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International Journal of Food... Jun 2024The impact of paprika and dextrose addition on the surface of dry cured loins was analysed attending to differences in microbiota composition and aroma profile. Three...
The impact of paprika and dextrose addition on the surface of dry cured loins was analysed attending to differences in microbiota composition and aroma profile. Three different types of loins containing either dextrose (D), paprika (P) or a mixture of dextrose and paprika (DP) were manufactured. The loins were characterized using physic-chemical parameters, free amino acids, volatile compounds and aroma sensorial analysis, as well as applying microbiological counts and metagenomics of the 16S rRNA gene and its rDNA region. The analysis of volatile compounds clearly distinguished all loins, whereas the total content of free amino acids only separated P from D and DP loins. The main sensory differences were linked to paprika addition, which increased the perception of paprika and smoky odors as well as cured, savoury and cheesy notes. Microbial counts analysis could not differentiate between the three loin types; however, metagenomics analysis revealed clear differences in key bacterial and fungal genera among the three loins. Paprika addition favoured dominance of Latilactobacillus in the microbiota of P loins. On the contrary, dextrose addition caused the dominance of Staphylococcus in the microbiota of D loins. In DP loins, both genera were similarly represented in the bacterial community. Regarding fungi, large differences could be observed within the P and D loins, whereas the proportion of Debaryomyces in DP loins increased. The microbiota composition of DP loins controlled the lipid oxidation phenomenon, reducing the generation of derived volatiles producing rancid notes and increase the volatile compounds derived from amino acids such as branched aldehydes, pyrazines and pyrroles, providing particular aroma notes to the loins.
PubMed: 38851175
DOI: 10.1016/j.ijfoodmicro.2024.110782 -
Phytomedicine : International Journal... Aug 2024A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce...
BACKGROUND
A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce proteotoxic stress. Phosphatase and tensin homolog (PTEN) have been reported to be involved in proteostasis, and PTEN-associated pathways are commonly altered in CCA. Celastrol, a triterpene from plants, exhibits cytotoxic effects in various types of cancer. However, the underlying mechanisms remain unclear.
PURPOSE
We investigated the therapeutic effect of celastrol in CCA and identified the molecular characteristics of tumors that were sensitive to celastrol. The target of celastrol was explored. We then evaluated the candidate combination therapeutic strategy to increase the effectiveness of celastrol in celastrol-insensitive CCA tumors.
METHODS
Various CCA cells were categorized as either celastrol-sensitive or celastrol-insensitive based on their response to celastrol. The molecular characteristics of cells from different groups were determined by RNA-seq. PTEN status and its role in proteasome activity in CCA cells were investigated. The CMAP analysis, molecular docking, and functional assay were performed to explore the effect of celastrol on proteasome activities. The correlation between PTEN status and clinical outcomes, as well as proteasomal activity, were measured in CCA patients. The synergistic therapeutic effect of autophagy inhibitors on celastrol-insensitive CCA cells were measured.
RESULTS
Diverse responses to celastrol were observed in CCA cells. PTEN expression varied among different CCA cells, and its status could impact cell sensitivity to celastrol: PTEN tumor cells were resistant to celastrol, while PTEN cells were more sensitive. Celastrol induced proteasomal dysregulation in CCA cells by directly targeting PSMB5. Cells with low PTEN status transcriptionally promoted proteasome subunit expression in an AKT-dependent manner, making these cells more reliant on proteasomal activities to maintain proteostasis. This caused the PTEN CCA cells sensitive to celastrol. A negative correlation was found between PTEN levels and the proteasome signature in CCA patients. Moreover, celastrol treatment could induce autophagy in PTEN CCA cells. Disrupting the autophagic pathway in PTEN CCA cells enhanced the cytotoxic effect of celastrol.
CONCLUSION
PTEN status in CCA cells determines their sensitivity to celastrol, and autophagy inhibitors could enhance the anti-tumor effect in PTEN CCA.
Topics: Cholangiocarcinoma; Pentacyclic Triterpenes; PTEN Phosphohydrolase; Humans; Cell Line, Tumor; Bile Duct Neoplasms; Triterpenes; Molecular Docking Simulation; Tripterygium; Antineoplastic Agents, Phytogenic; Proteasome Endopeptidase Complex; Autophagy; Bortezomib
PubMed: 38851099
DOI: 10.1016/j.phymed.2024.155790 -
Biochemical and Biophysical Research... Sep 2024Aging is characterized as the process of functional decline in an organism from adulthood, often marked by a progressive loss of cellular function and systemic...
Aging is characterized as the process of functional decline in an organism from adulthood, often marked by a progressive loss of cellular function and systemic deterioration of multiple tissues. Among the numerous molecular, cellular, and systemic hallmarks associated with aging, mitochondrial dysfunction is considered one of the pivotal factors that initiates the aging process. During aging, mitochondria undergo varying degrees of damage, resulting in impaired energy production and disruption of the homeostatic regulation of mitochondrial quality control systems, which in turn affects cellular energy metabolism and results in cellular dysfunction, accelerating the aging process. AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) are two central kinase complexes responsible for sensing intracellular nutrient levels, regulating metabolic homeostasis, modulating aging and play a crucial role in maintaining the homeostatic balance of mitochondria. Our previous studies found that the novel compound tetramethylpyrazine nitrone (TBN) can protect mitochondria via the AMPK/mTOR pathway in many animal models, extending healthy lifespan through the Nrf2 signaling pathway in nematodes. Building upon this foundation, we have posited a reasonable hypothesis, TBN can improve mitochondrial function to delay aging by regulating the AMPK/mTORC1 signaling pathway. This study focuses on the C. elegans, exploring the impact and underlying mechanisms of TBN on aging and mitochondrial function (especially the mitochondrial quality control system) during the aging process. The present studies demonstrated that TBN extends lifespan of wild-type nematodes and is associated with the AMPK/mTORC1 signaling pathway. TBN elevated ATP and NAD levels in aging nematodes while orchestrating mitochondrial biogenesis and mitophagy. Moreover, TBN was observed to significantly enhance normal activities during aging in C. elegans, such as mobility and pharyngeal pumping, concurrently impeding lipofuscin accumulation that were closely associated with AMPK and mTORC1. This study not only highlights the delayed effects of TBN on aging but also underscores its potential application in strategies aimed at improving mitochondrial function via the AMPK/mTOR pathway in C. elegans.
Topics: Animals; Caenorhabditis elegans; Mechanistic Target of Rapamycin Complex 1; Pyrazines; Mitochondria; Signal Transduction; AMP-Activated Protein Kinases; Aging; Caenorhabditis elegans Proteins; Nitrogen Oxides
PubMed: 38850811
DOI: 10.1016/j.bbrc.2024.150220 -
Chemical Record (New York, N.Y.) Jun 2024In the last past twenty years, research on luminescent platinum (II) complexes has been intensively developed for useful application such as organic light emitting... (Review)
Review
In the last past twenty years, research on luminescent platinum (II) complexes has been intensively developed for useful application such as organic light emitting diodes (OLEDs). More recently, new photoluminescent complexes based on diazine ligands (pyrimidine, pyrazine, pyridazine, quinazoline and quinoxaline) have been developed in this context. This review will summarize the photophysical properties of most of the phosphorescent diazine Pt(II) complexes described in the literature and compare the results to pyridine analogues whenever possible. Based on the emission color, and the photoluminescence quantum yield (PLQY) values, the relationship between structure modification, and photophysical properties are highlighted. Tuning of emission color, quantum yields in solution and solid state and, for some complexes, aggregation induced emission (AIE) or thermally activated delayed fluorescence (TADF) properties are described. When emitting OLEDs have been built from diazine Pt(II) complexes, the external quantum efficiency (EQE) values and luminance for different emission wavelengths and in some cases, chromaticity coordinates obtained from devices, are given. Finally, this review highlights the growing interest in studies of new luminescent diazine Pt(II) complexes for OLED applications.
PubMed: 38847061
DOI: 10.1002/tcr.202300335 -
Luminescence : the Journal of... Jun 2024Favipiravir (FVP) is an oral antiviral drug approved in 2021 for the treatment of COVID-19. It is a pyrazine derivative that can be integrated into anti-viral RNA...
Favipiravir (FVP) is an oral antiviral drug approved in 2021 for the treatment of COVID-19. It is a pyrazine derivative that can be integrated into anti-viral RNA products to inhibit viral replication. While, adenine is a purine nucleobase that is found in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) to generate genetic information. For the first time, the binding mechanism between FVP and adenine was determined using different techniques, including UV-visible spectrophotometry, spectrofluorimetry, synchronous fluorescence (SF) spectroscopy, Fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET), and metal ion complexation. The fluorescence spectra indicated that FVP is bound to adenine via Van der Waals forces and hydrogen bonding through a spontaneous binding process (ΔG < 0). The quenching mechanism was found to be static. Various temperature settings were used to investigate thermodynamic characteristics, such as binding forces, binding constants, and the number of binding sites. The reaction parameters, including the enthalpy change (ΔH) and entropy change (ΔS), were calculated using Van't Hoff's equation. The findings demonstrated that the adenine-FVP binding was endothermic. Furthermore, the results of the experiments revealed that some metal ions (K, Ca, Co, Cu, and Al) might facilitate the binding interaction between FVP and adenine. Slight changes are observed in the FTIR spectra of adenine, indicating the binding interaction between adenine and FVP. This study may be useful in understanding the pharmacokinetic characteristics of FVP and how the drug binds to adenine to prevent any side effects.
Topics: Pyrazines; Amides; Adenine Nucleotides; Antiviral Agents; Spectroscopy, Fourier Transform Infrared; Thermodynamics; Spectrometry, Fluorescence; Fluorescence Resonance Energy Transfer; Spectrophotometry, Ultraviolet; Binding Sites; Adenine
PubMed: 38845344
DOI: 10.1002/bio.4792 -
European Journal of Pharmacology Aug 2024Tetramethylpyrazine (TMP) has been demonstrated to alleviate neuronal ferroptosis following spinal cord injury (SCI), thereby promoting neural repair. However, the...
OBJECTIVE
Tetramethylpyrazine (TMP) has been demonstrated to alleviate neuronal ferroptosis following spinal cord injury (SCI), thereby promoting neural repair. However, the precise underlying mechanisms remain elusive.
METHODS
The SCI model was established using a modified version of Allen's method. TMP (40, 80, 120, and 160 mg/kg) and ras-selective lethal 3 (RSL3) (5 mg/kg) were administered intraperitoneally once daily for 7 days. HE and Nissl staining were employed to examine histomorphology and neurons, respectively. Perls staining was used to identify the distribution of iron. A transmission electron microscope was used to observe the microcosmic morphology of mitochondria. Immunofluorescence staining and Western blot were used to analyze neuronal nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) surrounding injury sites. Additionally, glutathione peroxidase 4 (GPX4)/NeuN + cells and acyl-CoA synthetase long-chain family member 4 (ACSL4)/NeuN + cells were observed. RT-qPCR was conducted to examine the mRNA expression levels of GPX4 and ACSL4. ELISA were used to quantify the concentrations of GPX4, reactive oxygen species (ROS), L-glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and tissue iron.
RESULTS
TMP had an inhibitory effect on the concentrations of tissue iron, ROS, GSH, MDA, and SOD. TMP improved the microcosmic morphology of mitochondria and increased GPX4 level while decreasing that of ACSL4. TMP reduced lesion sizes, enhanced neuronal survival, and inhibited glial scar formation. However, the effect of TMP can be effectively reversed by RSL3.
CONCLUSION
TMP alleviates neuronal ferroptosis by regulating the GPX4/ACSL4 axis, thereby protecting the remaining neurons surrounding injury sites and reducing glial scar formation.
Topics: Ferroptosis; Animals; Pyrazines; Spinal Cord Injuries; Phospholipid Hydroperoxide Glutathione Peroxidase; Coenzyme A Ligases; Recovery of Function; Male; Disease Models, Animal; Mice; Mitochondria; Neurons; Reactive Oxygen Species; Neuroprotective Agents
PubMed: 38843947
DOI: 10.1016/j.ejphar.2024.176710 -
Inorganic Chemistry Jun 2024The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired...
The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired by electronegative redox reactions, we designed a nitrogen-oxygen rich pyrazine connected COF (TQY-COF) with multiple redox sites as a platform for extracting uranium via combining superaffinity and enhanced photoinduction. The preorganized bisnitrogen-bisoxygen donor configuration on TQY-COF is entirely matched with the typical geometric coordination of hexavalent uranyl ions, which demonstrates high affinity (tetra-coordination). In addition, the presence of the carbonyl group and pyrazine ring effectively stores and controls electron flow, which efficaciously facilitates the separation of e/h and enhances photocatalytic performance. The experimental results show that TQY-COF removes up to 99.8% of uranyl ions from actual uranium mine wastewater under the light conditions without a sacrificial agent, and the separation coefficient reaches 1.73 × 10 mL g in the presence of multiple metal ions, which realizes the precise separation in the complex environment. Importantly, DFT calculations further elucidate the coordination mechanism of uranium and demonstrate the necessity of the presence of N/O atoms in the photocatalytic adsorption of uranium.
PubMed: 38842950
DOI: 10.1021/acs.inorgchem.4c01649 -
Expert Opinion on Therapeutic Patents May 2024PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation.... (Review)
Review
INTRODUCTION
PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer.
AREAS COVERED
A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted.
EXPERT OPINION
Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.
Topics: Humans; Patents as Topic; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1; Antineoplastic Agents; Animals; Neoplasms; Proto-Oncogene Proteins; Hematologic Neoplasms; Molecular Targeted Therapy; Drug Development; Drug Design; Protein Serine-Threonine Kinases
PubMed: 38842051
DOI: 10.1080/13543776.2024.2365411 -
Journal of Agricultural and Food... Jun 2024Liquor-pairing food is a common dietary combination. Baijiu and peanuts are unquestionably a classic pairing in China. But no one has explained why. Its alteration in...
Liquor-pairing food is a common dietary combination. Baijiu and peanuts are unquestionably a classic pairing in China. But no one has explained why. Its alteration in baijiu flavor was studied using multiple sensory evaluation, as well as nontargeted proton-transfer reaction mass spectrometry coupled with GC × GC-MS. Multiple statistical analyses were used to discover the changes in the retronasal aroma and its contribution to baijiu flavor. It showed that the consumption of peanuts enhances the burst intensity of ester aroma (0.814-1.00) and Jiao aroma (0.889-0.963) but decreases the aftertaste of baijiu ( < 0.05). Meanwhile, it increases the release intensity and advances the burst time of baijiu retronasal aroma ( < 0.05), suppressing its aftertaste through the retention effect of the food matrix, the changes in oral processing, and cross-modal interactions. Hydrophobicity, polarity, and chemical characteristics are key factors of the uneven impact of accompanying food to aroma compounds. Esters, especially ethyl caprylate (2103 ± 927 to 51.9 ± 4.05) is most impacted by peanuts and contributes most to baijiu flavor changes. Pyrazines from peanut enhance the Qu-aroma, grain aroma, and Chen aroma in baijiu flavor. Therefore, we revealed the chemical nature of baijiu-peanut combination and help to optimize baijiu consumption experience.
PubMed: 38841998
DOI: 10.1021/acs.jafc.4c00207 -
Food Chemistry: X Jun 2024The aim of this study deals with characterize the volatile profiles of gluten free flours and bakery products. An appropriate HS-SPME/GC-MS methods for the...
The aim of this study deals with characterize the volatile profiles of gluten free flours and bakery products. An appropriate HS-SPME/GC-MS methods for the quantification analyses was performed and corn starch solid as standards was used. 34 different samples were analysed, and 127 compounds distributed in 4 classes (alcohols, aldehydes and ketones, heterocyclic compounds, and terpenes), that make up the aroma of these gluten free, were identified. The developed method is characterized by detection limits of 0.0004 and 0.0047 mg/kg for camphor and pyrazine, respectively, and linearity of quantification standards were between 0.990 and 0.998 for a range of 3-50 mg/kg.
PubMed: 38840722
DOI: 10.1016/j.fochx.2024.101399