• MeSH
• akupresura MeSH
• akupunktura MeSH
• fytoterapie MeSH
• léky rostlinné čínské MeSH
• relaxace MeSH
• tradiční čínská medicína MeSH
• Publikační typ
• encyklopedie MeSH
• Geografické názvy
• Čína MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• terapie
• alternativní lékařství

Zearalenone (ZEN) is a toxic secondary metabolite of Fusarium sp. commonly found in wheat, corn, and other crops. In addition to economic losses, ZEN can seriously endanger the health of both humans and livestock, thus presenting an urgent need for ZEN-detoxifying enzymes that function in the extreme heat or pH conditions of industrial fermenters. Here, we identify and characterize the activity of the ZEN-degrading enzyme from Exophiala spinifera, ZHD_LD, which shares 60.15% amino acid identity and a conserved catalytic triad with the well-characterized ZEN-detoxifying protein ZHD101 from Clonostachys rosea. Biochemical activity and stability assays indicated that purified recombinant ZHD_LD exhibited high activity against ZEN with optimal reaction conditions of 50 °C and pH 7.0-10.0. Structural modeling of the ZHD_LD active site and comparison with ZHD101 revealed its likely mechanism of ZEN degradation. This research provides an industrially valuable candidate enzyme for ZEN detoxification in food and livestock feed.

• MeSH
• Fusarium * metabolismus   MeSH
• hydrolasy metabolismus   MeSH
• lidé MeSH
• pšenice metabolismus   MeSH
• zearalenon * chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Bortezomib (BTZ) is used as a chemotherapeutic agent for the treatment of multiple myeloma. Nevertheless, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. Thus, in this study we examined signaling pathways of interleukin-6 (IL-6) and transient receptor potential ankyrin 1 (TRPA1) in the sensory nerves responsible for neuropathic pain induced by BTZ and further determined if influencing the pathways can improve neuropathic pain. ELISA and western blot analysis were used to examine the levels of IL-6, and IL-6 receptor (IL-6R), TRPA1 and p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical and cold sensitivity in a rat model. Our results showed that systemic injection of BTZ increased mechanical pain and cold sensitivity as compared with control animals. Data also showed that protein expression of TRPA1 and IL-6R was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical and cold sensitivity in control rats and BTZ rats. Notably, the inhibitory effect of blocking TRPA1 was smaller in BTZ rats than that in control rats. In addition, a blockade of IL-6 signal attenuated intracellular p38-MAPK and JNK in the sensory neuron. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. In conclusion, we revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ, including IL-6-TRPA1, suggesting that blocking these signals is beneficial to alleviate neuropathic pain during BTZ intervention.

• MeSH
• acetanilidy farmakologie   MeSH
• analgetika farmakologie   MeSH
• bortezomib * MeSH
• chinoxaliny farmakologie   MeSH
• fosforylace MeSH
• inhibitory proteasomu * MeSH
• interleukin-6 antagonisté a inhibitory   metabolismus   MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• kationtový kanál TRPA1 antagonisté a inhibitory   metabolismus   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nervové receptory metabolismus   účinky léků   MeSH
• neuralgie chemicky indukované   farmakoterapie   metabolismus   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• práh bolesti účinky léků   MeSH
• puriny farmakologie   MeSH
• pyraziny farmakologie   MeSH
• receptory interleukinu-6 antagonisté a inhibitory   metabolismus   účinky léků   MeSH
• signální transdukce MeSH
• spinální ganglia metabolismus   patofyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dějiny 21. století MeSH
• dermatologie * dějiny   MeSH
• odměny a ceny * MeSH
• školy lékařské MeSH
• Check Tag
• dějiny 21. století MeSH
• Publikační typ
• biografie MeSH
• historické články MeSH
• portréty MeSH
• zprávy MeSH
• Geografické názvy
• Česká republika MeSH
• Čína MeSH
• Itálie MeSH

• O autorovi
• Třešňák Hercogová, Jana, 1959- Autorita

C-type natriuretic peptides (CNP) play an inhibitory role in smooth muscle motility of the gastrointestinal tract, but the effect of CNP on delayed rectifier potassium currents is still unclear. This study was designed to investigate the effect of CNP on delayed rectifier potassium currents and its mechanism by using conventional whole-cell patch-clamp technique in guinea-pig gastric myocytes isolated by collagenase. CNP significantly inhibited delayed rectifier potassium currents [I(K (V))] in dose-dependent manner, and CNP inhibited the peak current elicited by depolarized step pulse to 86.1+/-1.6 % (n=7, P<0.05), 78.4+/-2.6 % (n=10, P<0.01) and 67.7+/-2.3 % (n=14, P<0.01), at concentrations of 0.01 micromol/l, 0.1 micromol/l and 1 micromol/l, respectively, at +60 mV. When the cells were preincubated with 0.1 micromol/l LY83583, a guanylate cyclase inhibitor, the 1 ?micromol/l CNP-induced inhibition of I(K (V)) was significantly impaired but when the cells were preincubated with 0.1 micromol/l zaprinast, a cGMP-sensitive phosphodiesterase inhibitor, the 0.01 micromol/l CNP-induced inhibition of I(K (V)) was significantly potentiated. 8-Br-cGMP, a membrane permeable cGMP analogue mimicked inhibitory effect of CNP on I(K (V)). CNP-induced inhibition of I(K (V)) was completely blocked by KT5823, an inhibitor of cGMP-dependent protein kinase (PKG). The results suggest that CNP inhibits the delayed rectifier potassium currents via cGMP-PKG signal pathway in the gastric antral circular myocytes of the guinea-pig.

• MeSH
• antrum pyloricum cytologie   metabolismus   MeSH
• gastrointestinální motilita fyziologie   MeSH
• guanosinmonofosfát cyklický metabolismus   MeSH
• kultivované buňky MeSH
• membránové potenciály fyziologie   MeSH
• metoda terčíkového zámku MeSH
• morčata MeSH
• myocyty hladké svaloviny cytologie   metabolismus   MeSH
• natriuretický peptid typu C metabolismus   MeSH
• pozdní usměrňovače draslíkových kanálů metabolismus   MeSH
• relaxace svalu fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• systémy druhého messengeru fyziologie   MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH

AIMS: This study was designed to investigate the predictive value of serum collagen biomarkers on the outcomes of acute ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). METHODS: Two hundred and ten patients with STEMI were successfully treated with PCI within 6 hrs ofthe onset of chest pain. The levels of serum procollagen type I carboxyterminal peptide (PICP) and procollagen type III peptide (PIIINP) were measured by enzymelinked immunosorbent assay (ELISA) before, 3 and 6 months after PCI. Left ventricular ejection fraction was assessed by echocardiography at 3 and 6 months after PCI. The composite endpoints were death by any cause, recurrent myocardial infarction, heart failure or stroke. RESULTS: At the end of the 12-month follow up, 29 patients (13.8%) experienced an end point. The level of serum PICP in patients with an end point was higher than in patients without an end point 7 days (19.45 ± 2.17 vs 14.95 ± 3.07 ng/mL, P<0.05) or 3 month after the PCI (29.87 ± 3.02 vs 22.14 ± 3.33 ng/mL, P<0.05). The serum PIIINP level in patients with an end point was also higher than those without 7 days after PCI (59.34 ± 4.23 vs 48.78 ± 4.23 ng/mL, P<0.05). Multivariate logistic regression analysis showed day 7 (OR=2.170, 95% CI 1.583-4.345, P=0.01) and 3-month serum PICP (OR=2.340, 95% CI 1.431-4.650, P=0.01) were independent predictors of composite end points. CONCLUSIONS: Persistent elevation of serum collagen marker PICP three months after PCI predicts an adverse outcome for patients with acute ST-elevation myocardial infarction.

• MeSH
• analýza rozptylu MeSH
• biologické markery metabolismus   MeSH
• dysfunkce levé srdeční komory etiologie   MeSH
• infarkt myokardu krev   patofyziologie   terapie   MeSH
• koronární angioplastika * MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidové fragmenty metabolismus   MeSH
• prokolagen metabolismus   MeSH
• recidiva MeSH
• tepový objem fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glutamate is a well-characterized excitatory neurotransmitter in the central nervous system (CNS). Recently, glutamate receptors (GluRs) were also found in peripheral tissues, including the heart. However, the function of GluRs in peripheral organs remains poorly understood. In the present study, we found that N-methyl-D-aspartate (NMDA) could increase intracellular calcium ([Ca2+]i) level in a dose-dependent manner in cultured neonatal rat cardiomyocytes. NMDA at 10-4 M increased the levels of reactive oxygen species (ROS), cytosolic cytochrome c (cyto c), and 17-kDa caspase-3, but depolarized mitochondrial membrane potential, leading to cardiomyocyte apoptosis. In addition, NMDA treatment induced an increase in bax mRNA but a decrease in bcl-2 mRNA expression in the cardiomyocytes. The above effects of NMDA were blocked by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5Hdibenzo[ a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), and by ROS scavengers glutathione (GSH) and N-acetylcystein (NAC). These results suggest that stimulation of NMDA receptor in the cardiomyocyte may lead to apoptosis via a Ca2+, ROS, and caspase-3 mediated pathway. These findings suggest that NMDA receptor may play an important role in myocardial pathogenesis.

• MeSH
• apoptóza imunologie   účinky záření   MeSH
• cytochromy c genetika   účinky léků   MeSH
• financování organizované využití   MeSH
• kardiomyocyty fyziologie   patologie   MeSH
• kaspasa 3 genetika   účinky léků   MeSH
• mitochondriální myopatie etiologie   genetika   MeSH
• oxidační stres imunologie   účinky záření   MeSH
• receptory N-methyl-D-aspartátu antagonisté a inhibitory   fyziologie   metabolismus   MeSH
• techniky tkáňových kultur metody   využití   MeSH
• vápník metabolismus   MeSH

A mannanase-coding gene was cloned from Sphingobacterium sp. GN25 isolated from the feces of Grus nigricollis. The gene encodes a 371-residue polypeptide (ManAGN25) showing less than 74 % identity with a number of hypothetical proteins and putative glucanases and mannanases. Before experiment's performance, ManAGN25 was predicted to be a low-temperature active mannanase based on the molecular characterization, including (1) ManAGN25 shared the highest identity of 41.1 % with the experimentally verified low-temperature active mannanase (ManAJB13) from Sphingomonas sp. JB13; (2) compared with their mesophilic and thermophilic counterparts, ManAGN25 and ManAJB13 had increased number of amino acid residues around their catalytic sites; (3) these increased number of amino acid residues built longer loops, more α-helices, and larger total accessible surface area and packing volume. Then the experiments of biochemical characterization verified that the purified recombinant ManAGN25 is a low-temperature active mannanase: the enzyme showed apparently optimal activity at 35-40 °C and retained 78.2, 44.8, and 15.0 % of its maximum activity when assayed at 30, 20, and 10 °C, respectively; the half-life of the enzyme was approximately 60 min at 37 °C; the enzyme presented a K m of 4.2 mg/ml and a k cat of 0.4/s in McIlvaine buffer (pH 7.0) at 35 °C using locust bean gum as the substrate; and the activation energy for hydrolysis of locust bean gum by the enzyme was 36.0 kJ/mol. This study is the first to report the molecular and biochemical characterizations of a mannanase from a strain.

• MeSH
• bakteriální proteiny chemie   genetika   izolace a purifikace   metabolismus   MeSH
• beta-mannosidasa chemie   genetika   izolace a purifikace   metabolismus   MeSH
• kinetika MeSH
• konformace proteinů MeSH
• molekulární sekvence - údaje MeSH
• nízká teplota MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• Sphingobacterium chemie   enzymologie   genetika   MeSH
• stabilita enzymů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14(th) and 28(th) day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.

• MeSH
• aktivace enzymů účinky léků   fyziologie   MeSH
• analgetika metabolismus   MeSH
• bradykinin analogy a deriváty   farmakologie   MeSH
• galanin analogy a deriváty   farmakologie   MeSH
• krysa rodu rattus MeSH
• měření bolesti účinky léků   metody   MeSH
• neuralgie metabolismus   prevence a kontrola   MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• peptidové fragmenty farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• proteinkinasy závislé na cyklickém AMP antagonisté a inhibitory   metabolismus   MeSH
• receptor galaninu typ 1 agonisté   antagonisté a inhibitory   biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: This study aimed to explore the antioxidant properties and neuroprotective effects of Esc-1GN. MAIN METHODS: FRAP assay and ABTS, DPPH, and NO radicals radical scavenging assays were performed to investigated the Antioxidant activities of Esc-1GN in vitro. Hydrogen peroxide (H2O2)-induced cell damage model was used to determine the neuroprotective effects of Esc-1GN. Carrageenan-injected inflamed paw model was performed to analysis the antioxidant and anti-inflammatory properties of Esc-1GN in vivo. KEY FINDINGS: Esc-1GN scavenged the ABTS, DPPH, and NO radicals and reduced Fe3+ in a concentration-dependent manner. Moreover, Esc-1GN exhibited neuroprotective activity by decreasing malondialdehyde and reactive oxygen species accumulation, restoring endogenous antioxidant enzyme activity, and inhibiting H2O2-induced cell cycle arrest and apoptosis in PC12 cells. Esc-1GN significantly reversed the dysregulation of MAPK, AKT and NF-κB signaling caused by H2O2. In vivo, Esc-1GN decreased MDA, COX-2, NO, TNF-α, IL-6, and Il-1β levels and increased SOD, CAT activity and GSH level in carrageenan-injected inflamed paw tissues. SIGNIFICANCE: These findings suggest that Esc-1GN might serve as a potential antioxidant agent with therapeutic potential in human neurodegenerative diseases.

• MeSH
• antioxidancia farmakologie   MeSH
• MAP kinasový signální systém MeSH
• myši MeSH
• neuroprotektivní látky farmakologie   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH