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Background Gastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored areas of precision medicine. In this study, we aimed to establish an in vivo patient-derived xenograft (PDX) model based on zebrafish ( Danio rerio ) embryos, allowing for a rapid analysis of the angiogenic and invasive potentials, as well as a fast drug sensitivity testing. Methods Two human gastric cancer cell lines (AGS and SGC-7901) were xenografted into zebrafish embryos, their sensitivity to 5-FU were tested both in vitro and in vivo. Fourteen human primary cells from gastric cancer tissue were xenografted into zebrafish embryos, their proliferating, angiogenic and metastatic activities were evaluated in vivo. Sensitivity to 5-FU, docetaxel, and apatinib were also tested on primary samples from four patients. Results SGC-7901 showed higher sensitivity to 5-FU than AGS both in vitro (6.3 ± 0.9 μM vs.10.5 ± 1.8 μM) and in vivo. Nine out of fourteen patient samples were successfully transplanted in zebrafish embryos and all showed proliferating, angiogenic and metastatic potentials in the living embryos. Four cases showed varied sensitivity to the selected three chemotherapeutic drugs. Conclusions Our zebrafish PDX (zPDX) model is a preclinically reliable in vivo model for GC. The zPDX model is also a promising platform for the translational research and personalized treatment on GC.

Background Brain metastasis (BM) is thought to be related to the mortality and poor prognosis of non-small cell lung cancer (NSCLC). Despite promising development of NSCLC treatment, the treatment of NSCLC BM is still not optimistic due to the existence of the blood-brain barrier (BBB) that prevent drug penetration, as well as the short median survival time of the patients left for treatment. In this context, further development of quick and effective pre-clinical models is needed in NSCLC BM treatment. Here, we report a model system using zebrafish to promote the development of drugs for patients with NSCLC BM. Methods Three different NSCLC cell lines (H1975, A549 and H1299) were used to establish zebrafish BM models. The embryo age and cell number for injection were first optimized. Metastatic cells were observed in the brain blood vessels of zebrafish and were verified by hematoxylin-eosin (HE) staining. Then, the metastasis potentials of H1975 and A549 with manipulated microRNA-330-3p (miR-330-3p) expression were also investigated. Finally, sensitivities of H1975 and A549 to osimertinib and gefitinib were tested. Results This zebrafish BM model could distinguish NSCLC cell lines with different BM potential. Over-expressed miR-330-p significantly improved the BM potential of the A549 cells while knockdown miR-330-p reduced the BM ability of the H1975 cells. Both osimertinib and gefitinib showed inhibition effect in zebrafish BM model with the inhibition rate higher than 50 %. H1975 cell showed much higher sensitivity to osimertinib rather than gefitinib both in vivo and in vitro . Conclusions We established zebrafish brain metastasis model for studying mechanism and treatment of NSCLC BM. This study provided a useful model for NSCLC brain metastasis that could be used to study the mechanism that drive NSCLC cells to the brain as well as identify potential therapeutic options.

About half of NSCLC patients with EGFR mutation had secondary mutation T790M after treatment with a first-generation tyrosine kinase inhibitor (TKI), Gefitinib. The third-generation of EGFR-TKI Osimertinib is suitable for patients with EGFR mutation and T790M mutation. However, drug screening for NSCLC patients after the emergence of acquired resistance has become a difficult problem for clinicians. In this study, we established drug-resistant cell lines of Gefitinib and Osimertinib to evaluate cell proliferation in vitro. And we investigated the inhibitory effect of different drug concentration gradients on cancer cells. Zebrafish with high homology to human genes were selected as xenotransplantation models to compare the effects of different concentrations of Osimertinib on the proliferation and angiogenesis of zebrafish tumors after transplantation of different lung cancer cell lines. It was confirmed that Osimertinib could inhibit the proliferation of tumor cells with EGFR mutation and T790M resistance mutation in zebrafish, which was consistent with the clinical research conclusion.

Background Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive inherited disease caused by mutations in the arylsulfatase B ( ARSB ) gene. MPS VI is a multisystemic disease resulting from a deficiency in arylsulfatase B causing an accumulation of glycosaminoglycans in the tissues and organs of the body. In this report, we present the case of a 16-year-old Chinese male who presented with vision loss caused by corneal opacity. MPS VI was confirmed by genetic diagnosis. Case presentation A 16-year-old Chinese male presented with a one-year history of binocular vision loss. The best-corrected visual acuity was 0.25 in the right eye and 0.5 in the left eye. Although slit-lamp examination revealed corneal opacification in both eyes, the ocular examinations of his parents were normal. At the same time, the patient presented with kyphotic deformity, short stature, joint and skeletal malformation, thick lips, long fingers, and coarse facial features. Genetic assessments revealed that ARSB was the causative gene. Compound heterozygous missense mutations were found in the ARSB gene, namely c.1325G > A (p. Thr442Met) (M1) and c.1197G > C (p. Phe399Leu) (M2). Genetic diagnosis confirmed that the patient had MPS VI. Conclusions This paper reports a case of MPS VI confirmed by genetic diagnosis. MPS VI is a multisystem metabolic disease, with corneal opacity as a concomitant ocular symptom. As it is difficult for ophthalmologists to definitively diagnose MPS VI, genetic testing is useful for disease confirmation.

This study aimed to develop a human acellular amniotic membrane (HAAM) scaffold suitable for corneal endothelial transplantation. The HAAM was engineered using sequential chemical treatments and physical agitation to remove cellular components while preserving the extracellular matrix structure. The study sought to evaluate the biocompatibility and functional properties of the HAAM when seeded with immortalized human corneal endothelial cells (HCECs), with the ultimate goal of providing a potential therapeutic option for corneal endothelial dysfunction. The HAAM was fabricated through a series of chemical treatments involving trypsin/EDTA, Triton X-100, sodium deoxycholate, and peracetic acid/ethanol, combined with physical agitation. Following lyophilization, the HAAM was sterilized and coated with fibronectin and chondroitin sulfate (FNC) to enhance cell adhesion. HCECs were then seeded onto the HAAM scaffold. Biocompatibility was assessed by evaluating cell adhesion using microscopy, cell viability using CCK-8 and EdU assays, and cell proliferation. Functional validation included immunofluorescence detection of tight junction proteins (ZO-1), transcriptome sequencing (RNA-seq), and quantitative PCR (qPCR) to analyze the expression of genes regulating barrier function, ion transport, and extracellular matrix synthesis. Additionally, the expression of key genes critical for endothelial function was assessed to validate the functionality of the HAAM-based corneal endothelial transplantation membrane. The HAAM was successfully prepared, maintaining an intact collagen fiber structure. HCECs adhered closely to the HAAM scaffold, forming a continuous monolayer. The HAAM promoted cell viability and proliferation, as evidenced by positive expression of tight junction proteins and upregulation of key functional genes. Transcriptome analysis identified genes involved in proliferation and matrix synthesis, further supporting the biocompatibility and functional properties of the HAAM. The HAAM scaffold demonstrated excellent transparency, mechanical properties, and biocompatibility, making it suitable for the attachment and proliferation of HCECs. The effective maintenance of key functional gene expression levels suggests that the HAAM functionally mimics the characteristics of the natural corneal endothelial layer. These findings provide experimental evidence for the potential clinical application of the HAAM in corneal endothelial transplantation, offering a promising therapeutic option for patients with corneal endothelial dysfunction. Further studies are warranted to explore the long-term efficacy and safety of the HAAM in preclinical and clinical settings.

Brain metastasis (BM) remains a major challenge in non-small cell lung cancer (NSCLC) treatment, with poorly understood mechanisms. A zebrafish xenograft model was established using the H1299 cell line to study NSCLC BM. RNA-Seq identified differentially expressed genes (DEGs) in metastasized to brain vs. non-metastasized cells. Clinical relevance of DEGs was validated using The Cancer Genome Atlas (TCGA) and Kaplan-Meier survival analysis. The anti-proliferation, migration, and invasion effects of were also detected using CCK8 assay, scratch wound healing assay, and transwell assay . The effects of in proliferation and migration were further examined in zebrafish embryos. Additionally, real-time quantitative PCR (RT-qPCR) and Western Blot were performed to validate and explore the underlying molecular mechanisms. Through comprehensive RNA-Seq analysis of zebrafish xenograft model, we identified 177 DEGs significantly associated with NSCLC BM. KEGG and GO enrichment identified as a key mediator in NSCLC BM. Clinical correlation analysis confirmed that expression was associated with NSCLC BM and poor prognosis in lung cancer patients. Functional validation revealed that knockdown reduced H1299 cell viability, migration, and invasion, whereas overexpression in A549 cells increased viability migration, and invasion . These findings were further validated , where overexpression promoted tumor proliferation and metastatic potential. was shown to activate the Wnt/β-catenin signaling pathway and induce epithelial-mesenchymal transition (EMT), thereby enhancing the metastatic potential of lung cancer cells. This study identifies as a key gene of lung cancer BM. promotes EMT and enhances the proliferation and metastatic capacity of lung cancer cells by activating the Wnt/β-catenin signaling pathway. These findings suggest that may serve as a potential therapeutic target for preventing or treating BM in NSCLC.

ObjectiveWe investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3).MethodsCytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.ResultsDocosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).ConclusionsDocosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

Ischemic stroke is a heterogeneous brain injury with complex pathophysiology and it is also a time sensitive neurological injury disease. At present, the treatment options for ischemic stroke are still limited. 6S-5-methyltetrahydrofolate-calcium (MTHF-Ca) is the calcium salt of the predominant form of dietary folate in circulation. MTHF-Ca has potential neuroprotective effect on neurocytes, but whether it can be used for ischemic stroke treatment remains unknown. We established zebrafish ischemic stroke model through photothrombotic method to evaluate the protective effect of MTHF-Ca on the ischemic brain injury of zebrafish. We demonstrated that MTHF-Ca reduced the brain damage by reducing motor dysfunction and neurobehavioral defects of zebrafish with telencephalon infarction injury. MTHF-Ca counteracted oxidative damages after Tel injury by increasing the activities of GSH-Px and SOD and decreasing the content of MDA. RNA-seq and RT-qPCR results showed that MTHF-Ca played a neuroprotective role by alleviating neuroinflammation, inhibiting blood coagulation, and neuronal apoptosis processes. Overall, we have demonstrated that MTHF-Ca has neuroprotective effect in ischemic stroke and can be used as a potential treatment for ischemic stroke.

The SAGE Handbook of Curriculum and Instruction emerges from a concept of curriculum and instruction as a diverse landscape defined and bounded by schools, school boards and their communities, policy, teacher education, and academic research. Each contributing author was asked to comprehensively review the research literature in their assigned topic. These topics, however, are defined by practical places on the landscape e.g. schools and governmental policies for schools. Key Features: o Presents a different vision or re-conceptualization of the field o Provides a comprehensive and inclusive set of authors, ideas, and topics o Takes a global rather than North American parochial approach o Recognizes that curriculum and instruction is broader in scope than is suggested by university research and theory o Reflects post-1992 changes in curriculum policy, practice and scholarship o Represents a rethinking of how school subject matter areas are treated. Teacher education is included in the Handbook with the intent of addressing the role and place of teacher education in bridging state and national curriculum policies and curriculum as enacted in classrooms.