Search

The loss of hematopoietic stem cell donation (HSCD) volunteers is widespread worldwide. This study analyzed the distribution characteristics of volunteer retention between the swab sampling approach and blood sampling approach. The Shanghai branch of the China Bone Marrow Donation Program conducted a telephone follow-up with 18,963 volunteers to understand volunteer retention. Multiple logistic regression was used to analyze the distribution characteristics of volunteer retention between two different sampling approaches, and a forest plot was used to observe the distribution trend. Only 32.37% of the volunteers could be contacted, and the loss of volunteers was severe. The volunteer retention is influenced by sampling approaches and demographic characteristics, and Shanghai natives, the highly educated, and students had better retention. The volunteer retention of the swab group was better among young people and technicians, while the volunteer retention of the blood sample group was lower among public officials and workers, and the volunteer retention in the blood sample group was more significantly affected by changes in population characteristics. To enhance the stability of volunteers, managers should improve the contact channels and frequency, expand the ratio of stable volunteers, strengthen volunteer education in the process of collecting blood samples, and respect individuals’ willingness.

Aims: Explore the effect of compound lobelia oral liquid on acute pharyngitis rabbits model caused by ammonium hydroxide, evaluate its curative effect. Methods: Acute pharyngitis rabbit model was prepared by ammonia spray at pharyngeal. After 1 h of the last administration, score the pharyngeal tissue symptoms of rabbits under the condition of naked eyes (score according to the score criteria). Then, take blood from the marginal auricular vein for routine blood tests and serum TNF-α level measure. Take pharyngeal tissue for HE staining, and observe its pathological changes under the microscope. Results: Compared with the blank group, the pharyngeal tissue symptom score and serum TNF-α level in the model group were significantly increased (P

Objective: To study the effects of the different components of the total flavonoids and total saponins from Mao Dongqing's active site on the rats of TIA model, determine the optimal reactive components ratio of Mao Dongqing on the rats of TIA. Methods: TIA rat model was induced by tail vein injection of tert butyl alcohol, the blank group was injected with the same amount of physiological saline, then behavioral score wasevaluated.Determination the level of glutamic acid in serum, the activity of Na+-K+-ATP enzyme, CA++-ATP enzyme and Mg++-ATP enzyme in Brain tissue, observe the changes of hippocampus in brain tissue, the comprehensive weight method was used to evaluate the efficacy of each component finally. Results: The contents of total flavonoids and total saponins in the active part of Mao Dongqing can significantly improve the pathological changes of brain tissue in rats, improve the activity of Na+-K+-ATP enzyme, Ca++-ATP enzyme and Mg++-ATP enzyme in the brain of rats, and reduce the level of glutamic acid in serum. The most significant of the contents was the ratio of 10:6. Conclusion: The different proportions of total flavonoids and total saponins in the active part of Mao Dongqing all has a better effect on the rats with TIA, and the ratio of 10:6 is the best active component for preventing and controlling TIA. Keywords: Mao Dongqing'stotal flavonoids, Total saponins, TIA animal model, Optimal active ratio components

Aim: To establish a Friend murine leukemia virus (FLV)-induced immunodeficient BALB/C mouse model and investigate the effects of Fuzheng Paidu tablets on the body weight, thymus, spleen, and CD4+ and CD8+ T lymphocytes of FLV-infected mice. FLV was passaged twice in BALB/c mice. The infected mice were divided into six groups of ten mice based on their weights. The groups included the normal control group; virus control group; AZT group; high- (2.8 g/kg), medium- (1.4 g/kg), and low-dose (0.7 g/kg) Fuzheng Paidu tablet groups; and Fuzheng Paidu decoction (10 g/kg) group. The mice were administered Fuzheng Paidu tablets via gavage for 21 days. The body weight and changes in the thymus, spleen, and CD4+ and CD8+ T lymphocytes of each mouse were measured. Results: The splenic weight of the virus control group is significantly higher than that of the normal control group, with significant splenomegaly. In addition, the splenic inhibition indices of the AZT group and the high- and medium-dose Fuzheng Paidu tablet groups were approximately 93.80%, 37.80%, and 28.07%, respectively. Furthermore, the high and medium dose Fuzheng Paidu tablets could increase the thymus weights of the infected mice. Conclusion: Fuzheng Paidu tablets could inhibit splenomegaly, lower the splenic indices, and increase the thymic weights and thymic indices of FLV-induced immunodeficient mice. Keywords: Friend murine leukemia virus, BALB/c mice, AZT

To study the influence of stachydrine hydrochloride on the inflammatory cytokines and tissue morphology of the re-perfusion model of mice with repetitive cerebral ischemia and probe into the protection mechanism of stachydrine hydrochloride for cerebral ischemia reperfusion impairment. Build a repetitive cerebral ischemia reperfusion model by first blocking the common carotid artery on both sides for 10 min, then resuming perfusion for 10 min and then blocking the common carotid artery on both sides again for 10 min. Before the operation, all the mice in the Nimodipine group, and the big, medium and small stachydrine hydrochloride dose groups were given corresponding gastric perfusion, the mice in the sham operation group and the modeled groups were at the same time given 0.5% sodium carboxymethyl cellulose for gastric perfusion of the same volume. The medicine was fed daily for 7 consecutive days. The model was built 1 h after the last feed and the perfusion continued for 24 h after the operation. Then the death rate of the mice was calculated. The mouse brains were taken out to test the ICAM-1 level and the TNF-α level, and the serum was taken out to test the NSE level and the MPO level. The tissue morphology changes were also observed. All the repetitive cerebral ischemia reperfusion models were successfully duplicated. The stachydrine hydrochloride in all the dose groups significantly reduced the death rates of big and small mice, reduced the level of ICAM-1 and the level of TNF-α in the brain tissues and the NSE level and the MPO level in the serum, significantly alleviating the pathological impairment in the hippocampus. Stachydrine hydrochloride can significantly reduce the death rate of mice, improve the pathological changes in the hippocampus, inhibit inflammatory reactions after ischemia, thus reducing the re-perfusion impairment after cerebral ischemia.

Objective: Study the effect of the 3:7 ratio of Astragalus total saponins and Curcumin on the model of diabetic nephropathy rats, and explore its mechanisms. Methods: Diabetic nephropathy rats model was established by high-fat and high-sugar feed feeding combined with streptozotocin (STZ) injection in sublingual vein. Measured fasting blood glucose of rats on the 10, 20 and 30th day, and measured urine protein content in urine of rats on 30th days. Two hours after the last administration, measured glycated serum protein (GSP), insulin antibody (IA), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), malondialdehyde (MDA), insulin, superoxide dismutase (SOD), glutathione (GSH), urea nitrogen (BUN), creatinine (Cr) in the serum and calculated the renal index of rat. Take the viscera of pancreas and kidney, and HE staining, so as to observe pathological changes. Result: Astragalus total saponins and Curcumin 3:7 compatibility each dose group can significantly reduce the diabetic nephropathy rats blood glucose of 30th days, significantly reduce the level of GSP, IA, TG, TC, LDL (P 0.05); Astragalus total saponins and Curcumin 3:7 compatibility each dose group also can decrease renal index, UN, and Cr levels with different degrees and improve the pathological changes of pancreatic tissue and kidney tissue in diabetic nephropathy rats with different degrees (P 0.05). Conclusion: The 3:7 ratio of Astragalus total saponins and Curcumin can achieve the treatment and protection effects on diabetic nephropathy rats by improve the glycometableolism, insulin resistance, lipid metableolism, oxidative stress levels, and pathological changes. Keywords: Astragalus total saponins, Curcumin, Lipid metableolism, Diabetic nephropathy, Glycometableolism, Oxidative stress

Chloasma is a common skin disease among female patients.Due to its slow development, long course of disease, extremely high recurrence rate and other characteristics, it has a huge impact on the female population, seriously affecting the physical health of female patients and easily causing a series of psychological pressure or diseases.Therefore, by searching and sorting out the literature, this paper analyzes the literature on external treatment of chloasma with traditional Chinese medicine on cnki, and discusses the mechanism and main treatment methods of external treatment of chloasma with traditional Chinese medicine. According to this, a total of 54 articles related to “chloasma” and “external treatment” were counted on cnki, and various TCM external treatment methods involved in the literature were analyzed.

OBJECTIVE: Explore the possible protective effect of Sargentodoxa cuneata total phenolic acids on cerebral ischemia reperfusion injury rats. METHODS: Focal cerebral ischemia reperfusion rats model were established by linear thrombus. Nimodipine group, Naoluotong group, the high, middle and low dose of Sargentodoxa cuneata total phenolic acids groups were given related drugs via intragastric administration before operation for seven days, once a day. At the same time sham operation group, and ischemia reperfusion group were given the same volume of physiological saline. One hour after the last administration, establish focal cerebral ischemia- reperfusion model in rats by thread method, and the thread was taken out after 2 h ischemia to achieve cerebral ischemia reperfusion injury in rats. After reperfusion for 24 h, the rats were given neurologic deficit score. The brain tissue was taken to measure the levels of IL-6, IL-1β, TNF-α, Bcl-2, Bax, Casp-3 and ICAM-1; HE staining observed histopathological changes in the hippocampus and cortical areas of the brain; Immunohistochemistry was used to observe the expression of NGF and NF-KBp65. RESULT: Focal cerebral ischemia reperfusion rats model was copyed successed. Compared with model group, each dose group of Sargentodoxa cuneata total phenolic acids could decreased the neurologic deficit score (P

// Wen-Liang Chen 1,2 , Andrew Barszczyk 2 , Ekaterina Turlova 1,2 , Marielle Deurloo 2 , Baosong Liu 1,2 , Burton B. Yang 4 , James T. Rutka 1 , Zhong-Ping Feng 2 and Hong-Shuo Sun 1,2,3,5 1 Department of Surgery, University of Toronto, Toronto, Canada 2 Department of Physiology, University of Toronto, Toronto, Canada 3 Department of Pharmacology, University of Toronto, Toronto, Canada 4 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 5 Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada Correspondence to: Hong-Shuo Sun, email: // Zhong-Ping Feng, email: // Keywords : glioblastoma, carvacrol, TRPM7, cell viability, migration, invasion Received : November 24, 2014 Accepted : April 02, 2015 Published : April 19, 2015 Abstract Glioblastomas are progressive brain tumors with devastating proliferative and invasive characteristics. Ion channels are the second largest target class for drug development. In this study, we investigated the effects of the TRPM7 inhibitor carvacrol on the viability, resistance to apoptosis, migration, and invasiveness of the human U87 glioblastoma cell line. The expression levels of TRPM7 mRNA and protein in U87 cells were detected by RT-PCR, western blotting and immunofluorescence. TRPM7 currents were recorded using whole-cell patch-clamp techniques. An MTT assay was used to assess cell viability and proliferation. Wound healing and transwell experiments were used to evaluate cell migration and invasion. Protein levels of p-Akt/t-Akt, p-ERK1/2/t-ERK1/2, cleaved caspase-3, MMP-2 and phosphorylated cofilin were also detected. TRPM7 mRNA and protein expression in U87 cells is higher than in normal human astrocytes. Whole-cell patch-clamp recording showed that carvacrol blocks recombinant TRPM7 current in HEK293 cells and endogenous TRPM7-like current in U87 cells. Carvacrol treatment reduced the viability, migration and invasion of U87 cells. Carvacrol also decreased MMP-2 protein expression and promoted the phosphorylation of cofilin. Furthermore, carvacrol inhibited the Ras/MEK/MAPK and PI3K/Akt signaling pathways. Therefore, carvacrol may have therapeutic potential for the treatment of glioblastomas through its inhibition of TRPM7 channels.

Summary Dysfunction of PTEN-induced kinase 1 (PINK1) or DJ-1 promotes neuronal death and is implicated in the pathogenesis of Parkinson’s disease, but the underlying mechanisms remain unclear. Given the roles of N-methyl-d-aspartate receptor (NMDAr)-mediated neurotoxicity in various brain disorders including cerebral ischemia and neurodegenerative diseases, we investigated the effects of PINK1 and DJ-1 on NMDAr function. Using protein overexpression and knockdown approaches, we showed that PINK1 increased NMDAr-mediated whole-cell currents by enhancing the function of NR2A-containing NMDAr subtype (NR2ACNR). However, DJ-1 decreased NMDAr-mediated currents, which was mediated through the inhibition of both NR2ACNR and NR2B-containing NMDAr subtype (NR2BCNR). We revealed that the knockdown of DJ-1 enhanced PTEN expression, which not only potentiated NR2BCNR function but also increased PINK1 expression that led to NR2ACNR potentiation. These results indicate that NMDAr function is differentially regulated by DJ-1-dependent signal pathways DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR. Our results further showed that the suppression of DJ-1, while promoted NMDA-induced neuronal death through the overactivation of PTEN/NR2BCNR-dependent cell death pathway, induced a neuroprotective effect to counteract DJ-1 dysfunction-mediated neuronal death signaling through activating PTEN/PINK1/NR2ACNR cell survival–promoting pathway. Thus, PINK1 acts with DJ-1 in a common pathway to regulate NMDAr-mediated neuronal death. This study suggests that the DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR pathways may represent potential therapeutic targets for the development of neuroprotection strategy in the treatment of brain injuries and neurodegenerative diseases such as Parkinson’s disease.

Rabdosia rubescens contais many active ingredients such as terpenoids, flavonoids, polysaccharides and organic acids. Modern research has proved that Rabdosia rubescens has the effect of heat-clearing and detoxicating, antibacterial and anticancer, promoting blood circulation to arrest pain and anti-tumor. It is used in the treatment of sore throat, rheumatoid arthritis and various kinds of cancer. The clinical application of Rabdosia rubescens is restricted in the fat-soluble components, and the solubility of water solubility is ignored. The application of prescriptions, Chinese patent drug and food therapy of Rabdosia rubescens are less and fragmented. This paper inquires relevant literature, the application of Rabdosia rubescens in prescription, Chinese patent medicine and food therapy was reviewed, in order to make Rabdosiae rubescens play a greater role in the relevant area. On the basis of make the best use of everything, to promote the innovation and development of Chinese medicine and services to the people in our country.

Direct-current electrical fields (EFs) promote nerve growth and axon regeneration. We report here that at physiological strengths, EFs guide the migration of neuronal stem/progenitor cells (NSPCs) toward the cathode. EF-directed NSPC migration requires activation of N-methyl-d-aspartate receptors (NMDARs), which leads to an increased physical association of Rho GTPase Rac1-associated signals to the membrane NMDARs and the intracellular actin cytoskeleton. Thus, this study identifies the EF as a directional guidance cue in controlling NSPC migration and reveals a role of the NMDAR/Rac1/actin signal transduction pathway in mediating EF-induced NSPC migration. These results suggest that as a safe physical approach in clinical application, EFs may be developed as a practical therapeutic strategy for brain repair by directing NSPC migration to the injured brain regions to replace cell loss. Disclosure of potential conflicts of interest is found at the end of this article.

The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a lipid and protein phosphatase. We report here that PTEN physically associates with the NR1 and NR2B subunits of NMDA receptors (NMDARs) in rat hippocampus. Downregulating the protein expression of PTEN inhibits the function of extrasynaptic NMDARs and decreases NMDAR surface expression, suggesting a crucial role for endogenous PTEN in the modulation of NMDAR-mediated neuronal function. Reducing PTEN expression also enhances Akt/Bad phosphorylation in hippocampal neurons. Importantly, suppressing lipid and protein phosphatase activity of PTEN, respectively, activates Akt and inhibits extrasynaptic NMDAR activity and thereby protects against ischemic neuronal deathin vitroandin vivo. Thus, our study reveals a dual neuroprotective mechanism by which Akt/Bad and extrasynaptic NMDARs are regulated via downregulation of two distinct PTEN phosphatase activities and present the possibility of PTEN as a potential therapeutic target for stroke treatment.

We describe a manual prechop technique to divide the nucleus using a cystotome. In the cystotome-assisted prechop technique, after the capsulorhexis, the surgeon-bent cystotome is inserted into the lens while the Nagahara chopper is set around the lens equator. The cystotome and the chopper are then brought together in the center to create a bisecting crack in the nucleus, dividing it cleanly into 2 hemispheres. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Neonatal hypoxic-ischemic brain injury and its related illness hypoxic-ischemic encephalopathy (HIE) are major causes of nervous system damage and neurological morbidity in children. Hypoxic preconditioning (HPC) is known to be neuroprotective in cerebral ischemic brain injury. K(ATP) channels are involved in ischemic preconditioning in the heart; however the involvement of neuronal K(ATP) channels in HPC in the brain has not been fully investigated. In this study, we investigated the role of HPC in hypoxia-ischemia (HI)-induced brain injury in postnatal seven-day-old (P7) CD1 mouse pups. Specifically, TTC (2,3,5-triphenyltetrazolium chloride) staining was used to assess the infarct volume, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling) to detect apoptotic cells, Western blots to evaluate protein level, and patch-clamp recordings to measure K(ATP) channel current activities. Behavioral tests were performed to assess the functional recovery after hypoxic-ischemic insults. We found that hypoxic preconditioning reduced infarct volume, decreased the number of TUNEL-positive cells, and improved neurobehavioral functional recovery in neonatal mice following hypoxic-ischemic insults. Pre-treatment with a K(ATP) channel blocker, tolbutamide, inhibited hypoxic preconditioning-induced neuroprotection and augmented neurodegeneration following hypoxic-ischemic injury. Pre-treatment with a K(ATP) channel opener, diazoxide, reduced infarct volume and mimicked hypoxic preconditioning-induced neuroprotection. Hypoxic preconditioning induced upregulation of the protein level of the Kir6.2 isoform and enhanced current activities of K(ATP) channels. Hypoxic preconditioning restored the HI-reduced PKC and pAkt levels, and reduced caspase-3 level, while tolbutamide inhibited the effects of hypoxic preconditioning. We conclude that K(ATP) channels are involved in hypoxic preconditioning-induced neuroprotection in neonatal hypoxic-ischemic brain injury. K(ATP) channel openers may therefore have therapeutic effects in neonatal hypoxic-ischemic brain injury.

Fifty-five rabbits were subjected to left thoracic wall lateral blunt impact involving a relatively static impact pattern. The impact velocities ranged from 7.92 m/s to 16.33 m/s and the compression response ranged from 14.08% to 45.84% of the thoracic width. The surviving animals were sacrificed 6 hours after trauma and autopsies were performed. The lung was divided into bronchial and alveolar regions. Injury scores were assigned according to the hemorrhage area and the injury type (e.g., rupture or rib fracture). The results showed that the severity of bronchial injury was greater than alveolar injury when the impact velocity was low. However, alveolar injury was much more severe than bronchial injury at all levels of impact displacement when the impact velocity was high. The ratio of left/right lung injury decreased when the product of impact velocity and compression criterion increased. The latter was also well correlated with the severity of lung and heart injuries. In addition, the severity of rib injury was mainly related to compression response.

Microglia have a swelling-activated Cl− current (which we call IClswell), and while some of its biophysical properties and functional roles have been elucidated, its molecular identity is unknown. To relate this current to cell functions and determine whether it is regulated by mechanisms other than cell swelling, it is important to establish both biophysical and pharmacological fingerprints. Here, we used rat microglia and a cell line derived from them (MLS-9) to study biophysical, regulatory and pharmacological properties of IClswell. The whole-cell current was activated in response to a hypo-osmotic bath solution, but not by voltage, and was time-independent during long voltage steps. The halide selectivity sequence was I−>Br−>Cl− (Eisenman sequence I) and importantly, the excitatory amino acid, glutamate was permeant. Current activation required internal ATP, and was not affected by the guanine nucleotides, GTPγS or GDPβS, or physiological levels of internal Mg2+. The same current was activated by a low intracellular ionic strength solution without an osmotic gradient. IClswell was reversibly inhibited by known Cl− channel blockers (NPP B, flufenamic acid, glibenclamide, DCPIB), and by the glutamate release inhibitor, riluzole. Cell swelling evoked glutamate release from primary microglia and MLS-9 cells, and this was inhibited by the blockers (above), and by IAA-94, but not by tamoxifen or the Na+/K+/Cl− symport inhibitor, bumetanide. Together, these results confirm the similarity of IClswell in the two cell types, and point to a role for this channel in inflammation-mediated glutamate release in the CNS.

Dysfunction of PTEN-induced kinase 1 (PINK1) or DJ-1 promotes neuronal death and is implicated in the pathogenesis of Parkinson's disease, but the underlying mechanisms remain unclear. Given the roles of N-methyl-d-aspartate receptor (NMDAr)-mediated neurotoxicity in various brain disorders including cerebral ischemia and neurodegenerative diseases, we investigated the effects of PINK1 and DJ-1 on NMDAr function. Using protein overexpression and knockdown approaches, we showed that PINK1 increased NMDAr-mediated whole-cell currents by enhancing the function of NR2A-containing NMDAr subtype (NR2ACNR). However, DJ-1 decreased NMDAr-mediated currents, which was mediated through the inhibition of both NR2ACNR and NR2B-containing NMDAr subtype (NR2BCNR). We revealed that the knockdown of DJ-1 enhanced PTEN expression, which not only potentiated NR2BCNR function but also increased PINK1 expression that led to NR2ACNR potentiation. These results indicate that NMDAr function is differentially regulated by DJ-1-dependent signal pathways DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR. Our results further showed that the suppression of DJ-1, while promoted NMDA-induced neuronal death through the overactivation of PTEN/NR2BCNR-dependent cell death pathway, induced a neuroprotective effect to counteract DJ-1 dysfunction-mediated neuronal death signaling through activating PTEN/PINK1/NR2ACNR cell survival-promoting pathway. Thus, PINK1 acts with DJ-1 in a common pathway to regulate NMDAr-mediated neuronal death. This study suggests that the DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR pathways may represent potential therapeutic targets for the development of neuroprotection strategy in the treatment of brain injuries and neurodegenerative diseases such as Parkinson's disease.

Background and Purpose— Downregulation of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), is thought to be a novel neuroprotective strategy in ischemic stroke, but the underlying mechanisms remain unclear. In this study, we aimed to validate the use of PTEN regulation of γ-aminobutyric acid subtype A receptors (GABA A Rs) as a molecular target for the treatment of ischemic stroke. Because suppression of GABA A Rs contributes to ischemic neuron death, describing the intracellular signaling that interacts with GABA A Rs in ischemic neurons would provide a molecular basis for novel stroke therapies. Methods— We measured surface GABA A R expression by immunocytochemical labeling and surface protein biotinylation assay. Knockdown and overexpression approaches were used to test the effects of PTEN on the expression and function of GABA A Rs. Neuronal death was detected in both in vitro and in vivo stroke models. Results— The knockdown and overexpression approaches provided the first evidence that PTEN negatively regulated membrane expression and function of GABA A Rs in rat hippocampal neurons. Importantly, we demonstrated that a PTEN inhibitor prevented the reduction of surface GABA A Rs in injured hippocampal neurons subjected to oxygen-glucose deprivation, an in vitro insult that mimics ischemic injury, whereas a GABA A R antagonist significantly reduced this PTEN inhibitor–induced neuroprotection in both the in vitro and in vivo ischemic stroke models. Conclusions— Our study provides direct evidence that downregulation of PTEN protects against ischemic neuron death by preserving GABA A R function. Targeting this pathway may be an effective strategy for development of selective, potent stroke treatments.

Dysfunction of PTEN-induced kinase-1 (PINK1) is implicated in neurodegeneration. We report here that oxygen-glucose deprivation (OGD), an in vitro insult mimicking ischemic neuron injury, resulted in a significant reduction of PINK1 protein expression in cultured cortical neurons. The decrease of PINK1 expression was blocked by the antagonists of NMDA receptors. We revealed that the overactivation of NR2B-containing NMDA receptors (NR2BRs) was responsible for the OGD-induced PINK1 reduction. The overactivated NR2BRs also inhibited the phosphorylation, but not the protein expression, of the cell survival-promoting kinase Akt after OGD insult, indicating that OGD-induced reduction of PINK1 protein is specific in the injury paradigm. We further showed that enhancing the protein expression of PINK1 antagonized OGD-induced reduction of Akt phosphorylation, suggesting that Akt may be a downstream target of PINK1 in ischemic neuron injury. Importantly, we provided evidence that both NR2BR antagonist and PINK1 over-expression protected against OGD-induced neuronal death. These results suggest that the overactivation of NR2BRs may contribute to ischemic neuron death through suppressing PINK1-dependent survival signaling. Thus, selectively antagonizing NR2BR signal pathway-induced neurotoxicity may be a potential neuroprotection strategy.

The type A GABA receptors are thought to mediate synchronization of clock cell activity within the suprachiasmatic nuclei (SCN). Here we report that casein kinases I epsilon and delta (CKI epsilon and CKI delta), the crucial clock regulators, form a complex with GABA(A) receptors and inhibit the receptors' function within the SCN according to a circadian rhythm. These results indicate that circadian variation of the kinase-receptor association may mediate regulation of GABA(A) receptor function by CKI epsilon-CKI delta in the SCN.

OBJECTIVE: The dynamic response of the heart during chest impact and the characteristics of heart injuries were investigated to further understand the mechanisms of heart impact injuries. METHODS: Eleven dogs and thirty-four rabbits were subjected to front thoracic impact with different impact velocities and compression response. The accelerated movement of thoracic wall during the impact period was monitored. The pathological examination of the injured heart was done and the dynamic responses and mechanisms of injuries were analyzed with mathematics models. RESULTS: The analysis of mathematics model and experimental results showed that the injury severity of heart was well correlated with the viscous criterion. The thoracic wall was involved in bi-directional movement of compression and expansion. The injured heart showed spotty or stripy hemorrhages in the ventricle endocardium. Light microscopic examination showed interstitial bleeding and rupture of the myocardial fibers in the contusion area. The biomechanical analysis indicated that there was a large deformation caused by the stress concentration on the lateral ventricle wall. CONCLUSIONS: There is a high speed and excessive deformation of the heart during the impact period, which might be the key mechanism of heart injury. The strong impact and press coming from both sternum and vertebral column and the rapid elevation of pressure in the ventricle are the main cause of deformation.

To gain some quantitative understanding of the nature and properties of stress wave propagation and the pathological characteristics of lung injuries, pressure values at eight sites in the lungs during an impact period were recorded. The lung injury severity scores in the corresponding regions were determined in 11 dogs, which were subjected to blunt, left lateral impact at a velocity of 16.33 m/sec with a 24.5% compressive response. The results showed that the pressure value at the contact point was the greatest and that pressure decreased significantly from left side to right side. However, at the left hilum a second pressure peak developed. The pressure value at the contact point was 0.68 and 0.50 times greater than those at left lung and left hilum, respectively. The speed at which the pressure at the contact point rose was much faster than the speed at other points. The lung injury scores at different sites corresponded well with the pressure values (P < 0.001). The data indicated that the reflection and refraction of the stress waves result in the accumulation of forces at some points, transferring more energy to the tissues at those points. Therefore, the severity of injury at these points in these tissues was more severe.

Circadian regulation of GABA A receptor function by CKIe-CKIδ in the rat suprachiasmatic nuclei

The left thoracic walls of 28 rabbits were subjected to lateral blunt impact in a movable impact pattern. The impact velocities ranged from 7.95 m/s to 16.13 m/s, and the compression response ranged from 15.69% to 46.14% of the thoracic width. The surviving animals were sacrificed at 6 hours after trauma and were autopsied. Injury scores were assigned according to the hemorrhage area and the injury type (e.g., rupture or rib fracture). When compared with the pathologic characteristics of the thoracic injury involving a relatively static impact pattern, the severity of thoracic injury involving a movable impact pattern was milder. Also there were more significant differences in the severity of injury to lungs and ribs on the left as compared with the right sides. The viscous criterion is still a good parameter reflecting the severity of injury to lungs and heart. The severity of rib injury was mainly related to compression response.