PEG IFN alpha-2a (CAP/CTM HCV 2.0)

Development of an inactivated, oral immunogenic product against post-weaning colibacillosis caused by enterotoxigenic Escherichia coli in piglets.

Inglesi Alessia A, Filipe Joel J, Valli Giulia G, Riva Federica F et al.

Post-weaning diarrhea (PWD) caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 and F18 fimbriae remains a major challenge in pig production, contributing to economic losses and increased antimicrobial use. This study aimed to preliminary evaluate the immunogenic potential of an orally administered formulation comprising heat-inactivated ETEC strains expressing F4 and F18 fimbriae, combined with low-dose recombinant human interferon-alpha (IFN-α) as a mucosal adjuvant, in piglets. Piglets from two different litters were allocated into two experimental groups: a treated group (T) receiving the inactivated ETEC formulation with IFN-α for 26 days, and a control group (C) receiving only IFN-α. According to the farmer, the sows had not been vaccinated. Immune responses were evaluated in the sows colostrum and piglet serum, saliva, and feces by ELISA. In mesenteric lymph nodes anti-F4/F18 IgA and IgG antibodies were quantified by ELISPOT. The inactivated product preserved fimbrial antigenicity and remained sterile. Colostrum from both sows displayed elevated levels of fimbriae-specific IgA and IgG despite neither sow being vaccinated against E. coli. Treated piglets showed a transient serum IgA increase against F4 whereas serum IgG levels were often comparable to the controls. Notably, elevated mucosal IgA responses were observed in saliva and feces against both F4 and F18 (P < 0.01) in T group, accompanied by enhanced IgA-secreting B-cell activity in mesenteric lymph nodes. ELISA validation confirmed high assay reproducibility (R² > 0.98; CV < 10%). ELISPOT analysis underscored the adjuvant role of F4 and IFN-α in stimulating mucosal immunity. Our preliminary findings may represent a promising strategy to control PWD and reduce antimicrobial use in pig production.

Lycopene mitigates T-2 toxin-induced systemic inflammation and oxidative stress in association with gut microbiota and SCFAs regulation in mice.

Adam Saber Y SY, Ennab Wael W, Zhu Cuipeng C, Yuan Long L et al.

T-2 toxin is a trichothecene mycotoxin produced by Fusarium species and can cause disease after contaminated food or feed ingestion. This study aimed to investigate the impact of lycopene (Ly) on systemic inflammation, oxidative stress, and dysbiosis in mice exposed to T-2 toxin. A total of 20 male BALB/c mice (6 weeks old, weighing 23.5 ± 0.32 g) randomly divided into four groups (n = 5): Control (Cont), Ly, T-2, and T-2 + Ly groups. Findings revealed that Ly enhanced the body weight, feedd, and water intake that have been reduced by T-2. Ly increased the villus height (VH) and VH: crypt depth (CD) and decreased CD and villus width (VW) in ileum compared to the T-2 group. In alpha diversity, Staphylococcus and Corynebacterium were the most prevalent in Cont group; Staphylococcus, and Lactobacillus, were the most prevalent in T-2 group; Candidatus-Arthromitus and Staphylococcus were the most prevalent in T-2 + Ly group. Moreover, T-2 mice had significantly (p < 0.05) greater levels of interleukin-1 beta (IL-1β), interferon gamma (IFN-γ), Interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) than Cont, while the Ly significantly (p < 0.05) lowered their concentration. The T-2 mice had significantly (p < 0.05) higher levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while their catalase (CAT),, glutathione (GSH), adenosine triphosphate (ATP), and superoxide dismutase 1(SOD1) activities were significantly (p < 0.05) lower than Cont. Ly significantly (p < 0.05) restored their concentration. Moreover, there was a significant reduction (p < 0.05) of hexanoic, butyric, acetic, pentanoic, and Heptanoic acids in the T-2 mice compared to Cont. In contrast, treatment with Ly was found to significantly restore their levels compared to T-2 group. We conclude that Ly administration in the context of T-2-induced toxicity may help attenuate systemic oxidative stress and inflammation, possibly through modulation of gut microbiota and fecal short-chain fatty acids (SCFAs).

Synergistic effects of berberine and adipose stem cells in a silk fibroin-PEG hydrogel for diabetic wound healing via macrophage polarization modulation.

Hu Xiaohao X, Xu Jia J, Zhong Yanping Y, Zheng Weihao W et al.

Diabetic wound repair remains a considerable clinical challenge, largely due to the limited efficacy of current therapies. Herein, we engineered a novel silk fibroin (SF)-polyethylene glycol (PEG) hydrogel (SPB) incorporated with berberine (BBR) and adipose-derived stem cells (ASCs) to synergistically promote diabetic wound healing. By optimizing the physicochemical properties of SPB, we found that a 7:3 SF:PEG ratio provided an ideal balance of pore size (25.83 ± 3.94 μm), mechanical strength (32.33 ± 4.07 kPa) and sustained BBR release. In vitro, SPB significantly enhanced ASC paracrine function, promoting the production of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), stromal cell-derived factor 1 (SDF-1), platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor beta (TGF-β). Accordingly, SF-based hydrogel system (SPBA) markedly stimulated fibroblast proliferation and migration and enhanced endothelial cell angiogenesis. Moreover, SPBA effectively modulated macrophage repolarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, thereby suppressing inflammation. In vivo, SPBA demonstrated remarkable therapeutic efficacy in diabetic rat full-thickness skin wounds, accelerating wound closure, promoting re-epithelialization, collagen deposition and neovascularization, while reducing local inflammation. These results highlight SPBA as a highly efficient and promising biomaterial strategy for diabetic wound treatment.

Correction: Postoperative adding-on phenomenon in Lenke 1A/B and 2A/B adolescent idiopathic scoliosis: risk factors and predictive index.

Zhang Hongqi H, Li Tao T, Zhang Gengming G, Deng Ang A et al.