Search

Myeloid‐derived suppressor cells (MDSCs) play an important role in tumor immune escape. Recent studies have shown that MDSCs contribute to tumor progression under psychological stress, but the underlying mechanism of MDSCs mobilization and recruitment remains largely unknown. In the present study, a chronic restraint stress paradigm was applied to the H22 hepatocellular carcinoma (HCC) bearing mice to mimic the psychological stress. We observed that chronic restraint stress significantly promoted HCC growth, as well as the mobilization of MDSCs to spleen and tumor sites from bone marrow. Meanwhile, chronic restraint stress enhanced the expression of C‐X‐C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C‐X‐C motif) ligand 5 (CXCL5) expression in tumor tissues. In vitro, the treatments of MDSCs with epinephrine (EPI) and norepinephrine (NE) but not corticosterone (CORT)‐treated H22 conditioned medium obviously inhibited T‐cell proliferation, as well as enhanced CXCR2 expression and extracellular signal‐regulated kinase (Erk) phosphorylation. In vivo, β‐adrenergic blockade with propranolol almost completely reversed the accelerated tumor growth induced by chronic restraint stress and inactivated CXCL5‐CXCR2‐Erk signaling pathway. Our findings support the crucial role of β‐adrenergic signaling cascade in the mobilization and recruitment of MDSCs under chronic restraint stress. What's new? Myeloid derived suppressor cells (MDSCs) contribute to tumor progression under psychological stress, but the underlying mechanism of MDSCs mobilization and recruitment remains largely unknown. Using the chronic restraint stress paradigm in a mouse hepatocellular carcinoma model, here the authors reveal that stress‐induced β‐adrenergic signaling enhances the mobilization and immunosuppressive function of MDSCs via the CXCL5‐CXCR2 axis and Erk signaling activation. These findings support the crucial role of the β‐adrenergic signaling cascade in the harnessing of MDSCs under chronic stress conditions and highlight adrenergic receptor signaling antagonism as a potentially beneficial strategy in cancer therapy. [ABSTRACT FROM AUTHOR]

Piper laetispicum C. DC is one of the Chinese herbal medicines used for alleviating depressive disorders. G11‐5 [3‐(3, 4‐methylenedioxy‐5‐trifluoromethyl phenyl)‐2E‐propenoic acid isobutyl amide] is synthesized based on the chemical structure of an active integrant of Piper laetispicum C. DC. The present study assessed the antidepressant effect of G11‐5 and investigated the underlying mechanism with learned helplessness (LH) and social defeat stress (SDS) mice model of depression. In the LH model, mice were exposed to 60 inescapable electric shocks once a day for three consecutive days followed by 2‐week drug administration and helpless behaviour assessment. In the SDS model, mice were subjected to repeated social defeat by an aggressive CD‐1 mouse once a day for consecutive 10 days. Following oral administration for 2 weeks, the mice were subjected to a series of behavioural tests including social interaction test. G11‐5 significantly decreased the number of escape failures induced by LH paradigm, meanwhile increased the social interaction ratio and shortened the immobility time in forced swimming test for the SDS‐exposed mice, suggesting remarkable antidepressant effect. Moreover, G11‐5 ameliorated the changes in mitophagy‐related proteins induced by two stress exposures and restored retrograde axonal transport and neurotransmitter release. Our findings suggested that G11‐5 exhibited an obvious antidepressant through TSPO‐mediated mitophagy pathway. [ABSTRACT FROM AUTHOR]

This study validated the RisingSun RS-651 blood pressure (BP) monitor based on auscultation in adults according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2013 standard. The RS-651 device was evaluated in a study of 97 participants. The same arm simultaneous method, as defined in the ANSI/AAMI/ISO standard, was used. The mean differences±standard deviation for criterion 1 were 0.8±2.3 mm Hg for systolic BP (SBP) and -0.1±2.9 mm Hg for diastolic BP (DBP). Analysis for criterion 2 resulted in values of 0.8±1.5 mm Hg for SBP and -0.1±2.1 mm Hg for DBP. All of the data fulfilled the ANSI/AAMI/ISO 81060-2:2013 standard requirements to pass the validation. The RisingSun RS-651 device can be recommended for both clinical and self/home use in adults according to the ANSI/AAMI/ISO 81060-2:2013 standard. [ABSTRACT FROM AUTHOR]