Curcumin (1), a natural polyphenolic compound, has shown strong antioxidant and anticancer activities. Several molecular mechanisms have been attributed to its inhibitory effects on a wide range of tumor cells. In this study, the response of the chronic myeloid leukemia cell line K562 cells to 1 is investigated. Curcumin inhibited the viability of K562 cells in a dose- and time-dependent manner. Furthermore, curcumin-induced cell death was associated with the formation of the apoptosome complex, the collapse of the mitochondrial membrane potential, and caspase-3 activation. Curcumin treatment also induced Bid cleavage and downregulated the expression of Bcl-2 protein. Surprisingly, even with these molecular features of apoptosis, we showed that 1 stimulated autophagy, which was evidenced by microtubule-associated protein light chain 3 (LC3) immunoreactivty. Curcumin also increased the protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitor bafilomycin A1 and the pan-caspase inhibitor Z-VAD-fmk suppressed curcumin-induced K562 cell death. Overall, these results suggest that curcumin induces autophagic and apoptotic death of K562 cells. These findings suggest that both apoptotic and autophagic mechanisms contribute to the curcumin-induced K562 cell death.

ObjectiveWe aim to study the effect of precision repetitive transcranial magnetic stimulation (rTMS) over the left parietal cortex on the memory and cognitive function in Alzheimer’s disease (AD).MethodsBased on the resting-state functional magnetic resonance imaging, the left parietal cortex site with the highest functional connectivity to the hippocampus was selected as the target of rTMS treatment. Sixty-nine AD patients were randomized to either rTMS or sham treatment (five sessions/week for a total of 10 sessions). The Mini-Mental State Examination (MMSE), 12-Word Philadelphia Verbal Learning Test (PVLT), and Clinical Dementia Rating (CDR) were assessed at baseline and after the last session.ResultsAfter a 2-week treatment, compared to patients in the sham group, those in the rTMS group scored significantly higher on PVLT total score and its immediate recall subscale score. Moreover, in the rTMS group, there were significant improvements after the 2-week treatment, which were manifested in MMSE total score and its time orientation and recall subscale scores, as well as PVLT total score and its immediate recall and short delay recall subscale scores. In the sham group, the PVLT total score was significantly improved.ConclusionThe target site of the left parietal cortex can improve AD patients’ cognitive function, especially memory, providing a potential therapy.

Aim: To evaluate the contribution of an autophagic mechanism to the As 2 O 3 -induced death of human acute myeloid leukaemia cell line HL60 cells. Methods: The growth inhibition of HL60 cells induced by As 2 O 3 was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. The activation of autophagy was determined with monodansylcadaverine labeling and transmission electron microscope. The role of autophagy in the As 2 O 3 -induced death of HL60 cells was assessed using autophagic and lysosomal inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms. Results: After treatment with As 2 O 3 , the proliferation of HL60 cells was significantly inhibited and the formation of autophagosomes increased. The blockade of autophagy maturation with the autophagy-specific inhibitor 3-methyladenine (3-MA) or the lysosome-neutralizing agent NH 4 Cl 1 h before As 2 O 3 potentiated the As 2 O 3 -induced death of HL60 cells. In contrast, 3-MA attenuated As 2 O 3 -induced death when administered 30 min after As 2 O 3 . 3-MA and NH 4 Cl also inhibited As 2 O 3 -induced upregulation of microtubule-associated protein 1 light chain 3, the protein required for autophagy in mammalian cells. Following As 2 O 3 , lysosomes were activated as indicated by increased levels of cathepsins B and L. The apoptotic response of HL60 cells to As 2 O 3 was suggested by the collapse of mitochondrial membrane potential, release of cytochrome c from mitochondria, and the activation of caspase-3. Pretreatment with 3-MA prior to As 2 O 3 amplified these apoptotic signals, while posttreatment with 3-MA 30 min after As 2 O 3 attenuated the apoptotic pathways. Conclusion: Autophagy plays complex roles in the As 2 O 3 -induced death of HL60 cells; it inhibits As 2 O 3 -induced apoptosis in the initiation stage, but amplifies the As 2 O 3 -mediated apoptotic program if it is persistently activated.

Purpose The purpose of this paper is to explain how individuals form microblogging habits and why they continue to use microblogs from the perspective of direction social networks. Design/methodology/approach Drawing on the social network theory and the social presence theory, the authors develop a theoretical framework to explain how individuals form microblogging habits and why they continue to use microblogs. To test the proposed model and examine its external validity, the authors collected data from two microblogs: Twitter and Sina Weibo. Findings Satisfaction and habit have a significant influence on microblogging continuance intention. Whereas, users’ microblogging habits are developed by two key factors – satisfaction and frequency of past behavior – that are further determined by social presence and social network centrality. Research limitations/implications Larger sample size with diverse populations is highly recommended for future studies. In addition, exploring the distinct technical functionalities of microblogs when conceptualizing habit formation would be of benefit in future studies. Practical implications In this study, it was found that social presence increases both the satisfaction of users and the frequency of past use behavior. Hence, microblog designers should provide users with greater freedom to modify the form and content of their interface, and enable these modifications to be visible in real time to increase the interactivity of microblogs. Originality/value In contrast to past studies that have largely neglected the impacts of the directed social network structure, this study aims to focus on microblogging continuance intention from the directed social network perspective. The results from two independent data sets converge on the conclusion that users’ continuance intention to use is affected by both their conscious evaluations (i.e. satisfaction) and unconscious reactions (i.e. habit).