The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

Objective A novel compound based on near-infrared fluorescence(NIRF)probe was prepared to achieve dynamic monitoring of an inflammatory brain edema model in mice and real-time evaluation of therapeutic effects through in vivo imaging.Methods The NIRF probe IR-783 was chemically linked with clinical brain edema therapeutic drug furosemide(FSM)to obtain the new compound,IR-783-FSM.The ultraviolet fluorescence properties of the compound were evaluated using an ultraviolet spectrophotometer.The uptake of the compound by mouse macrophage cells RAW 264.7 was detected with in vitro cellular experiments.Its cytotoxicity was evaluated through CCK8 assays.A brain edema model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide(LPS),confirmed by HE staining and dry-wet weight methods for brain tissues.The mice in the brain edema model were divided into control group,IR-783,and IR-783-FSM treatment groups,receiving intraperitoneal injections of PBS,IR-783,and IR-783-FSM,respectively.Real-time in vivo fluorescence imaging was then performed.The mice in each group were euthanized after 10 hours.Ex vivo brain imaging and dry-wet weight measurements were performed to observe the NIRF imaging characteristics and therapeutic effects of IR-783-FSM on brain edema model.Results The newly synthesized compound,IR-783-FSM,retained the excellent near-infrared fluorescence characteristics of IR-783.It could target mouse macrophages with an IC50 of 48.82 μmol/L.A brain edema model could be successfully constructed with intraperitoneal injection of LPS,with significantly higher brain tissue water content compared to the control group(P＜0.01).In vivo imaging showed that IR-783-FSM had a significantly stronger fluorescence signal in the brain edema model than IR-783.Compared to the control group,the brain water content was significantly reduced in the 2,5,and 8 mmol/L IR-783-FSM treatment groups(P＜0.01).Conclusion The newly synthesized NIRF probe IR-783-FSM facilitates dynamic monitoring of brain edema and real-time evaluation of therapeutic effects.

Objective To establish an orthotopic transplantation tumor model of pancreatic cancer derived from transgenic LSL-KrasG12D/+ LSL-Trp53R172H/+ Pdx1-Cre(KPC)mice.To provide a stable and reliable drug preclinical research animal model to study the developmental mechanism and treatment strategies of pancreatic cancer.Methods Tumor tissue derived from KPC transgenic mice with spontaneous pancreatic cancer was transplanted into the C57BL/6J mouse pancreas.Ultrasound was used to monitor tumor growth.HE and immunofluorescence staining was used to evaluate the pathological characteristics of this model.Results The tumor derived from KPC mice grew steadily on the pancreas of C57BL/6J mice.Tumor cell proliferation index Ki67,matrix fibrosis marker αSMA,and immune cell markers CD45 and CD206 were all stably expressed in the tumor.The model stably retained the pathological features of primary pancreatic cancer.Widespread tumor metastases,which were similar to those observed in patients with pancreatic cancer,developed in this model.Conclusions An orthotopic transplantation model derived from a transgenic mouse with spontaneous pancreatic cancer was established successfully.The model simulates the stromal environment and immune cell infiltration of pancreatic cancer and retains strong stability and uniformity with the original tumor.It can be used as an effective drug preclinical research model to study pancreatic cancer progression and treatment strategies.

Objective In the traditional laboratory zoology lecture environment,there is less teacher-student interaction,less student interest,and less engagement in learning.To improve the teaching quality of laboratory animal science,this teaching and research department was based on different teaching environments of multimedia and intelligent classrooms,theoretical course teaching of Medical Laboratory Animal Science as the research object,the course lecture format,teaching mode,teaching method,and other aspects of innovation and exploration.Methods This study used questionnaires to understand changes in student engagement in learning and preferences for smart classroom use,and NVivo qualitative analysis software was used to code student classroom behavior.Results The smart teaching environment resulted in higher student interest and more frequent teacher-student interaction in the classroom.Students were significantly more engaged in learning than in traditional teaching with higher correct rates on in-class and post-lesson exercises and a better grasp of concepts related to laboratory animal science.Conclusions A smart teaching environment brings students a better feeling and experience,improves their interest in laboratory animal science,increases classroom learning engagement,and achieves good teaching result.

Objective To explore the dynamic changes in monoamine oxidase A(MAOA)and forkhead box A1(FOXA1)levels during neuroendocrine differentiation(NED)in prostate cancer,providing new strategies for the treatment of neuroendocrine prostate cancer.Methods Cell models and mouse transplantation models of NED were established through long-term sustained induction with enzalutamide(ENZ).Dynamic expression of MAOA and FOXA1 in NED was detected by Western Blot and Real-time PCR.GEO database data were selected to analyze the dynamic trends in MAOA and FOXA1 levels in multiple NED models.We constructed a mouse transplantation model of human prostate cancer cell lines and analyzed the dynamic expression of MAOA and FOXA1 in the in vivo NED model by immunohistochemistry.MAOA expression was disrupted with lentiviral transfection,and the impact on FOXA1 was detected.Results Both MAOA and FOXA1 concentrations showed dynamic characteristics,increasing and then decreasing during the NED process.Knockdown of MAOA in prostate cancer cells led to decreased expression of FOXA1.This MAOA may play different roles at different stages of NED by acting through FOXA1.Conclusions Both MAOA and FOXA1 levels showed increasing,then decreasing,trends during NED.The expression of MAOA affected the level of FOXA1,and MAOA/FOXA1 may play a dynamic regulatory role in the NED process.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

Prostate cancer is a prevalent malignant tumor in the male genitourinary system,characterized by a high propensity for bone metastasis.It is a leading cause of mortality,with approximately 70％of deaths attributed to this form of metastasis.Mouse models provide a crucial tool in the investigation of prostate cancer bone metastasis,and play a pivotal role in elucidating the underlying pathophysiological mechanisms and in the development and assessment of therapeutic agents.In this review,we summarize research progress in the construction method and evaluation strategies used in establishing prostate cancer bone metastasis mouse models.Notably,this review focuses on the exploration of the mechanisms responsible for prostate cancer bone metastasis,using mouse models,with the aim of offering insights and serving as a valuable reference for prostate cancer bone metastasis.

Monoamine oxidase A(MAOA)is a membrane-bound mitochondrial enzyme that exists in almost all vertebrate tissues,where it catalyzes the degradation of biogenic and dietary-derived monoamines.MAOA has the function of regulating neurotransmitter metabolism and is associated with anti-tumor immune responses.Most previous studies have focused on the role of MAOA in tumor cells,while more recent findings suggest that MAOA plays an equally significant role in tumor-associated immune cells.In this review,we summarize the regulatory effect of MAOA on the inhibitory tumor microenvironment.The suppressing function of MAOA on various types of tumor-associated immune cells(e.g.,CD8+T cells and tumor-associated macrophages)by its direct effect on monoamines and their metabolic characteristics are discussed.We propose that developing novel MAOA-inhibitor drugs and exploring multidrug-combination strategies may enhance the efficacy of immune therapy for tumors.In conclusion,MAOA may act as a novel target in tumor immunity and influence the effect of tumor immunotherapy.

Objective To construct a patient-derived pancreatic tumor organoid(PDO)and evaluate its effectiveness.Methods We collected fresh surgical specimens from pancreatic cancer patients for PDO culture and compared the pathological and genetic characteristics of the PDO model with those of primary tumors.The PDO model was used to evaluate the efficacy of clinical chemotherapy drugs,and the effectiveness of the model was assessed.Results A PDO model of pancreatic cancer was successfully established.Histomorphological analysis indicated that the PDO model maintained the basic pathological characteristics of the primary tumor.Whole-exon sequencing showed that both the organoids and original tumor tissue remained consistent in their gene mutation type and characteristics.Drug screening tests revealed that the PDO model had good sensitivity to gemcitabine and irinotecan.Conclusions A pancreatic cancer PDO was successfully constructed that reflected the histological and genetic characteristics of the original tumor.The model was shown to be effective for drug sensitivity experiments in vitro and is expected to have implications for precision medicine assays.