Alacrima-achalasia-mental retardation syndrome(AAMR) is an extremely rare autosomal recessive genetic disorder caused by mutation in the GMPPA gene. Its pathogenesis is associated with congenital disorders of glycosylation. The clinical manifestations involve multiple system impairments, with alacrima, achalasia, and mental retardation as the core features. This article reports the diagnosis, treatment process and long-term follow-up outcomes after deep brain stimulation in one patient with AAMR complicated with dystonia, aiming to improve clinicians' understanding of this disease.

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.

Japanese encephalitis virus(JEV)usually evades the inhibitory effect of the innate immunity factor type Ⅰ interferon(Ⅰ-IFN)when it infects human cells and tissues.The virus then causes a series of serious symptoms,such as spasticity,neurodegenerative lesions,neuroinflammation,and even death.Generally,JEV escapes innate immunity by inhibiting IFN-α/β production and the interferon Janus kinase-signal transducer and activator of transcription signaling pathway.Because of this special immune escape mechanism,various mouse infection models have been constructed for the study of the pathogenesis of and therapeutic regimens for JEV infections.In this review,based on an exposition of the IFN immune escape mechanism of JEV,we systematically introduce the concept of JEV-infected mouse models and analyze the characteristics of these models and the degree to which they simulate human symptoms.The intention is to develop various new JEV-infected mouse models based on potential new research targets and provide novel ideas for animal models for JEV 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.

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.

Japanese encephalitis virus(JEV)usually evades the inhibitory effect of the innate immunity factor type Ⅰ interferon(Ⅰ-IFN)when it infects human cells and tissues.The virus then causes a series of serious symptoms,such as spasticity,neurodegenerative lesions,neuroinflammation,and even death.Generally,JEV escapes innate immunity by inhibiting IFN-α/β production and the interferon Janus kinase-signal transducer and activator of transcription signaling pathway.Because of this special immune escape mechanism,various mouse infection models have been constructed for the study of the pathogenesis of and therapeutic regimens for JEV infections.In this review,based on an exposition of the IFN immune escape mechanism of JEV,we systematically introduce the concept of JEV-infected mouse models and analyze the characteristics of these models and the degree to which they simulate human symptoms.The intention is to develop various new JEV-infected mouse models based on potential new research targets and provide novel ideas for animal models for JEV research.

Peptidylarginine deiminases 2(PADI2)is an enzyme that catalyzes the conversion of arginine residues to citrulline on protein peptides.Aberrant activation of PADI2 can induce excessive tissue inflammation and immune responses,thereby exacerbating the progression of autoimmune diseases(ADs).Through citrullination,PADI2 modifies protein structure and immunogenicity,influencing the production of autoantibodies and regulating the activity of immune cells such as neutrophils and macrophages.This review provides an overview of PADI2's functions and its pivotal role in ADs,with the objective of elucidating the mechanisms underlying ADs pathogenesis and identifying novel therapeutic targets and strategies for related diseases.

Peptidylarginine deiminases 2(PADI2)is an enzyme that catalyzes the conversion of arginine residues to citrulline on protein peptides.Aberrant activation of PADI2 can induce excessive tissue inflammation and immune responses,thereby exacerbating the progression of autoimmune diseases(ADs).Through citrullination,PADI2 modifies protein structure and immunogenicity,influencing the production of autoantibodies and regulating the activity of immune cells such as neutrophils and macrophages.This review provides an overview of PADI2's functions and its pivotal role in ADs,with the objective of elucidating the mechanisms underlying ADs pathogenesis and identifying novel therapeutic targets and strategies for related diseases.

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.