The objective of this study was to investigate the immunomodulatory effects of whey protein isolate (WPI)-galacto-oligosaccharide conjugates following dynamic high-pressure microfluidics pretreatment (DHPM) in cyclophosphamide-induced immunosuppressed mice. DHPM facilitated the conjugation of WPI and galacto-oligosaccharide, and inhibited the generation of fluorescent advanced glycation end products (AGEs) and pentosidine. The conjugates demonstrated a significant immune recovery effect on CTX-induced immunosuppressed mice, as evidenced by the enhancement of IgG antibody levels (from 3.5 to 4.1) and the reduction of the levels of immunosuppressive effector factors TGF-β (from 148.1 to 111.2) and IFN-γ (from 34.4 to 17.9). Furthermore, the conjugates exhibited a notable ability to repair histological lesion in the spleen of CTX-induced immunosuppressed mice. Spleen transcriptomics revealed that the Marco, Klrc3 and Cd209b genes were associated with the immune enhancement activity of the conjugates. Metabolomic analysis identified arginine biosynthesis, sphingolipid metabolism, alanine, aspartate and glutamate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis as key pathways in the immune enhancement activity of the conjugates. Metabolomics combined with transcriptomics indicated the importance of macrophage activation in the restoration of immunosuppressed mice's immunity by the conjugates. Therefore, the improvement in immunity observed with WPI-galacto-oligosaccharide conjugates may be related to the activation of macrophages.
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http://dx.doi.org/10.1016/j.foodres.2024.115121 | DOI Listing |
Nat Commun
December 2024
Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Scienes, Guangzhou, China.
CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Inflammasomes are defense complexes that utilize cytokines and immunogenic cell death (ICD) to stimulate the immune system against pathogens. Inspired by their dual action, we present cytokine-armed pyroptosis as a strategy for boosting immune response against diverse types of tumors. To induce pyroptosis, we utilize designed tightly regulated gasdermin D variants comprising different pore-forming capabilities and diverse modes of activation, representing a toolbox of ICD inducers.
View Article and Find Full Text PDFJ Geriatr Cardiol
November 2024
Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, China.
Background: Human interleukin (IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes. It has been demonstrated extensive beneficial effects on various diseases; however, its role in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear.
Methods: , DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts (CFs) specific hIL-37b overexpression mice (IL-37-Tg).
Neuropharmacology
December 2024
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China. Electronic address:
Objective: Autoantibody-associated psychosis represents a distinct disease subgroup of patients with schizophrenia with a suspected autoimmune origin. Although preliminary studies have suggested adjunctive drug treatment strategies targeting the immune system, further validation of these findings is warranted. Autoantibodies against SFT2D2 have been identified in patients with schizophrenia.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
College of Food Science and Engineering, Shanxi Agricultural University, Taigu 030801, China. Electronic address:
The present study aimed to investigate the impact of Sparassis latifolia polysaccharides (SLPs) on hepatic immune function in cyclophosphamide (CTX)-induced immunocompromised mice. Our findings demonstrated that SLPs effectively suppressed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammatory factors, and acute phase proteins, while improving the hepatic oxidative stress state. Additionally, SLPs exerted inhibitory effects on inflammatory cell infiltration within hepatic tissue.
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