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8
result(s) for
"mtDNAcn"
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Anti-inflammatory and antioxidant activities of ginsenosides and ginseng root extract to counteract obesity
by
Aguzzi, Cristina
,
Eleuteri, Anna Maria
,
Bordoni, Laura
in
Anti-inflammatory agents
,
Antioxidants
,
Ginseng
2024
The objective of this research was to study the possible effects of ginsenosides and ginseng root extract against inflammation and oxidation, classic conditions in obese patients. Different procedures for ginsenoside extraction were evaluated and the best one was performed to obtain a dried extract from ginseng roots. Ginsenosides were quantified by LC–MS; ginsenosides and ginseng extract were tested for their antioxidant and anti-inflammatory properties using THP-1 LPS-stimulated cells. Ginsenosides and the extract were able to marked decrease the expression of interferon-γ while the extract down-regulated the mtDNAcn obtaining levels alike to the control. Moreover, the studied ginsenosides and the extract demonstrated to possess antioxidant activities in the tested cells decreasing the levels of ROS/RNS, markers for protein oxidation, and the activity and expression of NOS and NOX. These findings could pave the way to gain insight into the antioxidant and anti-inflammatory properties of ginseng with the aim to better examine its potential anti-obesity effects.
Journal Article
Inference of forensic body fluids/tissues based on mitochondrial DNA copy number: a preliminary study
2024
The inference of body fluids and tissues is critical in reconstructing crime scenes and inferring criminal behaviors. Nevertheless, present methods are incompatible with conventional DNA genotyping, and additional testing might result in excessive consumption of forensic scene materials. This study aims to investigate the feasibility of distinguishing common body fluids/tissues through the difference in mitochondrial DNA copy number (mtDNAcn). Four types of body fluids/tissues were analyzed in this study - hair, saliva, semen, and skeletal muscle. MtDNAcn was estimated by dividing the read counts of mitochondrial DNA to that of nuclear DNA (RR
mt/nu
). Results indicated that there were significant differences in RR
mt/nu
between different body fluids/tissues. Specifically, hair samples exhibited the highest RR
mt/nu
(log
10
RR
mt/nu
: 4.3 ± 0.28), while semen samples showed the lowest RR
mt/nu
(log
10
RR
mt/nu
: -0.1 ± 0.28). RR
mt/nu
values for DNA samples without extraction were notably higher (approximately 2.9 times) than those obtained after extraction. However, no significant difference in RR
mt/nu
was observed between various age and gender groups. Hierarchical clustering and Kmeans clustering analyses showed that body fluids/tissues of the same type clustered closely to each other and could be inferred with high accuracy. In conclusion, this study demonstrated that the simultaneous detection of nuclear and mitochondrial DNA made it possible to perform conventional DNA analyses and body fluid/tissue inference at the same time, thus killing two birds with one stone. Furthermore, mtDNAcn has the potential to serve as a novel and promising biomarker for the identification of body fluids/tissues.
Journal Article
The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood
2024
Background
Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old.
Methods
This research involved 895 mother–child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath’s epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones.
Results
The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), − 13.22 (− 23.21 to − 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), − 14.13 (− 21.59 to − 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (
P
= 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (
P
= 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than − 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than − 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than − 1.35, followed by a plateau between − 1.35 and − 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than − 0.67.
Conclusions
In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.
Journal Article
Mitochondrial DNA Copy Number Adaptation as a Biological Response Derived from an Earthquake at Intrauterine Stage
by
Libni A. Torres-Olascoaga
,
Robert O. Wright
,
Sandra B. Parra-Hernández
in
Body mass index
,
DNA Copy Number Variations
,
DNA, Mitochondrial
2021
An altered mitochondrial DNA copy number (mtDNAcn) at birth can be a marker of increased disease susceptibility later in life. Gestational exposure to acute stress, such as that derived from the earthquake experienced on 19 September 2017 in Mexico City, could be associated with changes in mtDNAcn at birth. Our study used data from the OBESO (Biochemical and Epigenetic Origins of Overweight and Obesity) perinatal cohort in Mexico City. We compared the mtDNAcn in the umbilical cord blood of 22 infants born before the earthquake, 24 infants whose mothers were pregnant at the time of the earthquake (exposed), and 37 who were conceived after the earthquake (post-earthquake). We quantified mtDNAcn by quantitative real-time polymerase chain reaction normalized with a nuclear gene. We used a linear model adjusted by maternal age, body mass index, socioeconomic status, perceived stress, and pregnancy comorbidities. Compared to non-exposed newborns (mean ± SD mtDNAcn: 0.740 ± 0.161), exposed and post-earthquake newborns (mtDNAcn: 0.899 ± 0.156 and 0.995 ± 0.169, respectively) had increased mtDNAcn, p = 0.001. The findings of this study point at mtDNAcn as a potential biological marker of acute stress and suggest that experiencing an earthquake during pregnancy or before gestation can have programing effects in the unborn child. Long-term follow-up of newborns to women who experience stress prenatally, particularly that derived from a natural disaster, is warranted.
Journal Article
Paternal Age Amplifies Cryopreservation-Induced Stress in Human Spermatozoa
by
Luddi, Alice
,
Luongo, Francesca Paola
,
Haxhiu, Alesandro
in
acrosomal reaction
,
Aging
,
Comparative analysis
2024
The global fall in male fertility is a complicated process driven by a variety of factors, including environmental exposure, lifestyle, obesity, stress, and aging. The availability of assisted reproductive technology (ART) has allowed older couples to conceive, increasing the average paternal age at first childbirth. Advanced paternal age (APA), most often considered male age ≥40, has been described to impact several aspects of male reproductive physiology. In this prospective cohort study including 200 normozoospermic patients, 105 of whom were ≤35 years (non-APA), and 95 of whom were ≥42 years (APA), we assessed the impact of paternal age on different endpoints representative of sperm quality and cryopreservation tolerance. Non-APA patients had superior fresh semen quality; DNA fragmentation was notably increased in APA as compared to non-APA individuals (21.7% vs. 15.4%). Cryopreservation further increased the DNA fragmentation index in APA (26.7%) but not in non-APA patients. Additionally, APA was associated with increased mtDNAcn in both fresh and frozen/thawed sperm, which is indicative of poorer mitochondrial quality. Cryopreservation negatively impacted acrosome integrity in both age groups, as indicated by reduced incidences of unreacted acrosome in relation to fresh counterparts in non-APA (from 71.5% to 57.7%) and APA patients (from 75% to 63%). Finally, cryopreservation significantly reduced the phosphorylation status of proteins containing tyrosine residues in sperm from young males. Therefore, the present findings shed light on the effects of paternal age and cryopreservation on sperm quality and serve as valuable new parameters to improve our understanding of the mechanisms underlying sperm developmental competence that are under threat in current ART practice.
Journal Article
Positive association and future perspectives of mitochondrial DNA copy number and telomere length – a pilot twin study
2021
Recent experimental and population studies have highlighted the existence of telomere-mitochondria interplay. Besides studies revealing the molecular mechanisms underlying the associations of telomere defects and mitochondrial functions, investigations of mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in healthy and disease phenotypes have likewise begun, with the aim of gaining more insights about their relationship in humans.
A total of 142 asymptomatic adult twins, comprising 96 monozygotic (MZ) and 46 dizygotic (DZ) twins (mean age: 50.54 ±15.43 years), members of the Hungarian Twin Registry, were included in the analysis. Applying the qPCR standard curve method, we investigated the relationship of mtDNA copy number, telomere length and clinical data, besides assessing co-twin similarities of MZ and DZ twins for their mtDNAcn and TL measures.
We found that twins were similar in their intraclass correlation coefficients irrespective of zygosity, suggesting a possibly more important role of common (shared) environmental factors compared to non-shared (unique) environmental and to a smaller degree also individual genetic influences. We confirmed a significant positive association between mtDNAcn and TL (
= 0.28,
< 0.01) in age- and sex-corrected analysis. Following bivariate estimates and correction with significant predictors, the independent positive associations were further verified.
Our results extend the until now modest number of studies investigating mtDNAcn and TL simultaneously in humans. In addition, we are the first to examine the relationship between mtDNAcn and telomere length in MZ and DZ twin subjects.
Journal Article
Differential Cellular Response to Mercury in Non-Farmed Fish Species Based on Mitochondrial DNA Copy Number Variation Analysis
by
Traina, Anna
,
Sprovieri, Mario
,
Pappalardo, Anna Maria
in
Analysis
,
Aquaculture
,
Aquatic ecosystems
2024
Mercury (Hg) pro-oxidant role on biological systems and its biogeochemical cycle represent a serious threat due to its persistence in marine environment. As the mitochondrial genome is exposed to reactive oxygen species (ROS), the aim of the present study is the validation of the variation in the number of mitochondrial DNA copies (mtDNAcn) as biomarker of oxidative stress in aquatic environment. During summer 2021, three selected fish species (Mullus barbatus, Diplodus annularis and Pagellus erythrinus) were collected in Augusta Bay, one of the most Mediterranean contaminated areas remarkable by past Hg inputs, and in a control area, both in the south-east of Sicily. The relative mtDNAcn was evaluated by qPCR on specimens of each species from both sites, characterized respectively by higher and lower Hg bioaccumulation. M. barbatus and P. erythrinus collected in Augusta showed a dramatic mtDNAcn reduction compared to their control groups while D. annularis showed an incredible mtDNAcn rising suggesting a higher resilience of this species. These results align with the mitochondrial dynamics of fission and fusion triggered by environmental toxicants. In conclusion, we suggest the implementation of the mtDNAcn variation as a valid tool for the early warning stress-related impacts in aquatic system.
Journal Article
Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers
2021
Background Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure workers has not been fully evaluated. Aim The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs‐Exposure. Methods and Results We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real‐time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1‐OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs‐exposure [β (95% CI) = −0.420 (−0.469, −0.372), p < .001], male [β (95% CI) = −0.058 (−0.103, −0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = −0.051 (−0.095, −0.008), p = .020]. Conclusion The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.
Journal Article