MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

Human tissue kallikrein promoted activation of the ipsilesional sensorimotor cortex after acute cerebral infarction.

BACKGROUND/AIMS: Kallikrein, a serine proteinase, has been reported to have many functions, such as selectively dilating arterioles in the ischemic area and enhancing angiogenesis and neurogenesis. Therefore, it may promote cerebral poststroke reorganization. We observed the effect of human tissue kallikrein on the brain motor activation of acute ischemic stroke patients and evaluated patient condition severity and prognosis. METHODS: Forty-four cases suffering from cerebral infarction between 6 and 72 h of onset were randomly assigned into the kallikrein group (n = 24) and the control group (n = 20). The control group was given conventional treatment, whereas the kallikrein group was given both conventional treatment and human tissue kallikrein over the course of 12-14 days. The activation of the sensorimotor cortex (SMC) and cerebellum, the affected forefinger strength and the NIHSS scores were evaluated before and after treatment. The MBI and MRS scores were assessed at 30 and 90 days after stroke onset. RESULTS: There were no differences between the two groups in activation volume, patient condition and scores before treatment. After treatment, the ipsilesional SMC activation volume was significantly larger and the increase in the volume was significantly greater in the kallikrein group than in the control group (p < 0.05 for both). The NIHSS score was significantly smaller and the improvement in the score was significantly greater in the kallikrein group after treatment (p < 0.05 for both). Moreover, the MBI scores at 30 days were significantly higher, whereas the MRS scores at 30 days were significantly lower in the kallikrein group than in the control group (p < 0.05 for both). CONCLUSIONS: Kallikrein improved neural function effectively and quickly after stroke, and promoting cerebral reorganization might be an important mechanism for kallikrein in the treatment of acute cerebral infarction.

Indirect to Direct Band Gap Transformation by Surface Engineering in Semiconductor Nanostructures.

Indirect band gap semiconductor materials are routinely exploited in photonics, optoelectronics, and energy harvesting. However, their optical conversion efficiency is low, due to their poor optical properties, and a wide range of strategies, generally involving doping or alloying, has been explored to increase it, often, however, at the cost of changing their material properties and their band gap energy, which, in essence, amounts to changing them into different materials altogether. A key challenge is therefore to identify effective strategies to substantially enhance optical transitions at the band gap in these materials without sacrificing their intrinsic nature. Here, we show that this is indeed possible and that GaP can be transformed into a direct gap material by simple nanostructuring and surface engineering, while fully preserving its "identity". We then distill the main ingredients of this procedure into a general recipe applicable to any indirect material and test it on AlAs, obtaining an increase of over 4 orders of magnitude in both emission intensity and radiative rates.

ICOS/B7RP-1 interference in mouse kidney transplantation.

BACKGROUND: Activated T cells play a key role in allograft rejection. T cell activation requires signaling via the T cell receptor as well as costimulatory signals. Inducible costimulatory molecule (ICOS), with its ligand B7RP-1, is a recently discovered costimulatory molecule of the CD28 family. The role of this signaling pathway during the early phases of kidney allograft rejection is not clear so far. METHODS: Kidneys were orthotopically transplanted from BALB/c to C57BL/6 mice. Animals were assigned to five experimental groups: blocking anti-ICOS monoclonal antibody, ICOS fusion protein, anti-B7RP1 monoclonal antibody, B7RP-1 fusion protein, and control immunoglobulin G. RESULTS: Survival was significantly reduced in animals treated with ICOS monoclonal antibody (mAb) and B7RP-1 Fc as compared with controls. These animals had also a lower number of apoptotic graft infiltrating T cells, whereas the expression of intracellular interferon-gamma in CD3CD4 T cells was increased. Animals treated with ICOS Fc and B7RP-1 mAb had similar survival and numbers of apoptotic T cells as compared with controls. CONCLUSIONS: In summary, the blockade of ICOS with ICOS mAb or B7RP-1 Fc reduced the amount of apoptosis of infiltrating lymphocytes and resulted in continuous inflammatory processes with progressive tissue damage and graft failure.

Recombinant adenovirus-mediated vascular endothelial growth factor gene transfer attenuates hypoxia-induced apoptosis of neural stem cells in vitro.

OBJECTIVE: To study the effects of vascular endothelial growth factor (VEGF) gene transfer on hypoxia-induced apoptosis of neural stem cells in vitro. METHODS: C17.2 neural stem cells cultured in vitro were infected by recombinant adenovirus containing VEGF gene and cultured under hypoxic condition. VEGF expression in these cells was detected by Western blotting, and the apoptotic index was calculated from results of triphosphate-biotin nick end-labeling (TUNEL) assay. Flow cytometry was employed to examine the changes in the cell apoptotic rate after VEGF gene transfer, and the apoptotic bodies were observed under fluorescence microscope with Hoechst33342 staining. RESULTS: The expression of VEGF was significantly increased in pAdCMV VEGF(165)-infected cells, resulting in inhibition of the apoptosis of C17.2 neural stem cells induced by hypoxia manifested by a significantly lower apoptotic rate of the stem cells transfected by pAdCMV VEGF(165) than that of the untransfected cells (10.38%;+/-0.48%; vs 19.98 %;+/-0.55%;, P<0.01) and of the cells transfected with pAdCMV VEGF(165) along with VEGF anti-sense oligodeoxynucleotide (19.07%;+/-0.64%;, <0.01) after hypoxia. CONCLUSIONS: Recombinant adenovirus can efficiently mediate VEGF gene transfer into C17.2 neural stem cells, resulting in high expression of the exogenous VEGF in vitro, which effectively reduces C17.2 neural stem cell apoptosis induced by hypoxia.

Correlation between the changes in ambulatory electroencephalography findings and epilepsy recurrence after medication withdrawal among the population in southern China.

Patients suffering from epilepsy need long-term medication. However, after the epilepsy is completely under control, the recurrence rate is high once the drug dose is reduced gradually. The present study investigated the possible correlation between the changes shown by ambulatory electroencephalography (EEG) and epilepsy recurrence after medication withdrawal, and assessed the value of ambulatory EEG findings in predicting the recurrence of epilepsy after medication withdrawal, in 265 patients from Southern China followed up for 5 years. Anticonvulsants were withdrawn until onset had been controlled thoroughly for over 3 years and ambulatory EEG detected no abnormalities. Ambulatory EEG was performed at least once per year, and findings at the first visit, during treatment, and before and after medication withdrawal were compared and analyzed. There were 47 patients with recurrent epilepsy in this study. Patients with normal ambulatory EEG findings at the first visit and during treatment had lower recurrence rate (about 8.1%) compared to patients with epileptic waves (25.0%), and patients with focal epileptic waves in the temporal, occipital, frontal, and parietal lobes, or in multiple areas was even higher. Patients with epileptic waves also showed higher clinical recurrence rate during the follow-up period. Abnormal ambulatory EEG findings are an important indicator of epileptic recurrence, and is of great value in predicting the recurrence of epilepsy after medication withdrawal.

Differentiation of HT22 neurons induces expression of NMDA receptor that mediates homocysteine cytotoxicity.

INTRODUCTION: Neurotoxic homocysteine (Hcy) is thought to be an independent risk factor for neurodegenerative diseases, including Alzheimer's disease. This study is to determine whether HT22 cells, a murine hippocampal neuronal model, can be used as an in vitro model, besides the primary neuronal cultures, to investigate the effects of Hcy. MATERIALS AND METHODS: MTS assay and Hoechst 33342/propidium iodide discrimination were used to assess the cell viability and cell death on undifferentiated and differentiated HT22 cells. Semi-quantitative reverse transcription polymerase chain reaction and western blot were used to determine the expression of N-methyl D-aspartate (NMDA) receptor. RESULTS: We found that undifferentiated and differentiated HT22 cells responded to Hcy toxicity differentially, with the undifferentiated cells resistant while the differentiated cells sensitive. The underlying mechanism appeared to be the differential expression levels of NMDA glutamate receptor between the undifferentiated and differentiated cells. Similar to what have been observed in primary neuronal cultures, the Hcy toxicity in the differentiated HT22 cells was largely attenuated by NMDA receptor antagonists, MK-801 and memantine. CONCLUSION: These results suggest for the first time that the differentiation of HT22 cells could induce the expression of NMDA receptors, which lead to Hcy mediate concentration-dependent apoptosis-necrotic continuum of HT22 cell death. The differentiation status of the HT22 cells is important for modeling neurons in vitro, with the differentiated HT22 neurons resembling more characteristics of primary hippocampal neurons while the undifferentiated HT22 cells being proliferating neuronal precursor cells. The differentiated HT22 neurons can be used as a platform to study Hcy toxicity.

Kallikrein gene transfer induces angiogenesis and further improves regional cerebral blood flow in the early period after cerebral ischemia/reperfusion in rats.

AIMS: The aims of this study were to find out whether kallikrein could induce angiogenesis and affect the cerebral blood flow (rCBF) in the early period after cerebral ischemia/reperfusion (CI/R). METHODS: The adenovirus carried human tissue kallikrein (HTK) gene was administrated into the periinfarction region after CI/R. At 12, 24, and 72 h after treatments, neurological deficits were evaluated; expression of HTK and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry staining; the infarction volume was measured; and rCBF was examined by( 14) C-iodoantipyrine microtracing technique. RESULTS: The expression of VEGF was enhanced significantly in pAdCMV-HTK group than controls over all time points (P < 0.05). Furthermore, the rCBF in pAdCMV-HTK group increased markedly than controls at 24 and 72 h after treatment (P < 0.05), and the improved neurological deficit was accompanied by reduced infarction volume in pAdCMV-HTK group 24 and 72 h posttreatment. CONCLUSION: In the early period after CI/R, kallikrein could induce the angiogenesis and improve rCBF in periinfarction region, and further reduce the infarction volume and improve the neurological deficits.

Expression and genetic analysis of tumor necrosis factor-alpha (TNF-alpha) G-308A polymorphism in sporadic Alzheimer's disease in a Southern China population.

Alzheimer's disease (AD) is one of most common chronic neurodegenerative diseases in the elderly. Tumor necrosis factor-alpha (TNF-alpha) was found elevated markedly in the serum and the cerebral spinal fluid of AD patients. And the elevation of TNF-alpha was thought to be associated with the occurrence of AD in China. However, it is still unclear whether the TNF-alpha polymorphism is related to the sporadic Alzheimer's disease (SAD) in China as well. Hence, in this study, we try to investigate the relationship between TNF-alpha G-308A polymorphism and its susceptibility to SAD in a Southern China population. The polymerase chain reaction-sequence specific primers (PCR-SSP) was performed to detect the frequencies of genotypes and alleles of TNF-alpha in 112 SAD patients and 121 controls. And the levels of TNF-alpha in serum were measured by radioimmunoassay. The differences of polymorphic distribution and the levels of TNF-alpha in serum between groups were then analyzed, and odds ratio was computed for association analysis. The frequency of A-allele was significantly increased in patients with SAD compared with that of the controls (chi(2)=4.256, P=0.039). A significantly increased risk of SAD was observed in the carriers of A-allele (OR=2.635, 95% CI 1.027-6.763, P<0.01). In parallel, the serum level of TNF-alpha in SAD group was much higher than that in control group (chi(2)=10.21, P=0.0042). And the elevation of serum level of TNF-alpha was closely associated with the risk of SAD (OR=3.542, 95% CI 2.304-8.854, P<0.05) as well. These results suggested that the TNF-alpha gene G-308A polymorphism might be a risk factor for SAD in Southern China. A-allele might play a role in the susceptibility of SAD.