Research progress on the mechanisms underlying poultry immune regulation by plant polysaccharides.

With the rapid development of poultry industry and the highly intensive production management, there are an increasing number of stress factors in poultry production. Excessive stress will affect their growth and development, immune function, and induce immunosuppression, susceptibility to a variety of diseases, and even death. In recent years, increasing interest has focused on natural components extracted from plants, among which plant polysaccharides have been highlighted because of their various biological activities. Plant polysaccharides are natural immunomodulators that can promote the growth of immune organs, activate immune cells and the complement system, and release cytokines. As a green feed additive, plant polysaccharides can not only relieve stress and enhance the immunity and disease resistance of poultry, but also regulate the balance of intestinal microorganisms and effectively alleviate all kinds of stress faced by poultry. This paper reviews the immunomodulatory effects and molecular mechanisms of different plant polysaccharides (Atractylodes macrocephala Koidz polysaccharide, Astragalus polysaccharides, Taishan Pinus massoniana pollen polysaccharide, and alfalfa polysaccharide) in poultry. Current research results reveal that plant polysaccharides have potential uses as therapeutic agents for poultry immune abnormalities and related diseases.

[Progress on signal pathways related to bone metabolism in animals].

Bone is a hard organ that makes up vertebrate endoskeleton, which plays a role in movement, support and protection for the body. The normal growth and development of bone is in the dynamic balance of bone metabolism, which is composed of bone formation and bone absorption. This balance is very important for maintaining bone mass and mineral homeostasis. In the process of bone growth and metabolism, there are many signaling pathways regulating bone formation and absorption, such as BMP (bone morphogenetic protein)/SMADs, TGF-ß (transforming growth factor ß), Wnt/ß-catenin, OPG (osteoprotegerin)/RANKL (receptor activator of NF-κB ligand)/RANK (receptor activator of NF-κB), FGF (fibroblast growth factor) and Notch signaling pathway. These signaling pathways have complex regulatory mechanisms and are involved in the regulation of bone metabolism. In this review, we summarize the mechanism and research progress of signal pathways that play key regulatory roles in the process of animal bone metabolism, thereby laying a foundation for research in animal bone metabolism.

Clinical and prognostic significance of preoperative lymphocyte-monocyte ratio, neutrophil-lymphocyte ratio and neutrophil-monocyte ratio on esophageal squamous cell carcinoma patients.

BACKGROUND: The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to evaluate whether preoperative lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), and neutrophil-monocyte ratio (NMR) could predict the prognosis of ESCC patients undergoing esophagectomy. METHODS: A total of 1,883 patients with histologically diagnosed ESCC who underwent radical esophagectomy from May 2005 to May 2015 were retrospectively reviewed. Besides clinicopathological factors, "Survminer" package in R® was applied to determine the optimal cut-off point for LMR, NLR and NMR. Meanwhile, we evaluated the prognostic value of LMR, NLR, and PLR using Kaplan-Meier curves and Cox regression models. RESULTS: The median follow-up was 28.77 months (range, 1.60-247.90 months). The optimal cut-off point of LMR, NLR and NMR is 3.83, 2.06 and 7.21, respectively. Kaplan-Meier survival analysis of patients with low preoperative LMR demonstrated a significant worse prognosis for 5-year OS (P<0.001) than those with high preoperative LMR. The high NLR cohort had lower 5-year OS (P<0.001). No significant difference with 5-year OS was found in NMR (P=0.405). On multivariate analysis, preoperative LMR (P=0.018; HR =0.786, 95% CI: 0.645, 0.959) and NLR (P=0.028; HR =1.247, 95% CI: 1.024, 1.519) were the independent prognostic factors in ESCC patients. Integrating LMR and NLR, we divided the ESCC patients in four groups according to their cut-off points and we found the patients in LMR ≥3.83 and NLR <2.06 group received the best prognosis while the prognosis of patients in LMR<3.83 and NLR ≥2.06 group was the worst. The difference was statistically significant. CONCLUSIONS: Preoperative LMR and NLR better predicts cancer survival in patients with ESCC undergoing esophagectomy, especially under the circumstances of LMR ≥3.83 and NLR <2.06.

Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation.

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

Expressions of Shell Matrix Protein Genes in the Pearl Sac and Its Correlation with Pearl Weight in the First 6 Months of Pearl Formation in Hyriopsis cumingii.

Matrix proteins regulate crystal nucleation, morphology, and polymorphism during pearl biomineralization and have significant correlations with pearl quality traits in nucleated pearls. However, there is little information about the connection between pearl quality traits and matrix proteins in non-nucleated pearls. In this study, we analyzed CaCO3 deposition during the first month of non-nucleated pearl formation and examined the expression patterns of ten shell matrix protein genes (Hcperlucin, hic31, silkmapin, hic22, hic74, hic52, HcTyr, HcCA3, hic24 and Hc-upsalin) in the pearl sac of Hyriopsis cumingii. During pearl formation, CaCO3 crystals were initially deposited in a disorderly manner during days 12 and 15 of pearl formation. On days 18 and 21, CaCO3 crystals gradually nucleated on an organic membrane, and the pattern of crystal deposition changed markedly. Between days 24 and 30, crystals similar to nacre tablets were deposited; they then grew and formed connections in a more orderly fashion, eventually forming the nacreous layer. We observed high expression levels of shell matrix proteins during the phases of disordered or ordered CaCO3 deposition, suggesting they were involved in non-nucleated pearl formation. Furthermore, the expressions of nine matrix proteins were significantly correlated with pearl weight during the first 6 months after grafting. The prismatic-layer matrix protein hic31 and nacreous-layer matrix protein hic22 showed negative correlations with pearl weight, but the other seven nacreous-layer matrix proteins had significantly positive correlations with pearl weight. These results show the involvement of matrix proteins in pearl formation and in determination of quality traits.

Screening of genes involved in epithelial-mesenchymal transition and differential expression of complement-related genes induced by PAX2 in renal tubules.

AIM: The aim of the present study was to screen and verify downstream genes involved in the epithelial mesenchymal transition (EMT) induced by paired box 2 (PAX2) in NRK-52E cells. METHODS: NRK-52E cells were transfected with lentivirus carrying PAX2 gene or no-load virus respectively. Total RNA was isolated 72 h after transfection from PAX2-overexpressing cells and control cells. Isolated RNA was then hybridized with the Rat OneArray Plus expression profile chip. The chips were examined by Agilent 0.1 XDR to screen for differentially expressed genes, which were further analyzed to investigate complement-related genes as genes of interest. RESULTS: In NRK-52E cells, PAX2 overexpression promoted EMT followed by upregulation of 298 genes and downregulation of 293 genes. KEGG analysis indicated the differential expression of genes related to cytokines and their receptors, extracellular matrix (ECM), MAPKs, local adhesion, cancer, the complement cascade, and coagulation. Gene oncology analysis screened out genes related to molecular functions (e.g., hydrolase activity, phospholipase activity, components of the ECM) and biological processes (e.g., cell development, signal transduction, phylogeny), and cell components (e.g., cytoplasm, cell membrane, and ECM). Analysis of the complement system revealed upregulation of C3 and downregulation of CD55 and complement regulator factor H (CFH). CONCLUSION: PAX2 overexpression upregulates EMT in vitro and may regulate C3, CD55, and CFH.

Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-ß1 signaling in a mouse model of osteoarthritis.

Transforming growth factor beta 1 (TGF-ß1) is implicated in osteoarthritis. We therefore studied the role of TGF-ß1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-ß receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-ß1 signaling protects adult knee joints in mice against the development of osteoarthritis.