The role of photoacoustic imaging in organ fibrosis

2021 ◽  
Author(s):  
Eno Hysi ◽  
Xiaolin He ◽  
Tianzhou Zhang ◽  
Darren A. Yuen ◽  
Michael C. Kolios
Keyword(s):  
Photoacoustic Imaging ◽  
Organ Fibrosis

scholarly journals BRD4 inhibition for the treatment of pathological organ fibrosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1015 ◽  
Author(s):  
Matthew S. Stratton ◽  
Saptarsi M. Haldar ◽  
Timothy A. McKinsey
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Fibrosis ◽  
Small Molecule ◽  
Regulatory Protein ◽  
Medical Need ◽  
Fibrotic Diseases ◽  
Brd4 Inhibition ◽  
Developed World ◽  
Organ Fibrosis

Fibrosis is defined as excess deposition of extracellular matrix, resulting in tissue scarring and organ dysfunction. It is estimated that 45% of deaths in the developed world are due to fibrosis-induced organ failure. Despite the well-accepted role of fibrosis in the pathogenesis of numerous diseases, there are only two US Food and Drug Administration–approved anti-fibrotic therapies, both of which are currently restricted to the treatment of pulmonary fibrosis. Thus, organ fibrosis represents a massive unmet medical need. Here, we review recent findings suggesting that an epigenetic regulatory protein, BRD4, is a nodal effector of organ fibrosis, and we highlight the potential of small-molecule BRD4 inhibitors for the treatment of diverse fibrotic diseases.

scholarly journals The fate of the primary cilium during myofibroblast transition

2014 ◽  
Vol 25 (5) ◽  
pp. 643-657 ◽  
Author(s):  
Matthew Rozycki ◽  
Monika Lodyga ◽  
Jessica Lam ◽  
Maria Zena Miranda ◽  
Károly Fátyol ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sonic Hedgehog ◽  
Primary Cilium ◽  
Potential Role ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Related Transcription Factor ◽  
Necessary And Sufficient ◽  
Organ Fibrosis

Myofibroblasts, the culprit of organ fibrosis, can originate from mesenchymal and epithelial precursors through fibroblast–myofibroblast and epithelial–myofibroblast transition (EMyT). Because certain ciliopathies are associated with fibrogenesis, we sought to explore the fate and potential role of the primary cilium during myofibroblast formation. Here we show that myofibroblast transition from either precursor results in the loss of the primary cilium. During EMyT, initial cilium growth is followed by complete deciliation. Both EMyT and cilium loss require two-hit conditions: disassembly/absence of intercellular contacts and transforming growth factor-β1 (TGFβ) exposure. Loss of E-cadherin–dependent junctions induces cilium elongation, whereas both stimuli are needed for deciliation. Accordingly, in a scratch-wounded epithelium, TGFβ provokes cilium loss exclusively along the wound edge. Increased contractility, a key myofibroblast feature, is necessary and sufficient for deciliation, since constitutively active RhoA, Rac1, or myosin triggers, and down-regulation of myosin or myocardin-related transcription factor prevents, this process. Sustained myosin phosphorylation and consequent deciliation are mediated by a Smad3-, Rac1-, and reactive oxygen species–dependent process. Transitioned myofibroblasts exhibit impaired responsiveness to platelet-derived growth factor-AA and sonic hedgehog, two cilium-associated stimuli. Although the cilium is lost during EMyT, its initial presence contributes to the transition. Thus myofibroblasts represent a unique cilium-less entity with profoundly reprogrammed cilium-related signaling.

Role of integrins in fibrosing liver diseases

2011 ◽  
Vol 301 (3) ◽  
pp. G425-G434 ◽  
Author(s):  
Eleonora Patsenker ◽  
Felix Stickel
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Liver Diseases ◽  
Extracellular Environment ◽  
Organ Fibrosis ◽  
Instrumental Role

Integrins and other cell adhesion molecules regulate numerous physiological and pathological mechanisms by mediating the interaction between cells and their extracellular environment. Although the significance of integrins in the evolution and progression of certain cancers is well recognized, their involvement in nonmalignant processes, such as organ fibrosis or inflammation, is only beginning to emerge. However, accumulating evidence points to an instrumental role of integrin-mediated signaling in a variety of chronic and acute noncancerous diseases, particularly of the liver.

scholarly journals Wnt/β-Catenin Signaling: a Promising New Target for Fibrosis Diseases

2012 ◽  
pp. 337-346 ◽  
Author(s):  
Y. GUO ◽  
L. XIAO ◽  
L. SUN ◽  
F. LIU
Keyword(s):  
Lung Fibrosis ◽  
Wnt Pathway ◽  
Therapeutic Strategy ◽  
Key Factors ◽  
Self Renewal ◽  
Fibrotic Disorders ◽  
Pathway Databases ◽  
Organ Fibrosis ◽  
Pathogenic Effects

Wnt/β-catenin signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Recently, emerging evidence from researches of organ fibrosis suggest that sustained Wnt/β-catenin pathway reactivation is linked to the pathogenesis of fibrotic disorders. Here we focus on Wnt/β-catenin-related pathogenic effects in different organs, such as lung fibrosis, liver fibrosis, skin fibrosis and renal fibrosis. Additionally, Wnt/β-catenin signaling works in a combinatorial manner with TGF-β signaling in the process of fibrosis, and TGF-β signaling can induce expression of Wnt/β-catenin superfamily members and vice versa. Moreover, network analysis, based on pathway databases, revealed that key factors in the Wnt pathway were targeted by some differentially expressed microRNAs detected in fibrosis diseases. These findings demonstrated the crosstalks between Wnt/β-catenin pathway and TGF-β signalings, and microRNAs, highlighting the role of Wnts in organ fibrogenesis. Most importantly, nowadays there is a variety of Wnt pathway inhibitors which give us the potential therapeutic feasibility, modulation of the Wnt pathway may, therefore, present as a suitable and promising therapeutic strategy in the future.

scholarly journals Targeting circPTPN12/1 miR-21-5p/ΔNp63α pathway as a therapeutic strategy for human endometrial fibrosis

2021 ◽  
Author(s):  
Minmin Song ◽  
Guangfeng Zhao ◽  
Haixiang Sun ◽  
Simin Yao ◽  
Zhenhua Zhou ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
The Novel ◽  
Mesenchymal Transition ◽  
Organ Fibrosis ◽  
Endometrial Epithelial Cells ◽  
Expression And Activity ◽  
Uterine Infertility

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/∆Np63α pathway.

scholarly journals Role of Ultrasound and Photoacoustic Imaging in Photodynamic Therapy for Cancer

2020 ◽  
Vol 96 (2) ◽  
pp. 260-279 ◽  
Author(s):  
Scott C. Hester ◽  
Maju Kuriakose ◽  
Christopher D. Nguyen ◽  
Srivalleesha Mallidi
Keyword(s):  
Photodynamic Therapy ◽  
Photoacoustic Imaging

scholarly journals Fibrosis Related Inflammatory Mediators: Role of the IL-10 Cytokine Family

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Erna Sziksz ◽  
Domonkos Pap ◽  
Rita Lippai ◽  
Nóra Judit Béres ◽  
Andrea Fekete ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Kidney Diseases ◽  
Public Health Problem ◽  
Interleukin 10 ◽  
Major Public Health Problem ◽  
Effector Cells ◽  
Inflammatory Bowel ◽  
The Common ◽  
Organ Fibrosis

Importance of chronic fibroproliferative diseases (FDs) including pulmonary fibrosis, chronic kidney diseases, inflammatory bowel disease, and cardiovascular or liver fibrosis is rapidly increasing and they have become a major public health problem. According to some estimates about 45% of all deaths are attributed to FDs in the developed world. Independently of their etiology the common hallmark of FDs is chronic inflammation. Infiltrating immune cells, endothelial, epithelial, and other resident cells of the injured organ release an orchestra of inflammatory mediators, which stimulate the proliferation and excessive extracellular matrix (ECM) production of myofibroblasts, the effector cells of organ fibrosis. Abnormal amount of ECM disturbs the original organ architecture leading to the decline of function. Although our knowledge is rapidly expanding, we still have neither a diagnostic tool to detect nor a drug to specifically target fibrosis. Therefore, there is an urgent need for the more comprehensive understanding of the pathomechanism of fibrosis and development of novel diagnostic and therapeutic strategies. In the present review we provide an overview of the common key mediators of organ fibrosis highlighting the role of interleukin-10 (IL-10) cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26), which recently came into focus as tissue remodeling-related inflammatory cytokines.

scholarly journals Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1956 ◽  
Author(s):  
Layla Pires ◽  
Valentin Demidov ◽  
Brian C. Wilson ◽  
Ana Gabriela Salvio ◽  
Lilian Moriyama ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Photoacoustic Imaging ◽  
Critical Role ◽  
Tumor Model ◽  
Optical Clearing ◽  
Treatment Regimes ◽  
Pigmented Lesions ◽  
Melanoma Model

Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both. The effect on tumor growth was measured by longitudinal ultrasound/photoacoustic imaging in vivo and by immunohistology after sacrifice. In a separate dorsal window chamber tumor model, angiographic optical coherence tomography (OCT) generated 3D tissue microvascular images, enabling direct in vivo assessment of treatment response. The optical clearing had minimal therapeutic effect on the in control, non-pigmented cutaneous melanomas but a statistically significant effect (p < 0.05) in pigmented lesions for both single- and dual-photosensitizer treatment regimes. The latter enabled full-depth eradication of tumor tissue, demonstrated by the absence of S100 and Ki67 immunostaining. These studies are the first to demonstrate complete melanoma response to PDT in an immunocompromised model in vivo, with quantitative assessment of tumor volume and thickness, confirmed by (immuno) histological analyses, and with non-pigmented melanomas used as controls to clarify the critical role of melanin in the PDT response. The results indicate the potential of OCA-enhanced PDT for the treatment of pigmented lesions, including melanoma.

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