Skovjama3221

Oligomycin was used to induce HEI-OC1 cell damage in vitro. In HEI-OC1 cells treated with oligomycin, 8-CPT and ESI-09 increased and reduced cell apoptosis, respectively. Moreover, 8-CPT promoted Ca2+ uptake in HEI-OC1 cells, while ESI-09 inhibited this process. In conclusion, our data provide strong evidence that the Epac1 signaling pathway mediates early pathological damage in NIHL, and that Epac1 inhibition protects from NIHL, identifying Epac1 as a new potential therapeutic target for NIHL.Neuronal excitability and susceptibility to excitotoxic damage can be sex-specific, with neurons from males usually being more 'easily excitable' compared to neurons from females, especially during development. Increased excitability at an individual neuronal level can lead to the formation of hyperexcitable neuronal networks, which, consequently can make the brain more seizure prone. Both animal and clinical data suggest that males experience more frequent and severe seizures than do females. Serotonin (5-hydroxytryptamine; 5-HT) can mediate neuronal excitability and seizure behavior, often serving as an anticonvulsant. Importantly, 5-HT signaling during parts of the perinatal period is sexually dimorphic. Sex differences during development have been reported in both serotonin levels and receptor type (excitatory vs. inhibitory) expression in a manner that may leave the male brain more vulnerable to over-excitation. Thus, we aimed to determine if the anticonvulsant effects of 5-HT were sex- and/or age-dependent in juvenile animals. We report a baseline sex difference in N-methyl-d-aspartate (NMDA)-induced seizure behavior and hippocampal neuronal loss, with postnatal day (PND) 14 males exhibiting more severe seizure behavior compared to females. this website Pretreatment with the general 5-HT receptor agonist 5-methoxytryptamine (5-MT) abolishes baseline sex differences, providing an anticonvulsant effect for males only. These sex differences appear to be at least in part organized by testosterone, as females given neonatal androgen exhibit a seizure behavior profile in between that of males and females.Radiation-induced cognitive dysfunction is a common complication associated with cranial radiation therapy. Inhibition of hippocampal neurogenesis and proliferation plays a critical role in this complication. Relieving hippocampal apoptosis may significantly protect hippocampal neurogenesis and proliferation. Previous studies have demonstrated that hyperactivity of cyclin-dependent kinase 5 (Cdk5) is closely related to apoptosis. The exact molecular changes and function of Cdk5 in radiation-induced cognitive dysfunction are still not clear. Whether inhibition of Cdk5 and the relevant caspase-3 could improve hippocampal neurogenesis and ameliorate radiation-induced cognitive dysfunction needs further exploration. We hypothesized that inhibition of the Cdk5/caspase-3 pathway by p5-TAT could protect hippocampal neurogenesis and alleviate radiation-induced cognitive dysfunction. In our study, we reported that radiation induced hyperactivity of Cdk5 accompanied by elevation of the levels of cleaved caspase-3, a marker of neuronal apoptosis. Inhibition of hippocampal neurogenesis and proliferation as well as cognitive dysfunction was also observed. p5-TAT, a specific inhibitor of Cdk5, decreased the overactivation of Cdk5 without affecting the levels of Cdk5 activators. Additionally, this treatment suppressed the expression of cleaved caspase-3. We further demonstrated that p5-TAT treatment reduced hippocampal dysfunction and improved behavioral performance. Therefore, Cdk5 inhibition by the small peptide p5-TAT is a promising therapeutic strategy for radiation-induced cognitive dysfunction.

The Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear.

This study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/β, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions.

TMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.

TMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.High-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-oxidative, anti-inflammatory, and antithrombotic activities, which are thought to be promoted by paraoxonase 1 (PON1), an HDL-associated enzyme. Reduced levels of PON1 are associated with increased oxidative stress and cardiovascular disease both in humans and Pon1-/- mice. However, molecular basis of these associations are not fully understood. We used label-free mass spectrometry and Ingenuity Pathway Analysis bioinformatics resources to examine plasma proteomes in four-month-old Pon1-/- mice (n = 32) and their Pon1+/+ siblings (n = 15) fed with a hyper-homocysteinemic (HHcy) diet. We found that inactivation of the Pon1 gene resulted in dysregulation of proteins involved in the maintenance of redox homeostasis in mice. Redox-responsive proteins affected by Pon1-/- genotype were more numerous in mice fed with HHcy diet (18 out of 89, 20%) than in mice fed with a control diet (4 out of 50, 8%). Most of the redox-related proteins affected by Pon1-/- genotype in mice fed with a control diet (3 out of 4, 75%) were also affected in HHcy mice, while the majority of Pon1-/- genotype-dependent redox proteins in HHcy mice (15 out of 18, 83%) were not affected by Pon1-/- genotype in control diet animals.