Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis

ECG measurement on a chair without conductive contact

For the purpose of long-term, everyday electrocardiogram (ECG) monitoring, we present a convenient method of ECG measurement without direct conductive contact with the skin while subjects sat on a chair wearing normal clothes. Measurements were made using electrodes attached to the back of a chair, high-input-impedance amplifiers mounted on the electrodes, and a large ground-plane placed on the chair seat. ECGs were obtained by the presented method for several types of clothing and compared to ECGs obtained from conventional measurement using Ag-AgCl electrodes. Motion artifacts caused by usual desk works were investigated. This study shows the feasibility of the method for long-term, convenient, everyday use

Characteristics of Sawdust and Cocopeat Beddings, and Their Usefulness According to the Fan and Pen Location for Rearing Hanwoo Cattle

This study was designed to examine the characteristics of sawdust and cocopeat bedding materials, including physicochemical properties (Exp. I) and on-farm trial (Exp. II). In Exp. I, the proportion of particle size was in the order of sawdust> cocopeat India>cocopeat Vietnam (pcocopeat Vietnam>sawdust (p<0.05), thus cocopeat treatments showed 4.4 times higher bedding cost than sawdust. The water absorption rates were 702.0% in cocopeat India, 678.3% in cocopeat Vietnam, and 444.0% in sawdust, showing cocopeat had approximately 1.5 times higher water absorption rate than sawdust. Moisture evaporation rates after 12 h of air blowing (2.00 m/s) were higher (p<0.05) in cocopeat Vietnam (80.4%) than sawdust (71.2%) and cocopeat India (72.8%). In vitro ammonia emissions were higher (p<0.05) in sawdust (2.71 mg/m2/h) than cocopeat India (1.59 mg/m2/h) and Vietnam (1.22 mg/m2/h), and total ammonia emissions were higher (p<0.05) in sawdust (37.02 mg/m2) than cocopeat India (22.51 mg/m2) and Vietnam (13.60 mg/m2). In Exp. II, an on-farm trial was conducted with 48 Hanwoo cattle in 16 pens using the same bedding materials as in Exp. I, with fan (blowing 2.00 m/s) and no fan treatments, and feed bunk side (FB) and water supply side (WS) within a pen (4.5 m, width×9.0 m, length). Beddings were replaced with fresh bedding materials when moisture concentrations were over 65%. No interactions among treatments were detected for moisture concentration and increment rates, and ammonia concentrations, but a significant effect was observed (p<0.01) for each of the treatments. Both concentrations and increment rate of moisture were higher (p<0.01) in the beddings without fan than with fan. Moisture concentrations and increment rate within a pen were also higher (p<0.01) in FB than WS. Thus, the whole no-fan-FB and sawdust-fan-FB were replaced with fresh bedding material between 4 to 5 experimental weeks. The ammonia concentrations and pH of beddings were not significantly different among treatments. Therefore, using cocopeat bedding with a blowing fan can extend twice the bedding utilization period, and WS within a pen showed twice the bedding-life compared to FB. Despite the outstanding characteristics of cocopeat compared with sawdust, using cocopeat as an alternative for sawdust bedding is not recommended for cattle management, considering it has 4.4 times higher bedding cost and a dust production problem

Korean Ginseng-Induced Occupational Asthma and Determination of IgE Binding Components

A number of case reports on occupational asthma caused by herbal medicines have been issued, for example, on Sanyak, Chunkung, Banha, and Brazilian ginseng. Recently, cases of occupational asthma induced by Sanyak and Korean ginseng have been reported, but the pathogenic mechanisms involved are unknown. This study was carried out to evaluate the immunologic mechanism underlying Korean ginseng-induced occupational asthma. A patient engaged in Korean ginseng wholesale was referred for recurrent dyspnea, wheezing, and nasal symptoms, which were aggravated at work. Allergen bronchial provocation testing to Korean ginseng extract showed a typical immediate response, and skin prick testing to Korean ginseng extract also showed a strong positive response. Moreover, serum-specific IgE levels to Korean ginseng extract were significantly higher than in controls. Enzyme-linked immunosorbent assay (ELISA) inhibition tests showed a dose-dependent inhibition by Korean ginseng, but not by Dermatophagoides farinae, wheat flour, or Chinese balloon flower. Sodium dodecylsulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblotting revealed four specific Immunoglobulin E (IgE) binding components at 26, 30, 47, and 60 kDa, which were not bound by control sera. These results strongly suggest that occupation asthma induced by Korean ginseng is induced via an IgE-mediated mechanism

GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base

The gap junction complex functions as a transport channel across the membrane. Among gap junction subunits, gap junction protein ??1 (GJA1) is the most commonly expressed subunit. A recent study showed that GJA1 is necessary for the maintenance of motile cilia; however, the molecular mechanism and function of GJA1 in ciliogenesis remain unknown. Here, we examined the functions of GJA1 during ciliogenesis in human retinal pigment epithelium-1 and Xenopus laevis embryonic multiciliated-cells. GJA1 localizes to the motile ciliary axonemes or pericentriolar regions beneath the primary cilium. GJA1 depletion caused malformation of both the primary cilium and motile cilia. Further study revealed that GJA1 depletion affected several ciliary proteins such as BBS4, CP110, and Rab11 in the pericentriolar region and basal body. Interestingly, CP110 removal from the mother centriole was significantly reduced by GJA1 depletion. Importantly, Rab11, a key regulator during ciliogenesis, was immunoprecipitated with GJA1 and GJA1 knockdown caused the mislocalization of Rab11. These findings suggest that GJA1 regulates ciliog

Increased O-GlcNAcylation of Drp1 by amyloid-beta promotes mitochondrial fission and dysfunction in neuronal cells.

As a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in mitochondria dynamics leads to their dysfunction, which implicated in neurodegenerative diseases. However, how mitochondria alteration and glucose defect contribute to pathogenesis of Alzheimer's disease (AD) is still largely unknown. Dynamin-related protein 1 (Drp1) is an essential regulator for mitochondria fission. Among various posttranslational modifications, O-GlcNAcylation plays a role as a sensor for nutrient and oxidative stress. In this study, we identified that Drp1 is regulated by O-GlcNAcylation in AD models. Treatment of Aβ as well as PugNAc resulted in mitochondrial fragmentation in neuronal cells. Moreover, we found that AD mice brain exhibits an upregulated Drp1 O-GlcNAcylation. However, depletion of OGT inhibited Drp1 O-GlcNAcylation in Aβ-treated cells. In addition, overexpression of O-GlcNAc defective Drp1 mutant (T585A and T586A) decreased Drp1 O-GlcNAcylation and Aβ-induced mitochondria fragmentation. Taken together, these finding suggest that Aβ regulates mitochondrial fission by increasing O-GlcNAcylation of Drp1

Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation

Vascular calcification, a pathologic response to defective calcium and phosphate homeostasis, is strongly associated with cardiovascular mortality and morbidity. In this study, we have observed that pyruvate dehydrogenase kinase 4 (PDK4) is upregulated and pyruvate dehydrogenase complex phosphorylation is increased in calcifying vascular smooth muscle cells (VSMCs) and in calcified vessels of patients with atherosclerosis, suggesting that PDK4 plays an important role in vascular calcification. Both genetic and pharmacological inhibition of PDK4 ameliorated the calcification in phosphate-treated VSMCs and aortic rings and in vitamin D3-treated mice. PDK4 augmented the osteogenic differentiation of VSMCs by phosphorylating SMAD1/5/8 via direct interaction, which enhances BMP2 signaling. Furthermore, increased expression of PDK4 in phosphate-treated VSMCs induced mitochondrial dysfunction followed by apoptosis. Taken together, our results show that upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification

Occupational Asthma and Rhinitis Induced by a Herbal Medicine, Wonji (Polygala tenuifolia)

Occupational asthma is induced by many agents, including herbal materials, that are exposed in working places. Although there are a few case reports for occupational allergy induced by herbal materials, there is none for that induced by Wonji (Polygala tenuifolia). This study was conducted to evaluate clinical characteristics and immunologic mechanism of Wonji-induced asthma in a exposed-worker. A patient who complained of asthma and rhinitis symptoms, and who had worked in a herbal manufacturing factory for 8 yr, underwent a skin prick test with crude extract of Wonji under the impression of occupational asthma induced by the agent. The patient had a strong positive response to the extract on the skin prick test. Allergen bronchial challenge to the extract demonstrated a typical dual response. Serum specific IgE level to the extract was higher in the patient than in healthy controls, and ELISA inhibition test revealed complete inhibition of IgE binding with the extract, but no inhibition with Der p 2 or mugwort extracts. Six IgE binding components to the extract (10, 25, 28, 36, 50, and 90 kDa) were detected using SDS-PAGE and immunoblot analysis. These findings suggest that Polygala tenuifolia, a herbal material, can induce IgE-mediated bronchoconstriction in exposed workers