Inhibitory effect of Aphidicolin - a tetracyclic diterpene - on the proliferation and apoptotic induction in human cervical cancer (HeLa) cells.

PURPOSE: The objective of the present work was to investigate the antitumor and apoptotic effect of aphidicolin against human cervical cancer (HeLa) cells. METHODS: Flow cytometry was performed to detect alterations in the mitochondrial membrane potential loss (ΔΨm) after aphidicolin treatment. Cell viability was assessed by the MTT assay while the apoptotic effects of the compound were examined by fluorescence microscopy and flow cytometry. RESULTS: Aphidicolin induced dose-dependent as well as time-dependent cytotoxic effects in HeLa cells. Chromatin condensation and formation of apoptotic bodies were observed by Hoechst 33258 staining after drug treatment. Aphidicolin induced both early and late apoptosis in HeLa cells which were correlated with strong concentration of the compound. ΔΨm was also observed following aphidicolin treatment at varying doses. CONCLUSION: Aphidicolin is a potent antitumor and apoptotic agent against human cervical carcinoma and its effects are mediated via chromatin condensation and mitochondrial membrane potential loss.

Low-dose clozapine-related seizure: A case report and literature review.

BACKGROUND: Treatment-resistant schizophrenia is a severe form of schizophrenia characterized by poor response to at least two antipsychotic drugs and is typically treated with clozapine. However, clozapine lowers the epileptic threshold, leading to seizures, which are severe side effects of antipsychotics that result in multiple complications. Clozapine-related seizures are generally considered to be dose-dependent and especially rare in the low-dose (150-300 mg/d) clozapine treated population. Due to clinical rarity, little is known about its clinical characteristics and treatment. CASE SUMMARY: A 62-year-old Chinese man with a 40-year history of treatment-resistant schizophrenia presented to the Emergency Department with symptoms of myoclonus, consciousness disturbance and vomiting after taking 125 mg clozapine. Upon admission, the patient had a suddenly generalized tonic-clonic seizure lasting for about half a minute with persistent disturbance of consciousness, fever, cough and bloody sputum, which was considered to be low-dose clozapine-related seizure. After antiepileptic and multiple anti-infection treatments, the patient was discharged without epileptic or psychotic symptoms. CONCLUSION: Our aim is to highlight the early prevention and optimal treatment of clozapine-related seizure through case analysis and literature review.

Inhibitory effect of Aphidicolin - a tetracyclic diterpene - on the proliferation and apoptotic induction in human cervical cancer (HeLa) cells.

Retraction of: 'Inhibitory effect of Aphidicolin - a tetracyclic diterpene - on the proliferation and apoptotic induction in human cervical cancer (HeLa) cells', by En-Yan Yu, Rui-Yan Zhao, Dong-Sheng Wang, JBUON 2015;20(6):1480-1486; PMID:26854444. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Salidroside protects PC-12 cells against amyloid ß-induced apoptosis by activation of the ERK1/2 and AKT signaling pathways.

Alzheimer's disease (AD) is one of the most frequent diseases in elderly people and causes high mortality. Its incidence is increasing annually and no effective therapeutic treatment currently exists. In the present study, salidroside, a major active ingredient of Rhodiola rosea, was able to protect PC­12 cells from the toxicity and apoptosis induced by AD inducer amyloid (A)ß1­42. Salidroside significantly protected PC­12 cells by inhibiting Aß1­42­induced cytotoxicity and mitochondria­mediated endogenous caspase apoptotic pathways. Mechanistic studies demonstrated that salidroside significantly activated the extracellular signal regulated kinase (ERK)1/2 and protein kinase B (AKT) signaling pathways. This observation was further confirmed using the ERK1/2 inhibitor PD98059 and the AKT inhibitor LY294002, which demonstrated that salidroside promoted PC­12 cell survival and proliferation by activating the ERK1/2 and AKT signaling pathways. Salidroside is a therapeutic candidate for the treatment of AD and provides a basis for further drug development.

EEG coherence characteristics at rest and during a three-level working memory task in normal aging and mild cognitive impairment.

BACKGROUND: The aim was to examine and compare the characteristics of intra- and inter-hemispheric EEG coherence in patients with mild cognitive impairment (MCI) and healthy controls at rest and during a working memory (WM) task having three levels. MATERIAL/METHODS: The subjects included 35 patients with MCI according to the DSM-IV criteria (mean age: 62.3+/-6.5 years) and 34 healthy controls (mean age: 57.4+/-4.0) selected from the community. All the subjects performed a simple calculation and recall task of WM with three levels of (WM1-3) while their EEG signal was recording. Inter- and intra-hemispheric EEG coherence was analyzed during the WM loads. RESULTS: Intra- and inter-hemispheric coherence during the WM task showed a "drop-to-rise" tendency compared with that at-rest condition. There was significantly higher coherence in MCI patients than in controls during the WM task. Intra-hemispheric ortical connectivity diminished while inter-hemispheric connectivity dominated in the MCI patients during WM with increasing task difficulty. CONCLUSIONS: MCI patients and normal controls may have differences in cortical connection and MCI patients have a cortical connection disturbance during WM tasks. With increasing task difficulty the MCI patients mobilized more inter-hemispheric than intra-hemispheric cognitive resources.

Interhemispheric functional connectivity for Alzheimer's disease and amnestic mild cognitive impairment based on the triple network model.

The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) based on a triple network model consisting of the default mode network (DMN), salience network (SN), and executive control network (ECN). The technique of voxel-mirrored homotopic connectivity (VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that: (1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions (i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions (i.e. frontoinsular cortex), and ECN-related brain regions (i.e. frontal middle gyrus and frontal inferior); (2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control (HC) groups, but no significant difference was observed between the aMCI and HC groups; and (3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination (MMSE) and Montreal Cognitive Scale (MOCA) scores and their factor scores in the AD, aMCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the aMCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.

Alpha spectral power and coherence in the patients with mild cognitive impairment during a three-level working memory task.

OBJECTIVE: The functional relationship between calculated alpha band spectral power and inter-/intra-hemispheric coherence during a three-level working memory task of patients with mild cognitive impairment (MCI) was investigated. METHODS: Subjects included 35 MCI patients according to the DSM-IV criteria (mean age: 62.3, SD: 6.5) and 34 healthy controls (mean age: 57.4, SD: 4.0) were selected from the community at large. All subjects performed a simple calculation and recall task with three levels of working memory load while electroencephalograph (EEG) signal was recorded. The spectral EEG power was computed over alpha1 (8.0-10.0 Hz) and alpha2 (10.5-13.0 Hz) frequency bands and was compared between rest stage and working memory processing stage by two-way ANOVA. Post hoc testing analyzed the differences between each two levels of working memory load during task processing. The inter-hemisphere EEG coherence of frontal (F3-F4), central (C3-C4), parietal (P3-P4), temporal (T5-T6) as well as occipital (O1-O2) was compared between MCI patients and normal controls. The EEG signals from F3-C3, F4-C4, C3-P3, C4-P4, P3-O1, P4-O2, T5-C3, T6-C4, T5-P3 and T6-P4 electrode pairs resulted from the intra-hemispheric action for alpha1 and alpha2 frequency bands. RESULT: There was significantly higher EEG power from MCI patients than from normal controls both at rest and during working memory processing. Significant differences existed between rest condition and three-level working memory tasks (P<0.001). The inter- and intra-hemispheric coherence during working memory tasks showed a "drop to rise" tendency compared to that at rest condition. There was significantly higher coherence in MCI patients than in the controls. When task difficulties increased, the cortical connectivity of intra-hemispheric diminished while the inter-hemispheric connectivity dominantly maintained the cognitive processing in MCI patients. CONCLUSION: The results of the present study indicate that the alpha frequency band may be the characteristic band in distinguishing MCI patients from normal controls during working memory tasks. MCI patients exhibit greater inter-hemispheric connectivity than intra-hemispheric connectivity when memory demands increase. MCI patients mobilize a compensatory mechanism to maintain the processing effectiveness while the processing efficiency is reduced.

Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant-like effect of Wuling mycelia powder in rat.

CONTEXT: Wuling mycelia powder is the dry powder of rare a fungi Xyla ria sp., Carbon species, with a long history of medicinal use in Chinese medicine. Recently it has shown a powerful antidepressant activity in clinic. OBJECTIVE: The present study explores the antidepressant activity of Wuling mycelia powder in chronic unpredictable mild stress (CUMS) rats and its possible involvement of l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway. MATERIALS AND METHODS: Experiments were performed in the rat CUMS model. CUMS rats were treated with Wuling mycelia powder (0.5, 1.0 or 2.0 g/kg, i.g.) to test behavioral changes including the sucrose preference, the crossing number and food consumption. Further, L-arginine (substrate for nitric oxide) (750 mg/kg), 7-nitroindazole (a specific neuronal nitric oxide synthase inhibitor) (25 mg/kg), sildenafil (phosphodiesterase 5 inhibitor) (5 mg/kg) and methylene blue (direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase) (10 mg/kg) were treated for 60 min before each test to detect the possible mechanism of antidepressant-like effect of Wuling mycelia powder. RESULTS: After 4 weeks of administration, both 1.0 or 2.0 g/kg Wuling mycelia powder suppressed the behavioral changes including the sucrose preference [F(3, 31)=50.87, p<0.001], the crossing number [F(3, 31)=68.98, p<0.05], and food consumption [F(3, 31)=19.04, p<0.05] in the CUMS rats. The antidepressant-like effect of Wuling mycelia powder was prevented by pretreatment with l-arginine and sildenafil. Pretreatment of rats with 7-nitroindazole and methylene blue potentiated the effect of Wulin mycelia powder. DISCUSSION AND CONCLUSION: Our findings demonstrate that Wuling mycelia powder has an antidepressant-like effect in the CUMS rats, and possible involvement of L-arginine-nitric oxide-cyclic GMP signaling pathway in its antidepressant effect.