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Tumor microenvironment-simulated organoids for personalized therapy prediction in head and neck squamous cell carcinoma.

Patient-derived organoids (PDOs) have emerged as promising models for predicting personalized drug responses in cancer therapy. However, the absence of essential immune and stromal components limits their ability to recapitulate the tumor microenvironment. Here, we established a total of 30 patient-derived organoids (PDOs) from 79 patients with locally advanced (LA) and recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). These PDOs maintained sustained expansion capacity and preserved the histopathological characteristics and genomic heterogeneity of their parental tumors

Чикоричная кислота в автоматическом иммунитете: обзор ее механизмов иммуномодуляции и терапевтического потенциала.

Аутоиммунные заболевания характеризуются падением иммунной самодостаточности, что ведет к аберральным иммунным атакам против самоантигенов и ведет к постоянному системному воспалению и многоорганическому ущербу. Несмотря на десятилетия достижений в области глюкокортикоидной, иммунодепрессантной и биологической терапии, клиническое управление АД по-прежнему сталкивается с проблемами в связи с неудовлетворительной долгосрочной эффективностью, высокими показателями серьезных неблагоприятных явлений и ограниченной доступностью пациентов. Чикоричная кислота (CA), естественно встречающаяся феноличес

Single-Cell Transcriptomics of Human Pericarotid Lymph Nodes Indicating Stability of Carotid Atherosclerotic Plaques.

BACKGROUND: The link between lymph node (LN) function and atherosclerosis is unclear, especially at the single-cell level. This study explores the relationship between pericarotid LNs and plaque stability using single-cell transcriptome analysis. METHODS: We enrolled 106 patients with severe internal carotid artery stenosis undergoing carotid endarterectomy. We recorded baseline clinical data and pericarotid LN size, and analyzed plaque composition to assess its association with enlarged LNs. Single-cell transcriptome and T/B-cell receptor sequencing were used to profile pericarotid LNs. RES

FOXP3 gene polymorphisms are associated with indeterminate clinical form of Chagas disease.

The forkhead box protein 3 (FOXP3) transcription factor is the main marker of regulatory T-cell (Treg) development and activation, a subpopulation involved in immune system regulation, self-tolerance, and protection against infections. We previously showed that Treg cells control the exacerbated immune response and morbidity in chronic Chagas disease, by modulating the cytokine environment and killing effector cells. Although FOXP3 gene polymorphisms have already been studied in several diseases, their role in Chagas disease is underreported. This study investigated FOXP3 gene polymorphism (rs

Harnessing the Immunomodulation of UV-Exposed Keratinocyte Extracellular Vesicles for Inflammatory Disorder Treatment.

Sunbathing excessively heightens the risk of skin carcinogenesis due to ultraviolet (UV)-mediated immunosuppression. Keratinocytes, the prim … e population of regulatory T cells. Animal studies confirm that UVKEV can result in robust systemic immune tolerance and significantly alleviate the symptoms of both IBD and psoriasis. This study presents the possibility of UVKEV as natural immunoregulatory therapeutics for the managing inflammatory disorders with promising clinical potential.

The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities.

Psoriasis is a chronic inflammatory disease driven by genetic and environmental factors, with pathogenesis closely linked to metabolic reprogramming and immune microenvironment dysregulation. The kynurenine pathway (KP), as the principal route of tryptophan catabolism, plays a pivotal role in regulating immune tolerance, oxidative stress, and neuroinflammation, thereby serving as a "metabolic bridge" that links cutaneous lesions to systemic comorbidities in psoriasis. This review systematically examines the pathological mechanisms of KP in psoriasis. Imbalances in the activities of indoleamine…

Exploring the Muco-Microbiotic Interface as a Hub for Microbial Metabolites and Immune Regulation in Gastroenteric Health and Disease.

The mucus layer covering the gastrointestinal tract forms a specialised interface where mucins, microbes, and extracellular vesicles create … ssociated microbiota, and vesicle-mediated signalling sustain barrier integrity, nutrient flux, and immune tolerance. Perturbations in any of these components lead to barrier failure, microbial encroachment, and inflammation, contributing to a broad spectrum of disorders, including gastritis, inflammatory bowel disease, colorectal cancer, and metabolic syndrome. M …

Eliciting antitumor immunity via therapeutic cancer vaccines.

Therapeutic cancer vaccines aim to expand and activate antigen-specific T cells for the targeted elimination of cancer cells. While early cl … elivery efficiency and adjuvant effects. Efficient antigen delivery and adjuvant selection overcome immune tolerance and tumor-induced immunosuppression. Furthermore, we examine recent clinical trial data and emerging combination approaches that integrate cancer vaccines with other immunotherapies to increase efficacy. While significant progress has been made, cha …

Redirecting Tryptophan Metabolism Through Host-Microbial Crosstalk to Enhance Precise Bioorthogonal Chemoimmunotherapy.

Bioorthogonal chemistry offers a promising approach for advancing chemoimmunotherapy, yet two critical challenges remain: (1) achieving deep … dole-3-aldehyde pathway through host-microbial crosstalk. Upon treatment, NP@ZIF-8@Apt-Lr overcomes immune tolerance and stimulates T lymphocyte infiltration into tumors. Furthermore, it significantly enhances the efficacy of chemoimmunotherapy by suppressing bilateral tumor development and inducing an immune memory response. This work presents a new strategy for …

Advances in Regulatory Cell Therapy for Type 1 Diabetes: Emerging Strategies and Future Directions.

Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of insulin-producing β-cells in the pancreas. Despite advances in insulin therapy and β-cell replacement, a definitive cure addressing the underlying cause of the disease, that is the loss of immune tolerance to β-cells remains elusive. Emerging strategies to reshape the immune response to pancreatic autoantigens include the adoptive transfer of ex vivo cultured regulatory cells, either mesenchymal stem cells (MSCs), regulatory T cells (Tregs), or dendritic cells (DCs), collectively known as regulatory cell therap…

Sustained allogeneic kidney graft operational tolerance despite discontinued conventional immunosuppression after CD19-CAR-T cell therapy for relapsed/refractory posttransplant lymphoproliferative disorder.

Management of immunosuppression after solid organ transplantation in context of chimeric antigen receptor T cell therapy (CART) is challenging. Although required to prevent graft rejection, systemic immunosuppression can interfere with biological functions of apheresis products and adoptively transferred T cells. We treated a 33-year-old kidney transplant recipient who developed relapsed/refractory posttransplant lymphoproliferative disorder with CD19-directed CART as a fourth-line therapy. Immunosuppression was discontinued before leukapheresis for CART and not reinitiated ever since. Althoug

CAR-T cell therapy in nephrology.

In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapeutic strategy beyond oncology, off … ent clinical data suggest that CAR-T therapies can induce profound immunological remission, restore immune tolerance, and improve renal outcomes. Novel platforms such as chimeric autoantibody receptor (CAAR)-T cells and bispecific T-cell engagers (BiTEs) further refine antigen targeting and may offer scalable alternatives. Importantly, early studies also point to …

Ocrelizumab модифицирует сигнальный путь IL-2 и связанные с ним IncRNA в множестве склерозов.

Ocrelizumab, CD20+B, разрушающий клетку моноклонального антитела, широко используется в множестве склероза (MS), однако его молекулярное воздействие на иммунное регулирование остается неполным. Учитывая важность интерлейкин-2 (IL-2) в иммунной терпимости, мы изучили выражение ключевых генов в этом пути и связанные с ними длинные некодирующие РНК в иранской когорте вновь излучающих MS пациентов. Периферальные МоноЯдерные клетки крови (PBMC) от 20 пациентов, не прошедших лечение, 20 пациентов Ocrelizumab (Xacrel) прошли курс лечения в условиях устойчивой RRMS, для которых со времени последней до

Совпадение в аннотации оригинала
Ocrelizumab, a CD20+ B cell-depleting monoclonal antibody, is widely used in multiple sclerosis (MS), yet its molecular impact on immune regulation remains incompletely defined. Given the importance of the interleukin-2 (IL-2) signaling axis in immune tolerance, we investigated the expression of key genes in this pathway, and their associated long non-coding…

Survival, serum biochemical parameters, hepatic antioxidant status, and gene expression of three Nile tilapia strains under pathogenic Streptococcus agalactiae challenge.

Streptococcosis is the leading bacterial disease impacting Nile tilapia (Oreochromis niloticus) and causes substantial economic losses in China. This study assessed the resistance and tolerance of three Nile tilapia (88, 99, and NG) to Streptococcus agalactiae infection. Survival rates were monitored, and samples were collected from blood, liver, and spleen at 0, 1, 2, 5, 7, and 14 days post-infection. Serum biochemical parameters, hepatic antioxidant enzymes, and the expression of related antioxidant and immune genes were measured. Results showed that strain 88 had superior resistance, with t

Activated PI3Kδ Specifically Perturbs Mouse Regulatory T Cell Homeostasis and Function Leading to Immune Dysregulation.

FOXP3+ regulatory T cells (Treg) are required for maintaining immune tolerance and preventing systemic autoimmunity. PI3Kδ is required for normal Treg development and function. However, the impacts of dysregulated PI3Kδ signaling on Treg function remain incompletely understood. In this study, we used a conditional mouse model of activated PI3Kδ syndrome to investigate the role of altered PI3Kδ signaling specifically within the Treg compartment. Activated mice expressing a PIK3CD gain-of-function mutation (aPIK3CD) specifically within the Treg compartment exhibited weight loss and evidence for …

Daucosterol regulates JAK2-STAT3 signaling pathway to promote megakaryocyte differentiation.

Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. Sarcandra glabra, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau coul…

Exploration of green preparation strategy for Lycium barbarum polysaccharide targeting Bacteroides proliferative and immune-enhancing activities and its potential use in geriatric foods.

Lycium barbarum polysaccharide (LBP) is beneficial for elderly people, but its use is limited in geriatric foods due to the lack of comprehensive information on its preparation strategy and physical property. In this study, the low-ester rhamnogalacturonan-I (RG-I) type pectic polysaccharide-protein complexes with varying physicochemical properties, structural characteristics, proliferative activities on Bacteroides, and immune-enhancing activities on RAW 264.7 cells, were obtained by moderate-temperature acid extraction within adjustment of enzymatic and physical pretreatments. LBP prepared b

Is the Complement System Dysregulated in Preeclampsia Comorbid with HIV Infection?

South Africa is the epicentre of the global HIV pandemic, with 13.9% of its population infected. Preeclampsia (PE), a hypertensive disorder of pregnancy, is often comorbid with HIV infection, leading to multi-organ dysfunction and convulsions. The exact pathophysiology of preeclampsia is triggered by an altered maternal immune response or defective development of maternal tolerance to the semi-allogenic foetus via the complement system. The complement system plays a vital role in the innate immune system, generating inflammation, mediating the clearance of microbes and injured tissue materials

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels.

Despite recent therapeutic advances, achieving optimal glycaemic control remains a challenge in managing Type 2 Diabetes (T2D). Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have emerged as effective treatments by promoting urinary glucose excretion. However, the full scope of their mechanisms extends beyond glycaemic control. At present, their immunometabolic effects remain elusive. To investigate the effects of SGLT2 inhibition or deletion, we compared the metabolic and immune phenotype between high fat diet-fed control, chronically dapagliflozin-treated mice and total-body SGLT2/S

Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of…