In recent years, the protective effect of hydrogensulfide donor sodium hydrosulfide (NaHS) on multiple organs has been widely reported. The study aimed to explorethe effect of commonly used concentration of NaHS on theliver and its potential damage mechanism. Rats divided into 4 groups: control, NaHS I (1 mg/kg), II (3 mg/kg) and III (5 mg/kg) groups, and each group is divided into four-timepoints (2, 6, 12, and 24 hours). Results showed that H2S concentration increased, mitochondrial complex IV activity inhibited, the COX I and IV subunits and mitochondrial apoptosis pathwayrelated proteins expression increased in atime-and dose-dependent manner. We confirmed that 1 mg/kg NaHS had no injuryeffect on the liver, 3 and 5 mg/kg NaHS inhibitsthe activity of mitochondrial complex IV by promoting COX I and IV subunits expression, leading to the increase in ROS and ultimately inducing apoptosis and liver injury.apoptosis, COX I and COX IV subunits, hepatotoxicity, hydrogen sulfide, reactive oxygen species

Dexmedetomidine (DEX) reportedly possessed multiple bioactivities. Here, we mainly investigated the neuroprotective role and detailed molecular mechanism of DEX against lipopolysaccharide (LPS)-induced hippocampal neurons apoptosis. In vivo, Sprague Dawley rats were administered with LPS (10 mg/kg) and/or DEX (30 µg/kg). We found that DEX improved LPS-induced hippocampal microstructure (necrosis and number reduction of neurons in the CA1 and CA3 regions) and ultrastructure (mitochondrial damage) lesions. DEX also attenuated LPS-induced hippocampal apoptosis by down-regulating the expression of mitochondrial apoptosis pathway-related proteins. Moreover, DEX prevented the activation of c-Myc/chloride intracellular channel 4 (CLIC4) pathway induced by LPS. Notably, DEX inhibited p38 MAPK pathway, not JNK and ERK. To further clarify whether DEX alleviated LPS-induced neuronal apoptosis through the p38 MAPK/c-Myc/CLIC4 pathway, PC12 cells were treated with p38 MAPK inhibitor SB203582 (10µM). As expected, DEX had the same effect as SB203582 in reducing the protein and mRNA expression of c-Myc and CLIC4. Furthermore, DEX and SB203582 diminished LPS-induced apoptosis, showing decreased Bax and Tom20 uorescent double-stained positive cells, reduced Annexin V-FITC/PI apoptosis rate, and lessened protein expression levels of Bax, cytochrome C, cleaved caspase-9 and cleaved caspase-3. Taken together, DEX attenuates LPS-induced hippocampal neuronal apoptosis by regulating the p38 MAPK/c-Myc/CLIC4 signaling pathway, which will provide new insights into the mechanism research and drug development of Alzheimer's disease and depression.

Ketamine has become a popular recreational drug due to its neuronal anesthesia effect and low price. The process of learning and memory is part of the distinctive high-level neural activities in animals. We investigated the effects of subanesthetic and anesthetic doses of ketamine on the learning and memory-related signal transduction mechanisms. We used the Morris water maze test to execute rats’ learning and memory ability and detected changes of Arc mRNA and Arc, cAMP-response element-binding protein (CREB), phospho-CREB (p-CREB), extracellular signal-regulated kinase (ERK), and phospho-ERK (p-ERK) protein expression in the hippocampus 10 min and 24 h after administration. Ten min after ketamine injection, the Arc gene and the protein expression levels increased in all groups; p-ERK only increased in the chronic subanesthetic dose group. After 24 h, the Arc gene and the protein expression levels of the subanesthetic dose group increased, but those of the chronic subanesthetic dose group and anesthetic dose group decreased. However, p-ERK increased in all groups. A chronic subanesthetic dose of ketamine could increase learning and memory ability through ERK, CREB, and Arc in a short time, and the high body temperature after the subanesthetic dose of ketamine injection was the main factor leading to changes in Arc. The subanesthetic dose of ketamine regulated learning and memory through ERK, CREB, and ARC 24 h after injection.

Bovine laminitis leads to huge economic losses and animal welfare problems in the dairy industry worldwide. Numerous studies suggested that several metalloproteinases (MPs) may play vital roles in the failure of epidermal attachment. To the best of our knowledge, the present study is the first to investigate and characterize the gene-level changes in distinct MPs and endogenous inhibitors using oligofructose (OF)-induced bovine laminitis model. The objective of this study was to determine aberrant MPs and related inhibitors of bovine laminitis in gene level, and to provide reasonable directions for the further protein-level research. Twelve normal Chinese Holstein dairy heifers were randomly divided into treatment group (n = 6) and control group (n = 6). The heifers in the treatment group were administered with OF solutions at a dose of 17 g/kg of body weight via a stomach tube. The heifers were then humanely euthanized when they met the criteria of bovine laminitis. The heifers in the control group were administered with deionized water at a dose of 2 L/100 kg of body weight. They humanely euthanized at 72 h. The gene expressions of MPs and endogenous inhibitors, namely, matrix metalloproteinases (MMPs), A disintegrin and metalloproteinases (ADAMs), and A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), and tissue inhibitors of metalloproteinases (TIMPs) in the lamellae from two groups were determined via real-time quantitative PCR. The gene expressions of MMP-2, MMP-9, ADAMTS-4, and ADAMTS-5 significantly increased (P < 0.05), whereas that of TIMP-2 significantly decreased (P < 0.05) in the treatment group relative to the control group. No significant difference was found in the gene expressions of ADAM-10, ADAM-17, TIMP-1, and TIMP-3. These results indicated that the gene-level imbalanced condition of MPs and their TIMPs may be the basic cause for the failure of epidermal attachment. At the same time, more detailed protein-level studies would be needed to further clarify the roles of MPs and TIMPs in the pathogenesis of bovine laminitis, especially to MMP-2, MMP-9, ADAMTS-4, ADAMTS-5, TIMP-2 as well as related substrates (e.g., aggrecan and versican).