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Frontiers in Cellular and Infection... 2024Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune...
BACKGROUND
Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender.
METHODS
We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4 ≥500 cells/mm, and CD4/CD8 ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value).
RESULTS
PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls.
CONCLUSION
PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.
Topics: Humans; Cross-Sectional Studies; Metabolomics; Biomarkers; Inflammation; HIV Infections
PubMed: 38550617
DOI: 10.3389/fcimb.2024.1340610 -
World Journal of Experimental Medicine Mar 2024The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques...
BACKGROUND
The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques for drug therapy. (), a perennial herb belonging to the family is extensively used in conventional medication.
AIM
To determine the existence of therapeutic components in leaf and callus extracts from wild plants using gas chromatography-mass spectrometry (GC-MS).
METHODS
In this study, we conducted GC-MS on wild plant leaf extracts and correlated the presence of constituents with those in callus extracts. Various growth regulators such as 6-benzylaminopurine (BAP), 2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthylacetic acid (NAA), and di-phenylurea (DPU) were added to plant leaves and callus and grown on MS medium.
RESULTS
The results clearly indicated that the addition of BAP (2.0 mg/L), 2,4-D (0.2 mg/mL), DPU (2.0 mg/L) and 2,4-D (0.2 mg/mL) in MS medium resulted in rapid callus development. The plant profile of extracts by GC-MS analysis showed that 24, 10, and 14 bioactive constituents were detected in the methanolic extract of leaf, green callus and the methanolic extract of white loose callus, respectively.
CONCLUSION
Octadecadienoic acid, hexadecanoic acid and methyl ester were the major constituents in the leaf and callus methanolic extract. Octadecadienoic acid was the most common constituent in all samples. The maximum concentration of octadecadienoic acid in leaves, green callus and white loose callus was 21.93%, 47.79% and 40.38%, respectively. These findings demonstrate that the concentration of octadecadienoic acid doubles compared to . In addition to octadecadienoic acid; butyric acid, benzene, 1-methoxy-4-(1-propenyl), dospan, tridecanedialdehyde, methylcyclohexenylbutanol, chlorpyrifos, n-secondary terpene diester, anflunine and other important active compounds were also detected. All these components were only available in callus formed . This study showed that the callus contained additional botanical characteristics compared with wild plants. Due to the presence of numerous bioactive compounds, the medical use of for various diseases has been accepted and the plant is considered an important source of therapeutics for research and development.
PubMed: 38590309
DOI: 10.5493/wjem.v14.i1.88064 -
The Journal of Biological Chemistry May 2024Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise...
Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise structures of the conjugates. Herein we reacted 13-keto-octadecadienoic acid (13-oxo-ODE or 13-KODE) with glutathione (GSH), N-acetyl-cysteine, and β-mercaptoethanol and identified the adducts. HPLC-UV analyses indicated none of the products exhibit a conjugated enone UV chromophore, a result that conflicts with the literature and is relevant to the mass spectral interpretation of 1,4 versus 1,6 thiol adduction. Aided by the development of an HPLC solvent system that separates the GSH diastereomers and thus avoids overlap of signals in proton NMR experiments, we established the two major conjugates are formed by 1,6 addition of GSH at the 9-carbon of 13-oxo-ODE with the remaining double bond α to the thiol in the 10,11 position. N-acetyl cysteine reacts similarly, while β-mercaptoethanol gives equal amounts of 1,4 and 1,6 addition products. Equine glutathione transferase catalyzed 1,6 addition of GSH to the two major diastereomers in 44:56 proportions. LC-MS in positive ion mode gives a product ion interpreted before as evidence of 1,4-thiol adduction, whereas here we find this ion using the authentic 1,6 adduct. LC-MS with negative ion APCI gave a fragment selective for 1,4 adduction. These results clarify the structures of thiol conjugates of a prototypical unsaturated keto-fatty acid and have relevance to the application of LC-MS for the structural analysis of keto-fatty acid glutathione conjugation.
Topics: Glutathione; Sulfhydryl Compounds; Mass Spectrometry; Chromatography, High Pressure Liquid; Chromatography, Liquid; Mercaptoethanol; Liquid Chromatography-Mass Spectrometry
PubMed: 38636660
DOI: 10.1016/j.jbc.2024.107293 -
BMC Genomics Jan 2024Alcohol dehydrogenases (ADHs) are the crucial enzymes that can convert ethanol into acetaldehyde. In tobacco, members of ADH gene family are involved in various stresses...
BACKGROUND
Alcohol dehydrogenases (ADHs) are the crucial enzymes that can convert ethanol into acetaldehyde. In tobacco, members of ADH gene family are involved in various stresses tolerance reactions, lipid metabolism and pathways related to plant development. It will be of great application significance to analyze the ADH gene family and expression profile under various stresses in tobacco.
RESULTS
A total of 53 ADH genes were identified in tobacco (Nicotiana tabacum L.) genome and were grouped into 6 subfamilies based on phylogenetic analysis. Gene structure (exon/intron) and protein motifs were highly conserved among the NtADH genes, especially the members within the same subfamily. A total of 5 gene pairs of tandem duplication, and 3 gene pairs of segmental duplication were identified based on the analysis of gene duplication events. Cis-regulatory elements of the NtADH promoters participated in cell development, plant hormones, environmental stress, and light responsiveness. The analysis of expression profile showed that NtADH genes were widely expressed in topping stress and leaf senescence. However, the expression patterns of different members appeared to be diverse. The qRT-PCR analysis of 13 NtADH genes displayed their differential expression pattern in response to the bacterial pathogen Ralstonia solanacearum L.
INFECTION
Metabolomics analysis revealed that NtADH genes were primarily associated with carbohydrate metabolism, and moreover, four NtADH genes (NtADH20/24/48/51) were notably involved in the pathway of alpha-linolenic acid metabolism which related to the up-regulation of 9-hydroxy-12-oxo-10(E), 15(Z)-octadecadienoic acid and 9-hydroxy-12-oxo-15(Z)-octadecenoic acid.
CONCLUSION
The genome-wide identification, evolutionary analysis, expression profiling, and exploration of related metabolites and metabolic pathways associated with NtADH genes have yielded valuable insights into the roles of these genes in response to various stresses. Our results could provide a basis for functional analysis of NtADH gene family under stressful conditions.
Topics: Nicotiana; Multigene Family; Phylogeny; Amino Acid Motifs; Gene Duplication; Gene Expression Regulation, Plant; Plant Proteins; Stress, Physiological; Gene Expression Profiling
PubMed: 38166535
DOI: 10.1186/s12864-023-09813-4 -
ACS Omega Apr 2024This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of . Initial phytochemical analysis of the...
This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of . Initial phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, glycosides, saponins, and tannins. Further characterization through high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses identified a diverse array of bioactive compounds, including hydroquinone, stearic acid, neophytadiene, 9,12-octadecadienoic acid (,), methyl ester, and others. The addition of methanolic extract to an AgNO solution resulted in a color change, confirming the green synthesis of Ag-NPs through the reduction of AgNO, as made evident by ultraviolet-visible (UV-vis) spectroscopy. X-ray diffraction (XRD) analysis provided valuable insights into the crystal structure, and scanning electron microscopy (SEM) analysis visualized the predominantly spherical shape of the Ag-NPs. However, the zeta (ζ)-potential and dynamic light scattering (DLS) analyses confirmed the stability and nanoscale dimensions of the synthesized Ag-NPs. Meanwhile, Fourier transform infrared (FT-IR) spectra exhibited peaks indicative of various functional groups, including carboxylic acids, phenols, alkanes, and isocyanates. These functional groups played a crucial role in both the reduction and capping processes of the Ag-NPs. The study further explored the antioxidant activity, cytotoxicity, acetylcholinesterase inhibition, and α-amylase inhibition activities of the Ag-NPs of the extract, demonstrating their potential for biomedical and therapeutic applications. In conclusion, this environmentally sustainable synthesis of Ag-NPs from the extract, enriched with bioactive secondary metabolites detected through HPLC and GC-MS analysis, holds promise for diverse applications in the burgeoning field of green nanotechnology.
PubMed: 38585127
DOI: 10.1021/acsomega.3c10119 -
Annals of Nutrition & Metabolism 2024Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the...
Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption.
INTRODUCTION
Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients.
METHODS
An LC-MS/MS-based method was performed to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 h after an iron-rich meal in HH patients.
RESULTS
Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal.
DISCUSSION
The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal, but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism.
Topics: Humans; Oxylipins; Male; Female; Hemochromatosis; Middle Aged; Iron, Dietary; Adult; Eicosanoids; Iron Overload; Hydroxyeicosatetraenoic Acids; Tandem Mass Spectrometry; Oxidative Stress; Principal Component Analysis; Aged; Linoleic Acids; Chromatography, Liquid
PubMed: 38354712
DOI: 10.1159/000536657 -
ACS Omega Mar 2024Medicinally valuable components derived from natural resources are highly desirable as prospective alternatives to synthetic drugs to treat fatal diseases, such as...
Medicinally valuable components derived from natural resources are highly desirable as prospective alternatives to synthetic drugs to treat fatal diseases, such as cancer and diabetes mellitus. (L.) Dumort () () is a halophyte plant that can thrive in saline environments and possesses excellent medicinal properties. Hence, for the present investigation, has been chosen, and its phytochemical constituents have been extracted utilizing various solvents, including hexane, acetone, and methanol, and identified by GC-MS, LC-MS, and HPLC analyses. The antioxidant activity of the compounds using DPPH, ABTS, and reducing power assays demonstrated that all three extracts of possessed significant radical scavenging activity comparable to standard ascorbic acid with lower IC values (69.20-95.58 μg/mL). In addition, the evaluation of antidiabetic activity by α-amylase inhibition and α-glucosidase inhibition methods revealed that the acetone extract of (SMAE) displayed equipotent activity of standard acarbose with an IC of 32.6 μg/mL. Advantageously, SMAE also exhibited better inhibition activity against the growth of lung cancer cells with an IC of 78.19. μg/mL and less toxicity on the noncancerous HUVEC cells with a high IC of 300 μg/mL. In addition, the cancer cell death mechanism via the apoptotic pathway induced by SMAE was confirmed by DAPI staining and ROS analysis. The analysis of ADME properties, including absorption, distribution, metabolism, and excretion, witnessed that the physicochemical and druglikeness factors were best catered by stigmasterol, γ-sitosterol, and vitamin E. Further, the key phytochemicals identified from SMAE were docked with CtBP1 and SOX2 bound to importin-α target proteins associated with carcinogenic pathways using Schrodinger software. The results showed that the phytochemicals, scilicet, stigmasterol, γ-sitosterol, octadecadienoic acid, and vitamin E, showed a good binding affinity with Glide scores in the range -2.845-4.018 kcal/mol. Overall, the findings support that the least investigated traditional edible medicinal mangrove-related is high in pharmacologically active constituents and might be one of the finest sources of naturally derived molecules for drug development and delivery systems.
PubMed: 38496978
DOI: 10.1021/acsomega.3c05591 -
ACS Omega Aug 2023Plant seeds are a renewable resource that can furnish access to medicinal natural products that can only otherwise be isolated from aerial or root parts, the harvest of...
Investigation of Small-Molecule Constituents in Seeds and Mapping of Their Spatial Distributions Using Laser Ablation Direct Analysis in Real-Time Imaging-Mass Spectrometry (LADI-MS).
Plant seeds are a renewable resource that can furnish access to medicinal natural products that can only otherwise be isolated from aerial or root parts, the harvest of which may be destructive to the plant or threaten its viability. However, optimization of the isolation of such compounds from seeds would be greatly assisted if the spatial distribution of the molecules of interest within the plant tissue were known. For example, iboga alkaloids that hold promise for the treatment of opioid use disorder are typically isolated from the leaves, bark, or roots of or spp. trees, but it would be more environmentally sustainable to isolate such compounds from their seeds. Here, we leveraged the unique capabilities of the ambient mass spectral imaging technique termed laser ablation direct analysis in real-time imaging-mass spectrometry (LADI-MS) to reveal the spatial distributions of a range of molecules, including alkaloids within seeds. In addition to six compounds previously reported in these seeds, namely, tetradecanoic acid, -hexadecanoic acid, (,)-9,12-octadecadienoic acid, ()-9-octadecenoic acid, octadecanoic acid, and Δ-vincamine, an additional 31 compounds were newly identified in seeds. The compound classes included alkaloids, terpenes, and fatty acids. The ion images showed that the fatty acids were localized in the embryo of the seed. The alkaloids, which were mainly localized in the seed endosperm, included strictamine, akuammidine, polyneruidine, vobasine, and Δ-vincamine. This information can be exploited to enhance the efficiency of secondary metabolite isolation from seeds while eliminating the destruction of other plant parts.
PubMed: 37546641
DOI: 10.1021/acsomega.3c02464 -
Molecular Diversity Apr 2024Fritillariae thunbergii bulbus (FTB) is a popular Chinese herbal medicine with various applications in respiratory diseases. The quality evaluation of FTB has been...
Fritillariae thunbergii bulbus (FTB) is a popular Chinese herbal medicine with various applications in respiratory diseases. The quality evaluation of FTB has been insufficient to date, as the active ingredients and mechanisms of action of FTB remain unclear. This study proposes a novel strategy for exploring the quality markers (Q-markers) of FTB based on UPLC-QTOF-MS analysis, network pharmacology, molecular docking, and molecular dynamics (MD) simulation. A total of 26 compounds in FTB were identified by UPLC-QTOF-MS. Ten of these compounds were screened as Q-markers based on network pharmacology for their anti-pneumonia effects, including imperialine, peimisine, peiminine, ebeiedinone, zhebeirine, puqiedine, 9-hydroxy-10,12-octadecadienoic acid, (9Z,12Z,15Z)-13-hydroxy-9,12,15-octadecatrienoic acid, 9,12,15-octadecatrienoic acid, and (2E,4Z,7Z,10Z,13Z,16Z,19Z)-2,4,7,10,13,16,19-docosaheptaenoic acid methyl ester (DAME). These Q-markers were predicted to act on multiple targets and pathways associated with pneumonia. Molecular docking results revealed that most of the Q-markers showed high affinity with at least one of the main targets of pneumonia, and the top ten complexes were confirmed with MD simulation. Network pharmacology indicated that FTB may act on the TNF signaling pathway, HIF-1 signaling pathway, JAK-STAT signaling pathway, etc. The results demonstrated that imperialine (P8), peimisine (P9), peiminine (P11), ebeiedine (P15), zhebeirine (P16), and puqiedine (P18) may be potential Q-markers of FTB, and AKT1, IL-6, VEGFA, TP53, EGFR, STAT3, PPARG, MMP9, and CASP3 may be promising therapeutic targets for pneumonia treatment that are worthy of further research.
Topics: Molecular Docking Simulation; Network Pharmacology; Fritillaria; Drugs, Chinese Herbal; Pneumonia; Chromatography, High Pressure Liquid; Molecular Dynamics Simulation; Biomarkers; Mass Spectrometry
PubMed: 36843054
DOI: 10.1007/s11030-023-10620-y -
Foods (Basel, Switzerland) Mar 2024The volatile composition of (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% /) from flowers (forestry wastes) was investigated by...
The volatile composition of (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% /) from flowers (forestry wastes) was investigated by gas chromatography-mass spectrometry. Thirty-one components were identified, with 3-acetoxy-7, 8-epoxylanostan-11-ol (38.16%), β-monoolein (14.4%), lycopene, 1,2-dihydro-1-hydroxy- (10.21%), and 9,12-octadecadienoic acid, 2-phenyl-1,3-dioxan-5-yl ester (9.21%) as main compounds. In addition, molecular docking was employed to identify potential protein targets for the 31 quantified essential oil components. Inhibition of these targets is typically associated with antibacterial or antioxidant properties. Molecular docking revealed that six of these components, namely, 13-heptadecyn-1-ol, ascabiol, geranylgeraniol, anethole, and quinol dimethyl ether, outperformed the native ligand (hypoxanthine) of xanthine oxidase in terms of theoretical binding affinity, therefore implying a significant in silico inhibitory potential against xanthine oxidase. These findings suggest that the essential oil extracted from flowers could be valuable for developing protein-targeted antioxidant compounds with applications in the food, pharmaceutical, and cosmetic industries.
PubMed: 38611313
DOI: 10.3390/foods13071007