Search Results (55,386)

To develop new hybrid anticancer agents, 3,5-bis(benzylidene)-4-piperidone scaffolds (compounds 1–6) were functionalized with (1R)-borneoyl chloroacetate (8) or (1S)-camphorsulfonyl chloride (10). Covalent attachment of the camphorsulfonyl moiety via N-sulfonylation yielded hybrid molecules (16–21) that exhibited selective cytotoxic and cytostatic activity against cancer cells, with submicromolar IC₅₀ values. In silico ADME analysis indicated that these camphorsulfonyl-conjugated piperidones have improved drug-like properties (enhanced absorption, metabolism, and bioavailability) compared to curcumin. The most potent analogs were halogen-substituted and trimethoxy-substituted analogs, which showed the strongest tumor cell growth inhibition while sparing normal cells. Overall, this terpene-functionalization strategy addresses curcumin’s pharmacokinetic limitations and improves its anticancer profile. These hybrid molecules hold promise as potential anticancer agents. Full article

Astragalus aitosensis, also known as Astracantha arnacantha (M. Bieb.) Podlech subsp. aitosensis (Ivanisch.) Réer & Podlech, a Bulgarian endemic species, was investigated for its phenolic profile and neuroprotective potential. A targeted extraction approach led to the isolation of 14 phytochemicals. According to our literature review, none of the isolated chemicals have been reported before for A. aitosensis. Two of them are previously undescribed molecules—an isomer of odoratin and 6-hydroxy-3-(2-hydroxy-4-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one—and four of them had not been observed before our study in the genus Astragalus: 3′-methoxydaidzein, fujikinetin, sayanedine, and 6,4′-dimethoxy-7,2′-dihydroxyisoflavone. Five of the phytochemicals—maackiain, cajanin, onogenin, afrormosin, and sayanedine—exhibited selective inhibition of human monoamine oxidase-B (MAO-B), with maackiain reducing activity by 45%, nearing the effect of selegiline. The investigated phytochemicals also showed significant antioxidant and neuroprotective effects in ex vivo models using isolated rat brain synaptosomes, mitochondria, and microsomes, mitigating oxidative stress by preserving glutathione levels and reducing lipid peroxidation. Molecular docking confirmed favorable binding of active phytochemicals, particularly maackiain, within the MAO-B active site. Structure–activity relationship (SAR) analysis highlighted the role of specific substituents and fused-ring systems in MAO-B inhibition. This study expands our knowledge of the phytochemical diversity of A. aitosensis and supports the therapeutic relevance of its phenolic compounds in neurodegenerative disorders such as Parkinson’s disease. Full article

Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neuropathological hallmarks, including amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Since the amyloid cascade hypothesis was proposed, Aβ has remained a central therapeutic target, with interventions aiming to reduce Aβ production, aggregation, or downstream toxicity. This review first outlines the historical development of the Aβ hypothesis and the two major APP processing pathways (α-cleavage and β-cleavage), highlighting the role of biomarkers in early diagnosis, patient stratification, and regulatory approval. We then summarize the development and clinical outcomes of anti-Aβ small-molecule drugs, including β-secretase inhibitors, γ-secretase modulators, Aβ aggregation inhibitors, receptor/synapse modulators, and metabolic or antioxidant modalities. We further review the progression of biologic therapies, with a particular focus on monoclonal antibodies, vaccines, and emerging gene-silencing strategies, such as small interfering RNA (siRNA) and antisense oligonucleotides. Finally, we discuss future perspectives, including next-generation biologics, multi-target approaches, optimized delivery platforms, and early-prevention strategies. Collectively, these efforts underscore both the challenges and opportunities in translating anti-Aβ therapies into meaningful clinical benefits for patients with AD. Full article

Producing solid biofuels with high calorific value and high storage stability under limited energy consumption has become a crucial focus in the global energy field. Low temperature torrefaction below 300 °C is a common method for producing solid biofuels. However, this approach limits the carbon content and higher heating value (HHV) of the resulting biochar. Sodium percarbonate is a solid oxidant that can assist in the pyrolysis of organic molecules during the torrefaction to increase carbon content of biochar. Incorporating sodium percarbonate as a strategic additive presents a viable means to address the constraints associated with the torrefaction technologies. This study blended sodium percarbonate with spent coffee grounds (SCGs) to prepare torrefied SCG solid biofuels with high calorific value and high carbon content. Based on the Taguchi method with L9 orthogonal arrays, torrefaction temperature is identified as the most influential factor affecting higher heating value (HHV). Results from FTIR, water activity, hygroscopicity, and mold observation confirmed that torrefied SCGs blended with 0.5 wt% sodium percarbonate (0.5TSSCG) exhibited good storage stability. They were not prone to mold growth under ambient temperature and pressure. 0.5TSSCG with a carbon content of 61.88 wt% exhibited a maximum HHV of 29.42 MJ∙kg⁻¹. These findings indicate that sodium percarbonate contributes to increasing the carbon content and HHV of torrefied SCGs, enabling partial replacement of traditional coal consumption. Full article

In order to find the biochemical effects of Aeromonas hydrophila and its therapeutic chemical, enrofloxacin (ENR), on American shad (Alosa sapidissima A. Wilson), four groups were set up: a control group (C), an A. hydrophila group (A), an A. hydrophila + 70 mg·L⁻¹ enrofloxacin (ENR) group (E1), and an A. hydrophila + 140 mg·L⁻¹ ENR group (E2). Histological, enzymatic activities, transcriptome, and proteomics have been performed. MDA, PPO, AKP, TNF-α, and AMPK were significantly increased, while AhR and EROD were decreased in the liver of American shad after treatment with A. hydrophila. AhR and EROD showed a significant decrease in E1 group; MDA, PPO, AKP, and AMPK were significantly increased, while AhR and EROD decreased in E2 group. A. hydrophila significantly increased ferroptosis, TGF-β signaling pathway, etc. Ferroptosis, pyrimidine metabolism, and glycerolipid metabolism significantly increased in E1 group, while protein processing in endoplasmic reticulum significantly increased in E2 group. A total of 126 shared metabolites were found in the comparisons of A vs. C and E2 vs. C, and the main enriched pathway were organic oxygen compounds, lipids, and lipid-like molecules. Except for fluorobenzoate degradation, the pathways of ascorbate and aldarate metabolism, pyrimidine metabolism significantly increased in A and E2 groups, which further resulted in vacuolization, cell shedding, and necrosis in the liver. A. hydrophila led to a significant decrease in lipid metabolism, leading to oxidative stress and energy expenditure. The addition of ENR in aquaculture significantly enhanced liver metabolic abnormalities caused by A. hydrophila. Excessive use of ENR leads to oxidative stress in American shad, affecting its immune system as well as lipid, carbohydrate, and energy metabolism. Full article

Background: The emergence of the COVID-19 pandemic has accelerated research into diverse immune response mechanisms. One key area of interest is the regulation of cytotoxic activity by Natural Killer (NK) cells. These cells rely on a dynamic interplay between activating and inhibitory surface receptors that recognize specific ligands on target cells. Among these, receptors from the NKG2 family are particularly important, as maintaining their proper balance and function is essential for controlling NK cell cytotoxicity. Methods: In this study we employed qPCR to assess the genetic variability using single-nucleotide polymorphisms (SNPs) of NKG2A and NKG2D receptors and their ligands HLA-E and MICA/MICB. NKG2C deletion was determined by PCR-SSP, and serum-soluble levels of HLA-E and MICA/MICB molecules were measured by ELISA and Luminex methods. Results: Genotyping studies revealed that both NKG2A rs7301582 T and HLA-E rs1264457 A (HLA-E*01:01) alleles were predominant among infected individuals (OR = 2.21, p = 0.0258 and OR = 2.84, p = 0.0257, respectively). In contrast to MICB rs1065075 A, the MICA rs1051792 A (129Met) allele was most commonly found in hospitalized patients (OR = 14.95, p = 0.0114). The presence of the NKG2C del variant tended to be associated with an increased risk of SARS-CoV-2 infection (OR = 2.02, p = 0.0694). Moreover, higher concentrations of serum-soluble MICB was detected in infected individuals as compared to the control group (p = 0.008). Conclusions: Genetic variability of NK cell receptors and ligands as well as serum levels of their soluble forms showed associations with the risk of development of COVID-19 and the severity of its symptoms. Full article

Background: Inflammatory Bowel Disease (IBD), including Ulcerative Colitis and Crohn’s Disease, is a multifactorial inflammatory condition of the intestinal tract driven by a complex interplay of genetic factors, immune system dysfunction, and gut microbiota alterations. This review aims to synthesize current advancements in modern drug development strategies for IBD. It emphasizes the integration of computational modelling, cell-based experiments, and animal model studies to enhance translational outcomes. Methods: To compile this review, an extensive literature search was performed utilizing PubMed, Scopus, and Google Scholar databases for English-language research and review articles published between 2000 and 2025 using keywords such as “IBD,” “molecular docking,” “bioinformatics,” “organoids,” “animal models,” and “network pharmacology,” among others. A total of 199 peer-reviewed studies were identified for inclusion based on relevance, transparency, and methodological robustness. Results: The review outlines a range of cutting-edge approaches to IBD drug discovery. These include computer modelling, molecular docking, and network analysis to accelerate early-stage target prediction and drug screening. The review further highlights the critical importance of utilizing 2D and 3D cell culture systems in parallel with advanced animal models. It emphasizes the critical integration of computational predictions with biologically relevant in vitro and in vivo validations to improve the reliability and efficiency of drug development. Conclusions: The integration of computer modelling, cell culture systems, and animal studies provides a revolutionary paradigm for accelerating drug discovery to IBD and other diseases enabling personalized and more effective treatment approaches. Full article

Wheat is often used as a raw material in the brewing of special styles of beer. Hydrocolloids naturally present in wheat are called pentosans. They constitute approximately 2% of wheat flour. Arabinoxylans (pentosanes) and β-glucan are common compounds in wheat and are mostly found in the cell wall. Hydrocolloids are commonly used to retain moisture in bread and baked goods. Besides the moisture content, they affect the texture and retrogradation enthalpy of starch molecules. In the baking industry, they can be useful and improve the dough properties, but in the brewing industry, they are commonly designated as problematic compounds. Namely, to a certain extent, they can improve the foam stability; however, they can hinder the filtration process. This review paper aims to give an overview of non-starch compounds and their properties and to emphasize the significance of these macromolecules in the malting and brewing industries, especially in wheat varieties. The objective of this review is to gather information by searching different databases with scientific papers to broaden knowledge on arabinoxylans and β-glucans in brewing. Full article

Feline calicivirus (FCV) is among the few members of the Caliciviridae family that can replicate efficiently in vitro. Our recent studies have found the Transferrin Receptor Protein (TFRC) is an entry receptor that facilitates the internalization of FCV. To explore the potential involvement of additional host factors in conjunction with TFRC during the viral entry process, we identified metabotropic glutamate receptor 2 (mGluR2) as a specific interacting partner for both TFRC and the FCV VP1 protein by Co-IP analysis. Our findings indicate that the downregulation of mGluR2, along with its downstream signaling molecule, Calcium-activated potassium channel subunit alpha-1 (KCa1.1), significantly inhibits FCV replication by impairing viral internalization. Importantly, the knockout of TFRC did not diminish the effects of mGluR2 and KCa1.1 on FCV infection. Furthermore, mGluR2 was found to interact directly with FCV VP1, rather than with TFRC, and the rate of F-actin polymerization induced by FCV infection was reduced solely by the downregulation of mGluR2 protein expression, not by TFRC knockout. These results suggest that mGluR2 may independently mediate FCV internalization, operating independently of TFRC, and plays a critical role in the formation of endocytic vesicles. Overall, the results indicate that multiple host factors, including TFRC and mGluR2, are involved in the internalization of FCV into host cells. Further research is necessary to explore the propagation of other caliciviruses, such as norovirus, in vitro. Full article

This work investigates the influence of chemical composition, grain boundary (GB) type, and atomic distribution on the thermal conductivity of Hf–Nb–Ta–Zr refractory high-entropy alloys (RHEAs) via atomistic simulations. Three compositions—equiatomic HfNbTaZr (M1), Hf₁₀Nb₄₀Ta₁₀Zr₄₀ (M2), and Hf₄₀Nb₁₀Ta₄₀Zr₁₀ (M3)—were studied in single-crystalline and bicrystalline models containing Σ3 or Σ5 GBs. The effect of chemical short-range order (SRO) and GB segregation was probed by comparing results for non-relaxed structures with those obtained for corresponding materials relaxed using combined Monte Carlo/molecular dynamics (MC/MD) simulation. Material relaxation is accompanied by the formation of coherent nanoclusters (NbTa in M1, Nb or Zr in M2, Hf or Ta in M3) and Hf/Zr segregation to GBs. In single crystals, SRO reduces thermal conductivity by up to ~2.7% (e.g., from 3.66 to 3.56 W/m·K in M1), which is explained by the phonon scattering effect from matrix–cluster interfaces, densely distributed in the structures. In contrast, in certain bicrystals, the combined effects of GB healing and intragranular cluster coarsening lead to a 6.9% increase in thermal conductivity (from 4.59 to 4.93 W/m·K), despite the presence of high-energy Σ5 GBs. These results demonstrate that the interplay between SRO, GB segregation, and microstructural evolution governs phonon transport in RHEAs, revealing a counterintuitive pathway to enhance thermal conductivity through controlled atomic redistribution. Full article

Intervertebral disc degeneration is a leading contributor to chronic back pain and disability worldwide. This review comprehensively explores the complex interplay of cellular, molecular, and biomechanical alterations within the disc microenvironment that underlie intervertebral disc degeneration pathophysiology. Emphasis is placed on extracellular matrix degradation, cellular senescence, inflammation, oxidative stress, angiogenesis, and multiple forms of programmed cell death including apoptosis, pyroptosis, and ferroptosis. An in-depth analysis of key signaling pathways and regulatory molecules illustrates how these processes disrupt homeostasis and drive disease progression. Additionally, the review highlights emerging therapeutic approaches aimed at modifying the disc microenvironment, including mesenchymal and notochordal cell-based therapies, senolytics, ferroptosis inhibitors, gene therapy, and biomaterial innovations such as hydrogels, scaffolds, and nanocarriers. These strategies target degenerative cascades at the molecular level and represent a shift toward regenerative and disease-modifying interventions. While several approaches show promise in preclinical and early clinical studies, challenges related to safety, delivery, and long-term efficacy remain. This review underscores the importance of integrating molecular insights with translational innovations to develop targeted therapies for intervertebral disc degeneration and guide future research efforts. Full article

Mollusks, such as bivalves, face increasing threats, such as disease, in aquaculture. Exosomes, widely derived from living cells carrying diverse bioactive molecules, affect the immune response. To overcome these challenges, bivalves utilize exosomal miRNAs as critical regulators of immune responses. This study investigates the role of exosomal miRNAs in modulating immune and metabolic responses in Pinctada fucata martensii following lipopolysaccharide (LPS) stimulation. Exosomes (75–150 nm) were isolated from hemolymph and characterized. High-throughput sequencing identified 30 differentially expressed miRNAs (DEMs) and 1349 differentially expressed genes (DEGs) in LPS-treated oysters, with significant enrichment in TNF, TLR/NF-κB, and metabolic pathways. This study revealed exosomal miRNA-mediated regulation of immune genes (IκBα, TRAF6, IRAK1, and BIRC2/3) and metabolic enzymes (PCK and CYP2J), demonstrating their role in apoptosis, inflammation, and metabolic reprogramming. Network analysis highlighted miRNA–mRNA interactions, including miR-7/IκBα (TNF pathway) and miR-34_5/IRAK1 (TLR pathway). Additionally, exosomal miRNAs (miR-92_2 and novel_mir5) were found to regulate oxidative stress (SOD1) and gluconeogenesis (PCK), linking immune defense with metabolic adaptation. These findings provide novel insights into exosomal miRNA-mediated immune regulation in bivalves, revealing conserved mechanisms with potential implications for molluscan health and disease management. Full article

Acute pancreatitis (AP) and chronic pancreatitis (CP) are distinct inflammatory conditions with significant clinical burden, including associated complications and mortality. These pancreatic conditions share overlapping pathophysiologic features. Although AP can be followed by recurrent episodes (recurrent acute pancreatitis, RAP), most CP does not follow a simple linear progression from AP; rather, CP reflects sustained processes causing injury to the pancreas (e.g., toxic-metabolic, genetic, obstructive), leading to fibrosis and organ dysfunction. Lipidomics and metabolomics can provide insights into the pathophysiology of the disease. Although researchers have extensively explored lipids and metabolites to better understand disease mechanisms, comprehensive detailed insights into the pathways and intricate roles these molecules play in pancreatitis remain unidentified. This gap can be partially attributed to limited availability of human samples from disease subgroups in pancreatitis, and current technological constraints in analytical methods, particularly regarding complete lipid and metabolite detection, identification, and quantification. In this review, we summarize lipidomic and metabolomic workflows in the context of understanding pancreatitis pathophysiology, including their design and analytical strategies. We also highlight clinical studies on pancreatitis, utilizing lipidomics and metabolomics as a tool to identify altered or dysregulated lipids or metabolites, and their association with the disease state and its progression. Full article

Cardiac inflammation and hypertrophy develop as a pathologic response to an array of insults, such as myocardial infarctions, chronic systemic hypertension, and valvular defects. Due to the high prevalence of such conditions, there is an increasing need to prevent and halt cardiac hypertrophy. Because cardiac damage and subsequent remodeling can lead to arrhythmias, heart failure, and even sudden cardiac death, inhibition of cardiac hypertrophy is key to reducing cardiovascular-related mortality. The immune system is the driving force behind inflammatory reactions. All three pathways of complement system activation—classical, lectin, and alternative—are implicated in developing cardiac damage, inflammation, and hypertrophy due to infectious and non-infectious causes, autoimmune diseases, genetic polymorphisms, and forms of complement dysregulation. Of interest in this review is the role of the complement system, a collection of soluble and membrane-bound proteins that mediate inflammatory processes through interactions with signaling molecules and immune cells. This review comprehensively discusses the roles of these complement pathways in contagious, chronic inflammatory, genetic, and metabolic diseases. An overview of the completed and terminated clinical trials aimed at preventing cardiovascular mortality by targeting various aspects of the complement system and inflammatory reaction is included. Most current treatments for cardiac inflammation and remodeling primarily target the renin–angiotensin–aldosterone system (RAAS), which prevents further remodeling by reducing myocardial workload. However, moving forward, there may be a place for emerging anti-complement therapeutics, which impair the inflammatory response that generates hypertrophy itself. Full article