Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.     

A study on craniofacial morphology of Japanese subjects with normal occlusion and esthetic profile

This study was designed to properly characterize the cephalometric values of Japanese individuals with both normal occlusion and esthetic profiles. Multivariate statistics were applied to analyze the collected data. Cephalometric values identified are expected to help in the simplification of orthodontic diagnosis. Lateral cephalometric radiographs from 50 men and 50 women with normal occlusion were traced and the dimensions of hard and soft tissues recorded. The corresponding values were classified by cluster analysis, and selected representative values were subjected to principal component analysis. From these values, characteristics of hard and soft tissue morphology were extracted. The subjects were grouped by sex, and subdivided into esthetic and unesthetic profile groups. The principal component scores from each group were plotted on a scattergram and the characteristics of each group investigated. The hard tissue characteristics in men with esthetic profiles were primarily vertical factors, including a tendency for smaller lower facial heights, a smaller mandibular plane angle, and a larger Nasion-ANS/ANS-Menton (N-ANS/ANS-Me). Soft tissue features included a more posteriorly placed maxilla and a high nasal crest. These features yield a less marked maxillary prognathism and a greater nose prominence. In females, hard tissue characteristics associated with esthetic profiles primarily involved the cranial base and posterior facial area. These included a smaller saddle angle, larger articulare angle, and smaller Sella-Articulare/Articlare-Gonion (S-Ar/Ar-Go). Female soft tissue characteristics primarily included retracted upper and lower lips, a shallow inferior sulcus with a smaller lower lip-Frankfort plane angle, and a shorter mentolabial sulcus and subnasale perpendicular-upper lip.     

Hydrogen sulfide causes apoptosis in human pulp stem cells

Introduction

Untreated dental caries will eventually lead to pulpal inflammation. Although much is known regarding the interaction of microbial antigens and the immunologic defense systems of pulp, many aspects of the pathogenesis of pulpitis are not fully understood. The relationship between human pulp stem cells (HPSCs) and the pathogenesis of pulpitis remains among the poorly understood areas. Many of the invading bacteria are known to produce considerable amounts of hydrogen sulfide (H₂S), which causes apoptosis in some tissues. The aims of this study were to determine whether H₂S causes apoptosis in HPSCs and to examine its signaling pathway.

Methods

Stem cells were isolated from human dental pulp and incubated with 50 ng/mL H₂S for 48 hours. To detect apoptosis, the cells were analyzed by using flow cytometry. The mitochondrial signaling pathway was examined by determining mitochondrial membrane depolarization. Activation of the key apoptotic enzymes caspase-9, caspase-8, and caspase-3 was assessed by using enzyme-linked immunosorbent assay. Release of cytochrome C from mitochondria was also determined.

Results

The number of apoptotic cells increased significantly with H₂S treatment from 1.6% to 16.3% (P < .01). Significant increases were also measured in the amounts of caspase-9 and caspase-3 and in cytochrome C release (all P < .01) and in mitochondrial membrane depolarization (P < .05), whereas caspase-8 activity was not found.

Conclusions

H₂S causes apoptosis in HPSCs by activating the mitochondrial pathway. It is suggested that H₂S might be one of the factors modifying the pathogenesis of pulpitis by causing loss of viability of HPSCs through apoptosis.     

Mitochondria as a Platform for Dictating the Cell Fate of Cultured Human Corneal Endothelial Cells

PurposeAiming to clarify the role of mitochondria in cell fate decision of cultured human corneal endothelial cell (cHCEC) subpopulations.MethodsThe mitochondrial respiratory ability were examined with Mito stress and Mito fuel flex test assays using an extracellular flux analyzer (XFe24; Agilent Technologies; Santa Clara, CA) for human corneal endothelium tissues, mature cHCECs and a variety of cell state transitioned cHCECs. Tricarboxylic acid cycle and acetyl-coenzyme A–related enzymes was analyzed by proteomics for cell lysates using liquid chromatography–tandem mass spectrometry for cHCEC subpopulations.ResultsThe maximum oxygen consumption rate was found to become stable depending on the maturation of cHCECs. In the Mito stress tests, culture supplements, epidermal growth factor, SB203580, and SB431543 significantly repressed oxygen consumption rate, whereas a Rho-associated protein kinase inhibitor Y-27632 increased. Tricarboxylic acid cycle and mitochondria acetyl-coenzyme A–related enzymes were selectively upregulated in mature cHCECs, but not in cell state transitioned cHCECs. The maximum oxygen consumption rate was found to be higher in healthy human corneal endothelium tissues than those with deeply reduced cell density. An upregulated tricarboxylic acid cycle was linked with metabolic rewiring converting cHCECs to acquire the mitochondria-dependent oxidative phenotype.ConclusionsMitochondrial metabolic intermediates and energy metabolism are tightly linked to the endothelial cell fate and function. These findings will help us to standardize a protocol for endothelial cell injection.     

Health-related quality of life and prognosis in patients with chronic kidney disease: a 3-year follow-up study

Background

Chronic kidney disease (CKD) is a major global problem and is also associated with a decreased health-related quality of life (HRQOL). The aim of this study was to evaluate measured HRQOL based on the new CKD classification including proteinuria stage, and the effect of measured HRQOL on CKD progression and clinical outcomes over a 3-year period.

Methods

EuroQol (EQ-5D), a generic preference-based questionnaire, was administered to 537 CKD outpatients at the University of Tsukuba Hospital between November and December 2008. We evaluated disease progression in CKD patients including the incidence of end-stage kidney disease (ESKD), cardiovascular disease (CVD) and all-cause mortality over a 3-year follow-up period.

Results

The proportions progressing to the higher stages were 32.6, 20.0, 36.6, 39.5, and 45.8 % from glomerular filtration rate (GFR) stages (G) 1–4, respectively. The proportion progressing to ESKD (G5D) was 0.7 % from G2, 3.9 % from G3b, 20.8 % from G4 and 63.4 % from G5. The incidence of CVD and/or death was 1.2, 4.6, 4.9, 5.3, 8.3 and 21.1 % from G1?G5, respectively. The quality-adjustment weights at G4–5 were significantly lower than at G1–2 and the weights at proteinuria stage (A) 3 were significantly lower than at A1–2. The quality-adjustment weights of patients with events such as 50 % estimated GFR decline, dialysis, CVD, and/or death were significantly lower than those without events.

Conclusion

We showed CKD progression and clinical outcomes over a 3-year period. Quality-adjustment weights in CKD patients were associated with not only disease progression such as initiation of dialysis treatment and incidence of CVD events and all-cause death, but also the level of proteinuria at baseline.