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Cell Biochemistry and Function Jun 2024Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration... (Review)
Review
Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron-dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano-drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions.
Topics: Ferroptosis; Osteosarcoma; Humans; Bone Neoplasms; Antineoplastic Agents; Immunotherapy; Animals
PubMed: 38924104
DOI: 10.1002/cbf.4080 -
Cannabis and Cannabinoid Research Jun 2024Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a...
Acute Cannabis Administration Transiently Reduces Mitochondrial DNA in Young Adults: Findings from a Secondary Analysis of a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.
Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a resurgence of research into the effects of plant-derived cannabinoids on mitochondrial health. In particular, a number of studies implicate mitochondrial-Δ9-tetrahydrocannabinol (Δ9-THC) interactions with altered memory, metabolism, and catalepsy in mice. Although the research in this field is expanding rapidly, there is little known about the effects of cannabis on mitochondria health in human subjects either in acute or chronic term use. Blood samples were obtained from a double-blind, placebo-controlled, parallel-group randomized clinical trial in which adults who regularly use cannabis (1-4 days/week) aged 19-25 years were randomized 2:1 to receive either an active (12.5% Δ9-THC) cigarette or placebo (<0.01% Δ9-THC) cigarette containing 750 mg of cannabis before driving simulator testing. DNA was extracted from whole blood using commercial spin columns, followed by measurement of mt-ND1, mt-ND4, and β2M using quantitative polymerase chain reaction. One-way repeated measures analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test was used to observe changes in mitochondrial DNA (mtDNA) copy number over time. A two-tailed Pearsons R test was used to assess correlations between mtDNA copy number and cannabinoid levels (Δ9-THC and metabolites) in blood. We found that exposure to active cannabis containing Δ9-THC, as opposed to placebo, was associated with an acute reduction in mitochondrial DNA copy number in whole blood at 15 min and 1 h after smoking. The observed decrease in mtDNA copy number negatively correlated with blood concentrations of 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the two primary metabolites of Δ9-THC, but not Δ9-THC itself. Further, the negative correlation between 11-OH THC and THC-COOH concentrations and mtDNA copy number was found in only a subgroup of participants who use cannabis infrequently, suggesting a tolerance effect. These results illuminate mitochondrial alterations attributed to Δ9-THC consumption, which may be mediated by metabolites. These results appear to suggest stronger effects in individuals who consume cannabis less frequently, suggesting some form of tolerance to the effects of Δ9-THC and its metabolites on mtDNA content in whole blood. Mitochondria; mtDNA; cannabis; THC; THC metabolites; blood; THC-COOH; 11-OH-THC.
PubMed: 38923954
DOI: 10.1089/can.2023.0282 -
Biomedical Chromatography : BMC Jun 2024Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide...
Revealing the material basis and mechanism for the inhibition of intestinal peristalsis by Zingiber officinale Roscoe through integrated metabolomics, serum pharmacochemistry, and network pharmacology.
Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.
PubMed: 38922712
DOI: 10.1002/bmc.5932 -
Toxins May 2024Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate... (Review)
Review
Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It's crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components.
Topics: Animals; Polyamines; Spider Venoms; Insecticides; Wasps; Humans; Spiders
PubMed: 38922129
DOI: 10.3390/toxins16060234 -
Marine Drugs Jun 2024Ichthyotoxic red tide is a problem that the world is facing and needs to solve. The use of antialgal compounds from marine macroalgae to suppress ichthyotoxic red tide...
Ichthyotoxic red tide is a problem that the world is facing and needs to solve. The use of antialgal compounds from marine macroalgae to suppress ichthyotoxic red tide is considered a promising biological control method. Antialgal substances were screened and isolated from , , , , , , and sp. to obtain new materials for the development of algaecides against ichthyotoxic red tide microalgae using bioactivity-guided isolation methods. The fractions of seven macroalgae exhibited selective inhibitory activities against and , of which the ethyl acetate fractions had the strongest and broadest antialgal activities for the two tested red tide microalgae. Their inhibitory effects on . and . were even stronger than that of potassium dichromate, such as ethyl acetate fractions of . , . , and sp. Thin-layer chromatography and ultraviolet spectroscopy were further carried out to screen the ethyl acetate fraction of sp. Finally, a new glycolipid derivative, 2--eicosanoyl-3--(6-amino-6-deoxy)--D-glucopyranosyl-glycerol, was isolated and identified from sp., and it was isolated for the first time from marine macroalgae. The significant antialgal effects of 2--eicosanoyl-3--(6-amino-6-deoxy)--D-glucopyranosyl-glycerol on . and . were determined.
Topics: Seaweed; Glycolipids; Harmful Algal Bloom; Microalgae; Dinoflagellida
PubMed: 38921590
DOI: 10.3390/md22060279 -
Marine Drugs May 2024In this research, the chemical compositions of various extracts obtained from , a type of green seaweed collected from the Nador lagoon in the northern region of...
In this research, the chemical compositions of various extracts obtained from , a type of green seaweed collected from the Nador lagoon in the northern region of Morocco, were compared. Their antioxidant and anti-diabetic properties were also studied. Using GC-MS technology, the fatty acid content of the samples was analyzed, revealing that palmitic acid, eicosenoic acid, and linoleic acid were the most abundant unsaturated fatty acids present in all samples. The HPLC analysis indicated that sinapic acid, naringin, rutin, quercetin, cinnamic acid, salicylic acid, apigenin, flavone, and flavanone were the most prevalent phenolic compounds. The aqueous extract obtained by maceration showed high levels of polyphenols and flavonoids, with values of 379.67 ± 0.09 mg GAE/g and 212.11 ± 0.11 mg QE/g, respectively. This extract also exhibited an impressive ability to scavenge DPPH radicals, as indicated by its IC value of 0.095 ± 0.12 mg/mL. Additionally, the methanolic extract obtained using the Soxhlet method demonstrated antioxidant properties by preventing β-carotene discoloration, with an IC of 0.087 ± 0.14 mg/mL. Results from in-vitro studies showed that extracts from were able to significantly inhibit the enzymatic activity of α-amylase and α-glucosidase. Among the various extracts, methanolic extract (S) has been identified as the most potent inhibitor, exhibiting a statistically similar effect to that of acarbose. Furthermore, molecular docking models were used to evaluate the interaction between the primary phytochemicals found in these extracts and the human pancreatic α-amylase and α-glucosidase enzymes. These findings suggest that extracts contain bioactive substances that are capable of reducing enzyme activity more effectively than the commercially available drug, acarbose.
Topics: Hypoglycemic Agents; Antioxidants; Ulva; Phytochemicals; Plant Extracts; Glycoside Hydrolase Inhibitors; alpha-Amylases; alpha-Glucosidases; Molecular Docking Simulation; Morocco; Humans; Chromatography, High Pressure Liquid; Polyphenols; Flavonoids; Edible Seaweeds
PubMed: 38921551
DOI: 10.3390/md22060240 -
Marine Drugs May 2024Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on...
Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on the modulation of the inflammatory response mainly by microglia/macrophages. The extracts and metabolites of marine sponges have been presented as anti-inflammatory. This study evaluated the toxicity of an extract and purified compound from the Brazilian marine sponge as well as its neuroprotection against inflammatory damage associated with the modulation of microglia response. PC12 neuronal cells and neonatal rat microglia were treated with the methanolic extract of (AF-MeOH, 0.1-200 μg/mL) or with its purified dimethyl ketal of 3,5-dibromoverongiaquinol (AF-H1, 0.1-100 μM). Cytotoxicity was determined by MTT tetrazolium, Trypan blue, and propidium iodide; microglia were also treated with the conditioned medium (CM) from PC12 cells in different conditions. The microglia phenotype was determined by the expression of Iba-1 and CD68. AF-MeOH and AF-H1 were not toxic to PC12 or the microglia. Inflammatory damage with lipopolysaccharide (LPS, 5 μg/mL) was not observed in the PC12 cells treated with AF-MeOH (1-10 μg/mL) or AF-H1 (1-10 μM). Microglia subjected to the CM from PC12 cells treated with LPS and AF-MeOH or AF-H1 showed the control phenotype-like (multipolar, low-CD68), highlighting the anti-neuroinflammatory and neuroprotective effect of components of this marine sponge.
Topics: Animals; Microglia; Rats; Porifera; Neuroprotective Agents; PC12 Cells; Brazil; Anti-Inflammatory Agents; Hydrocarbons, Brominated; Inflammation
PubMed: 38921546
DOI: 10.3390/md22060235 -
Metabolites Jun 2024With a rising demand of cocaine over the last years, it is likely that unregulated new psychoactive substances with similar effects such as indatraline...
With a rising demand of cocaine over the last years, it is likely that unregulated new psychoactive substances with similar effects such as indatraline ((1,3)-3-(3,4-dichlorophenyl)--methyl-2,3-dihydro-1-inden-1-amine) and troparil (Methyl (1,2,3,5)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate) become popular as well. Both substances share a similar pharmacological profile as cocaine, while their potency is higher, and their duration of action is longer. This study investigated their metabolic fate in rat urine and incubations using pooled human liver S9 fraction (pHLS9). Indatraline formed two phase I and four phase II metabolites, with aromatic hydroxylation and glucuronidation being the main metabolic steps. All metabolites were detected in rat urine, while the parent compound was not detectable. Although low in abundance, indatraline metabolites were well identifiable due to their specific isotopic patterns caused by chlorine. Troparil formed four phase I and three phase II metabolites, with demethylation being the main metabolic step. Hydroxylation of the tropane ring, the phenyl ring, and combinations of these steps, as well as glucuronidation, were found. Phase I metabolites were detectable in rat urine and pHLS9, while phase II metabolites were only detectable in rat urine.
PubMed: 38921476
DOI: 10.3390/metabo14060342 -
Metabolites Jun 2024Tongmai Sini decoction (TSD), the classical prescriptions of traditional Chinese medicine, consisting of three commonly used herbal medicines, has been widely applied...
Tongmai Sini decoction (TSD), the classical prescriptions of traditional Chinese medicine, consisting of three commonly used herbal medicines, has been widely applied for the treatment of myocardial infarction and heart failure. However, the absorbed components and their metabolism in vivo of TSD still remain unknown. In this study, a reliable and effective method using ultra-performance liquid chromatography coupled with hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Exactive-MS/MS) was employed to identify prototype components and metabolites in vivo (rat plasma and urine). Combined with mass defect filtering (MDF), dynamic background subtraction (DBS), and neutral loss filtering (NLF) data-mining tools, a total of thirty-two major compounds were selected and investigated for their metabolism in vivo. As a result, a total of 82 prototype compounds were identified or tentatively characterized in vivo, including 41 alkaloids, 35 phenolic compounds, 6 saponins. Meanwhile, A total of 65 metabolites (40 alkaloids and 25 phenolic compounds) were tentatively identified. The metabolic reactions were mainly hydrogenation, demethylation, hydroxylation, hydration, methylation, deoxylation, and sulfation. These findings will be beneficial for an in-depth understanding of the pharmacological mechanism and pharmacodynamic substance basis of TSD.
PubMed: 38921468
DOI: 10.3390/metabo14060333 -
Biosensors May 2024Human sulfotransferase 1As (hSULT1As) play a crucial role in the metabolic clearance and detoxification of a diverse range of endogenous and exogenous substances, as...
Human sulfotransferase 1As (hSULT1As) play a crucial role in the metabolic clearance and detoxification of a diverse range of endogenous and exogenous substances, as well as in the bioactivation of some procarcinogens and promutagens. Pharmacological inhibiting hSULT1As activities may enhance the in vivo effects of most hSULT1As drug substrates and offer protective strategies against the hSULT1As-mediated bioactivation of procarcinogens. To date, a fluorescence-based high-throughput assay for the efficient screening of hSULT1As inhibitors has not yet been reported. In this work, a fluorogenic substrate () for hSULT1As was developed through scaffold-seeking and structure-guided molecular optimization. Under physiological conditions, could be readily sulfated by hSULT1As to form , which emitted brightly fluorescent signals around 450 nm. was then used for establishing a novel fluorescence-based microplate assay, which strongly facilitated the high-throughput screening of hSULT1As inhibitors. Following the screening of an in-house natural product library, several polyphenolic compounds were identified with anti-hSULT1As activity, while pectolinarigenin and hinokiflavone were identified as potent inhibitors against three hSULT1A isozymes. Collectively, a novel fluorescence-based microplate assay was developed for the high-throughput screening and characterization of hSULT1As inhibitors, which offered an efficient and facile approach for identifying potent hSULT1As inhibitors from compound libraries.
Topics: High-Throughput Screening Assays; Humans; Sulfotransferases; Fluorescence; Enzyme Inhibitors
PubMed: 38920579
DOI: 10.3390/bios14060275