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Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides' dua

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… For instance, the deep-sea bacterium Bacillus licheniformis KDM612 biotransforms seriniquinone into a new glycoside with enhanced solubility, demonstrating microbial potential in glycoside biosynthesis [ 104 ]. … Additionally, the schematic depicts S14’s biotransformation into S14-Glu via UDP-glucuronosyltransferases (UGTs), which enhances renal distribution and pharmacokinetic properties—including an increased area under the curve (AUC) and shortened half-life (t 1/2 ). …

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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… Beyond these, the gut microbiome engages in a number of complementary metabolic processes that are not fully developed in the human host, including the breakdown of undigestible plant polysaccharides ( Hooper et al., 2002 ), synthesis of certain vitamins ( Hill, 1997 ), biotransformation of conjugated … Biotransformation of monoterpenes, bile acids, and other isoprenoids in anaerobic ecosystems. FEMS Microbiol. Rev. 22 (5), 475–488. 10.1111/j.1574-6976.1998.tb00382.x Ishimitsu A., Tojo A., Satonaka H., Ishimitsu T. (2021). …

Prevention of Anthracycline-Induced Cardiotoxicity: The Good and Bad of Current and Alternative Therapies.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) remains a serious health burden, especially in developing countries. Unfortunately, the high cost of current preventative strategies has marginalized numerous cancer patients because of socio-economic factors. In addition, the efficacy of these strategies, without reducing the chemotherapeutic properties of Dox, is frequently questioned. These limitations have widened the gap and necessity for alternative medicines, like flavonoids, to be investigated. However, new therapeutics may also present their own shortcomings, ruling out the idea of "natur

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… Furthermore, the reduction in the biotransformation of Dox to its secondary metabolites could also be considered beneficial in eradicating cancer since Dox, in its unmetabolized form, is reported to have a more potent tumoricidal effect than its metabolites, which are suggested to suppress the anti-cancer … In-vivo absorption of pinocembrin-7-O-β-D-glucoside in rats and its in-vitro biotransformation . Sci Rep . ( 2016 ) 6 : 1 . 10.1038/srep29340 27378517 PMC4932520 100. KondŽa M Bojić M Tomić I Maleš Z Rezić V Cavar I . …

Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence.

Chemoprevention is referred to as a strategy to inhibit, suppress, or reverse tumor development and progression in healthy people along with high-risk subjects and oncologic patients through using pharmacological or natural substances. Numerous phytochemicals have been widely described in the literature to possess chemopreventive properties, although their clinical usefulness remains to be defined. Among them, caryophyllane sesquiterpenes are natural compounds widely occurring in nature kingdoms, especially in plants, fungi, and marine environments. Several structures, characterized by a commo

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… responsiveness of cancer to the pharmacological treatments and improve the rate of relapse-free survival in post-treated cancer patients by targeting specific mechanisms of chemoresistance, such as alterations in drug fate (i.e., uptake, export by ATP-binding cassette (ABC) transporters and intracellular biotransformation …

Сосуществование Лактиплантацилла и Виккерхамомиц в верхнем слое сахарного тростника стимулирует потенциальное подавление патогенов и аэробную стабильность за счет увеличения производства лактической кислоты и уксусной кислоты.

Чтобы определить сосуществующие бактерии и дрожжи в верхнем слое сахарного тростника, которые определяют качество ферментации и повышают безопасность корма, мы манипулировали эпифитической микробиотой сверху сахарного тростника путем селективного подавления дрожжей (АФ) или бактерий с лактической кислотой (АБ) перед повторной цензурой, используя в качестве контроля неочищенные (КК) и стерилизованные стерилизованные силизы (НА). Результаты показывают, что высокоурожайное производство лактической кислоты и уксусной кислоты (p) < 0.05), лучшая аэробная стабильность и высокая плотность Лактипланта

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… EtK3 during fruit waste biotransformation Int Biodeterior Biodegrad 2019 145 104795 10.1016/j.ibiod.2019.104795 Sarkar D, Prajapati S, Poddar K, Sarkar A. Production of ethanol by Enterobacter sp. EtK3 during fruit waste biotransformation. …

Exploring the Contribution of Curcumin to Cancer Therapy: A Systematic Review of Randomized Controlled Trials.

Although the anticancer role of curcumin has been extensively addressed in preclinical research, only a few studies were carried out in humans, with conflicting results. The aim of this systematic review is to collate together the results of the therapeutic effect of curcumin in cancer patients. A literature search was carried out in Pubmed, Scopus, and the Cochrane Central Register of Controlled Trials up to 29 January 2023. Only randomized controlled trials (RCTs) designed to evaluate the effects of curcumin on cancer progression, patient survival, or surgical/histological response were incl

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… Drug Biotransformation. In: Katzung B.G., Vanderah T.W., editors. Basic & Clinical Pharmacology. 15th ed. McGraw Hill; New York, NY, USA: 2021. pp. 57–76. Associated Data Data Availability Statement See Section 2.1 . …

Clinical Genetics of Cancer 2017 : Szczecin, Poland. 21-22 September 2017

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… cancer patients Pamuła-Piłat J, Tęcza K, Mazur M, Grzybowska E Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland Xenobiotic metabolizing enzymes and transporters (XMETs) are involved in biotransformation …

Мукоадгезивные наноэмульсии для доставки нозы в мозг диметилфумарат: разработка, характеристика и доказательство согласия

Фон. Диметилфумарат (ДМП) является утвержденным терапевтическим агентом для лечения множественного склероза, известным своими противовоспалительными и нейрозащитными свойствами. Однако его пероральное управление часто сопровождается побочными эффектами желудочно-кишечного кишечника, что ограничивает его терапевтический потенциал. В настоящем исследовании была разработана новая формула наноэмульсии (NE), которая была охарактеризована с целью усиления воздействия ДМП в цереброспинарной жидкости (CSF) после внутринационального администрирования. Методы: Состав был подготовлен методом самоэмульсиф

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… These characteristics make intranasal delivery particularly attractive for DMF, whose therapeutic potential may be limited by rapid systemic biotransformation. … Metabolism, pharmacokinetics and excretion of [14C]dimethyl fumarate in healthy volunteers: An example of xenobiotic biotransformation following endogenous metabolic pathways Xenobiotica 2023 53 163 172 10.1080/00498254.2023.2217506 37216617 15. Wipke B. Hoepner R. Strassburger-Krogias K. …

Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid.

Parkinson's disease (PD), a neurodegenerative disorder, causes severe motor impairment due to loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). MPTP, a neurotoxin that causes dopaminergic cell loss in mice, was used in an animal model to study the pathogenic mechanisms leading to neurodegeneration. We observed the activation of apoptosis signal regulating kinase (ASK1, MAPKKK) and phosphorylation of its downstream targets MKK4 and JNK, 12 h after administration of a single dose of MPTP. Further, Daxx, the death-associated protein, translocated to the cytosol selectively in

Research progress on arsenic, arsenic-containing medicinal materials, and arsenic-containing preparations: clinical application, pharmacological effects, and toxicity.

Introduction: The toxicity of arsenic is widely recognized globally, mainly harming human health by polluting water, soil, and food. However, its formulations can also be used for the clinical treatment of diseases such as leukemia and tumors. Arsenic has been used as a drug in China for over 2,400 years, with examples such as the arsenic-containing drug realgar mentioned in Shennong's Herbal Classic. We have reviewed references on arsenic over the past thirty years and found that research has mainly focused on clinical, pharmacological, and toxicological aspects. Results and Discussion: The f

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… The interaction of arsenic with arachidonic acid biotransformation ( Bunderson et al., 2004 ), affecting vasoconstriction and diastole, may be one of the mechanisms responsible for cardiovascular toxicity. … Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice . Archives Toxicol. 93 ( 1 ), 25 – 35 . 10.1007/s00204-018-2332-7 PMC7727877 30357543 Christen K. ( 2001 ). The arsenic threat worsens . Environ. Sci. …

Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice.

AimTo investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphoma-bearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone..MethodsThe hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine amino

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… Absorption and biotransformation of the coenzyme A precursor D-pantethine in rat hippocampus. Neurochem J. 2010;4:257–64. doi: 10.1134/S1819712410040033. 18. Aguilar F, Charrondiere U, Dusemund B, Galtier P, Gilbert J, Gott D, et al. …

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

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… However, recent research has also identified several mechanisms through which gut microbiota may support the host’s fight against cancer, such as the use of antigenic mimicry, biotransformation of chemotherapeutic agents, boosting of anti-cancer immune responses (to improve the efficacy of cancer immunotherapy …

Гут Микробиота Нарушение гематологовой терапии рака: Молекулярное понимание и последствия для эффективности лечения.

Гематологическая магнелезность (ГМ), включая лейкемию, лимфому и множественные миеломы, связана с бесконтрольным распространением аномальных кровеносных клеток, что создает серьезные клинические проблемы из-за их неоднородности и различных методов лечения. Несмотря на недавние достижения в области лечения, благодаря которым повысились показатели выживаемости, особенно в случае хронической лимфоцитической лейкемии и острой лимфоболической лейкемии, такие методы лечения, как химиотерапия и трансплантация стволовых клеток, часто нарушают микробиоту, что может негативно сказаться на результатах ле

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… Additionally, E. coli expresses p-aminobenzoyl-glutamate hydrolase, which also contributes to this biotransformation. The low solubility of MTX and its by-products at acidic pH levels increases the risk of renal precipitation, leading to kidney toxicity. … A novel approach for the prediction of species-specific biotransformation of xenobiotic/drug molecules by the human gut microbiota. Sci. Rep. 2017;7:9751. doi: 10.1038/s41598-017-10203-6. 51. Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics. [(accessed on 20 August 2024)]. …

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

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… Particular metabolic products and biotransformation processes remain to be clarified. There is a lack of information about the toxicity and overdose of this drug. …

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution.

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amo

Antibody-drug conjugates in urinary tumors: clinical application, challenge, and perspectives.

Urinary tumors primarily consist of kidney, urothelial, and prostate malignancies, which pose significant treatment challenges, particularly in advanced stages. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach, combining monoclonal antibody specificity with cytotoxic chemotherapeutic payloads. This review highlights recent advancements, opportunities, and challenges in ADC application for urinary tumors. We discuss the FDA-approved ADCs and other novel ADCs under investigation, emphasizing their potential to improve patient outcomes. Furthermore, we explore stra

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… Moreover, further insights are needed regarding ADC biotransformations, toxicity profiles, and resistance mechanisms ( 35 ). To encapsulate, ADC technology represents an emerging molecular platform that is expected to become a mainstay in anti-cancer therapeutics. …

Current Status and Perspectives of Protease Inhibitors and Their Combination with Nanosized Drug Delivery Systems for Targeted Cancer Therapy.

In cancer treatments, many natural and synthetic products have been examined; among them, protease inhibitors are promising candidates for anti-cancer agents. Since dysregulated proteolytic activities can contribute to tumor development and metastasis, antagonization of proteases with tailored inhibitors is an encouraging approach. Although adverse effects of early designs of these inhibitors disappeared after the introduction of next-generation agents, most of the proposed inhibitors did not pass the early stages of clinical trials due to their nonspecific toxicity and lack of pharmacological

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… Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4: potential contribution to high first-pass metabolism. Drug Metab Dispos . 1997;25(2):256–266. 81. Tatham LM, Rannard SP, Owen A. …

Advanced Technologies for Large Scale Supply of Marine Drugs.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain t

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… The microbial-mediated enzymatic cis -dihydroxylation of aromatic substrates facilitated by genetically engineered bacterial strains that overexpress the enzyme toluene dioxygenase represents a valuable biotransformation process for the production of chiral synthons with high optical purity, necessary … Biotransformations with whole Escherichia coli cells containing heterologously expressed protein gave a comparable conversion on a gram scale to that observed on analytical scales. Within 2 h, a complete conversion of Stipitatic acid ( 64 ) had been achieved [ 157 ]. …

Uncertainties about the benefit-risk balance of oncology medicines assessed by the European Medicines Agency.

BackgroundDrug regulators assess and describe uncertainties regarding treatment outcomes and the benefit-risk balance of newly authorised medicines. We aimed to evaluate the type and number of uncertainties described in the benefit-risk assessment for initial marketing authorisations of oncology medicines assessed by the European Medicines Agency (EMA). We also aimed to develop a systematic classification of uncertainties to contribute to improved communication about uncertainties.Materials and methodsWe included all medicines containing a new active substance assessed by the EMA and granted a

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… “Osimertinib was shown to undergo significant metabolism mediated clearance presumably with the liver as a major site of biotransformation and hence, hepatic impairment might be expected to lead to increased exposure of osimertinib.” (Osimertinib, Tagrisso, 2013) 46. …

Post-transplant cyclophosphamide-induced cardiotoxicity: A comprehensive review.

Cyclophosphamide-induced cardiotoxicity, associated with its toxic metabolite acrolein, is a significant concern and unresolved issue, especially when cyclophosphamide is administrated in high doses. However, cardiotoxicity following low-dose cyclophosphamide has been also documented, especially in post-hematopoietic stem cell transplantation (post-HSCT) settings. Despite the involvement of multiple signaling pathways in cyclophosphamide-induced cardiomyopathy, the exact underlying mechanisms remain to be fully elucidated. This review outlines the current challenges of cyclophosphamide therapy

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… various cytochrome p450 (CYP450) isoenzymes, such as CYPs 3A4, 2B6, 2C19. 14 , 15 The further structural modification produces phosphoramide mustard, an ultimate alkylating agent, with an anti-neoplastic activity. 14 , 15 Following oral or parenteral administration, cyclophosphamide undergoes hepatic biotransformation …