scholarly journals NEUROINFLAMMATION

2021 ◽  
pp. 16
Author(s):  
Keyword(s):  
Inflammatory Mediators ◽  
Molecular Mechanisms ◽  
Local Blood Flow ◽  
Functional Changes ◽  
Sequence Of Events ◽  
Complex Process ◽  
Affected Tissue ◽  
Local Manifestation ◽  
Systemic Responses ◽  
Chemotactic Effect

Inflammation is a complex process, mediated by cellular and molecular mechanisms caused by a response to a tissue damage from an aggressive agent, whether if biological, chemical or physical origin. This process occurs, ultimately, with the purpose of promoting defense, repair and tissue regeneration. The inflammatory process leads to changes in blood vessels that have their diameter and flow altered, with the objective of leading to increased vascular permeability and consequent leakage of fluids and cells into the extracellular space of the affected tissue. This sequence of events generates the cardinal signs of inflammation, which are: pain, heat, redness, edema, with loss or alteration of function. The process occurs through mechanisms induced by cytokines and that despite having local manifestation, it can lead to systemic responses involving the whole organism with fever, chills, tremors, tachycardia, leukocytosis, sweating, diuresis and blood dyscrasias. In the cascade of events related to inflammation, there is initially a local stimulus that promotes morphological and functional changes in the attacked tissue that trigger the release of signaling molecules, the defensins that have a chemotactic effect on monocytes, neutrophils and lymphocytes, and pro-inflammatory mediators. that are directly involved in the next inflammatory phases. There is, then, the recognition of aggression and the aggressor agent by the receptors of cells of the immune system and release of inflammatory mediators, of the cyclooxygenase pathway that will release prostaglandin, prostacyclins and thromboxanes and by the lipooxygenase pathway that will produce leukotrienes (Figure 1). Then, there is a modification of the local microcirculation promoting vasodilation, initially arteriolar and subsequently of the venules by the action of histamine release by mast cells, and associated with an increase in local blood flow, generate the cardinal flushing and heat signals.

scholarly journals Structural and Functional Changes and Possible Molecular Mechanisms in Aged Skin

2021 ◽  
Vol 22 (22) ◽  
pp. 12489
Author(s):  
Hyunji Lee ◽  
Yongjun Hong ◽  
Miri Kim
Keyword(s):  
Molecular Mechanisms ◽  
Skin Aging ◽  
Extrinsic Factors ◽  
Functional Changes ◽  
Complex Process ◽  
Wide Range ◽  
Aged Skin ◽  
And Function ◽  
Epidermal Atrophy ◽  
Aging Skin

Skin aging is a complex process influenced by intrinsic and extrinsic factors. Together, these factors affect the structure and function of the epidermis and dermis. Histologically, aging skin typically shows epidermal atrophy due to decreased cell numbers. The dermis of aged skin shows decreased numbers of mast cells and fibroblasts. Fibroblast senescence contributes to skin aging by secreting a senescence-associated secretory phenotype, which decreases proliferation by impairing the release of essential growth factors and enhancing degradation of the extracellular matrix through activation of matrix metalloproteinases (MMPs). Several molecular mechanisms affect skin aging including telomere shortening, oxidative stress and MMP, cytokines, autophagic control, microRNAs, and the microbiome. Accumulating evidence on the molecular mechanisms of skin aging has provided clinicians with a wide range of therapeutic targets for treating aging skin.

Towards Better Drug Repositioning: Targeted Immunoinflammatory Therapy for Diabetic Nephropathy

2019 ◽  
Vol 26 ◽  
Author(s):  
Qin zhang ◽  
Ming Yang ◽  
Ying Xiao ◽  
Yachun Han ◽  
Shikun Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Inflammatory Process ◽  
Drug Repositioning ◽  
Microvascular Complications ◽  
Pathogenic Factor ◽  
Progressive Decline ◽  
Functional Changes ◽  
Sequence Of Events ◽  
Novel Treatment

: Diabetic nephropathy (DN) is one of the most common and important microvascular complications of diabetes mellitus (DM). The main clinical features of DN are proteinuria and a progressive decline in renal function , which are associated with structural and functional changes in the kidney. The pathogenesis of DN is multifactorial, including genetic, metabolic and haemodynamic factors, which can trigger a sequence of events. Controlling metabolic risks such as hyperglycaemia, hypertension and dyslipidaemia is not enough to slow the progression of DN. Recent studies have emphasized immunoinflammation as a critical pathogenic factor in the progression of DN. Therefore, targeting inflammation is considered a potential and novel treatment strategy for DN. In this review, we will briefly introduce the inflammatory process of DN and discuss the anti-inflammatory effects of antidiabetic drugs when treating DN.

scholarly journals Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes

2005 ◽  
Vol 34 (3) ◽  
pp. 889-908 ◽  
Author(s):  
S Bauersachs ◽  
S E Ulbrich ◽  
K Gross ◽  
S E M Schmidt ◽  
H H D Meyer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cdna Array ◽  
Transforming Growth Factor Β ◽  
Early Embryo ◽  
Oestrous Cycle ◽  
Cdna Libraries ◽  
Functional Changes ◽  
Retinoic Acid Signalling ◽  
Subtracted Cdna Libraries

The endometrium plays a central role among the reproductive tissues in the context of early embryo–maternal communication and pregnancy. It undergoes typical changes during the sexual/oestrous cycle, which are regulated by the ovarian hormones progesterone and oestrogen. To identify the underlying molecular mechanisms we have performed the first holistic screen of transcriptome changes in bovine intercaruncular endometrium at two stages of the cycle – end of day 0 (late oestrus, low progesterone) and day 12 (dioestrus, high progesterone). A combination of subtracted cDNA libraries and cDNA array hybridisation revealed 133 genes showing at least a 2-fold change of their mRNA abundance, 65 with higher levels at oestrus and 68 at dioestrus. Interestingly, genes were identified which showed differential expression between different uterine sections as well. The most prominent example was the UTMP (uterine milk protein) mRNA, which was markedly upregulated in the cranial part of the ipsilateral uterine horn at oestrus. A Gene Ontology classification of the genes with known function characterised the oestrus time by elevated expression of genes, for example related to cell adhesion, cell motility and extracellular matrix and the dioestrus time by higher expression of mRNAs encoding for a variety of enzymes and transport proteins, in particular ion channels. Searching in pathway databases and literature data-mining revealed physiological processes and signalling cascades, e.g. the transforming growth factor-β signalling pathway and retinoic acid signalling, which are potentially involved in the regulation of changes of the endometrium during the oestrous cycle.

scholarly journals Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

2020 ◽  
Author(s):  
Ali Hashmi ◽  
Sham Tlili ◽  
Pierre Perrin ◽  
Alfonso Martinez-Arias ◽  
Pierre-François Lenne
Keyword(s):  
Spatial Organization ◽  
Embryonic Stem ◽  
Cell Movement ◽  
Body Plan ◽  
The Body ◽  
State Transitions ◽  
Sequence Of Events ◽  
Complex Process ◽  
Cell Layers ◽  
Sorting Process

AbstractShaping the animal body plan is a complex process that involves the spatial organization and patterning of different cell layers. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned cell ensemble into structured territories is largely unknown. Here, using 3D aggregates of mouse embryonic stem cells, we study the formation of one of the three germ layers, the endoderm. We show that the endoderm is generated from an epiblast-like state by a three-step mechanism: a release of islands of Ecadherin expressing cells, their flow toward the aggregate tip, and their segregation. Unlike the prevailing view, this mechanism does not require epithelial-to-mesenchymal transitions and vice-versa but rather a fragmentation, which is mediated by Wnt/β-catenin, and a sorting process. Our data emphasize the role of signaling and cell flows in the establishment of the body plan.

scholarly journals The cross-bridge cycle and skeletal muscle fatigue

2008 ◽  
Vol 104 (2) ◽  
pp. 551-558 ◽  
Author(s):  
Robert H. Fitts
Keyword(s):  
Peak Power ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Low Ph ◽  
Forward Rate ◽  
Maximal Velocity ◽  
Functional Changes ◽  
Cross Bridge ◽  
The Cross

The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P0), maximal velocity, and peak power. Establishing the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle. With actin-myosin binding, the cross-bridge transitions from a weakly bound low-force state to a strongly bound high-force state. Low pH reduces the number of high-force cross bridges in fast fibers, and the force per cross bridge in both fast and slow fibers. The former is thought to involve a direct inhibition of the forward rate constant for transition to the strong cross-bridge state. In contrast, inorganic phosphate (Pi) is thought to reduce P0 by accelerating the reversal of this step. Both H+ and Pi decrease myofibrillar Ca2+ sensitivity. This effect is particularly important as the amplitude of the Ca2+ transient falls with fatigue. The inhibitory effects of low pH and high Pi on P0 are reduced as temperature increases from 10 to 30°C. However, the H+-induced depression of peak power in the slow fiber type, and Pi inhibition of myofibrillar Ca2+ sensitivity in slow and fast fibers, are greater at high compared with low temperature. Thus the depressive effects of H+ and Pi at in vivo temperatures cannot easily be predicted from data collected below 25° C. In vitro, reactive oxygen species reduce myofibrillar Ca2+ sensitivity; however, the importance of this mechanism during in vivo exercise is unknown.

scholarly journals Immunomodulatory effects of interferon-γ on human fetal cardiac mesenchymal stromal cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Karl-Henrik Grinnemo ◽  
Marie Löfling ◽  
Lubov Nathanson ◽  
Roland Baumgartner ◽  
Daniel F. J. Ketelhuth ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
First Trimester ◽  
Interferon Γ ◽  
Systematic Evaluation ◽  
Immunomodulatory Effects ◽  
Functional Changes

Abstract Background Mesenchymal stromal cells (MSCs), due to their regenerative and immunomodulatory properties, are therapeutically used for diseases, including heart failure. As early gestational-phase embryonic tissues exhibit extraordinary regenerative potential, fetal MSCs exposed to inflammation offer a unique opportunity to evaluate molecular mechanisms underlying preferential healing, and investigate their inherent abilities to communicate with the immune system during development. The principal aim of this study was to evaluate the effects of interferon-γ (IFNγ) on the immunomodulatory effects of first-trimester human fetal cardiac (hfc)-MSCs. Methods hfcMSCs (gestational week 8) were exposed to IFNγ, with subsequent analysis of the whole transcriptome, based on RNA sequencing. Exploration of surface-expressed immunoregulatory mediators and modulation of T cell responses were performed by flow cytometry. Presence and activity of soluble mediators were assessed by ELISA or high-performance liquid chromatography. Results Stimulation of hfcMSCs with IFNγ revealed significant transcriptional changes, particularly in respect to the expression of genes belonging to antigen presentation pathways, cell cycle control, and interferon signaling. Expression of immunomodulatory genes and associated functional changes, including indoleamine 2,3-dioxygenase activity, and regulation of T cell activation and proliferation via programmed cell death protein (PD)-1 and its ligands PD-L1 and PD-L2, were significantly upregulated. These immunoregulatory molecules diminished rapidly upon withdrawal of inflammatory stimulus, indicating a high degree of plasticity by hfcMSCs. Conclusions To our knowledge, this is the first study performing a systematic evaluation of inflammatory responses and immunoregulatory properties of first-trimester cardiac tissue. In summary, our study demonstrates the dynamic responsiveness of hfcMSCs to inflammatory stimuli. Further understanding as to the immunoregulatory properties of hfcMSCs may be of benefit in the development of novel stromal cell therapeutics for cardiovascular disease.

Molecular Interactions of α-Synuclein, Mitochondria, and Cellular Degradation Pathways in Parkinson's Disease

2020 ◽  
pp. 212-234
Author(s):  
Mansi Verma ◽  
Sujata Basu ◽  
Manisha Singh ◽  
Rachana R. ◽  
Simrat Kaur ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Interactions ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Degradation Pathways ◽  
Functional Changes ◽  
The World ◽  
Novel Therapeutic

Parkinson's disease (PD) has been reported to be the most common neurodegenerative diseases all over the world. Several proteins are associated and responsible for causing PD. One such protein is α-synuclein. This chapter discusses the role of α-synuclein in PD. Various genetic and epigenetic factors, which cause structural and functional changes for α-synuclein, have been described. Several molecular mechanisms, which are involved in regulating mitochondrial and lysosomal related pathways and are linked to α-synuclein, have been discussed in detail. The knowledge gathered is further discussed in terms of using α-synuclein as a diagnostic marker for PD and as a novel therapeutic target for the same.

scholarly journals Drug Resistance in Non-Hodgkin Lymphomas

2020 ◽  
Vol 21 (6) ◽  
pp. 2081 ◽  
Author(s):  
Pavel Klener ◽  
Magdalena Klanova
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Front Line ◽  
Mechanisms Of Resistance ◽  
Treatment Algorithms ◽  
Acquired Drug Resistance ◽  
Complex Process ◽  
Medical Need ◽  
Druggable Targets

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

scholarly journals miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bin Xie ◽  
Can Lu ◽  
Chen Chen ◽  
Jianhua Zhou ◽  
Zhenghao Deng
Keyword(s):  
Cell Proliferation ◽  
Pulmonary Fibrosis ◽  
Inflammatory Response ◽  
Inflammatory Mediators ◽  
Protein Level ◽  
Molecular Mechanisms ◽  
Cancer Cell Proliferation ◽  
Inflammatory Signaling ◽  
Silica Exposure ◽  
Collective Data

Silica exposure triggers inflammatory response and pulmonary fibrosis that is a severe occupational or environmental lung disease with no effective therapies. The complicated biological and molecular mechanisms underlying silica-induced lung damages have not yet been fully understood. miR-135a inhibits inflammation, apoptosis, and cancer cell proliferation. But the roles of miRNA135a involved in the silica-induced lung damages remain largely unexplored. We investigated the roles and mechanisms of miR-135a underlying silica-induced pulmonary fibrosis. The present study showed silica exposure caused the decrease in miR-135a level but the increase in inflammatory mediators. Transduction of lentivirus expressing miR-135a reduced the level of inflammatory mediators in lung tissues from silica-treated mice and improved pulmonary fibrosis which was consistent with the downregulated α-SMA but enhanced E-cadherin. Moreover, miR-135a overexpression inhibited p-p65 level in lung tissues. Overexpression of miR-135a inhibitor strengthened TLR4 protein level and NF-κB activation in BEAS-2B cells. Injection of PDTC, an inhibitor of NF-κB, further reinforced miR-135a-mediated amelioration of inflammation and pulmonary fibrosis induced by silica. The collective data indicate miR-135a restrains NF-κB activation probably through targeting TLR4 to alleviate silica-induced inflammatory response and pulmonary fibrosis.

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