-
Frontiers in Cellular and Infection... 2024Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic...
INTRODUCTION
Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs.
METHODS
This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts.
RESULTS
Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against , with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of . Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect.
DISCUSSION
In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.
Topics: Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Metal-Organic Frameworks; Drugs, Chinese Herbal; Staphylococcus aureus; Drug Synergism; Powders; Humans; Chromatography, Liquid
PubMed: 38912207
DOI: 10.3389/fcimb.2024.1376312 -
MedComm Jul 2024Cancer is increasingly acknowledged as a metabolic disease, characterized by metabolic reprogramming as its hallmark. However, the precise mechanisms behind this...
Cancer is increasingly acknowledged as a metabolic disease, characterized by metabolic reprogramming as its hallmark. However, the precise mechanisms behind this phenomenon and the factors contributing to tumorigenicity are still poorly understood. In a recent publication in , Mossmann and colleague reported a study unveiling arginine as a molecule with second messenger-like properties that reshapes metabolism to facilitate the tumor development in hepatocellular carcinoma (HCC). Their research revealed that the RNA-binding motif protein 39 (RBM39)-mediated increase in asparagine synthesis results in increased arginine uptake. This establishes a positive feedback loop that sustains elevated levels of arginine and facilitates oncogenic metabolic reprogramming. Additionally, Mossmann et al. demonstrated that depleting RBM39 with indisulam effectively disrupts the proto-oncogenic metabolic reprogramming in HCC. This discovery presents a novel treatment strategy for arginine-dependent liver cancers.
PubMed: 38903537
DOI: 10.1002/mco2.581 -
Frontiers in Plant Science 2024The development and commercialisation of sunflower varieties tolerant to acetolactate synthase (ALS)-inhibiting herbicides some 20 years ago provided farmers with an...
The development and commercialisation of sunflower varieties tolerant to acetolactate synthase (ALS)-inhibiting herbicides some 20 years ago provided farmers with an alternative method for the cost-effective control of . In 2020, however, two independent sunflower broomrape populations from Drama (GR-DRA) and Orestiada (GR-ORE), Greece, were reported to be heavily infested with after application of the ALS-inhibiting herbicide imazamox. Here we have investigated the race of GR-DRA and GR-ORE and determined the basis of resistance to imazamox in the two Greek samples. Using a set of five diagnostic sunflower varieties characterised by different resistant genes with respect to infestation, we have clearly established that the GR-ORE and GR-DRA populations belong to the invasive broomrape races G and G+, respectively. Live underground tubercles and emerged shoots were identified at the recommended field rate of imazamox for GR-DRA and GR-ORE but not for two other standard sensitive populations in a whole plant dose response test using two different herbicide-tolerant sunflower hybrids as hosts. Sequencing of the ALS gene identified an alanine 205 to aspartate mutation in all GR-ORE samples. Most GR-DRA tubercles were characterised by a second serine 653 to asparagine ALS mutation whilst a few GR-DRA individuals contained the A205D mutation. Mutations at ALS codons 205 and 653 are known to impact on the binding and efficacy of imazamox and other imidazolinone herbicides. The knowledge generated here will be important for tracking and managing broomrape resistance to ALS-inhibiting herbicides in sunflower growing regions.
PubMed: 38895610
DOI: 10.3389/fpls.2024.1420009 -
Nutrients May 2024Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been...
Mediterranean Diet Combined with Regular Aerobic Exercise and Hemp Protein Supplementation Modulates Plasma Circulating Amino Acids and Improves the Health Status of Overweight Individuals.
Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO's recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired -test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (-54.0%), and TAG levels (-49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome.
Topics: Humans; Diet, Mediterranean; Male; Amino Acids; Dietary Supplements; Female; Exercise; Middle Aged; Adult; Overweight; Health Status; Cannabis; Metabolic Syndrome; Plant Proteins
PubMed: 38892526
DOI: 10.3390/nu16111594 -
Human Genomics Jun 2024Sex-related differences in colorectal (CRC) incidence and mortality are well-documented. However, the impact of sex on metabolic pathways that drive cancer growth is not...
BACKGROUND
Sex-related differences in colorectal (CRC) incidence and mortality are well-documented. However, the impact of sex on metabolic pathways that drive cancer growth is not well understood. High expression of asparagine synthetase (ASNS) is associated with inferior survival for female CRC patients only. Here, we used a CRISPR/Cas9 technology to generate HCT116 ASNS and HCT 116 ASNS cancer cell lines. We examine the effects of ASNS deletion on tumor growth and the subsequent rewiring of metabolic pathways in male and female Rag2/IL2RG mice.
RESULTS
ASNS loss reduces cancer burden in male and female tumor-bearing mice (40% reduction, q < 0.05), triggers metabolic reprogramming including gluconeogenesis, but confers a survival improvement (30 days median survival, q < 0.05) in female tumor-bearing mice alone. Transcriptomic analyses revealed upregulation of G-protein coupled estrogen receptor (GPER1) in tumors from male and female mice with HCT116 ASNS xenograft. Estradiol activates GPER1 in vitro in the presence of ASNS and suppresses tumor growth.
CONCLUSIONS
Our study indicates that inferior survival for female CRC patients with high ASNS may be due to metabolic reprogramming that sustains tumor growth. These findings have translational relevance as ASNS/GPER1 signaling could be a future therapeutic target to improve the survival of female CRC patients.
Topics: Animals; Humans; Female; Male; Mice; Aspartate-Ammonia Ligase; HCT116 Cells; Colorectal Neoplasms; Receptors, Estrogen; Cell Proliferation; Receptors, G-Protein-Coupled; Gene Expression Regulation, Neoplastic; Xenograft Model Antitumor Assays; Heterografts; Sex Factors; Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor
PubMed: 38886847
DOI: 10.1186/s40246-024-00635-3 -
Nature Communications Jun 2024The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are...
The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face of the ER, generating Man5GlcNAc2-PP-Dol (M5GN2-PP-Dol). M5GN2-PP-Dol is then flipped across the bilayer into the lumen by an ER translocator. Genetic studies identified Rft1 as the M5GN2-PP-Dol flippase in vivo but are at odds with biochemical data suggesting Rft1 is dispensable for flipping in vitro. Thus, the question of whether Rft1 plays a direct or an indirect role during M5GN2-PP-Dol translocation has been controversial for over two decades. We describe a completely reconstituted in vitro assay for M5GN2-PP-Dol translocation and demonstrate that purified Rft1 catalyzes the translocation of M5GN2-PP-Dol across the lipid bilayer. These data, combined with in vitro results demonstrating substrate selectivity and rft1∆ phenotypes, confirm the molecular identity of Rft1 as the M5GN2-PP-Dol ER flippase.
Topics: Endoplasmic Reticulum; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae; Biological Transport; Oligosaccharides; Dolichol Phosphates; Lipid Bilayers; Phospholipid Transfer Proteins; Intracellular Membranes; Lipopolysaccharides
PubMed: 38886340
DOI: 10.1038/s41467-024-48999-3 -
The Journal of Biological Chemistry Jun 2024Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np),...
Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np), a type-1 transmembrane glycoprotein, display deafness, multiple cognitive deficiencies, and reduced expression of plasma membrane calcium (Ca) ATPases (PMCAs) in cochlear hair cells and brain neurons. In this study, we transferred the deafness causing missense mutations pitch (C315S) and audio-1 (I122N) into human Np (hNp) constructs and investigated their effects at the molecular and cellular level. Computational molecular dynamics show that loss of the disulfide bridge in hNp causes structural destabilization of immunoglobulin-like domain (Ig) III and that the novel asparagine in hNp results in steric constraints and an additional N-glycosylation site in IgII. Additional N-glycosylation of hNp was confirmed by PNGaseF treatment. In comparison to hNp, transfection of hNp and hNp into HEK293T cells resulted in normal mRNA levels but reduced the Np protein levels and their cell surface expression due to proteasomal/lysosomal degradation. Furthermore, hNp and hNp failed to promote exogenous PMCA levels in HEK293T cells. In hippocampal neurons, expression of additional hNp or hNp was less efficient than hNp to elevate endogenous PMCA levels and to accelerate the restoration of basal Ca levels after electrically-evoked Ca transients. We propose that mutations leading to pathological Np variants, as exemplified here by the deafness causing Np mutants, can affect Np-dependent Ca regulatory mechanisms and may potentially cause intellectual and cognitive deficits in humans.
PubMed: 38879011
DOI: 10.1016/j.jbc.2024.107474 -
Heliyon Jun 2024Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a...
Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a crispy texture. Frying potato slices initiates the Maillard reaction, resulting in chemical changes that enhance taste, color, and texture, but also undesired acrylamides, which are suspected carcinogens. The application of pulsed electric field (PEF) technology is commonly used in French fry processing operations to prolong cutting blade sharpness and reduce waste, energy consumption, and water usage. Despite these attributes, PEF systems have not yet gained widespread adoption by potato chip producers. In the current study, Lamoka potatoes were PEF-treated prior to continuous frying into potato chips. The effect of specific energy at 0.75 kJ/kg (Low-PEF) and 1.5 kJ/kg (High-PEF) and electric field strength of 1 kV/cm, frequency of 24 kV, and pulse width of 6 μs versus untreated (control) samples was studied, then batches of 250 g of slices were fried at 170 °C or 185 °C for two frying times to obtain potato chips with acrylamide levels below the California Proposition 65 limit (275 ng/g). The Lamoka potato chip product quality metrics that were assessed include moisture, fat, reducing sugars, asparagine, acrylamide, chip color, and texture. PEF treatment of Lamoka potatoes resulted in chips fried in 10 % less time, lower oil content by 8 %, and a decrease of reducing sugars by 19.2 %, asparagine by 42.0 %, and acrylamide by 28.9 %. The PEF fried chips were lighter in color but maintained textural attributes compared to continuous frying cooking. The process of frying potato slices at 170 °C for 150 s with High-PEF yielded potato chips with acrylamide content below the California Proposition 65 limit; which speaks to the health implications for consumers and the quality and safety of these chips.
PubMed: 38873662
DOI: 10.1016/j.heliyon.2024.e31790 -
The Journal of Physical Chemistry. B Jun 2024Particulate MMO (pMMO) catalyzes the oxidation of methane to methanol and also ammonia to hydroxylamine. Experimental characterization of the active site has been very...
Particulate MMO (pMMO) catalyzes the oxidation of methane to methanol and also ammonia to hydroxylamine. Experimental characterization of the active site has been very difficult partly because the enzyme is membrane-bound. However, recently, there has been major progress mainly through the use of cryogenic electron microscopy (cryoEM). Electron paramagnetic resonance (EPR) and X-ray spectroscopy have also been employed. Surprisingly, the active site has only one copper. There are two histidine ligands and one asparagine ligand, and the active site is surrounded by phenyl alanines but no charged amino acids in the close surrounding. The present study is the first quantum chemical study using a model of that active site (Cu). Low barrier mechanisms have been found, where an important part is that there are two initial proton-coupled electron transfer steps to a bound O ligand before the substrate enters. Surprisingly, this leads to large radical character for the oxygens even though they are protonated. That result is very important for the ability to accept a proton from the substrates. Methods have been used which have been thoroughly tested for redox enzyme mechanisms.
Topics: Oxidation-Reduction; Methane; Oxygenases; Ammonia; Catalytic Domain; Models, Molecular; Electron Spin Resonance Spectroscopy
PubMed: 38850249
DOI: 10.1021/acs.jpcb.4c01807 -
Amino Acids Jun 2024Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often...
Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma D-asparagine and the D/L-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma D-asparagine and the D/L-serine ratio, but dexamethasone treatment did not. Thus, plasma D-asparagine and the D/L-serine ratio can be useful markers for renal function in children.
Topics: Child; Animals; Humans; Asparagine; Renal Insufficiency, Chronic; Child, Preschool; Serine; Mice; Male; Female; Adolescent; Biomarkers; Prospective Studies; Dexamethasone; Stereoisomerism; Creatinine; Kidney
PubMed: 38844708
DOI: 10.1007/s00726-024-03400-x