Search

Indiscriminate drug administration may lead to drug therapy results with varying effects on patients, and the proposal of personalized medication can help patients to receive effective drug therapy. Conventional ways of personalized medication, such as pharmacogenomics and therapeutic drug monitoring (TDM), can only be implemented from a single perspective. The development of pharmacometabolomics provides a research method for the realization of precise drug administration, which integrates the environmental and genetic factors, and applies metabolomics technology to study how to predict different drug therapeutic responses of organisms based on baseline metabolic levels. The published research on pharmacometabolomics has achieved satisfactory results in predicting the pharmacokinetics, pharmacodynamics, and the discovery of biomarkers of drugs. Among them, the pharmacokinetics related to pharmacometabolomics are used to explore individual variability in drug metabolism from the level of metabolism of the drugs in vivo and the level of endogenous metabolite changes. By searching for relevant literature with the keyword pharmacometabolomics on the two major literature retrieval websites, PubMed and Web of Science, from 2006 to 2023, we reviewed articles in the field of pharmacometabolomics that incorporated pharmacokinetics into their research. This review explains the therapeutic effects of drugs on the body from the perspective of endogenous metabolites and pharmacokinetic principles, and reports the latest advances in pharmacometabolomics related to pharmacokinetics to provide research ideas and methods for advancing the implementation of personalized medication.

Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor‐peroxisome proliferator‐activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator‐activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry‐quadrupole‐time‐of‐flight mass spectrometry‐based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator‐activated receptor alpha activity negatively correlated with glyoxylate‐induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism. [ABSTRACT FROM AUTHOR]

The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analyzing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry and hydrophilic interaction liquid chromatography mass spectrometry that are based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram and echocardiograph monitoring of cardiac function and pathological examination were performed on mice in both the control and VN groups, and it was verified that acute heart injury was caused. Meanwhile, comparing the results of the control and VN groups, we detected 36 differential endogenous metabolites of heart tissue, including taurine, riboflavin, purine and lipids, which are related to many possible pathways such as purine metabolism, taurine and hypotaurine metabolism and energy metabolism. Our study provides a scientific approach for evaluating and revealing the mechanisms of VN-induced cardiotoxicity via the metabolomic strategy. [ABSTRACT FROM AUTHOR]

The slope erosion in the distribution area of completely weathered granite is often relatively severe, causing serious ecological damage and property loss. Ecological restoration is the most effective means of soil erosion control. Taking completely weathered granite backfill soil as the research object, two types of slope protection plants, Vetiver grass and Pennisetum hydridum, were selected. We analyzed these two herbaceous plants' soil reinforcement and slope protection effects through artificial planting experiments, indoor simulated rainfall experiments, and direct shear tests. The test results showed that the runoff and sediment production rates of the two herbaceous plant slopes were significantly lower than those of the bare slope, with the order of bare slope > Vetiver grass slope > Pennisetum hydridum slope. Compared with the bare slope, the cumulative sediment production of the Vetiver grass slope at 60 min decreased by 56.73–60.09%, and the Pennisetum hydridum slope decreased by 75.97–78.45%. The indoor direct shear test results showed that soil cohesion decreases with increasing water content. As the root content of Vetiver grass roots increases, soil cohesion first increases and then decreases, reaching a maximum value when the root content is 1.44%. As the root content of Pennisetum hydridum increases, soil cohesion increases. The internal friction angle increases slightly with increasing water content, while the root content does not significantly affect the internal friction angle. Therefore, the shear strength of soil decreases when the water content increases. The shear strength of the Vetiver grass root-soil composite reaches a peak at a root content of 1.44%, while the shear strength of the giant king grass root-soil composite increases as the root content increases. At the same root content, the shear strength of the Vetiver grass root-soil composite is slightly higher than that of giant king grass. The reinforcement effect of roots on shallow soil is better than on deep soil. Both herbaceous plants have an excellent soil-fixing and slope-protecting impact on the fully weathered granite backfill slope. Pennisetum hydridum's soil and water conservation effect is significantly better than that of the Vetiver grass. In contrast, Vetiver grass roots slightly outperform Pennisetum hydridum in enhancing the shear strength of the soil. The research results can provide a theoretical basis for the vegetation slope protection treatment of fully weathered granite backfill slopes. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Computer Engineering & Applications is the property of Beijing Journal of Computer Engineering & Applications Journal Co Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Pharmaceutial Care & Research is the property of Editorial Board of Pharmaceutial Care & Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To protect themselves against the invasion of microorganisms, amphibians, especially the Rana frogs, are possibly equipped with complex combinations of antimicrobial peptides (AMPs). The two major AMP families, ranid skin secretion AMPs and cathelicidins might together constitute the host innate immune system of amphibians. Cathelicidins are a group of cationic peptides found in leukocytes and epithelial cells, and they play a central role in the early innate immune defense found in virtually all species of mammals. However, they have rarely been reported from amphibians. Here, we report the identification and discovery of polymorphism cathelicidins in Limnonectes fragilis. The expression profile indicated high cathelicidin transcript levels in frog spleen, liver and kidney, but lower levels in lung, skin and stomach. According to the amphibian's unique proteolytic pattern, R125 and L121 of the prepropeptides are predicted to be the processing positions for protease to generate the mature peptides, Lf-CATH1 and -2, respectively. Both consist of 30 amino acid residues, of which two were cysteines positionally conserved among a few known amphibian cathelicidins. Homology modeling analysis revealed that Lf-CATH1 and -2 adopt a tertiary structure with a mostly α helix that is representative of small cationic cathelicidin family peptides. Recombinant Lf-CATH1 ( rLf-CATH1) was produced in Escherichia coli. Synthetic Lf-CATH1 and -2 displayed potent antimicrobial activities in vitro against a broad spectrum of microorganisms, including standard and clinically isolated drug-resistant strains, while showing neglectable hemolysis and cytotoxicities. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type (Asic3+/+) but not Asic3-knockout (Asic3−/−) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in 1H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3+/+ mice were taurine and hypotaurine, cysteine and methionine, glycerophospholipid, and ascorbate and aldarate metabolisms, and the major pathways in Asic3−/− mice involved amino acid-related metabolism. Finally, we developed an algorithm for the impactful metabolites in the FM model including cis-aconitate, kynurenate, taurine, pyroglutamic acid, pyrrolidonecarboxylic acid, and 4-methoxyphenylacetic acid in urine as well as carnitine, deoxycholic acid, lysoPC(16:0), lysoPC(20:3), oleoyl-L-carnitine, and trimethylamine N-oxide in serum. Asic3−/− mice were impaired in only muscle allodynia development but not other pain symptoms in the ICS model, so the ASIC3-dependent metabolomics changes could be useful for developing diagnostic biomarkers specific to chronic widespread muscle pain, the core symptom of FM. Further pharmacological validations are needed to validate these metabolomics changes as potential biomarkers for FM diagnosis and/or treatment responses. [ABSTRACT FROM AUTHOR]