scholarly journals Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 1755
Author(s):  
Mohd N. Mat Nor ◽  
Ilva D. Rupenthal ◽  
Colin R. Green ◽  
Monica L. Acosta
Keyword(s):  
Calcium Binding ◽  
Retinal Function ◽  
Tissue Response ◽  
Retinal Diseases ◽  
Potential Treatment ◽  
Rat Retina ◽  
Connexin Hemichannel ◽  
Connexin Hemichannels ◽  
Differential Action

Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.

scholarly journals Mechanisms Underlying Connexin Hemichannel Activation in Disease

2021 ◽  
Vol 22 (7) ◽  
pp. 3503
Author(s):  
Raf Van Campenhout ◽  
Ana Rita Gomes ◽  
Timo W.M. De Groof ◽  
Serge Muyldermans ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Cell Death ◽  
Gap Junctions ◽  
Connexin Hemichannel ◽  
Extracellular Environment ◽  
Connexin Hemichannels

Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.

In vivo behavior of trimethylene carbonate and ε-caprolactone-based (co)polymer networks: Degradation and tissue response

2010 ◽  
Vol 95A (3) ◽  
pp. 940-949 ◽  
Author(s):  
Erhan Bat ◽  
Josée A. Plantinga ◽  
Martin C. Harmsen ◽  
Marja J. A. van Luyn ◽  
Jan Feijen ◽  
...  
Keyword(s):  
Polymer Networks ◽  
Tissue Response ◽  
Trimethylene Carbonate

scholarly journals Improvement of biohistological response of facial implant materials by tantalum surface treatment

2019 ◽  
Vol 41 (1) ◽  
Author(s):  
Mohammed Mousa Bakri ◽  
Sung Ho Lee ◽  
Jong Ho Lee
Keyword(s):  
Foreign Body ◽  
Soft Tissue ◽  
Surface Treatment ◽  
Clinical Applications ◽  
Tissue Response ◽  
Bone Surface ◽  
Tissue Thickness ◽  
Implant Materials ◽  
Soft Tissue Thickness

Abstract Background A compact passive oxide layer can grow on tantalum (Ta). It has been reported that this oxide layer can facilitate bone ingrowth in vivo though the development of bone-like apatite, which promotes hard and soft tissue adhesion. Thus, Ta surface treatment on facial implant materials may improve the tissue response, which could result in less fibrotic encapsulation and make the implant more stable on the bone surface. The purposes of this study were to verify whether surface treatment of facial implant materials using Ta can improve the biohistobiological response and to determine the possibility of potential clinical applications. Methods Two different and commonly used implant materials, silicone and expanded polytetrafluoroethylene (ePTFE), were treated via Ta ion implantation using a Ta sputtering gun. Ta-treated samples were compared with untreated samples using in vitro and in vivo evaluations. Osteoblast (MG-63) and fibroblast (NIH3T3) cell viability with the Ta-treated implant material was assessed, and the tissue response was observed by placing the implants over the rat calvarium (n = 48) for two different lengths of time. Foreign body and inflammatory reactions were observed, and soft tissue thickness between the calvarium and the implant as well as the bone response was measured. Results The treatment of facial implant materials using Ta showed a tendency toward increased fibroblast and osteoblast viability, although this result was not statistically significant. During the in vivo study, both Ta-treated and untreated implants showed similar foreign body reactions. However, the Ta-treated implant materials (silicone and ePTFE) showed a tendency toward better histological features: lower soft tissue thickness between the implant and the underlying calvarium as well as an increase in new bone activity. Conclusion Ta surface treatment using ion implantation on silicone and ePTFE facial implant materials showed the possibility of reducing soft tissue intervention between the calvarium and the implant to make the implant more stable on the bone surface. Although no statistically significant improvement was observed, Ta treatment revealed a tendency toward an improved biohistological response of silicone and ePTFE facial implants. Conclusively, tantalum treatment is beneficial and has the potential for clinical applications.

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

scholarly journals Neuroprotective Effect of Optimized Yinxieling Formula in 6-OHDA-Induced Chronic Model of Parkinson’s Disease through the Inflammation Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Renrong Wei ◽  
Cuiping Rong ◽  
Qingfeng Xie ◽  
Shouhai Wu ◽  
Yuchao Feng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Binding ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Cox 2

Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN)-striatum circuit, which is associated with glial activation and consequent chronic neuroinflammation. Optimized Yinxieling Formula (OYF) is a Chinese medicine that exerts therapeutical effect and antiinflammation property on psoriasis. Our previous study has proven that pretreatment with OYF could regulate glia-mediated inflammation in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Given that PD is a chronic degeneration disorder, this study applied another PD animal model induced by striatal injection of 6-hydroxydopamine (6-OHDA) to mimic the progressive damage of the SN-striatum dopamine system in rats. The OYF was administrated in the manner of pretreatment plus treatment. The effects of the OYF on motor behaviors were assessed with the apomorphine-induced rotation test and adjusting steps test. To confirm the effect of OYF on dopaminergic neurons and glia activation in this model, we analyzed the expression of tyrosine hydroxylase (TH) and glia markers, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP) in the SN region of the rat PD model. Inflammation-associated factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were further evaluated in this model and in interferon-γ- (INF-γ-) induced murine macrophages RAW264.7 cells. The results from the in vivo study showed that OYF reversed the motor behavioral dysfunction in 6-OHDA-induced PD rats, upregulated the TH expression, decreased the immunoreactivity of Iba-1 and GFAP, and downregulated the mRNA levels of TNF-α and COX-2. The OYF also trended to decrease the mRNA levels of IL-1β and iNOS in vivo. The results from the in vitro study showed that OYF significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. Therefore, this study suggests that OYF exerts antiinflammatory effects, which might be related to the protection of dopaminergic neurons in 6-OHDA-induced chronic neurotoxicity.

scholarly journals The Biological Effects of Combining Metals in a Posterior Spinal Implant: In Vivo Model Development Report of the First Two Cases

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Christine L. Farnsworth ◽  
Peter O. Newton ◽  
Eric Breisch ◽  
Michael T. Rohmiller ◽  
Jung Ryul Kim ◽  
...  
Keyword(s):  
Galvanic Corrosion ◽  
Biological Effects ◽  
Model Development ◽  
Spinal Instrumentation ◽  
Pedicle Screws ◽  
Tissue Response ◽  
In Vivo Model ◽  
Particle Count ◽  
Spinal Implant

Study Design. Combinations of metal implants (stainless steel (SS), titanium (Ti), and cobalt chrome (CC)) were placed in porcine spines. After 12 months, tissue response and implant corrosion were compared between mixed and single metal junctions. Objective. Model development and an attempt to determine any detriment of combining different metals in posterior spinal instrumentation. Methods. Yucatan mini-pigs underwent instrumentation over five unfused lumbar levels. A SS rod and a Ti rod were secured with Ti and SS pedicle screws, SS and Ti crosslinks, SS and CC sublaminar wires, and Ti sublaminar cable. The resulting 4 SS/SS, 3 Ti/Ti, and 11 connections between dissimilar metals per animal were studied after 12 months using radiographs, gross observation, and histology (foreign body reaction (FBR), metal particle count, and inflammation analyzed). Results. Two animals had constructs in place for 12 months with no complications. Histology of tissue over SS/SS connections demonstrated 11.1 ± 7.6 FBR cells, 2.1 ± 1.7 metal particles, and moderate to extensive inflammation. Ti/Ti tissue showed 6.3 ± 3.8 FBR cells, 5.2 ± 6.7 particles, and no to extensive inflammation (83% extensive). Tissue over mixed components had 14.1 ± 12.6 FBR cells and 13.4 ± 27.8 particles. Samples surrounding wires/cables versus other combinations demonstrated FBR (12.4 ± 13.5 versus 12.0 ± 9.6 cells, P = 0.96), particles (19.8 ± 32.6 versus 4.3 ± 12.7, P = 0.24), and inflammation (50% versus 75% extensive, P = 0.12). Conclusions. A nonfusion model was developed to study corrosion and analyze biological responses. Although no statistical differences were found in overlying tissue response to single versus mixed metal combinations, galvanic corrosion between differing metals is not ruled out. This pilot study supports further investigation to answer concerns when mixing metals in spinal constructs.

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