Progress in Molecular Biology and Translational Science 

About: Progress in Molecular Biology and Translational Science is an academic journal published by Academic Press. The journal publishes majorly in the area(s): Medicine & G protein-coupled receptor. It has an ISSN identifier of 1877-1173. Over the lifetime, 1319 publications have been published receiving 37840 citations.

Biochemical and Biological Attributes of Matrix Metalloproteinases.

Abstract: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in the degradation of various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs. MMPs are secreted by many cells including fibroblasts, vascular smooth muscle (VSM), and leukocytes. MMPs are regulated at the level of mRNA expression and by activation of their latent zymogen form. MMPs are often secreted as inactive pro-MMP form which is cleaved to the active form by various proteinases including other MMPs. MMPs cause degradation of ECM proteins such as collagen and elastin, but could influence endothelial cell function as well as VSM cell migration, proliferation, Ca2+ signaling, and contraction. MMPs play a role in tissue remodeling during various physiological processes such as angiogenesis, embryogenesis, morphogenesis, and wound repair, as well as in pathological conditions such as myocardial infarction, fibrotic disorders, osteoarthritis, and cancer. Increases in specific MMPs could play a role in arterial remodeling, aneurysm formation, venous dilation, and lower extremity venous disorders. MMPs also play a major role in leukocyte infiltration and tissue inflammation. MMPs have been detected in cancer, and elevated MMP levels have been associated with tumor progression and invasiveness. MMPs can be regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines the extent of ECM protein degradation and tissue remodeling. MMPs have been proposed as biomarkers for numerous pathological conditions and are being examined as potential therapeutic targets in various cardiovascular and musculoskeletal disorders as well as cancer.

Exercise and the Regulation of Immune Functions.

Abstract: Exercise has a profound effect on the normal functioning of the immune system. It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular moderate intensity exercise is beneficial. Single bouts of exercise evoke a striking leukocytosis and a redistribution of effector cells between the blood compartment and the lymphoid and peripheral tissues, a response that is mediated by increased hemodynamics and the release of catecholamines and glucocorticoids following the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Single bouts of prolonged exercise may impair T-cell, NK-cell, and neutrophil function, alter the Type I and Type II cytokine balance, and blunt immune responses to primary and recall antigens in vivo. Elite athletes frequently report symptoms associated with upper respiratory tract infections (URTI) during periods of heavy training and competition that may be due to alterations in mucosal immunity, particularly reductions in secretory immunoglobulin A. In contrast, single bouts of moderate intensity exercise are "immuno-enhancing" and have been used to effectively increase vaccine responses in "at-risk" patients. Improvements in immunity due to regular exercise of moderate intensity may be due to reductions in inflammation, maintenance of thymic mass, alterations in the composition of "older" and "younger" immune cells, enhanced immunosurveillance, and/or the amelioration of psychological stress. Indeed, exercise is a powerful behavioral intervention that has the potential to improve immune and health outcomes in the elderly, the obese, and patients living with cancer and chronic viral infections such as HIV.

Breast Cancer Epidemiology, Prevention, and Screening

Abstract: Globally, breast cancer is both the most commonly occurring cancer and the commonest cause of cancer death among women. Available data suggest that incidence and mortality in high-resource countries has been declining whereas incidence and mortality in low-resource countries has been increasing. This pattern is likely to be due to changing risk factor profiles and differences in access to breast cancer early detection and treatment. Risk factors for breast cancer include increasing age, race, menarche history, breast characteristics, reproductive patterns, hormone use, alcohol use, tobacco use, diet, physical activity, and body habitus. Mutations in the BRCA 1 and BRCA 2 tumor suppressor genes are significantly associated with the development of breast and ovarian cancer by the age of 70. Survival depends on both stage and molecular subtype. As there are few signs and symptoms early on, early detection is an important strategy to improve outcomes. Major professional organizations in the United States and elsewhere recommend screening with mammography with appropriate follow up for an abnormal screening test, although they differ somewhat by recommended ages and frequency of screening. Studies suggest a 15%-40% mortality reduction secondary to screening, however, there are also concerns about harms, such as overdiagnosis (5%-54%) and overtreatment leading to long term complications, and false negatives (6%-46%). Identification of women at risk for BRCA1 and BRCA 2 mutations is also recommended with referral for genetic testing. Preventive interventions, such as lifestyle, medical, and surgical options are available for women testing positive for BRCA mutations.

Immunoproteasomes: structure, function, and antigen presentation.

Abstract: Immunoproteasomes contain replacements for the three catalytic subunits of standard proteasomes. In most cells, oxidative stress and proinflammatory cytokines are stimuli that lead to elevated production of immunoproteasomes. Immune system cells, especially antigen-presenting cells, express a higher basal level of immunoproteasomes. A well-described function of immunoproteasomes is to generate peptides with a hydrophobic C terminus that can be processed to fit in the groove of MHC class I molecules. This display of peptides on the cell surface allows surveillance by CD8 T cells of the adaptive immune system for pathogen-infected cells. Functions of immunoproteasomes, other than generating peptides for antigen presentation, are emerging from studies in immunoproteasome-deficient mice, and are complemented by recently described diseases linked to mutations or single-nucleotide polymorphisms in immunoproteasome subunits. Thus, this growing body of literature suggests a more pleiotropic role in cell function for the immunoproteasome.

Cadherins and epithelial-to-mesenchymal transition.

Abstract: Epithelial–mesenchymal transition (EMT) is a process whereby epithelial cells are transcriptionally reprogrammed, resulting in decreased adhesion and enhanced migration or invasion. EMT occurs during different stages of embryonic development, including gastrulation and neural crest cell delamination, and is induced by a panel of specific transcription factors. These factors comprise, among others, members of the Snail, ZEB, and Twist families, and are all known to modulate cadherin expression and, in particular, E-cadherin. By regulating expression of the cadherin family of proteins, EMTinducing transcription factors dynamically modulate cell adhesion, allowing many developmental processes to take place. However, during cancer progression EMT can be utilized by cancer cells to contribute to malignancy. This is also reflected at the level of the cadherins, where the cadherin switch between E- and N-cadherins is a classical example seen in cancer-related EMT. In this chapter, we give a detailed overview of the entanglement between EMT-inducing transcription factors and cadherin modulation during embryonic development and cancer progression. We describe how classical cadherins such as E- and N-cadherins are regulated during EMT, as well as cadherin 7, -6B, and 11.