JMJD3 in the regulation of human diseases

In recent years,many studies have shown that histone methylation plays an important role in maintaining the active and silent state of gene expression in human diseases.The Jumonji domain-containing protein D3(JMJD3),specifically demethylate di-and trimethyllysine 27 on histone H3(H3K27me2/3),has been widely studied in immune diseases,infectious diseases,cancer,developmental diseases,and aging related diseases.We will focus on the recent advances of JMJD3 function in human diseases,and looks ahead to the future of JMJD3 gene research in this review.

Recent advances of biomaterials in biotherapy

Biotherapy mainly refers to the intervention and the treatment of major diseases with biotechnologies or bio-drugs,which include gene therapy,immunotherapy(vaccines and antibodies),bone marrow transplantation and stem-cell therapy.In recent years,numerous biomaterials have emerged and were utilized in the field of biotherapy due to their biocompatibility and biodegradability.Generally,biomaterials can be classified into natural or synthetic polymers according to their source,both of which have attracted much attention.Notably,biomaterials-based non-viral gene delivery vectors in gene therapy are undergoing rapid development with the emergence of surface-modified or functionalized materials.In immunotherapy,biomaterials appear to be attractive means for enhancing the delivery efficacy and the potency of vaccines.Additionally,hydrogels and scaffolds are ideal candidates in stem-cell therapy and tissue engineering.In this review,we present an introduction of biomaterials used in above biotherapy,including gene therapy,immunotherapy,stem-cell therapy and tissue engineering.We also highlighted the biomaterials which have already entered the clinical evaluation.

JMJD family proteins in cancer and inflammation

The occurrence of cancer entails a series of genetic mutations that favor uncontrollable tumor growth.It is believed that various factors collectively contribute to cancer,and there is no one single explanation for tumorigenesis.Epigenetic changes such as the dysregulation of enzymes modifying DNA or histones are actively involved in oncogenesis and inflammatory response.The methylation of lysine residues on histone proteins represents a class of post-translational modifications.The human Jumonji C domain-containing(JMJD)protein family consists of more than 30 members.The JMJD proteins have long been identified with histone lysine demethylases(KDM)and histone arginine demethylases activities and thus could function as epigenetic modulators in physiological processes and diseases.Importantly,growing evidence has demonstrated the aberrant expression of JMJD proteins in cancer and inflammatory diseases,which might serve as an underlying mechanism for the initiation and progression of such diseases.Here,we discuss the role of key JMJD proteins in cancer and inflammation,including the intensively studied histone lysine demethylases,as well as the understudied group of JMJD members.In particular,we focused on epigenetic changes induced by each JMJD member and summarized recent research progress evaluating their therapeutic potential for the treatment of cancer and inflammatory diseases.

Role of tumor gene mutations in treatment response to immune checkpoint blockades

Early studies shed light on the immune suppression of immune checkpoint molecules in the cancer microenvironment,with later studies applying immune checkpoint blockade(ICB)in treatment of various malignancies.Despite the encouraging efficacy of ICBs in a substantial subset of cancer patients,the treatment response varies.Gene mutations of both tumor cells and immune cells in the tumor microenvironment have recently been identified as potential predictors of the ICB response.Recent developments in gene expression profiling of tumors have allowed identification of a panel of mutated genes that may affect tumor cell response to ICB treatment.In this review,we discuss the association of the ICB response with gene expression and mutation profiles in tumor cells,which it is hoped will help to optimize the clinical application of ICBs in cancer patients.