Macrophage-orchestrated, low-grade chronic inflammation plays a pivotal role in obesity and atherogenesis. However, the underlying regulatory mechanisms remain incompletely understood. Here, we identify major vault protein (MVP), the main component of unique cellular ribonucleoprotein particles, as a suppressor for NF-κB signaling in macrophages. Both global and myeloid-specific MVP gene knockout aggravates high-fat diet induced obesity, insulin resistance, hepatic steatosis and atherosclerosis in mice. The exacerbated metabolic disorders caused by MVP deficiency are accompanied with increased macrophage infiltration and heightened inflammatory responses in the microenvironments. In vitro studies reveal that MVP interacts with TRAF6 preventing its recruitment to IRAK1 and subsequent oligomerization and ubiquitination. Overexpression of MVP and its α-helical domain inhibits the activity of TRAF6 and suppresses macrophage inflammation. Our results demonstrate that macrophage MVP constitutes a key constraint of NF-κB signaling thereby suppressing metabolic diseases.

The objective of this study was to determine the effects of different transport times on broilers during summer on stress, meat quality, and early postmortem muscle metabolites. Arbor Acres broiler chickens (n = 105) were randomly categorized into 5 treatments: unstressed control, 0.5 h, 1 h, 2 h, and 4 h transport. Each treatment consisted of 3 replicates with 7 birds each. All birds (except the control group) were transported according to a designed protocol. With the extension of transport time, the activities of plasma creatine kinase (CK) and lactate dehydrogenase (LDH) gradually increased. The content of heat shock protein 70 (Hsp70) did not change significantly during 0.5 h transport compared to the control group, but was significantly higher (P < 0.05) at 1 h or more of transport time. Also, transport times of 2 h or more resulted in a death rate of 20%-33% of broilers. We found that the breast meat in the 0.5 h transport group had significantly (P < 0.05) higher L* values, drip loss, cooking loss, AMP/ATP ratio, and phosphorylation of AMP-activated protein kinase (p-AMPK). In addition, pH24h was lower compared to the control group, increasing the likelihood of pale, soft, and exudative (PSE)-like meat. However, no significant variations were found in meat color, drip loss, or cooking loss in other transport groups compared to the control group under the condition of this study. Muscle glycogen content decreased with time of transportation. There were significant correlations among p-AMPK and meat quality (P < 0.05). These results indicate that preslaughter transport during summer may cause severe physiological and biochemical changes of broilers. Further investigations studying the deeper relationship between biological indicators and meat quality according to the similar transport conditions would provide a better understanding of the effect of transport duration on meat quality.

Heat stress impairs growth performance and alters body protein and amino acid metabolism. This study was investigated to explore how body protein and amino acid metabolism changed under heat stress ( HS ) and the stress adaptation mechanism. A total of 144 broilers (28 d old) were divided into 3 treatment groups for 1 wk: HS group (32°C), normal control group (22°C), and pair-feeding group (22°C). We found that HS elevated the feed-to-gain ratio, reduced the ADFI and ADG, decreased breast muscle mass and plasma levels of several amino acids (glycine, lysine, threonine, and tyrosine), and increased serum glutamic oxaloacetic transaminase ( GOT ) activity and corticosterone ( CORT ) level and liver GOT and glutamic pyruvic transaminase activities. Heat stress elevated muscle atrophy F-box mRNA expression and reduced mRNA expression of the 70-kD ribosomal protein S6 kinase in the breast muscle of broilers. Broilers in the HS group exhibited striking increases of mRNA expressions of solute carrier family 1 member 1, family 3 member 1, family 7 member 1, and family 7 member-like in the liver and liver gluconeogenesis genes ( PCKc , PCKm , PC , and FBP1 ) in comparison with the other 2 groups. In conclusion, HS increased the circulating CORT level and subsequently caused muscle protein breakdown to provide amino acid substrates to liver gluconeogenesis responsible for energy supply.

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To improve bone regeneration in oral microenvironment, we generated a novel biodegradable, antibacterial, and osteoconductive electrospun PLGA/PCL membrane as an ideal osteogenic scaffold. The novel three-layer membranes were structured with serial layers of electrospun chlorhexidine-doped-PLGA/PCL (PPC), PLGA/PCL (PP), and β-tricalcium phosphate-doped-PLGA/PCL (PPβ). To characterize osteoconductive properties of these membranes, MC3T3-E1 (MC) cultures were seeded onto the membranes for 14 days for evaluation of cell proliferation, morphology and gene/protein expression. In addition, MC cells were cultured onto different surfaces of the three-layer membranes, PPC layer facing MC cells (PPβ-PP-PPC) and PPβ layer facing MC cells (PPC-PP-PPβ) to evaluate surface-material effects. Membrane properties and structures were evaluated. Antibacterial properties against Streptococcus mutans and Staphylococcus aureus were determined. Scanning electron microscope demonstrated smaller interfiber spaces of PPC and PPβ-PP-PPC compared to PPβ, PPC-PP-PPβ, and PP. PPC and PPβ-PP-PPC exhibited hydrophilic property. The three-layer membranes (PPC-PP-PPβ and PPβ-PP-PPC) demonstrated significantly higher Young's modulus (94.99 ± 4.03 MPa and 92.88 ± 4.03 MPa) compared to PP (48.76 ± 18.15 MPa) or PPC (7.92 ± 3.97 MPa) (p < 0.05). No significant difference of cell proliferation was found among any groups at any time point (p > 0.05). Higher expression of integrins were detected at 12 h of cultures on PPC-PP-PPβ compared to the controls. Promoted osteoconductive effects of PPC-PP-PPβ were revealed by alkaline phosphatase assays and Western blot compared with the controls at 7 and 14 days. PPC, PPC-PP-PPβ and PPβ-PP-PPC exhibited a significantly wider antibacterial zone against the tested bacteria compared to PP and PPβ (p < 0.05). These results suggested that the three-layer electrospun membranes demonstrated superior properties: higher strength, better cell adhesion, and promoted osteoconductive properties compared to single-layer membrane: however, antibacterial properties were exhibited in three-layer electrospun membranes and chlorhexidine-doped single-layer membrane. We concluded that the novel three-layer membranes could be used as a biocompatible scaffold for intraoral bone regeneration due to its enhanced osteoconductive activity and antibacterial effect.

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Dysfunctional megakaryopoiesis hampers platelet production, which is closely associated with thrombocytopenia (PT). Macrophages (MФs) are crucial cellular components in the bone marrow (BM) microenvironment. However, the specific effects of M1 MФs or M2 MФs on regulating megakaryocytes (MKs) are largely unknown. In the current study, aberrant BM-M1/M2 MФ polarization, characterized by increased M1 MФs and decreased M2 MФs and accompanied by impaired megakaryopoiesis-supporting abilities, was found in patients with PT post-allotransplant. RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MФs of PT patients. Moreover, in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MФs from PT patients. Furthermore, we found M1 MФs suppress, whereas M2 MФs support MK maturation and platelet formation in humans. Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MФs, as indicated by decreased MK count, colony-forming unit number, high-ploidy distribution, and platelet count. Importantly, genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MФs both in vitro and in a MФ-specific PI3K-knockdown murine model, indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 MФs. Furthermore, our preliminary data indicated that TGF-β released by M2 MФs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs. Taken together, our data reveal that M1 and M2 MФs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner, which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.