highest in SCLC tissue samples and was highly consistent with E2F1 expression. ChIP-seq data and dual luciferase reporter system analysis confirmed that E2F1 could regulate ZEB2 gene expression. CONCLUSION: Our data supports that E2F1 promotes EMT by regulating ZEB2 gene expression in SCLC.

Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice.

UNLABELLED: Matrine has been demonstrated to attenuate allergic airway inflammation. Elevated suppressor of cytokine signaling 3 (SOCS3) was correlated with the severity of asthma. The aim of this study was to investigate the effect of matrine on SOCS3 expression in airway inflammation. In this study, we found that matrine significantly inhibited OVA-induced AHR, inflammatory cell infiltration, goblet cell differentiation, and mucous production in a dose-dependent manner in mice. Matrine also abrogated the level of interleukin (IL)-4 and IL-13, but enhanced interferon (IFN)-γ expression, both in BALF and in lung homogenates. Furthermore, matrine impeded TNF-α-induced the expression of IL-6 and adhesion molecules in airway epithelial cells (BEAS-2B and MLE-12). Additionally, we found that matrine inhibited SOCS3 expression, both in asthmatic mice and TNF-α-stimulated epithelial cells via suppression of the NF-κB signaling pathway by using pcDNA3.1-SOCS3 plasmid, SOCS3 siRNA, or nuclear factor kappa-B (NF-κB) inhibitor PDTC. CONCLUSIONS: Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice.

Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-ß1.

Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-ß1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally, the overexpression of TGF-ß1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-ß1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC.

Discovery of potent, selective, and orally bioavailable inhibitors of interleukin-1 receptor-associate kinase-4.

In this Letter, we report the continued optimization of the N-acyl-2-aminobenzimidazole series, focusing in particular on the N-alkyl substituent and 5-position of the benzimidazole based on the binding mode and the early SAR. These efforts led to the discovery of 16, a highly potent, selective, and orally bioavailable inhibitor of IRAK-4.

Pharmacokinetics and metabolism of AMG 232, a novel orally bioavailable inhibitor of the MDM2-p53 interaction, in rats, dogs and monkeys: in vitro-in vivo correlation.

1. AMG 232 is a novel inhibitor of the p53-MDM2 protein-protein interaction currently in Phase I clinical trials for multiple tumor indications. The objectives of the investigations reported in this article were to characterize the pharmacokinetic and drug metabolism properties of AMG 232 in pre-clinical species in vivo and in vitro, and in humans in vitro, and to predict its pharmacokinetics in humans through integrating PKDM data. 2. AMG 232 exhibited low clearance (<0.25 × Qh) and moderate to high oral bioavailability in mice, rats and monkeys (>42%), but high clearance (0.74 × Qh) and low oral exposure in dogs (18%). 3. Biotransformation was the major route of elimination of AMG 232 in rats, with only 7% of intravenously administered (14)C-labeled AMG 232 recovered as parent molecule in bile. The major metabolite was an acyl glucuronide as measured by in vivo rat studies and in vitro hepatocyte incubations in multiple species. 4. The in vitro-in vivo correlation of AMG 232 clearance was within 2-fold in pre-clinical species using hepatocytes. AMG 232 was predicted to exhibit low clearance, high volume distribution and long half-life in humans. The predictions are consistent with the preliminary human pharmacokinetic parameters of AMG 232 in clinical trials.

Optimization beyond AMG 232: discovery and SAR of sulfonamides on a piperidinone scaffold as potent inhibitors of the MDM2-p53 protein-protein interaction.

We recently reported on the discovery of AMG 232, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. AMG 232 is being evaluated in human clinical trials for cancer. Continued exploration of the N-alkyl substituent of this series, in an effort to optimize interactions with the MDM2 glycine-58 shelf region, led to the discovery of sulfonamides such as compounds 31 and 38 that have similar potency, hepatocyte stability and rat pharmacokinetic properties to AMG 232.

Construction and validation of nomogram prognostic model for predicting survival in hepatoblastoma patients: a population-based study.

For patients with hepatoblastoma (HB), current staging system is not accurate in predicting survival outcomes. The aim of this study was to develop two accurate survival prediction models to guide clinical decision making. A retrospective analysis of 424 HB patients was performed from 2004 to 2015 using the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis was used to screen for variables. The identified variables were used to build survival prediction model. The performance of the nomogram models was assessed based on the concordance index (C-index), calibration plot, and receiver operating characteristic (ROC) curve. The Cox regression analysis identified six variables affecting overall survival (OS) in HB patients, including race, tumor size, lymph node involvement, distant metastases, surgery and chemotherapy. And the Cox regression analysis identified five variables including race, lymph node involvement, distant metastases, surgery, and chemotherapy that affect cancer-specific survival (CCS) in HB patients. In the training cohort, the C-index of the nomogram in predicting the OS was 0.791 [95% confidence intervals (95% CI) 0.717-0.865], CSS was 0.805(95% CI 0.728-0.882). In the validation cohort, the C-index of the nomogram in predicting the OS was 0.712 (95% CI 0.511-0.913), the CSS was 0.751 (95% CI 0.566-0.936). In the training cohort, the area under the receiver operator characteristics curve (AUC) values of the nomogram in prediction of the 1-, 3-, and 5-year OS were 0.842 (95% CI 0.739-0.944), 0.759 (95% CI 0.670-0.849), and 0.770 (95% CI 0.686-0.852), respectively. In the validation cohort, the AUC values for prediction of the 1-, 3-, and 5-year OS were 0.920 (95% CI 0.806-1.034), 0.863 (95% CI 0.750-0.976), and 0.844 (95% CI 0.721-0.967), respectively. Two nomogram models were developed and validated in this study which provided accurate prediction of the OS and CSS in HB patients. The constructed models can be used for predicting survival outcomes and guide treatment for HB patients.

Association of dietary inflammatory index with constipation: Evidence from the National Health and Nutrition Examination Survey.

The association of dietary inflammatory index (DII) with constipation has not been well studied in general population. Therefore, the aim of this cross-sectional study was to investigate whether DII is associated with constipation in a large representative sample of the US population. Data were obtained from the 2005-2010 National Health and Nutrition Examination Survey (NHANES). A total of 12,308 participants aged ≥20 years were included in the analysis. DII was calculated based on a single 24-h dietary recall, and constipation was defined as having fewer than three bowel movements per week by the questionnaire on bowel health. Logistic regression analysis demonstrated a significant positive association between DII score and constipation, with each unit increase in DII score associated with a 20% increase in constipation risk (95% CI: 1.13-1.28). Subgroup analysis revealed high odds ratios (ORs) among individuals classified as "Other Race" (OR: 1.42, 95% CI: 1.12-1.80) and "Non-Hispanic White" (OR: 1.31, 95% CI: 1.12-1.54). In addition, RCS analysis indicated a nonlinear relationship between DII and constipation among individuals with a BMI less than 25 (OR: 1.17, 95% CI: 1.07-1.28), while the overall trend remained positive correlation (OR: 1.20, 95% CI: 1.10-1.31). Briefly, our study suggests that there may be a link between DII and constipation, which has implications for the development of dietary interventions aimed at preventing and managing constipation. However, this association was complex and variable depending on individual factors such as BMI and racial background and needed to establish longitudinal studies to confirm the underlying mechanisms between DII and constipation.

The causal relationship between gut microbiota and nine infectious diseases: a two-sample Mendelian randomization analysis.

Background: Evidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear. Methods: We identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality. Results: Herein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis. Conclusion: Through MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research.

Comparing overall survival between pediatric and adult retinoblastoma with the construction of nomogram for adult retinoblastoma: A SEER population-based analysis.

BACKGROUND: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. METHODS: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. CONCLUSION: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients' prognoses.

FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.

PURPOSE: Cisplatin is a low-cost clinical anti-tumor drug widely used to treat solid tumors. However, its use could damage cochlear hair cells, leading to irreversible hearing loss. Currently, there appears one drug approved in clinic only used for reducing ototoxicity associated with cisplatin in pediatric patients, which needs to further explore other candidate drugs. METHODS: Here, by screening 1967 FDA-approved drugs to protect cochlear hair cell line (HEI-OC1) from cisplatin damage, we found that Tedizolid Phosphate (Ted), a drug indicated for the treatment of acute infections, had the best protective effect. Further, we evaluated the protective effect of Ted against ototoxicity in mouse cochlear explants, zebrafish, and adult mice. The mechanism of action of Ted was further explored using RNA sequencing analysis and verified. Meanwhile, we also observed the effect of Ted on the anti-tumor effect of cisplatin. RESULTS: Ted had a strong protective effect on hair cell (HC) loss induced by cisplatin in zebrafish and mouse cochlear explants. In addition, when administered systemically, it protected mice from cisplatin-induced hearing loss. Moreover, antitumor studies showed that Ted had no effect on the antitumor activity of cisplatin both in vitro and in vivo. RNA sequencing analysis showed that the otoprotective effect of Ted was mainly achieved by inhibiting phosphorylation of ERK. Consistently, ERK activator aggravated the damage of cisplatin to HCs. CONCLUSION: Collectively, these results showed that FDA-approved Ted protected HCs from cisplatin-induced HC loss by inhibiting ERK phosphorylation, indicating its potential as a candidate for preventing cisplatin ototoxicity in clinical settings.