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Association between mycophenolic acid treatment and infection with specific strains of Pneumocystis jirovecii in solid organ transplant recipients in France and Switzerland: a multicentre, retrospective, cross-sectional study.

BACKGROUND: Pneumocystis pneumonia (PCP) case clusters involving solid organ transplant (SOT) recipients have been reported worldwide. Mycophenolic acid, an immunosuppressant used to prevent rejection in SOT recipients that targets the inosine 5'-monophosphate dehydrogenase (IMPDH) protein, has been hypothesised to exert selective pressure on Pneumocystis jirovecii, with the missense mutation G1020A (Ala261Thr) in the impdh gene a possible marker of such selective pressure. The aim of this study was to test the hypothesis that SOT recipients harbour P jirovecii with mutations in the impdh gene…

Cerebral Blood Flow after Acute Bypass with Parent Artery Trapping in Patients with Ruptured Supraclinoid Internal Carotid Artery Aneurysms.

BACKGROUND: Bypass with parent artery trapping is an alternative treatment method for ruptured internal carotid artery (ICA) aneurysms when clipping or coiling is contraindicated. However, the efficacy and safety of this strategy during the acute stage of subarachnoid hemorrhage (SAH) is undetermined. METHODS: A retrospective review of 955 consecutive patients presenting SAH between 2006 and 2014 identified 17 patients with ruptured ICA aneurysms treated by bypass with parent artery trapping within 72 hours after the bleeding (bypass group). The 26 cases with ruptured posterior communicating

Enzymes involved in purine metabolism--a review of histochemical localization and functional implications.

Many enzymes are involved in the biosynthesis, interconversion, and degradation of purine compounds. The exact function of these enzymes is … be involved in a number of physiological processes, such as the conversion of adenine nucleotide to inosine or guanine nucleotide, stabilizing the adenylate energy charge, and the reaction of the purine nucleotide cycle. There are three distinct isozymes (A, B, C) with different kinetic, physical, and immunological properties. Isozymes A, B, C have been i …

The contribution of intracellular calcium stores to mEPSCs recorded in layer II neurones of rat barrel cortex.

Loading slices of rat barrel cortex with 50 microM BAPTA-AM while recording from pyramidal cells in layer II induces a marked reduction in both the frequency and amplitudes of mEPSCs. These changes are due to a presynaptic action. Blocking the refilling of Ca(2+) stores with 20 microM cyclopiazonic acid (CPA), a SERCA pump inhibitor, in conjunction with neuronal depolarisation to activate Ca(2+) stores, results in a similar reduction of mEPSCs to that observed with BAPTA-AM, indicating that the source for intracellular Ca(2+) is the endoplasmic reticulum. Block or activation of ryanodine recep

8-Oxo-7,8-dihydropurines as Building Blocks to Enhance the Selectivity of an RNA Aptamer for Aminoglycosides.

The use of nucleic acids as potential therapeutic tools, sensors, or biomaterials, among other applications, has dramatically increased. Amo … r hand, the corresponding RNA analogues containing 8-oxoG or other modifications, specifically 8-oxoinosine, inosine, 8-oxoadenosine, or uridine, resulted in a high level of promiscuity toward most aminoglycosides, with kanamycin and streptomycin generally exhibiting higher dissociation constants. The presence of 2'-OMe-modified ribose led to trends simil …

Microbiota-derived metabolites as modulators of cancer immunotherapy response.

The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to

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… Molecules like, but not limited to, inosine 55 , butyrate 56 , and phenylacetylglutamine (PAGln) 57 have established immune signalling-modulating functions. … Inosine and phytosphingosine improve antigen presentation through upregulation of MHC class I on tumour cells, promoting their detectability by the immune system. …

Ксантин Оксидореводаза: Меч с двойным отростком в неврологических заболеваниях.

Неинфекционные неврологические расстройства являются второй основной причиной смерти, и их бремя продолжает расти по мере роста и старения населения мира. Окисляющий стресс и воспаление во многом связаны с активацией и развитием множественных склерозов, болезни Альцгеймера, амиотропического бокового склероза, болезни Хантингтона, болезни Паркинсона и даже инсульта. В ходе этого обзора мы изучаем роль деятельности и продуктов " xanthine oxidoreducase " (XOR) во всех вышеупомянутых неврологических заболеваниях. Редоксальный дисбаланс, вызывающий окислительный стресс, может возникнуть и

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… A pilot study was conducted on 25 participants with ALS to test inosine treatment for 12 weeks. Inosine appeared to be safe, well tolerated, and capable of increasing serum urate levels in ALS patients and led to increased plasma antioxidant capacity related to changes in serum urate level [ 90 ]. … It is essential to test inosine treatment at an early stage of the pathology, with the aim of reducing the spread of neuronal damage. …

[Design of ZIF-L-based boronate affinity molecularly imprinted material and its application in the detection of ribavirin in environmental water].

Ribavirin （RBV） is a broad-spectrum antiviral drug. It is widely used to treat various viral infections. However， its entry into water bodie … onolayer adsorption. In mixed solutions of RBV and three interfering substances （lamivudine，uridine，inosine） with mass concentration ratios of 1∶1 and 1∶10， the adsorption capacity of RBV by ZIF@B-MIPs remained high. The interfering substances had minimal impact on the adsorption performance. The reusability experiment results showed that the material ret …

Two novel mutations of Wiskott-Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling.

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326-1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101

Drug repurposing for disease-modifying effects in multiple system atrophy.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder lacking any proven disease-modifying therapy. Drug repurposing offers a strategy to accelerate the development of treatments by utilizing agents originally approved for other indications. This review summarizes repurposed drugs investigated as disease-modifying therapies for MSA, spanning preclinical in vitro and animal studies and clinical trials. We focus on agents targeting key pathogenic mechanisms in MSA-including α-synuclein aggregation (e.g., sirolimus/rapamycin, rifampicin, lithium, nilotinib, epigallocat

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… Uric acid and inosine Uric acid, a byproduct from purine metabolism with antioxidant properties, acts as a scavenger of reactive oxygen species, a peroxynitrite scavenger, and an iron chelator. … This approach leverages the role of inosine in purine metabolism to boost the antioxidant capacity, potentially slowing MSA progression by enhancing the neuroprotective effects of uric acid. …

The neuroprotective role of eucalyptol in a type-2 diabetes induced neuropathy rat model.

This review aims to provide an extensive overview of the literature on the clinical pharmacokinetics of mycophenolate in solid organ transpl … nd enteric-coated (EC) mycophenolate sodium. MPA is a potent, selective and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), leading to eventual arrest of T- and B-lymphocyte proliferation. Mycophenolate mofetil and EC-mycophenolate sodium are essentially completely hydrolysed to MPA by esterases in the gut wall, blood, liver and tissu …

Total adenosine deaminase cases as an inflammatory biomarker of pleural effusion syndrome.

BACKGROUND: Although inflammatory diseases commonly affect the pleura and pleural space, their mechanisms of action remain unclear. The presence of several mediators emphasizes the concept of pleural inflammation. Adenosine deaminase (ADA) is an inflammatory mediator detected at increased levels in the pleural fluid. AIM: To determine the role of total pleural ADA (P-ADA) levels in the diagnosis of pleural inflammatory diseases. METHODS: 157 patients with inflammatory pleural effusion (exudates, n = 124, 79%) and non-inflammatory pleural effusion (transudates, n = 33, 21%) were included in t

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… Once released into the extracellular space, adenosine can be deaminated to inosine by adenosine deaminase enzyme (ADA) or taken up directly by cells by specific nucleoside transporters and re-phosphorylated to ATP[ 3 - 5 ]. … Briefly, the P-ADA assay is based on the enzymatic deamination of adenosine to inosine, which is then converted to hypoxanthine by purine nucleoside phosphorylase. Hypoxanthine is transformed to uric acid and hydrogen peroxide by xanthine oxidase. …

The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.

Adenosine, an immunosuppressive metabolite, is produced by adenosine triphosphate (ATP) released from dying or stressed cells and is found at high levels in the tumor microenvironment of most solid tumors. It mediates pro-tumor activities by inducing tumor cell proliferation, migration or invasion, tumor tissue angiogenesis, and chemoresistance. In addition, adenosine plays an important role in regulating anti-tumor immune responses and facilitating tumor immune escape. Adenosine receptors are broadly expressed by tumor-infiltrated immune cells, including suppressive tumor-associated macrophag

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… Adenosine is degraded into inosine by adenosine deaminase (ADA), which occurs both intracellularly and extracellularly. … Once inside the cell, adenosine is phosphorylated to AMP by adenosine kinase (ADK) or degraded to inosine by ADA. …

The Gut Microbiota in Hematologic Malignancies: Mechanisms, Clinical Associations, and Translational Opportunities.

Hematologic malignancies arise and progress within a systemic ecosystem in which the gut microbiota is an increasingly recognized, partially modifiable component. Across acute leukemias, chronic lymphocytic leukemia, plasma cell disorders, lymphomas, and clonal myeloid neoplasms, human studies consistently report reduced microbial diversity, depletion of barrier-supportive, short-chain fatty acid-producing commensals, and enrichment of Gram-negative, pro-inflammatory, or hospital-adapted taxa. These alterations are associated with pre-leukemic clonal expansion, adverse genetic and immunologica

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… In RR-DLBCL treated with CD19-directed CAR T-cell therapy, baseline abundance of Bacteroides fragilis is enriched in responders and correlates with longer progression-free survival; functional profiling reveals enrichment of inosine biosynthesis pathways, and circulating inosine correlates with both … Notably, the association of Bacteroides fragilis and inosine pathways with CAR T-cell efficacy, and of SCFA producers with reduced toxicity, mirrors findings from solid-tumor immunotherapy and suggests convergent microbiome–immunotherapy interactions across oncology. 3.5. …

Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release.

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously in

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… NOR, C57BL/6 or BALB/c normal control mice; CAC, CT26/LLC cachexia mice; AM, amiloride-treated mice; KD, mice inoculated with Rab27-knockdown CT26/LLC cells; BCAAs, branch-chain amino acids; IMP, inosine monophosphate; 2PG, 2-phosphoglycerate; 3-HB, 3-hydroxybutyrate; MLC, myosin light chain; MHC, myosin … NOR, C57BL/6 or BALB/c normal control mice; CAC, CT26/LLC cachexia mice; AM, amiloride-treated mice; KD, mice inoculated with Rab27-knockdown CT26/LLC cells; BCAAs, branch-chain amino acids; IMP, inosine monophosphate; 2PG, 2-phosphoglycerate; 3-HB, 3-hydroxybutyrate; MLC, myosin light chain; MHC, myosin …

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer

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… C Adenine base editors (ABEs) utilize adenosine deaminase to convert adenine (A) into inosine (I), which is interpreted as guanine (G) during DNA repair or replication. … C Adenosine Deaminases Acting on RNA (ADAR)-mediated adenosine (A)-to-inosine (I) RNA editing enables transient suppression of oncogenic transcripts without permanent genomic modification. …

Неверный перевод из эндогенного варианта ТРНА в пангеномных линиях клеток человека.

Варианты антикодона для передачи человека RNA (tRNA) являются источником ошибки перевода. :: tRNASerAGA-2-3 Вариант (G35A) 2% популяции человека и приводит к неправильной инкорпорации серин в фениланинских кодонах. Здесь мы разработали двойной флуоресцентный репортер для количественной оценки уровней неправильной инкорпорации в живых человеческих и муринных клетках и подтвердили неправильную трансляцию с помощью масс-спектрометрии. В β-лимфоцитах от отдельных лиц 1000 Проект по геномам, мы подтвердили предполагаемый генотип клеток с маленькими аллеями A35, и последовательность tRNA продемонстр

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… As noted in the section below, the A34 base in tRNA Ser AAA is modified to inosine. The I34 base can in principle read codons ending in U, C, or A. Thus, explaining our finding ample evidence at the UUC codons and at UUU151 in the GFP-mCherry reporter. … S8C ), inosine 34 (I34) ( Supplementary Fig. S8D ), and methylations of bases G26, Ce2, and A58 ( Supplementary Fig. S8E ). …

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor.

Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR's clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient's quality of life. With regard to the genetic basis of drug responses, preemptive pharmacogenomic testing and simultaneous blood level monitoring could be helpful for the transformation of various findings into

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… The enzyme ITPase hydrolyzes inosine triphosphate and deoxyinosine triphosphate into monophosphate nucleotide and diphosphate. … Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency . Hum. Genet. 111 ( 4-5 ), 360 – 367 . 10.1007/s00439-002-0798-z 12384777 Sun J. Y. Xu Z. J. Sun F. Guo H. L. Ding X. S. Chen F. ( 2018 ). …

RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

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… I (adenosine‐to‐inosine editing): writers: ADAR1, ADAR2, ADAR3; readers: unknown; erasers: unknown. … We also introduced the writers involved in Ψ and adenosine‐to‐inosine changes. …

Распознавание ксантиновой реберосколочной структуры и металлическое ионопосредованное распознавание лиганда.

Рибосколки сохраняют функциональные области в MRNA, которые в основном существуют в бактериях. Они регулируют генное выражение в ответ на различные концентрации метаболитов или металлических ионов. Недавно был выявлен мотив РНК NMT1 для селективной привязки ккантиновой и мочевой кислот, соответственно, к метаболическому пути деградации пурины. Вот, мы сообщаем о кристаллической структуре этой РНК, связанной с ксантиной. В целом рибосуха имеет стержень, постоянно сложенный в сложенном виде three стебли и two внутренние перекрестки. Связующий карман определяется высокоохранной соединенной послед

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… Ligands Xanthine, uric acid, hypoxanthine, adenosine, adenine and inosine were purchased from Yuanye Bio-Technology Co. Ltd. (Shanghai). Xanthine sodium salt and 8-azaxanthine monohydrate were purchased from Sigma-Aldrich. … Furthermore, inosine and adenosine do not bind to the NMT1 RNA and steric hindrance of the large ribose group at N9 is the likely reason for this observation (Figure 3C , Supplementary Figures S13 and S15 ). …