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International Journal of Molecular... Feb 2024The present study aimed to evaluate the anti-inflammatory effects of ginger () root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w....
The present study aimed to evaluate the anti-inflammatory effects of ginger () root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by up to 55% ( ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% ( ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.
Topics: Diclofenac; Zingiber officinale; Inflammation; Plant Extracts; Anti-Inflammatory Agents; Carrageenan; Tumor Necrosis Factor-alpha; Cyclooxygenase 2; Edema
PubMed: 38339059
DOI: 10.3390/ijms25031781 -
Foods (Basel, Switzerland) Jan 2024Fermented soy foods can effectively improve the unpleasant odor of soybean and reduce its anti-nutritional factors while forming aromatic and bioactive compounds....
Fermented soy foods can effectively improve the unpleasant odor of soybean and reduce its anti-nutritional factors while forming aromatic and bioactive compounds. However, a differential analysis of characteristic flavor and function among different fermented soy foods has yet to be conducted. In this study, a systematic comparison of different fermented soy foods was performed using E-nose, HS-SMPE-GC×GC-MS, bioactivity validation, and correlation analysis. The results showed that soy sauce and natto flavor profiles significantly differed from other products. Esters and alcohols were the main volatile substances in furu, broad bean paste, douchi, , and soy sauce, while pyrazine substances were mainly present in natto. Phenylacetaldehyde contributed to the sweet aroma of furu, while 1-octene-3-ol played a crucial role in the flavor formation of broad bean paste. 2,3-Butanediol and ethyl phenylacetate contributed fruity and honey-like aromas to douchi, , and soy sauce, respectively, while benzaldehyde played a vital role in the flavor synthesis of douchi. All six fermented soy foods demonstrated favorable antioxidative and antibacterial activities, although their efficacy varied significantly. This study lays the foundation for elucidating the mechanisms of flavor and functionality formation in fermented soy foods, which will help in the targeted development and optimization of these products.
PubMed: 38338550
DOI: 10.3390/foods13030415 -
The Journal of Physical Chemistry. B Feb 2024Amyloid β (Aβ) is a hallmark protein of Alzheimer's disease. One physiologically important Aβ variant is formed by initial N-terminal truncation at a glutamic acid...
Amyloid β (Aβ) is a hallmark protein of Alzheimer's disease. One physiologically important Aβ variant is formed by initial N-terminal truncation at a glutamic acid position (either E or E), which is subsequently cyclized to a pyroglutamate (either pE or pE). Both forms have been found in high concentrations in the core of amyloid plaques and are likely of high importance in the pathology of Alzheimer's disease. However, the molecular structure of the fibrils of these variants is not entirely clear. Solid-state NMR spectroscopy studies have reported a molecular contact between Gly and Ile, which would disagree with the conventional hairpin model of wildtype (WT-)Aβ fibrils, most often described in the literature. We investigated the conformation of the monomeric unit of pE-Aβ and pE-Aβ (and for comparison also wildtype (WT)-Aβ) fibrils to find out whether the hairpin or a newly suggested extended structure dominates the structure of the Aβ monomers in these fibrils. To this end, solid-state NMR spectroscopy was applied probing the inter-residual contacts between Phe/Leu, Ala/Leu, and especially Gly/Ile using suitable isotopic labeling schemes. In the second part, the flexible turn of the Aβ peptides was replaced by a (3-(3-aminomethyl)phenylazo)phenylacetic acid (AMPP)-based photoswitch, which can predefine the peptide conformation to either an extended () or hairpin () conformation. This enables simultaneous spectroscopic assessment of the conformation of the AMPP-photoswitch, allowing in situ structural investigations during fibrillation in contrast to structural techniques such as NMR spectroscopy or cryo-EM, which can only be applied to stable conformers. Both methods confirm an extended structure for the peptidic monomers in fibrils of all investigated Aβ variants. Especially the Gly/Ile contact is a decisive indicator for the extended structure along with the characteristic absorption spectra of -AMPP-Aβ.
Topics: Humans; Amyloid beta-Peptides; Alzheimer Disease; Molecular Conformation; Molecular Structure; Magnetic Resonance Spectroscopy; Amyloid; Peptide Fragments
PubMed: 38334278
DOI: 10.1021/acs.jpcb.3c07285 -
RSC Advances Feb 2024Herein, an in-syringe gas-controlled density tunable solidification of a floating organic droplet-based dispersive liquid-liquid microextraction method was employed for...
HPLC-FLD determination of aflatoxins M and M in raw cow milk samples using in-syringe gas-controlled density tunable solidification of a floating organic droplet-based dispersive liquid-liquid microextraction method.
Herein, an in-syringe gas-controlled density tunable solidification of a floating organic droplet-based dispersive liquid-liquid microextraction method was employed for the extraction of aflatoxin M and M from cow milk samples prior to their quantification with high-performance liquid chromatography equipped with a fluorescence detector. In this method, after precipitating the proteins of the sample using a zinc sulfate solution, the supernatant phase was transferred into a barrel of a glass syringe, with the end closed with a septum containing a mixture of menthol, phenylacetic acid DES (as the extraction solvent), and chloroform (as a density modifier). After that, an inert gas was bubbled into the syringe. In this manner, chloroform was evaporated and fine droplets of extractant were released, which extracted the analytes during their passing. Finally, the syringe was placed in an ice bath and the obtained solidified drop was injected into the separation system after diluting with a mobile phase. Under the best analysis conditions, low limits of detection (1.45 and 1.86 ng L for AFM and AFM, respectively) and quantification (4.83 and 6.21 ng L for AFM and AFM, respectively), high extraction recovery (75 and 70% for AFM and AFM, respectively), and good precision (relative standard deviations ≤ 4.8%) were obtained by employing the approach reported in this study. In the end, this method was successfully employed to determine AFM and AFM in raw cow milk samples collected from Tabriz, Iran.
PubMed: 38332794
DOI: 10.1039/d3ra04149b -
Neuropsychopharmacology : Official... May 2024The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced... (Randomized Controlled Trial)
Randomized Controlled Trial
The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = -0.54, p < 0.001). GBC showed "fast>slow" associations in dorsal prefrontal cortex, insula, posterior thalamus and brainstem, caudate and precuneus; and "slow>fast" associations in ventral striatum, orbitofrontal cortex, and frontopolar cortex (p < 0.05). "Fast>slow" GBC patterns showed significant spatial correspondence with D1 receptor availability (estimated via normative maps of [C]SCH23390 binding; rho = 0.22, p < 0.05). Further, hippocampal GBC to fast dopamine increases was significantly negatively correlated with self-reported 'high' ratings to intravenous MP across individuals (r = -0.68, p = 0.015). Different routes of MP administration produce divergent patterns of brain connectivity. Fast dopamine increases are uniquely associated with connectivity patterns that have relevance for the subjective experience of drug reward.
Topics: Humans; Male; Adult; Female; Brain; Positron-Emission Tomography; Magnetic Resonance Imaging; Dopamine; Methylphenidate; Double-Blind Method; Young Adult; Raclopride; Central Nervous System Stimulants; Receptors, Dopamine D1; Neural Pathways; Dopamine Antagonists; Brain Mapping
PubMed: 38326458
DOI: 10.1038/s41386-024-01803-8 -
Genomics Mar 2024Cell differentiation agent II (CDA-II) exhibits potent anti-proliferative and apoptosis-inducing properties against a variety of cancer cells. However, its mechanism of...
BACKGROUND
Cell differentiation agent II (CDA-II) exhibits potent anti-proliferative and apoptosis-inducing properties against a variety of cancer cells. However, its mechanism of action in chronic myeloid leukemia (CML) remains unclear.
METHODS
Cell counting Kit 8 (CCK-8) and flow cytometry were used to investigate the effects of CDA-II on the biological characteristics of K562 cells. Gene (mRNA and lncRNA) expression profiles were analyzed by bioinformatics to screen differentially expressed genes and to perform enrichment analysis. The Pearson correlation coefficients of lncRNAs and mRNAs were calculated using gene expression values, and a lncRNA/mRNA co-expression network was constructed. The MCODE and cytoHubba plugins were used to analyze the co-expression network.
RESULTS
The Results, derived from CCK-8 and flow cytometry, indicated that CDA-II exerts dual effects on K562 cells: it inhibits their proliferation and induces apoptosis. From bioinformatics analysis, we identified 316 mRNAs and 32 lncRNAs. These mRNAs were predominantly related to the meiotic cell cycle, DNA methylation, transporter complex and peptidase regulator activity, complement and coagulation cascades, protein digestion and absorption, and cell adhesion molecule signaling pathways. The co-expression network comprised of 163 lncRNA/mRNA interaction pairs. Notably, our analysis results implicated clustered histone gene families and five lncRNAs in the biological effects of CDA-II on K562 cells.
CONCLUSION
This study highlights the hub gene and lncRNA/mRNA co-expression network as crucial elements in the context of CDA-II treatment of CML. This insight not only enriches our understanding of CDA-II's mechanism of action but also might provide valuable clues for subsequent experimental studies of CDA-II, and potentially contribute to the discovery of new therapeutic targets for CML.
Topics: Humans; RNA, Long Noncoding; Gene Expression Profiling; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; RNA, Messenger; Gene Regulatory Networks; Peptides; Phenylacetates
PubMed: 38325533
DOI: 10.1016/j.ygeno.2024.110806 -
Journal of Attention Disorders Mar 2024Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response...
OBJECTIVE
Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response rate. This study aimed to identify neural and cognitive markers predictive of longitudinal improvement in response to stimulant treatment in drug-naïve adults with ADHD.
METHOD
We used diffusion tensor imaging (DTI) and executive function measures with 36 drug-naïve adult ADHD patients in a prospective study design.
RESULTS
Structural connectivity (measured by fractional anisotropy, FA) in striatal regions correlated with ADHD clinical symptom improvement following stimulant treatment (amphetamine or methylphenidate) in better medication responders. A significant positive correlation was also found between working memory performance and stimulant-related symptom improvement. Higher pre-treatment working memory scores correlated with greater response.
CONCLUSION
These findings provide evidence of pre-treatment neural and behavioral markers predictive of longitudinal treatment response to stimulant medications in adults with ADHD.
Topics: Adult; Humans; Attention Deficit Disorder with Hyperactivity; Diffusion Tensor Imaging; Central Nervous System Stimulants; Prospective Studies; Methylphenidate; Amphetamine; Treatment Outcome; Cognition
PubMed: 38321936
DOI: 10.1177/10870547231222261 -
Journal of Medicine and Life Oct 2023Ursodeoxycholic acid (UDCA) is known for its major effects on the liver, but its impact on autoimmune diseases is not well understood. This study aimed to assess the...
Ursodeoxycholic acid (UDCA) is known for its major effects on the liver, but its impact on autoimmune diseases is not well understood. This study aimed to assess the effectiveness of UDCA in controlling rheumatoid arthritis (RA) in an setting. Experimental RA was induced in rats using Freund's complete adjuvant, and the effects of UDCA (50,100 mg/kg) were compared to those of dexamethasone and diclofenac by measuring changes in paw size, IL-17, pro-inflammatory cytokines, oxidative stress (GSH, MDA), and radiological changes. The administration of UDCA resulted in decreased cartilage damage, reduced paw edema, and a decrease in the release of pro-inflammatory cytokines and oxidative stress. Additionally, X-ray joint alterations were observed in the UDCA-treated group compared to the dexamethasone and diclofenac groups. These results suggest that UDCA has anti-rheumatoid arthritis properties due to its ability to minimize oxidative stress and inflammation in arthritis-affected rats.
Topics: Rats; Animals; Diclofenac; Ursodeoxycholic Acid; Arthritis, Rheumatoid; Cytokines; Dexamethasone
PubMed: 38313166
DOI: 10.25122/jml-2023-0107 -
Microbiology Resource Announcements Feb 2024We present genome sequences of three strains isolated from an abandoned century-old oil exploration well. A sp. genome showed a size of 5,378,420 bp, while genomes...
We present genome sequences of three strains isolated from an abandoned century-old oil exploration well. A sp. genome showed a size of 5,378,420 bp, while genomes sized 3,522,593 and 3,864,311 bp. Genomes included catabolic genes for benzoate, 4-hydroxybenzoate, salicylate, vanillate, indoleacetate, anthranilate, -alkanes, 4-hydroxyphenylacetate, phenylacetate, among others.
PubMed: 38289048
DOI: 10.1128/mra.01076-23 -
BMC Pregnancy and Childbirth Jan 2024Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to...
BACKGROUND
Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques.
METHODS
We conducted a study on 20 postpartum mothers from August 2019-March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach.
RESULTS
For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093.
CONCLUSIONS
While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.
Topics: Infant; Pregnancy; Female; Child; Humans; Infant, Newborn; Milk, Human; Diclofenac; Acetaminophen; Breast Feeding; Analgesics
PubMed: 38287321
DOI: 10.1186/s12884-024-06287-4