Optical Genomic Mapping and Next-Generation Sequencing Identified Retrotransposon Insertion and Missense Variant Disrupting Gene in Dyskeratosis Congenita.

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by defects in telomere biology and clinical manifestations such as nail dystrophy, skin pigmentation abnormalities, and mucosal leukoplakia. Here, using whole exome sequencing (WES), whole genome sequencing (WGS), optical mapping sequencing (OGM), third-generation sequencing, and mRNA sequencing, we diagnosed a participant with gene complex compound heterozygous variants. In addition, protein structure simulation, immunohistochemistry, and western blot were conducted to investigate the structure and expression level of the PARN protein.

Platelet-Derived Extracellular Vesicles Alleviate Psoriatic Inflammation via Mitochondrial Transfer to Macrophages.

Platelet-rich plasma (PRP) is a safe, autologous plasma component abundant in cytokines and extracellular vesicles, frequently applied to treat inflammatory disorders. Although PRP demonstrates potential for psoriasis therapy, its underlying mechanism remains insufficiently understood. In this study, various PRP constituents were evaluated in an imiquimod (IMQ)-induced mouse model of psoriasis.

Spongiotic Psoriasiform Dermatitis with Dual Features of Eczema and Psoriasis: JAK Inhibition as a Potential Therapeutic Option.

Background: Psoriasis and eczema are inflammatory skin disorders with distinct immune mechanisms. Psoriasis is mainly driven by Th17 immune responses, while eczema, notably atopic dermatitis (AD), is Th2-mediated. Spongiotic psoriasiform dermatitis (SD/PSO), a hybrid phenotype of both, lacks precise immunophenotypic characterization and treatment strategies.

First successful treatment of epidermolytic Ichthyosis with Vunakizumab: A Case Report.

Ichthyoses, a group of skin cornification disorders caused by protein and lipid abnormalities that disrupt epidermal functions, are mainly characterized by generalized scaling. This study is the first to report the use of Vunakizumab, China's first self-developed anti-IL-17A monoclonal antibody, in treating ichthyosis. We presented a case of a 4-year-old boy with epidermolytic ichthyosis (EI) due to a gene mutation.

Ultra-high gene transfection efficiency in suspension cells mediated by highly branched-linear poly(β-amino ester)s.

Suspension cells, particularly 293F cells, are widely used for the production of therapeutic proteins, antibodies, virus-like particles (VLPs) for vaccines, and viral vectors for gene and cell therapies. However, DNA-encapsulated polyplexes typically exhibit poor interaction with the cellular membrane of suspension cells, resulting in low cellular uptake and transfection efficiency, which underscores the need for the development of more effective gene delivery systems for suspension cells. Molecular weight (MW) and topological structure are two of the most critical structural parameters that indicate the gene transfection performance of highly branched-linear poly(β-amino ester)s (H-LPAEs).

Nootkatone Derivative Nootkatone-(E)-2-iodobenzoyl hydrazone Promotes Megakaryocytic Differentiation in Erythroleukemia by Targeting JAK2 and Enhancing JAK2/STAT3 and PKCδ/MAPK Crosstalk.

Erythroleukemia, a complex myeloproliferative disorder presenting as acute or chronic, is characterized by aberrant proliferation and differentiation of erythroid cells. Although nootkatone, a sesquiterpene derived from grapefruit peel and Alaska yellow cedar, has shown anticancer activity predominantly in solid tumors, its effects in erythroleukemia remain unexplored. This study aimed to investigate the impact of nootkatone and its derivatives on erythroleukemia.

Successfully treated with siltuximab and prednisone in a 7-year-old girl with -deficiency presenting as recurrent wart-like lesions: a case report.

Dedicator of cytokinesis 8 (DOCK8) deficiency represents a primary immunodeficiency with a wide range of clinical symptoms, including recurrent infections, atopy, and increased malignancy risk. This study presents a case of a 6-year-old girl with deficiency, characterized by severe, treatment-resistant herpetic infections who was successfully treated with siltuximab and glucocorticoids. The successful use of siltuximab in achieving remission highlights the pivotal role of interleukin-6 (IL-6) in deficiency pathogenesis and suggests that IL-6 modulation can be critical in managing deficiency-related viral infections, which may inform future therapeutic strategies for deficiency and similar immunodeficiencies.

A Carbon 21 Steroidal Glycoside with Pregnane Skeleton from Bunge Promotes Megakaryocytic and Erythroid Differentiation in Erythroleukemia HEL Cells through Regulating Platelet-Derived Growth Factor Receptor Beta and JAK2/STAT3 Pathway.

Erythroleukemia is a rare form of acute myeloid leukemia (AML). Its molecular pathogenesis remains vague, and this disease has no specific therapeutic treatments. Previously, our group isolated a series of Carbon 21 (C-21) steroidal glycosides with pregnane skeleton from the root of Bunge.

ADAM17 variant causes hair loss via ubiquitin ligase TRIM47-mediated degradation.

Hypotrichosis is a genetic disorder characterized by a diffuse and progressive loss of scalp and/or body hair. Nonetheless, the causative genes for several affected individuals remain elusive, and the underlying mechanisms have yet to be fully elucidated. Here, we discovered a dominant variant in a disintegrin and a metalloproteinase domain 17 (ADAM17) gene caused hypotrichosis with woolly hair.

OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome.

Purpose: In this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism.

Methods: Exome sequencing and Sanger sequencing was conducted in affected and unaffected family members.

Superior COL7A1 and TGM1 gene expression in difficult-to-transfect skin cell mediated by highly branched poly(β-amino esters) through stepwise fractionation.

Delivering functional gene into targeted skin cells or tissues to modulate the genes expression, has the potential to treat various hereditary cutaneous disorders. Nevertheless, the lack of safe and effective gene delivery vehicles greatly limits the clinical translation of gene therapy for inherited skin diseases. Herein, we developed a facile elution fractionation strategy to isolate eight HPAEs with M ranging from 7.

Mosaic GJB2 mutations in widespread porokeratotic adnexal ostial nevus: Report of two patients.

Porokeratotic adnexal ostial nevus (PAON) is a rare adnexal hamartoma characterized by keratotic papules following Blaschko's lines, typically located on the unilateral distal extremities. Cutaneous somatic GJB2 mutations have been linked to the pathogenesis of PAON. However, the genetic mechanism underlying bilateral or extended forms, which are less documented, remains unknown.

Superior TRAIL gene expression and cancer cell apoptosis mediated by highly branched-linear poly(β-amino ester)s.

Extensive efforts have been dedicated to enhancing the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cancer cells for the development of effective cancer treatments. However, highly safe and efficient delivery of TRAIL gene remains a significant challenge, especially using cationic polymers. Here, a series of highly branched-linear poly(β-amino ester)s (H-LPAEs) are developed through a unique oligomer branching strategy.

Potent gene delivery from fluorinated poly(β-amino ester) in adhesive and suspension difficult-to-transfect cells for apoptosis and ferroptosis.

Tremendous efforts have been made to improve polymeric property in gene delivery performances, especially when obstacle of transferring gene construct into difficult-to-transfect cells occurs. Innovations in the area of fluorination and fluorinated compounds with biomedical potential in medicinal chemistry are believed to assist in the development of new therapeutics. Fluorine modified polymers have shown to navigate the gene transfection cellular barriers and promoted the transfection outcomes.

Biologics and oral small-molecule inhibitors for treatment of pediatric atopic dermatitis: Opportunities and challenges.

Atopic dermatitis (AD) is a complex disease characterized by recurrent eczematous lesions and refractory pruritus that drastically impairs quality of life. Due to the chronic and relapsing course, patients are easily trapped in the debilitating condition. Classical therapies show limitations, especially for patients with moderate-to-severe phenotypes.