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International Journal of Molecular... Apr 2024With genetic information gained from next-generation sequencing (NGS) and genome-wide association studies (GWAS), it is now possible to select for genes that encode... (Review)
Review
With genetic information gained from next-generation sequencing (NGS) and genome-wide association studies (GWAS), it is now possible to select for genes that encode reporter molecules that may be used to detect abnormalities such as alcohol-related liver disease (ARLD), cancer, cognitive impairment, multiple sclerosis (MS), diabesity, and ischemic stroke (IS). This, however, requires a thorough understanding of the gut-brain axis (GBA), the effect diets have on the selection of gut microbiota, conditions that influence the expression of microbial genes, and human physiology. Bacterial metabolites such as short-chain fatty acids (SCFAs) play a major role in gut homeostasis, maintain intestinal epithelial cells (IECs), and regulate the immune system, neurological, and endocrine functions. Changes in butyrate levels may serve as an early warning of colon cancer. Other cancer-reporting molecules are colibactin, a genotoxin produced by polyketide synthetase-positive strains, and spermine oxidase (SMO). Increased butyrate levels are also associated with inflammation and impaired cognition. Dysbiosis may lead to increased production of oxidized low-density lipoproteins (OX-LDLs), known to restrict blood vessels and cause hypertension. Sudden changes in SCFA levels may also serve as a warning of IS. Early signs of ARLD may be detected by an increase in regenerating islet-derived 3 gamma (REG3G), which is associated with changes in the secretion of mucin-2 (Muc2). Pro-inflammatory molecules such as cytokines, interferons, and TNF may serve as early reporters of MS. Other examples of microbial enzymes and metabolites that may be used as reporters in the early detection of life-threatening diseases are reviewed.
Topics: Humans; Gastrointestinal Microbiome; Brain-Gut Axis; Animals; Genome-Wide Association Study; Bacteria
PubMed: 38674014
DOI: 10.3390/ijms25084431 -
International Journal of Molecular... Apr 2024This study investigated the effect of polycationic and uncharged polymers (and oligomers) on the catalytic parameters and thermostability of L-asparaginase from (TsA)....
This study investigated the effect of polycationic and uncharged polymers (and oligomers) on the catalytic parameters and thermostability of L-asparaginase from (TsA). This enzyme has potential applications in the food industry to decrease the formation of carcinogenic acrylamide during the processing of carbohydrate-containing products. Conjugation with the polyamines polyethylenimine and spermine (PEI and Spm) or polyethylene glycol (PEG) did not significantly affect the secondary structure of the enzyme. PEG contributes to the stabilization of the dimeric form of TsA, as shown by HPLC. Furthermore, neither polyamines nor PEG significantly affected the binding of the L-Asn substrate to TsA. The conjugates showed greater maximum activity at pH 7.5 and 85 °C, 10-50% more than for native TsA. The pH optima for both TsA-PEI and TsA-Spm conjugates were shifted to lower pH ranges from pH 10 (for the native enzyme) to pH 8.0. Additionally, the TsA-Spm conjugate exhibited the highest activity at pH 6.5-9.0 among all the samples. Furthermore, the temperature optimum for activity at pH 7.5 shifted from 90-95 °C to 80-85 °C for the conjugates. The thermal inactivation mechanism of TsA-PEG appeared to change, and no aggregation was observed in contrast to that of the native enzyme. This was visually confirmed and supported by the analysis of the CD spectra, which remained almost unchanged after heating the conjugate solution. These results suggest that TsA-PEG may be a more stable form of TsA, making it a potentially more suitable option for industrial use.
Topics: Asparaginase; Thermococcus; Hydrogen-Ion Concentration; Enzyme Stability; Biocatalysis; Polyethylene Glycols; Temperature; Archaeal Proteins
PubMed: 38673759
DOI: 10.3390/ijms25084174 -
DAB-APT: a Fluorescence-Based Assay for Determining Aminopropyl Transferase Activity and Inhibition.BioRxiv : the Preprint Server For... Apr 2024Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs),...
Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), promising targets in antimicrobial, antineoplastic and antineurodegenerative therapies. A major limitation, however, is the lack of high-throughput assays to measure their activity. We developed the first fluorescence-based assay, DAB-APT, for measurement of APT activity using 1,2-diacetyl benzene, which forms fluorescent conjugates with putrescine, spermidine and spermine with fluorescence intensity increasing with increasing carbon chain length. The assay has been validated using APT enzymes from and and is suitable for high-throughput screening of large chemical libraries. Given the importance of APTs in infectious diseases, cancer and neurobiology, our DAB-APT assay has broad applications, holding promise for advancing research and drug discovery efforts.
PubMed: 38645036
DOI: 10.1101/2024.04.09.588734 -
Food Science & Nutrition Apr 2024This study aimed at investigating the quality attributes of Turkish fermented sausage (sucuk) incorporated with bay leaf extract obtained as a natural antioxidant and a...
This study aimed at investigating the quality attributes of Turkish fermented sausage (sucuk) incorporated with bay leaf extract obtained as a natural antioxidant and a source of phytochemicals. Five different bay leaf extracts were obtained with distilled water and 60%, 70%, 80%, and 90% ethanol. The total phenolic contents and antioxidant activity values indicated that ultrasound-assisted 70% ethanol extract was the most suitable extract. Furthermore, five groups of sucuks were manufactured with the addition of bay leaf extract (1, 5, and 10 mL/kg), ascorbic acid (500 mg/kg), and control. The extracts were produced similar pH values when compared to control and ascorbic acid samples. The treatments had no significant effect on moisture contents of sucuks. Bay leaf extracts produced comparable color, texture profile analysis, and TBARS values to control and ascorbic acid samples. Biogenic amine contents (mg/kg dry weight) of sucuks including tryptamine (6.43-30.66), 2-phenylethylamine (2.24-32.04), putrescine (2.19-7.98), cadaverine (3.28-12.21), histamine (7.01-11.38), tyramine (3.27-71.07), spermidine (4.44-8.01), and spermine (53.96-68.25) were mostly within the lower ranges typically associated with sucuk. However, the lowest cadaverine values observed at the end of storage in the bay leaf extract added samples indicated that bay leaf extract might be effective in decreasing cadaverine values during storage. The addition of bay leaf extract caused similar sensory attributes to the control and ascorbic acid samples. This study revealed that Turkish fermented sucuks could be effectively incorporated with bay leaf extracts without a negative effect on the quality attributes or consumer acceptability.
PubMed: 38628223
DOI: 10.1002/fsn3.3929 -
Food Chemistry: X Jun 2024The mitochondrial calcium uniporter (MCU) occupies a noteworthy position in the regulation of mitochondrial calcium uptake. This study investigated the effects of MCU...
The mitochondrial calcium uniporter (MCU) occupies a noteworthy position in the regulation of mitochondrial calcium uptake. This study investigated the effects of MCU modulator-mediated mitochondrial calcium on mitochondrial dysfunction, oxidative stress, endogenous enzyme activities, and tenderness during postmortem aging. Spermine, as an activator of MCU, resulted in an increase in mitochondrial calcium levels, not only disrupting mitochondrial morphology but also triggering mitochondrial oxidative stress and downregulation of antioxidant factors. Additionally, the spermine group underwent later activation of calpain and earlier activation of caspases, as well as the myofibril fragmentation index was initially lower and then higher compared with control group, indicating that endogenous enzymes played an indispensable role in different aging periods. Interestingly, the results of the Ru360 (an inhibitor of MCU) group were opposite to those aforementioned findings. Our data provide a novel perspective on the regulatory mechanism of mitochondrial calcium homeostasis mediated by MCU on tenderness.
PubMed: 38623508
DOI: 10.1016/j.fochx.2024.101366 -
International Journal of Nanomedicine 2024Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral...
BACKGROUND
Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral bioavailability of active compounds has not been elucidated. Using Xie-Bai-San decoction (XBSD) as an example, the purpose of this study was to isolate, characterize and elucidate the mechanism of the nanoparticles (N-XBSD) in XBSD, and further to explore whether the bioavailability of the main active compounds could be enhanced by N-XBSD.
METHODS
N-XBSD were isolated from XBSD, and investigated its characterization and study of its formation mechanism, and evaluation of its ability to enhance bioavailability of active compounds.
RESULTS
The N-XBSD was successfully isolated with the average particle size of 104.53 nm, PDI of 0.27 and zeta potential of -5.14 mV. Meanwhile, all the eight active compounds were most presented in N-XBSD. Kukoamine B could self-assemble with mulberroside A or liquiritin to form nanoparticles, respectively. And the FT-IR and HRMS results indicated the possible binding of the ammonium group of kukoamine B with the phenolic hydroxyl group of mulberroside A or liquiritin, respectively. The established UPLC-MS/MS method was accurate and reliable and met the quantitative requirements. The pharmacokinetic behaviors of the N-XBSD and decoction were similar in rats. Most notably, compared to that of free drugs, the , AUC, AUC, and MRT values of index compounds were the higher in N-XBSD, with a slower plasma clearance rate in rats.
CONCLUSION
The major active compounds of XBSD were mainly distributed in N-XBSD, and N-XBSD was formed through self-assembly among active compounds. N-XBSD could obviously promote the bioavailability of active compounds, indicating natural nanoparticles of decoctions play an important role in therapeutic effects.
Topics: Animals; Rats; Biological Availability; Chromatography, Liquid; Spectroscopy, Fourier Transform Infrared; Tandem Mass Spectrometry; Nanoparticles; Caffeic Acids; Disaccharides; Spermine; Stilbenes
PubMed: 38617795
DOI: 10.2147/IJN.S449268 -
International Journal of Medical... 2024Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer....
Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.
Topics: Humans; Polyamines; Spermidine; Spermine; Apoptosis; Biological Products; Colorectal Neoplasms; Quercetin
PubMed: 38617002
DOI: 10.7150/ijms.93903 -
International Journal of Molecular... Apr 2024D-arginine (D-Arg) can promote embryogenic callus (EC) proliferation and increase the rate of somatic embryo induction of litchi ( Sonn.), yet the mechanism underlying...
Physiological, Metabolic, and Transcriptomic Analyses Reveal Mechanisms of Proliferation and Somatic Embryogenesis of Litchi ( Sonn.) Embryogenic Callus Promoted by D-Arginine Treatment.
D-arginine (D-Arg) can promote embryogenic callus (EC) proliferation and increase the rate of somatic embryo induction of litchi ( Sonn.), yet the mechanism underlying the processes is incompletely understood. To investigate the mechanism, physiological responses of polyamines (PAs) [putrescine (Put), spermidine (Spd), and spermine (Spm)] were investigated for D-Arg-treated litchi EC and enzyme activity related to polyamine metabolism, plant endogenous hormones, and polyamine- and embryogenic-related genes were explored. Results showed that the exogenous addition of D-Arg reduces the activity of diamine oxidase (DAO) and polyamine oxidase (PAO) in EC, reduces the production of HO, promotes EC proliferation, and increases the (Spd + Spm)/Put ratio to promote somatic embryo induction. Exogenous D-Arg application promoted somatic embryogenesis (SE) by increasing indole-3-acetyl glycine (IAA-Gly), kinetin-9-glucoside (K9G), and dihydrozeatin-7-glucoside (DHZ7G) levels and decreasing trans-zeatin riboside (tZR), N-[(-)-jasmonoyl]-(L)-valine (JA-Val), jasmonic acid (JA), and jasmonoyl-L-isoleucine (Ja-ILE) levels on 18 d, as well as promoting cell division and differentiation. The application of exogenous D-Arg regulated EC proliferation and somatic embryo induction by altering gene expression levels of the WRKY family, AP2/ERF family, C3H family, and C2H2 family. These results indicate that exogenous D-Arg could regulate the proliferation of EC and the SE induction of litchi by changing the biosynthesis of PAs through the alteration of gene expression pattern and endogenous hormone metabolism.
Topics: Litchi; Hydrogen Peroxide; Embryonic Development; Polyamines; Spermidine; Putrescine; Spermine; Arginine; Cell Division; Glucosides; Cyclopentanes; Isoleucine; Oxylipins
PubMed: 38612774
DOI: 10.3390/ijms25073965 -
Foods (Basel, Switzerland) Mar 2024A new chitosan-based protective film containing rosemarinic acid (0.282% /) has been elaborated. The film was formed from a water-oil emulsion system and applied to...
A new chitosan-based protective film containing rosemarinic acid (0.282% /) has been elaborated. The film was formed from a water-oil emulsion system and applied to poultry meat samples using a dip-coating technique. Various physicochemical parameters of the coatings, such as thickness, Young's modulus, elongation at break, water vapor transmission rates, and antioxidant activity, were tested with free-standing film samples peeled from a Petri dish. Compared to neat chitosan films obtained similarly, new films cast from the emulsion showed significantly better elasticity (Young's modulus was diminished from 1458 MPa to about 29 MPa). Additionally, barrier properties for moisture transition decreased from 7.3 to 5.8 g mm m day kPa. The coated poultry samples were subsequently evaluated in juxtaposition with uncoated ones in a storage test. Levels of selected biogenic amines (histamine, tyramine, tryptamine, phenylethylamine, putrescine, cadaverine, spermine, and spermidine), total bacterial count, and lipid oxidation levels in the meat samples were analyzed during storage at 4 °C (up to 96 h). The results obtained for the biogenic amines, total bacterial content, calculated biogenic amine index, and the ratio of spermidine to spermine in meat samples suggest the advantage of the proposed coatings with rosmarinic acid in protecting poultry meat against environmental factors and rapid spoilage.
PubMed: 38611289
DOI: 10.3390/foods13070985 -
Journal of Medicinal Chemistry Apr 2024Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant...
Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to PdSpermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/resistance mechanisms and (ii) the potential cytotoxic role of PdSpm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites. CDDP-exposed S cells experienced enhanced antioxidant protection and small deviations in the tricarboxylic acid cycle (TCA), pyrimidine metabolism, and lipid oxidation (proposed cytotoxicity signature). R cells responded more strongly to cDDP, suggesting a resistance signature of activated TCA cycle, altered AMP/ADP/ATP and adenine/uracil fingerprints, and phospholipid biosynthesis (without significant antioxidant protection). PdSpm impacted more markedly on R/S cell metabolisms, inducing similarities to cDDP/S cells (probably reflecting high cytotoxicity) and strong additional effects indicative of amino acid depletion, membrane degradation, energy/nucleotide adaptations, and a possible beneficial intracellular γ-aminobutyrate/glutathione-mediated antioxidant mechanism.
Topics: Humans; Triple Negative Breast Neoplasms; Cisplatin; Drug Resistance, Neoplasm; Antineoplastic Agents; Cell Line, Tumor; Female; Spermine; Palladium
PubMed: 38590144
DOI: 10.1021/acs.jmedchem.4c00435