Effect of dialyzer membranes on mortality in uremic patients undergoing long-term hemodialysis: A Nationwide population-based study using the Taiwan Dialysis Registry Data System 2005-2012.

The characteristics in dialyzer are associated with mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This study is to investigate the effects of dialyzer membranes on 3-year mortality in ESRD patients. From the long-term nationwide population database. Prevalent HD patients during 2005-2012 were enrolled. Our main analysis to calculate the effect was cox regression multivariate model. Overall, the mean age of all population (N = 73 565) was 61.0 ± 13.6 years, the observation period is 2.46 years ±0.98 within 3 years and 64.6% used polysulfone (PS), polymethyl methacrylate (PMMA) (11.6%), polyethersulfone (11.4%), and cellulose triacetate (CTA) (10.7%), ethylene vinyl alcohol (EVAL) (hazard ratio [HR] 2.72, 95% confidence interval [CI] 1.71-4.33) and CTA (HR 1.35, 95% CI 1.12-1.64) were associated with higher mortality than PS, but PMMA was not. EVAL and CTA adversely affected mortality and PMMA had no protective role. Further investigations on membrane characters on HD patients are warranted. Taipei Medical University (TMU) (TMU-JIRB (No. N201804051).

Modulation of mitochondrial nucleoid structure during aging and by mtDNA content in Drosophila.

Mitochondrial DNA (mtDNA) encodes gene products that are essential for oxidative phosphorylation. They organize as higher order nucleoid structures (mtNucleoids) that were shown to be critical for the maintenance of mtDNA stability and integrity. While mtNucleoid structures are associated with cellular health, how they change in situ under physiological maturation and aging requires further investigation. In this study, we investigated the mtNucleoid assembly at an ultrastructural level in situ using the TFAM-Apex2 Drosophila model. We found that smaller and more compact TFAM-nucleoids are populated in the mitochondria of indirect flight muscle of aged flies. Furthermore, mtDNA transcription and replication were cross-regulated in the mtTFB2-knockdown flies as in the mtRNAPol-knockdown flies that resulted in reductions in mtDNA copy numbers and nucleoid-associated TFAM. Overall, our study reveals that the modulation of TFAM-nucleoid structure under physiological aging, which is critically regulated by mtDNA content.

Drosophila MICOS knockdown impairs mitochondrial structure and function and promotes mitophagy in muscle tissue.

The mitochondrial contact site and cristae organizing system (MICOS) is a multi-protein interaction hub that helps define mitochondrial ultrastructure. While the functional importance of MICOS is mostly characterized in yeast and mammalian cells in culture, the contributions of MICOS to tissue homeostasis in vivo remain further elucidation. In this study, we examined how knocking down expression of Drosophila MICOS genes affects mitochondrial function and muscle tissue homeostasis. We found that CG5903/MIC26-MIC27 colocalizes and functions with Mitofilin/MIC60 and QIL1/MIC13 as a Drosophila MICOS component; knocking down expression of any of these three genes predictably altered mitochondrial morphology, causing loss of cristae junctions, and disruption of cristae packing. Furthermore, the knockdown flies exhibited low mitochondrial membrane potential, fusion/fission imbalances, increased mitophagy, and limited cell death. Reductions in climbing ability indicated deficits in muscle function. Knocking down MICOS genes also caused reduced mtDNA content and fragmented mitochondrial nucleoid structure in Drosophila Together, our data demonstrate an essential role of Drosophila MICOS in maintaining proper homeostasis of mitochondrial structure and function to promote the function of muscle tissue.

Coordinated organization of mitochondrial lamellar cristae and gain of COX function during mitochondrial maturation in Drosophila.

Mitochondrial cristae contain electron transport chain complexes and are distinct from the inner boundary membrane (IBM). While many details regarding the regulation of mitochondrial structure are known, the relationship between cristae structure and function during organelle development is not fully described. Here, we used serial-section tomography to characterize the formation of lamellar cristae in immature mitochondria during a period of dramatic mitochondrial development that occurs after Drosophila emergence as an adult. We found that the formation of lamellar cristae was associated with the gain of cytochrome c oxidase (COX) function, and the COX subunit, COX4, was localized predominantly to organized lamellar cristae. Interestingly, 3D tomography showed some COX-positive lamellar cristae were not connected to IBM. We hypothesize that some lamellar cristae may be organized by a vesicle germination process in the matrix, in addition to invagination of IBM. OXA1 protein, which mediates membrane insertion of COX proteins, was also localized to cristae and reticular structures isolated in the matrix additional to the IBM, suggesting that it may participate in the formation of vesicle germination-derived cristae. Overall, our study elaborates on how cristae morphogenesis and functional maturation are intricately associated. Our data support the vesicle germination and membrane invagination models of cristae formation.

3D Mitochondrial Ultrastructure of Drosophila Indirect Flight Muscle Revealed by Serial-section Electron Tomography.

Mitochondria are cellular powerhouses that produce ATP, lipids, and metabolites, as well as regulate calcium homeostasis and cell death. The unique cristae-rich double membrane ultrastructure of this organelle is elegantly arranged to carry out multiple functions by partitioning biomolecules. Mitochondrial ultrastructure is intimately linked with various functions; however, the fine details of these structure-function relationships are only beginning to be described. Here, we demonstrate the application of serial-section electron tomography to elucidate mitochondrial structure in Drosophila indirect flight muscle. Serial-section electron tomography may be adapted to study any cellular structure in three-dimensions.

Management of viral oral ulcers in children using Chinese herbal medicine: A report of two cases.

OBJECTIVE: Viral oral ulcers are common presentations in pediatric clinics. Although self-limiting, painful ulcerative lesions and inflamed mucosa can decrease oral intake and lead to dehydration. Despite the widespread use of Chinese herbal medicine (CHM) for pediatric upper respiratory disease in Taiwan, there is little evidence for its effectiveness as an antipyretic or in aiding ulcer healing for children with viral oral ulcers. We report two cases of children who presented with viral oral ulcers to illustrate the potential efficacy of CHM treatment in recovery from herpangina (HA) and herpetic gingivostomatitis (HGS). CLINICAL FEATURES AND OUTCOME: A 10-year-old girl with HA presented with an acute febrile illness associated with small vesicular or ulcerative lesions on the posterior oropharyngeal structures. The family refused western medicine due to a prior anaphylactic skin rash when she had taken sulfa drugs. The other patient was a 4-year-old boy with complaints of painful ulcers and hemorrhagic crusts on the lips. He was diagnosed with HGS and had received ibuprofen and supportive treatments such as hydration and local anesthesia spray for days, characterized by fever, anorexia, and nausea to no effect. Because the patients were suffering from the damp-heat syndrome according to Traditional Chinese Medicine (TCM) differentiation, both were treated using the same herbal formulas powder prescription, named Liang Ge San (LGS) and Gan Lu Xiao Du Dan (GLXDD). After several days of CHM treatment, the oral ulcers were in regression. Follow-up of the frontal view in both patients showed satisfactory disappearance of the sick furred tongue. CONCLUSIONS: The results of these case reports show that the early prescription of CHM is an effective modality of alternative treatment for viral oral ulcers. To our knowledge, this is the first report of CHM treatment hastening the recovery from febrile disease with viral oral ulcers in Taiwan. Future experimental studies to determine the definitive mechanism and clinical trials are warranted.