Prognostic value of early glycosylated hemoglobin and blood glucose levels in patients with basal ganglia cerebral hemorrhage.

OBJECTIVE: This study was performed to analyze the relationships of the early glycosylated hemoglobin (GHb) level and blood glucose level (BGL) with prognosis in patients with basal ganglia cerebral hemorrhage (BGCH). METHODS: In total, 186 patients with BGCH were included in this prospective study. The GHb level, fasting BGL, bleeding volume, degree of consciousness disorder, intracerebral hemorrhage (ICH) score, functional outcome in patients with primary ICH (FUNC) score, ICH grading scale (ICH-GS) score, and neurological impairment were recorded during a 30-day observation period. RESULTS: The mean BGCH volume was 58.42 mL. The 30-day mortality rate was 22.32%. The ICH-GS score [odds ratio (OR) = 0.815, 95% confidence interval (95% CI) = 0.504-0.688, R = 0.624] and bleeding volume (OR = 0.882, 95% CI = 0.785-0.918, R = 0.784) were significant predictors of 30-day mortality. The GHb level (OR = 6.138, R = 0.705) and BGL (OR = 1.055, R = 0.418) were independent predictors of 30-day mortality according to the multivariate logistic regression analysis. CONCLUSION: The GHb level and BGL are strong predictors of 30-day mortality in patients with BGCH and accurately predict the prognosis in these patients.

Study on Umbilical Cord-Matrix Stem Cells Transplantation for Treatment of Acute Traumatic Brain Injury in Rats.

AIM: To evaluate the effect of umbilical cord derived mesenchymal stem cells (UC-MSCs) transplantation on traumatic brain injury (TBI). MATERIAL AND METHODS: UC-MSCs were isolated from human umbilical cord and TBI rat model was constructed. 30 male SD rats were randomly divided into 3 groups: control group, TBI group and MSCs transplantation group. Rats in MSCs group received the injection of a total of 1.5 C- 106 MSCs (25 I»l) via ventricle at operated ventricular coordinates (0 at bregma, 1.5 mm at lateral, 1.1 mm at behind, 4.5 mm in depth). RESULTS: 80% confluence of cells was formed from tissue at day 10 and the amount of CD90, CD73, CD105 positive cells increased correspondingly. In TBI model, clear hyperemia, edema and obvious infiltration of inflammatory cells in brain tissue were found. However, the manifestations were alleviated after the treatment of MSCs. In MSCs group, GFP in the brain tissue and the area around the vessels were found after the injection, while the expression levels of micro-vessel density (MVD), brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were elevated. CONCLUSION: UC-MSCs transplantation for treatment of acute TBI could effectively reduce the injury and improve the vascular reconstruction.

Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo.

BACKGROUND: Malignant glioma is refractory to conventional treatment, highlighting a need to develop novel efficacious therapies. Biguanides, a class of oral antidiabetic drug, have been thought to inhibit proliferation and metastasis in a variety of cancers. PURPOSE: The objective of this study was to investigate the affections of biguanides, phenformin (Phen) and metformin (Met), on growth and migration of glioma cells LN229 in vitro and in vivo. METHODS: Glioma cells LN229 were treated with Phen or Met, then cell proliferation and death were evaluated by MTT assay and PI stain, and cell cycle were evaluated using flow cytometric analysis, meantime wound healing assay and transwell migration assay were performed to detect cell migration ability. In addition, LN229 were injected in thigh of nude mice, and the mice were treated with Phen or Met to detect the effect of Phen and Met in vivo. RESULTS: Phen and Met could significantly inhibit cell growth through inhibiting cell proliferation, promoting cell death and disturbing cell cycle, and these drugs also could inhibit cell colony formation in glioma cells LN229 in vitro. Meanwhile, both Phen and Met could significantly inhibit cell migration of LN229 in vitro, through effecting the expression of E-cadherin and Vimentin. In addition, both Phen and Met inhibited the growth and migration of LN229 in a tumor xenograft model. Furthermore, Phen and Met were associated with the increased level of ROS of cell mitochondrial, and ROS inhibitor NAC could significantly rescue the cell death induced by Phen and Met. CONCLUSION: Phen and Met displayed powerful antitumor effects of LN229, and our findings powerfully suggest the possibility of Phen and Met being used as an adjuvant agent in the treatment of glioma patients.

Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein.

Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mechanism underlying this action remains unknown. This study investigated human SH-SY5Y cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 µM genistein), a rotenone group (treated with 50 µM rotenone), and a rotenone + genistein group (incubated with 20 µM genistein and then treated with 50 µM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's disease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.

A Randomized Controlled Trial of Puncturing and Bloodletting at Twelve Hand Jing Points to Treat Acute Carbon Monoxide Poisoning as Adjunct to First Aid Treatment: A Study Protocol.

Background. Acute carbon monoxide poisoning (ACOP) is a significant cause of morbidity and mortality in many countries. Twelve Hand Jing Points (THJP) have been believed to be effective to treat all kinds of emergency calls in traditional Chinese medicine (TCM) for more than 3000 years. This randomized controlled trial (RCT) is designed to evaluate the effectiveness of THJP in curing acute carbon monoxide poisoning in first aid treatment. This paper reports the protocol of the trial. Methods/Design. This RCT is a multicenter, randomized, controlled study undergoing in China. The compliant patients are divided into the bloodletting group and standard of care group. With first aid treatments given to both of the groups, the bloodletting group is bleeding at THJP upon being hospitalized. Primary outcomes and secondary outcomes will be measured and compared between these two groups. Before treatment, immediately after treatment, and 30 minutes, 1 hour, and 4 hours after treatment, patients' basic vital signs and state of consciousness were observed. Before treatment and 1 and 4 hours after treatment, carboxyhemoglobin concentration in venous blood samples was detected. Discussion. The objective of this study is to provide convincing evidence to clarify the efficacy and safety of THJP for early treatment of acute carbon monoxide poisoning.

[Comparative study on the brain protection in patients of traumatic cerebral infarction treated with bloodletting at Jing-well points and semen coicis].

OBJECTIVE: To verify the effect of bloodletting therapy at Jing-well points and semen coicis on patients with traumatic cerebral infarction. METHODS: Ninety patients were randomized into a bloodletting therapy at Jing-well points group (bloodletting group), a semen coicis group and a comprehensive therapy group, 30 cases in each one. The conventional basic medication was applied in all of the three groups. In the bloodletting group, the bloodletting therapy was done at twelve Jing-well points with three-edged needle, 3 drops of blood required at each one, three times a day. In the semen coicis group, the semen coicis preparation was applied via nasal feeding or oral administration, 90 g each day, three times a day. In the comprehensive therapy group, the bloodletting therapy at twelve Jing-well points and semen coicis preparation were used in combination and the methods were same as the above two groups. After 4 weeks of treatment, the efficacy was assessed with nerve function defectscale (NDS). Fugl-Meyer scale of the upper and lower limb function was used to evaluate the motor function of the affected limbs of the patients before and after treatment. RESULTS: The scores of Fugl-Meyer scale of the upper and lower limb function were increased apparently after treatment in the patients of every group (P < 0.01, P < 0.05). The score increase was much more obvious in the bloodletting group and the comprehensive therapy group as compared with the semen coicis group (all P < 0.01). The result in the comprehensive therapy group was superior to the bloodletting group (all P < 0.05). The total effective rates of NDS in the comprehensive therapy group, bloodletting group and semen coicis group were 96.7% (29/30), 83.3% (25/30) and 76.7% (23/30) separately. The result in the comprehensive therapy group was higher apparently than those in the bloodletting group and semen coicis group separately (both P < 0.05). The result in the bloodletting group was better than that in the semen coicis group (P < 0.05). CONCLUSION: The bloodletting therapy at Jing-well points and semen coicis alleviate apparently nerve function defect, improve the motor function of the affected limbs and achieve the better efficacy.

Tropism mechanism of stem cells targeting injured brain tissues by stromal cell-derived factor-1.

OBJECTIVE: To explore the role and function of stromal cell-derived factor-1 (SDF-1) in stem cells migrating into injured brain area. METHODS: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF-1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively. RESULTS: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro. CONCLUSIONS: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.

Stem cells modified by brain-derived neurotrophic factor to promote stem cells differentiation into neurons and enhance neuromotor function after brain injury.

OBJECTIVE: To promote stem cells differentiation into neurons and enhance neuromotor function after brain injury through brain-derived neurotrophic factor (BDNF) induction. METHODS: Recombinant adenovirus vector was applied to the transfection of BDNF into human-derived umbilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to determine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively. RESULTS: The BDNF expression achieved its stabilization at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly. CONCLUSION: BDNF gene can promote the differentiation of the stem cells into neurons rather than glial cells, and enhance neuromotor function after brain injury.