It has been proved that erythropoietin has neuroprotective effect and therapeutic action on cerebral ischemia in vivo and in vitro. The mechanisms of these actions may be involved in anti-exitotoxicity of aminoglutaric acid, regulating the synthesis of nitric oxide, antioxidation, antiinflammatory, inhibiting neuron apoptosis, accelerating angiogenesis, neurogenesis, neurotrophy and others. In addition, exogenous erythropoietin can enter brain tissue through blood-brain barrier and exert neuroprotection. So it is indicated that erythropoietin can be expected to be a new drug to prevent and treat cerebral ischemia.

Phosphodiesterase(PDE) is hydrolase of 3',5'-cyclic adenosine monophosphate(cAMP) and 3',5'-cyclic guanosine monophosphate(cGMP).PDE3 are composed of two genes and distributed widely in vivo.Its inhibitors have been applied in antiplatelet aggregation and vasodilation.It has been reported that PDE3 inhibitors have neuroprotective effects on cerebral ischemia,which may provide new methods to prevention and therapy of cerebral ischemia.

Objective Using video tracking system to compare the effects of the locomotor activity between theophylline and caffeine in mice.Methods The KM mice were treated by theophylline and caffeine(both at 1,3,10,30,100 mg/kg)intraperitoneally respectively.After 10 min,the locomotor activity in the open field was recorded for 2 hours.The locomotor track,the total distance,the distances and distance ratio to total distance in central region were analyzed to evaluate the effects of these drugs on locomotor in mice.Results The mice administrated theophylline and caffeine both increased the total distances,and had similar bell-shaped dose-effect relationship.The distances reached the highest at 30 mg/kg theophylline((311±128)m)and 10 mg/kg caffeine ((279±89)m).The larger doses of caffeine inhibited the activity,and the total distance during 0～0.5 h was significantly decreased at the dose of 100 mg/kg(P＜0.05).Theophylline(30 and 100 mg/kg)and caffeine (30 mg/kg)significantly increased the distance ratio in central region(P＜0.01)and decreased the distance ratio in peripheral region(P＜0.01).Conclusion Theophylline and caffeine increase the total distance and the distance ratio in central region in mice,but have different valency and efficacy.

Aim To investigate the protective effect of flavonoids from Radix tetrastigmae (RTFs)on lipopo-lysaccharide (LPS)induced acute lung injury (ALI) of aged mice and the mechanism.Methods Aged C57BL/6J mice were bronchially instillated LPS to in-duce ALI.RTFs were orally administered to treat ALI. After 3 days,bronchoalveolar lavage fluid (BALF) was collected to enumerate leukocytes with Wright-Gi-emsa staining,and to detect inflammatory cytokines with ELISA.ELISA and Western blot methods were al-so used to detect the expression of MAPKs and NF-κB in lung tissues.The activity of NF-κB in nucleic pro-tein extract was detected with TransAMkit.Results
ALI models were successfully induced through LPS in-stillation.RTFs significantly reduced leukocyte,espe-cially neutrophil infiltration in BALF,inhibited IL-1 β, IL-6,IL-1 2p40,TNF-αand sTNF-R1 secretion,and improved pathohistological change of lung tissues.Be-sides,RTFs significantly attenuated the phosphoryla-tion of p38MAPK,NF-κB and the activity of NF-κB. Conclusion RTFs inhibits LPS-induced ALI through p38MAPK and NF-κB pathway and exhibits significant anti-inflammation effect on aged mice.

To investigate the effect of crocin on the progression and generalized seizure of temporal lobe epilepsy in mice.Hippocampus rapid kindling model was established in C57BL/6J mice. The effects of crocin on seizure stage, afterdischarge duration (ADD), number of stimulation in each stage and final state, the incidence of generalized seizure (GS), average seizure stage and ADD were observed.Crocin (20 mg/kg) significantly retarded behavioral seizure stages (<0.05) and shortened cumulative ADD (<0.01) during hippocampus rapid kindling acquisition in mice compared with vehicle group. Meanwhile, number of stimulations in stage 1-2 was significantly increased (<0.05) and the incidence of fully kindled animals was significantly decreased (<0.01). However, 10 or 50 mg/kg crocin showed no significant effect on the above indexes (all>0.05). Crocin (100 or 200 mg/kg) significantly decreased the incidence of GS (all<0.01) and reduced average seizure stages (all<0.01) in fully-kindled mice compared with vehicle group; Fifty mg/kg crocin only reduced average seizure stages (<0.05).Low-dose crocin can retard the progression in hippocampus rapid kindling acquisition in mice, while high-dose crocin relieves the GS in fully-kindled mice, which suggests that crocin may be a potential anti-epileptic compound.
Animals ; Anticonvulsants ; pharmacology ; Carotenoids ; pharmacology ; therapeutic use ; Dose-Response Relationship, Drug ; Electric Stimulation ; Epilepsy, Temporal Lobe ; chemically induced ; drug therapy ; Hippocampus ; drug effects ; physiopathology ; Kindling, Neurologic ; drug effects ; physiology ; Mice ; Mice, Inbred C57BL ; Seizures ; classification ; drug therapy

The application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) can be limited due to a lack of compatible protospacer adjacent motif (PAM) sequences in the DNA regions of interest. Recently, SpRY, a variant of Streptococcus pyogenes Cas9 (SpCas9), was reported, which nearly completely fulfils the PAM requirement. Meanwhile, PAMs for SpRY have not been well addressed. In our previous study, we developed the PAM Definition by Observable Sequence Excision (PAM-DOSE) and green fluorescent protein (GFP)‍-reporter systems to study PAMs in human cells. Herein, we endeavored to identify the PAMs of SpRY with these two methods. The results indicated that 5'-NRN-3', 5'-NTA-3', and 5'-NCK-3' could be considered as canonical PAMs. 5'-NCA-3' and 5'-NTK-3' may serve as non-priority PAMs. At the same time, PAM of 5'-NYC-3' is not recommended for human cells. These findings provide further insights into the application of SpRY for human genome editing.
CRISPR-Associated Protein 9/metabolism* ; CRISPR-Cas Systems ; DNA ; Gene Editing/methods* ; Humans ; Streptococcus pyogenes/metabolism*