Search

TNFα is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNFα exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, we show here that TNFα contributes to the aggressive properties of triple negative breast cancer (TNBC) cell lines via upregulation of TNFAIP3(A20). In a striking contrast, TNFα induces a potent cytotoxic cell death in luminal (ER+) breast cancer cell lines which fail to upregulate A20 expression. Overexpression of A20 not only protects luminal breast cancer cell lines from TNFα-induced cell death via inducing HSP70-mediated anti-apoptotic pathway but also promotes a robust EMT/CSC phenotype by activating the pStat3-mediated inflammatory signaling. Furthermore, A20 overexpression in luminal breast cancer cells induces aggressive metastatic properties in mouse xenografts via generating a permissive inflammatory microenvironment constituted by granulocytic-MDSCs. Collectively, our results reveal a mechanism by which A20 mediates pleiotropic effects of TNFα playing role in aggressive behaviors of TNBC subtype while its deficiency results in TNFα-induced apoptotic cell death in luminal breast cancer subtype.

Salmonella is a prevalent foodborne pathogen causing millions of global cases annually. Antimicrobial resistance is a growing public health concern, leading to search for alternatives like bacteriophages. A total of 97 bacteriophages, isolated from cattle farms (n = 48), poultry farms (n = 37), and wastewater (n = 5) samples in Türkiye, were subjected to host-range analysis using 36 Salmonella isolates with 18 different serotypes. The broadest host range belonged to an Infantis phage (MET P1-091), lysing 28 hosts. A total of 10 phages with the widest host range underwent further analysis, revealing seven unique genomes (32−243 kb), including a jumbophage (>200 kb). Except for one with lysogenic properties, none of them harbored virulence or antibiotic resistance genes, making them potential Salmonella reducers in different environments. Examining open reading frames (ORFs) of endolysin enzymes revealed surprising findings: five of seven unique genomes contained multiple endolysin ORFs. Despite sharing same endolysin sequences, phages exhibited significant differences in host range. Detailed analysis unveiled diverse receptor-binding protein sequences, with similar structures but distinct ligand-binding sites. These findings emphasize the importance of ligand-binding sites of receptor-binding proteins. Additionally, bacterial reduction curve and virulence index revealed that Enteritidis phages inhibit bacterial growth even at low concentrations, unlike Infantis and Kentucky phages. [ABSTRACT FROM AUTHOR]

Background and Objectives: The production of high‐quality gluten‐free bread still poses a major technological challenge. The objective of this study was to investigate the effects of sourdough fermentation and structural/nutritional enrichment on gluten‐free sorghum bread quality. Lactic acid bacteria (Lactobacillus casei and Lactobacillus acidophilus) and yeast (Saccharomyces cerevisiae) were used as starter cultures. Findings: The bread crust color and titratable acidity were comparable; although, the crumb color of sourdough bread made with L. acidophilus was measured darker. In both starter cultures, sourdough bread had a softer texture than the control, with significant (p <.05) differences in hardness, adhesiveness, cohesiveness, and gumminess values. The sourdough bread showed similar Fourier Transformed Infraredtransformed infrared (FTIR) spectra with the control bread, with four major peaks in the functional group region (4000–1200 cm−1) and a unique peak in the fingerprint region (1200–600 cm−1). Conclusion: Breads made with L. acidophilus (at 20% and 30% addition levels) showed better quality attributes such as softer texture, higher total phenolic content (97.75 mg GAE/100 g), and antioxidant capacity (341.49 µmol TEAC/100 g). Significance and Novelty: The results suggested that selected lactic acid bacteria‐based sorghum sourdough might be a promising ingredient for the development of gluten‐free bread with improved quality and nutritional value. [ABSTRACT FROM AUTHOR]