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This study evaluated the immunostimulatory potential of garlic fermented with (Aglio) and identified the underlying mechanisms using and models. Aglio significantly enhanced macrophage activity, with increased TNF-α (9.3-46.6 fold), MCP-1 (5.3-41.4 fold), IL-6 (2.1-32.1 fold), and IL-12 (1.1-5.5 fold) secretion compared to those of the standard garlic extract. This macrophage-stimulatory activity was associated with MAPK (ERK, JNK, and p38) and NF-κB (IκBα and p65) signaling pathway activation. Aglio significantly increased splenocyte proliferation (1.8-2.9 fold) and TNF-α (32.5-96.6 fold), IFN-γ (26.6-362.3 fold), GM-CSF (2.1-3.9 fold), and IL-6 (10.3-11.6 fold) secretion. Gene expression analysis revealed Th1-related upregulation and Th2- and Th17-related and downregulation, indicating a Th1-mediated splenocyte activation mechanism. Oral administration of Aglio (125 and 250 mg kg) to BALB/c mice increased splenocyte proliferation (2.1-3.3 fold) and elevated splenic cytokine (TNF-α, 1.9-2.7 fold; GM-CSF, 2.2-2.3 fold; IL-6, 1.9 fold) and antibody (IgA, 1.4-1.8 fold; IgG, 1.0-1.7 fold) levels. Aglio administration also increased serum TNF-α (2.1-3.3 fold), IL-6 (1.0-1.1 fold), and IgG (1.6-1.9 fold) levels. Nutrient analysis indicated that Aglio lacked detectable carbohydrates and had negligible protein and polyphenol contents compared to standard garlic extract, suggesting complete biotransformation during fermentation. These findings demonstrate Aglio-mediated immune activation, highlighting its potential as a functional food or nutraceutical agent for immune enhancement.
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http://dx.doi.org/10.1039/d4fo03598d | DOI Listing |
Nephrol Dial Transplant
September 2025
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Background: We investigated circulating protein profiles and molecular pathways among various chronic kidney disease (CKD) etiologies to study its underlying molecular heterogeneity.
Methods: We conducted a proteomic biomarker analysis in the DAPA-CKD trial recruiting adults with and without type 2 diabetes with an eGFR of 25 to 75 mL/min/1.73m2 and a UACR of 200 to 5000 mg/g.
Nano Lett
September 2025
State Key Laboratory of Materials Low-Carbon Recycling, College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, P. R. China.
Two-dimensional (2D) nanofluidic architectures with nanoconfined interlayer channels and excess surface charges have revolutionized membrane-based reverse electrodialysis systems, demonstrating highly efficient osmotic energy collection through strong electrostatic screening of electric double layer (EDL). However, the ion-transport dynamics in 2D nanofluidic anion-selective membranes (2D-NAMs) still remain unexplored. Here, we combine density functional theory and molecular dynamics (MD) simulations to systematically explore ion transport in the 2D-NAMs.
View Article and Find Full Text PDFInt Microbiol
September 2025
Department of Microbiology, The University of Burdwan, Bardhaman, West Bengal, 713104, India.
Biofilm formation and other virulence phenotypes under quorum sensing regulation play a vital role in the pathogenicity of Aeromonas hydrophila, triggering the emergence of multi-drug resistance (MDR) which increases fish mortality, environmental issues, and economic loss in aquaculture, necessitating the discovery of novel drugs to bypass standard antibiotics. Here, quorum quenching (QQ) may be a sustainable anti-virulent approach. β-Lactamase enzyme obtained from Chromohalobacter sp.
View Article and Find Full Text PDFArch Microbiol
September 2025
Department of Infectious Disease, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
Highly pathogenic avian influenza (HPAI) H5N1 virus poses a continuing global public health threat due to its outbreaks in poultry farms and zoonotic transmission from birds to humans. In the quest of effective therapeutics against H5N1 infection, antibodies with broad neutralizing activity have attracted significant attention. In this study, we employed a phage display technique to select and identify VHH antibodies with specific neutralizing activity against H5N1 hemagglutinin (HA) from an immune llama-derived antibody library.
View Article and Find Full Text PDFJ Med Chem
September 2025
Applied Pharmaceutical Science, Inc., Building 10-1, No.2, Jingyuan North Street, BDA, Beijing 100176, China.
This study reports the discovery and preclinical activity of APS03118, a novel selective RET inhibitor featuring a novel tricyclic pyrazolo[3',4':3,4]pyrazolo[1,5-]pyridine hinge-binding scaffold designed to overcome acquired resistance to first-generation selective RET inhibitors (SRIs). By enhancing hydrogen bonding with conserved hinge residues (Glu805, Ala807), APS03118 potently inhibits wild-type RET and diverse resistance mutations, including solvent-front (G810R/S/C), gatekeeper (V804M/L/E), roof (L730I/M), and hinge (Y806C/N/H) variants. In preclinical models, APS03118 induced complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient-derived xenografts (PDXs) and significantly prolonged survival in an intracranial CCDC6-RET metastasis model.
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