Preparation of Neuropeptide Nanoparticle and Its Mechanism in Corneal Nerve Regeneration in Substance P-Neurokinin 1 Receptor Signaling Pathway

2021 ◽  
Vol 13 (2) ◽  
pp. 254-263
Author(s):  
Juan Liu ◽  
Ming Li
Keyword(s):  
Substance P ◽  
Nerve Regeneration ◽  
Signaling Pathway ◽  
Loading Rate ◽  
Ganglion Cells ◽  
Drug Loading ◽  
Multiple Emulsion ◽  
High Concentration ◽  
Corneal Nerve ◽  
Neurokinin 1

The multiple emulsion method was applied to prepare the 1.5 mL solution of ciliary neurotrophic factor (CNTF), and dichloromethane solution with 2.5% polylactic acid (PLA) was added into the CNTF solution during the colostrum process, and then, polyethylene glycol solution was added into the mixed solution under ultrasonic conditions to form multiple emulsion; finally, it was stirred magnetically and centrifuged to obtain CNTF nanoparticles. The transmission electron microscope (TEM) was applied to characterize the prepared nanoparticles that detected their drug loading rate, encapsulation rate, and their drug release in vitro and in vivo. In the demonstration of neuropeptide nanoparticles participating in corneal nerve regeneration in the substance p-neurokinin 1 receptor (SP-NK-1R) signaling pathway, it was to detect the gene expression in the trigeminal ganglion cells based on the different groups like normal group, advanced glycation end products (AGE)/Stattic group, and AGE + CNTF/Stattic + CNTF group. In the characterization experiment of CNTF nanoparticles, their surfaces were smooth, they evenly distributed, and the average drug loading rate reached 1.27% ± 0.032%; the nanoparticles were able to continuously release CNTF molecules within 30 hours; what’s more, CNTF group (low concentration to high concentration) and CNTF nanoparticles group (low concentration to high concentration) could both enhance the expression of mouse optic nerve cells. Compared to AGE group, the expressions of substance p-signal transducer and activator of transcription 3 (p-STAT3) in trigeminal ganglion cells increased after adding CNTF and CNTF nanoparticles, respectively (P < 0.05); and the expression of p-STAT3 increased remarkably after the addition of CNTF nanoparticles (P < 0.05), with an obvious increase on the growth of nerve axon. On the other hand, it had the same results as the above, compared with Stattic group.

The effect of human platelet lysate on corneal nerve regeneration

2019 ◽  
pp. bjophthalmol-2019-314408 ◽  
Author(s):  
Chin-Te Huang ◽  
Hsiao-Sang Chu ◽  
Kuo-Chi Hung ◽  
Lily Wei Chen ◽  
Mei-Yun Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Nerve Regeneration ◽  
Neurotrophic Factors ◽  
Ganglion Cells ◽  
Human Platelet ◽  
Platelet Lysate ◽  
Human Platelet Lysate ◽  
Corneal Nerve

AimThis study aimed to test whether human platelet lysate (HPL) has neurotrophic ability for corneal nerve regeneration.MethodsWe measured the neurotrophic factors in human peripheral serum (HPS) and two commercially available HPLs, UltraGRO and PLTMax. In vitro, we compared the growth rates, neuronal differentiation and immunostaining of neuron markers in mouse neuroblastoma cell line (Neuro-2a) and primary culture of mouse trigeminal ganglion cells that were cultivated in different concentrations of fetal bovine serum, HPS and HPL. In vivo, we created corneal wounds on Sprague Dawley rats with a rotating burr and evaluated the effects of topical HPL on wound healing and corneal nerve regeneration by in vivo confocal microscopy and corneal aesthesiometry.ResultsHPLs had significantly higher concentrations of various neurotrophic factors compared with HPS (p<0.05). In Neuro-2a cells, 3% HPL was better at promoting neuronal growth and differentiation compared with HPS at the same concentration. HPL was also found to have superior neurotrophic effects compared with HPS in primary cultures of mouse trigeminal ganglion cells. In vivo, HPL-treated eyes had better corneal epithelial wound healing rate, nerve regeneration length and corneal touch threshold compared with eyes treated with artificial tears (p<0.05).ConclusionHPL has significantly higher concentrations of neurotrophic factors compared with HPS. It showed not only in vitro but also in vivo corneal neurotrophic abilities. Our results suggest that HPL may have a potential role in the treatment of diseases related to corneal nerve damage or degeneration.

scholarly journals Up-Regulation of the Biosynthesis and Release of Substance P through Wnt/β-Catenin Signaling Pathway in Rat Dorsal Root Ganglion Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0129701 ◽  
Author(s):  
Yu-Sang Li ◽  
Yang Xi ◽  
Xiao-Jun Li ◽  
Chang-Long Leng ◽  
Mei-Mei Jia ◽  
...  
Keyword(s):  
Substance P ◽  
Dorsal Root Ganglion ◽  
Signaling Pathway ◽  
Dorsal Root ◽  
Ganglion Cells ◽  
Dorsal Root Ganglion Cells

scholarly journals Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush

2019 ◽  
Vol 12 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Nobuhiko Seki ◽  
Ryosuke Ochiai ◽  
Terunobu Haruyama ◽  
Masashi Ishihara ◽  
Maika Natsume ◽  
...  
Keyword(s):  
Substance P ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Subsequent Treatment ◽  
Treatment Schedule ◽  
Weekly Schedule ◽  
Patient Centered ◽  
Neurokinin 1 ◽  
Dermatological Side Effects

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.

scholarly journals Insulin resistance limits corneal nerve regeneration in patients with Type 2 diabetes undergoing intensive glycemic control

2021 ◽  
Author(s):  
Georgios Ponirakis ◽  
Muhammad A. Abdul‐Ghani ◽  
Amin Jayyousi ◽  
Mahmoud A. Zirie ◽  
Salma Al‐Mohannadi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Nerve Regeneration ◽  
Intensive Glycemic Control ◽  
Corneal Nerve

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

2007 ◽  
Vol 292 (4) ◽  
pp. L915-L923 ◽  
Author(s):  
Jaime Chávez ◽  
Patricia Segura ◽  
Mario H. Vargas ◽  
José Luis Arreola ◽  
Edgar Flores-Soto ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Smooth Muscle Contraction ◽  
In Vivo Experiments ◽  
Intracellular Ca ◽  
Neurokinin 1 ◽  
Substance P Release

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.

The effect of Rho Kinase inhibition on corneal nerve regeneration in vitro and in vivo

2021 ◽  
Author(s):  
Sonja Mertsch ◽  
Inga Neumann ◽  
Cosima Rose ◽  
Marc Schargus ◽  
Gerd Geerling ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Rho Kinase ◽  
Kinase Inhibition ◽  
Corneal Nerve ◽  
Regeneration In Vitro

scholarly journals Substance P Signaling Contributes to Granuloma Formation inTaenia crassicepsInfection, a Murine Model of Cysticercosis

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Armandina Garza ◽  
David J. Tweardy ◽  
Joel Weinstock ◽  
Balaji Viswanathan ◽  
Prema Robinson
Keyword(s):  
Substance P ◽  
Potential Role ◽  
Cytokine Production ◽  
Taenia Solium ◽  
Granuloma Formation ◽  
Wild Type ◽  
Granulomatous Reaction ◽  
Pain Transmission ◽  
Neurokinin 1 ◽  
The Brain

Cysticercosis is an infection with larval cysts of the cestodeTaenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a neuropeptide involved in pain-transmission, contributes to inflammation and previously was detected in granulomas associated with deadT. crassicepscysts. To determine if SP contributes to granuloma formation, we measured granuloma-size and levels of IL-1β, TNF-α, and IL-6 within granulomas inT. crassiceps-infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP-receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout mice were reduced by 31 and 36%, respectively, compared to WT mice (P<.05for both) and produced up to 5-fold less IL-1β, TNF-α, and IL-6 protein. Thus, SP signaling contributes to granuloma development and proinflammatory cytokine production inT. crassicepsinfection and suggests a potential role for this mediator in human cystercercosis.

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