Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI).@*METHODS@#Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- β and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively.@*RESULTS@#The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01).@*CONCLUSION@#CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior / 神经科学通报·英文版

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

Antioxidant Activity of Graptopetalum paraguayense E. Walther Leaf Extract Counteracts Oxidative Stress Induced by Ethanol and Carbon Tetrachloride Co-Induced Hepatotoxicity in Rats.

(1) Background: Graptopetalum paraguayense E. Walther is a traditional Chinese herbal medicine. In our previous study, 50% ethanolic G. paraguayense extracts (GE50) demonstrated good antioxidant activity. (2) Methods: To investigate the hepatoprotective effects of GE50 on ethanol and carbon tetrachloride (CCl4) co-induced hepatic damage in rats, Sprague-Dawley rats were randomly divided into five groups (Control group; GE50 group, 0.25 g/100 g BW; EC group: Ethanol + CCl4, 1.25 mL 50% ethanol and 0.1 mL 20% CCl4/100 g BW; EC + GE50 group: Ethanol + CCl4 + GE50; EC + silymarin group: ethanol + CCl4 + silymarin, 20 mg/100 g BW) for six consecutive weeks. (3) Results: Compared with the control group, EC group significantly elevated the serum aspartate aminotransferase (AST), alanine aminitransferase (ALT), and lactate dehydrogenase (LDH). However, GE50 or silymarin treatment effectively reversed these changes. GE50 had a significant protective effect against ethanol + CCl4 induced lipid peroxidation and increased the levels of glutathione (GSH), vitamin C, E, total antioxidant status (TAS), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferases (GST). Furthermore, in EC focal group, slight fat droplet infiltration was observed in the livers, while in the GE50 or silymarin treatment groups, decreased fat droplet infiltration. HPLC phytochemical profile of GE50 revealed the presence of gallic acid, flavone, genistin, daidzin, and quercetin. (4) Conclusions: The hepatoprotective activity of GE50 is proposed to occur through the synergic effects of its chemical component, namely, gallic acid, flavone, genistin, daidzin, and quercetin. Hence, G. paraguayense can be used as a complementary and alternative therapy in the prevention of alcohol + CCl4-induced liver injury.

Vascular endothelial growth factor gene-460 C/T polymorphism is a biomarker for oral cancer.

Oral cancer is one of the most common malignant diseases in Taiwan. The incidence of male oral cancer is 9.01 times than that of female. The formation or progression of oral cancer may be associated with a polymorphism of the vascular endothelial growth factor (VEGF) gene. The most frequently seen polymorphism is BstUI (C to T) located at the -460th nucleotide upstream of the VEGF gene. We investigated whether this polymorphism could be a genetic marker of oral cancer. A normal control group of 230 healthy people and 137 patients with oral cancer were examined. The polymorphism was detected by polymerase chain reaction-based restriction analysis. The analysis revealed significant differences between normal individuals and patients with cancer (P<0.001). The distribution of the "TT" homozygote in the patient group was greater than that in the control group. The odds ratio per copy of the "T/C" ratio was 9.62 (95% confidence interval 5.81-15.87), which means that for a group of people with a higher T/C ratio have higher risk in getting oral cancer. There is no gender difference in this VEGF gene polymorphism. Therefore, the BstUI polymorphism of the VEGF gene is a suitable genetic marker of oral cancer.

Spontaneous discharges of pyramidal cells in the dorsal hippocampus of guinea pig / 生理学报

To determine the characteristics of spontaneous discharges of hippocampal pyramidal cells (PCs), extracellular neuronal firing in CA1 and CA3 regions of dorsal hippocampus was recorded, the firing modes and interspike interval (ISI) were analyzed with the conventional and nonlinear methods. PCs were discriminated from interneurons using the measurement of action-potential duration and firing rate in this study. There was no significant difference in duration, mean firing frequency, complexity and firing mode between the neurons in CA1 and CA3 regions both in anesthetized and awake animals. The complexity of neurons was higher in awake group than that in anesthetized group, though no difference was found in firing rate. There were differences in the type of pyramidal cells and the coefficient of variance of ISI of neurons. The results obtained from the spontaneous discharges of dorsal hippocampal pyramidal cells reveal some nonlinear and linear aspects in anesthetized and awake states. It seems likely that the combination of conventional and non-linear measurements of the hippocampal pyramidal cells encoding may reflect genuine characteristics of the hippocampal pyramidal cells.

he roles of hypoxia and glutamic acid on NMDA receptor channel of hypothalamic neuron in rats / 第三军医大学学报

Objective　To study the effects of hypoxia and glutamic acid on the kinetic properties of NMDA receptor channel of the hypothalamic neurons in rats. Methods　Cell-attached mode patch clamp technique was employed to record the single channel current of the NMDA receptor. Results　The open probability of NMDA receptor channel was increased after acute hypoxia compared with that of normal state, the open time τ1,τ2 was changed from (0.33±0.10)ms，(4.36±0.26)ms to (0.93±0.22)ms，(7.64±0.72)ms, and the close time τ1,τ2 was from (18.03±3.50)ms，(171.50±19.10)ms to (3.42±1.02)ms，(19.39±3.07)ms. The mean open probability was changed from 0.12±0.05 in normal state to 0.66±0.36 in hypoxia state. Furthermore, glutamic acid can increase open time and open probability of NMDA receptor channel,decrease close time. Conclusion　The excitability and the open probability of NMDA receptor channel of hypothalamic neurons increased by hypoxia is related to glutamate.

he roles of hypoxia and glutamic acid on NMDA receptor channel of hypothalamic neuron in rats / 第三军医大学学报

Objective　To study the effects of hypoxia and glutamic acid on the kinetic properties of NMDA receptor channel of the hypothalamic neurons in rats. Methods　Cell-attached mode patch clamp technique was employed to record the single channel current of the NMDA receptor. Results　The open probability of NMDA receptor channel was increased after acute hypoxia compared with that of normal state, the open time τ1,τ2 was changed from (0.33±0.10)ms，(4.36±0.26)ms to (0.93±0.22)ms，(7.64±0.72)ms, and the close time τ1,τ2 was from (18.03±3.50)ms，(171.50±19.10)ms to (3.42±1.02)ms，(19.39±3.07)ms. The mean open probability was changed from 0.12±0.05 in normal state to 0.66±0.36 in hypoxia state. Furthermore, glutamic acid can increase open time and open probability of NMDA receptor channel,decrease close time. Conclusion　The excitability and the open probability of NMDA receptor channel of hypothalamic neurons increased by hypoxia is related to glutamate.