Search Results (1,722)

In this study, a series of novel β-phenylalanine derivatives were synthesised and evaluated for their anticancer activity. The 3-(4-methylbenzene-1-sulfonamido)-3-phenylpropanoic acid (2) was prepared using β-phenylalanine as a core scaffold. The β-amino acid derivative 2 was converted to the corresponding hydrazide 4, which enabled the development of structurally diverse heterocyclic derivatives including pyrrole 5, pyrazole 6, thiadiazole 8, oxadiazole 11, triazoles 9 and 12 with Schiff base analogues 13 and series1,2,4-triazolo [3,4-b][1,3,4]thiadiazines 14. These modifications were designed to enhance chemical stability, solubility, and biological activity. All compounds were initially screened for cytotoxicity against the A549 human lung adenocarcinoma cell line, identifying N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo-1-phenylpropyl]-4-methylbenzenesulfonamide (5) and (E)-N-{2-[4-[(4-chlorobenzylidene)amino]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1-phenylethyl}-4-methylbenzenesulfonamide (13b) as the most active. The two lead candidates were further evaluated in H69 and H69AR small cell lung cancer lines to assess activity in drug-sensitive and multidrug-resistant models. Schiff base 13b containing a 4-chlorophenyl moiety, retained potent antiproliferative activity in both H69 and H69AR cells, comparable to cisplatin, while compound 5 lost efficacy in the resistant phenotype. These findings suggest Schiff base derivative 13b may overcome drug resistance mechanisms, a limitation commonly encountered with standard chemotherapeutics such as doxorubicin. These results demonstrate the potential role of β-phenylalanine derivatives, azole-containing sulphonamides, as promising scaffolds for the development of novel anticancer agents, particularly in the context of lung cancer and drug-resistant tumours. Full article

Over the years, macromycete fungi have been used as a source of food, part of religious rites and rituals, and as a medicinal remedy. Species with strong health-promoting potential include Hericium erinaceus, Cordyceps militaris, Ganoderma lucidum, Pleurotus ostreatus, Flammulina velutipes, and Inonotus obliquus. These species contain many bioactive compounds, including β-glucans, endo- and exogenous amino acids, polyphenols, terpenoids, sterols, B vitamins, minerals, and lovastatin. The level of some biologically active substances is species-specific, e.g., hericenones and erinacines, which have neuroprotective properties, and supporting the production of nerve growth factor in the brain for Hericium erinaceus. Due to their high health-promoting potential, mushrooms and substances isolated from them have found applications in livestock nutrition, improving their welfare and productivity. This phenomenon may be of particular importance in the nutrition of laying hens and broiler chickens, where an increase in pathogen resistance to antibiotics has been observed in recent years. Gallus gallus domesticus is a key farm animal for meat and egg production, so the search for new compounds to support bird health is important for food safety. Studies conducted to date indicate that feed supplementation with mushrooms has a beneficial effect on, among other things, bird weight gain; bone mineralisation; and meat and egg quality, including the lipid profile and protein content and shell thickness, and promotes the development of beneficial microbiota, thereby increasing immunity. Full article

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_i value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

Background/Objectives: Blunt cardiac injury (BCI) is a severe medical condition that may arise as a result of various traumas, including motor vehicle accidents and falls. The main objective of this study was to explore the role and underlying mechanisms of the TRPV4 gene in BCI. Elucidating the function of TRPV4 in BCI may reveal potential novel therapeutic targets for the treatment of this condition. Methods: Rats in each group, including the SD control group (SDCON), the SD blunt-trauma group (SDBT), the TRPV4 gene-knockout control group (KOCON), and the TRPV4 gene-knockout blunt-trauma group (KOBT), were all freely dropped from a fixed height with a weight of 200 g and struck in the left chest with a certain energy, causing BCI. After the experiment, the levels of serum IL-6 and IL-1β were detected to evaluate the inflammatory response. The myocardial tissue structure was observed by HE staining. In addition, cardiac transcriptome analysis was conducted to identify differentially expressed genes, and metabolomics studies were carried out using UHPLC-Q-TOF/MS technology to analyze metabolites. The results of transcriptomics and metabolomics were verified by qRT-PCR and Western blot analysis. Results: Compared with the SDCON group, the levels of serum IL-6 and IL-1β in the SDBT group were significantly increased (p < 0.001), while the levels of serum IL-6 and IL-1β in the KOBT group were significantly decreased (p < 0.001), indicating that the deletion of the TRPV4 gene alleviated the inflammation induced by BCI. HE staining showed that myocardial tissue injury was severe in the SDBT group, while myocardial tissue structure abnormalities were mild in the KOBT group. Transcriptome analysis revealed that there were 1045 upregulated genes and 643 downregulated genes in the KOBT group. These genes were enriched in pathways related to inflammation, apoptosis, and tissue repair, such as p53, apoptosis, AMPK, PPAR, and other signaling pathways. Metabolomics studies have found that TRPV4 regulates nucleotide metabolism, amino-acid metabolism, biotin metabolism, arginine and proline metabolism, pentose phosphate pathway, fructose and mannose metabolism, etc., in myocardial tissue. The combined analysis of metabolic and transcriptional data reveals that tryptophan metabolism and the protein digestion and absorption pathway may be the key mechanisms. The qRT-PCR results corroborated the expression of key genes identified in the transcriptome sequencing, while Western blot analysis validated the protein expression levels of pivotal regulators within the p53 and AMPK signaling pathways. Conclusions: Overall, the deletion of the TRPV4 gene effectively alleviates cardiac injury by reducing inflammation and tissue damage. These findings suggest that TRPV4 may become a new therapeutic target for BCI, providing new insights for future therapeutic strategies. Full article

Cell proliferation plays a pivotal role in multiple physiological processes, including osteoporosis alleviation, wound healing, and immune enhancement. Numerous novel peptides with cell proliferation-promoting activity have been identified. These peptides exert their functions by modulating key cellular signaling pathways, thereby regulating diverse biological processes related to cell proliferation. This work summarizes peptides derived from animals and plants that stimulate cell proliferation, focusing on their amino acid composition, physicochemical properties, and preparation techniques. Furthermore, we highlight the major signaling pathways—such as the PI3K/Akt, MAPK/ERK, and Wnt/β-catenin pathways—that have been implicated in the mechanistic studies of food-derived peptides. Through the analysis and summary of previous studies, we observe a notable lack of in vivo animal models and clinical trials, indicating that these may represent promising directions for future research on food-derived bioactive peptides. Meanwhile, the potential safety concerns of proliferation-enhancing peptides—such as immunogenicity, appropriate dosage, and gastrointestinal stability—warrant greater attention. In summary, this review provides a comprehensive overview of the sources and mechanisms of cell proliferation-promoting peptides and addresses the challenges in industrializing bioactive peptide-based functional foods; therefore, further research in this area is encouraged. Full article

Pleurotus eryngii is an edible mushroom with previously characterized β-glucans. Its potential to ameliorate postprandial glycemia and regulate appetite at the postprandial state has been previously shown. However, its effect on protein digestion remains unexplored. We aimed to investigate the effect of baked P. eryngii with a known β-glucan content (4.5 g) on plasma free amino acids of patients with central obesity and metabolic abnormalities at a postprandial state. In this acute, randomized controlled cross-over study, thirteen healthy male volunteers consumed one meal that was prepared with P. eryngii and one control meal; each meal was separated by one month. Blood was collected, and plasma was isolated at different timepoints before and after the consumption. Gas chromatography–mass spectrometry was used to quantify 24 free amino acids in the plasma samples. The area under the curve with respect to increase (AUCi) was computed, and the AUCi for aromatic amino acids was found to be higher after the consumption of the control meal compared to the P. eryngii meal (p = 0.027 for phenylalanine, p = 0.008 for tyrosine, and p = 0.003 for tryptophan). The above novel findings suggest that the β-glucans present in P. eryngii mushrooms are potential modulators of AA release into the bloodstream. Full article

The B-cell lymphoma 2 (Bcl-2)-related ovarian killer (BOK), a member of the Bcl-2 protein family, shares a similar domain structure and amino acid sequence homology with the pro-apoptotic family members BAX and BAK. Although BOK is involved in the development of various types of cancer, its mechanism of action in breast cancer remains unclear. This study found that BOK was involved in the process of MG132, inhibiting the migration and epithelial–mesenchymal transition (EMT) of breast cancer cells induced by transforming growth factor-β. Furthermore, interfering BOK reversed the inhibition of breast cancer cell migration and the EMT process by MG132. Additional studies revealed that BOK silencing promoted the expression of EMT-related markers in breast cancer cells, while BOK overexpression inhibited EMT and migration. Using RNA-seq sequencing and Western blotting, we confirmed that the Wnt signaling pathway is involved in BOK regulating the EMT process in breast cancer cells. Therefore, we conclude that low BOK expression promotes breast cancer EMT and migration by activating the Wnt signaling pathway. This study enhances our understanding of breast cancer pathogenesis and suggests that BOK may serve as a potential prognostic marker and therapeutic target for breast cancer. Full article

Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided into four groups and equally intraperitoneally injected with LPS at doses of 0 μg/kg (control), 50 μg/kg (L-LPS), 100 μg/kg (M-LPS) and 150 μg/kg (H-LPS) body weight, respectively. The results showed that total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) were decreased, while malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO) and D-lactic acid (D-LA) were increased in the M-LPS and H-LPS group on day 1 in comparison with the control group, but no differences were found among treatments on day 7. However, LPS treatments gave rise to varying degrees of pathological injury in the intestines, livers and spleens on day 7. Metabolomics analysis indicated that compared with the control group, glycyl-valine, histamine and lepidine F were decreased in the M-LPS group. Most differentially expressed metabolites were enriched in amino acid-related metabolism pathways on both day 1 and day 7. Microbiome analysis identified that Oscillibacter_sp._CAG:241 was decreased in the M-LPS group compared with the control group on day 1, while Bacteroides_thetaiotaomicron and Lactobacillus_amylovorus were reduced in the M-LPS group on day 7. Collectively, an LPS dose of 100 μg/kg body weight is optimal for inducing acute inflammation in Wuzhishan miniature pigs. These findings highlight the importance of considering both the duration of OS induction and the specific research objectives when establishing OS models. Full article

Diabetic wounds are a devastating complication that cause chronic pain, recurrent infections, and limb amputations due to impaired healing. Despite advances in wound care, existing therapies often fail to address the underlying molecular dysregulation, highlighting the need for innovative and safe therapeutic approaches. Among these, D-amino acids such as D-tryptophan (D-Trp) have emerged as key regulators of cellular processes; however, their therapeutic potential in diabetic wounds remains largely unexplored. Here, we investigate the therapeutic potential of D-Trp in streptozotocin (STZ)-induced diabetic mice, comparing it with phosphate-buffered saline (PBS) controls and vascular endothelial growth factor (VEGF) as a positive control. Wound healing, inflammation, and histopathology were assessed. Protein and gene expression were analyzed via Western blot and RT-qPCR, respectively. Biolayer interferometry (BLI) measured the binding of D-Trp to hypoxia-inducible factor-1α (HIF-1α). D-Trp accelerated wound healing by modulating extracellular matrix (ECM) remodeling, signaling, and apoptosis. It upregulated matrix metalloproteinases (MMP1, MMP3, MMP-9), Janus kinase 2 (JAK2), and mitogen-activated protein kinase (MAPK) proteins while reducing pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6). D-Trp also suppressed caspase-3 and enhanced angiogenesis through HIF-1α activation. These findings suggest that D-Trp promotes healing by boosting ECM turnover, reducing inflammation, and activating MAPK/JAK pathways. Thus, D-Trp is a promising therapeutic for diabetic wounds. Full article

This study integrated non-targeted metabolomics and transcriptomics to investigate dynamic changes in Antheraea pernyi pupae across five developmental stages. Metabolomic analysis identified 1246 metabolites, primarily organic acids, lipids, heterocyclic compounds, and oxygen-containing organics. Principal component analysis revealed stage-specific metabolic profiles: amino acid derivatives (pyruvate, proline, lysine) declined, while pyrimidines (cytidine, uridine, β-alanine) and monosaccharides (glucose, mannose) increased. 18β-glycyrrhetinic and ursolic acids accumulated significantly in the middle and late stages. Transcriptomic analysis identified 7230 differentially expressed genes (DEGs), with 366, 1705, and 5159 significantly differentially expressed genes in the T1, T3, and T5 comparison groups, respectively. KEGG enrichment highlighted ABC transporters, amino acid/pyrimidine metabolism, and tyrosine pathways as developmentally critical, with aminoacyl-tRNA biosynthesis upregulated in later phases. Integrated multi-omics analysis revealed coordinated shifts in metabolites and genes across developmental phases, reflecting dynamic nutrient remodeling during pupal maturation. This study systematically delineates the molecular transitions driving pupal development in Antheraea pernyi pupae, uncovering conserved pathway interactions and mechanistic insights into nutrient metabolism. These findings provide a scientific foundation for leveraging pupal resources in functional food innovation and bioactive compound discovery for pharmaceutical applications. Full article

In recent years, amino-gem-bisphosphonic acids and their esters have been considered a family of compounds of great chemical and pharmacological interest due to their important biological properties and their value as key synthons in the synthesis of more complex molecules with biological interest. This explains why several research groups are interested in developing new methods for the preparation of these compounds. Therefore, we would like to report here a summary of the synthetic strategies published in the last fifteen years for the synthesis of acyclic and heterocyclic α-, β- and γ-amino-gem-bisphosphonates, as well as their application in the preparation of selected compounds of chemical and pharmacological interest. This information can be of general knowledge to researchers working in this area, as it provides the starting point for new methods and applications of these compounds. Full article

This study investigated mealworm frass as a sustainable substrate for Pleurotus ostreatus cultivation while valorizing mushroom stems as aquaculture feed. Mushrooms were grown on substrates containing 0–15% frass, and nutritional analyses were conducted on both fruiting bodies (for human consumption) and stems (for fish feed). Increasing frass levels significantly enhanced protein content, rising from 7.78% to 22.31% in stems and 24.74% to 30.99% in fruiting bodies. Lipid concentrations showed minor fluctuations while, in contrast, β-glucan content declined with high frass inclusion percentages. Essential amino acid levels peaked at 7.37% in stems (15% frass) and 8.08% in fruiting bodies (12.5% frass). Polyunsaturated fatty acids dominated the fatty acid profile, increasing with high frass levels. Mushroom bodies and stems were additionally investigated for their antimicrobial activity to determine whether they could offer protection against common fish and human pathogens. Antimicrobial assays revealed that dichloromethane extracts from stems grown on 12.5% and 15% frass exhibited inhibitory activity (inhibition zones of 10–11 mm) against Tenacibaculum maritimum, a microorganism that poses a significant threat to aquaculture. These findings highlight mealworm frass as a promising substrate for enhancing mushroom nutritional value while providing a sustainable, protein-rich feed ingredient for aquaculture. Full article

This study chemically characterized three Pleurotus ostreatus fruiting bodies cultivated in the Iberian Peninsula under different conditions (biological and industrial), with emphasis on polysaccharide analysis. Comprehensive comparative data on cultivation-dependent nutritional variations will potentially improve their nutritional and therapeutic applications. Industrial mushrooms (POC and POA) contained significantly higher carbohydrate content (74%), while the biologically cultivated mushroom (POL) exhibited more protein (22.6%), fat (4.2%), and ashes (8.0%). Monosaccharide analysis showed glucose dominance (28.7–45.5%), with mannose, galactose, xylose, and arabinose also present. Trehalose was the primary free sugar (4.8–14.9%). The (1→3)(1→6)-β-glucans varied significantly across samples (POL: 20.5%; POC: 29.3%; POA: 34.3%). Nuclear magnetic resonance analysis suggested complex polysaccharide arrangements. Water-soluble carbohydrates and proteins showed molecular weight distributions of 0.18–21 kDa and 0.20–75 kDa, respectively. All mushrooms were rich in essential amino acids, phosphorus (2.79–3.07%), potassium (0.56–0.68%), linoleic acid (0.82–1.14%), and oleic acid (0.22–0.31%). Fourier transform infrared confirmed a mushroom-specific biochemical profile. These findings corroborate the high nutritional value of POL, POC, and POA, with a significant contribution to the daily requirements of fiber, protein, and minerals (phosphorus, potassium, magnesium, iron, zinc, copper, and selenium), making them suitable for functional foods and nutraceuticals with cultivation-dependent nutritional profiles. Full article

This research centers on the sand-fixing plant known as Stipagrostis pennata, from which the β-glucosidase gene SpBGLU25 was successfully cloned using the molecular cloning method. SpBGLU25 encodes a hydrophilic and stable protein made up of 193 amino acids, located in the cell membrane. qRT-PCR analysis indicated that the expression of the SpBGLU25 is closely linked to the drought stress tolerance of S. pennata. Following this, functional validation was performed using an Arabidopsis overexpression system. The overexpression of transgenic Arabidopsis lines showed significantly improved drought tolerance under PEG and mannitol treatments. Assessments of germination, root length, and physiological indicators such as proline, malondialdehyde content, soluble sugars, and relative leaf water content (RLWC) further confirmed the enhanced performance of the overexpressing plants. Additionally, the comparative transcriptomic analysis of SpBGLU25-OE Arabidopsis compared to the wild-type (WT) showed that differentially upregulated genes were primarily enriched in categories of “cellular process,” “cell,” and “catalytic activity.” KEGG pathway enrichment analysis indicated that the genes were mainly concentrated in the pathways of phenylpropanoid biosynthesis and plant hormone signal transduction. These findings provide a crucial foundation for further investigation into the function of the SpBGLU25 and its role in regulating plant tissue development and adaptation to stress. This research is anticipated to offer new theoretical insights and genetic resources for enhancing plant stress tolerance through genetic engineering. Full article

The reaction of either the L (2S3R) or D (2R3S) enantiomers of H₂N-C*H(R)CO₂⁻ (R = -C*H(OH)CH₃ or -C*H(OH)CH(CH₃)₂) and the L (2S) or D (2R) enantiomers of H₂N-C*H(C(CH3)₂OH)CO₂⁻ with imidazole-4-carboxaldehyde and nickel(II) acetate in methanol yields a single stereoisomer of an oxazolidine. There is retention of chirality on ring positions 4 and 5 (if C_β is chiral) of the oxazolidine, C_α and C_β of the parent amino acid, and transfer of chirality to the newly generated stereogenic centers, ring positions 3, the amino acid nitrogen atom, N_AA, and 2, the aldehyde carbon atom, C_ald. Specifically, when C_α has an S configuration, both N_AA and C_ald are formed as R. Likewise, a C_α which is R results in both N_AA and C_ald being formed as S. For example, the reaction of L threonine (C_α is S and C_β is R) with 4-imidazolecarboxaldehyde in the presence of nickel(II) gives the facial Λ NiL₂, where L is (2R, 3R, 4S, 5R) 4-carboxylato-5-methyl-2-(4-imidazolyl)-1,3-oxazolidine. The same reaction with D threonine produces the enantiomeric Δ complex of (2S, 3S, 4R, 5S) 4-carboxylato-5-methyl-2-(4-imidazoyl)-1,3-oxazolidine. The high stereospecificity is thought to be based on the fused three-ring structure of the characterized nickel complexes in which the hydrogen atoms of C_α, N_AA, and C_ald must be cis to one another. Identical reactions occur with 2-pyridine carboxaldehyde and LT or DT. In contrast, the reactions of L allo threonine (2S3S) and the primary alcohols, L or D serine, give the conventional meridionally coordinated aldimine product. Full article