scholarly journals Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroya Takada ◽  
Jun Yonekawa ◽  
Masami Matsumoto ◽  
Kishio Furuya ◽  
Masahiro Sokabe
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Atp Release ◽  
Aqueous Solubility ◽  
P2y Receptors ◽  
Hacat Keratinocytes ◽  
Wound Edge ◽  
Atopic Skin ◽  
Intracellular Ca ◽  
Mechanical Stretching

Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via TRPC6. This process might facilitate wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca2+ signaling. We also applied hyperforin/HP-β-CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin.

Curcumin-Loaded Self-Microemulsifying Gel for Enhancing Wound Closure

2021 ◽  
pp. 1-9
Author(s):  
Jiun Wen Guo ◽  
Chi-Ming Pu ◽  
Chih-Yi Liu ◽  
Shih-Lun Lo ◽  
Yu-Hsiu Yen
Keyword(s):  
Wound Healing ◽  
Therapeutic Effect ◽  
Delivery System ◽  
Wound Closure ◽  
Ex Vivo ◽  
Aqueous Solubility ◽  
Punch Biopsy ◽  
Full Thickness ◽  
Sampling System

<b><i>Introduction:</i></b> Wound healing is a process in which damaged cutaneous tissues are repaired and is a dynamic physiological interaction involving several types of cells, tissues, and proteins. Compared with typical treatments, specifically in terms of multifunctional properties, bioactive drug-loaded wound dressing in a controlled and sustained delivery system is an advanced tool that significantly improves wound healing. Curcumin substantially enhances wound healing and prevents oxidative damage. However, the effects of this compound on improving wound healing are limited by its aqueous solubility, poor tissue absorption, and rapid metabolism. Hence, the current study aimed to investigate the therapeutic effect of curcumin-loaded self-microemulsifying gel on wound healing. <b><i>Methods:</i></b> Ex vivo permeation studies of the skin of BALB/c mice were performed using a diffusion cell sampling system. The in vivo therapeutic effect was investigated with a full-thickness wound model. Two 6-mm full-thickness circular wounds were created on the back of the mice via punch biopsy. Then, they received different topical gels for 12 days to enhance wound closure. <b><i>Results:</i></b> The curcumin-loaded self-microemulsifying gel had higher skin flux, cumulative amount, and permeability coefficient than the commercial gels. In addition, it enhanced wound healing. <b><i>Conclusions:</i></b> This is the first study that utilized self-microemulsifying gel loaded with curcumin as a delivery system for wound healing. However, the effect of this delivery system on wound healing or skin disease treatment should be further investigated.

scholarly journals Sustained Ca2+ mobilizations: a quantitative approach to predict their importance in cell-cell communication and wound healing

2019 ◽  
Author(s):  
Yoonjoo Lee ◽  
Min Tae Kim ◽  
Garrett Rhodes ◽  
Kelsey Sack ◽  
Sung Jun Son ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Cell Communication ◽  
In Vitro Models ◽  
Wound Edge ◽  
Communication Events ◽  
Epithelial Wound Healing ◽  
Culture Models ◽  
Cell Cell

AbstractEpithelial wound healing requires the coordination of cells to migrate as a unit over the basement membrane after injury. To understand the process of this coordinated movement, it is critical to study the dynamics of cell-cell communication. We developed a method to characterize the injury-induced sustained Ca2+ mobilizations that travel between cells for periods of time up to several hours. These events of communication are concentrated along the wound edge and are reduced in cells further away from the wound. Our goal was to delineate the role and contribution of these sustained mobilizations and using MATLAB analyses, we determined the probability of cell-cell communication events in in vitro models and ex vivo organ culture models. We demonstrated that the injury response was complex and represented the activation of a number of receptors. In addition, we found that pannexin channels mediated the cell-cell communication and motility. Furthermore, the sustained Ca2+ mobilizations are associated with changes in cell morphology and motility during wound healing. The results demonstrate that both purinoreceptors and pannexins regulate the sustained Ca2+ mobilization necessary for cell-cell communication in wound healing.

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

2020 ◽  
Vol 21 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rural Communities ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Aortic Ring ◽  
Treated Group ◽  
Control Group ◽  
Dependent Manner ◽  
Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

2002 ◽  
Vol 283 (2) ◽  
pp. C569-C578 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Release ◽  
Anion Channel ◽  
P2y Receptors ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Medium Osmolarity ◽  
Subsequent Activation

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.

In Vivo and ex Vivo Approaches to Studying the Biomechanical Properties of Healing Wounds in Rat Skin

2013 ◽  
Vol 135 (10) ◽  
Author(s):  
Clare Y. L. Chao ◽  
Gabriel Y. F. Ng ◽  
Kwok-Kuen Cheung ◽  
Yong-Ping Zheng ◽  
Li-Ke Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Normal Skin ◽  
Biomechanical Properties ◽  
Skin Wound ◽  
Sprague Dawley ◽  
Rat Skin ◽  
Mechanical Stiffness ◽  
Air Jet

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.

Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies

2017 ◽  
Vol 101 ◽  
pp. 569-579 ◽  
Author(s):  
Lydia Thomas ◽  
Foziyah Zakir ◽  
Mohd. Aamir Mirza ◽  
Md. Khalid Anwer ◽  
Farhan Jalees Ahmad ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Nanoemulsion Gel

scholarly journals 932 Development of an early wound model in human ex vivo skin explant as a preclinical model of wound healing

2019 ◽  
Vol 139 (5) ◽  
pp. S161
Author(s):  
A.V. Caserta ◽  
J.E. Neil ◽  
J. Volmer ◽  
L. Ring ◽  
J. Lenn ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Preclinical Model ◽  
Wound Model ◽  
Early Wound

Calcium Signaling Mediated by P2Y Receptors in Mouse Taste Cells

2003 ◽  
Vol 90 (5) ◽  
pp. 3283-3294 ◽  
Author(s):  
Sergey G. Baryshnikov ◽  
Olga A. Rogachevskaja ◽  
Stanislav S. Kolesnikov
Keyword(s):  
Cellular Response ◽  
P2y Receptors ◽  
Taste Bud ◽  
P2y Receptor ◽  
Complex Cell ◽  
Inhibitory Analysis ◽  
Taste Cells ◽  
Intracellular Ca ◽  
Mouse Taste ◽  
Soc Channels

Evidence implicates a number of neuroactive substances and their receptors in mediating complex cell-to-cell communications in the taste bud. Recently, we found that ATP, a ubiquitous neurotransmitter/neuromodulator, mobilizes intracellular Ca2+ in taste cells by activating P2Y receptors. Here, P2Y receptor-cellular response coupling was characterized in detail using single cell ratio photometry and the inhibitory analysis. The sequence of underlying events was shown to include ATP-dependent activation of PLC, IP3 production, and IP3 receptor-mediated Ca2+ release followed by Ca2+ influx. Data obtained favor SOC channels rather than receptor-operated channels as a pathway for Ca2+ influx that accompanies Ca2+ release. Intracellular Ca2+ mobilized by ATP is apparently extruded by the plasma membrane Ca2+-ATPase, while a contribution of the Na+/Ca2+ exchange and other mechanisms of Ca2+ clearance is negligible. Cyclic AMP-dependent phosphorylation is likely to control a gain of the phosphoinositide cascade involved in ATP transduction. ATP-responsive taste cells are abundant in circumvallate, foliate, and fungiform papillae. Taken together, our observations point to a putative role for ATP as a neurotransmitter operative in the taste bud.

scholarly journals Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP

2020 ◽  
Vol 318 (4) ◽  
pp. R669-R676 ◽  
Author(s):  
Yang Chen ◽  
Jacob J. Schaefer ◽  
Seethalakshmi R. Iyer ◽  
Gerald E. Harders ◽  
Shuchong Pan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Subcutaneous Injection ◽  
Ex Vivo ◽  
Subcutaneous Administration ◽  
Therapeutic Drug ◽  
Hypertensive Rats ◽  
Pressure Lowering ◽  
Intracellular Ca ◽  
Isolated Arteries

Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP-lowering and cGMP-activating actions of acute and chronic subcutaneous delivery in normal and hypertensive rats. Furthermore, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. In normal rats with a single subcutaneous injection, MANP promoted robust dose-dependent BP-lowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once-a-day subcutaneous injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared with vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II-mediated increases in intracellular Ca2+ levels while directly vasorelaxing arterial rings. Our study demonstrates for the first time the effectiveness of subcutaneous administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension.

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