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Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases.

Inflammation, being a hallmark of many chronic diseases, including cancer, inflammatory bowel disease, rheumatoid arthritis, and chronic kidney disease, negatively affects iron homeostasis, leading to iron retention in macrophages of the mononuclear phagocyte system. Functional iron deficiency is the consequence, leading to anemia of inflammation (AI). Iron deficiency, regardless of anemia, has a detrimental impact on quality of life so that treatment is warranted. Therapeutic strategies include (1) resolution of the underlying disease, (2) iron supplementation, and (3) iron redistribution str

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… In humans, iron is essential for many biochemical processes, including electron transfer reactions in mitochondria, the citric acid cycle, gene expression, binding and transport of oxygen, regulation of cell growth and differentiation as well as the cellular immune response [ 1 ]. …

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, link

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… Chandna et al. 124 used a polyethylene glycol (PEG) polymeric carrier to link the anticancer drug camptothecin (CPT) with the tumor-targeting peptide LRHR and a cellular anti-apoptosis inhibitor (BH3 peptide) via a citric acid spacer to form a polymer‒peptide‒drug conjugate (PPDC) capable of exhibiting …

Mechanisms of chemotherapy-induced behavioral toxicities.

While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of lif

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… Within the mitochondria, pyruvate is oxidized into citric acid and enters the tricarboxylic acid (TCA) cycle and electron transport chain. …

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effe

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… It is also used as a fuel molecule after being converted by enzymes into isovaleryl-CoA and is used in the citric acid cycle (TCA) to produce ATP [ 99 ]. During cancer progression, cells need to utilize alternative energy molecules to compensate for the fast rhythm of growth [ 100 ]. …

Delayed gastric emptying in critical illness: is enhanced enterogastric inhibition with cholecystokinin and peptide YY involved?

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… WB contains approximately 1.8 g of citrate/citric acid per unit in the plasma fraction. Patients with normal liver function can metabolize the citrate load in 1 unit of WB in 5 minutes, but hepatic impairment may extend removal to 15 minutes or longer. …

Нацеливаюсь на гормональное лечение мозга в менопаузе.

Эстрогены являются нейрозащитными, и менопауза может способствовать нейродегенерации. Эстриол преимущественно связывает бета-рецептор эстрогена (ERβ) в мозге для обеспечения нейрозащиты. Ранее пероральный эстриол повышал скорость когнитивной обработки и уменьшил атрофию коры головного мозга в месяц лечения twelve в случае женщин с множественным склерозом (МС). В данном случае лечение с помощью волдыря, предназначенного для здоровых менопаузальных женщин, содержащих эстриол и прогестерон (Pearlpak), оценивалось с точки зрения его воздействия на когнитивные симптомы, характерные для домена, в ря

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… After heat antigen retrieval with heated 10 mM Citric Acid—0.05% Tween 20, pH6.0, all tissue sections were permeabilized with 0.3% Triton-X and 2% normal serum in 1X PBS for 10 min on ice and blocked with 10% normal serum in 1X PBST for 1 h. …

Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease.

The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1mut and KMT2A-rearranged AML. With so many new drugs approved, the number of potential combinator

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… Drug interactions between venetoclax, gilteritinib and CYP3A4 inhibitors such as azole antifungals should also be considered and relevant-dose adjustments made. 11 , 70 , 71 IDH MUTATIONS Isocitrate dehydrogenase (IDH) 1 and 2 are enzymes in the citric acid cycle. …

Construction and validation of renal cell carcinoma tumor cell differentiation-related prognostic classification (RCC-TCDC): an integrated bioinformatic analysis and clinical study.

BackgroundRenal cell carcinoma (RCC) is a heterogeneous malignancy with diverse gene expression patterns, molecular landscapes, and differentiation characteristics of tumor cells. It is imperative to develop molecular RCC classification based on tumor cell differentiation for precise risk stratification and personalized therapy.MethodsWe obtained scRNA-seq profiles from GSE159115 and bulk RNA-seq profiles from TCGA-KIRC cohort. We then performed scRNA-seq cluster analysis, monocle2 pseudotime analysis, and prognostic analysis to obtain tumor cell differentiation-related prognostic genes (TCDGs

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… Subsequently, dewaxing and rehydration procedures were carried out, followed by antigen retrieval to expose specific antigens (markers of each subtype) via EDTA (pH = 9.0) or citric acid (pH = 6.0) antigen-retrieving buffers. …

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer.

Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significantrole in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Someof the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeuticwindow and undesired side effects of available anticancer drugs and the limitations of anticancerdrugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranosticcarriers, liposomes, carbon nano

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… In order to enhance the solubility, initially MWCNTs) were first modified to include hyperbranched poly citric acid (PCA) and then, PTX was conjugated to the carboxyl functional groups of PCA via a cleavable ester bond to obtain a MWCNT-g-PCA-PTX conjugate. …

DNA methyltransferase inhibitors in hematological malignancies and solid tumors.

Epigenetic modifications such as DNA methylation play a fundamental role in oncogenesis and the progression of neoplasms neoplasias. DNA methyltransferase inhibitors (DNMTi) constitute a family of therapeutic agents that impede the methylation at the 5-position on cytosine nucleotides, thereby modulating the epigenetic regulation of tumor suppressor genes, oncogenes, and other key regulatory genes. The first-generation DNMTi azacitidine and decitabine have demonstrated substantial efficacy in the treatment of medically non-fit, older patients with acute myeloid leukemia (AML) or myelodysplasti

The crosstalk between non-coding RNAs and oxidative stress in cancer progression.

As living standards elevate, cancers are appearing in growing numbers among younger individuals globally and these risks escalate with advancing years. One of the reasons is that instability in the cancer genome reduces the effectiveness of conventional drug treatments and chemotherapy, compared with more targeted therapies. Previous research has discovered non-coding RNAs' crucial role in shaping genetic networks involved in cancer cell growth and invasion through their influence on messenger RNA production or protein binding. Additionally, the interaction between non-coding RNAs and oxidativ

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… In ovarian cancer cells, miR-450a targets aconitase 2, suppresses TIMMDC1 and MT-ND2, acts on the citric acid cycle, and affects glutamine metabolism and mitochondrial activity, 186 resulting in the accumulation of oxygen in the cell, sparking oxidative stress that exacerbates the outcome. …

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

Anticancer natural products from the Middle East and North Africa: biodiversity, mechanisms, and translational challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, imposing substantial clinical, societal, and economic burdens. Despite major advances in surgical oncology, systemic chemotherapy, radiation therapy, molecularly targeted therapeutics, and immune checkpoint inhibition, contemporary cancer treatment remains constrained by dose-limiting toxicities, intratumoral and intertumoral heterogeneity, and the inexorable emergence of multifaceted drug resistance mechanisms. These persistent therapeutic challenges have reinstated interest in natural products (NPs) as evolutionar

Отчет о ДИД 1st Ежегодный Всемирный конгресс биомедицинской инженерии, проводимый в Сиане, Китай, 9-11 ноябрь 2017.

Мы рады представить на этом заседании резюме доклада "ДИД" 1st Всемирный конгресс биомедицинской инженерии 2017которая была проведена в Сиане в Китае [...].

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… This analysis corroborates known studies of metformin action: (a) pathway analysis indicated known mechanisms related to metformin action, including the citric acid (TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction ( p -value < 1 × 10 −9 ); (b) 70% of these 230 genes were functionally …

Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy arising from the biliary epithelium, with an increasing incidence and poor prognosis worldwide. Recent advances in next-generation sequencing have revealed a variety of genomic alterations-such as FGFR2 fusions, IDH1 mutations, and ERBB2 amplification-that may serve as therapeutic targets. However, the influence of underlying etiologic factors, including chronic liver and biliary diseases, on the molecular landscape of CCA remains unclear. Objective: This review aimed to synthesize the current knowledge on the genomic an

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… Genetic Abnormalities in CCA as Therapeutic Targets IDH is an enzyme that converts isocitrate to α-ketoglutarate as part of the citric acid cycle and has three subtypes, IDH1, IDH2, and IDH3, depending on the site of action. …

Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve ove

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… IDH1 is a citric acid (Krebs) cycle enzyme that converts isocitrate to a-ketoglutarate (a-KG) and is essential to produce adenosine triphosphate (ATP) during cellular energy production. During the Krebs cycle, isocitrate, produced by the isomerization of citrate, is oxidized and decarboxylated. …

Cuproptosis Inducers in Cancer Therapy: State of the Art and Challenges.

Cancer continues to be the primary cause of death despite significant progress in medicine, and finding effective therapies remains a challenge. New treatments are needed to minimize the harmful effects on the body and increase the selectivity of drugs. These therapies must also overcome cancer cell resistance and prevent metastasis. Metal-based drugs are becoming increasingly crucial for treating tumors, and copper ion-based systems and nanoparticles have been identified as having unique properties and anticancer potential. Given the key role exerted by Cu in the etiology, severity, and progr

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… HA‐functionalized ZCu (HA‐ZCu) were synthesized via a solvothermal reaction between Cu ions and citric acid, followed by HA modification through electrostatic and coordination interactions between the carboxyl groups of HA and Cu ions. …

Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enha

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… Relapsed or refractory follicular lymphoma (FL) IDH1 inhibitor: Inhibition leads to the production of oncometabolite 2-hydroxyglutarate (2-HG) instead of α-KG in the citric acid cycle; 2-HG inhibits histone demethylases and TET (ten-eleven translocation) enzymes involved in DNA demethylation, affecting …

Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.

Ammonium metabolism represents a critically understudied yet pivotal driver of prostate tumorigenesis and tumor microenvironment (TME) remodeling. The interplay between tumor metabolic reprogramming and the tumor microenvironment has emerged as a critical frontier in oncology research. While previous studies on prostate cancer metabolism have predominantly focused on lipid metabolism and the Warburg effect, the role of ammonium metabolism, particularly the urea cycle in tumor immune regulation remains insufficiently explored. This metabolic reprogramming constitutes a central node connecting c

Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familia