A study of extracellular matrix-cell adhesion peptidic epitopes related to human serum amyloid A (SAA)

Summary Serum amyloid A (SAA), an acute-phase protein, exists normally in the serum while complexed with high-density lipoprotein 3 (SAA-HDL₃). Its levels increase markedly during inflammatory diseases. The pentapeptide Tyr-Ile-Gly-Ser-Asp (YIGSR-like) and the tripeptide Arg-Gly-Asn (RGD-like), related to the cell adhesion domains of laminin and fibronectin, respectively, exist in SAA within close proximity (YIGSDKYFHARGNY; amino acid residues 29–42). A structure-function study of linear and head-to-tail cyclic peptides, related to the amino acid residues 29–42) and 70–76 (GRGAEDS) of human SAA, was performed in order to evaluate their ability to inhibit adhesion of human T-lymphocytes to surfaces coated with extracellular matrix purified from bovine corneal cells.     

Change in the Concentration and Tissue localization of Endogenous IAA During the Regeneration of Vascular Tissues After Xylem Removal in Broussonetia papyrifera

Change in the concentration of endogenous IAA was monitored with enzyme-linked immunesorbent assay (ELISA), and IAA localization in the tissues was demonstrated by means of immunogold-silver microscopy, with authors' modification, during the regeneration after removal of xylem in Broussonetia popyrifera (L.) Vent. The stimulation exerted from xylem removal produced a rapid increase of about 70% of the endogenous IAA concentration. However, the concentration decreased during differentiation of the vascular tissues. Although removal of the tree crown inhibited the regeneration of vascular tissues, the change tendency in the concentration of endogenous IAA during the regeneration remained the same as if the tree crown was intact. This suggested that rapid increase of endogenous IAA induced by wounding could be a result from a release of the combined form into free IAA. Tissue-localization showed that there were more silver-grains labelled in the rays, callus and the regenerated differentiating vascular tissue cells than in other tissues. It could suggest that the high concentration of endogenous IAA triggered the dedifferentiation of the vascular tissues after removal of xylem, and the less concentrated IAA flow could promote the initiation and activity of the regenerated cambium.     

Intestinal microflora and the interaction with immunocompetent cells

The intestinal mucosal surface is colonised by the comensal microflora that attains very high numbers of bacterial cells in the distal intestine, more specifically in the colon. At the same time these extensive areas are the interface with the external environment, through which most pathogens initiate infectious processes in mammals. Intestinal mechanisms of defense need to discriminate accurately between comensal, symbiotic microflora, and exogenous pathogens. Today we do not fully understand the essence of the mechanism of discrimination but, probably, innate as well as adaptive immune responses participate in this process. We have explored , in in vitro models, the capacity of mucosal immunocompetent cells to discriminate amongst signals delivered by different types of bacteria. We have found at least two different patterns of innate response to gram-negative and gram-positive bacteria, and within this last group big differences are observed between species. We have only wo rked with non-pathogenic bacteria in what may represent the modulation of the physiological host status. The understanding of these modulatory functions could render a unique possibility for the use of food-borne bacteria to prevent or correct intestinal problems associated with food allergy, inflammatory bowel disease, and autoimmunity.     

Vascular Bundle Distribution Within Broad Bean Seed Coat and the Structure of Unloading Region

Cytological observations were made on developing seed coat of broad bean (Vicia faba L.) by use of light and electron microscopy. Attention was focused on vascular distribution. The seeds were attached by the funiculus to tile large vascular bundles of pericarp of broad bean. The vascular bundle passed through hilum and two layers of palisade, entered the pa- renchyma of seed coat, then diverged in to two routes. One was a complete vascular bundle composed of both'phloem and xylem elements, it stretched down through seed raphe, then upward and terminated near the radical. The other was a two-recurrent-vascular-bundle with only phloem constitutents, they extended forward detoured the micropyle and extended downward, but did not join with the upward complete vascular bundle. The recurrent vascular bundles branched out many small short branches. The obvious difference between phloem of recurrent vascular bundle and of complete vascular bundle was that the companion ceils of the former did not normally modify to transfer ceils, but connected to the adjoining parenchyma cells through abundant plasmodesmata. It is deduced from the structural analysis that the symplastic route may play an important role, particularly in the region of recurrent vascular bundle, in the course of importing assimilates unloading in seed coat and transporting to the embryo.     

Neuropathy in COVID-19 associated with dysbiosis-related inflammation

Although COVID-19 affects mainly lungs with a hyperactive and imbalanced immune response, gastrointestinal and neurological symptoms such as diarrhea and neuropathic pains have been described as well in patients with COVID-19. Studies indicate that gut–lung axis maintains host homeostasis and disease development with the association of immune system, and gut microbiota is involved in the COVID-19 severity in patients with extrapulmonary conditions. Gut microbiota dysbiosis impairs the gut permeability resulting in translocation of gut microbes and their metabolites into the circulatory system and induce systemic inflammation which, in turn, can affect distal organs such as the brain. Moreover, gut microbiota maintains the availability of tryptophan for kynurenine pathway, which is important for both central nervous and gastrointestinal system in regulating inflammation. SARS-CoV-2 infection disturbs the gut microbiota and leads to immune dysfunction with generalized inflammation. It has been known that cytokines and microbial products crossing the blood-brain barrier induce the neuroinflammation, which contributes to the pathophysiology of neurodegenerative diseases including neuropathies. Therefore, we believe that both gut–lung and gut–brain axes are involved in COVID-19 severity and extrapulmonary complications. Furthermore, gut microbial dysbiosis could be the reason of the neurologic complications seen in severe COVID-19 patients with the association of dysbiosis-related neuroinflammation. This review will provide valuable insights into the role of gut microbiota dysbiosis and dysbiosis-related inflammation on the neuropathy in COVID-19 patients and the disease severity.     

Dipeptidyl peptidase-4 inhibition prevents lung injury in mice under chronic stress via the modulation of oxidative stress and inflammation

Exposure to chronic psychosocial stress is a risk factor for various pulmonary diseases. In view of the essential role of dipeptidyl peptidase 4 (DPP4) in animal and human lung pathobiology, we investigated the role of DPP4 in stress-related lung injury in mice. Eight-week-old male mice were randomly divided into a non-stress group and a 2-week immobilization stress group. Non-stress control mice were left undisturbed. The mice subjected to immobilized stress were randomly assigned to the vehicle or the DPP4 inhibitor anagliptin for 2 weeks. Chronic stress reduced subcutaneous and inguinal adipose volumes and increased blood DPP4 levels. The stressed mice showed increased levels in the lungs of genes and/or proteins related to oxidative stress (p67^phox, p47^phox, p22^phox and gp91^phox), inflammation (monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), apoptosis (caspase-3, -8, -9), senescence (p16^INK4A, p21, and p53) and proteolysis (matrix metalloproteinase-2 to -9, cathepsin S/K, and tissue inhibitor of matrix metalloproteinase-1 and -2), and reduced levels of eNOS, Sirt1, and Bcl-2 proteins; and these effects were reversed by genetic and pharmacological inhibitions of DPP4. We then exposed human umbilical vein endothelial cells in vitro to hydrogen peroxide; anagliptin treatment was also observed to mitigate oxidative and inflammatory molecules in this setting. Anagliptin can improve lung injury in stressed mice, possibly by mitigating vascular inflammation, oxidative stress production, and proteolysis. DPP4 may become a new therapeutic target for chronic psychological stress-related lung disease in humans and animals.     

Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.     

The interleukin-1β converting enzyme family of cysteine proteases

Interleukin-1β converting enzyme (ICE) is the first enzyme of a new family of cysteine endoproteinases to be isolated and characterized. An overview of the structure and activity of ICE is outlined together with highlights of salient features common to members of each of the family members. J. Cell. Biochem. 64:2–10. © 1997 Wiley-Liss, Inc.     

Heterogeneity of microvascular endothelial cells isolated from human term placenta and macrovascular umbilical vein endothelial cells

The present study compares some phenotypic and physiologic characteristics of microvascular and macrovascular endothelial cells from within one human organ. To this end microvascular endothelial cells from human full-term placenta (PLEC) were isolated using a new method and compared with macrovascular human umbilical vein endothelial cells (HUVEC) and an SV40-transformed placental venous endothelial cell line (HPEC-A2). PLEC were isolated by enzymatic perfusion of small placental vessels, purified on a density gradient and cultured subsequently. Histological sections of the enzyme-treated vessels showed a selective removal of the endothelial lining in the perfused placental cotyledons. The endothelial identity of the cells was confirmed by staining with the endothelial markers anti-von Willebrand factor, Ulex europaeus lectin and anti-QBEND10. The cells internalized acetylated low-density lipoprotein and did not show immunoreactivity with markers for macrophages, smooth muscle cells and fibroblasts. The spindle-shaped PLEC grew in swirling patterns similar to that described for venous placental endothelial cells. However, scanning electron microscopic examination clearly showed that PLEC remained elongated at the confluent state, in contrast to the more polygonal phenotype of HPEC-A2 and HUVEC that were studied in parallel. The amount of vasoactive substances (endothelin-1,2, thromboxane, angiotensin II, prostacyclin) released into the culture medium and the proliferative response to cytokines was more similar to human dermal microvessels (MIEC) derived from non-fetal tissue than to HUVEC. Potent mitogens such as vascular endothelial growth factors (VEGF121, VEGF165) and basic fibroblast growth factor (FGF-2) induced proliferation of all endothelial cell types. Placental growth factors PIGF-1 and PIGF-2 effectively stimulated cell proliferation on PLEC (142 +/- 7% and 173 +/- 10%) and MIEC (160 +/- 20% and 143 +/- 28%) in contrast to HUVEC (9 +/- 8% and 15 +/- 20%) and HPEC-A2 (15 +/- 7% and 24 +/- 6%) after 48 h incubation time under serum-free conditions. These data support evidence for (1) the microvascular identity of the isolated PLEC described in this study, and (2) the phenotypic and physiologic heterogeneity of micro- and macrovascular endothelial cells within one human organ.