CaMKII is essential for long-term potentiation (LTP), a process in which synaptic strength is increased following the acquisition of information. Among the four CaMKII isoforms, γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons (LTP_E→I). However, the molecular mechanism underlying how γCaMKII mediates LTP_E→I remains unclear. Here, we show that γCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10-30 Hz range. Following stimulation, γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95. Knocking down γCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors (AMPARs) in putative inhibitory interneurons, which are restored by overexpression of γCaMKII but not its kinase-dead form. Taken together, these data suggest that γCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Hippocampus/metabolism* ; Interneurons/physiology* ; Long-Term Potentiation/physiology* ; N-Methylaspartate/metabolism* ; Receptors, AMPA/physiology* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Synapses/physiology*

Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Cyclic AMP Response Element-Binding Protein ; genetics ; metabolism ; Male ; MicroRNAs ; radiation effects ; Microwaves ; adverse effects ; Neuronal Plasticity ; radiation effects ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Aspartate Aminotransferases ; blood ; Chalcone ; analogs & derivatives ; pharmacology ; Creatine Kinase ; blood ; Interleukin-6 ; metabolism ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardial Reperfusion Injury ; drug therapy ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUND: Influenza-associated myositis (IAM) is a rare and poorly recognized complication of influenza infection in children, and is characterized by acute onset of severe pain in the lower extremities and a refusal to ambulate walk. We sought to understand the association between IAM and influenza B infection and to investigate its clinical and laboratory characteristics in affected children. METHODS: Influenza B-associated myositis (IBAM) cases diagnosed in the pediatrics department of Wonkwang University Hospital from January 2010 and March 2016 were analyzed retrospectively. RESULTS: Medical records of affected children were examined, and clinical characteristics and laboratory findings were recorded. Of the 536 children diagnosed with influenza B infection, 47 children complained of bilateral calf pain with or without gait disturbance. All children exhibited elevated serum aspartate aminotransferase (AST) level. The median serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels, reportedly elevated in myositis, were 2,597 IU/L and 678 IU/L, respectively. While the immunofluorescence test results were negative for some patients, the polymerase chain reaction test results indicated influenza B infection in all 47 children. At the time of hospital discharge, the patients' symptoms had resolved, and their CK levels had improved. CONCLUSION: IBAM was generally benign and short, and although the blood AST, CK, and LDH levels were markedly high, the erythrocyte sedimentation rate and C-reactive protein levels were normal. Further, the duration of IBAM symptoms correlated with the duration of fever. The IBAM-associated clinical and laboratory findings are highly characteristic and may allow its rapid diagnosis during the influenza season.
Aspartate Aminotransferases ; Blood Sedimentation ; C-Reactive Protein ; Child ; Creatine Kinase ; Diagnosis ; Fever ; Fluorescent Antibody Technique ; Gait ; Humans ; Influenza B virus ; Influenza, Human ; L-Lactate Dehydrogenase ; Lower Extremity ; Medical Records ; Myalgia ; Myositis ; Pediatrics ; Polymerase Chain Reaction ; Retrospective Studies ; Seasons

Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ. In addition, the expression of NMDAR subunits 1, 2A, and 2B; postsynaptic density-95 (PSD-95); phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII); phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2); and phosphorylation of cAMP response element binding (CREB) proteins were examined by Western blot. In vivo, we found that treatment with LQ significantly improved memory performance in both behavioral tests. In vitro, LQ significantly increased NMDARs in the hippocampus. Furthermore, LQ significantly increased PSD-95 expression as well as CaMKII, ERK, and CREB phosphorylation in the hippocampus. Taken together, our results suggest that LQ has cognition enhancing activities and that these effects are mediated, in part, by activation of the NMDAR and CREB signaling pathways.
Animals ; Behavior Rating Scale ; Blotting, Western ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Cognition ; Glycyrrhiza ; Hippocampus ; In Vitro Techniques ; Learning ; Medicine, East Asian Traditional ; Memory ; Mice* ; N-Methylaspartate* ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Receptors, N-Methyl-D-Aspartate* ; Response Elements

PURPOSE: Virus-associated rhabdomyolysis is very rare. We report 15 patients with rhabdomyolysis caused by various viruses. METHODS: Fifteen patients who were diagnosed with rhabdomyolysis and a viral infection were included in this study. Clinical, laboratory, and radiologic findings were evaluated through retrospective chart reviews. RESULTS: Chief complaints were severe bilateral lower leg pain and leg weakness. The median age was 5.7 years. The male:female ratio was 2:5. The viral infections were caused by influenza virus B, parainfluenza virus, and rhinovirus. One patient with influenza virus B had coinfection with coronavirus. Median initial laboratory values and ranges were as follows:serum creatinine, 0.4 (0.1-0.5) mg/dL; serum aspartate transaminase, 124 (48-1,098) IU/L; serum alanine transaminase, 30 (16-1,455) IU/L; serum creatine kinase, 2,965 (672-16,594) IU; serum lactate dehydrogenase, 400 (269-7,394) IU/L; serum myoglobin, 644 (314-3,867) ng/mL; urine myoglobin, 3 (3-10,431) ng/mL. All patients recovered without complications. CONCLUSION: This is the first report of the simultaneous occurrence of rhabdomyolysis caused by various viruses. This is also the first report of rhinovirus-associated rhabdomyolysis.
Alanine Transaminase ; Aspartate Aminotransferases ; Child* ; Coinfection ; Coronavirus ; Creatine Kinase ; Creatinine ; Humans ; Influenza B virus ; L-Lactate Dehydrogenase ; Leg ; Myoglobin ; Orthomyxoviridae ; Paramyxoviridae Infections ; Retrospective Studies ; Rhabdomyolysis* ; Rhinovirus

PURPOSE: Virus-associated rhabdomyolysis is very rare. We report 15 patients with rhabdomyolysis caused by various viruses. METHODS: Fifteen patients who were diagnosed with rhabdomyolysis and a viral infection were included in this study. Clinical, laboratory, and radiologic findings were evaluated through retrospective chart reviews. RESULTS: Chief complaints were severe bilateral lower leg pain and leg weakness. The median age was 5.7 years. The male:female ratio was 2:5. The viral infections were caused by influenza virus B, parainfluenza virus, and rhinovirus. One patient with influenza virus B had coinfection with coronavirus. Median initial laboratory values and ranges were as follows:serum creatinine, 0.4 (0.1-0.5) mg/dL; serum aspartate transaminase, 124 (48-1,098) IU/L; serum alanine transaminase, 30 (16-1,455) IU/L; serum creatine kinase, 2,965 (672-16,594) IU; serum lactate dehydrogenase, 400 (269-7,394) IU/L; serum myoglobin, 644 (314-3,867) ng/mL; urine myoglobin, 3 (3-10,431) ng/mL. All patients recovered without complications. CONCLUSION: This is the first report of the simultaneous occurrence of rhabdomyolysis caused by various viruses. This is also the first report of rhinovirus-associated rhabdomyolysis.
Alanine Transaminase ; Aspartate Aminotransferases ; Child* ; Coinfection ; Coronavirus ; Creatine Kinase ; Creatinine ; Humans ; Influenza B virus ; L-Lactate Dehydrogenase ; Leg ; Myoglobin ; Orthomyxoviridae ; Paramyxoviridae Infections ; Retrospective Studies ; Rhabdomyolysis* ; Rhinovirus

Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme Q10 (CoQ10) with statins. The goal of the current research is to assess the efficacy of combined treatment of CoQ10 with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of CoQ10 (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin only-treatment, CoQ10 supplementation significantly reduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, CoQ10 supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and CoQ10 were increased in the CoQ10 co-treated group. These results indicate that CoQ10 treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary CoQ10 is helpful for solving problem of obese metabolism, so the multiple prescription of CoQ10 makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism.
Animals ; Aspartate Aminotransferases ; Cholesterol ; Creatine Kinase ; Diet ; Diet, High-Fat ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperlipidemias ; Male ; Metabolism ; Muscular Diseases ; Myositis ; Obesity ; Oxidoreductases ; Prescriptions ; Rats* ; Rats, Sprague-Dawley ; Triglycerides ; Atorvastatin Calcium

OBJECTIVETo explore the etiology and clinical characteristics of hypoxic hepatitis (HH) in children.

METHODClinical data of 7 patients with HH in Shenzhen Children's Hospital from January 2011 to March 2014 were retrospectively reviewed.

RESULTSeven cases diagnosed as HH, age from 4 months to 11 years, were admitted to pediatric intensive care unit (PICU), and accounted for 0.32% of patients in PICU during the same period. The primary causes of HH were respiratory failure and cardiac shock caused by severe hand-foot-and-mouth disease, fulminant myocarditis, infant muggy syndrome . Serologic tests for hepatitis B virus, hepatitis C virus, as well as serum antibody and DNA for Epstein-Barr virus and cytomegalovirus were all negative. There was an increase of alanine aminotransferase (ALT) (≥20 time supper limit of normal (ULN), the highest ALT was more than 130 times ULN in all the patients, which was decreased to 2 times ULN from peak within 10 days. There was a significant relationship between ALT and aspartate aminotransferase(AST)in 3 cases(r=1.000, 1.000, and 0.833, respectively, P<0.05), ALT and lactate dehydrogenase (LDH)in 2 cases(r=1.000 and 0.886, respectively, P<0.05), ALT and blood urea nitrogen(BUN)in 1 case(r=1.000, P<0.05), and ALT and creatine kinase(CK)in 1 case(r=0.964, P<0.05). The ALT, AST and LDH returned to normal soon after the primary diseases were controlled.

CONCLUSIONSevere heart failure, hypoxemia, shock, etc. are the leading primary diseases causing HH. The sharp increase in ALT, AST and LDH is the typical laboratory manifestion in HH after the onset, which may decline to normal shortly after the treatment, sometimes complicated with reversible change in BUN or CK.

Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Child ; Child, Preschool ; Creatine Kinase ; Heart Failure ; Hepatitis ; Herpesvirus 4, Human ; Humans ; Hypoxia ; Infant ; L-Lactate Dehydrogenase ; Respiratory Insufficiency ; Retrospective Studies

Hydrogen sulfide (HS) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of HS and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Western blot analysis was performed to detect protein expression in the ARC. CP markedly upregulated cystathionine β-synthetase (CBS) expression but did not alter cystathionine-γ-lyase level in the ARC at 4 weeks after TNBS injection. Although the expression of total GluN2B was not altered, CP greatly enhanced the phosphorylation level of GluN2B in the ARC when compared with age- and sex-matched control rats. CP also significantly increased expression of protein kinase Cγ (PKCγ) in the ARC. Arcuate microinjection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA, an inhibitor of CBS) significantly attenuated abdominal pain in CP rats in a dose-dependent manner and reversed the CP-induced upregulation of p-GluN2B and PKCγ in the ARC. Furthermore, the GluN2B inhibitor or specific PKC inhibitor chelerythrine significantly attenuated abdominal hyperalgesia in CP rats. The p-GluN2B expression was also suppressed by PKC inhibitor. Taken together, our results suggest that the upregulation of CBS in the ARC leads to an activation of GluN2B via PKCγ, which may play an important role in generation of pain hypersensitivity of CP.
Acute Disease ; Animals ; Arcuate Nucleus of Hypothalamus ; Cystathionine beta-Synthase ; Hyperalgesia ; Male ; Pain ; Pancreatitis, Chronic ; Phosphorylation ; Protein Kinase C ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Up-Regulation