Cuproptosis and copper deficiency in ischemic vascular injury and repair.

Ischemic vascular diseases are on the rise globally, including ischemic heart diseases, ischemic cerebrovascular diseases, and ischemic peripheral arterial diseases, posing a significant threat to life. Copper is an essential element in various biological processes, copper deficiency can reduce blood vessel elasticity and increase platelet aggregation, thereby increasing the risk of ischemic vascular disease; however, excess copper ions can lead to cytotoxicity, trigger cell death, and ultimately result in vascular injury through several signaling pathways. Herein, we review the role of cuproptosis and copper deficiency implicated in ischemic injury and repair including myocardial, cerebral, and limb ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of copper biology in understanding the pathogenesis of ischemic vascular disease states.

Chalcone-Based Synthesis of Tetrahydropyridazines via Cloke-Wilson-Type Rearrangement-Involved Tandem Reaction between Cyclopropyl Ketones and Hydrazines.

A facile and efficient approach for the synthesis of multisubstituted tetrahydropyridazines starting from cyclopropyl ketones and hydrazines has been developed. The transformation is chalcone-based and takes place via a Cloke-Wilson-type rearrangement-involved tandem reaction catalyzed by TfOH in HFIP.

Assessing the quality of life in patients with drug-resistant tuberculosis: a cross-sectional study.

BACKGROUND: This study investigated the current status of the quality of life (QOL) of drug-resistant tuberculosis (DR-TB) patients in Nanjing, China, and analyzed the influencing factors. METHODS: The survey was conducted among patients with DR-TB who were hospitalized in the tuberculosis department of the Second Hospital of Nanjing (Nanjing Public Health Medical Center) from July 2022 to May 2023. The Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to investigate the QOL levels of patients with DR-TB, and a multiple linear regression model was used to analyze the QOL influencing factors. RESULTS: A total of 135 patients participated in the study; 69.6% were male, the average age was 46.30 ± 17.98 years, 13.33% had an education level of elementary school or below, and 75.56% were married. The QOL scores were 51.35 ± 17.24, 47.04 ± 20.28, 43.89 ± 17.96, and 35.00 ± 11.57 in the physiological, psychological, social, and environmental domains, respectively. The differences between the four domain scores and the Chinese normative results were statistically significant (P < 0.05). The results of multiple linear regression analysis showed that the factors related to the physiological domain included residence, family per-capita monthly income, payment method, adverse drug reactions (ADRs), and comorbidities; psychological domain correlates included educational level, family per-capita monthly income, course of the disease, and caregivers; social domain correlates included age and comorbidities; and factors related to the environmental domain included age, education level, and comorbidities. CONCLUSIONS: In Nanjing, China, patients with younger age, higher education level, living in urban areas, high family per-capita monthly income, no adverse drug reactions, no comorbidities, and having caregivers have better quality of life. Future interventions to improve the quality of life of patients with drug-resistant tuberculosis could be tailored to a specific factor.

Noncanonical functions of microRNAs in the nucleus.

MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that play their roles in the regulation of physiological and pathological processes. Originally, it was assumed that miRNAs only modulate gene expression posttranscriptionally in the cytoplasm by inducing target mRNA degradation. However, with further research, evidence shows that mature miRNAs also exist in the cell nucleus, where they can impact gene transcription and ncRNA maturation in several ways. This review provides an overview of novel models of nuclear miRNA functions. Some of the models remain to be verified by experimental evidence, and more details of the miRNA regulation network remain to be discovered in the future.

Experience of rehabilitation specialist nurses in providing bowel care for stroke patients: A qualitative study.

AIMS: This study aims to explore the experiences of rehabilitation specialist nurses in providing bowel care to stroke patients and to identify the factors that either facilitate or hinder their practice. DESIGN: This was a descriptive qualitative design study. METHODS: Between May 2022 and October 2022, we conducted in-depth and semi-structured interviews with 12 rehabilitation specialist nurses from two tertiary hospitals in Changsha, China. Thematic analysis was employed to analyse the interview transcripts. FINDINGS: Three key themes were revealed from our analysis: (1) acceptance of bowel care as a process, (2) high level of recognition improves the experience and (3) challenges stemming from limited knowledge and rights. Acceptance of bowel care as a dynamic process, coupled with a high level of recognition, enabled nurses to prioritize the health and safety of patients over personal feelings and achieve professional accomplishments. However, they encountered challenges in terms of professional development and restricted prescribing rights for bowel care. CONCLUSION: The experiences of rehabilitation specialist nurses in providing bowel care are dynamic. These findings have important implications for healthcare improvement, including the need for collaboration with healthcare professionals and nurturing nurses' self-identity, comprehensive training plans, innovative programs and expanding the scope of rehabilitation specialist nurses' rights. IMPACT: This study enhances our understanding of the challenges faced by rehabilitation specialist nurses caring for stroke patients with neurogenic bowel dysfunction. The findings provide insights into how to enhance bowel care experience and develop further in this field. REPORTING METHOD: This study adhered to the EQUATOR guideline and utilized the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTIONS: This study involved participants who were registered nurses, and there were no contributions from patients or public.

Lycopene inhibits endothelial-to-mesenchymal transition of choroidal vascular endothelial cells in laser-induced mouse choroidal neovascularization.

Choroidal neovascularization (CNV), is a major cause of irreversible blindness among the elderly population in developed countries, which is resulted from subretinal fibrosis without effective therapeutic strategies. Endothelial-to-mesenchymal transition (EndMT) of choroidal vascular endothelial cells (CVECs) contributes to subretinal fibrosis. Lycopene (LYC), a non-pro-vitamin A carotenoid, plays an anti-fibrotic role. Herein, we explored the effect and mechanism of LYC on the EndMT of CVECs during CNV. Firstly, LYC inhibited EndMT in hypoxic human choroidal endothelial cells (HCVECs). Meanwhile, LYC inhibited proliferation, androgen receptor (AR) expression and nuclear localization in hypoxic HCVECs. Then LYC-inhibited AR promotes the activation of microphthalmia-associated transcription factor (MITF) in hypoxic HCVECs. In addition, LYC down-regulated AR and induced MITF up-regulated pigment epithelium-derived factor (PEDF) transcription and expression in hypoxic HCVECs. Moreover, LYC-induced PEDF bound to laminin receptor (LR), inhibiting EndMT of hypoxic HCVECs via down-regulating protein kinase B (AKT)/ß-catenin pathway. In vivo, LYC alleviated mouse laser-induced subretinal fibrosis secondary to CNV via up-regulating PEDF without any ocular or systemic toxicity. These results indicate that LYC inhibits EndMT of CVECs via modulating AR/MITF/PEDF/LR/AKT/ß-catenin pathway, showing LYC is a promising therapeutic agent for CNV.

Vascular endothelial-derived Von Willebrand factor inhibits lung cancer progression through the αvß3/ERK1/2 axis.

Lung cancer remains a common malignant tumor causing death due to the rapid industrialization and serious pollution of the environment. The Von Willebrand Factor (vWF) protein is an endothelial marker and is widely used to diagnose cancer and other inflammations, however its exact mechanism of action remains largely unexplored. In particular, how it plays two opposing roles in tumor development is not clear. Our study aimed to the impact of endothelial-derived vWF on tumor development by co-culturing human umbilical vein endothelial cells (HUVECs) with lung cancer cells (95D and A549). A knockdown of endothelial-derived vWF assisted lung cancer cell in proliferation, migration and inhibited apoptosis in vitro, while overexpression of endothelial-derived vWF inhibited the proliferation, migration and induced apoptosis of lung cancer cells. The results of further experiments indicated that the vWF secreted by endothelial cells could affect lung cancer cell migration and apoptosis via its binding to integrin αvß3 on the surface of lung cancer cells. Furthermore, a novel finding was the fact that endothelial-derived vWF inhibited lung cancer cell apoptosis by phosphorylating ERK1/2. At the same time, we established experimental lung metastasis model and xenograft model in normal mice and vWF-/- mice, and found that knockout of vWF in mice significantly promoted lung cancer growth and metastasis. In conclusion, our research found that endothelial-derived vWF could directly combine to αvß3 on the exterior of A549 and 95D, thereby mediating lung cancer proliferation, migration and apoptosis and inhibiting the development of lung cancer.

The dyadic coping experience of ICU transfer patients and their spouses: A qualitative study.

BACKGROUND: The patient's spouse, in their role as the primary caregiver, assumes responsibility for the patient's care during the recovery process and provides the most robust social support. Previous research has primarily focused on the coping experiences and thoughts of individual ICU patients or caregivers, with limited attention afforded to the relationship between patients and their spouses. AIMS AND OBJECTIVES: This study aims to explore the dyadic coping experiences of ICU transfer patients and their spouses, with the goal of providing evidence to support the subsequent development of an individualized intervention program. STUDY DESIGN: A qualitative study using a phenomenological research approach was undertaken. Purposive sampling was employed to select participants for face-to-face semi-structured in-depth interviews. The interviews took place at a tertiary general hospital in Nanjing from January 2023 to February 2023.Twelve ICU transfer patients and their twelve spouses were interviewed. The data were then summarized, and themes were derived using the Colaizzi 7-step analysis method. FINDINGS: A total of four themes and eleven sub-themes emerged from the analysis. The identified themes include positive coping (actively seeking solutions, and facing challenges together), negative coping (avoiding problems, displaying overprotective behaviour, and bearing the burden alone), difficulties and challenges (a lack of information, high physical and psychological stress, and significant financial burden), and needs and suggestions (strengthening transition care, fostering increased intimacy, and reducing negative emotions). CONCLUSION: Both patients and spouses experience physical and psychological stress during the transfer from the ICU to the ward. Therefore, any intervention developed for caregivers should be designed in a dyadic manner. Increasing dyadic coping skills may represent an important area for future research and intervention. RELEVANCE TO CLINICAL PRACTICE: This study provides valuable evidence to inform the formulation of a comprehensive dual disease management plan for ICU transfer patients and their spouses.

Lung adenocarcinoma-derived vWF promotes tumor metastasis by regulating PHKG1-mediated glycogen metabolism.

Tumor metastasis is a series of complicated biological events. Hematogenous metastasis mediated by von Willebrand factor (vWF) is critical in tumor metastasis. However, the source of vWF and its role in tumor metastasis are controversial, and the further mechanism involved in mediating tumor metastasis is still unclear. In this study, we first demonstrated that lung adenocarcinoma cells could express vWF de novo and promotes tumor metastasis. Through the analysis of transcriptome sequencing, the metastasis promotion effect of vWF may be related to phosphorylase kinase subunit G1 (PHKG1), a catalytic subtype of phosphorylase kinase (PhK). PHKG1 was highly expressed in lung adenocarcinoma patients and led to poor prognosis. Further experiments found that lung adenocarcinoma-derived vWF induced the upregulation of PHKG1 through the PI3K/AKT pathway to promote glycogenolysis. Glycogen was funneled into glycolysis, leading to increased metastasis. Tumor metastasis assayed in vitro and in vivo showed that knockdown of PHKG1 or synergistic injection of phosphorylase inhibition based on the overexpression of vWF could inhibit metastasis. In summary, our research proved that lung adenocarcinoma-derived vWF may mediate tumor metastasis by regulating PHKG1 to promote glycogen metabolism and suggested potential targets for inhibition of lung adenocarcinoma metastasis.

Breast cancer cells-derived Von Willebrand Factor promotes VEGF-A-related angiogenesis through PI3K/Akt-miR-205-5p signaling pathway.

The metastasis and angiogenesis of breast cancer has always been a difficult problem for treatment. It has recently been discovered that Von Willebrand Factor (vWF), in addition to hemostasis, also plays a role in tumor metastasis and angiogenesis. We noticed that besides endothelial cells, breast cancer cells (MDA-MB-231 and MCF-7) could also express vWF. In vitro experiments showed that knocking down vWF inhibited breast cancer cell metastasis. And we found that overexpression of vWF significantly promoted VEGF-A-dependent vascular proliferation in vitro by activating the PI3K/Akt signaling pathway. Further studies indicated that inhibition of PI3K/Akt signaling pathway up-regulated the expression of miR-205-5p, and miR-205-5p could bind to the 3'UTR region of VEGF-A to hinder the production of VEGF-A. Furthermore, when a spontaneous lung metastasis model was established in Balb/c female mice, knockdown of vWF in 4 T1 cells resulted in a decrease in tumor blood vessel density and effectively inhibited lung metastasis, accompanied by a decrease in the expression level of VEGF-A and an increase in the expression level of miR-205-5p. In summary, our findings provide experimental evidence that overexpression of vWF in breast cancer cells down-regulates the expression of miR-205-5p and up-regulates the expression of VEGF-A through the PI3K/Akt signaling pathway, thereby promoting tumor angiogenesis and metastasis.

An enhanced antioxidant strategy of astaxanthin encapsulated in ROS-responsive nanoparticles for combating cisplatin-induced ototoxicity.

BACKGROUND: Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback. METHODS AND RESULTS: In the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an H2O2 ON/OFF stimulated model. Enhanced release profiles stimulated by H2O2 were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway. CONCLUSIONS: Thus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss.

TNF-α released from retinal Müller cells aggravates retinal pigment epithelium cell apoptosis by upregulating mitophagy during diabetic retinopathy.

Retinal pigment epithelium (RPE) cell damage, including mitophagy-associated cell apoptosis, accelerates the pathogenesis of diabetic retinopathy (DR), a common complication of diabetes that causes blindness. Müller cells interact with RPE cells via pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α). Herein, we investigated the role of the RPE cell epidermal growth factor receptor (EGFR)/p38 mitogen-activated protein kinase (p38)/nuclear factor kappa B (NF-κB) pathway in Müller cell-derived TNF-α-induced mitophagy-associated apoptosis during DR. Our results showed that TNF-α released from Müller cells activated the EGFR/p38/NF-κB/p62 pathway to increase mitophagy and apoptosis in RPE cells under high glucose (HG) conditions. Additionally, blockade of the TNF-α/EGFR axis alleviates blood-retina barrier breakdown in diabetic mice. Our data further illustrate the effects of the Müller cell inflammatory response on RPE cell survival, implying potential molecular targets for DR treatment.

Geniposide alleviates choroidal neovascularization by downregulating HB-EGF release from RPE cells by downregulating the miR-145-5p/NF-κB axis.

Age-related macular degeneration (AMD), mainly wet AMD, is the major reason for nonreversible vision loss worldwide. Choroidal neovascularization (CNV) is a characteristic pathological manifestation of wet AMD. Stress or injury to the retinal pigment epithelium (RPE) induces proangiogenic factors that drive CNV. An iridoid glycoside extracted from the fruit of gardenia, geniposide (GEN) plays an antiangiogenic role. In this study, GEN inhibited the transcription and expression of heparin-binding epidermal growth factor (HB-EGF), a proangiogenic factor, in hypoxic RPE cells and a mouse laser-induced CNV model. Inhibition of glucagon-like peptide-1 receptor (GLP-1R), a GEN receptor blocker, eliminated the protective effect of GEN. Additionally, GEN decreased the transcription and expression of HB-EGF in hypoxia-exposed RPE cells by downregulating the miR-145-5p/NF-κB axis. Therefore, our research provides a promising novel strategy for wet AMD therapy.

Photoredox Catalyzed Radical Cascade Aroylation (Sulfonylation)/Cyclization Enables Access to Fused Indolo-pyridones.

A visible-light-initiated radical cascade reaction toward the synthesis of structurally diverse fused Indolo-pyridones is described. The reaction involves the addition of aroyl or sulfonyl radicals to N-alkyl-acryloyl-1H-indole-3-carboxamides, cyclization, and oxidative aromatization. This telescoped method circumvents lengthy prefunctionalization steps of radical precursors, which is further underpinned by the superior compatibility with a series of C-centered radicals, allowing the rapid and facile construction of numerous valuable architectures.

The psychosocial impact of premature ovarian insufficiency on male partners and their perceptions of the disease.

Premature ovarian insufficiency (POI) is affecting about 1% women of reproductive age. However, current studies have primarily focused on women with the views of male partners greatly absent from the literature. We conduct this research to investigate the psychosocial effect of POI on male partners and their perceptions of the disease.52 male partners of POI patient (experiment group) and 52 controls (control group) were available for analysis. Anxiety, depression, and marital relationship were assessed for male partners in both groups. A questionnaire about perceptions of POI was completed by the experiment group. Male partners of POI patient experienced greater levels of anxiety (10.96 versus 4.88; P < 0.01) and depression (12.23 versus 5.19; P < 0.01) compared with controls. In addition, they experienced worse marital relationship in several aspects than their counterparts. The findings also demonstrate that most POI patient male partners had inadequate and inaccurate knowledge about their partners' disease, which may be the results of insufficient professional counseling from health-care practitioners. Moreover, their understanding level of the disease was correlated to anxiety (r = -0.64; P < 0.01), depression (r = -0.38; P < 0.01), and communication (r = 0.28; P < 0.05).The study highlights the need for health-care services, as well as support and professional information resources aimed at POI patients' male partners.

Brivanib, a multitargeted small-molecule tyrosine kinase inhibitor, suppresses laser-induced CNV in a mouse model of neovascular AMD.

In age-related macular degeneration (AMD), choroidal neovascularization (CNV), a major pathologic feature of neovascular AMD (nAMD), affects 10% of patients, potentially causing serious complications, including vision loss. Vascular endothelial growth factor receptor 2 (VEGFR2) and fibroblast growth factor receptor 1 (FGFR1) contribute to the pathogenesis of CNV. Brivanib is an oral selective dual receptor tyrosine kinase (RTK) inhibitor of FGFRs and VEGFRs, especially VEGFR2 and FGFR1. In this study, brivanib inhibited zebrafish embryonic angiogenesis without impairing neurodevelopment. In a mouse CNV model, brivanib intravitreal injection blocked phosphorylation of FGFR1 and VEGFR2 and reduced CNV leakage, area, and formation without causing intraocular toxicity. Moreover, brivanib oral gavage reduced CNV leakage and area. Accordingly, brivanib remained at high concentrations (above 14,000 ng/ml) in retinal/choroidal/scleral tissues following intravitreal injection. Similarly, brivanib remained at high concentrations (over 10,000 ng/ml) in retinal/choroidal/scleral tissues following oral gavage. Finally, in vitro cell experiments demonstrated that brivanib inhibited the proliferation, migration and tube formation of microvascular endothelial cells. In conclusion, our study suggested that brivanib treatment could be a novel therapeutic strategy for nAMD.

Andrographolide attenuates choroidal neovascularization by inhibiting the HIF-1α/VEGF signaling pathway.

Choroidal neovascularization (CNV), a characteristic of wet age-related macular degeneration (AMD), leads to severe vision loss amongst the elderly in the developed countries. Currently, the premier treatment for AMD is anti-VEGF therapy, which has limited efficacy, and is still controversial. Previous studies have showed that Andrographolide (Andro) had various biological effects, including anti-angiogenesis, anti-inflammation, and antioxidant. However, the effect of Andro on the formation of CNV has not been studied thus far. Here our results showed that Andro reduced the expression levels of HIF-1α and VEGF in the RF/6A cells chemical hypoxia model and the laser-induced CNV mouse model. Moreover, Andro inhibited the tube formation activity of RF/6A cells under hypoxic conditions. Furthermore, intraperitoneal injection of Andro reduced the severity of choroidal vascular leakage and the size of CNV in the laser-induced CNV mouse model, indicating that Andro attenuated the development of CNV by inhibiting the HIF-1α/VEGF signaling pathway. These results suggest that Andro could be a potential novel therapeutic agent for AMD.

Physician and patient acceptance of policies to reduce kidney discard.

Despite the shortage of kidneys for transplantation in the United States, approximately 18%-20% of deceased donor kidneys are discarded each year. These discarded kidneys can offer a survival benefit to suitable patients. Revisions to the current kidney allocation policy may be needed to reduce deceased donor kidney discard. We surveyed transplant physicians and patients to assess their perceived acceptability of policy proposals to reduce the discard of deceased donor kidneys. Members of professional societies (AST, ASTS) and a patient organization (AAKP) were invited to complete the survey. Responses were obtained from 97 physicians and 107 patients. The majority of physicians (73.4%) and patients (73.8%) "somewhat" or "completely" accepted a policy for fast-tracking kidneys at risk of discard. Physicians and patients also supported returning a proportion of waiting time to patients who accept KDPI >85 kidneys and experience graft failure within the first 12 months, with 36% of physicians and 50% of patients electing to return 100% of the waiting time. The majority of physicians (75%) "somewhat or completely" accepted a policy to skip less aggressive centers for KDPI 90 + offers. Physicians and patients provided insights into factors researchers, and policymakers should consider in the design and implementation of these policies.

Correction to: Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects.

An amendment to this paper has been published and can be accessed via the original article.

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects.

BACKGROUND: Ototoxicity is one of the major side effects of platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, ototoxicity is generally believed to be produced by excessive generation of reactive oxygen species (ROS) in the inner ear, thus leading to the development of various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) is an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies, owing to its unique antioxidant capacity. METHODS AND RESULTS: In this study, we aimed to evaluate the potential antioxidant properties of ATX in the inner ear by using the HEI-OC1 cell line, zebrafish, and guinea pigs. Because ATX has poor solubility and cannot pass through round window membranes (RWM), we established lipid-polymer hybrid nanoparticles (LPN) for loading ATX. The LPN enabled ATX to penetrate RWM and maintain concentrations in the perilymph in the inner ear for 24 h after a single injection. ATX-LPN were found to have favorable biocompatibility and to strongly affect cisplatin-induced generation of ROS, on the basis of DCFHDA staining in HEI-OC1 cells. JC-1 and MitoTracker Green staining suggested that ATX-LPN successfully reversed the decrease in mitochondrial membrane potential induced by cisplatin in vitro and rescued cells from early stages of apoptosis, as demonstrated by FACS stained with Annexin V-FITC/PI. Moreover, ATX-LPN successfully attenuated OHC losses in cultured organ of Corti and animal models (zebrafish and guinea pigs) in vivo. In investigating the protective mechanism of ATX-LPN, we found that ATX-LPN decreased the expression of pro-apoptotic proteins (caspase 3/9 and cytochrome-c) and increased expression of the anti-apoptotic protein Bcl-2. In addition, the activation of JNK induced by CDDP was up-regulated and then decreased after the administration of ATX-LPN, while P38 stayed unchanged. CONCLUSIONS: To best of our knowledge, this is first study concluded that ATX-LPN as a new therapeutic agent for the prevention of cisplatin-induced ototoxicity.