Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-alpha-induced NF-kappa B transcriptional activity in the NF-kappa B luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of I kappa B and NF-kappa B in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-kappa B phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes

Ca2+ Signaling Triggered by Shear-Autocrine P2X Receptor Pathway in Rat Atrial Myocytes

Background/Aims: The atrium is exposed to high shear stress during heart failure and valvular diseases. We aimed to understand atrial shear-induced Ca2+ signaling and its underlying mechanisms. Methods: Pressurized micro-flow was applied to single rat atrial myocytes, and Ca2+ signal, membrane potential, and ATP release were assessed using confocal imaging, patch clamp technique, and luciferin-luciferase assay, respectively. Results: Shear stress (∼16 dyn/cm2) induced global Ca2+ waves (∼0.1 events/s) from the periphery to the center of cells in a transverse direction (“T-wave”; ∼145 μm/s). Pharmacological interventions and simultaneous recording of membrane potential and Ca2+ demonstrated that shear-induced T-waves resulted from action potential (AP)-triggered Ca2+ release from the sarcoplasmic reticulum. T-waves were not sensitive to inhibitors of known shear signaling mechanisms except connexin hemichannels and ATP release. Shear stress caused ATP release from these myocytes (∼1.1x10-17 moles/unit membrane, µm2); ATP release was increased by enhancement of connexin hemichannels and suppressed by inhibition of the hemichannels, but not affected by inhibitors of other ATP release pathways. Blockade of P2X receptor, but not pannexin or the Na+-Ca2+ exchanger, eliminated shear-induced T-wave initiation. Conclusion: Our data suggest that shear stress triggers APs and concomitant Ca2+ signaling via activation of P2X receptors by connexin hemichannel-mediated ATP release in atrial myocytes

Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study

Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD

Influence of Friction Stir Welding on Mechanical Properties of Butt Joints of AZ61 Magnesium Alloy

In this study, the effect of heat input on the mechanical properties and fracture behaviors of AZ61 magnesium alloy joints has been studied. Magnesium alloy AZ61 plates with thickness of 5 mm were welded at different ratios of tool rotational speed to welding speed (ω/ν). The average ultimate tensile strength of all weld conditions satisfying a ω/ν ratio of 3 reached 100% of the strength of the base material. Fractures occurred at the interface between the thermomechanical affected zone at advancing side and the stir zone in all welded specimens. From the scanning electron microscope and electron backscatter diffraction analysis, it was determined that the interface between the thermomechanical affected zone and the stir zone, which is the region where the grain orientation changes, was the weakest part; the advancing side region was relatively weaker than the retreating side region because the grain orientation change occurred more dramatically in the advancing side region