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Antioxidants (Basel, Switzerland) Jun 2024Scutellarein is a key active constituent present in many plants, especially in Georgi and (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative...
Scutellarein is a key active constituent present in many plants, especially in Georgi and (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities.
PubMed: 38929149
DOI: 10.3390/antiox13060710 -
Antioxidants (Basel, Switzerland) May 2024The excessive production of melanin can cause skin diseases and hyperpigmentation. In this study, resveratrol contained in Dongjin rice seed (DJ526) was increased...
The excessive production of melanin can cause skin diseases and hyperpigmentation. In this study, resveratrol contained in Dongjin rice seed (DJ526) was increased through callus induction. The antioxidant capacity of resveratrol-enriched rice callus was evaluated using the ABTS radical scavenging method and was equivalent to that of vitamin C. DJ526 rice callus extract significantly increased antioxidant activities in a concentration-dependent manner. The anti-melanogenesis effects of DJ526 rice callus extract were also evaluated in melan-a cells. Resveratrol-enriched rice callus extract significantly (i) decreased the size and number of melanin-containing cells, (ii) suppressed the activity of cellular tyrosinase and melanin content, (iii) downregulated the expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2, (iv) increased the expression of phosphorylated extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) inhibited the activation of phosphorylated p38 in melan-a cells. From the above observations, DJ526 rice callus extract showed strong antioxidant and anti-melanogenesis activity at the concentration test. These findings indicate the potential of resveratrol-enriched rice callus as a novel agent for controlling hyperpigmentation.
PubMed: 38929064
DOI: 10.3390/antiox13060625 -
Foods (Basel, Switzerland) Jun 2024Recently, phosphorylation has been applied to peptides to enhance their physiological activity, taking advantage of its modification benefits and the extensive study of...
Recently, phosphorylation has been applied to peptides to enhance their physiological activity, taking advantage of its modification benefits and the extensive study of functional peptides. In this study, water-soluble peptides (WSPs) of sea cucumber ovum were phosphorylated in order to improve the latter's calcium binding capacity and calcium absorption. Enzymatic hydrolysis methods were screened via ultraviolet-visible absorption spectroscopy (UV-Vis), the fluorescence spectrum, and calcium chelating ability. Phosphorylated water-soluble peptides (P-WSPs) were characterized via high-performance liquid chromatography, the circular dichroism spectrum, Fourier transform infrared spectroscopy (FTIR), UV-Vis spectroscopy, surface hydrophobicity, and fluorescence spectroscopy. The phosphorus content, calcium chelation rate and absorption rate were investigated. The results demonstrated that phosphorylation enhanced the calcium chelating capacity of WSPs, with the highest capacity reaching 0.96 mmol/L. Phosphate ions caused esterification events, and the carboxyl, amino, and phosphate groups of WSPs and P-WSPs interacted with calcium ions to form these bonds. Calcium-chelated phosphorylated water-soluble peptides (P-WSPs-Ca) demonstrated outstanding stability (calcium retention rates > 80%) in gastrointestinal processes. Our study indicates that these chelates have significant potential to develop into calcium supplements with superior efficacy, bioactivity, and stability.
PubMed: 38928883
DOI: 10.3390/foods13121943 -
Foods (Basel, Switzerland) Jun 2024Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O...
Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O improves lipopolysaccharide (LPS)-induced macrophage inflammation. In this study, LPS-stimulated mouse RAW264.7 macrophages were used as a model to analyze the effects of T-4-O on macrophage inflammatory factors and related metabolic pathways in an inflammatory environment. The results showed that T-4-O significantly decreased the expression levels of inflammatory cytokines induced by LPS. Cellular metabolism results showed that T-4-O significantly decreased the ratio of the extracellular acidification rate and oxygen consumption rate. Non-targeted metabolomics results showed that T-4-O mainly affected glutamine and glutamate metabolism and glycine, serine, and threonine metabolic pathways. qPCR results showed that T-4-O increased the transcript levels of GLS and GDH and promoted glutamine catabolism. Western blotting results showed that T-4-O inhibited the mTOR and IκB, thereby decreasing NF-κB activity. The overall results showed that T-4-O inhibited mTOR phosphorylation to promote glutamine metabolism and increased cell oxidative phosphorylation levels, thereby inhibiting the expression of LPS-induced inflammatory cytokines.
PubMed: 38928786
DOI: 10.3390/foods13121842 -
International Journal of Molecular... Jun 2024Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins...
Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells ( < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased ( < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.
Topics: Humans; Foam Cells; Cholesterol; Liver X Receptors; Toll-Like Receptors; ATP Binding Cassette Transporter 1; Lipoproteins, LDL; PPAR gamma; THP-1 Cells; Macrophages; ATP Binding Cassette Transporter, Subfamily G, Member 1; Lipopolysaccharides; Scavenger Receptors, Class B
PubMed: 38928513
DOI: 10.3390/ijms25126808 -
International Journal of Molecular... Jun 2024Cutaneous melanoma is the most dangerous and deadly form of human skin malignancy. Despite its rarity, it accounts for a staggering 80% of deaths attributed to cutaneous...
Cutaneous melanoma is the most dangerous and deadly form of human skin malignancy. Despite its rarity, it accounts for a staggering 80% of deaths attributed to cutaneous cancers overall. Moreover, its final stages often exhibit resistance to drug treatments, resulting in unfavorable outcomes. Hence, ensuring access to novel and improved chemotherapeutic agents is imperative for patients grappling with this severe ailment. Pyrazole and its fused systems derived thereof are heteroaromatic moieties widely employed in medicinal chemistry to develop effective drugs for various therapeutic areas, including inflammation, pain, oxidation, pathogens, depression, and fever. In a previous study, we described the biochemical properties of a newly synthesized group of imidazo-pyrazole compounds. In this paper, to improve our knowledge of the pharmacological properties of these molecules, we conduct a differential proteomic analysis on a human melanoma cell line treated with one of these imidazo-pyrazole derivatives. Our results detail the changes to the SKMEL-28 cell line proteome induced by 24, 48, and 72 h of imidazo-pyrazole treatment. Notably, we highlight the down-regulation of the Ras-responsive element binding protein 1 (RREB1), a member of the zinc finger transcription factors family involved in the tumorigenesis of melanoma. RREB1 is a downstream element of the MAPK pathway, and its activation is mediated by ERK1/2 through phosphorylation.
Topics: Humans; Melanoma; Pyrazoles; Proteomics; Cell Line, Tumor; Transcription Factors; Antineoplastic Agents; Skin Neoplasms; DNA-Binding Proteins; Imidazoles; Gene Expression Regulation, Neoplastic; Proteome
PubMed: 38928466
DOI: 10.3390/ijms25126760 -
International Journal of Molecular... Jun 2024Bone marrow mesenchymal stem cells (BMSCs) are key players in promoting ovarian cancer cell proliferation, orchestrated by the dynamic interplay between cytokines and...
Bone marrow mesenchymal stem cells (BMSCs) are key players in promoting ovarian cancer cell proliferation, orchestrated by the dynamic interplay between cytokines and their interactions with immune cells; however, the intricate crosstalk among BMSCs and cytokines has not yet been elucidated. Here, we aimed to investigate interactions between BMSCs and ovarian cancer cells. We established BMSCs with a characterized morphology, surface marker expression, and tri-lineage differentiation potential. Ovarian cancer cells (SKOV3) cultured with conditioned medium from BMSCs showed increased migration, invasion, and colony formation, indicating the role of the tumor microenvironment in influencing cancer cell behavior. BMSCs promoted SKOV3 tumorigenesis in nonobese diabetic/severe combined immunodeficiency mice, increasing tumor growth. The co-injection of BMSCs increased the phosphorylation of p38 MAPK and GSK-3β in SKOV3 tumors. Co-culturing SKOV3 cells with BMSCs led to an increase in the expression of cytokines, especially MCP-1 and IL-6. These findings highlight the influence of BMSCs on ovarian cancer cell behavior and the potential involvement of specific cytokines in mediating these effects. Understanding these mechanisms will highlight potential therapeutic avenues that may halt ovarian cancer progression.
Topics: Mesenchymal Stem Cells; Female; Ovarian Neoplasms; Humans; Animals; Cell Proliferation; Cytokines; Mice; Cell Line, Tumor; Coculture Techniques; Tumor Microenvironment; Cell Movement; Culture Media, Conditioned; Bone Marrow Cells; Mice, SCID; Mice, Inbred NOD; Cell Differentiation
PubMed: 38928452
DOI: 10.3390/ijms25126746 -
International Journal of Molecular... Jun 2024Prebiotic pre-Darwinian reactions continued throughout biochemical or Darwinian evolution. Early chemical processes could have occurred on Earth between 4.5 and 3.6... (Review)
Review
Prebiotic pre-Darwinian reactions continued throughout biochemical or Darwinian evolution. Early chemical processes could have occurred on Earth between 4.5 and 3.6 billion years ago when cellular life was about to come into being. Pre-Darwinian evolution assumes the development of hereditary elements but does not regard them as self-organizing processes. The presence of biochemical self-organization after the pre-Darwinian evolution did not justify distinguishing between different types of evolution. From the many possible solutions, evolution selected from among those stable reactions that led to catalytic networks, and under gradually changing external conditions produced a reproducible, yet constantly evolving and adaptable, living system. Major abiotic factors included sunlight, precipitation, air, minerals, soil and the Earth's atmosphere, hydrosphere and lithosphere. Abiotic sources of chemicals contributed to the formation of prebiotic RNA, the development of genetic RNA, the RNA World and the initial life forms on Earth and the transition of genRNA to the DNA Empire, and eventually to the multitude of life forms today. The transition from the RNA World to the DNA Empire generated new processes such as oxygenic photosynthesis and the hierarchical arrangement of processes involved in the transfer of genetic information. The objective of this work is to unite earlier work dealing with the formose, the origin and synthesis of ribose and RNA reactions that were published as a series of independent reactions. These reactions are now regarded as the first metabolic pathway.
Topics: RNA; Ribose; Origin of Life; Evolution, Molecular
PubMed: 38928433
DOI: 10.3390/ijms25126727 -
International Journal of Molecular... Jun 2024Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The...
Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from the Genomic Data Commons, allow for integrative molecular studies of cancer. The ProteoCancer Analysis Suite (PCAS), our newly developed R package and Shinyapp, leverages these resources to facilitate in-depth analyses of proteomics, phosphoproteomics, and transcriptomics, enhancing our understanding of the tumor microenvironment through features like immune infiltration and drug sensitivity analysis. This tool aids in identifying critical signaling pathways and therapeutic targets, particularly through its detailed phosphoproteomic analysis. To demonstrate the functionality of the PCAS, we conducted an analysis of GAPDH across multiple cancer types, revealing a significant upregulation of protein levels, which is consistent with its important biological and clinical significance in tumors, as indicated in our prior research. Further experiments were used to validate the findings performed using the tool. In conclusion, the PCAS is a powerful and valuable tool for conducting comprehensive proteomic analyses, significantly enhancing our ability to uncover oncogenic mechanisms and identify potential therapeutic targets in cancer research.
Topics: Humans; Proteomics; Neoplasms; Tumor Microenvironment; Software; Computational Biology; Proteome
PubMed: 38928396
DOI: 10.3390/ijms25126690 -
International Journal of Molecular... Jun 2024Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed...
Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed myocardial titin expression and titin hypophosphorylation leading to titin filament stiffening. Beside these well-studied alterations at the cardiomyocyte level, exercise intolerance is another hallmark of HFpEF caused by molecular alterations in skeletal muscle (SKM). Currently, there is a lack of data regarding titin modulation in the SKM of HFpEF. Therefore, the aim of the present study was to analyze molecular alterations in limb SKM (tibialis anterior (TA)) and in the diaphragm (Dia), as a more central SKM, with a focus on titin, titin phosphorylation, and contraction-regulating proteins. This study was performed with muscle tissue, obtained from 32-week old female ZSF-1 rats, an established a HFpEF rat model. Our results showed a hyperphosphorylation of titin in limb SKM, based on enhanced phosphorylation at the PEVK region, which is known to lead to titin filament stiffening. This hyperphosphorylation could be reversed by high-intensity interval training (HIIT). Additionally, a negative correlation occurring between the phosphorylation state of titin and the muscle force in the limb SKM was evident. For the Dia, no alterations in the phosphorylation state of titin could be detected. Supported by data of previous studies, this suggests an exercise effect of the Dia in HFpEF. Regarding the expression of contraction regulating proteins, significant differences between Dia and limb SKM could be detected, supporting muscle atrophy and dysfunction in limb SKM, but not in the Dia. Altogether, these data suggest a correlation between titin stiffening and the appearance of exercise intolerance in HFpEF, as well as a differential regulation between different SKM groups.
Topics: Animals; Heart Failure; Rats; Diaphragm; Connectin; Phosphorylation; Disease Models, Animal; Female; Muscle, Skeletal; Stroke Volume; Muscle Contraction; Physical Conditioning, Animal; Muscle Proteins
PubMed: 38928324
DOI: 10.3390/ijms25126618