The function of nicotinamide phosphoribosyl transferase (NAMPT) and its role in diseases.

Nicotinamide phosphoribosyl transferase (NAMPT) is a rate-limiting enzyme in the mammalian nicotinamide adenine dinucleotide (NAD) salvage pathway, and plays a vital role in the regulation of cell metabolic activity, reprogramming, aging and apoptosis. NAMPT synthesizes nicotinamide mononucleotide (NMN) through enzymatic action, which is a key protein involved in host defense mechanism and plays an important role in metabolic homeostasis and cell survival. NAMPT is involved in NAD metabolism and maintains intracellular NAD levels.

The role of actin cytoskeleton CFL1 and ADF/cofilin superfamily in inflammatory response.

Actin remodeling proteins are important in immune diseases and regulate cell cytoskeletal responses. These responses play a pivotal role in maintaining the delicate balance of biological events, protecting against acute or chronic inflammation in a range of diseases. Cofilin (CFL) and actin depolymerization factor (ADF) are potent actin-binding proteins that cut and depolymerize actin filaments to generate actin cytoskeleton dynamics.

The structure and function of multifunctional protein ErbB3 binding protein 1 (Ebp1) and its role in diseases.

ErbB3-binding protein 1(Ebp1) has two isoforms, p42 Ebp1 and p48 Ebp1, both of which can regulate cell growth and differentiation. But these isoforms often have opposite effects, including contradictory roles in regulation of cell growth in different tissues and cells. P48 Ebp1 belongs to the full-length sequence, while conformational changes in the crystal structure of p42 Ebp1 reveals a lack of an α helix at the amino terminus.

Downregulation of lysine 2-hydroxyisobutyrylation of ErbB3 binding protein 1 at amino acid 210 promotes keratinocyte proliferation via induction of transcription initiation factor IA-mediated rRNA synthesis.

Background: Psoriasis is a prevalent chronic inflammatory dermatosis characterized by the excessive proliferation of keratinocytes (KCs). Lysine 2-hydroxyisobutyrylation (Khib) is a newly identified post-translational modification that regulates various biological processes. Abnormal Khib modification has been associated with the development of autoimmune diseases.

The mRNA Expression Profile of Psoriatic Lesion Distinct from Non-Lesion.

Purpose: Psoriasis is a chronic recurring autoimmune skin disease with a complex etiology and chronic progression; however, its molecular mechanisms remain unclear.

Patients And Methods: We performed transcriptomic analysis to profile the mRNA expression of psoriatic lesions (PL) and non-lesion (NL) tissues from psoriasis patients along with normal skin from healthy donors. RT-qPCR was used to validate the mRNA expression profiles.

Psoriatic Dermal-Derived Mesenchymal Stem Cells Induced C3 Expression in Keratinocytes.

Purpose: Our recent studies found a splice region mutation in C3 accompanied by a significantly increased C3 in psoriatic peripheral blood. Mesenchymal stem cells (MSCs) are a key immunological suppression cell. We further investigate the regulation of MSCs on C3 in psoriasis.

Variants in PRKCE and KLC1, Potential Regulators of Type I Psoriasis.

Purpose: Psoriasis is a multifactorial disease with a complex genetic predisposition. The pathophysiology of psoriasis is associated with genetic variants. To better characterize gene variants in psoriasis and identify the relationship between clinical characteristics and variant genes in its pathogenesis.

Normal mesenchymal stem cells can improve the abnormal function of T cells in psoriasis via upregulating transforming growth factor-β receptor.

Psoriasis, a chronic inflammatory skin disease, is a refractory disorder. Previous studies have shown that the imbalance of the T-helper (Th)17/regulatory T cells (Treg) results in the immune imbalance of T cells in psoriatic patients, and that mesenchymal stem cells display an immunosuppressive role by promoting the differentiation of T cells into Treg, leading to a reduction in the proportion of Th17/Treg. Utility of mesenchymal stem cells is becoming a new approach for the treatment of immune disorders.

The effects of human dermal-derived mesenchymal stem cells on the keratinocyte proliferation and apoptosis in psoriasis.

Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperproliferation. Mesenchymal stem cells (MSCs) regulate inflammation and vascular proliferation in the psoriasis lesions. Whether dermal-derived mesenchymal stem cells (DMSCs), the main MSCs in the dermis, regulate keratinocyte proliferation and apoptosis remains unknown.

Dysregulated Dermal Mesenchymal Stem Cell Proliferation and Differentiation Interfered by Glucose Metabolism in Psoriasis.

Background And Objectives: Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation , we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis.

The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis.

Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing.

Cross-sectional study reveals that HLA-C*07:02 is a potential biomarker of early onset/lesion severity of psoriasis.

Psoriasis is a common chronic autoimmune skin disease, with T cells playing a predominant role in its pathogenesis. Here, we aimed to investigate the relation of T-cell repertoires (TCR) and major histocompatibility complex (MHC) in psoriatic patients to further understand mechanisms in disease pathogenesis. We conducted a cross-sectional study involving nine pairs of monozygotic twins with inconsistent psoriasis and examined the TCR diversity and MHC haplotype of the individuals using multiple-PCR and high-throughput sequencing.

Different epigenome regulation and transcriptome expression of CD4 and CD8 T cells from monozygotic twins discordant for psoriasis.

Objectives: Psoriasis is an immunodeficient skin disorder, and its exact pathogenesis is unclear. Monozygotic twins are presumed to be genetically identical, and their phenotypic differences may be due to transcriptional regulation or epigenome factors. To explain the inconsistency between twins, we have collected 3 pairs of monozygotic twins who are discordant for psoriasis.

Role of SPRED1 in keratinocyte proliferation in psoriasis.

Psoriasis is a recurrent inflammatory skin disease, affecting approximately 2% of the population. Previous studies have demonstrated that psoriatic dermal mesenchymal stem cells (DMSC) stimulated keratinocyte (KC) proliferation and that psoriasis exhibited missense SPRED1 mutations. To further investigate the molecular mechanism by which psoriatic DMSC stimulate KC proliferation, and the role of missense SPRED1 mutations in psoriasis, we assessed expression levels of miRNA, and both mRNA and protein of SPRED1 in normal human epidermal keratinocyte cells (NHEK) cocultured with either psoriatic or control DMSC.

Expression and functional regulation of gap junction protein connexin 43 in dermal mesenchymal stem cells from psoriasis patients.

Background: Psoriasis is a chronic recurrent inflammatory disease. Mesenchymal stem cells (MSCs) can regulate the inflammatory microenvironment, thereby controlling the proliferation, differentiation, and migration of immune cells. Connexin 43(Cx43), a key gap junction protein, has been shown to form gap junctions for communication between neighboring cells.

Psoriatic Dermal-derived Mesenchymal Stem Cells Reduce Keratinocyte Junctions, and Increase Glycolysis.

Although it is known that psoriatic dermal-derived mesenchymal stem cells (DMSCs) dysregulate keratinocyte proliferation, the biological activity profile of keratinocytes influenced by psoriatic DMSCs remain unknown. In the present study, we assessed the impact of psoriatic DMSCs on keratinocyte proliferation, differentiation, and glucose metabolism in normal human epidermal keratinocytes co-cultured with or without psoriatic DMSCs. Co-culture of normal human epidermal keratinocytes with psoriatic DMSCs downregulated expression levels of proteins associated with cell junction assembly (alpha-actinin-1, catenin beta-1, poliovirus receptor-related protein 4 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), while upregulating proteins associated with keratinocyte proliferation and differentiation (involucrin, isoform 2 of Histone-binding protein, isoform 3 of Telomeric repeat-binding factor 2 and keratin 13).

Variation at ACOT12 and CT62 locus represents susceptibility to psoriasis in Han population.

Background: Psoriasis is a chronic inflammatory disorder of the skin, and genetic factors are reported to be involved in the disease pathogenesis. Many studies have named psoriasis candidate genes.

Objective: In this study, we determined the mutation frequency of 7 variable genes in 1,027 psoriatic patients and investigated its possible mechanism associated with psoriasis.

Comparison of two commonly used methods for stimulating T cells.

Objective: Although several methods have been reported and used for in vitro T cell amplification, there are no consistent reports on the optimal stimulation conditions and the characterization of these stimulated T cells. The current study aimed to determine the optimal conditions for efficient T cell amplification by two commonly used methods involving CD3/CD28 antibody and phytohemagglutinin (PHA), respectively.

Results: Orthogonal design and CCK8 assay showed that 5 μg/mL CD3, 5 μg/mL CD28, and 100 ng/mL IL2 for the first method and 50 μg/mL PHA for the second method was optimal for T cell stimulation.

Multi-omics study in monozygotic twins confirm the contribution of de novo mutation to psoriasis.

Background: Genome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.