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Microbiological Research Feb 2020Bacterial cell surface adhesins play a major role in facilitating host colonization and subsequent establishment of infection. The surface of Mycobacterium tuberculosis,... (Review)
Review
Bacterial cell surface adhesins play a major role in facilitating host colonization and subsequent establishment of infection. The surface of Mycobacterium tuberculosis, owing to the complex architecture of its cell envelope, expresses numerous adhesins with varied chemical nature, including proteins, lipids, lipoproteins, glycoproteins and glycopolymers. Studies on mycobacterial adhesins show that they bind with multifarious host receptors and extracellular matrix (ECM) components. In this review we have highlighted the adhesins that are abundantly present on the mycobacterial surface and their interactions with host receptors. M. tuberculosis interacts with various host cell surface receptors such as toll like receptors, C-type lectin receptors, scavenger receptors, and Fc and complement receptors. Apart from these, ECM components like fibronectin, collagen, elastin, laminin, fibrillin and vitronectin also provide binding sites for surface adhesins of the tubercle bacilli. M. tuberculosis adhesins include proteins with and without signal peptide sequence and transmembrane proteins. Other surface adhesin macromolecules of M. tuberculosis comprises of lipids, glycolipids and glycopolymers. The interaction between the mycobacterial adhesins and their host receptors result in adhesion of the microbe to the host cells, induction of immune response and aid in the pathogenesis of the disease. A thorough understanding of the different M. tuberculosis surface adhesins and host receptors will provide a better picture of interaction between them at molecular level. The information gained on adhesins and host receptors will prove beneficial in developing novel therapeutic strategies such as the use of anti-adhesin molecules to hinder the adhesion of bacteria to the host cells, thereby preventing establishment of infection. The surface molecules discussed in this review will also benefit in identification of new drug targets, diagnostic markers or vaccine candidates against the deadly pathogen.
Topics: Adhesins, Bacterial; Antitubercular Agents; Bacterial Proteins; Binding Sites; Extracellular Matrix Proteins; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Protein Sorting Signals; Receptors, Cell Surface; Vesicular Transport Proteins
PubMed: 31841935
DOI: 10.1016/j.micres.2019.126392 -
Journal of Dental Research Nov 2022Exposed dental pulp can maintain its vitality through a pulp-capping procedure with biocompatible materials, followed by reparative dentin formation. Our previous study...
Exposed dental pulp can maintain its vitality through a pulp-capping procedure with biocompatible materials, followed by reparative dentin formation. Our previous study demonstrated that a vitronectin-derived peptide (VnP-16) promotes osteoblast differentiation and concomitantly restrains osteoclast differentiation and resorptive function. In this study, we aimed to demonstrate that VnP-16 promotes odontoblast differentiation, mineralization, and reparative dentin formation in a pulp exposure model using a rat tooth. VnP-16 showed no cytotoxicity and promoted cellular behavior in human dental pulp cells, enhancing their differentiation into odontoblast-like cells and mineralization, effects that are comparable to those obtained with vitronectin. In a rat pulp exposure model, VnP-16 showed mild inflammatory responses at 2 and 4 wk or none. Mineral trioxide aggregate (MTA) demonstrated a tendency of early formation of reparative dentin at 2 wk when compared with recombinant human bone morphogenetic protein 2 (rhBMP-2) and VnP-16. However, VnP-16 induced reparative dentin formation similar to MTA and rhBMP-2 without inflammation at 4 wk. In addition, VnP-16 showed a thicker and homogeneous reparative dentin formation versus MTA and rhBMP-2. Collectively, these results suggest that VnP-16 can be a useful, direct pulp-capping agent for highly qualified reparative dentin formation by promoting cell behavior and odontoblastic differentiation of human dental pulp cells.
Topics: Animals; Humans; Rats; Biocompatible Materials; Bone Morphogenetic Protein 2; Dental Pulp; Dentin, Secondary; Vitronectin
PubMed: 35708468
DOI: 10.1177/00220345221101506 -
International Journal of Molecular... Mar 2023Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is... (Review)
Review
Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.
Topics: Female; Humans; Uterine Cervical Neoplasms; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Extracellular Matrix; Matrix Metalloproteinases; Endometrial Neoplasms; Tumor Microenvironment
PubMed: 36982551
DOI: 10.3390/ijms24065463 -
PloS One 2020Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early...
Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection. Vitronectin, a glycoprotein that is abundantly found in serum, extracellular matrix, and bone, binds to integrin αvβ3, and promotes cell adhesion and migration. Current studies indicate that patients with amplified vitronectin levels have lower survival rates than patients without amplified vitronectin levels. In this study, we focused on the role of vitronectin in breast cancer survival and its functional role as a non-invasive biomarker for early stage and stage specific breast cancer detection. To confirm that the expression of vitronectin is amplified in breast cancer, a total of 240 serum samples (n = 240), 200 from breast cancer patients and 40 controls were analyzed using the Reverse Phase Protein Array (RPPA) technique. Of the 240 samples, 120 samples were of African American (AA) descent, while the other 120 were of White American (WA) descent. Data indicated that there were some possible racial disparities in vitronectin levels and, differences also seen in the recurrent patient samples. Next, we tried to uncover the underlying mechanism which plays a critical role in vitronectin expression. The cellular data from four different breast cancer cell lines- MCF7, MDA-MB-231, MDA-MB-468, and HCC1599 indicated that the PI3K/AKT axis is modulating the expression of vitronectin. We believe that vitronectin concentration levels are involved and connected to the metastasis of breast cancer in certain patients, specifically based on recurrence or ethnicity, which is detrimental for poor prognosis. Therefore, in this current study we showed that the serum vitronectin levels could be an early marker for the breast cancer survival and we also determine the cellular signaling factors which modulate the expression and concentration of vitronectin.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Disease-Free Survival; Electrophoresis, Capillary; Ethnicity; Extracellular Matrix; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Neoplasm Recurrence, Local; Phosphatidylinositol 3-Kinases; ROC Curve; Vitronectin
PubMed: 33211735
DOI: 10.1371/journal.pone.0242141 -
International Journal of Molecular... Jul 2021Classic hairy cell leukemia (HCL) is a rare mature B-cell malignancy associated with pancytopenia and infectious complications due to progressive infiltration of the... (Review)
Review
Classic hairy cell leukemia (HCL) is a rare mature B-cell malignancy associated with pancytopenia and infectious complications due to progressive infiltration of the bone marrow and spleen. Despite tremendous therapeutic advances achieved with the implementation of purine analogues such as cladribine into clinical practice, the culprit biologic alterations driving this fascinating hematologic disease have long stayed concealed. Nearly 10 years ago, BRAF V600E was finally identified as a key activating mutation detectable in almost all HCL patients and throughout the entire course of the disease. However, additional oncogenic biologic features seem mandatory to enable HCL transformation, an open issue still under active investigation. This review summarizes the current understanding of key pathogenic mechanisms implicated in HCL and discusses major hurdles to overcome in the context of other BRAF-mutated malignancies.
Topics: Animals; Humans; Leukemia, Hairy Cell; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 34360545
DOI: 10.3390/ijms22157780 -
Neuro-oncology Advances 2023Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at...
BACKGROUND
Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD are unclear. The Abelson (ABL) tyrosine kinase family members, ABL1 and ABL2, have been implicated in cancer cell migration, invasion, adhesion, metastasis, and chemotherapy resistance, and are upstream mediators of the oncogene in fibroblasts and lung cancer cells. However, their role in medulloblastoma has not yet been explored. The purpose of this work was to elucidate the role of ABL1/2 in medulloblastoma LMD.
METHODS
and mRNA expression of patient specimens was analyzed. shRNA knockdowns of ABL1/2 and pharmacologic inhibition of ABL1/2 were used for in vitro and in vivo analyses of medulloblastoma LMD. RNA sequencing of ABL1/2 genetic knockdown versus scrambled control medulloblastoma was completed.
RESULTS
mRNA is highly expressed in human medulloblastoma and pharmacologic inhibition of ABL kinases resulted in cytotoxicity. Knockdown of resulted in decreased adhesion of medulloblastoma cells to the extracellular matrix protein, vitronectin ( = .0013), and significantly decreased tumor burden in a mouse model of medulloblastoma LMD with improved overall survival ( = .0044). Furthermore, both pharmacologic inhibition of ABL1/2 and knockdown resulted in decreased expression of c-MYC, identifying a putative signaling pathway, and genes/pathways related to oncogenesis and neurodevelopment were differentially expressed between knockdown and control medulloblastoma cells.
CONCLUSIONS
ABL1 and ABL2 have potential roles in medulloblastoma LMD upstream of c-MYC expression.
PubMed: 37781087
DOI: 10.1093/noajnl/vdad095 -
Frontiers in Bioengineering and... 2021Beyond their fundamental role in hemostasis, platelets importantly contribute to other processes aimed at maintaining homeostasis. Indeed, platelets are a natural source... (Review)
Review
Beyond their fundamental role in hemostasis, platelets importantly contribute to other processes aimed at maintaining homeostasis. Indeed, platelets are a natural source of growth factors and also release many other substances-such as fibronectin, vitronectin, sphingosine 1-phosphate-that are important in maintaining healthy tissues, and ensuring regeneration and repair. Despite rare thrombotic events have been documented in astronauts, some and studies demonstrate that microgravity affects platelet's number and function, thus increasing the risk of hemorrhages and contributing to retard wound healing. Here we provide an overview about events linking platelets to the impairment of wound healing in space, also considering, besides weightlessness, exposure to radiation and psychological stress. In the end we discuss the possibility of utilizing platelet rich plasma as a tool to treat skin injuries eventually occurring during space missions.
PubMed: 34760877
DOI: 10.3389/fbioe.2021.716184 -
International Journal of Molecular... Dec 2022Corneal endothelial cells (CECs) do not proliferate or recover after illness or injury, resulting in decreased cell density and loss of pump/barrier function....
Corneal endothelial cells (CECs) do not proliferate or recover after illness or injury, resulting in decreased cell density and loss of pump/barrier function. Considering the shortage of donor cornea, it is vital to establish robust methods to generate CECs from induced pluripotent stem cells (iPSCs). We investigated the efficacy and safety of transplantation of iPSC-derived CECs into a corneal endothelial dysfunction (CED) rabbit model. iPSCs were generated from human fibroblasts. We characterized iPSCs by demonstrating the gene expression of the PSC markers , , , and , teratoma formation, and differentiation into three germ layers. Differentiation of iPSCs into CECs was induced via neural crest cell (NCC) induction. CEC markers were detected using immunofluorescence and gene expression was analyzed using quantitative real-time PCR (qRT-PCR). After culturing iPSC-derived NCCs, we found the expression of zona occludens-1 (ZO-1) and Na/K ATPase and a hexagonal morphology. , , and mRNA expression was higher in iPSC-derived CECs than in iPSCs and NCCs. We performed an injection of iPSC-derived CECs into the anterior chamber of a CED rabbit model and found improved levels of corneal transparency. We also found increased numbers of ZO-1- and ATP1A1-positive cells in rabbit corneas in the iPSC-derived CEC transplantation group. Usage of the coating material vitronectin (VTN) and fasudil resulted in good levels of CEC marker expression, demonstrated with Western blotting and immunocytochemistry. Combination of the VTN coating material and fasudil, instead of FNC mixture and Y27632, afforded the best results in terms of CEC differentiation's in vitro and in vivo efficacy. Successful transplantation of CEC-like cells into a CED animal model confirms the therapeutic efficacy of these cells, demonstrated by the restoration of corneal clarity. Our results suggest that iPSC-derived CECs can be a promising cellular resource for the treatment of CED.
Topics: Animals; Humans; Rabbits; Induced Pluripotent Stem Cells; Endothelium, Corneal; Endothelial Cells; Cornea; Cell Differentiation; Cells, Cultured
PubMed: 36614165
DOI: 10.3390/ijms24010701 -
International Journal of Bioprinting 2023This article provides an overview of the different types of blood-derived biomaterials that can be used as solvent additives in the formulation of inks/bioinks for use... (Review)
Review
This article provides an overview of the different types of blood-derived biomaterials that can be used as solvent additives in the formulation of inks/bioinks for use in solvent extrusion printing/bioprinting. We discuss the properties of various blood sub-products obtained after blood fractionation in terms of their use in tailoring ink/bioink to produce functional constructs designed to improve tissue repair. Blood-derived additives include platelets and/or their secretome, including signaling proteins and microvesicles, which can drive cell migration, inflammation, angiogenesis, and synthesis of extracellular matrix proteins. The contribution of plasma to ink/bioink functionalization relies not only on growth factors, such as hepatocyte growth factor and insulin growth factors, but also on adhesive proteins, such as fibrinogen/fibrin, vitronectin, and fibronectin. We review the current developments and progress in solvent-based extrusion printing/bioprinting with inks/bioinks functionalized with different blood-derived products, leading toward the development of more advanced patient-specific 3D constructs in multiple medical fields, including but not limited to oral tissues and cartilage, bone, skin, liver, and neural tissues. This information will assist researchers in identifying the most suitable blood-derived product for their ink/bioink formulation based on the intended regenerative functionality of the target tissue.
PubMed: 37457947
DOI: No ID Found -
Progress in Molecular Biology and... 2023Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem... (Review)
Review
Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem cells such as bone marrow-derived stem cells and adipose-derived stem cells have problems with aging. When hPSCs are intended to be cultured on feeder-free or xeno-free conditions without utilizing mouse embryonic fibroblasts or human fibroblasts, they cannot be cultured on conventional tissue culture polystyrene dishes, as adult stem cells can be cultured but should be cultivated on material surfaces grafted or coated with (a) natural or recombinant extracellular matrix (ECM) proteins, (b) ECM protein-derived peptides and specific synthetic polymer surfaces in xeno-free and/or chemically defined conditions. This review describes current developing cell culture biomaterials for the proliferation of hPSCs while maintaining the pluripotency and differentiation potential of the cells into 3 germ layers. Biomaterials for the cultivation of hPSCs without utilizing a feeder layer are essential to decrease the risk of xenogenic molecules, which contributes to the potential clinical usage of hPSCs. ECM proteins such as human recombinant vitronectin, laminin-511 and laminin-521 have been utilized instead of Matrigel for the feeder-free cultivation of hPSCs. The following biomaterials are also discussed for hPSC cultivation: (a) decellularized ECM, (b) peptide-grafted biomaterials derived from ECM proteins, (c) recombinant E-cadherin-coated surface, (d) polysaccharide-immobilized surface, (e) synthetic polymer surfaces with and without bioactive sites, (f) thermoresponsive polymer surfaces with and without bioactive sites, and (g) synthetic microfibrous scaffolds.
Topics: Animals; Mice; Adult; Humans; Laminin; Fibroblasts; Adult Stem Cells; Biocompatible Materials; Cell Proliferation
PubMed: 37678982
DOI: 10.1016/bs.pmbts.2023.02.008