Urease-powered nanobots for radionuclide bladder cancer therapy

Nature Nanotechnology, Год журнала: 2024, Номер 19(4), С. 554 - 564

Опубликована: Янв. 15, 2024

Abstract Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs passive nanoparticles. However, translational treating bladder are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered an orthotopic mouse model cancer. In vivo ex results demonstrated nanobot accumulation at tumour site, eightfold increase revealed by positron emission tomography vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy cleared bladders confirmed penetration Treating tumour-bearing mice intravesically administered radio-iodinated for radionuclide therapy resulted a size reduction about 90%, positioning as efficient delivery nanosystems therapy.

Язык: Английский

---

An immunoresponsive three-dimensional urine-tolerant human urothelial model to study urinary tract infection

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Март 27, 2023

Introduction Murine models of urinary tract infection (UTI) have improved our understanding host-pathogen interactions. However, given differences between rodent and human bladders which may modulate host bacterial response, including certain biomarkers, urothelial thickness the concentration urine, development new human-based is important to complement mouse studies provide a more complete picture UTI in patients. Methods We originally developed three-dimensional (3D) model was urine tolerant demonstrated several but it only achieved heterogenous, multi-layered zones did not demonstrate comprehensive differentiation status needed achieve barrier function. optimised this by altering variety conditions validated with microscopy, flow cytometry, transepithelial electrical resistance FITC-dextran permeability assays confirm tissue architecture, integrity response infection. Results an 3D urine-tolerant (3D-UHU), after 18-20 days growth, stratified uniformly 7-8 layers comprised three expected, distinct cell types. The apical surface differentiated into large, CD227+ umbrella-like cells expressing uroplakin-1A, II, III, cytokeratin 20, all are terminal markers, glycosaminoglycan layer. Below layer, intermediate were present, single underlying layer CD271+ basal cells. also expressed E-cadherin, ZO-1, claudin-1 -3, possessed good Infection both Gram-negative Gram-positive classes elicited elevated levels pro-inflammatory cytokines chemokines characteristic humans caused decrease Discussion Taken together, 3D-UHU holds promise for studying interactions immune response.

Язык: Английский

---

Comprehensive analysis of human tissues reveals unique expression and localization patterns of HSF1 and HSF2

Cell Stress and Chaperones, Год журнала: 2024, Номер 29(2), С. 235 - 271

Опубликована: Март 6, 2024

Heat shock factors (HSFs) are the main transcriptional regulators of evolutionarily conserved heat response. Beyond cell stress, several studies have demonstrated that HSFs also contribute to a vast variety human pathologies, ranging from metabolic diseases cancer and neurodegeneration. Despite their evident role in mitigating cellular perturbations, functions HSF1 HSF2 physiological proteostasis remained inconclusive. Here, we analyzed comprehensive selection paraffin-embedded tissue samples with immunohistochemistry. We demonstrate both display distinct expression sub-cellular localization patterns benign tissues. localizes nucleus all epithelial types, whereas nuclear was limited only few especially spermatogonia urothelial umbrella cells. observed consistent robust cytoplasmic across studied smooth muscle endothelial cells, including cells surrounding vasculature high-endothelial venules lymph nodes. Outstandingly, localized specifically at cell-cell adhesion sites broad such as cardiac muscle, liver, epididymis. To best our knowledge, this is first study systematically describe Thus, work expands biological landscape these creates foundation for identification specific roles normal processes.

Язык: Английский

---

BCG induced lower urinary tract symptoms during treatment for NMIBC—Mechanisms and management strategies

Frontiers in Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Янв. 8, 2024

Non-muscle invasive bladder cancer (NMIBC) accounts for ~70–75% of total tumors and requires effective early intervention to avert progression. The cornerstone high-risk NMIBC treatment involves trans-urethral resection the tumor followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, BCG therapy is commonly accompanied significant lower urinary tract symptoms (LUTS) including urgency, frequency, dysuria, pelvic pain which can undermine adherence clinical outcomes. Despite this burden, mechanisms underlying development BCG-induced LUTS have yet be characterized. This review provides a unique perspective on thought responsible focussing sensory nerves transduction. focuses how physiological response BCG, inflammation, urothelial permeability, direct interactions between could drive afferent sensitization leading LUTS. Additionally, an up-to-date summary latest data exploring interventions relieve LUTS, therapeutic targeting contractions, increased inhibition signaling. Addressing burden holds potential enhance patient quality life, compliance, overall outcomes in management. lack knowledge pathophysiological that has limited novel efficacious options. Further research urgently required unravel

Язык: Английский

---

Pictorial review of multiparametric MRI in bladder urothelial carcinoma with variant histology: pearls and pitfalls

Abdominal Radiology, Год журнала: 2024, Номер unknown

Опубликована: Июнь 7, 2024

Язык: Английский

---

Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury

JCI Insight, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 8, 2025

The oral mucosa undergoes daily insults, and stem cells in the epithelial basal cell layer regenerate gingiva tissue to maintain health. Iroquois Homeobox 1 (IRX1) protein is expressed niches human/mouse epithelium mesenchyme under homeostasis. We found that Irx1+/- heterozygous (Het) mice have delayed wound closure, morphological changes of regenerated epithelium, defective keratinocyte proliferation differentiation during healing. RNA-Seq analyses between WT at 3 days postinjury (dpi) impaired migration decreased keratinocyte-related genes upon injury. IRX1-expressing are gingival layer, a niche for maintenance. also underlying stroma. IRX1 activates SOX9 transient amplifying increase proliferation, EGF signaling activated induce migration. Krt14CreERT lineage tracing experiments reveal defects stratification HET mouse epithelium. primed base facilitating rapid scarless healing through activating pathway.

Язык: Английский

---

The Role of Innate Immunity in Healthy Aging Through Antimicrobial Peptides

Immunology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

ABSTRACT In a super‐aging society, the increase in elderly population is closely tied to rise infectious diseases due factors such as weakened immune systems and decreased vaccine efficacy older adults. Various opportunistic pathogens commonly encountered everyday life can cause infections when an individual's defence aging. These underscore importance of preventive measures against pathogenic aging elderly. The response acts mechanism foreign substances, including abnormal cells. Specifically, innate body's first line defence, offering rapid nonspecific pathogens. Advances study immunity's regulatory functions both non‐immune cells have broadened our understanding responses' impact on health. This includes focus effectors like antimicrobial peptides (AMPs) their potential implications for health longevity. review summarises common principles evolutionary adaptations immunity via AMPs, mammals invertebrates. Especially, this discusses conserved mechanisms regulating AMP production role AMPs modulating from invertebrate human. Therefore, it highlights addressing through AMPs.

Язык: Английский

---

Analysis of human urinary extracellular vesicles reveals disordered renal metabolism in myotonic dystrophy type 1

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 5, 2025

Chronic kidney disease (CKD) and the genetic disorder myotonic dystrophy type 1 (DM1) each are associated with progressive muscle wasting, whole-body insulin resistance, impaired systemic metabolism. However, CKD is undocumented in DM1 molecular pathogenesis driving unknown to involve kidney. Here we use urinary extracellular vesicles (EVs), RNA sequencing, droplet digital PCR, predictive modeling identify downregulation of metabolism transcripts Phosphoenolpyruvate carboxykinase-1, 4-Hydroxyphenylpyruvate dioxygenase, Dihydropyrimidinase, Glutathione S-transferase alpha-1, Aminoacylase-1, Electron transfer flavoprotein B DM1. Expression these genes localizes kidney, especially proximal tubule, correlates strength function. In autopsy tissue, characteristic ribonuclear inclusions evident throughout nephron. We show that organic acids acylglycines elevated DM1, correspond enzyme deficits downregulated genes. Our study identifies a previously unrecognized site highlights potential EVs as biomarkers renal metabolic disturbance individuals.

Язык: Английский

---

Effective Treatments of UTI—Is Intravesical Therapy the Future?

Pathogens, Год журнала: 2023, Номер 12(3), С. 417 - 417

Опубликована: Март 6, 2023

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority UTIs are successfully treated with orally administered antibiotics, impact oral antibiotics on host microbiota is under close research scrutiny and potential for dysbiosis a cause concern. Optimal treatment UTI relies upon selection an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in urinary after administration. Alternatively, local antibiotic at urothelial surface can be achieved by direct instillation into tract. For physicochemical properties, this critical importance cases intracellular bacterial reservoir suspected. In review, we summarise underpinning biopharmaceutical barriers to effective provide overview evidence deployment intravesical administration route antibiotics.

Язык: Английский

---

The role of vitamin A in non-ruminant immunology

Frontiers in Animal Science, Год журнала: 2023, Номер 4

Опубликована: Июнь 22, 2023

Vitamin A (retinol) is an essential micronutrient with a crucial role in the immune system of non-ruminant animals, such as swine and poultry. It includes three chemical compounds distinct properties functions body: retinol, retinal, retinoic acid. In monogastric feed, vitamin primarily present form retinyl esters. The metabolism dietary esters involves their conversion to which then transported different tissues cells for further into active forms These have been found play regulating both innate adaptive responses. Specifically, they are involved differentiation, proliferation, function T B lymphocytes, well dendritic cells. deficiency can lead impaired cellular immunity, reduced antibody production, consequently increased susceptibility infections. poultry, hypovitaminosis also affect gut-associated lymphoid tissues, leading gut-related health problems compromised growth performance. On other hand, supplementation has shown immunomodulatory effects on By administering or supplementing cell cytokine secretion be enhanced, ultimately result improved disease resistance. Therefore, potential applications immuno-micronutrient improving preventing diseases However, optimal dosage timing need carefully determined based specific requirements species production stages. Overall, better understanding nutritional immunology could significant implications animal productivity inform development effective strategies optimize prevent domestic fowl. This review paper aims offer valuable insights non-ruminants while emphasizing current gaps knowledge areas research.

Язык: Английский

---