As activated microglia is an early sign that often precedes and triggers neuronal death,inhibition of microglial activation and reduction of subsequent neurotoxicity may offer therapeutic *** present study demonstrate...
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As activated microglia is an early sign that often precedes and triggers neuronal death,inhibition of microglial activation and reduction of subsequent neurotoxicity may offer therapeutic *** present study demonstrates that rat primary cultured microglia expressed Kir6.1 and SUR2 subunits of K channel,which was identical to that expressed in BV-2 microglial cell *** classic Kchannel opener pinacidil and selective mitochondrial K(mito-K)channel opener diazoxide prevented rotenone-induced microglial activation and production of proinflammatory factors（TNF-αand PGE）. And the effects of pinacidil and diazoxide were reversed by mito-Kblocker 5-hydroxydecanoate（5-HD）, indicating that mito-Kchannels participate in the regulation of microglial ***,the underlying mechanisms involved the stabilization of mitochondrial membrane potential and inhibition of p38/JNK activation in ***,the in vivo study confirmed that diazoxide exhibited neuroprotective effects against rotenone along with the inhibition of microglial activation and ***,microglial mito-Kchannel might be a novel prospective target for the treatment of neuroinflammation-related degenerative disorders such as Parkinson's disease.
The transmission of pain signals at the spinal level is crucially dependent on voltage-dependent calcium channels(VDCCs)in nociceptive *** rapid entry of calcium into cells through activation of VDCCs directly affects...
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The transmission of pain signals at the spinal level is crucially dependent on voltage-dependent calcium channels(VDCCs)in nociceptive *** rapid entry of calcium into cells through activation of VDCCs directly affects membrane potential and contributes to electrical excitability,repetitive firing patterns,excitation-contraction coupling,and gene *** dorsal horn of the spinal cord is a critical integration site in painful sensation transduction and modulation processes.N-type calcium channels,as a member of VDCCs family,are highly concentrated in both dorsal root ganglia cell bodies and also in the synaptic terminals they make in dorsal horn of the spinal cord(laminaeⅠandⅡ)where they regulate the release of the key nocieeptive neurotransmitters such as substance P and *** primary afferents(mainly C-fibers and A-fibers)are implicate in the sensation of a variety of noxious painful stimuli including thermal,mechanical,and ***,N-type VDCCs play a fundamental role in the transmission of noxious somatosensory stimuli and endogenous neuropathic pain signals. Pharmacological and gene-knockout studies implicate N-type calcium channels as key mediators of nociceptive signaling in dorsal root ganglion(DRG)neurons,which may represent a novel target for pain *** chronic pain afflicts a large number of people worldwide but satisfactory relief from such pain is difficult to achieve with drugs that are currently available,and so there is a great need for the development of new,efficacious and safe *** current investigation suggest that selective blockade of the N-type calcium channels can produce powerful antinociceptive action even in morphine-unresponsive clinical situations and the general lack of serious opioid-related side effects such as addiction,respiratory depression,and tolerance has made the N-type calcium channel an attractive therapeutic target for a variety of chronic and neuropathic pain conditions
Hyperbaric oxygen preconditioning(HBO-PC)increases the level of HIF-1αand its target gene VEGF which is involved in *** regeneration is an angiogenesis-dependent *** hypothesized that HIF-1αand VEGF mediated the ang...
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Hyperbaric oxygen preconditioning(HBO-PC)increases the level of HIF-1αand its target gene VEGF which is involved in *** regeneration is an angiogenesis-dependent *** hypothesized that HIF-1αand VEGF mediated the angiogenesis effect of HBO-PC on regenerating rat *** Sprague Dawley rats received HBO-PC followed by 70% partial *** of hepatocytes and endothelial cells was evaluated by BrdU staining. Microvascular density was assessed by immunohistochemistry,mRNA expression of HIF-1αwas assessed by quantitative RT-PCR and protein levels of HIF-1αand VEGF were assessed by western ***-1αDNA-binding activity was determined with an ELISA-based ***-PC increased the proliferation index of endothelial cells and microvascular density at 48 hr after partial hepatectomy. The protein level and DNA-binding activity of HIF-1αand the protein level of VEGF were increased by HBO-PC before and after partial *** hepatectomy alone also increased proliferation index and the expressions of HIF-1αand *** results indicated that the angiogenesis effect of HBO-PC on liver after partial hepatectomy could be achieved by increased HIF-1αactivity and VEGF ***,the angiogenic effect of HBO-PC is moderate and HBO-PC failed to produce additional effect on the enhancement of HIF-1αand VEGF induced by partial hepatectomy alone.
Helicobacter pylori(***)-infected patients have a significantly higher risk of developing peptic ulcer or gastric *** produce cytotoxic products(CagA and VacA)that can interfere in the balance between apoptosis and pr...
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Helicobacter pylori(***)-infected patients have a significantly higher risk of developing peptic ulcer or gastric *** produce cytotoxic products(CagA and VacA)that can interfere in the balance between apoptosis and proliferation of the gastric epithelial cells in the early *** infection-induced alteration of the balance contributes to the gastric mucosal damage and favors the carcinogenetic *** herbal remedies have been used to treat gastric *** the present study,the medicated serum *** Qi and Cleaning Re(NQCR)Prescription and its main components Radix Astragali(RA)and Scutellaria Baicalensis Georgi(SBG)significantly prevented the H. pylori-induced imbalance between the apoptosis and the proliferation in human gastric epithelial cell line GES-1 *** medicated serum inhibited the increased levels of two cellular proteins,COX-2 and ki67, that are closely related to the status of apoptosis and *** implies that the alteration of COX-2 and ki67 may contribute to the protective effects of RA,SBG and NQCR *** on the above findings,we infer that RA,SBG and NQCR Prescription balance the homeostasis between apoptosis and proliferation of the gastric epithelial cells,thereby preventing or delaying the pathological process of gastric diseases such as chronic gastritis and gastric cancer.
Cytochrome P450(CYP)ω-hydroxylases and their arachidonic acid(AA)metabolites play important roles in myocardial ischemia-reperfusion(MI/R)*** this study we investigated the effects of several selective CYPω-hydroxyl...
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Cytochrome P450(CYP)ω-hydroxylases and their arachidonic acid(AA)metabolites play important roles in myocardial ischemia-reperfusion(MI/R)*** this study we investigated the effects of several selective CYPω-hydroxylase inhibitiors on MI/R-induced myocardial apoptosis. Rats were subjected 30 minutes of ischemia and 2 hours of *** received either 17-octadecanoic acid(17-ODYA,0.3 or 3 mg/kg),N-methylsulfonyl-12, 12-dibromododec-11-enamide(DDMS,0.4 or 0.8 mg/kg),N-hydroxy-N'-(4-butyl-2-methylphenyl) formamidine(HET0016,0.1 or 1 mg/kg)or vehicle 10 minutes prior to *** further assess the role of mitogen-activated protein kinases(MAPKs)in the CYPω-hydroxylase inhibitor-induced antiapoptotic effect,rats also received PD98059(1 mg/kg),SB203580(1 mg/kg)or SP600125(6 mg/kg)15 minutes prior to ischemia,with subsets of rats also receiving HET0016 10 minutes prior to *** with vehicle group,17-ODYA,DDMS and HET0016 significantly inhibited myocardial apoptosis as evidenced by decreased DNA ladder formation,terminal dUTP deoxynucleotidyltransferase nick end-labeling(TUNEL)positive nuclear *** also decreased caspase-3 activity and Bax protein expression but up-regulated the expression of Bc1-2. Conversely,exogenous 20-HETE administration exerted opposite ***,HET0016 increased the activity of extracellular signal-related protein kinases 1 and 2(ERK1/2)but had no significant effect on p38 MAPK or c-Jun N-terminal kinase(JNK)during I/*** with PD98059,the inhibitor of ERK1/2,but not SB203580 or SP600125,almost completely blocked the effect exerted by *** together,these data suggest that CYPω-hydroxylase inhibition exerts significant anti-apoptosis effects,at least in pact,by activation of ERK1/2 in I/R heart.
Objective Hypoxic cells in tumors are believed to limit the complete control of tumors with *** order to enhanced radiosensitivity of hypoxic cell to radiation. Nicotinoylamino acid compounds were synthesized and test...
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Objective Hypoxic cells in tumors are believed to limit the complete control of tumors with *** order to enhanced radiosensitivity of hypoxic cell to radiation. Nicotinoylamino acid compounds were synthesized and tested for radiosensitizing activity. Methods①Compounds 4,5,9a,9b,9c,10a and 10b were synthesized by nicotinoyl chlorideor or nicotinoyl azide as acetylation agents of amino acid esters or amino acids.②The cytotoxicity and radiosensitization effect of compounds（4,5,9a,9b,9c,10a,10b）were tested in Leukemia cell *** cytotoxicity of compounds were using endpoint dilution technique.③1×10～5/5μl of LA-795 lung adenocarcinoma cells were planted into right hind limbs of T-739 *** started when the tumors grew to'*** tumors were irradiated locally with dose 2Gy/day, continuous 5 days,1000mg/kg of 9c was injected（i.p.）into T-739 mice 60 min before irradiation or combined of 9c and hyperthermia or 9c and hyperthermia breathing carbogea（5%CO+95%O） *** the results showed that compounds 9a and 9c showed significant radiosensitizing effects,the sensitizer enhancement ration（SER）was 1.64 and 1.58 respectively,and nicotinamide don't show good radiosensitizing effect under the same *** 9c was used alone the average time required for the tumors to grow to three times the original mean volume is 5.8 days. When 9c and hyperthermia were combined,the average time required was 12.9 days.9c was given （i.p）60min before irradiation,then the tumors were treated with hyperthermia（43℃）for 30min and breathing carborgen 5min after irradiation,the average time required was 13.0 days. Conclusion Compound 9a and 9c showed radiosensitization effect for Leukemia cell L,9c combined hyperthermia and breathing carbogen can enhance radiesesitizing acticity for tumor and radiation-induced growth delay.
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