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.

Prostaglandin D2(PGD2)is a biologically active substance with important roles in a variety of physiological and pathological processes.PGD2 exerts its biological functions mainly through prostaglandin D2 synthase(PGDS),which is closely related to inflammation and immune regulation.Recent studies have found that PGD2 and its synthase,PGDS,are able to directly inhibit tumor cell proliferation,induce apoptosis,suppress migration and invasion,and further regulate the tumor immune microenvironment to affect the immunotherapy of tumors,demonstrating good tumor therapeutic potential.In this paper,we review the biological properties of PGD2 and its synthase,focusing on its role in the immunotherapy of tumor models.We explore the immunotherapeutic efficacy of PGD2 and its synthase,and their roles in promoting immune cell infiltration in the tumor microenvironment,and discuss their potential as new targets for tumor therapy.

Prostaglandin D2(PGD2)is a biologically active substance with important roles in a variety of physiological and pathological processes.PGD2 exerts its biological functions mainly through prostaglandin D2 synthase(PGDS),which is closely related to inflammation and immune regulation.Recent studies have found that PGD2 and its synthase,PGDS,are able to directly inhibit tumor cell proliferation,induce apoptosis,suppress migration and invasion,and further regulate the tumor immune microenvironment to affect the immunotherapy of tumors,demonstrating good tumor therapeutic potential.In this paper,we review the biological properties of PGD2 and its synthase,focusing on its role in the immunotherapy of tumor models.We explore the immunotherapeutic efficacy of PGD2 and its synthase,and their roles in promoting immune cell infiltration in the tumor microenvironment,and discuss their potential as new targets for tumor therapy.

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 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.

Objective To systematically study the efficacy and safety of KRAS^G12C inhibitors in advanced solid tumors with KRAS^G12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRAS^G12C inhibitors in advanced solid tumors with KRAS^G12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRAS^G12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRAS^G12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.

Objective:To explore the clinical and pathological characteristics and prognostic factors of gastric neuroendocrine carcinoma(G-NEC)and gastric mixed adenoendocrine carcinoma(G-MANEC).Methods:Retrospective analysis was conducted on the clinical data of 67 patients with G-NEC and G-MANEC who underwent surgical treatment at Heping Hospital Affiliated to Changzhi Medical College from May 2015 to May 2023.The study included an analysis of the pathological characteristics distinguishing G-NEC from G-MANEC.Results:Com-pared to gastric adenocarcinoma,patients with G-NEC and G-MANEC in the stomach showed a higher incidence of gastric cancer in the male gastric cardia and were diagnosed at a later age.Tumors with larger diameters increase susceptibility to anemia,low albumin levels,and in-vasion of nerves and vasculature.Deeper tumor infiltration is associated with increased local lymph node metastases,later TNM staging,and a higher likelihood of distant metastasis post-surgery.The prognosis of G-NEC and G-MANEC is worse than that of gastric adenocarcinoma(P=0.001).However,there is no statistically significant difference in the pathological characteristics(P>0.05)and prognosis analysis(P=0.212)between G-NEC and G-MANEC.Univariate survival analysis identified age,preoperative albumin,preoperative CEA,number of lymph node metastases,TNM staging,and postoperative distant metastasis as risk factors affecting patient's overall survival(OS).In the multivariate ana-lysis,age,preoperative albumin,TNM staging,and postoperative distant metastasiswere identified as independent risk factors for OS.Con-clusions:There is a significant difference in clinical characteristics between G-NEC,G-MANEC,and gastric adenocarcinoma,often diagnosed at an advanced stage,which is prone to distant metastasis post-surgery.Poor prognosis is observed in patients aged over 60 years,with pre-operative albumin<40g/L,TNM stage Ⅱ/Ⅲ,and postoperative distant metastasis.

Zinc-α2-glycoprotein (ZAG), encoded by the AZGP1 gene, is a major histocompatibility complex I molecule and a lipid-mobilizing factor. ZAG has been demonstrated to promote lipid metabolism and glucose utilization, and to regulate insulin sensitivity. Apart from adipose tissue, skeletal muscle, liver, and kidney, ZAG also occurs in brain tissue, but its distribution in brain is debatable. Only a few studies have investigated ZAG in the brain. It has been found in the brains of patients with Krabbe disease and epilepsy, and in the cerebrospinal fluid of patients with Alzheimer disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. Both ZAG protein and AZGP1 mRNA are decreased in epilepsy patients and animal models, while overexpression of ZAG suppresses seizure and epileptic discharges in animal models of epilepsy, but knowledge of the specific mechanism of ZAG in epilepsy is limited. In this review, we summarize the known roles and molecular mechanisms of ZAG in lipid metabolism and glucose metabolism, and in the regulation of insulin sensitivity, and discuss the possible mechanisms by which it suppresses epilepsy.
Adipocytes ; metabolism ; Animals ; Brain ; metabolism ; Carrier Proteins ; metabolism ; Epilepsy ; metabolism ; Glucose ; metabolism ; Glycoproteins ; metabolism ; Humans ; Insulin Resistance ; Lipid Metabolism ; Neurons ; metabolism ; Signal Transduction

In the original publication, the author name was incorrectly published as "Lifeng Chen".