Genetic Polymorphism of Matrix Metalloproteinase-9 and Susceptibility to Myocardial Infarction: A Meta-Analysis

Objective. Current findings on the association between MMP-9 rs3918242 and susceptibility to myocardial infarction (MI) are inconsistent, and their definite relationship is discussed in this meta-analysis. Methods. Eligible literatures reporting MMP-9 rs3918242 and susceptibility to MI were searched in PubMed, Cochrane Library, CNRI, and VIP using keywords such as “MMP-9”, “matrix metallopeptidase-9” and “myocardial infarction”, “acute myocardial infarction”, “AMI”, and “polymorphism”. Data from eligible literatures were extracted for calculating OR and corresponding 95% CI using RevMan 5.3 and STATA12.0. Results. Ten independent literatures reporting MMP-9 rs3918242 and susceptibility to MI were enrolled. Compared with subjects carrying CT&TT genotype of MMP-9 rs3918242, susceptibility to MI was lower in those carrying CC genotype ( OR = 1.49 , 95 % CI = 1.19 – 1.86 , P = 0.0004 ). Such a significance was observed in the overdominant ( OR = 1.27 , 95 % CI = 1.14 – 1.41 , P < 0.0001 ) and allele genetic models ( OR = 1.43 , 95 % CI = 1.17 – 1.74 , P = 0.0005 ) as well. This finding was also valid in the Asian population. Conclusions. Mutation on MMP-9 rs3918242 has a potential relevance with susceptibility to MI.

Exosome miR-155-5p Derived from Lung Cancer Hcc827 Promotes Macrophage Activation and Lung Cancer Progression

This stud intends to assess whether exosome miR-155-5p derived from human non-small cell lung cancer cells (Hcc827) activates macrophages in lung cancer. Lung cancer Hcc827 cells were assigned into control group and expeirmental group (cultured with macrophages, THP-1 activated by exosome miR-155-5P derived from Hcc827) followed by analysis of macrophage markers inducible nitric oxide synthase (INOS), recombinant human CD163 (CD163), matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 2 (MMP2), and E-cadherin by real-time fluorescent quantitative PCR (RFQ-PCR), IL-10, IL-6 and IL-8 levels by chemiluminescence, cell invasion by Transwell assay and related protein expression by Western blot. miR-155-5p treatment significantly reduced INOS and TNF-β expressions and increased CD163, TNF-α, IL-8, IL-6 and IL-10 expressions along with enhanced cell invasion. In addition, MMP9 and MMP2 expressions in experimental group were significantly increased and E-cdherin was reduced. In conclusion, exosome miR-155-5p derived from lung cancer Hcc827 cells activates macrophages and enhanced lung cancer cell invasion.

Proteomic profiling of human amnion for preterm birth biomarker discovery

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

MMP-9 and IL-1β as Targets for Diatoxanthin and Related Microalgal Pigments: Potential Chemopreventive and Photoprotective Agents

Photochemoprevention can be a valuable approach to counteract the damaging effects of environmental stressors (e.g., UV radiations) on the skin. Pigments are bioactive molecules, greatly attractive for biotechnological purposes, and with promising applications for human health. In this context, marine microalgae are a valuable alternative and eco-sustainable source of pigments that still need to be taken advantage of. In this study, a comparative in vitro photochemopreventive effects of twenty marine pigments on carcinogenic melanoma model cell B16F0 from UV-induced injury was setup. Pigment modulation of the intracellular reactive oxygen species (ROS) concentration and extracellular release of nitric oxide (NO) was investigated. At the cell signaling level, interleukin 1-β (IL-1β) and matrix metallopeptidase 9 protein (MMP-9) protein expression was examined. These processes are known to be involved in the signaling pathway, from UV stress to cancer induction. Diatoxanthin resulted the best performing pigment in lowering MMP-9 levels and was able to strongly lower IL-1β. This study highlights the pronounced bioactivity of the exclusively aquatic carotenoid diatoxanthin, among the others. It is suggested increasing research efforts on this molecule, emphasizing that a deeper integration of plant ecophysiological studies into a biotechnological context could improve the exploration and exploitation of bioactive natural products.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflects the Severity for the Acute and Chronic Infectious Diseases

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.