Clozapine Use for Bipolar Disorder: An Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling. RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months. CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

Identification of circRNA-miRNA networks for exploring an underlying prognosis strategy for breast cancer.

Aim: Circular RNAs (circRNAs) still have many potential functions in the process of tumor development that are not completely understood. The study aims to explore novel circRNAs and their mechanisms of action in breast cancer (BCa). Materials & methods: A combination strategy of RNA-sequencing (RNA-seq) technique, quantitative real-time PCR and bioinformatic analysis was employed to identify the potential mechanisms involving differentially expressed circRNAs in the serum exosomes and tissues of BCa patients. Results: The expression levels of hsa-circRNA-0005795 and hsa-circRNA-0088088 were significantly different both in serum exosomes and tissues and might function as competing endogenous RNAs and play vital roles in BCa development. Conclusion: We constructed two circRNA-miRNA networks and provided new insight into the prognosis and therapy of BCa using circRNAs from serum exosomes.

The acute toxic effects of silver nanoparticles on myocardial transmembrane potential, INa and IK1 channels and heart rhythm in mice.

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10-9-10-6 g/ml) concentration-dependently depolarized the resting potential, diminished the action potential, and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes, AgNPs (10-9-10-7 g/ml) concentration-dependently decreased the Na+ currents (INa), accelerated the activation, and delayed the inactivation and recovery of Na+ channels from inactivation within 5 min. AgNPs at 10-8 g/ml also rapidly decreased the inwardly rectifying K+ currents (IK1) and delayed the activation of IK1 channels. Intravenous injection of AgNPs at 3 mg/kg only decreased the heart rate, while at ≥4 mg/kg sequentially induced sinus bradycardia, complete atrio-ventricular conduction block, and cardiac asystole. AgNPs at 10-10-10-6 g/ml did not increase reactive oxygen species (ROS) generation and only at 10-6 g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5 min. Endocytosis of AgNPs by cardiomyocytes was not observed within 5 min, but was observed 1 h after exposing to AgNPs. Comparative Ag+ (≤0.02% of the AgNPs) could not induce above toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on ion channels at the nano-scale level, but not caused by Ag+, ROS, and membrane injury. These findings provide warning to the nanomedical practice using AgNPs.

The miR-30 family: Versatile players in breast cancer.

The microRNA family, miR-30, plays diverse roles in regulating key aspects of neoplastic transformation, metastasis, and clinical outcomes in different types of tumors. Accumulating evidence proves that miR-30 family is pivotal in the breast cancer development by controlling critical signaling pathways and relevant oncogenes. Here, we review the roles of miR-30 family members in the tumorigenesis, metastasis, and drug resistance of breast cancer, and their application to predict the prognosis of breast cancer patients. We think miR-30 family members would be promising biomarkers for breast cancer and may bring a novel insight in molecular targeted therapy of breast cancer.

A novel role of microRNA 17-5p in the modulation of circadian rhythm.

The circadian clock helps living organisms to adjust their physiology and behaviour to adapt environmental day-night cycles. The period length of circadian rhythm reflects the endogenous cycle transition rate and is modulated by environmental cues or internal molecules, and the latter are of substantial importance but remain poorly revealed. Here, we demonstrated that microRNA 17-5p (miR-17-5p), which has been associated with tumours, was an important factor in controlling the circadian period. MiR-17-5p was rhythmically expressed in synchronised fibroblasts and mouse master clock suprachiasmatic nuclei (SCN). MiR-17-5p and the gene Clock exhibited a reciprocal regulation: miR-17-5p inhibited the translation of Clock by targeting the 3'UTR (untranslated region) of Clock mRNA, whereas the CLOCK protein directly bound to the promoter of miR-17 and enhanced its transcription and production of miR-17-5p. In addition, miR-17-5p suppressed the expression of Npas2. At the cellular level, bidirectional changes in miR-17-5p or CLOCK resulted in CRY1 elevation. Accordingly, in vivo, both increase and decrease of miR-17-5p in the mouse SCN led to an increase in CRY1 level and shortening of the free-running period. We conclude that miR-17-5p has an important role in the inspection and stabilisation of the circadian-clock period by interacting with Clock and Npas2 and potentially via the output of CRY1.

High eosinophil cationic protein level in asthmatic patients with "heat" Zheng.

In traditional Chinese medicine (TCM), the imbalance of yin and yang is one of the basic pathogeneses of a disease. Preponderance of yang leads to "heat" manifestations including thirst, dryness of the throat, dark scanty urine and constipation. Treatment of asthma in TCM is based on the differentiation of "heat" Zheng according to the manifestations. Some of the patients with allergic asthma also present typical "heat" manifestations. To investigate the essence of "heat" manifestation in asthma, we measured the serum level of eosinophil cationic protein (ECP) in asthmatic patients. ECP usually represents the activation of eosinophils which are the main effectors in late allergic reactions. Our results demonstrated that asthmatic patients with "heat" manifestations had higher serum ECP levels, compared to those without "heat" manifestations (34.3 +/- 4 microg/l versus 15.3 +/- 3 microg/l). However, total immunoglobulin B (IgE), and the eosinophil count in peripheral blood did not show any difference between the "heat" and "non-heat" groups. Therefore, we conclude that ECP in asthmatic patients plays an important role in the development of "heat" manifestations as diagnosed by TCM.