Результаты поиска

Endometriosis from initiation to innovation: Immune microenvironments, clonal lesion biology, and the emerging therapeutic pipeline.

Endometriosis is a chronic, estrogen-dependent inflammatory disease that, despite its benign histology, displays several cancer-relevant features, including clonal expansion, somatic alteration-associated lesion evolution, tissue invasion, apoptosis resistance, immune evasion, angiogenesis, fibrosis, and metabolic adaptation. These features are particularly important in ovarian endometriosis, where recurrent hemorrhage, iron-driven oxidative stress, and chronic inflammatory remodeling may promote malignant transformation. This review examines endometriosis through an oncologic framework by int

Hyaluronic acid in Peyronie's disease: focus on injection procedures and clinical practice.

BACKGROUND: Peyronie's disease is an acquired connective tissue disorder of the tunica albuginea of the corpus cavernosum, characterized by fibrotic plaque formation that impairs normal penile expansion during erection, potentially leading to shaft deformity and erectile dysfunction. Although diagnosis and follow-up are guided by well-established recommendations, significant variability persists in clinical practice regarding intralesional therapy, particularly following the recent introduction of a new hyaluronic acid device for Peyronie's disease treatment. MATERIALS AND METHODS: An Italian

In Vitro Platforms in Bone Tissue Engineering: From Biological Foundations to Advanced Models.

Large bone defects and related diseases affect millions worldwide, while conventional treatments such as autologous grafting remain limited by donor supply and high complication rates. Bone tissue engineering (BTE) has therefore emerged as a potential strategy to complement existing therapies. Over the past four decades, BTE has progressed from simple scaffold-based methods toward advanced bone-on-a-chip (BOC) systems. Despite substantial advances, current in vitro models still fail to fully capture the complexity of the bone microenvironment, hindering preclinical future translation. This stu

MicroRNA profiling in post-mortem spinal cord of C9ORF72-related ALS patients reveals molecular pathways involved in motor neuron degeneration.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder causing progressive motor neuron death in cortex, brainstem and spinal cord. The most common genetic cause is the G4C2 hexanucleotide repeat expansion in the non-coding region of exon 1 of C9ORF72, accounting for ~40% of familial and ~7% of sporadic ALS. RNA dysregulation is increasingly recognized as a key contributor to ALS pathogenesis. This study aimed to identify specific microRNAs (miRNAs) involved in motor neuron degeneration in C9ORF72-ALS. METHODS: We profiled 754 miRNAs in human post-mortem spina

Fat, muscle, and anti-obesity medications in cardiovascular disease prevention.

The rapid expansion of anti-obesity treatments with glucagon-like peptide-1 receptor agonists has redefined weight management. A consistent component of this weight loss, however, involves not only fat mass but also lean body mass, including skeletal muscle. This raises concerns regarding sarcopenia, frailty, and metabolic resilience that may attenuate long-term cardiovascular risk reduction. Muscle loss with these drugs is multifactorial, related to caloric restriction, anabolic resistance, and hormonal shifts. Emerging agents targeting the myostatin/activin pathway, ligand traps, and selecti

Hypoxia restricts the generation of BCG-responsive polycytotoxic T cells.

The Bacillus Calmette-Guérin (BCG) vaccine protects infants from severe tuberculosis by eliciting cellular immune responses, particularly through the activation of CD8+ cytotoxic T lymphocytes. Given that hypoxia is a defining feature of the pulmonary microenvironment during Mycobacterium tuberculosis infection, especially within granulomatous lesions, we investigated how limited oxygen availability influences the expansion and effector functions of BCG-induced cytotoxic T cells. Mycobacteria-specific short-term T-cell lines were generated and restimulated with BCG-infected macrophages under n

The Role of Gut Microbiota in Osteoporosis Triggered by High-Fat Diets: Mechanisms and Targeted Therapeutic Strategies.

Overnutrition, and specifically a high-fat diet (HFD) in which more than 30% of energy intake is derived from fat, has been unequivocally identified as a modifiable risk factor for several major diseases including osteoporosis, cardiovascular disorders, diabetes, and metabolic syndrome. The continued rise in prevalence of osteoporosis, particularly among younger populations, along with widespread adoption of HFD, has made the underlying mechanisms and preventative strategies related to HFD-induced osteoporosis a primary focus in the field of bone metabolism research. Early studies suggested th

Regulation of hepatic mitochondrial function by AIBP mitigates MASLD development.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder characterized by dysregul … AMLN diet-induced mouse model, we found that AIBP deficiency exacerbates hepatic steatosis, adipose tissue expansion, and lipid droplet (LD) accumulation. Notably, loss of AIBP was associated with reduced mitochondrial number and size, altered expression of mitochondrial proteins, and decreased LD-mitochondria contacts in the liver, as determined by electron micro …

Bilateral Mandibular Simple Bone Cysts: A Report of an Unusual Case.

Simple bone cysts are intraosseous cavities that are surrounded by bony walls, and they are either empty or contain liquid and/or connective tissue. They have similar radiological findings to those of true cysts, but they do not have an epithelial lining and are thus regarded as pseudocysts. They are frequently asymptomatic and most often an incidental finding on radiographic examination. The purpose of this case report is to present a rare case of bilateral occurrence of mandibular simple bone cysts. A 23-year-old female patient presented to the Department of Oral Diagnosis and Radiology of t

Non-invasive MRI of choroid plexus vascular function.

Choroid plexus (ChP) is a highly vascularized tissue in the ventricles of the brain, and it plays an important role in the production of cerebrospinal fluid (CSF) and formation of the blood-CSF barrier. The function of ChP vessels has been implicated in waste clearance efficiency during aging and neurodegenerative diseases. At present, postmortem studies are the main method to assess choroid plexus vascular integrity, with a few tools to measure ChP function in living humans. Here, we proposed a non-invasive MRI approach to assess ChP vascular elasticity based on the detection of MRI signal ch

Psoriatic lesions show an epidermal transcriptional pattern liking lactate-associated niche-state imbalance with hypoxia-regulatory activity.

Lactate handling sits at the interface of glycolytic stress, hypoxia and immune regulation in inflamed skin. However, the tissue and immune contexts in which these lactate-associated features are embedded in psoriatic lesions remain poorly defined. To resolve this organisation, spatial transcriptomics mapped lactate-associated transcriptional inflammatory states, separating lactate-disconnected niches, defined by inflammation without lactate-handling transcriptional activity, from lactate-coupled niches, marked by coordinated lactate-handling and inflammatory transcriptional activity. This fra

Erythropoietin in Tumor Immunity: Mechanistic Evidence, Clinical Cautions, and Translational Opportunities.

Erythropoietin (EPO) is a hypoxia-responsive glycoprotein hormone that sustains erythroid progenitor survival through the erythropoietin receptor (EPOR). Beyond erythropoiesis, emerging evidence places the EPO/EPOR axis at the interface of tumor adaptation, stromal remodeling, and immune tolerance. Interpretation has been complicated by nonspecific antibodies, low receptor abundance, and failure to distinguish EPOR transcripts or intracellular proteins from ligand-accessible, functional cell-surface receptors. Recent mechanistic studies have established immunoregulatory roles: tumor-derived EP

T-bet+ tissue-resident regulatory T cells are enriched in the neonatal mouse liver and promoted by IL-27 and IFN-γ.

Neonatal regulatory T (Treg) cells in secondary lymphoid organs have greater proliferative capacity and more potent suppressive functions than adult Treg cells. However, the phenotypic and functional features of Tregs in neonatal nonlymphoid organs are not well understood. Our prior work demonstrated that thymus-derived Treg cells entering the neonatal mouse liver enhance immune tolerance and periportal liver maturation. Compared to splenic Treg cells, these hepatic Tregs have faster turnover and superior suppression of naïve T-cell proliferation. To further define this population, we conducte

Pathophysiology of chronic subdural hematoma-new insights.

Chronic subdural hematoma (CSDH) is an increasingly common disorder characterized by persistent accumulation of blood products and inflammatory exudate within the dural border cell (DBC) layer. Its pathogenesis represents a self-sustaining cycle of inflammation, pathological angiogenesis, and impaired resolution. Injury of the head, which may be traumatic or nontraumatic, initiates cleavage of the DBC layer, leading to fibroproliferative membrane formation mediated by collagen synthesis and TGF-β1/SMAD signaling. The resulting outer membrane develops fragile neovasculature, driven primarily by

Стойкость мукосальных клеток CAR-T и провокационное переоснащение в энтеноколитах, связанных с клеточной терапией BCMA CAR-T.

Клеточная терапия расширяется с точки зрения онкологовых и аутоиммунных признаков, однако их последствия для мукозального иммунитета еще не полностью изучены. Здесь мы определим патофизиологию цилтакабтагена автолейкеля химерика антигенного рецептора (CAR)-T, вызванного клеткой энтероколитома (EC) (CAR-TEC) - серьезное осложнение антигенной клеточной терапии CAR-T в нескольких миеломах. Используя одноклеточную транскриптомику, цитометрию потока и тканевую съемку кишечных биопсий у пациентов с КАР-ТЕК (n = 10), клеточным лечением CAR-T без EC (n = 7) и здоровыми добровольцами (n = 26), мы выявл

Early enhanced control of Plasmodium yoelii infection in IL-10-deficient mice is independent of IFN-γ, IL-12, and the humoral response.

The outcome of a Plasmodium infection depends on the timely regulation of the robust pro-inflammatory response required to eliminate the parasite, but this response can cause tissue damage if not properly controlled. Interleukin-10 (IL-10) is an important regulatory cytokine that prevents immunopathology during many Plasmodium infections; however, this protection comes at the expense of less effective parasite control. This is illustrated by infection with blood-stage Plasmodium yoelii, in which mice exhibit a lower parasite load in the absence of IL-10. However, the immune components that lim

Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens.

Whole-body irradiation (WBI) consistently induces radiation-associated lymphopenia, a complication linked to poor prognosis and reduced overall survival. Understanding the quantitative and qualitative changes in naïve CD4 T cells after WBI is critical because these cells play key roles in both host defense and the propagation of autoimmunity. Here, we show that WBI triggers a rapid decline in the naïve CD4 T-cell pool, followed by thymus-dependent numerical recovery. Shortly after WBI, mice exhibit a reduced frequency of lymphocytic choriomeningitis virus (LCMV) epitope GP66-77-specific naïve

Biological Insights into Intestinal Adaptation from Preclinical Models of Short Bowel Syndrome.

Short bowel syndrome is a rare and clinically heterogeneous condition resulting from extensive intestinal resections or functional impairment, leading to malabsorption, fluid and electrolyte losses, and potential progression to intestinal failure requiring long-term parenteral nutrition. The long-term outcome of SBS is largely determined by intestinal adaptation, a progressive physiological response involving epithelial remodeling, intestinal stem cell expansion, lineage-specific proliferation, vascular remodeling, and the activity of trophic mediators-most notably glucagon-like peptide-2 (GLP

Смолдинг нейроинфламмации в прогрессивном множественном склерозе: механизмы, визуальные биомаркеры и терапевтические возможности.

Прогрессивный множественный склероз (MS) по-прежнему является серьезной терапевтической проблемой, поскольку инвалидность часто продолжает накапливаться, несмотря на эффективный контроль за рецидивами и новыми головными провокационными повреждениями. Эта диссоциация говорит о том, что прогресс определяется не только острым воспалением, но и отдельным процессом, который все чаще называется задушающим нейро-воспалением. Последние данные подтверждают, что хронические активные повреждения являются важным, но не эксклюзивным патологическим субстратом этого процесса. Эти повреждения характеризуются

Совпадение в полном тексте источника
… These lesions are characterized by persistent lesion-edge inflammation, resident myeloid activation, astrocyte–immune crosstalk, iron accumulation, slow tissue expansion, and incomplete repair ( 10 – 12 ). …

MCL‑1 safeguards activated hair follicle stem cells to enable adult hair regeneration.

Hair follicles cycle through expansion, regression and quiescence. To investigate the role of MCL‑1, a BCL‑2 family protein with anti‑apoptotic and apoptosis‑unrelated functions, we delete Mcl‑1 within the skin epithelium using constitutive and inducible systems. Constitutive Mcl‑1 deletion does not impair hair follicle organogenesis but leads to gradual hair loss and elimination of hair follicle stem cells. Acute Mcl‑1 deletion rapidly depletes activated hair follicle stem cells and completely blocks depilation‑induced hair regeneration in adult mice, while quiescent hair follicle stem cells