AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression.

Neuroblastoma (NB) is an aggressive cancer and has poor prognosis in children. TP-0903, a multi-kinase inhibitor, shows inhibitory effects on NB but the mechanistic act is not completely explored. Here, we aimed to explore the anticancer activity of TP-0903 against NB cells and its underlying mechanism.

Antitumor efficacy achieved by targeting PEGylated nanomedicines to netrin-1 in the extracellular matrix or EphA2 on the cancer cell membrane.

Targeting nanocarriers to tumors to increase their therapeutic efficacy requires selection of appropriate cancer targets and may depend on the particular formulation under investigation. Here, we compare the effectiveness of targeting PEGylated liposomal doxorubicin (PLD) or glycosidic switch liposomes (GSL) formulated with a glucuronide prodrug of 9-aminocamptothecin to ephrin receptor A2 (EphA2) present on the membrane of cancer cells or netrin-1 present in the tumor extracellular matrix. Targeting PLD to EphA2 or netrin-1 with bispecific PEG engagers significantly decreased the IC value of PLD from 1.

Severe enterovirus A71 pathogenesis and immune responses in human nucleolin transgenic mice.

Enterovirus A71 (EV-A71) infection is known to cause hand-foot-mouth disease, which may develop severe symptoms such as encephalitis, herpangina, and paralysis, leading to pulmonary edema and even death in children under five years old. Existing animal models for EV-A71 pathogenesis have limitations, necessitating novel models to study human-relevant disease mechanisms. Using glycoproteomic profiling to identify EV-A71-interacting proteins, we previously discovered human nucleolin (hNCL) as an attachment molecule that enhances viral binding and infection in vitro.

Long-Term Effects of Daily Versus Alternate-Day Chlorhexidine Bathing on Central-Line-Associated Blood Stream Infection in Medical Intensive Care Units: A Four-Year Observational Study.

Background: Daily chlorhexidine gluconate (CHG) bathing may reduce central line-associated bloodstream infections (CLABSI) in critically ill patients, but evidence remains inconclusive, particularly regarding long-term effects and varying frequencies of use.

Aim: This study aimed to examine the association between different CHG bathing frequencies and CLABSI rates in medical intensive care units (MICUs).

Study Design: A retrospective analysis was conducted in three MICUs in northern Taiwan from March 2018 to June 2022.

Safety and Efficacy of Nurse-Led Weaning Protocols on ICU Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Mechanical ventilation (MV) is a critical intervention for critically ill patients in intensive care units (ICUs). However, extended durations of MV are associated with adverse outcomes such as prolonged ICU stays, elevated mortality rates, and increased health-care costs. To address these challenges, nurse-led weaning protocols have been identified to be a promising strategy for enhancing the weaning process.

Comparison of the Efficacy of 15- and 19-Week Chemotherapy Protocols Based on Vincristine, L-Asparaginase, Doxorubicin, and Prednisolone for Dogs with Multicentric Lymphoma.

Multicentric lymphoma is the most common type of hematopoietic neoplasm in dogs. Chemotherapeutic protocols typically consist of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The 15- and 19-week CHOP protocols exhibit similar outcomes, indicating that a shorter treatment duration may be a feasible treatment option.

NUPR1 contributes to endocrine therapy resistance by modulating BIRC5 expression and inducing luminal B-ERBB2 subtype-like characteristics in estrogen receptor-positive breast cancer cells.

Acquired resistance to endocrine therapy is a major clinical challenge in the treatment of luminal A [estrogen receptor (ER) and/or progesterone receptor (PR), human epidermal growth factor receptor 2 (ERBB2/HER2), and low Ki-67] breast cancer. Recently, molecular subtype conversion has been suggested as one of the possible causes of the development of drug-resistant breast cancer. However, the molecular mechanism underlying the molecular subtype conversion and the induction of endocrine therapy resistance in luminal A breast cancer is still incompletely understood.

Auditory Brainstem Response (ABR) Recording of Simultaneous Electric-Acoustic Stimulation between Round Window Membrane and Basal Part of Cochlear Bone in guinea Pigs.

Hypothesis: Extracochlear electric-acoustic stimulation (EAS) between the round window membrane and the basal part of the cochlear bone exhibits distinct auditory brainstem response (ABR) characteristics.

Background: The use of EAS in individuals with residual hearing is becoming increasingly common in clinical settings. Ongoing research has explored the characteristics of EAS-induced responses in hearing cochleae.

The Anti-Metastatic Action of Oxyresveratrol via Suppression of Phosphoryl-ERK/-PKCα-Mediated Sp1/MMP1 Signaling in Human Renal Carcinoma Cells.

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells.

Antiviral activity of extract against feline coronavirus .

Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from (L.

Engineering stable and non-immunogenic immunoenzymes for cancer therapy via in situ generated prodrugs.

Engineering human enzymes for therapeutic applications is attractive but introducing new amino acids may adversely affect enzyme stability and immunogenicity. Here we used a mammalian membrane-tethered screening system (ECSTASY) to evolve human lysosomal beta-glucuronidase (hBG) to hydrolyze a glucuronide metabolite (SN-38G) of the anticancer drug irinotecan (CPT-11). Three human beta-glucuronidase variants (hBG3, hBG10 and hBG19) with 3, 10 and 19 amino acid substitutions were identified that display up to 40-fold enhanced enzymatic activity, higher stability than E.

Prediction of extranodal extension in head and neck squamous cell carcinoma by CT images using an evolutionary learning model.

Background: Extranodal extension (ENE) in head and neck squamous cell carcinoma (HNSCC) correlates to poor prognoses and influences treatment strategies. Deep learning may yield promising performance of predicting ENE in HNSCC but lack of transparency and interpretability. This work proposes an evolutionary learning method, called EL-ENE, to establish a more interpretable ENE prediction model for aiding clinical diagnosis.

Nucleus accumbens deep brain stimulation improves depressive-like behaviors through BDNF-mediated alterations in brain functional connectivity of dopaminergic pathway.

Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway.

Assessing traffic-related air pollution-induced fiber-specific white matter degradation associated with motor performance declines in aged rats.

Fine particulate matter (PM) is thought to exacerbate Parkinson's disease (PD) in the elderly, and early detection of PD progression may prevent further irreversible damage. Therefore, we used diffusion tensor imaging (DTI) for probing microstructural changes after late-life chronic traffic-related PM exposure. Herein, 1.

Pediatric Cardiac Lymphoblastic Lymphoma: A Case Report and Review of the Literature.

Cardiac lymphoma is rare in children. Treatment typically includes chemotherapy, combination of radiotherapy, or surgery. We report a case of stage IV precursor B lymphoblastic lymphoma with secondary involvement of the heart in an 11-year-old girl who was treated with acute lymphoblastic leukemia-based chemotherapy.

Antibodies against Poly(ethylene glycol) Activate Innate Immune Cells and Induce Hypersensitivity Reactions to PEGylated Nanomedicines.

Nanomedicines and macromolecular drugs can induce hypersensitivity reactions (HSRs) with symptoms ranging from flushing and breathing difficulties to hypothermia, hypotension, and death in the most severe cases. Because many normal individuals have pre-existing antibodies that bind to poly(ethylene glycol) (PEG), which is often present on the surface of nanomedicines and macromolecular drugs, we examined if and how anti-PEG antibodies induce HSRs to PEGylated liposomal doxorubicin (PLD). Anti-PEG IgG but not anti-PEG IgM induced symptoms of HSRs including hypothermia, altered lung function, and hypotension after PLD administration in C57BL/6 and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice.

Mouse Abdominal Aortic Aneurysm Model Induced by Periarterial Incubation of Papain.

For decades, numerous experimental animal models have been developed to examine the pathophysiologic mechanisms and potential treatments for abdominal aortic aneurysms (AAAs) in diverse species with varying chemical or surgical approaches. This study aimed to create an AAA mouse model by the periarterial incubation with papain, which can mimic human AAA with advantages such as simplicity, convenience, and high efficiency. Eighty C57BL/6J male mice were randomly assigned to 1 of the 4 groups: papain (1.

Motivating Individuals to Take Responsible Ocean Action: The Mediatory Effects of Attitude toward the Ocean.

When considering how to improve public literacy and behavior related to specific themes, top priority is usually given to strategies that enhance relevant knowledge. Fostering attitude comes later. Understanding the mechanisms of behavior may help us develop better policy and educational strategies.