Role of Polysaccharides from Marine Seaweed as Feed Additives for Methane Mitigation in Ruminants: A Critical Review.

Given the increasing concerns regarding greenhouse gas emissions associated with livestock production, the need to discover effective strategies to mitigate methane production in ruminants is clear. Marine algal polysaccharides have emerged as a promising research avenue because of their abundance and sustainability. Polysaccharides, such as alginate, laminaran, and fucoidan, which are extracted from marine seaweeds, have demonstrated the potential to reduce methane emissions by influencing the microbial populations in the rumen. This comprehensive review extensively examines the available literature and considers the effectiveness, challenges, and prospects of using marine seaweed polysaccharides as feed additives. The findings emphasise that marine algal polysaccharides can modulate rumen fermentation, promote the growth of beneficial microorganisms, and inhibit methanogenic archaea, ultimately leading to decreases in methane emissions. However, we must understand the long-term effects and address the obstacles to practical implementation. Further research is warranted to optimise dosage levels, evaluate potential effects on animal health, and assess economic feasibility. This critical review provides insights for researchers, policymakers, and industry stakeholders dedicated to advancing sustainable livestock production and methane mitigation.

PU.1 interaction with p50 promotes microglial-mediated inflammation in secondary spinal cord injury in SCI rats.

Purpose/aim of the study Secondary spinal cord injury is the inflammatory damage to surrounding tissues caused by activated microglial-mediated neuroinflammatory responses. The nuclear factor-κB (p65/p50) pathway and PU.1 are closely correlated with inflammatory responses; thus, we examined the relationship and function between PU.1 and p50 in secondary spinal cord injury.Materials and methods In this study, we established an adult rat acute spinal cord injury model to simulate the pathological process of spinal cord injury.Results: We found that the expression of PU.1 was significantly increased at three days after spinal cord injury and mainly expressed in activated microglia. Moreover, p-p50 expression was increased in SCI rats and the protein interacted with PU.1. Lipopolysaccharide was used to induce microglia activation in vitro.Conclusions: The results showed that PU.1 and p-p50 expression was significantly increased and PU.1 interacted with p50 in the nucleus. The levels of tumor necrosis factor-α and interleukin-1ß secreted by microglia were detected by enzyme-linked immunosorbent assay. The results showed that when both PU.1 and p50 were overexpressed, tumor necrosis factor-α and interleukin-1ß secretion was significantly increased to levels higher than in cells overexpressing PU.1 or p50 alone. These results suggest that PU.1 and p50 interact to promote p65 transcription and the expression of inflammatory factors, which is an important mechanism of the microglial-mediated inflammatory response to secondary injury after spinal cord injury.

Downregulation of USP4 Promotes Activation of Microglia and Subsequent Neuronal Inflammation in Rat Spinal Cord After Injury.

NF-κB is involved in the activation of microglia, which induces secondary spinal cord injury (SCI). This process involves the activation of NF-κB signaling pathway by TRAF6 through its polyubiquitination function. We know that deubiquitination of TRAF6 mediated by deubiquitinating enzyme (DUB) significantly inhibits activation of NF-κB pathway. The ubiquitin-specific protease 4 (USP4) belongs to the deubiquitinase family. Therefore, we hypothesize that USP4 is involved in the microglial activation and subsequent neuronal inflammation after SCI. In this study, we examined the expression and the role of USP4 after SCI. Western blot analysis showed that the expression of USP4 was downregulated and the expression of p-p65 was upregulated in the spinal cord after SCI. Immunohistochemical and immunofluorescence staining showed that USP4 was expressed in microglia but its expression decreased after SCI. In vitro LPS-induced activation of microglia showed decreased expression of USP4 and increased expression of p-p65 and TRAF6. USP4 silencing in LPS-induced activation of microglia promoted the expression of p-p65 and TRAF6 and the secretion of TNF-α and IL-1ß. In conclusion, our study provides the first evidence that in microglial cells expression of USP4 decreases after SCI in rats. The downregulation of USP4 expression may promote microglial activation and subsequent neuronal inflammation through NF-κB by attenuating the deubiquitination of TRAF6. This mechanism is of great significance in the pathophysiology of secondary SCI.

EphA4 promotes cell proliferation and cell adhesion-mediated drug resistance via the AKT pathway in multiple myeloma.

Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular (Eph) family, has been reported to upregulate in several tumors. However, the role of EphA4 in multiple myeloma has not been clarified yet. In this study, we found that EphA4 promoted proliferation of multiple myeloma cells via the regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of multiple myeloma cells and promoted cell adhesion-mediated drug resistance by enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple myeloma. More interestingly, we discovered that EphA4 can interact with cyclin-dependent kinase 5 (CDK5) and regulate its expression in multiple myeloma. CDK5 has been reported to be overexpressed in multiple myeloma which mediated bortezomib resistance and also participated in AKT pathway. And we have also proved the fact. So, we supposed that EphA4 interacted with CDK5 and promoted its expression which in turn enhanced p-AKT expression and promoted cell adhesion-mediated drug resistance in multiple myeloma. Therefore, this study clarifies the molecular mechanism of cell adhesion-mediated drug resistance and may be useful in identifying potential target for treatment of multiple myeloma.