Neuroprotective effect of ischemic postconditioning on sciatic nerve transection

Ischemic preconditioning or postconditioning has been shown to have neuroprotective effect on cerebral ischemia, but it has not been studied in peripheral nerve injury. In this study, a rat model of sciatic nerve transection was established, and subjected to three cycles of ischemia for 10 minutes ＋ reperfusion for 10 minutes, once a day. After ischemic postconditioning, serum insulin-like growth factor 1 expression increased; sciatic nerve Schwann cell myelination increased; sensory function and motor function were restored. These findings indicate that ischemic postconditioning can effectively protect injured sciatic nerve. The protective effect is possibly associated with upregulation of insulin-like growth factor 1.

Synthesis and Evaluation of a Novel Small-molecule Compound as an Anticancer Inhibitor of CD147

Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.

Polymorphisms of the maternal Slug gene in fetal neural tube defects in a Chinese population

Several studies have demonstrated that Slug,which encodes a zinc finger of the Snail family of transcription factors,is a potential risk factor for neural tube defects.Neural tube defects tend to occur with a high rate in Shanxi province,China.The present case-control study investigated genotypic distributions and allele frequencies of Slug C1548A polymorphisms in DNA samples from59 women with a history of neural tube defect pregnancies and 73 controls during the same period from Shanxi Province,China.Results demonstrated that women with a history of neural tube defect pregnancies had significantly greater genotypic distributions of Slug AA genotypes and A allele frequencies compared with controls,and A allele Slug C1548A was a risk factor for neural tube defects（odds ratio = 3.444;95% confidence interval;2.021-5.868,P 〈 0.05）.Three-dimensional structure prediction revealed that Slug C1548A resulted in transition of aspartic acid into glutamate at position 119.This indicated that these mutations could lead to damaged protein structure and function.These findings suggest that Slug C1548A gene polymorphism is closely related to neural tube defects in a population of Han Chinese origin from Shanxi Province,China

Effect of Xiaoqinglong decoction on mucus hypersecretion in the airways and cilia function in a murine model of asthma

Objective:Xiaoqinglong decoction (XQL) has been used in traditional Chinese medicine as a prescription for asthma treatment.We explored the effects of XQL on mucus hypersecretion and ciliophagy in the airways of mice in which asthma had been induced by ovalbumin (OVA).Methods:Thirty-six mice were sensitized by OVA injection (i.p.) on day-0 and day-14 and challenged with 1% OVA on day 18-22.Then,they were divided into three groups:model,carbocysteine and XQL.From day-15 to day-22,the XQL group was administered XQL (10 g/kg,p.o.) 1 hour before each aerosol challenge with OVA.To evaluate the effect of XQL on mucus hypersecretion,AB-PAS staining,measurement of serum levels of interleukin (IL)-13,bronchoalveolar lavage fluid (BALF) analyses,ciliophagy analyses,as well as coexpression of Light Chain 3 (LC3) and acetylated α-tubulin by immunofluorescence staining were undertaken.Results:Treatment with XQL (10 g/kg) attenuated mucus secretion in the airways,and reduced the positive areas of AB-PAS staining in histopathologic lung tissues (P <.05).IL-13 expression in serum (P <.01),OVA-induced inflammatory changes,and the number of white blood cells (P <.01) in BALF samples were also reduced.However,the effect on mucus secretion was less apparent in the carbocysteine group compared with the XQL group.XQL treatment also improved the cilia length and elicited a substantial reduction in ciliophagy and LC3 expression in the tracheal epithelium.Conclusion:XQL can attenuate cilia shortening,aid the clearance function of ciliated epithelial cells,and reduce mucus production in an OVA-induced asthma model in mice.XQL can inhibit mucus hypersecretion and could be a new type of pharmacotherapy.

Lysine-specific demethylase 1 expression in zebrafish during the early stages of neuronal development

Lysine-specific demethylase 1 （Lsdl） is associated with transcriptional coregulation via the modulation of histone methylation. The expression pattern and function of zebrafish Lsdl has not, however, been studied. Here, we describe the pattern of zebrafish Lsdl expression during different development stages. In the zebrafish embryo, Isdl mRNA was present during the early cleavage stage, indicating that maternally derived Lsdl protein is involved in embryonic patterning. During embryogenesis from 0 to 48 hours post-fertilization （hpf）, the expression of Isdl mRNA in the embryo was ubiquitous before 12 hpf and then became restricted to the antedor of the embryo （particularly in the brain） from 24 hpf to 72 hpf. Inhibition of Lsdl activity （by exposure to tranylcypromine） or knockdown of Isdl expression （by morpholino antisense oligonucleotide injection） led to the loss of cells in the brain and to a dramatic downregulatJon of neural genes, including gad65, gad75, and reelin, but not hey1. These findings indicate an important role of Lsdl during nervous system development in zebrafish.

Detection and analysis of biochemical indicators, antioxidant enzymes and related factors in patients with Parkinson

Objective: To explore the changes and clinical significance of biochemical indexes, antioxidant enzymes and related factors in patients with Parkinson. Methods: 50 patients with Parkinson's disease who were treated in our hospital from March 2016 to March 2017 were selected as observation group. 50 healthy volunteers who were received physical examination in this hospital during the same period were selected as control group. The levels of bilirubin, blood uric acid, superoxide dismutase, glutathione peroxidase, catalase, TNF-α, tumor necrosis factor-α receptor-1, tumor necrosis factor-α receptor-2, monocyte chemoattractant protein-1 and macrophage inflammatory protein -1 of the patients in the two group were compared. Results: The level of serum bilirubin, uric acid, SOD, GSH-PX and CAT of patients in the observation group were (5.65±0.61) μmoL/L, (262.96±26.38) μmoL/L, (92.65±9.35) U/mL, (18.96±2.03) U/mL and (56.94±16.23) U/mL. The above indexes of patients in the observation group were significantly lower than those of patients in the control group (P<0.05). The serum level of TNF-α, sTNFR1, MCP-1 and MIP-1 of patients in the observation group were (19.65±2.07) pg/mL, (798.96±80.20) pg/mL, (43.65±4.27) ng/L and (23.96±2.41) ng/L. The above indexes of patients in the observation group were significantly higher than those of patients in the control group (P<0.05). Conclusion: Bilirubin, uric acid, antioxidant enzymes and inflammatory factors are all related to the progression of Parkinson's disease and can be used as auxiliary index in the diagnosis and treatment of Parkinson's disease.

Lactic acidosis during telbivudine treatment for HBV: A case report and literature review

All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy.A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B.After 11 mo of therapy,he developed anorexia,nausea,and vomiting with mild muscle weakness.The patient was found with elevated serum creatine phosphokinase up to 3683 U/L(upper limit of normal 170 U/L)and marked LA.LA did not resolve immediately following discontinuation of telbivudine.His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid.The patient fully recovered after 16 wk of treatment.This is the first documented case with severe LA caused by telbivudine monotherapy.Besides serum creatine phosphokinase,blood lactate level should also be closely monitored in patients receiving telbivudine.

A novel microcurrent dressing for wound healing in a rat skin defect model

Background:The exogenous application of low-intensity electric stimulation(ES)may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds.This study designed a novel microcurrent dressing(MCD)and evaluated its potential effects on wound healing in a rat skin defect model.Methods:First,wireless ES was integrated into a medical cotton cushion to fabricate the MCD,and its electrical property was examined by using a universal power meter.Then,animal experiments were conducted to evaluate the MCD’s effect.Forty-five rats were randomized into control(Con)group,Vaseline gauze(VG)group and MCD group.A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal.Apart from routine disinfection,the Con rats were untreated,whereas the other two groups were treated with VG or MCD.On days 3,7 and 14 post injury,the wound areas were observed and measured using image analysis software following photography,and the skin samples were harvested from wound tissue.Then,histopathological morphology was observed routinely by hematoxylin and eosin(HE)staining;tumor necrosis factorα(TNF-α)and interleukin(IL)-1βexpression were detected by Western blotting.Vascular endothelial growth factor(VEGF)and epidermal growth factor(EGF)expression were detected with immunohistochemistry.Results:The MCD generated a sf electric potential greater than 0.95 V.Animal experiments showed that the woundhealing rate in the MCD group was significantly increased compared with the Con and VG groups(P<0.05 or P<0.01).Histopathological observation revealed an alleviated inflammatory response,induced vascular proliferation and accelerated epithelization in the MCD group.Moreover,samples from the MCD group expressed reduced TNF-αand IL-1βlevels and increased VEGF and EGF levels compared with those of the other two groups(P<0.05 or P<0.01).However,no significant difference was noted between the Con and VG groups at each time point.Conclusions:The MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression.Thus,MCD may act as a promising biomaterial device for skin wound healing.

Single nucleotide polymorphisms of the maternal gene and their association with fetal neural tube defects in Han ethnic group in Shanxi Province, China

Background Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population.Methods We studied 59 mothers with at least one previous child with a neural tube defect （the case group） and 73case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T poiymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests.Results Significant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups （CT： 32% vs. 15%, P=0.0073 and TT 15% vs. 4%, P=0.013, respectively）. Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects （P 〈0.05; OR： 3.466;95%CI： 1.831-6.560）. Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2.Conclusion Maternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.

Multiple factor analysis of symptomatic intracranial arterial stenosis

Objective: To discuss the correlation among intracranial arterial stenosis and its risk factors. Methods: A total of 486 patients with transient ischemic attack(TIA) or ischemic cerebral infarction were examined using color doppler flow imaging(CDFI) and transcranial doppler ultrosonography(TCD). According to the degrees of extracranial arterial stenosis, patients with mild-to-moderate extracranial stenosis were classified into group A(435 cases) while those with constant severe stenosis or occlusion were classified into group B(51 cases). The differences between the two groups of risk factors were compared, and the multi-factor logistic regression analysis of risk factors associated with moderately severe intracranial arterial stenosis was performed. Results:(1) The risk factors that were significantly associated with intracranial arterial stenosis included age(P = 0.034) and gender(P = 0.044).(2) Intracranial artery stenosis was observed in both anterior and posterior cerebral arteries in patients with hypertension, diabetes, and coronary heart disease respectively(P < 0.05).(3) Compared with group A, patients in group B were older(P = 0.000), with a higher proportion of men(P = 0.037), and the intracranial arterial stenosis degrees were significantly higher(P = 0.013).(4) Multi-factor logistic regression analysis showed that diabetes is a risk factor for moderately severe intracranial arterial stenosis(P < 0.05), and hyperlipidemia is a protective factor(P = 0.012). Conclusions: Age, gender, hypertension, diabetes, coronary heart disease, and smoking are risk factors for the distribution of intracranial arterial stenosis. The degrees of intracranial arterial stenosis are related with extracranial arterial stenosis. Diabetes is a risk factor for moderately severe intracranial arterial stenosis while hyperlipidemia is a protective factor.

Generation of genetically modified olfactory ensheathing cells that secrete VEGF: Potential application in cell-based treatment of leukoaraiosis

Objective: We aimed to provide an alternative cell source for cell therapy in leukoaraiosis(LA). Methods: Olfactory ensheathing cells(OECs) from the olfactory bulb were isolated,cultured, and purified. Next, the lentivirus carrying human VEGF165 gene was constructed and transfected into OECs. Results: The proliferative capacity of primary OECs was strong. OECs were infected with different multiplicity of infection. The expression level of VEGF was confirmed by real-time PCR with specific primers for GAPDH and VEGF, indicating that the genetically engineered OECs-VEGF produced VEGF with functional activity. Conclusions: Our data showed that these engineered OECs-VEGF highly express functional VEGF and retain the characteristics of astrocytes and Schwann cells,providing an alternative cell source for cell therapy in LA.