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Indian Journal of Clinical Biochemistry... Jun 2017The mechanical properties of extracellular matrix (ECM) and connective tissues is largely dependent on the collagen and elastin structure. Lysyl oxidase (LOX) plays a... (Review)
Review
The mechanical properties of extracellular matrix (ECM) and connective tissues is largely dependent on the collagen and elastin structure. Lysyl oxidase (LOX) plays a critical role in the formation and repair of the ECM by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent cross linkages which stabilize these fibrous proteins. Due to its multiple functions both extracellularly and intracellularly, lysyl oxidase is involved in several processes in the tumorigenic pathway, in many different cancer types and stages. Alteration in LOX activity is implicated in many diseases and disorders including inflammation and inflammatory diseases, fibrosis of distinct organs and fibrotic disorders, cancer promotion and progression. There are only sparse reports of mutations or epigenetic alterations in the LOX gene. This review provides the recent clinical developments in the molecular mechanisms and pathologic process, pointing out LOX as a potential therapeutic target in translational medicine.
PubMed: 28428687
DOI: 10.1007/s12291-016-0576-7 -
International Ophthalmology Clinics 2014PEX stems from a pathologic elastotic process involving the cross-linking gene lysyl oxidase-like-1 (LOXL1), and is associated with abnormal formation of elastic... (Review)
Review
PEX stems from a pathologic elastotic process involving the cross-linking gene lysyl oxidase-like-1 (LOXL1), and is associated with abnormal formation of elastic extracellular matrix. We previously described a protein sink model to explain PEX material deposition on the lens capsule and other intraocular surfaces. Recent research findings not only provide evidence to support this hypothesis, but also further our understanding of the fundamental disease process. A key aspect of the pathogenic process is the compromise of blood-aqueous barrier integrity in PEXG. Decreased level of LOXL1 is associated with decreased elastin incorporation into elastic tissues, including the elastic lamina of blood vessels. This results in unincorporated elastin that is released as soluble elastin, and leakage of serum proteins, inflammatory cytokines, and extracellular matrix components into aqueous humor. This ultimately leads to aggregation and precipitation of large protein complexes, or PEX material, throughout intraocular surfaces as described in the protein sink model. The pathologic PEX process also affects the biomechanical properties of elastic tissues, such as the trabecular meshwork, lens zonules, and lamina cribrosa. This may be part of the primary pathologic process with intrinsically altered extracellular matrix proteins. This fundamental change in the structural composition of these tissues may alter their rigidity, elasticity, and other biomechanical properties. This likely contributes to increased trabecular meshwork outflow resistance and high intraocular pressure, and mechanical injury to retinal ganglion cell axons at the lamina cribrosa, which are conducive to glaucoma. These pathophysiologic processes combined may underlie some of the clinical hallmarks observed in PEXG.
Topics: Exfoliation Syndrome; Eye Proteins; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Proteome
PubMed: 25171640
DOI: 10.1097/IIO.0000000000000047 -
Journal of Andrology 2011Prostatic development is a dynamic process in which basic mechanisms of epithelial outgrowth and epithelial-mesenchymal interaction are initiated by androgens and... (Review)
Review
Prostatic development is a dynamic process in which basic mechanisms of epithelial outgrowth and epithelial-mesenchymal interaction are initiated by androgens and androgen receptor signaling. Even in adulthood, the prostate's function remains tightly regulated by androgens--without them, pathologic diseases, including hyperplastic and malignant growth that together plague nearly 50% of aging males, do not occur. Unraveling the etiology of these pathologic processes is a complex and important goal. In fact, many insights into these processes have come from an intimate understanding of the complex signaling networks that regulate physiologic prostatic growth in development. This review aims to highlight important key molecules such as Nkx3.1, sonic hedgehog, and Sry box 9, as well as key signaling pathways including the fibroblast growth factor and wingless pathways. These molecules and pathways are critical for prostate development with both known and postulated roles in prostatic pathology.
Topics: Androgens; Animals; Bone Morphogenetic Proteins; Cell Differentiation; Epithelial-Mesenchymal Transition; Fibroblast Growth Factors; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Genes, Homeobox; Hedgehog Proteins; Humans; Male; Mice; Prostate; Receptors, Notch; Signal Transduction; Wnt Proteins
PubMed: 20930191
DOI: 10.2164/jandrol.110.011577 -
Cells May 2022Tumorigenesis is a multistep process, during which cells acquire a series of mutations that lead to unrestrained cell growth and proliferation, inhibition of cell... (Review)
Review
Tumorigenesis is a multistep process, during which cells acquire a series of mutations that lead to unrestrained cell growth and proliferation, inhibition of cell differentiation, and evasion of cell death. Growing tumors stimulate angiogenesis, providing them with nutrients and oxygen. Ultimately, tumor cells invade the surrounding tissue and metastasize; a process responsible for about 90% of cancer-related deaths. Adhesion G protein-coupled receptors (aGPCRs) modulate the cellular processes closely related to tumor cell biology, such as adhesion and detachment, migration, polarity, and guidance. Soon after first being described, individual human aGPCRs were found to be involved in tumorigenesis. Twenty-five years ago, CD97/ was discovered to be induced in one of the most severe tumors, dedifferentiated anaplastic thyroid carcinoma. After decades of research, the time has come to review our knowledge of the presence and function of CD97 in cancer. In summary, CD97 is obviously induced or altered in many tumor entities; this has been shown consistently in nearly one hundred published studies. However, its high expression at circulating and tumor-infiltrating immune cells renders the systemic targeting of CD97 in tumors difficult.
Topics: Antigens, CD; Cell Proliferation; Cell Transformation, Neoplastic; Humans; Neoplasms; Neovascularization, Pathologic; Receptors, G-Protein-Coupled
PubMed: 35563846
DOI: 10.3390/cells11091538 -
International Journal of Medical... 2014The aim of the present work is to analyze all scientific evidence to verify whether similarities supporting a unified explanation for odontomas and supernumerary teeth... (Review)
Review
The aim of the present work is to analyze all scientific evidence to verify whether similarities supporting a unified explanation for odontomas and supernumerary teeth exist. A literature search was first conducted for epidemiologic studies indexed by PubMed, to verify their worldwide incidence. The analysis of the literature data shows some interesting similarities between odontomas and supernumerary teeth concerning their topographic distribution and pathologic manifestations. There is also some indication of common genetic and immuno-histochemical factors. Although from a nosological point of view, odontomas and supernumeraries are classified as distinct entities, they seem to be the expression of the same pathologic process, either malformative or hamartomatous.
Topics: Female; Humans; Male; Models, Dental; Odontogenesis; Odontoma; Signal Transduction; Syndrome; Tooth, Supernumerary
PubMed: 25419174
DOI: 10.7150/ijms.10501 -
Canadian Medical Association Journal Nov 1978Fibrosing alveolitis is a disease of unknown cause mainly involving the gas-exchanging portions of the lungs. It may occur in isolation and be called cryptogenic or... (Review)
Review
Fibrosing alveolitis is a disease of unknown cause mainly involving the gas-exchanging portions of the lungs. It may occur in isolation and be called cryptogenic or idiopathic, in which case the clinical manifestations are mainly respiratory, or it may be associated with other disorders, such as rheumatoid arthritis. The histopathologic abnormalities of the pulmonary tissue are identical in either instance. Other names used for the disease have included usual interstitial pneumonia, desquamative interstitial pneumonia and the Hamman-Rich syndrome; these terms may describe different stages of the same pathologic process. Many authors in North America and those in the United Kingdom favour the term fibrosing alveolitis when describing chronic interstitial pneumonias. There may be accompanying nonspecific Immunologic abnormalities, which may denote that fibrosing alveolitis is part of the wide spectrum of diseases known as connective tissue disorders. Recently immune complexes have been found in the lung parenchyma; they probably result in the granulocyte destruction and reticuloendothelial proliferation seen in the acute phase of the disease.There are no specific diagnostic tests for the disease apart from lung biopsy, which can be performed at the time of thoracotomy or transbronchially, with the use of a flexible fibreoptic bronchoscope. Lavaged cells from the alveoli have also been obtained via the bronchoscope; in persons with fibrosing alveolitis a high proportion of these cells are neutrophils, and after corticosteroid treatment the proportion decreases. The progress of the disease can be followed by examination of these washings as well as by lung scanning with gallium-67 citrate. Newer methods of treatment using combinations of corticosteroids and immunosuppressant drugs are being evaluated and are initially proving to be successful.
Topics: Adult; Aged; Humans; Lung; Middle Aged; Prednisone; Prognosis; Pulmonary Alveoli; Pulmonary Fibrosis; Radiography; Radionuclide Imaging; Respiratory Function Tests; Terminology as Topic
PubMed: 369671
DOI: No ID Found -
Current Opinion in Hematology Sep 2022Factor XII (FXII), the precursor of the protease FXIIa, contributes to pathologic processes including angioedema and thrombosis. Here, we review recent work on... (Review)
Review
PURPOSE OF REVIEW
Factor XII (FXII), the precursor of the protease FXIIa, contributes to pathologic processes including angioedema and thrombosis. Here, we review recent work on structure-function relationships for FXII based on studies using recombinant FXII variants.
RECENT FINDINGS
FXII is a homolog of pro-hepatocyte growth factor activator (Pro-HGFA). We prepared FXII in which domains are replaced by corresponding parts of Pro-HGA, and tested them in FXII activation and activity assays. In solution, FXII and prekallikrein undergo reciprocal activation to FXIIa and kallikrein. The rate of this process is restricted by the FXII fibronectin type-2 and kringle domains. Pro-HGA replacements for these domains accelerate FXII and prekallikrein activation. When FXII and prekallikrein bind to negatively charged surfaces, reciprocal activation is enhanced. The FXII EGF1 domain is required for surface binding.
SUMMARY
We propose a model in which FXII is normally maintained in a closed conformation resistant to activation by intramolecular interactions involving the fibronectin type-2 and kringle domains. These interactions are disrupted when FXII binds to a surface through EGF1, enhancing FXII activation and prekallikrein activation by FXIIa. These observations have important implications for understanding the contributions of FXII to disease, and for developing therapies to treat thrombo-inflammatory disorders.
Topics: Blood Coagulation; Factor XII; Fibronectins; Humans; Kallikreins; Prekallikrein
PubMed: 35916558
DOI: 10.1097/MOH.0000000000000727 -
Platelet-rich plasma in the pathologic processes of tendinopathy: a review of basic science studies.Frontiers in Bioengineering and... 2023Tendinopathy is a medical condition that includes a spectrum of inflammatory and degenerative tendon changes caused by traumatic or overuse injuries. The pathological... (Review)
Review
Tendinopathy is a medical condition that includes a spectrum of inflammatory and degenerative tendon changes caused by traumatic or overuse injuries. The pathological mechanism of tendinopathy has not been well defined, and no ideal treatment is currently available. Platelet-rich plasma (PRP) is an autologous whole blood derivative containing a variety of cytokines and other protein components. Various basic studies have found that PRP has the therapeutic potential to promote cell proliferation and differentiation, regulate angiogenesis, increase extracellular matrix synthesis, and modulate inflammation in degenerative tendons. Therefore, PRP has been widely used as a promising therapeutic agent for tendinopathy. However, controversies exist over the optimal treatment regimen and efficacy of PRP for tendinopathy. This review focuses on the specific molecular and cellular mechanisms by which PRP manipulates tendon healing to better understand how PRP affects tendinopathy and explore the reason for the differences in clinical trial outcomes. This article has also pointed out the future direction of basic research and clinical application of PRP in the treatment of tendinopathy, which will play a guiding role in the design of PRP treatment protocols for tendinopathy.
PubMed: 37545895
DOI: 10.3389/fbioe.2023.1187974 -
American Journal of Physiology. Cell... Feb 2023Activins and inhibins are unique members of the transforming growth factor-β (TGFβ) family of growth factors, with the ability to exert autocrine, endocrine, and... (Review)
Review
Activins and inhibins are unique members of the transforming growth factor-β (TGFβ) family of growth factors, with the ability to exert autocrine, endocrine, and paracrine effects in a wide range of complex physiologic and pathologic processes. Although first isolated within the pituitary, emerging evidence suggests broader influence beyond reproductive development and function. Known roles of activin and inhibin in angiogenesis and immunity along with correlations between gene expression and cancer prognosis suggest potential roles in tumorigenesis. Here, we present a review of the current understanding of the biological role of activins and inhibins as it relates to ovarian cancers, summarizing the underlying signaling mechanisms and physiologic influence, followed by detailing their roles in cancer progression, diagnosis, and treatment.
Topics: Humans; Female; Inhibins; Activins; Ovarian Neoplasms; Signal Transduction; Endocrine System
PubMed: 36622068
DOI: 10.1152/ajpcell.00178.2022 -
Journal of Clinical Orthopaedics and... Feb 2022Spinal cord injury (SCI) is the most common disabling spinal injury, a complex pathologic process that can eventually lead to severe neurological dysfunction. The... (Review)
Review
Spinal cord injury (SCI) is the most common disabling spinal injury, a complex pathologic process that can eventually lead to severe neurological dysfunction. The Wnt/mTOR signaling pathway is a pervasive signaling cascade that regulates a wide range of physiological processes during embryonic development, from stem cell pluripotency to cell fate. Numerous studies have reported that Wnt/mTOR signaling pathway plays an important role in neural development, synaptogenesis, neuron growth, differentiation and survival after the central nervous system (CNS) is damaged. Wnt/mTOR also plays an important role in regulating various pathophysiological processes after spinal cord injury (SCI). After SCI, Wnt/mTOR signal regulates the physiological and pathological processes of neural stem cell proliferation and differentiation, neuronal axon regeneration, neuroinflammation and pain through multiple pathways. Due to the characteristics of the Wnt signal in SCI make it a potential therapeutic target of SCI. In this paper, the characteristics of Wnt/mTOR signal, the role of Wnt/mTOR pathway on SCI and related mechanisms are reviewed, and some unsolved problems are discussed. It is hoped to provide reference value for the research field of the role of Wnt/mTOR pathway in SCI, and provide a theoretical basis for biological therapy of SCI.
PubMed: 35070684
DOI: 10.1016/j.jcot.2022.101760