Characterization and Comparison Analysis of Milk Fat Globule Membrane Proteins between Human and Porcine Milk.

This study aimed to explore the differences in milk fat globule membrane (MFGM) proteins between human milk (HM) and porcine milk (PM) using a label-free quantitative proteomic approach. A total of 3920 and 4001 MFGM proteins were identified between PM and HM, respectively. Among them, 3520 common MFGM proteins were detected, including 956 significant differentially expressed MFGM proteins (DEPs). Gene ontology (GO) enrichment analysis showed that the DEPs were highly enriched in the lipid metabolic process and intrinsic component of membrane. Kyoto Encyclopedia of Genes and Genomes pathways suggested that protein processing in the endoplasmic reticulum was the most highly enriched pathway, followed by peroxisome, complement, and coagulation cascades. This study reflects the difference in the composition of MFGM proteins between HM and PM and provides a scientific and systematic reference for the development of MFGM protein nutrition.

Label-free quantitative proteomic analysis of milk fat globule membrane proteins in porcine colostrum and mature milk.

Milk fat globule membrane (MFGM) proteins are nutritional components with various biological functions. This study aimed to analyze and compare MFGM proteins in porcine colostrum (PC) and porcine mature milk (PM), via label-free quantitative proteomics. In total, 3917 and 3966 MFGM proteins were identified in PC and PM milk, respectively. A total of 3807 common MFGM proteins were found in both groups, including 303 significant differentially expressed MFGM proteins. Gene Ontology (GO) analysis revealed that the differentially expressed MFGM proteins were mainly related to the cellular process, cell, and binding. The dominant pathway of the differentially expressed MFGM proteins was related to the phagosome according to Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. These results reveal crucial insights into the functional diversity of MFGM proteins in porcine milk during lactation and provide theoretical guidance for the development of MFGM proteins in the future.

A scoring system for gallbladder polyps based on the cross-sectional area and patient characteristics.

BACKGROUND: Current management guidelines for gallbladder polyps (GBPs) focus on a diameter more than 1 cm as an indication for cholecystectomy. Since most GBPs are not malignant, unnecessary cholecystectomies can lead to unnecessary complications and costs. We developed a score to identify true polyps focusing on their cross-sectional area (CSA). METHODS: We retrospectively analyzed the demographic, clinical, laboratory, and sonographic characteristics of 522 patients with GBPs who had undergone cholecystectomy at our hospital between January 2010 and July 2020 (reference group). We used univariate analysis to compare these parameters between 88 true polyps and 434 pseudopolyps and multivariate logistic regression analysis to identify parameters to include in our scoring model. Receiver operating characteristics and area under the curve were used to identify cut-off values. The model was tested on a validation group of 98 patients. RESULTS: In the multivariate analysis, a CSA >123 mm2, positive blood flow signal, age >55.5 years, alanine aminotransferase (ALT) levels > 50 U/L, and an ALT/aspartate aminotransferase ratio > 0.77 were significantly associated with true polyps (odds ratio 6.528, 2.377, 2.617, 2.445, and -0.372, respectively). A prediction model based on cut-off values was used to distinguish a low-risk and high-risk GBP group; true polyps accounted for 6.54% and 58.72%, respectively (p < 0.001). In the low-risk and high-risk validation groups, true polyps comprised 12.35% and 82.35%, respectively (p < 0.001). CONCLUSIONS: Our scoring system shows high accuracy and specificity in identifying true polyps and helps determine the need for surgical resection.

PINK1/PARK2 dependent mitophagy effectively suppresses NLRP3 inflammasome to alleviate acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a clinically common acute inflammatory disease in digestive system, leading to systemic inflammatory response syndrome (SIRS) and severe acute pancreatitis (SAP). It was reported that PINK1/PARK2 dependent mitophagy played an important role in various inflammatory diseases. However, its role in AP has not been elucidated. Herein, we explore the effect of mitophagy in the pathogenesis of AP. METHODS: Firstly, we established cerulein-induced AP group and arginine-induced SAP group based on wild, PINK1-/- and PARK2-/- mice. Pancreatic samples were harvested for further investing the mitochondrial dynamics, mitophagy alterations, NLRP3 inflammatory pathway etc. Furthermore, peripheral blood mononuclear cells from SAP patients were collected to examine the expression of mitophagy-related indicators. Additionally, the interrelationship between mitophagy and NLRP3 inflammasome was also explored in AP. RESULTS: It was confirmed that mitochondria were damaged in both AP and SAP models. The expressions of PINK1, PARK2 and mitochondrial autophagosomes were elevated in wild AP group, which were decreased in SAP group over time. Similarly, the expressions of PINK1 and PAKR2 in peripheral blood mononuclear cells were significantly lower in SAP patients. Besides, in PINK1-/- and PARK2-/- mice AP groups, more pronounced inflammatory infiltration, increased apoptotic and necrotic levels and upregulated NLRP3 inflammasome pathway were detected. After injection with MCC950, NLRP3 inflammasome production was notably reduced in PINK1-/-and PARK2-/-mice, which effectively alleviated the pancreatic damage and inflammatory cell infiltration. CONCLUSION: Our study suggested that mitochondrial dysfunction activated PINK1/PARK2-mediated mitophagy in AP, while mitophagy was impaired in SAP. PINK1-/- and PARK2-/- mice were more sensitive to onset of SAP and the deficiency of mitophagy could lead to the formation of NLRP3 inflammasome.