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Objectives: We aimed to explore mitochondrial DNA (mtDNA) copy number, damage, repair and degradation in peripheral blood mononuclear cells (PBMCs) of patients with depression and to compare the results with healthy subjects. Meth...
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Objectives: We aimed to explore mitochondrial DNA (mtDNA) copy number, damage, repair and degradation in peripheral blood mononuclear cells (PBMCs) of patients with depression and to compare the results with healthy subjects. Methods: Total genomic DNA was isolated from PBMCs of 25 depressed and 60 healthy subjects before, immediately after, and 3 h after the exposure to H2O2. Evaluation of mtDNA copy number was performed using real-time PCR and 2-Delta Ct methods. Semi-long run real-time PCR was used to estimate the number of mtDNA lesions. Results: Baseline mtDNA copy number did not differ in cells of healthy and depressed subjects; however, it was negatively correlated with the severity of the episode. After a 10-min challenge with hydrogen peroxide (H2O2), depressed patients' PBMCs exhibited slower changes of the copy number, indicating a lower efficiency of mtDNA degradation compared to controls. Moreover, a significantly higher number of mtDNA lesions was found in depressed patients at the baseline as well as at other experimental time points. mtDNA lesions were also elevated in depressed patient cells immediately after H2O2 exposure. Induction of oxidative stress had no significant influence on the cells of controls. Conclusions: We are the first to show that impairment in repair and degradation of mtDNA may be involved in the pathophysiology of depression.
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Energy balance in dairy cows changes during the course of lactation due to alterations in voluntary feed intake and energy required for milk synthesis. To adapt to the demands of lactation, energy metabolism needs to be regulated ...
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Energy balance in dairy cows changes during the course of lactation due to alterations in voluntary feed intake and energy required for milk synthesis. To adapt to the demands of lactation, energy metabolism needs to be regulated and coordinated in key organs such as adipose tissue (AT), liver, and mammary gland. Mitochondria are the main sites of energy production in mammalian cells and their number varies depending on age, organ, and physiological condition. The copy number of the mitochondrial genome, the mitochondrial DNA (mtDNA), reflects the abundance of mitochondria within a cell and is regulated by transcriptional and translational factors. Environmental, physiological, and energetic conditions change during lactation and we thus hypothesized that these changes may influence the mtDNA copy number and the abundance of genes regulating mitochondrial biogenesis. Therefore, we aimed to provide an overview of mitochondrial biogenesis in liver, subcutaneous (sc)AT, mammary gland, and peripheral blood cells during early and late lactation in dairy cows. German Holstein cows (n - 21) were fed according to their requirements, and biopsies from scAT, liver, mammary gland, and blood were collected in early and late lactation and assayed for relative mtDNA copy numbers and the mRNA abundance of genes regulating mitochondrial biogenesis, such as nuclear-respiratory factor 1 and 2 (NRF-1, NRF-2), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α). The number of mtDNA copies increased from early to late lactation in all tissues, whereas that in peripheral blood cells was greater in early compared with late lactation. Moreover, mitochondrial activity enzymes (i.e., citrate synthase and cytochrome c oxidase) increased from early to late lactation in scAT. Comparing the number of mtDNA copies between tissues and blood in dairy cows, the highest mtDNA content was observed in liver. The mRNA abundance of genes related to mitochondrial biogenesis changed in a tissue-specific manner when comparing early versus late lactation. The mtDNA copy number was associated with transcriptional factors only in AT, suggesting nontranscriptional regulation of mtDNA in the other tissues. We detected strong correlations between peripheral blood mtDNA and tissue mtDNA content in early lactation. Peripheral blood forms an appropriate medium to display the cellular content of mtDNA copy numbers and consequently the cellular energy status of tissues during early lactation.
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Abstract Objective To investigate the association between mitochondrial DNA copy number (mtDNAcn) and semen quality. Design A cross‐sectional study. Setting Hubei Province Human Sperm Bank of China (from April 2017 to July 2018)....
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Abstract Objective To investigate the association between mitochondrial DNA copy number (mtDNAcn) and semen quality. Design A cross‐sectional study. Setting Hubei Province Human Sperm Bank of China (from April 2017 to July 2018). Population A total of 1164 healthy male sperm donors with 5739 specimens. Main outcome measures Real‐time quantitative polymerase chain reaction (RT‐PCR) was used to measure sperm mtDNAcn. We also determined semen volume, concentration and motility parameters (progressive motility, nonprogressive motility and immotility). Methods Mixed‐effect models and general linear models were uses. Results After adjusting for relevant confounding factors, mixed‐effect models revealed diminished sperm motility (progressive and total), concentration, and total count across the quartiles of mtDNAcn (all P?收起
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Objectives: Oxidative stress has been hypothesized as a central component of both placental and endothelial dysfunction, leading to PE. This oxidative stress leading to mitochondrial dysfunction may be due to variations in mtDNA c...
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Objectives: Oxidative stress has been hypothesized as a central component of both placental and endothelial dysfunction, leading to PE. This oxidative stress leading to mitochondrial dysfunction may be due to variations in mtDNA copy numbers as an adaptive response. In the present study we aimed to analyse mtDNA copy numbers in the placenta obtained after delivery from the women with PE as compared to the controls.
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Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and m...
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Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and mitochondrial dysfunction are thought to be central to the cellular aging process. The present study examined the association between mitochondrial DNA (mtDNA) copy number and telomere length in a sample of medically healthy adults. Participants (total n = 392) were divided into 4 groups based on the presence or absence of early life adversity and lifetime psychopathology: No Adversity/No Disorder, n = 136; Adversity/No Disorder, n = 91; No Adversity/Disorder, n = 46; Adversity/Disorder, n = 119. Telomere length and mtDNA copy number were measured using quantitative polymerase chain reaction. There was a positive correlation between mtDNA and telomere length in the entire sample (r = 0.120, p < 0.001) and in each of the four groups of participants (No Adversity/No Disorder, r = 0.291, p = 0.001; Adversity/No Disorder r = 0.279, p = 0.007; No Adversity/Disorder r = 0.449, p = 0.002; Adversity/Disorder, r = 0.558, p < 0.001). These correlations remained significant when controlling for age, smoking, and body mass index and establish an association between mtDNA and telomere length in a large group of women and men both with and without early adversity and psychopathology, suggesting co-regulation of telomeres and mitochondrial function. The mechanisms underlying this association may be important in the pathophysiology of age-related medical conditions, such as heart disease and cancer, as well as for stress-associated psychiatric disorders. (C) 2015 Elsevier Inc. All rights reserved.
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摘要 :
Background: Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colore...
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Background: Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colorectal cancer (CRC) diagnosis and CRC prognosis, findings have been inconsistent, and no study has specifically investigated the association of pre-diagnostic mtDNAcn with CRC survival.
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摘要 :
Telomeres cap the ends of eukaryotic chromosomes,
and the telomere length (TL) is related to cellular age.
The mitochondrial DNA copy number (mtDNAcn)
reflects the abundance of mitochondria in a cell. In
addition to generating...
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Telomeres cap the ends of eukaryotic chromosomes,
and the telomere length (TL) is related to cellular age.
The mitochondrial DNA copy number (mtDNAcn)
reflects the abundance of mitochondria in a cell. In
addition to generating energy, mitochondria are also
the main producers of reactive oxygen species, which in
turn can accelerate TL attrition and impair mitochondrial
function. Nutrition in early life could influence
mtDNAcn and TL in later life. In the present study,
we investigated the effects of feeding different levels
of milk replacer (MR) on TL shortening and energetic
status by examining mtDNAcn of heifers during their
first year of life. In this study, whole blood samples
were obtained from German Holstein heifer calves 36
to 48 h after birth (wk 1) and at wk 12 and wk 16 of
life (n = 37), as well as from 31 calves when reaching
1 yr of age. Calves were fed either a high level of MR
(14% solids) at 10 L/d (1.4 kg of MR/d; n = 18) or a
restrictive low level at 5.7 L/d (0.8 kg of MR/d; n = 19)
until linear weaning in wk 13 to 14 of life. Additional
whole blood samples were taken from their respective
dams 36 to 48 h after calving. Relative TL (qT) and
mtDNAcn in cells from whole blood were measured by
multiplex quantitative PCR. The greatest qT values
were observed in neonates (36–48 h after birth), with
decreasing qT values thereafter. Delta qT values were
calculated as ΔqT = qT (first year of life) − initial qT
(36–48 h after birth). We found no effect of the feeding
regimen on qT values, but qT decreased with age.
The mtDNAcn was lowest in neonates, increased until
wk 12 of life, and then remained at a constant level
until after weaning (wk 16). After the first year of life,
mtDNAcn was decreased and returned to levels comparable
to those of the neonatal stage. No differences
in mtDNAcn were detectable between feeding groups
within each time point. When comparing the values of
qT and mtDNAcn between the calves and their dams
after calving (36–48 h after birth and after calving),
greater values were observed in calves than in dams.
Delta qT values were negative in all but 2 calves (on
the restricted diet), indicating that the change in TL
with age was not uniform among individual animals,
whereas no difference in mean ΔqT values occurred
between the feeding groups. Additional analyses of the
correlation between qT, mtDNAcn, and various indicators
of oxidative status from birth until wk 16 of life
did not indicate major interactions between oxidative
status, qT and mtDNAcn. The results of this study
support an age-dependent decrease of TL in calves
independent of the MR feeding level and show the dynamic
changes of mtDNAcn in early life.
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摘要 :
Research question: To examine associations between sperm mitochondrial DNA copy number (mtDNAcn), sperm mitochondrial DNA deletions (mtDNAdel), semen parameters and clinical infertility in an IVF setting.
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Background Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)-infected persons. This study evaluated the cross-sectional and...
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Background Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)-infected persons. This study evaluated the cross-sectional and longitudinal change of mtDNA CN by HIV markers.
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Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset The mutant huntingtin protein leads to mitochondri...
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Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led to the investigation of the mitochondrial DNA (mtDNA) copy number relative to nuclear DNA (nDNA) in leukocytes from carriers of the HD mutation compared to healthy individuals. We found significantly reduced mtDNA/nDNA in HD mutation carriers compared to controls. A longitudinal study of archive DNA sample pairs from HD patients revealed a biphasic pattern of increasing mtDNA/nDNA before onset of motor symptoms and decreasing mtDNA/nDNA after. (C) 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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