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Role of macrophages in the pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is one of the most common and most intensively studied chronic inflammatory skin diseases. Several cofactors, such as an impaired skin barrier function, modifications of the immune system, and a complex genetic background, direct the course of AD. Within this complex network, macrophages play a pivotal role in enhanced susceptibility to cutaneous infections and act as central connecting components in the pathogenesis of AD on the cellular level. In AD, macrophages are known to accumulate in acutely and chronically inflamed skin. During the early and short inflammatory ph

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… M2 macrophages are characterized by efficient phagocytic activity, high expression of several receptors such as class A scavenger receptor (CD204), MR, dectin-1, CD209, CD163, production of ornithine and polyamines through the arginase pathway, and an IL-12 lo IL-10 hi IL-1decoyR hi IL-1RA hi phenotype …

Acitretin. A review of its pharmacology and therapeutic use.

SYNOPSIS: Acitretin (etretin), a second generation monoaromatic retinoid for use in the treatment of severe psoriasis and other dermatoses, … squamous carcinoma cell lines. Cyclic adenosine monophosphate (cAMP)-dependent protein kinases and ornithine decarboxylase are probable mediators of the clinical response. In addition, acitretin demonstrates immunomodulatory and anti-inflammatory effects. It is hypothesised that the mechanisms entail inhibition of polymorphonuclear leucocyte accumulation i …

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients.

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3,

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… Ornithine decarboxylase antizyme ( OAZ1 gene) is a potential therapeutic target in various malignant tumors because it plays relevant roles in cellular functions, including genomic stability, proliferation, differentiation, and apoptosis [ 42 ]. …

Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

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… editing using ZFNs to treat MPS types I and II through phase 1/2 trials ( NCT02702115 and NCT03041324 ), demonstrating favorable safety profiles and evidence of targeted genome editing in the liver, although long-term enzyme expression remains a challenge. 29 In parallel, iECURE, Inc. is conducting the ornithine … transcarbamylase-HBB on-target precision editing (OTC-HOPE) trial ( NCT06255782 ) for neonatal-onset ornithine transcarbamylase deficiency (OTCD), employing a dual-vector AAV system that integrates a functional OTC gene into the hepatocyte genome. 179 Initial results from the first treated infant showed …

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

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… Interestingly, mTOR-C2 is necessary for synthesis of ornithine decarboxylase (ODC) antizyme (ODC-AZ) 101 , which negatively regulates ODC, one of two rate-limiting enzymes in polyamines synthesis. …

Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening.

Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effect

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… Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-kappa …

Естественные и синтетические АМП из Латинской Америки по всему спектру технологий и приложений в области разнообразия.

Биоразнообразие в Латинской Америке примерно 60% в целом по миру, подпитывая научные исследования в области природных продуктов, весьма значимой области открытия наркотиков по сей день. Это сопровождается увеличением числа антимикробных пептидов (АМП), полученных из натуральных продуктов в регионе, которые за последнее десятилетие были переработаны путем модификации, усовершенствования и уточнения их физико-химических свойств и антимикробной эффективности с использованием подходов, которые варьируются от изучения рациональной конструкции и соотношения структуры-активности (САР) до методов иску

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… Orn is ornithine. Y­(NO 2 ) is nitrotyrosine. Aib is α-aminoisobutyric acid. Vxx is valaline or isovaline. Lxx is leucine or isoleucine. Pheol is phenylalaninol. Peptide name | Family/Class | Molecular mass | Sequence | MIC range | Specie | Ref. … Predictions from NRP biosynthetic pathways enabled the design of eight analogs (five linear and three cyclic) that incorporate D -amino acids, nitrotyrosine (Y­(NO 2 )), and ornithine (Orn) to enhance stability and cationic charge. …

Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly

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… CRISPR/CAS-based gene therapy has been employed to treat other liver diseases such as Tyrosinemia type I (HT1) [ 245 ], Argininemia [ 274 ], Alpha-1 antitrypsin deficiency (AATD) [ 275 ], hemophilia [ 276 ], and ornithine transcarbamylase (OTC) deficiency [ 104 , 277 ]. 7.7. …

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

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… COX-2 overexpression and increased CYP1A1 and ornithine decarboxylase (ODC) activity are frequently observed patterns in human breast cancer ( Half et al., 2002 ; Deng et al., 2008 ; Androutsopoulos et al., 2009 ). … Role of Ornithine Decarboxylase in Breast Cancer. Acta Biochim. Biophys. Sinica 40 (3), 235–243. 10.1111/j.1745-7270.2008.00397.x Dhillon N., Aggarwal B. B., Newman R. A., Wolff R. A., Kunnumakkara A. B., Abbruzzese J. L., et al. (2008). …

Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide.

Current standard adjuvant therapy of glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to therapy resistance. Thus, novel therapeutic approaches are highly demanded. We tested the therapeutic efficacy of the second-generation XPO1 inhibitor Eltanexor using assays for cell viability and apoptosis in GBM cell lines and GBM stem-like cells. For most GBM-derived cells, IC50 concentrations for Eltanexor were below 100 nM. In correlation with reduced cell viability, apoptosis rates were significantly increased. GBM stem-like cells presented a combinatorial effect of Eltanex

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… Additionally, 2 × 10 3 or 4 × 10 3 NPCs were seeded on poly-ornithine hydrochloride (15 µg/mL diluted in distilled deionized H 2 O, Thermo Fisher Scientific, Cat#P2533-100MG) and Laminin (5 µg/mL diluted in phosphate-buffered saline (PBS), Sigma-Aldrich, Cat#L2020-1MG) coated 96-well plates in neuronal …

Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

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… They markedly upregulate the expression of ARG1 and iNOS, which catalyze the breakdown of arginine into ornithine/urea and nitric oxide (NO), respectively. This localized nutrient deprivation directly inhibits T-cell proliferation and downregulates expression of the TCR ζ chain ( 36 , 40 ). …

Manipulating Macrophage/Microglia Polarization to Treat Glioblastoma or Multiple Sclerosis.

Macrophages and microglia are implicated in several diseases with divergent roles in physiopathology. This discrepancy can be explained by their capacity to endorse different polarization states. Theoretical extremes of these states are called M1 and M2. M1 are pro-inflammatory, microbicidal, and cytotoxic whereas M2 are anti-inflammatory, immunoregulatory cells in favor of tumor progression. In pathological states, these polarizations are dysregulated, thus restoring phenotypes could be an interesting treatment approach against diseases. In this review, we will focus on compounds targeting ma

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… It is biosynthesized from putrescine, which is obtained in the body from the amino-acid ornithine. Spermidine has been shown in vitro to inhibit pro-inflammatory cytokine secretion by LPS-stimulated microglia. …

Histone deacetylase in inflammatory bowel disease: novel insights.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is characterized by chronic nonspecific intestinal inflammation. Despite considerable efforts, IBD remains a heavy burden on society and human health, with increasing morbidity. Posttranslational modification, especially histone acetylation, is a key process in controlling DNA transcriptional activity. Histone deacetylases (HDACs) play a vital role in the mechanism of IBD pathogenesis through histone and nonhistone protein deacetylation. Herein, we present a summary of different categories of HDACs as well as H

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… interleukin-2 IL-2R IL-2 receptor iTreg inducible regulatory T LP lamina propria LPS lipopolysaccharide MeCP2 methyl-CpG binding protein 2 MFG-E8 milk fat globule-epidermal growth factor 8 MSIE mouse small intestinal epithelial cells NETs neutrophil extracellular traps NO nitric oxide ODC ornithine …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… In 1999, an 18-year-old patient with ornithine-cytosine transferase deficiency died as a direct consequence of adenoviral gene therapy. A replication defective adenovirus expressing the ornithine-cytokine transferase enzyme was administered through the hepatic artery. …

Клемастин фумарат ускоряет аккумуляцию инвалидности в прогрессивном множественном склерозе, усиливая пироптоз.

Множественный склероз (MS) — иммунопосредованное демиелинизирующее заболевание CNS. Клемастин фумарат, внезапный антигистамин и мускариновый блокатор рецепторов, обладает ремиелионирующим потенциалом в MS. Климастичная рука была добавлена в текущее клиническое исследование платформы, нацеленное на остаточную активность на основе точности, биомаркированной комбинированной терапии множественных склерозов (TRAP-MS) (Clinical Procures.gov). NCT03109288), для выявления сигнатуры ремиелинирования цереброспиновой жидкости (CSF) и для сбора данных о безопасности клемастина у пациентов независимо от ре

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… Neurospheres enriched for OLIG2 glia progenitors were plated into 96-well plates coated with poly- l -ornithine and laminin (one sphere per well) and cells were allowed to migrate out of the sphere. …

Effects of Obesity and Calorie Restriction on Cancer Development.

The risk of malignant tumor development is increasing in the world. Obesity is an established risk factor for various malignancies. There are many metabolic alterations associated with obesity which promote cancerogenesis. Excessive body weight leads to increased levels of estrogens, chronic inflammation and hypoxia, which can play an important role in the development of malignancies. It is proved that calorie restriction can improve the state of patients with various diseases. Decreased calorie uptake influences lipid, carbohydrate and protein metabolism, hormone levels and cell processes. Ma

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… The decreased metabolites consisted mainly of amino acids or related metabolites, including ornithine, citrulline and taurine. The level of the pro-aging amino-acid methionine was also depleted. Fasting led to an increase in the beta-hydroxybutyrate levels. …

Communication between gut microbiota-derived metabolites and the tumor microenvironment.

The gut microbiota has been increasingly recognized as a critical player in maintaining human health and influencing disease development. The tumor microenvironment (TME) is pivotal in tumor development and progression, comprising immune cells, stromal elements, extracellular matrix components, and cytokines. Recent studies have highlighted the promising potential of gut microbiota-derived metabolites (e.g., short-chain fatty acids, bile acids, polyamines, and tryptophan derivatives) to reshape the TME in various ways, generating significant interest for the development of novel therapeutic st

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… Similarly, ornithine decarboxylase-dependent polyamine production is crucial for maintaining the fidelity of CD4+ T cells ( 41 ). Finally, tryptophan derivatives have been suggested to affect the number of Treg cells and induce apoptosis in Th1/Th17 cells ( 42 , 43 ). …

Unlocking the potential: advancements and applications of gene therapy in severe disorders.

INTRODUCTION: Several severe disorders, such as inherited diseases (e.g. cystic fibrosis and beta thalassemia), genetic diseases (e.g. malignant tumors and diabetes), and infectious diseases (e.g. HIV) are pose significant challenges to human health. BACKGROUND: Over the past few decades, researchers have been working on gene therapies, and currently, terrible dreams have come true. To date, the Food and Drug Administration (FDA) has approved multiple gene therapies such as Kynamro for familial hypercholesterolaemia, Exondys51 for duchenne muscular dystrophy, Spinraza for spinal muscular atro

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… Jesse Gelsinger has a rare ornithine transcarbamoylase (OTC) deficiency and willingly participated in gene therapy clinical trials. Unfortunately, in 1999, his death during the clinical trial was shocked the entire world, and gene therapy research absolutely collapsed due to safety issues [ 6 ]. …

The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?

The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the

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… GPRC6A receptor detects L-arginine, L-lysine, and L-ornithine amino acids, but some divalent cations, testosterone, and osteocalcin can be activated in a tissue-specific manner. In an animal model study, Gprc6−/− KO mice had osteopenia, feminization, and metabolic syndrome. …

Derivation and elimination of uremic toxins from kidney-gut axis.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relati

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… One ammonia molecule combines with carbon dioxide and the currently available precursor from the previous ornithine cycle to subsequently form citrulline. The other ammonia is then combined to form arginine. …