Nerve Growth
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PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260496
Siravit Sitprija ◽  
Lawan Chanhome ◽  
Onrapak Reamtong ◽  
Tipparat Thiangtrongjit ◽  
Taksa Vasaruchapong ◽  

The venomic profile of Asian mountain pit viper Ovophis monticola is clarified in the present study. Using mass spectrometry-based proteomics, 247 different proteins were identified in crude venom of O. monticola found in Thailand. The most abundant proteins were snake venom metalloproteases (SVMP) (36.8%), snake venom serine proteases (SVSP) (31.1%), and phospholipases A2 (PLA2) (12.1%). Less abundant proteins included L-amino acid oxidase (LAAO) (5.7%), venom nerve growth factor (3.6%), nucleic acid degrading enzymes (3.2%), C-type lectins (CTL) (1.6%), cysteine-rich secretory proteins (CRISP) (1.2%) and disintegrin (1.2%). The immunoreactivity of this viper’s venom to a monovalent antivenom against green pit viper Trimeresurus albolabris, or to a polyvalent antivenom against hemotoxic venom was investigated by indirect ELISA and two-dimensional (2D) immunoblotting. Polyvalent antivenom showed substantially greater reactivity levels than monovalent antivenom. A titer for the monovalent antivenom was over 1:1.28x107 dilution while that of polyvalent antivenom was 1:5.12x107. Of a total of 89 spots comprising 173 proteins, 40 spots of predominantly SVMP, SVSP and PLA2 were specific antigens for antivenoms. The 49 unrecognized spots containing 72 proteins were characterized as non-reactive proteins, and included certain types of CTLs and CRISPs. These neglected venom constituents could limit the effectiveness of antivenom-based therapy currently available for victims of pit viper envenomation.

2021 ◽  
Qianqian Chen ◽  
Qianyan Liu ◽  
Pan Wang ◽  
Tianmei Qian ◽  
Xinghui Wang ◽  

Abstract Proper supporting factor can possess the ability to enhance neuron regeneration, for instance, neurotrophic effects especially nerve growth factor (NGF). However, the in vivo applications of NGF are largely limited by its intrinsic disadvantages. Considering that let-7 targets and regulates NGF, and let-7 is also the core and harbor regulators in peripheral nerve repair and regeneration, we evaluated the potential application in clinical. We firstly screened the let-7a as the most ideal let-7 family molecular by gene expression analysis and functional approach. We further evaluated the in vivo safety, the cell permeability of 3 main cells in regeneration micro-environment, and the morphological and functional indicators. Our study provides an essential basis for in vivo application of let-7 and pictured a vision for the clinical translation of miRNA as a prospective alternative for regenerative medicine.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6023
Christina Hassiepen ◽  
Aashish Soni ◽  
Ines Rudolf ◽  
Vivian Boron ◽  
Sebastian Oeck ◽  

High expression of the receptor tyrosine kinase TrkA/NTRK1 is associated with a favorable outcome in several solid tumors of childhood including neuroblastoma. During development, TrkA/NTRK1 governs migration and differentiation of neuronal precursor cells, while it is associated with mitotic dysfunction and altered DNA damage response, among others, in neuroblastoma. Here, we used human neuroblastoma cell lines with inducible TrkA/NTRK1 expression to mechanistically explore the role of TrkA/NTRK1 signaling in checkpoint activation after DNA damage induced by ionizing radiation (IR). TrkA/NTRK1 activated cells showed increased short-term cell viability upon IR compared to vector control cells. This was accompanied by a deficient G2/M-checkpoint at both low (1 Gy) and high doses (4 Gy) of IR. In a tightly controlled setting, we confirmed that this effect was strictly dependent on activation of TrkA/NTRK1 by its ligand, nerve growth factor (NGF). TrkA/NTRK1-expressing cells displayed impaired ATM and CHK1 phosphorylation, resulting in stabilization of CDC25B. In line with these findings, ATM or ATR inhibition recapitulated the effects of TrkA/NTRK1 activation on the IR-induced G2/M-checkpoint. In conclusion, we here provide first evidence for a previously unrecognized function of NTRK signaling in checkpoint regulation and the response to IR.

2021 ◽  
Vol 33 (3) ◽  
pp. 182
Khairina Nasution ◽  
Deryne Anggia Paramita ◽  
Nova Zairina Lubis

Background: Atopic dermatitis (AD) is the most common skin disease in infants and children. AD is influenced by hereditary and environmental factors, and it is characterized by an inflammatory reaction in the skin. In developing countries, children suffering from AD are estimated around 10–20%, of which 60% of the cases persist into adulthood. Substance P is a cutaneous neuropeptide that contributes to the pathogenesis of AD. Substance P promotes the production of nerve growth factors from keratinocytes, and the release of histamine, leukotriene, or tumor necrosis factor from mast cells, which cause the growth of sensory nerve fibers, augmentation of skin inflammation, and are considered pruritogenic factors. Purpose: This study aims to determine the description of substance P in children with atopic dermatitis using a descriptive observational study with a cross-sectional approach. Methods: This is a destructive observational study with a crossectional approach samples were selected from AD patients at the Universitas Sumatera Utara Hospital. Result: The largest group of subjects were childhood (2–12 years old), there was 60%, followed by the adolescent group (12–18 years old) and the infant group (<2 years old). In the childhood group, the highest level of substance P was found in girls with a mean of 349.03 ± 146.7. On the other hand, the highest levels of substance P in the adolescent were found in males with a mean of 243.73 ± 64.57 ng/L. Conclusion: In this study, we found that the level of substance p was higher in the childhood group.

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4290
Hyunseong Kim ◽  
Wanjin Jeon ◽  
Jinyoung Hong ◽  
Junseon Lee ◽  
Changhwan Yeo ◽  

Gongjin-dan (GJD) is a multiherbal formula produced from 10 medicinal herbs and has been traditonally used as an oriental medicine to treat cardiovascular diseases, alcoholic hepatitis, mild dementia, and anemia. Additionally, increasing evidence suggests that GJD exerts neuroprotective effects by suppressing inflammation and oxidative stress-induced events to prevent neurological diseases. However, the mechanism by which GJD prevents oxidative stress-induced neuronal injury in a mature neuron remains unknown. Here, we examined the preventive effect and mechanism of GJD on primary cortical neurons exposed to hydrogen peroxide (H2O2). In the neuroprotection signaling pathway, Sirtuin1 is involved in neuroprotective action as a therapeutic target for neurological diseases. After pre-treatment with GJD at three concentrations (10, 25, and 50 µg/mL) and stimulation by H2O2 (30 µM) for 24 h, the influence of GJD on Sirtuin1 activation was assessed using immunocytochemistry, real-time PCR, western blotting, and flow cytometry. GJD effectively ameliorated H2O2-induced neuronal death against oxidative damage through Sirtuin1 activation. In addition, GJD-induced Sirtuin1 activation accelerated elongation of new axons and formation of synapses via increased expression of nerve growth factor and brain-derived neurotrophic factor, as well as regeneration-related genes. Thus, GJD shows potential for preventing neurological diseases via Sirtuin1 activation.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Yan Ke ◽  
Lina Huang ◽  
Bingheng Chen ◽  
Jing Sima ◽  
Jiaguo Cao ◽  

With an increasing incidence in recent years, glaucoma (GL) has gradually become a global public health problem for humans of all ages. Nerve growth factor (NGF) eye drops, with well-documented stable effect in the treatment of GL, can be potentiated by the administration of NGF drugs via ultrasound contrast agent (UCA). This study analyzed the efficacy of NGF+UCA on GL mice and the influencing mechanism on retinal ganglion cells and further explored the pathological changes of GL mice under different UCA irradiation duration. In this study, we established GL mouse models and treated the mouse with NGF+UCA. The effect of NGF+UCA on intraocular pressure in mice was observed; the flash visual evoked potential of mice was compared; the changes of retinal structure, inflammation index, and oxidative stress index were observed, and autophagic protein levels were tested. Finally, the influence of UCA irradiation duration on GL symptoms was observed. The results showed that the intraocular pressure of mice decreased greatly, while their flash visual evoked potential and nervous layer of retina increased, and their ganglion cells showed stronger proliferation activity and weaker apoptosis and autophagy, indicating that UCA-mediated NGF can strongly improve the pathological condition of GL mice. In addition, PI3K/AKT pathway-associated proteins were inhibited in retina under the intervention of NGF+UCA, which further suggests that the influence of UCA-mediated NGF on GL is achieved by inhibiting autophagy of retinal ganglion cells and enhancing their apoptosis via the PI3K/AKT signaling pathway. Moreover, we found that in the treatment of GL, three weeks of UCA irradiation and six weeks caused no significant difference in the pathological manifestations and ganglion cells of mice, while after six weeks of irradiation, the level of NLRP3 in mice increased. In conclusion, UCA-mediated NGF can significantly improve the pathological condition of GL mice and improve the apoptosis of retinal ganglion cells by inhibiting autophagy, which is associated with the inhibition of the PI3K/AKT signal pathway. In terms of selection of UCA irradiation duration, three weeks of irradiation is enough to yield good clinical results.

2021 ◽  
Vol 11 (12) ◽  
pp. 1561
Igor Manzhulo ◽  
Olga Manzhulo ◽  
Anna Tyrtyshnaia ◽  
Arina Ponomarenko ◽  
Sophia Konovalova ◽  

The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca2+ in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI.

2021 ◽  
Vol 12 (12) ◽  
Huey-En Tzeng ◽  
Syuan-Ling Lin ◽  
Louis Anoop Thadevoos ◽  
Ming-Yu Lien ◽  
Wei-Hung Yang ◽  

AbstractChondrosarcoma is a malignancy of soft tissue and bone that has a high propensity to metastasize to distant organs. Nerve growth factor (NGF) is critical for neuronal cell growth, apoptosis, and differentiation, and also appears to promote the progression and metastasis of several different types of tumors, although the effects of NGF upon chondrosarcoma mechanisms are not very clear. We report that NGF facilitates lysyl oxidase (LOX)-dependent cellular migration and invasion in human chondrosarcoma cells, and that NGF overexpression enhances lung metastasis in a mouse model of chondrosarcoma. NGF-induced stimulation of LOX production and cell motility occurs through the inhibition of miR-149-5p expression, which was reversed by PI3K, Akt, and mTOR inhibitors and their respective short interfering RNAs. Notably, levels of NGF and LOX expression correlated with tumor stage in human chondrosarcoma samples. Thus, NGF appears to be a worthwhile therapeutic target for metastatic chondrosarcoma.

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