Current Issue : July - September Volume : 2019 Issue Number : 3 Articles : 5 Articles
There is an unmet medical need for the development of non-addicting pain therapeutics\nwith enhanced efficacy and tolerability. The current study examined the effects of AQU-118, an orally\nactive inhibitor of metalloproteinase-2 (MMP-2) and MMP-9, in the spinal nerve ligation (SNL)\nrat model of neuropathic pain. Mechanical allodynia and the levels of various biomarkers were\nexamined within the dorsal root ganglion (DRG) before and after oral dosing with AQU-118. The rats\nthat received the SNL surgery exhibited significant mechanical allodynia as compared to sham\ncontrols. Animals received either vehicle, positive control (gabapentin), or AQU-118. After SNL\nsurgery, the dorsal root ganglion (DRG) of those rats dosed with vehicle had elevated messenger\nRNA (mRNA) expression levels for.................
Objective. To investigate the intervention effect and functioning mechanismof citrus alkaline extract (CAE) on bleomycin- (BLM-)\ninduced pulmonary fibrosis in mice. Methods. 42 C57BL/6 male mice were assigned randomly to the normal group, model group,\nlow (16mg/kg), medial (32mg/kg) and high (64mg/kg) CAE dosage groups, prednisone group (6mg/kg), and pirfenidone group\n(100mg/kg), respectively. One day after model construction, intragastric administration was applied to the mice once a day for 28\ndays and then killed. Body weights of mice were recorded. Their pulmonary tissues were subjected to HE staining and Massonâ??s\nstaining and then their degree of pulmonary alveolitis as well as pulmonary fibrosis was scored. Contents of hydroxyproline (HYP)\nand prostaglandin E2 (PGE2) in pulmonary tissues and levels of interleukin-17 (IL-17) in serum and bronchoalveolar lavage fluid\n(BALF) were determined by ELISA method. Expression of collagen I, collagen III, and Prosurfactant protein C (Pro-SPC) proteins\nin pulmonary tissue weremeasured immunohistochemically and that of nuclear transcription factor kB (NF-kB) and vimentin was\ndetermined by the immunofluorescence method.Apoptosis of pulmonary tissue was tested by the Tunel stainingmethod, while the\nexpression ofMAPK-relatedproteinwas recorded byWestern Blot assay. Results.AfterCAE treatment, the bodyweight, PGE2 level,\nand Pro-SPC protein expression of pulmonary fibrosismice were increased, while the score of pulmonary alveolitis and pulmonary\nfibrosis, levels of HYP and cell apoptosis, IL-17 contents of serum and BALF in pulmonary tissues, and expression of collagen\nI, collagen III, vimentin, NF-kB, and p-p38 were reduced. Conclusion. CAE effectively delayed the progression of BLM-induced\npulmonary fibrosis in pulmonary fibrosis mice and a possiblemechanismis the inhibition of cell apoptosis of NF-kB/p38-mediated\nsignaling pathway kB (NF-kB) and vimentin was\ndetermined by the immunofluorescence method.Apoptosis of pulmonary tissue was tested by the Tunel stainingmethod, while the\nexpression ofMAPK-relatedproteinwas recorded byWestern Blot assay. Results.AfterCAE treatment, the bodyweight, PGE2 level,\nand Pro-SPC protein expression of pulmonary fibrosismice were increased, while the score of pulmonary alveolitis and pulmonary\nfibrosis, levels of HYP and cell apoptosis, IL-17 contents of serum and BALF in pulmonary tissues, and expression of collagen\nI, collagen III, vimentin, NF-kB, and p-p38 were reduced. Conclusion. CAE effectively delayed the progression of BLM-induced\npulmonary fibrosis in pulmonary fibrosis mice and a possiblemechanismis the inhibition of cell apoptosis of NF-kB/p38-mediated\nsignaling pathway...
Lentiviral vectors have been used for gene therapy in the clinical phase in recent years.These vectors provide a tool for gene insertion,\ndeletion, or modification in organisms. The K562 human cell line has been used extensively in hematopoietic research. Despite its\nbroad application, it is hard-to-transfection and transduction. So, this study presents a simple method to increase the transduction\nefficiency of K562 cells with a low multiplicity of infection (MOI) of the virus particle. For this purpose, 24-well plate was coated\nby 300 microl fetal bovine serum (FBS) before seeding. Then 2*10^4 K562 cells were seeded in each FBS coated plate. After 24h, K562\ncells were attached and doubled. Different amount of lentivirus-based GFP vector according to MOI (5, 10, 15, and 20) along with\n8 microg polybrene was added to the attached K562 cells and after 6h cells and viral particle complex were spinfected. Then cells were\nreturned to the plate and incubated in 37 DegreeC overnight. After 48h transduction efficiency was established by measuring the GFPexpressing\ncells by flow cytometry. Flow cytometry analysis showed that, after plate treatment by FBS, 64.5% transduction rate in\nK562 cells was achieved atMOI=20. Therefore, this method can be an effective and simple way to increase the lentiviral transduction\nrate for suspended cells such as K562....
Ethanol (EtOH) binge drinking is characterized by high EtOH intake during few hours followed by withdrawal. Protection\nstrategies against the damages generated by this binge are poorly explored. Thus, this study is aimed at investigating the\nprotective role of treadmill physical exercise (PE) on the damage caused after repeated cycles of binge-like EtOH exposure in the\noxidative biochemistry, morphology, and cerebellar function of rats from adolescence to adulthood. For this, animals were\ndivided into four groups: control group (sedentary animals with doses of distilled water), exercised group (exercised animals\nwith doses of distilled water), EtOH group (sedentary animals with doses of 3 g/kg/day of EtOH, 20% w/v), and exercised+EtOH\ngroup (exercised animals with previous mentioned doses of EtOH). The PE occurred on a running treadmill for 5 days a week\nfor 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in a\nbinge-like manner. After the EtOH protocol and PE, animals were submitted to open field and beam walking tests. In sequence,\nthe cerebellums were collected for the biochemical and morphological analyses. Biochemical changes were analyzed by\nmeasurement of Trolox equivalent antioxidant capacity (TEAC), reduced glutathione content measurements (GSH), and\nmeasurement of nitrite and lipid peroxidation (LPO). In morphological analyses, Purkinje cell density evaluation and\nimmunohistochemistry evaluation were measured by antimyelin basic protein (MBP) and antisynaptophysin (SYP). The present\nfindings demonstrate that the binge drinking protocol induced oxidative biochemistry misbalance, from the decrease of TEAC\nlevels and higher LPO related to tissue damage and motor impairment. In addition, we have shown for the first time that\ntreadmill physical exercise reduced tissue and functional alterations displayed by EtOH exposure....
Intraocular pressure (IOP) has a tendency to fluctuate throughout the day, reaching its peak\nin the early morning in healthy subjects or glaucoma patients. Likewise, histamine tone also fluctuates\nover time, being lower at nighttime. Numerous studies have demonstrated a correlation between\nshort-term IOP fluctuation and glaucoma progression; however, it has not yet been determined\nwhether histamine plays a role in IOP fluctuations. The aim of this research was to establish the\ndistribution of the histamine receptor proteins and respective mRNAs in the eye by western blot,\nimmunohistochemistry and RT-PCR in New Zealand rabbits. Furthermore, we used a transient ocular\nhypertension (OHT) model induced by injection of 50 microL of 5% hypertonic saline into the vitreous\nand a stable OHT model (100 microL 0.1% carbomer in the anterior chamber) to address the potential\nIOP-lowering ability of H3 receptor (H3R) antagonists (ciproxifan, DL76 and GSK189254). IOPs were\nperformed with a Tono-Pen at baseline and 60, 120 and 240 min post treatment after transient OHT\ninduction and, every day for 12 days in the stable OHT model. All histamine receptor subtypes were\nlocalized in the rabbit retina and ciliary body/trabecular meshwork. All the treatments lowered IOP\nin a dose-dependent fashion between 0.3% and 1%. More specifically, the effects were maximal with\nciproxifan at 60 min post-dose........................
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