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Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.

BACKGROUND: Early identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-based cohorts. METHODS AND FINDINGS: 106 candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy of non-fasting plasma samples from a random subset of the Estonian Biobank (n = 9,842; age range 18-103 y; 508 deaths during a median of 5.4 y of follow-up). Biomarkers for all-cause mortality were

Antibacterial efficacy of MTAD final rinse and two percent chlorhexidine gel medication in teeth with apical periodontitis: a randomized double-blinded clinical trial.

INTRODUCTION: Clinical assessment of the efficacy of novel root canal disinfection protocols is an important focus in endodontic research. This randomized double-blinded study assessed the antibacterial efficacy of a final rinse with BioPure MTAD (MTAD) and intracanal medication with 2% chlorhexidine gel (CHX) in teeth with apical periodontitis. METHODS: Canals in 30 teeth (single-rooted and multi-rooted) were prepared by using 1.3% NaOCl, rinsed with MTAD or saline in random sequence, medicated with CHX for 7 days, irrigated with 1.3% NaOCl, and filled. Bacteriologic root canal samples were

Strain differences in carcinogenic and hematopoietic responses of mice after injection of plutonium citrate.

The carcinogenicity of injected (239)Pu citrate was compared in female mice of the C3H, C57BL/6 and BC3F(1) hybrid strains with different spectra of spontaneous or radiation-induced tumors. A significant reduction in survival due to early death caused particularly by the induction of osteosarcomas was noted in each strain after injection of 500 Bq or more. The dose response of osteosarcomas appeared to have a similar pattern in each strain except for the differences in the skeletal dose ranges for the maximum induction. While the incidence of lymphoid tumors decreased as that of osteosarcomas

Bortezomib alters sour taste sensitivity in mice.

Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the co

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… : 0.86 vs 0.59, CI: 0.061–0.464, p < 0.01; 30 mM citric acid: 0.54 vs 0.27, CI: 0.061–0.465, p < 0.01; 16 mM HCl: 0.56 vs 0.25, CI: 0.085–0.535, p < 0.01; 32 mM HCl: 0.37 vs 0.06, CI: 0.078–0.528, p < 0.01) and 26 (10 mM citric acid: 0.87 vs 0.59, CI: 0.074–0.481, p < 0.01; 30 mM citric acid: 0.54 vs … Fig. 2 Behavioral responses to citric acid solutions in bortezomib-administered mice. The lick ratios for 5–100 mM citric acid (A–I) were determined in control and bortezomib-administered mice on days 0 (Base), 2, 5, 9, 12, 16, 19, 23 and 26. …

AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia.

AMP-activated protein kinase (AMPK) regulates the balance between cellular anabolism and catabolism dependent on energy resources to maintain proliferation and survival. Small-compound AMPK activators show anti-cancer activity in preclinical models. Using the direct AMPK activator GSK621, we show that the unfolded protein response (UPR) is activated by AMPK in acute myeloid leukemia (AML) cells. Mechanistically, the UPR effector protein kinase RNA-like ER kinase (PERK) represses oxidative phosphorylation, tricarboxylic acid (TCA) cycle, and pyrimidine biosynthesis and primes the mitochondrial

IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via i

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… Citric Acid Cycle Rewiring in IDH Mutant Cells The citric acid cycle is the cornerstone of cellular metabolism [ 101 ]. This pathway is directly involved in energy production and supplies metabolic intermediates for the generation of fatty acids, amino acids and nucleotides. … These findings are supported by studies showing that citric acid cycle intermediates downstream of IDH, including αKG, succinate and fumarate, are decreased [ 102 , 103 ]. Anaplerotic reactions serve to replenish citric acid cycle intermediates, maintaining cycle flux [ 101 ]. …

Cov-hep study: heparin in standard anticoagulation based on citrate for continuous veno-venous hemodialysis in patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to re … vely. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilir …

Research Hotspots and Trends in Global Cancer immunometabolism:A Bibliometric Analysis from 2000 to 2023.

BackgroundCancer poses a major global health challenge, and immunotherapy, known as the third revolution in cancer treatment, has brought new hope to patients. The emerging field of immunometabolism has further enhanced the safety and efficacy of immunotherapy. Over the past two decades, this field has rapidly evolved in oncology, leading to numerous significant findings. This review systematically examines the literature on immunometabolism in cancer, visualizing research trends and identifying future directions.MethodsA comprehensive literature search was conducted in the Web of Science, Pub

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… Citric acid promotes immune function by modulating the intestinal barrier . Int J Mol Sci . 2024 ; 25 ( 2 ). doi: 10.3390/ijms25021239 PMC10817003 38279237 57. Tang T , Huang X , Lu M , et al. … Citric acid promoting B lymphocyte differentiation and anti-epithelial cells apoptosis mediate the protective effects of hermetia illucens feed in ETEC induced piglets diarrhea . Front Vet Sci . 2021 ; 8 : 751861 . doi: 10.3389/fvets.2021.751861 34917669 PMC8669560 67. …

The impact of cancer treatment on the diets and food preferences of patients receiving outpatient treatment.

Patients undergoing cancer treatment experience a multitude of symptoms that can influence their ability to complete treatment as well as their quality of life during and after treatment. This cross-sectional study sought to describe the dietary changes experienced by cancer patients and to identify associations between these changes and common treatment symptoms. A convenience sample of 1199 cancer patients aged 18 yr and older undergoing active treatment were recruited from 7 cancer centers to complete a self-administered paper-and-pencil survey. Descriptive analyses were conducted to estima

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention i

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… Several proteins involved in metabolism have been implicated in a variety of malignancies, including enzymes of the citric acid cycle, the Myc family of proteins, and the hypoxia inducible factors 1 and 2. Iron regulates the activity of several enzymes involved in the citric acid cycle. … Iron-dependent changes in cellular energy metabolism: Influence on citric acid cycle and oxidative phosphorylation. Biochim. Biophys. Acta. 1999;1413:99–107. doi: 10.1016/s0005-2728(99)00088-2. 49. King A., Selak M.A., Gottlieb E. …

mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells.

Although glycolysis is substantially elevated in many tumors, therapeutic targeting of glycolysis in cancer patients has not yet been successful, potentially reflecting the metabolic plasticity of tumor cells. In various cancer cells exposed to a continuous glycolytic block, we identified a recurrent reprogramming mechanism involving sustained mTORC1 signaling that underlies escape from glycolytic addiction. Active mTORC1 directs increased glucose flux via the pentose phosphate pathway back into glycolysis, thereby circumventing a glycolysis block and ensuring adequate ATP and biomass producti

Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: in silico, multi-spectroscopic, thermodynamic, and in vitro approaches.

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1-35). The designed analogues (T1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T30 with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal m

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… Reagents and conditions: (i) citric acid, TEOF, absolute ethanol, and reflux 10 h. … The preparation of ethyl 6-(chloromethyl)-1-methyl-2-oxo-4-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate (T 30 ) A mixture of ethyl 4-chloroacetoacetate 2 (4 mmol, 658 mg), 3,4,5-trimethoxybenzaldehyde 1 (2 mmol 392 mg), N -methyl urea 3 (4 mmol 412 mg), citric acid (2 mmol 384 …

Saliva как матрица для терапевтического мониторинга наркотиков и биомаркеров заболеваний у детей и подростков.

Saliva — более доступная, менее напряженная и менее дорогостоящая биологическая матрица, чем кровь, и она может применяться в терапевтическом мониторинге лекарственных средств (ПТМ). Концентрации слюны отражают фармацевтический активный ненавязанный препарат. В этом обзоре содержится последняя информация о слюне в качестве матрицы для лечебного контроля за наркотиками и определения биомаркеров у младенцев, детей и подростков. К октябрю 2024 года по базе данных PubMed были проведены обыски литературы, 64 исследования были включены в TDM, стероиды, добавки, биомаркеры заболеваний, стоматология,

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… Citric acid [ 41 , 59 ] and sodium bicarbonate [ 59 ] are the most popular reagents. Saliva production may also be enhanced by applying citric acid cotton swabs to the buccal mucosa and subsequent collection with a Salivette pipette (Sarstedt BV, Etten-Leur, The Netherlands) [ 58 ]. … Therapeutic range: 10–50 µg/mL defined previously [ 82 ]; the corresponding saliva concentrations should be 40% (as a minimum) of this range (C min 4 µg/mL) [ 72 ] Carbamazepine, phenytoine, phenobarbital stimulated with citric acid; collected by commercially available saliva collecting device saliva …

Metabolic stress controls mTORC1 lysosomal localization and dimerization by regulating the TTT-RUVBL1/2 complex.

The metabolism of glucose and glutamine, primary carbon sources utilized by mitochondria to generate energy and macromolecules for cell growth, is directly regulated by mTORC1. We show that glucose and glutamine, by supplying carbons to the TCA cycle to produce ATP, positively feed back to mTORC1 through an AMPK-, TSC1/2-, and Rag-independent mechanism by regulating mTORC1 assembly and its lysosomal localization. We discovered that the ATP-dependent TTT-RUVBL1/2 complex was disassembled and repressed by energy depletion, resulting in its decreased interaction with mTOR. The TTT-RUVBL complex w

Transferrin-conjugated SNALPs encapsulating 2'-O-methylated miR-34a for the treatment of multiple myeloma.

Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2'-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs.

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… Cholesterol (CHOL), human transferrin (Tf), sodium chloride, sodium phosphate, HEPES, citric acid, and sodium citrate were purchased from Sigma Aldrich (USA). Ethanol and other solvents were obtained from Carlo Erba Reagenti (Italy). … In a separated tube, 0.2 mg of miRNA was dissolved in 0.6 mL of 20 mM citric acid at pH 4.0. The two solutions were warmed for 2-3 min to 65°C and the lipid solution was quickly added to the miRNA solution under stirring. …

Иммунометаболизм в старении мозга и нейродегенерации: преодоление метаболических путей и иммунные ответные меры.

Сложный набор взаимодействий между иммунной системой и метаболизмом, известный как иммунометаболизм, стал критическим регулятором последствий заболеваний в центральной нервной системе. В ходе многочисленных исследований метаболические расстройства увязывались с ослабленной иммунной реакцией при старении мозга, нейродегенеративных расстройствах и травме мозга. В этом обзоре мы обсудим вопрос о том, как нарушения баланса иммунометаболизма мозга способствуют патофизиологии дисфункции мозга. В первой части обзора резюмируется вклад таких критических групп иммунной клетки, как микроглии, астроциты,

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… By converting citric acid into isocitric acid, isocitrate dehydrogenase (IDH) induces macrophages and dendritic cells to release nitric oxide (NO) and prostaglandins. Ketoglutarate stimulates TH1 cells to produce interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα.) … By converting citric acid into isocitric acid, isocitrate dehydrogenase (IDH) induces macrophages and dendritic cells to release nitric oxide (NO) and prostaglandins. Ketoglutarate stimulates TH1 cells to produce interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα.) …

Тела эндогенных кетонов связаны с метаболической уязвимостью и инвалидностью при множественном склерозе.

Цель: Тела кетона могут быть полезными биомаркерами в множестве склероза (МС), поскольку патофизиологические процессы, лежащие в основе развития заболеваний MS, вызывают метаболический стресс. Цель заключалась в оценке связей кетоновых тел с биомаркерами метаболического, подстрекательского и окислительного стресса в MS. Методы: Образцы крови и неврологические оценки были получены от 153 здоровых контрольных приборов (HC), 187 релапсирующих излучающих веществ (RRMS) и 91 пациента с прогрессивным MS (PMS). AcAc, BHB и ацетон измерялись с помощью спектроскопии протонного ядерного магнитного резон

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… During ketolysis, energy is produced from ketone bodies by converting AcAc back to acetyl-CoA, which enters the citric acid cycle to generate adenosine triphosphate (ATP). The liver is a net exporter of ketone bodies because it lacks succinyl-CoA-3-oxaloacid CoA transferase (SCOT). … Leucine is a ketogenic amino acid that is catabolized into acetyl-CoA and acetoacetate to enter the citric acid cycle. Alanine and valine are glucogenic amino acids and are catabolized to glucose, and isoleucine is amphibolic. …

An expanding horizon of complex injectable products: development and regulatory considerations.

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" produ

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… . | Invega Hafyera ® | Paliperidone palmitate | Small molecule | Extended release suspension Pre-filled syringe | 1092 mg/3.5 mL, 1560 mg/5 mL | Polysorbate 20, PEG 4000, citric acid monohydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide, WFI | Schizophrenia in adults | I.M. | Gluteal … acid, sodium phosphate, ethanol, sodium chloride | Acute lymphoblastic leukemia treatment | I.V. …

APOE4 ослабляет липофагическую липофагию и поощряет демиэлизацию спиральных ганглионов в мышином кохлее.

АпоЭ-4 Ген представляет собой прочно установившийся генетический фактор риска для нейродегенеративных заболеваний, таких, как болезнь Альцгеймера и множественный склероз, которые характеризуются аксонной демиелинацией в центральной нервной системе. В недавних исследованиях были замешаны АпоЕ-4 в связи с возрастной потерей слуха (ARHL), что предполагает потенциальную роль изоформы APOE4 в дегенерации периферической нервной системы. Однако роль APOE4 в ARHL по-прежнему не ясна. В этом исследовании мы изучили потенциальную роль APOE4 в аксонной демиелиции спиральных ганглионов (SGN). АпоЭ-4/ __4

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… Paraffin sections were dewaxed with xylene, washed with gradient alcohol and citric acid for antigen retrieval, and then washed in PBS buffer three times for 5 min each. … Paraffin sections were dewaxed with xylene, washed with gradient alcohol and citric acid for antigen retrieval, and then rinsed in PBS three times for 5 min each. …

Abemaciclib, A Selective CDK4/6 Inhibitor, Restricts the Growth of Pediatric Ependymomas.

Pediatric ependymomas are a type of malignant brain tumor that occurs in children. The overall 10-year survival rate has been reported as being 45-75%. Maximal safe surgical resection combined with adjuvant chemoradiation therapy is associated with the highest overall and progression-free survival rates. Despite aggressive treatment, one-third of ependymomas exhibit recurrence within 2 years of initial treatment. Therefore, this study aimed to find new agents to overcome chemoresistance and defer radiotherapy treatment since, in addition, radiation exposure may cause long-term side effects in

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… The cells were pelleted by centrifugation and incubated in 0.1 mL of phosphate–citric acid buffer (0.2 M NaHPO 4 and 0.1 M citric acid, pH 7.8) for 15 min at room temperature and then resuspended in propidium iodide staining buffer containing Triton X-100 (0.1%, v / v ), RNase A (100 μg/mL), and propidium …