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Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway.

Pancreatic cancer is an exceptionally aggressive disease, the treatment of which has largely been unsuccessful due to higher resistance offered by pancreatic cancer cells to conventional approaches such as surgery, radiation and/or chemotherapy. The aberration of Ras oncoprotein has been linked to the induction of multiple signaling pathways and to the resistance offered by pancreatic cancer cells to apoptosis. Therefore, there is a need for development of new and effective chemotherapeutic agents which can target multiple pathways to induce responsiveness of pancreatic cancer cells to death s

Pathological implications of iNOS expression in central white matter: an ex vivo study of optic nerves from rats with experimental allergic encephalomyelitis.

Excessive nitric oxide (NO) production from the inducible isoform of nitric oxide synthase (iNOS) has been invoked as a causative factor in many neurodegenerative disorders, including multiple sclerosis. This hypothesis has been supported by in vitro studies showing that glial iNOS expression results in toxic NO concentrations (near 1 microm). To investigate the relevance of such findings, experiments were carried out ex vivo on optic nerves from rats with exacerbated experimental allergic encephalomyelitis, a model of multiple sclerosis. The nerves displayed characteristic immunopathology and

A Case of Autoimmune Hepatitis Initially Manifesting as Hepatic Encephalopathy.

Autoimmune hepatitis (AIH) is a T-cell-mediated liver disease characterized by elevated transaminases, circulating autoantibodies, hypergammaglobulinemia, and interface hepatitis. A 66-year-old female patient visited our department due to recurrent episodes of altered consciousness, sleep-wake inversion, and asterixis, indicating hepatic encephalopathy (HE). Her liver biopsy results clearly demonstrated interface hepatitis. The patient's severe HE does not parallel her relatively stable liver function and was attributed to a wide retroperitoneal collateral vein shunting blood directly into the

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… Treatment with arginine and ornithine aspartate ameliorated the neurological issues within one day, preventing recurrence thereafter. … Medication for HE prevention (ornithine aspartate granules one packet twice daily, oral lactulose 10 g twice daily, and intermittent glycerin enemas), liver protection (glutathione 50 mg three times daily), diuresis (furosemide 20 mg daily, spironolactone 20 mg twice daily), and bile stasis reduction …

Keyword Index for Volume 88

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… oesophageal squamous cell cancer 115 oesophageal squamous cell carcinoma 1217, 1735 oestrogen 50 oestrogen receptor 579, 871, 1071 oncological interviews 502 oral 648 oral contraceptives 50, 1713 oral leukoplakia 366 oral route 965 oral squamous cell carcinoma 1105 oral submucous fibrosis 366 ornithine … 613 ornithine cycle 447 oropharyngeal carcinoma 1095 osteoclast 1318 osteosarcoma 396, 1995 ovarian cancer 470, 654, 666, 839, 848, 1781 ovary 1828 oxaliplatin 1942 oxidative stress 902 oxygen 1462 P-glycoprotein 878 P-subunit 1223 p14 217 p16 217 p21 protein 754 p21 ras 1971 p27 KIP1 …

Drugging the efferocytosis process: concepts and opportunities.

The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infe

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… Macrophages have been shown to utilize the arginine and ornithine derived from the first round of engulfed apoptotic cells to facilitate subsequent rounds of efferocytosis 64 . … Arginine and ornithine were shown to be converted to putrescine via the action of macrophage-expressed ornithine decarboxylate and arginase 1 . …

Creatine biosynthesis and transport in health and disease.

Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders. Primary creatine disorders are inherited as

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… Arginine/Ornithine and Polyamine Biosynthesis Arginine plays a central role in the polyamine biosynthesis pathway, since its hydrolysis by cytosolic or mitochondrial arginases generates ornithine and urea [ 112 ]. … Ornithine is a precursor of putrescine, which is generated by ornithine-decarboxylase (ODC) through ornithine decarboxylation. …

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects.

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactat

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… Curcumin extensively intervenes in amino acid metabolism by inhibiting the activity of glutaminase (GLS), ornithine decarboxylase (ODC), and other enzymes, thereby disrupting polyamine homeostasis and amino acid balance, which affects tumor proliferation and antioxidant defense [ 14 ]. … As the key rate-limiting enzyme in polyamine synthesis, ODC catalyzes the conversion of L-ornithine to putrescine, representing the sole pathway for putrescine generation in mammals, and subsequently generates spermidine and spermine. …

Targeted therapies in pediatric oncology: A start.

The treatment of cancers was revolutionized by the use of combination "conventional" chemotherapy, first in children, during the 20th century. That foundation of therapy, while having achieved significant advances in survival, has reached its limits. Innovations in targeted therapies are now building upon that foundation to further improve outcomes in pediatric oncology. These targeted agents are designed to narrowly utilize specific biologic processes for greater efficacy and optimally fewer generalized toxicities. I will provide an overview of the current spectrum of targeted therapies avail

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… It has been recognized that cancers often utilize alternative energy pathways, including the Warburg effect 395 and the ornithine decarboxylase cycle 396 , 397 (ODC), to remain viable independently of oxidative phosphorylation. …

GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.

Estrogens promote beneficial effects in the cardiovascular system mainly through the estrogen receptor (ER)α and ERβ, which act as ligand-gated transcription factors. Recently, the G protein-coupled estrogen receptor (GPER) has been implicated in the estrogenic signaling in diverse tissues, including the cardiovascular system. In this study, we demonstrate that left ventricles of male Spontaneously Hypertensive Rats (SHR) express higher levels of GPER compared to normotensive Wistar Kyoto (WKY) rats. In addition, we show that the selective GPER agonist G-1 induces negative inotropic and lusitr

Gene therapy: principles, challenges and use in clinical practice.

INTRODUCTION: Gene therapy is an emerging topic in medicine. The first products have already been licensed in the European Union for the treatment of immune deficiency, spinal muscular atrophy, hemophilia, retinal dystrophy, a rare neurotransmitter disorder and some hematological cancers, while many more are being assessed in preclinical and clinical trials. OBJECTIVE: The purpose of this review is to provide an overview of the core principles of gene therapy along with information on challenges and risks. Benefits, adverse effects and potential risks are illustrated based on the examples of

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… The 18-year-old patient who died in 1999 had partial ornithine transcarbamoylase (OTC) deficiency, a genetically determined metabolic disorder of the urea cycle, and received an infusion of corrective OTC gene encased in a recombinant adenoviral vector [ 8 ]. … Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003;80(1–2:148–58. 5. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, et al. …

Connection between nutrition and oncology in dogs and cats: perspectives, evidence, and implications-a comprehensive review.

Oncology has become one of the most influential and studied areas in both human and companion animal health. In veterinary practice, cancer represents a significant challenge, especially concerning cats and dogs. Nutrition plays a crucial role in the management of oncology patients in veterinary medicine; however, is often nonspecific and reliant on data from other species and diseases, highlighting the need for a comprehensive review of the latest developments in this field. Since the intricate relationship between nutrition and cancer encompasses various aspects, this review therefore intend

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… Blood sample collections were performed at the end of each 11-day treatment period to evaluate the possible effects of high-protein intake and arginine and ornithine supplementation on cat immune cells. … This effect was significant with increasing concentrations of arginine and ornithine ( 169 ). …

Sudden severe hyperammonemia and status epilepticus -a case report-.

There are various causes to a low level of consciousness in patients in the intensive care unit. Neurological injury, infection, and metabolic disarray are considered as some of the causes. A 39 year-old female patient was transferred to our hospital with septic shock due to ascending colon perforation. The patient had previously received ovarian cancer surgery and a cycle of chemotherapy at another hospital. Emergent operation for colon perforation was successful. After the operation, she was treated in the intensive care unit for infectious and pulmonary complications. She suddenly showed de

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… Heart Lung Transplant 2008 27 801 803 18582813 10.1016/j.healun.2008.03.019 11 Tse N Cederbaum S Glaspy JA Hyperammonemia following allogeneic bone marrow transplantation Am J Hematol 1991 38 140 141 1951305 10.1002/ajh.2830380213 12 Hu WT Kantarci OH Merritt JL 2nd McGrann P Dyck PJ Lucchinetti CF Ornithine …

Acute hepatic encephalopathy presenting as cortical laminar necrosis: case report.

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest th

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… Kucharczyk W Acute hyperammonemic encephalopathy in adults: imaging findings AJNR Am J Neuroradiol 2011 32 413 418 21087942 10.3174/ajnr.A2290 PMC7965708 4 Takanashi J Barkovich AJ Cheng SF Kostiner D Baker JC Packman S Brain MR imaging in acute hyperammonemic encephalopathy arising from late-onset ornithine …

Твердая неэптическая гипераммония, связанная с уреаплазмой парвума и инфекциями гомини Микопласмы в двойном иммунозапугивании женщины, представляющей как предполагаемый перитональный карциноматоз.

Острая гипераммония, не связанная с гепатической гипераммонией, является редким, но потенциально опасным для жизни заболеванием у пациентов, страдающих иммунокомпромиссной болезнью. Виды Ureaplasma и Mycoplasma являются быстродействующими врожденными организмами, которые генерируют аммиак и могут вызывать распространенную культурно-отрицательную инфекцию. Мы сообщаем о случае 63-year-old Женщина, получающая двойную биологическую терапию, оклелизумаб от множественных склерозов и секукинуумаб от псориаза, которая имела историю стерильности пюрии и симптомов мочи ниже. В течение двух месяцев ее с

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… In adults, nonhepatic hyperammonemia may result from impaired ammonia clearance, including late-onset urea-cycle disorders, particularly partial ornithine transcarbamylase deficiency, and portosystemic shunting, or from increased ammonia production associated with urease-producing urinary tract infections … Plasma amino acid analysis obtained during active hyperammonemia showed no pattern suggestive of a primary urea-cycle disorder: glutamine, citrulline, and arginine were within their respective reference ranges, while ornithine was marginally reduced. …

Использование реальных доказательств в США. Управление по контролю за продуктами питания и лекарственными препаратами и Европейское агентство по лекарственным препаратам утверждают онкологические продукты, поддерживаемые односторонними испытаниями (Advisory and Drug Argency and the European Medicals Agency (European Medicals Agency)2022-2025).

ВВЕДЕНИЕ: Усилился интерес регулирующих органов к реальным доказательствам (РВЭ) в дополнение к односторонним испытаниям (САТ) в области онкологии, однако по-прежнему отсутствует полное понимание того, как Управление по контролю за продуктами питания и лекарствами (ДПП) и Европейское агентство по медицине (ЕМА) оценивают такие доказательства. ЦЕЛЬ: Всеобъемлющая оценка недавних решений по онкологии, в которых СТА поддерживаются РВЭ, с описанием обратной связи по вопросам нормативного регулирования, методологических подходов, роли РВЭ в процессе принятия решений. Мы рассмотрели новые прикладные

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… group 5 member D; HIF-2α: hypoxia-inducible factor 2-alpha; HSPC: hematopoietic stem and progenitor cell; MEK 1/2: mitogen-activated protein kinase kinase 1/2; MET: mesenchymal–epithelial transition factor; MoA: mechanism of action; NF1: neurofibromatosis type 1; NSCLC: non–small cell lung cancer; ODC: ornithine … FDA | Priority review; fast track; orphan drug | December 18, 2024 | Pediatric | Acute steroid-refractory GVHD | Mesenchymal stromal cells | MSB-GVHD001 | Phase 3 Eflornithine | FDA | Orphan drug; breakthrough therapy; priority review | December 13, 2023 | Adults and pediatric | Neuroblastoma | Oral ornithine …

Construction of two YAC contigs in human Xp11.23-p11.22, one encompassing the loci OATL1, GATA, TFE3, and SYP, the other linking DXS255 to DXS146.

We have constructed two YAC contigs in the Xp11.23-p11.22 interval of the human X chromosome, a region that was previously poorly characterized. One contig, of at least 1.4 Mb, links the pseudogene OATL1 to the genes GATA1, TFE3, and SYP and also contains loci implicated in Wiskott-Aldrich syndrome and synovial sarcoma. A second contig, mapping proximal to the first, is estimated to be over 2.1 Mb and links the hypervariable locus DXS255 to DXS146, and also contains a chloride channel gene that is responsible for hereditary nephrolithiasis. We have used plasmid rescue, inverse PCR, and Alu-PCR

[Effects and mechanism of diammonium glycyrrhizinate on liver injury in severely scalded rats].

Objective: To investigate the effects and mechanism of diammonium glycyrrhizinate (DG) on liver injury in severely scalded rats. Methods: Th … tal protein, and albumin was measured by automatic biochemical assay analyzer, and serum content of ornithine carbamoyl transferase (OCT) was measured by enzyme-linked immunosorbent assay method at PIH 24, 48, and 72; hepatic histopathological changes at PIH 72 were observed by hematoxylin-eosin staining; the mRNA expressions of B-cell lymphoma 2 (Bcl-2), B …

Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases.

Osteoarthritis and inflammatory arthropathies are a cause of significant morbidity globally. New research elucidating the metabolic derangements associated with a variety of bone and joint disorders implicates various local and systemic metabolites, which further elucidate the underlying molecular mechanisms associated with these destructive disease processes. In osteoarthritis, atty acid metabolism has been implicated in disease development, both locally and systemically. Several series of rheumatoid arthritis patients have demonstrated overlapping trends related to histidine and glyceric aci

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… Further investigation demonstrated that ornithine and proline concentrations were also 2.2 and 1.2 times greater, respectively, in OA patients compared to controls, implicating an imbalance between cartilage repair and degradation associated with the ornithine pathway [ 8 ]. …