Specific Antigen Research Articles

A Programmatic Approach to En Bloc Transurethral Enucleation of the Prostate with Bipolar System (TUEB): A Single-Center Retrospective Report

Introduction: This study presents a systematic approach for en bloc transurethral enucleation of the prostate utilizing a bipolar system (TUEB), evaluating its effectiveness and safety. Furthermore, the research aims to pinpoint risk factors contributing to early stress urinary incontinence (SUI) after undergoing en bloc TUEB. Methods: The en bloc TUEB procedure is visually demonstrated through images and videos. A retrospective analysis was conducted based on the data of 88 patients diagnosed with benign prostatic hyperplasia (BPH) who underwent en bloc TUEB between January 2018 and April 2023. Detailed perioperative and follow-up clinical data were collected and analyzed. Patients were categorized based on the occurrence of SUI, and their clinical characteristics were analyzed. Results: The mean surgical duration was 113.1 ± 50.0 minutes, resulting in an excised prostate gland weighing 58.0 ± 34.3 g and a hemoglobin drop of 14.3 ± 11.2 g/L. The average enucleation rate was 79.00 ± 11.01 %, enucleation efficiency was 0.54 ± 0.26 g/min and prostate specific antigen (PSA) reduction rate was 42.08 ± 22.85 %. There were no major complications during operation. Twenty-three patients (26.13%) developed early SUI after catheter removal, and 74% of them were in remission within 1 month. Importantly, no cases of persistent SUI were observed. Lower urinary tract symptoms (LUTS) duration was significantly different between patients with and without post-operative SUI. Residual urine volume, International Prostate Symptom Score (IPSS) and Quality of Life (QoL) score were significantly improved in BPH patients after surgery (P < 0.05). Twelve months after surgery, only 2 patients (2.27%) had urethral stricture, although it recovered after transurethral dilation. Conclusions: En bloc TUEB is proven to be effective, practical, efficient and safe with minimal complications. This procedure could be standardized and widely adopted. LUTS duration can predict the risk of early SUI.

Harm reduction techniques among cisgender gay, bisexual, and queer men using anabolic androgenic steroids: a qualitative study

BackgroundAnabolic androgenic steroids (AAS) are synthetic forms of testosterone frequently used as performance enhancing drugs among gay, bisexual, and queer (GBQ) men. Despite widespread use, associated harms, and the likely existence of an AAS use disorder, there is no medical consensus on standards of care for people who use AAS, with most medical providers focusing exclusively on abstinence. Individuals using AAS have developed community-based harm reduction strategies to mitigate these harms.MethodsThis paper is a sub-analysis of qualitative data obtained through semi-structured interviews with GBQ men using AAS for 8 or more weeks recruited through convenience and snowball sampling from clinical sites and LGBTQ + venues in New York City as well as through social media. Interviews were coded with themes developed using reflexive thematic analysis. Data related to harm reduction techniques were then re-analyzed through a prevention strategies framework lens of primary, secondary, and tertiary harm prevention.ResultsThematic saturation was reached at twelve interviews in the primary analysis, with men reporting frequent use of multiple harm reduction techniques. For primary prevention, men avoided oral steroids and simultaneous substance use, tried to obtain AAS from reputable sources, used “cycling” to dose steroids, and practiced sterile injection techniques. Secondary prevention methods included patient-directed lab testing for hematocrit, liver and kidney function, cholesterol, prostate specific antigen, testosterone, and self-performed blood pressure checks. Tertiary prevention included donating blood and the use of medications without a prescription, including aromatase inhibitors, selective estrogen receptor blockers, aspirin, statins, angiotensin receptor blockers, clomiphene, and human chorionic gonadotropin.ConclusionsDespite many GBQ men experiencing harms from anabolic androgenic steroids, community members have often sought harm reduction techniques in lieu of abstinence. Though many of these techniques embrace clinical reasoning and may be more broadly applicable, additional research is needed to understand the impact of each intervention on the overall health of individuals using AAS.

GelMA microneedle-loaded bio-derived nanovaccine shows therapeutic potential for gliomas

ABSTRACT Glioma is the most common primary malignant tumor of the central nervous system in adults. Although immunotherapy, especially tumor vaccines, has made some progress in the treatment of gliomas compared with surgery and radiotherapy. However, the lack of specific or relevant tumor antigens severely limits the further development of tumor vaccines. Here, we report a bio-derived vaccine (TMV@CpG) derived from glioma cell membrane vesicles and carrying TLR9 agonist CpG as adjuvant, which was loaded onto the GelMA microneedle to obtain the microneedle vaccine (MN-TMV@CpG). Microneedle vaccine fully utilize the innate immune cells rich in the skin, inducing stronger cellular immune responses. In subcutaneous tumor models, MN-TMV@CpG reversed the immune-suppressing microenvironment of tumor, and effectively inhibited tumor progression. In an intracranial tumor model, MN-TMV@CpG significantly prolonged the survival duration and induced stronger immune memory responses in tumor bearing mice when combined with anti-PD1 mAb. These results suggest that bio-derived nanovaccines can be used as a potential antitumor immunotherapy strategy.

The Quantitative Impact of Prostate Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (PSMA PET/CT) staging in Newly Diagnosed Metastatic Prostate Cancer and Treatment-Decision Implications

Abstract Objectives To quantify the stage-shift with PSMA PET/CT imaging in metastatic prostate cancer and explore treatment implications. Methods Single-centre, retrospective analysis of patients with newly diagnosed [18F]PSMA-1007 or [68Ga]Ga-PSMA-11 PET/CT-detected metastatic prostate cancer who had baseline bone scintigraphy between January 2015 and May 2021. Patients were subclassified into oligometastatic and polymetastatic disease utilising the STAMPEDE2 trial (ISRCTN66357938/NCT06320067) definition. Patient, tumour, and treatment characteristics were collected. PSMA PET/CT concordance with conventional imaging (bone scintigraphy and low-dose CT of PET) was identified by number and site of metastases, and subgroup assigned. Spearman’s rank correlation and linear regression modelling determined the association between the imaging modalities. Results We analysed 62 patients with a median age was 72 years (range 48-86). On PSMA PET/CT, 31/62 (50%) patients had oligometastatic disease, and 31/62 (50%) had polymetastatic disease. Prostate radiotherapy was delivered in 20/31 (65%) patients with oligometastatic disease and 17/31 (55%) with polymetastatic disease. 23/62 (37%) patients were reclassified as M0 on conventional imaging. PSMA PET/CT had a 2.9-fold increase in detecting bone metastases. Bone metastases concordance was found in 10/50 (20%) by number and 30/33 (91%) by site. PSMA PET/CT had a 2.2-fold increase in detecting nodal metastases. Nodal metastases concordance was found in 5/46 (11%) by number and 25/26 (96%) by site. There was significant positive correlation between PSMA PET/CT and conventional imaging for detecting bone (R2= 0.25 [p < 0.001]) and nodal metastases (R2= 0.19 [p < 0.001]). 16/31 (52%) had oligometastatic disease concordance. Conclusion The magnitude of PSMA PET/CT-driven stage-shift is highly variable and unpredictable with implications on treatment decisions, future trial design and potentially clinical outcomes.

Nanoparticles in Subunit Vaccines: Immunological Foundations, Categories, and Applications.

Subunit vaccines, significant in next-generation vaccine development, offer precise targeting of immune responses by focusing on specific antigens. However, this precision often comes at the cost of eliciting strong and durable immunity, posing a great challenge to vaccine design. To address this limitation, recent advancements in nanoparticles (NPs) are utilized to enhance antigen delivery efficiency and boost vaccine efficacy. This review examines how the physicochemical properties of NPs influence various stages of the immune response during vaccine delivery and analyzes how different NP types contribute to immune activation and enhance vaccine performance. It then explores the unique characteristics and immune activation mechanisms of these NPs, along with their recent advancements, and highlights their application in subunit vaccines targeting infectious diseases and cancer. Finally, it discusses the challenges in NP-based vaccine development and proposes future directions for innovation in this promising field.

Prediction of antibody-antigen interaction based on backbone aware with invariant point attention.

Antibodies play a crucial role in disease treatment, leveraging their ability to selectively interact with the specific antigen. However, screening antibody gene sequences for target antigens via biological experiments is extremely time-consuming and labor-intensive. Several computational methods have been developed to predict antibody-antigen interaction while suffering from the lack of characterizing the underlying structure of the antibody. Beneficial from the recent breakthroughs in deep learning for antibody structure prediction, we propose a novel neural network architecture to predict antibody-antigen interaction. We first introduce AbAgIPA: an antibody structure prediction network to obtain the antibody backbone structure, where the structural features of antibodies and antigens are encoded into representation vectors according to the amino acid physicochemical features and Invariant Point Attention (IPA) computation methods. Finally, the antibody-antigen interaction is predicted by global max pooling, feature concatenation, and a fully connected layer. We evaluated our method on antigen diversity and antigen-specific antibody-antigen interaction datasets. Additionally, our model exhibits a commendable level of interpretability, essential for understanding underlying interaction mechanisms. Quantitative experimental results demonstrate that the new neural network architecture significantly outperforms the best sequence-based methods as well as the methods based on residue contact maps and graph convolution networks (GCNs). The source code is freely available on GitHub at https://github.com/gmthu66/AbAgIPA .

Prostate cancer screening : to be recommended in 2024?

The Prostate Specific Antigen (PSA) blood test is still the only screening tool for prostate cancer. It is recommended between the ages of 50 and 69 as part of a shared decision making process between a patient and his or her doctor using a decision aid, as the test carries a significant risk of overdiagnosis. If a patient wishes to be screened, either because he is at higher risk, or because he places greater importance on a modest reduction in cancer-related mortality, the frequency of screening depends on his age, family history, and whether he is part of a high-risk group. The use of multiparametric MRI after a positive PSA result can reduce the number of biopsies and, consequently, the risk of overdiagnosis.

IL-10 promotes Th17 cell differentiation by enhancing STAT1-dependent IL-6 production via IgE-stimulated mast cells

Mast cells (MCs) are tissue-resident cells of hematopoietic origin that play an important role in host’s defense mechanism against nematodes. However, excessive activation of these cells contributes to the development of certain allergic diseases. Immunoglobin E (IgE) is one of the well-known molecules that activate MCs. Even in the absence of specific antigens, the binding of highly cytokinergic IgE to FcεRI on MCs prolongs their survival and induces cytokine production without enhancing their degranulation. In the present study, we examined the effects of the members of the interleukin-10 (IL-10) family of cytokines on IgE-mediated MCs functions. The receptors including Il10r1, Il10r2, and Il20r2, but not Il20r1, Il22r1 or Il28r1, were constitutively expressed in mouse bone marrow cell-derived cultured MCs (BMCMCs), suggesting that IL-10 may influence MCs function. Indeed, we found that only IL-10 could influence upon BMCMCs function; IL-10 enhanced prolongation of survival, promoted IL-6 and/or IL-13 production dependently of STAT1 and STAT3, and suppressed tumor necrosis factor production independently of STAT1 and STAT3 on IgE-stimulated BMCMCs. Moreover, the IL-10-mediated enhancement of IL-6 production by IgE-stimulated BMCMCs promotes Th17 cell expansion. These results suggest that IL-10 has a dual role as an anti-inflammatory and pro-inflammatory cytokine in MCs functions.

Prognostic role of prostate specific antigen kinetics in primary high volume metastatic hormonal sensitive prostate cancer treated with novel hormonal therapy agents

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting.

Engineering M2 macrophage-derived exosomes modulate activated T cell cuproptosis to promote immune tolerance in rheumatoid arthritis

Nanomedicines for immune modulation have made advancements in the treatment of rheumatoid arthritis (RA). However, due to aberrations in patients' immune systems, inducing antigen-specific immune tolerance while halting disease progression remains a significant challenge. Here, we develop a highly targeted multifunctional nanocomplex, termed M2Exo@CuS-CitP-Rapa (M2CPR), with the aim of selectively inhibiting inflammatory immune reactions while promoting immune tolerance towards specific antigens. M2CPR specifically targets inflammatory tissues in RA, delivering CuS NPs, CitP, Rapa, and endogenous anti-inflammatory factors, thereby ameliorating the inflammatory joint microenvironment. CuS NPs induce Cuproptosis of activated T cells, whose fragments are engulfed by resident or recruited macrophages, resulting in abundant production of TGF-β. TGF-β acts synergistically with Rapa to induce the iDCs into tDCs. tDCs present CitP to Naive T cells, promoting Tregs differentiation. Tregs, in turn, produce more TGF-β, inducing tDCs differentiation, thereby establishing a cycle of immune tolerance. Through in vitro and in vivo experiments, we validate that M2CPR can induce robust and durable antigen-specific immune tolerance, offering a new paradigm for RA therapy.

Beclin1/LC3II/P62 autophagy pathway activation is involved in the protective action of C-peptide against prostate injury in a rat model of type 1 diabetes

One of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and focusing on exploring the role of the autophagy pathway in diabetic prostate and whether it is involved in C-peptide action. Forty adult male Wistar albino rats were separated into control group, diabetic group, diabetic + C-peptide and diabetic + C-peptide + 3-Methyladenine (autophagy inhibitor). Serum metabolic parameters and prostatic specific antigen (PSA) were measured. Markers of oxidative stress, inflammation, fibrosis, cell proliferation and cell autophagy were evaluated in prostate tissues using biochemical, western blotting and immunohistochemical techniques. C-peptide administration ameliorated the effects of diabetes on the prostate through its hypoglycaemic, antioxidant, anti-inflammatory, and antiproliferative effects which were reversed with autophagy inhibition. Thus, we concluded that C-peptide prevented the effects of diabetes on the prostate through stimulation of the autophagy pathway.

Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus

Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R+sM1R+sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35+ M1+ B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

P058 Treatment of prostate cancer with photoimmunotherapy targeting the prostate specific membrane antigen

P058 Treatment of prostate cancer with photoimmunotherapy targeting the prostate specific membrane antigen

P069 Risk-based Prostate Specific Antigen (PSA) monitoring reduces follow-up burden after radical prostatectomy

P069 Risk-based Prostate Specific Antigen (PSA) monitoring reduces follow-up burden after radical prostatectomy

Comparison of Prostate Specific Antigen and Neuropeptide Y Parameters in Patients with Prostate Cancer

Comparison of Prostate Specific Antigen and Neuropeptide Y Parameters in Patients with Prostate Cancer

Emerging CART Therapies for Pediatric Acute Myeloid Leukemia.

The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last decades. However, at relapse, overall survival (OS) ∼40% to 50% and is even lower for patients with chemorefractory disease. Effective and less-toxic therapies are urgently needed for these children. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies. CART therapies are being developed for AML on the basis of the results obtained for other hematologic malignancies. The biggest challenge of CART therapy for AML is to identify a specific target antigen, since antigens expressed in AML cells are usually shared with healthy hematopoietic stem cells. An overview of prospects of CART in pediatric AML, focused on the common antigens targeted by CART in AML that have been tested or are currently under investigation, is provided in this manuscript.

Epidemiology, Pathogenesis, and Vaccine Development of Acne

Acne is a widespread and chronic inflammatory disease of the pilosebaceous glands affecting millions of people worldwide, particularly among adolescents. The current treatment method is mainly oral and smear medication, combined with a variety of physical and chemical therapy used as adjuvant therapy, alternative therapy or sequelae treatment. However, due to antibiotic resistance and bacteria evolve over time, need a vaccine as a new alternative treatment, in recent years, with the rapid development of molecular biology and immunology, based on specific antigen antibody technology acne vaccine has made significant progress, but there is still no successful development of acne vaccine. This paper analyzes the main four pathogenesis of acne and the current treatment, including oral and daub anti-inflammatory drugs and antibacterial drugs, supplemented by physical and chemical therapy, focus on the development of acne vaccine, present situation, challenges and future trend, hope to further promote the research and development of acne vaccine provide certain theoretical basis and reference value, and provide new ideas and methods for the prevention and treatment of acne. And acne pathogenesis complex and cannot determine the vaccine clinical trial effect these two problems are not solved, pathogenic mechanism involves multiple complex factors, a single vaccine may not have enough protective effect, difficult to completely prevent or cure acne, therefore, the next step need to consider targeting multiple pathogens and virulence factors combination of multivalent vaccine, and need for long-term clinical trials and observation.

A minority of proliferating human CD4+ T cells in antigen-driven proliferation assays are antigen specific

Antigen-driven T-cell proliferation is often measured using fluorescent dye dilution assays, such as the CFSE-based proliferation assay. Dye dilution assays have been powerful tools to detect human CD4+ T-cell responses, particularly against autoantigens. However, it is not known how many cells within the proliferating population are specific for the stimulating antigen. Here we determined the frequency of CD4+ T cells specific for the stimulating antigen within the antigen-responsive population of CFSE-based proliferation assays. We compared CD4+ T-cell responses to a type 1 diabetes autoantigen (proinsulin C-peptide) and to a vaccine antigen (tetanus toxoid). The TCRs expressed by antigen-responsive CD4+ T cells were sequenced, and their antigen specificity was tested functionally by expressing them in a reporter T-cell line. Responses to C-peptide were weak, but detectable, in PBMC from individuals with T1D, whereas responses to tetanus toxoid were much stronger. The frequency of antigen-specific CD4+ T cells correlated with the strength of the response to antigen in the proliferation assay. However, antigen-specific CD4+ T cells were rare among antigen-responsive CD4+ T cells. For C-peptide, an average frequency of 7.5% (1%–11%, n = 4) of antigen-responsive CD4+ T cells were confirmed to be antigen specific. In the tetanus-toxoid-stimulated cultures, on average, 45% (16%–78%, n = 5) of the antigen-responsive CD4+ T cells were tetanus toxoid specific. These data show that antigen-specific CD4+ T cells are a minority of the cells that proliferate in response to antigen and have important implications for in vitro CD4+ T-cell proliferation assays.

Comprehensive single-cell profiling of monocytes in HLA-B27-positive ankylosing spondylitis with acute anterior uveitis.

Acute anterior uveitis (AAU) is a common extra-articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)-B27 genetic marker. To explore the underlying mechanisms of HLA-B27+ AS-associated AAU, we employed single-cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA-B27+ AS-associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune-associated proteins, Th17-related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X-inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA-B27+ AS-associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

Overview of Immunological Response in Urological Membranous Nephropathy: Focus on Cytokine and Treatment Options.

Membranous nephropathy (MN) is an autoimmune disease that is caused by the production of autoantibody against glomerular podocyte antigens by immune cells due to the lack of self-tolerance mechanisms. Similar to many autoimmune diseases, the pathogenesis of MN is still vague and many experiments are being conducted to detect the antigens and genetic reasons for MN illness. Recently, new antigens, such as exotosin 1/exotosin 2, neural EGF-like-1, semaphorin 3B, and protocadherin 7 have been identified in MN patients who did not have presence of antiphospholipase A2 receptor antigen. What is more, cytokines, which are molecules that regulate immune responses, have been found to have harmful effects in various autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and MN. The role of cytokines and treatment strategies in MN patients is discussed in this article. As the understanding of the disease improves, targeted therapies that focus on specific antigens or cytokines may be developed to effectively manage MN.