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Food Chemistry May 2024Manuka honey (MH) is a highly prized natural product from the nectar of Leptospermum scoparium flowers. Increased competition on the global market drives MH product... (Review)
Review
Manuka honey (MH) is a highly prized natural product from the nectar of Leptospermum scoparium flowers. Increased competition on the global market drives MH product innovations. This review updates comparative and non-comparative studies to highlight nutritional, therapeutic, bioengineering, and cosmetic values of MH. MH is a good source of phenolics and unique chemical compounds, such as methylglyoxal, dihydroxyacetone, leptosperin glyoxal, methylsyringate and leptosin. Based on the evidence from in vitro, in vivo and clinical studies, multifunctional bioactive compounds of MH have exhibited anti-oxidative, anti-inflammatory, immunomodulatory, anti-microbial, and anti-cancer activities. There are controversial topics related to MH, such as MH grading, safety/efficacy, implied benefits, and maximum levels of contaminants concerned. Artificial intelligence can optimize MH studies related to chemical analysis, toxicity prediction, multi-functional mechanism exploration and product innovation.
Topics: Honey; Artificial Intelligence; Plant Nectar; Flowers; Pyruvaldehyde; Leptospermum
PubMed: 38211407
DOI: 10.1016/j.foodchem.2023.138060 -
Infection and Immunity Feb 2024is a leading cause of medical device-associated biofilm infections. This is influenced by the ability of biofilm to evade the host immune response, which is partially...
is a leading cause of medical device-associated biofilm infections. This is influenced by the ability of biofilm to evade the host immune response, which is partially driven by the anti-inflammatory cytokine interleukin-10 (IL-10). Here, we show that treatment of human monocyte-derived macrophages (HMDMs) with IL-10 enhanced biofilm formation, suggesting that macrophage anti-inflammatory programming likely plays an important role during the transition from planktonic to biofilm growth. To identify genes that were important for intracellular survival in HMDMs and how this was affected by IL-10, transposon sequencing was performed. The size of the essential genome was similar between unstimulated HMDMs and the outgrowth control (18.5% vs 18.4%, respectively, with 54.4% overlap) but increased to 22.5% in IL-10-treated macrophages, suggesting that macrophage polarization status exerts differential pressure on . Essential genes for survival within IL-10-polarized HMDMs were dominated by negative regulatory pathways, including nitrogen and RNA metabolism, whereas essential genes within untreated HMDMs were enriched in biosynthetic pathways such as purine and pyrimidine biosynthesis. To explore how IL-10 altered the macrophage intracellular metabolome, targeted metabolomics was performed on HMDMs from six individual donors. IL-10 treatment led to conserved alterations in distinct metabolites that were increased (dihydroxyacetone phosphate, glyceraldehyde-3-phosphate, and acetyl-CoA) or reduced (fructose-6-phosphate, aspartic acid, and ornithine) across donors, whereas other metabolites were variable. Collectively, these findings highlight an important aspect of population-level heterogeneity in human macrophage responsiveness that should be considered when translating results to a patient population.IMPORTANCEOne mechanism that biofilm elicits in the host to facilitate infection persistence is the production of the anti-inflammatory cytokine interleukin-10 (IL-10). Here, we show that exposure of human monocyte-derived macrophages (HMDMs) to IL-10 promotes biofilm formation and programs intracellular bacteria to favor catabolic pathways. Examination of intracellular metabolites in HMDMs revealed heterogeneity between donors that may explain the observed variability in essential genes for survival based on nutrient availability for bacteria within the intracellular compartment. Collectively, these studies provide novel insights into how IL-10 polarization affects intracellular survival in HMDMs and the importance of considering macrophage heterogeneity between human donors as a variable when examining effector mechanisms.
Topics: Humans; Interleukin-10; Staphylococcus aureus; Macrophages; Cytokines; Anti-Inflammatory Agents; Staphylococcal Infections; Biofilms
PubMed: 38179975
DOI: 10.1128/iai.00474-23 -
Nature Communications Dec 2023One-carbon (C1) substrates, such as methanol or formate, are attractive feedstocks for circular bioeconomy. These substrates are typically converted into formaldehyde,...
One-carbon (C1) substrates, such as methanol or formate, are attractive feedstocks for circular bioeconomy. These substrates are typically converted into formaldehyde, serving as the entry point into metabolism. Here, we design an erythrulose monophosphate (EuMP) cycle for formaldehyde assimilation, leveraging a promiscuous dihydroxyacetone phosphate dependent aldolase as key enzyme. In silico modeling reveals that the cycle is highly energy-efficient, holding the potential for high bioproduct yields. Dissecting the EuMP into four modules, we use a stepwise strategy to demonstrate in vivo feasibility of the modules in E. coli sensor strains with sarcosine as formaldehyde source. From adaptive laboratory evolution for module integration, we identify key mutations enabling the accommodation of the EuMP reactions with endogenous metabolism. Overall, our study demonstrates the proof-of-concept for a highly efficient, new-to-nature formaldehyde assimilation pathway, opening a way for the development of a methylotrophic platform for a C1-fueled bioeconomy in the future.
Topics: Escherichia coli; Methanol; Formaldehyde; Sarcosine; Fructose-Bisphosphate Aldolase; Metabolic Engineering
PubMed: 38123535
DOI: 10.1038/s41467-023-44247-2 -
Scientific Reports Dec 2023Nowadays, dealing with the growing chemical and energy demands is important without compromising the environment. So, this work studies photocatalytic glycerol...
Nowadays, dealing with the growing chemical and energy demands is important without compromising the environment. So, this work studies photocatalytic glycerol conversion (as biomass derivativ feedstock) into value-added products using an eco-friendly synthesized catalyst. Graphene quantum dots (GQDs) were prepared from available/cheap precursors like glucose via the hydrothermal method and used as a support for TiO. TiO/GQDs were characterized via different analytical techniques, revealing very small particle sizes of ~ 3-6 nm with a large surface area of ~ 253 m/g and a band gap of ~ 2.6 eV. The prepared photocatalyst shows good efficiency during photocatalytic glycerol conversion to dihydroxyacetone (DHA). Different reaction conditions were tested: reaction time, catalyst amount, presence of oxidant (HO), and biphasic media (aqueous/organic phases). Comparing a monophasic (HO) photoreactor with a biphasic reactor containing 90% organic phase (ethyl acetate) and 10% aqueous phase (HO and/or HO) indicates that the presence of HO increases glycerol conversion and liquid selectivity to reach 57% and 91%, respectively after 120 min. However, it still suffers a low DHA/GA ratio (2.7). On the other hand, using a biphasic reactor in the presence of an HO oxidant increases the DHA/GA ratio to ~ 6.6, which was not reached in previous research. The formation of HO/HO as micro-reactors dispersed in the ethyl acetate phase increased the average light intensity effect of the glycerol/photocatalyst system in the micro-reactors. Unlike previous work, this work presents a facile way to prepare eco-friendly/cheap (noble metal free) photocatalysts for glycerol conversion to ultrapure DHA using a biphasic photoreactor.
PubMed: 38071356
DOI: 10.1038/s41598-023-48781-3 -
Journal of Cellular and Molecular... Feb 2024Diabetic kidney disease (DKD) can lead to accumulation of glucose upstream metabolites due to dysfunctional glycolysis. But the effects of accumulated glycolysis...
Diabetic kidney disease (DKD) can lead to accumulation of glucose upstream metabolites due to dysfunctional glycolysis. But the effects of accumulated glycolysis metabolites on podocytes in DKD remain unknown. The present study examined the effect of dihydroxyacetone phosphate (DHAP) on high glucose induced podocyte pyroptosis. By metabolomics, levels of DHAP, GAP, glucose-6-phosphate and fructose 1, 6-bisphosphate were significantly increased in glomeruli of db/db mice. Furthermore, the expression of LDHA and PKM2 were decreased. mRNA sequencing showed upregulation of pyroptosis-related genes (Nlrp3, Casp1, etc.). Targeted metabolomics demonstrated higher level of DHAP in HG-treated podocytes. In vitro, ALDOB expression in HG-treated podocytes was significantly increased. siALDOB-transfected podocytes showed less DHAP level, mTORC1 activation, reactive oxygen species (ROS) production, and pyroptosis, while overexpression of ALDOB had opposite effects. Furthermore, GAP had no effect on mTORC1 activation, and mTORC1 inhibitor rapamycin alleviated ROS production and pyroptosis in HG-stimulated podocytes. Our findings demonstrate that DHAP represents a critical metabolic product for pyroptosis in HG-stimulated podocytes through regulation of mTORC1 pathway. In addition, the results provide evidence that podocyte injury in DKD may be treated by reducing DHAP.
Topics: Mice; Animals; Diabetic Nephropathies; Podocytes; Dihydroxyacetone Phosphate; Reactive Oxygen Species; Pyroptosis; Glucose; Mechanistic Target of Rapamycin Complex 1; Diabetes Mellitus
PubMed: 38063077
DOI: 10.1111/jcmm.18073 -
Heliyon Nov 2023Aluminum phosphide (AlP), known as "rice tablet," is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such...
BACKGROUND AND OBJECTIVES
Aluminum phosphide (AlP), known as "rice tablet," is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture or acid. Phosphine is a potent mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various and experimental models.
METHODS
Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning with poisons other than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n = 18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5 % DHA solution w/v, i.v.) as an adjuvant therapy in addition to the routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and hospitalization time were evaluated in DHA-treated and AlP-poisoned patients without DHA administration. Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K and Na), WBC, RBC, hemoglobin, INR, carbonate (HCO), blood pH, PaCO, and PaO and SGPT, SGOT, BUN, Cr.
RESULTS
Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO, and HCO levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients' survival rate (65.52 % in DHA-treated 33.34 % in the control group) compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.
INTERPRETATION AND CONCLUSIONS
These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning to be used as an adjuvant in addition to routine supportive treatment.
TRIAL REGISTRATION
IR.SUMS.REC.1394.102.
PubMed: 38053886
DOI: 10.1016/j.heliyon.2023.e22165 -
Cureus Oct 2023The skin, hair, and nails can all present with yellow discoloration secondary to exogenous etiologies. Xanthoderma, yellow discoloration of the skin, can occur not only...
The skin, hair, and nails can all present with yellow discoloration secondary to exogenous etiologies. Xanthoderma, yellow discoloration of the skin, can occur not only from exogenous sources secondary to topical contact with various substances but also from endogenous causes such as diseases from the liver and kidney, or oral medications. A 64-year-old man developed asymptomatic, yellow staining of his distal left forearm, hand, and fingertips. He was not receiving antimalarials, did not have hepatic or renal dysfunction, and had not applied any sunless tanning solutions to his skin. Prior to the appearance of his xanthoderma, he had been tending to a tomato plant in his yard; the yellow staining appeared on the areas of his left upper extremity that had contacted the stems and leaves of the tomato plant. Within two days, the yellow skin discoloration resolved spontaneously after several washings of the affected areas with soap and water. Tomato plants have trichomes that appear as hair-like structures on the stems and produce an oily substance; the trichomes not only produce the scent of the plant, but also provide protection from cold, drought, disease, and pests. Initially, when the oily substance contacts the skin, the skin appears yellow; subsequently, the skin may become black. The skin that has been stained by a tomato plant is referred to as "tomato skin" (TOMASK). In addition to reviewing the etiology of exogenous xanthoderma, this paper also summarizes the causes of exogenous yellow hair and yellow nails. Exogenous yellowing of the skin can result from various topical causes. Common topical etiologies of xanthoderma include not only contact with tomato plants, but also sunless tanning solutions (that contain dihydroxyacetone) and tobacco (that not only causes yellow staining of the white hair on men's upper lip referred to as "smoker's mustache", but also yellow staining of the nail plate and fingertips used to hold the cigarette or cigar). In summary, tomato plant-associated xanthoderma is a benign exogenous etiology of yellow staining of the skin which eventually resolves after several washings of the affected sites with soap and water.
PubMed: 38021483
DOI: 10.7759/cureus.47218 -
Journal of Traditional Chinese Medicine... Oct 2023To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor...
OBJECTIVE
To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor beta1 (TGF-β1)/Smads signaling pathway.
METHODS
One hundred rats were treated with saline [normal control (NC) group] or complete Freund's adjuvant (CFA) by right plantar injection for the RA model group, and the latter were randomly divided into 4 groups. Tripterygium wilfordii polyglycoside tablets (, TPT) have anti-inflammatory and are widely used in the clinical treatment of RA, therefore serving as a positive control group. Three days post injection rats were given TPT tablet (TPT group), acupuncture therapy (APT group), and moxibustion treatment (MOX group) for 15 consecutive days, while NC group and model group were equally grasped and fixed and received normal saline. Rat joint swelling scores and arthritis index (AI) were evaluated in each group before the CFA challenge, therapy and after receiving therapy. Myocardial ultrastructure was observed by electron microscope. Enzyme-linked immunosorbent assay was used to detect cardiac troponin I (cTnI) levels in rat myocardial tissue. Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-β signaling molecules including TGF-β1, Smad2, Smad3, Smad4, and Smad7. Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.
RESULTS
Compared with model group, RA model rats receiving TPT, acupuncture, or moxibustion therapy all showed reduced joint swelling scores and AI (all 0.01) and improved myocardial damage, whereas rats treated with moxibustion were found to be more marked. Consistently, the expressions of cTnI, TGF-β1, Smad2, Smad3, and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT, APT and MOX group when compared with model group, while the levels of Smad7 showed the opposite result (all 0.01). Moreover, the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate, dihydroxyacetone phosphate, arachidonic acid, etc was defined and implicated in amino acid, glucose, and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.
CONCLUSION
Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions. The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.
Topics: Rats; Animals; Transforming Growth Factor beta1; Moxibustion; Signal Transduction; Drugs, Chinese Herbal; Arthritis, Rheumatoid
PubMed: 37946481
DOI: 10.19852/j.cnki.jtcm.20230802.005 -
Plant Biotechnology Journal Mar 2024Heat stress causes dysfunction of the carbon-assimilation metabolism. As a member of Calvin-Benson-Bassham (CBB) cycle, the chloroplast triose phosphate isomerases (TPI)...
Heat stress causes dysfunction of the carbon-assimilation metabolism. As a member of Calvin-Benson-Bassham (CBB) cycle, the chloroplast triose phosphate isomerases (TPI) catalyse the interconversion of glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). The tomato (Solanum lycopersicum) genome contains two individual SlTPI genes, Solyc10g054870 and Solyc01g111120, which encode the chloroplast-located proteins SlTPI1 and SlTPI2, respectively. The tpi1 and tpi2 single mutants had no visible phenotypes, but the leaves of their double mutant lines tpi1tpi2 had obviously reduced TPI activity and displayed chlorotic variegation, dysplasic chloroplasts and lower carbon-assimilation efficiency. In addition to altering carbon metabolism, proteomic data showed that the loss of both SlTPI1 and SlTPI2 severely affected photosystem proteins, reducing photosynthetic capacity. None of these phenotypes was evident in the tpi1 or tpi2 single mutants, suggesting that SlTPI1 and SlTPI2 are functionally redundant. However, the two proteins differed in their responses to heat stress; the protein encoded by the heat-induced SlTPI2 showed a higher level of thermotolerance than that encoded by the heat-suppressed SlTPI1. Notably, heat-induced transcription factors, SlWRKY21 and SlHSFA2/7, which negatively regulated SlTPI1 expression and positively regulated SlTPI2 expression, respectively. Our findings thus reveal that SlTPI1 and SlTPI2 have different thermostabilities and expression patterns in response to heat stress, which have the potential to be applied in thermotolerance strategies in crops.
Topics: Triose-Phosphate Isomerase; Solanum lycopersicum; Proteomics; Photosynthesis; Plastids; Protein Isoforms; Carbon
PubMed: 37878418
DOI: 10.1111/pbi.14212 -
BioRxiv : the Preprint Server For... Oct 2023The bacterial determinants that facilitate (Mtb) adaptation to the human host environment are poorly characterized. We have sought to decipher the pressures facing the...
The bacterial determinants that facilitate (Mtb) adaptation to the human host environment are poorly characterized. We have sought to decipher the pressures facing the bacterium by assessing Mtb genes that are under positive selection in clinical isolates. One of the strongest targets of selection in the Mtb genome is , which encodes a quinone-dependent L-lactate dehydrogenase (LldD2) that catalyzes the oxidation of lactate to pyruvate. Lactate accumulation is a salient feature of the intracellular environment during infection and is essential for Mtb growth in macrophages. We determined the extent of variation across a set of global clinical isolates and defined how prevalent mutations modulates Mtb fitness. We show the stepwise nature of evolution that occurs as a result of ongoing selection in the background of ancestral lineage defining mutations and demonstrate that the genetic evolution of additively augments Mtb growth in lactate. Using quinone-dependent antibiotic susceptibility as a functional reporter, we also find that the evolved mutations functionally increase the quinone-dependent activity of LldD2. Using C-lactate metabolic flux tracing, we find that is necessary for robust incorporation of lactate into central carbon metabolism. In the absence of , label preferentially accumulates in methylglyoxal precursors dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) and is associated with a discernible growth defect, providing experimental evidence for accumulated lactate toxicity via a methylglyoxal pathway that has been proposed previously. The evolved variants increase lactate incorporation to pyruvate but also alter flux in the methylglyoxal pathway, suggesting both an anaplerotic and detoxification benefit to evolution. We further show that the mycobacterial cell is transcriptionally sensitive to the changes associated with altered activity which affect the expression of genes involved in cell wall lipid metabolism and the ESX-1 virulence system. Together, these data illustrate a multifunctional role of LldD2 that provide context for the selective advantage of mutations in adapting to host stress.
PubMed: 37873410
DOI: 10.1101/2023.10.09.561592