Monoclonal Antibodies in the Pathogenesis of Heparin-Induced Thrombocytopenia

New England Journal of Medicine · 2025-09-03 · 6 citations

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated platelet disorder caused by antibodies that target complexes of platelet factor 4 (PF4) and heparin. HIT has been characterized as a polyclonal immune response; however, studies of other rare anti-PF4 disorders have identified clonally restricted antibodies. METHODS: In this study, we investigated the clonality of pathogenic HIT antibodies. Antibodies against PF4-heparin were affinity-purified with the use of PF4-heparin beads from serum samples obtained from nine patients with clinically and serologically confirmed HIT. Antibody clonality was assessed by means of immunofixation electrophoresis and mass spectrometry. Antibody binding to PF4 was evaluated by an enzyme immunoassay, and functional platelet activation was evaluated with the use of a P-selectin expression assay. HIT antibody epitopes were mapped in two patients with the use of a PF4 mutant library. RESULTS: Serum samples from all nine patients with HIT were positive for platelet-activating antibodies against PF4-heparin by enzyme immunoassay, as well as the P-selectin expression assay, and six samples (67%) had a monoclonal antibody detectable by immunofixation electrophoresis. The affinity-purified antibodies against PF4-heparin from all nine samples activated platelets in the P-selectin expression assay, and mass spectrometry showed monoclonality. After affinity purification, antibody-depleted serum samples lost binding activity in the enzyme immunoassay and functional activity in the P-selectin expression assay, which confirmed the removal of the pathogenic antibodies. The epitopes on PF4 targeted by anti-PF4-heparin antibodies from serum samples were the same as those targeted by the affinity-purified monoclonal antibodies. CONCLUSIONS: The pathogenic antibodies in all nine patients with HIT were found to be monoclonal. This finding provides insight into the pathogenesis of HIT and has implications for improved diagnostics and targeted therapeutics. (Funded by the Canadian Institutes of Health Research and the National Institutes of Health.).

Spätzle promotes hemocytes phagocytosis and phagocytosis-associated genes expression in Portunus trituberculatus

Aquaculture · 2025-12-20

The experience of transition preparation for children and adolescents with mental disorders in China: a qualitative study

Frontiers in Psychology · 2025-09-01

Background: Adolescence represents a critical transitional phase from pediatric to adult healthcare, during which young individuals with mental disorders encounter unique challenges; however, research on their transition experiences, particularly in non-English-speaking contexts such as China, remains limited. Objectives: This study aimed to explore the transition preparation experiences of adolescents with mental disorders in China as they move from pediatric to adult healthcare. Methods: Qualitative semi-structured interviews were conducted with 15 children and adolescents diagnosed with mental disorders in China, and the data were analyzed using interpretive phenomenological analysis. Findings: The study identified five primary themes related to the transition experiences of children and adolescents with mental disorders: (1) a discrepancy between transitional awareness and action; (2) gaps in transitional care throughout the healthcare transition process; (3) multidimensional needs within transitional care; (4) a contradiction between desire for self-management of illness and limited capacity; and (5) the dual attributes of family support, encompassing both enabling and constraining aspects. Conclusion: The study underscores the concerning transition readiness of adolescents with psychiatric disorders in China, marked by complex challenges and diverse needs, while highlighting the dual role of family support as both a motivating and obstructive force.

In vivo CAR-T cell therapy: New breakthroughs for cell-based tumor immunotherapy

Human Vaccines & Immunotherapeutics · 2025-09-11 · 7 citations

Chimeric antigen receptor (CAR)-T cell immunotherapy represents an evolutionary advance in the treatment of cancer, yet it faces challenges such as manufacturing complexity, high cost, and time-consuming process. In recent years, the strategy of in vivo CAR-T cell therapy is emerging as a promising approach to improve anti-tumor effectiveness and safety. Briefly, T cells are genetically modified to express CAR protein directly in the body by delivery of vectors. With the continuous optimization of gene delivery systems, gene editing technologies and CAR structures, advancements in in vivo CAR-T therapies have notably enhanced safety, effectiveness, and application in clinical settings. Here, we review the key platforms of in vivo gene delivery and the progress of in vivo CAR-T cell therapy for cancers. We discuss the challenges of in vivo CAR-T cell therapy, such as safety issues of gene delivery, the persistence and function of CAR-T cell, and the immunosuppressive microenvironment in solid tumors.

dsHMGB1, released from IL-17A-induced pyroptotic prostate epithelial cells, drives M1 polarization by promoting Pfkp-mediated glycolysis via Jak2/Stat1 transcription in experimental autoimmune prostatitis

International Journal of Biological Sciences · 2025-09-03

IL-17A-mediated pyroptosis in prostate epithelial cells triggers the release of dsHMGB1, which transcriptional regulates the key glycolytic enzyme Pfkp through the Jak2/Stat1 transcription to promote the M1 polarization of macrophages. Targeting dsHMGB1 or Stat1 could be potential therapeutic strategies for managing CP/CPPS by regulating M1 macrophage polarization and reducing inflammatory cytokines.

P3.12.74 IMM2510, an Anti-PD-L1/VEGF Bispecific Antibody Fusion Protein for Advanced IO-treated SQ-NSCLC: A Phase I Study

Journal of Thoracic Oncology · 2025-10-01

Current Trends in Revision Surgery After Breast Reconstruction in China: Insights from a Nationwide Cross-Sectional Survey

Aesthetic Plastic Surgery · 2025-12-05

INTRODUCTION: Revision surgery is an integral component of post-mastectomy breast reconstruction, aimed at enhancing breast aesthetics and improving patient satisfaction. While developed countries have established high rates of revision surgery, its implementation in China remains limited. We aimed to evaluate the current practices and challenges of revision surgery in Mainland China using a nationwide cross-sectional survey. METHODS: A nationwide questionnaire authorized by the Chinese Anti-Cancer Association and related committees was distributed to 215 hospitals in China performing over 200 annual breast cancer surgeries, with 198 hospitals completed the survey. Data on nipple-areola complex reconstruction (NAR), autologous fat grafting (AFG), and contralateral breast symmetry surgery were collected and analyzed. RESULTS: Of the 198 surveyed hospitals, 23.2% performed NAR, 17.2% conducted AFG, and 26.8% carried out contralateral breast symmetry surgery, with only 6.6% providing all three. (1) NAR: Both the time intervals between primary breast reconstruction and NAR and the diverse techniques of NAR were to note. The use of autologous or allogenic implants has proven to improve long-term nipple projection (median nipple shrinkage rate 5.5% vs 30%; P < 0.001), but its usage was still limited. (2) AFG: AFG has wide application in breast reconstruction, with the most common use remaining the correction of deformities after lumpectomy (28/34, 82.4%) or breast reconstruction after mastectomy (21/34, 61.8%). (3) Contralateral breast symmetry surgery: Contralateral breast symmetry surgery was widely accepted by patients, and a simultaneous procedure was more favored (median 80% vs 20%; P < 0.001). CONCLUSION: The implementation of revision surgery in China remains insufficient and unevenly distributed. Targeted efforts to expand specialized training, especially in plastic surgery, improve resource allocation, and adopt advanced techniques are essential. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multi-omics identifies L-rhamnose as a metabolic regulator that enhances glycolysis to promote hair follicle growth

Phytomedicine · 2025-11-21

BACKGROUND: Hair follicle-regenerating drugs are essential for alopecia treatment, yet their discovery remains a key challenge in dermatology. PURPOSE: This study aims to identify small molecule compounds that promote hair growth and investigate their underlying mechanisms. METHODS: A gene panel was designed based on single-cell and bulk RNA-sequencing data, and chemical genomics was employed to screen potential hair-inducing compounds. The lead candidate was validated using an in vivo mouse model of anagen induction and an ex vivo human hair follicle organ culture system. Transcriptomic, metabolomic, and cellular bioenergetics assays were performed to elucidate the potential mechanism, while molecular docking and surface plasmon resonance confirmed its direct protein targets. RESULTS: Rhamnose was identified as a compound that restored the expression of hair-inducing genes in human dermal papilla cells (hDPCs). Rhamnose accelerated hair follicle regeneration by stimulating the hair cycle progression from telogen to anagen in mice and promoting ex vivo cultured human scalp hair follicle growth. Rhamnose promoted glycolysis in both the mouse model and hDPCs at both transcriptional and metabolic levels. Mechanically, rhamnose exerted its metabolic effects not as a hexose energy substrate, but rather by upregulating hexokinase 2 (HK2)-a key rate-limiting glycolytic enzyme-and directly binding to HK2 to stimulate its activity. CONCLUSION: This study identifies the natural monosaccharide rhamnose as a metabolic regulator to enhance glycolysis, thereby promoting hair follicle growth, and highlights its potential therapeutic application in alopecia.

P08.03.A DOUBLE-PUNCH STRATEGY: MACROPHAGE MEMBRANE-ENVELOPED IMIPRAMINE AND ACD47 REPROGRAMS TUMOR MICROENVIRONMENT TO ENHANCE GLIOBLASTOMA IMMUNOTHERAPY

Neuro-Oncology · 2025-10-01

Abstract BACKGROUND The immune response rates of patients with glioblastoma (GBM) are relatively low for the complex immunosuppressive tumor microenvironment, which is mainly attributed to the presence of M2-type tumor-associated macrophages (TAMs). Herein, to enhance anti-GBM immune response, we designed a novel biomimetic cascade nanoreactor (Mam@NPs) with “double-punch” strategy for reshaping M2-type TAMs into M1-type. MATERIAL AND METHODS The Mam@NPs were fabricated by a dual pH-responsive CDM-PEG-PDPA diblock copolymer loaded with imipramine (IM) and aCD47 followed by macrophage membrane (Mam) encapsulation. The physio-chemical features of Mam@NPs were analyzed and characterized by dynamic light scattering, transmission electron microscopy and western blot. The BBB transcytosis and GBM targeting capability of Mam@NPs were tested by using BBB model in vitro and bioluminescence/fluorescence in vivo. The antitumor ability of Mam@NPs was evaluated by using CCK8, EdU assay in vitro and bioluminescence in vivo. The immune phenotyping and antitumor immunity were examined by using flow cytometry ELISA and immunohistochemistry. RESULTS This biomimetic cascade-nanoreactor significantly ablated the tumor cells directly by releasing IM and simultaneously bolstering the anti-GBM effects of aCD47. This augmentation arose from the synergistic remodeling effect of IM and aCD47 on the immunosuppressive tumor microenvironment by enhancing CCL3 secretion, reshaping M2-type TAMs into M1-type, promoting the maturation of dendritic cells, stimulating the proliferation/activation of CD8+ T cells, and reducing regulatory T cells. CONCLUSION This work generates a safe and effective “double-punch” biomimetic cascade-nanoreactor, offering an innovative combination treatment strategy for aCD47 together with IM in GBM immunotherapy.