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1.
J Clin Lab Anal ; 37(21-22): e24987, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37968799

ABSTRACT

BACKGROUND: An accurate genetic diagnosis of Becker muscular dystrophy (BMD) can be sometimes challenging due to deep intronic DMD variants. Here, we report on the genetic diagnosis of a BMD patient with a novel deep-intronic splice-altering variant in DMD. METHODS: The index case was a 3.8-year-old boy who was suspected of having a diagnosis of BMD based on his clinical, muscle imaging, and pathological features. Routine genomic detection approaches did not detect any disease-causing variants in him. Muscle-derived DMD mRNA studies, followed by genomic Sanger sequencing and in silico bioinformatic analyses, were performed in the patient. RESULTS: DMD mRNA studies detected a cryptic exon-containing transcript and normally spliced DMD transcript in the patient. The cryptic exon-containing transcript encoded a frameshift and premature termination codon (NP_003997.1:p.[=,Asp2740Valfs*52]). Further genomic Sanger sequencing and bioinformatic analysis identified a novel deep-intronic splice-altering variant in DMD (c.8217 + 23338A > G). The novel variant strengthened a cryptic donor splice site and activated a cryptic acceptor splice site in the deep-intronic region of DMD intron 55, resulting in the activation of a new dystrophin cryptic exon found in the patient. CONCLUSION: Our case report expands the genetic spectrum of BMD and highlights the essential role of deep-intronic cryptic exon-activating variants in genetically unsolved BMD patients.


Subject(s)
Muscular Dystrophy, Duchenne , Humans , Male , Child, Preschool , Muscular Dystrophy, Duchenne/genetics , Dystrophin/genetics , Mutation , Exons/genetics , Frameshift Mutation , RNA, Messenger/genetics
2.
Phys Rev E ; 107(1-1): 014606, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36797868

ABSTRACT

Collective motion of animal groups such as fish schools and bird flocks in three-dimensional (3D) space are modeled by considering a topological (Voronoi) neighborhood. The tridimensionality of the group is quantified. Apart from the patterns of swarming, schooling, and milling, we identify a 3D bait ball around the phase transition boundary. More significantly, we find that by considering a blind angle in this topology based model, an individual interacts statistically with six to seven neighbors, consistent precisely with the previous field observations of the starling flocks. This model could be expected to enable more insightful investigation on realistic collective motion of shoals or flocks.

3.
Sci Rep ; 12(1): 15784, 2022 09 22.
Article in English | MEDLINE | ID: mdl-36138093

ABSTRACT

The collapse lake area due to coal mining in Huaibei shows high biodiversity, but the bacterial community composition and diversity in the lake sediments are still rarely studied. Therefore, based on 16S rRNA high-throughput sequencing and combined with analysis of environmental factors, we comparatively analyzed the bacterial community composition and diversity of surface sediments from East Lake (DH) and South Lake (NH) and Middle Lake (ZH) in the collapse lake area of Huaibei. The bacterial community compositions are significantly different in the sediments among Huaibei collapsed lakes, with DH having the largest number of species, and NH having a higher species diversity. Pseudomonadota is the most abundant phylum in the sediments of DH and NH, while the most abundant phyla in ZH are Bacteroidales, Chloroflexales, Acidobacteriales, and Firmicutes. Anaerolineae (24.05% ± 0.20%) is the most abundant class in the DH sediments, and Gammaproteobacteria (25.94% ± 0.40%) dominates the NH sediments, Bacteroidia (32.12% ± 1.32%) and Clostridia (21.98% ± 0.90%) contribute more than 50% to the bacteria in the sediments of ZH. Redundancy analysis (RDA) shows that pH, TN, and TP are the main environmental factors affecting the bacterial community composition in the sediments of the collapsed lake area. The results reveal the bacterial community composition and biodiversity in the sediments of the Huaibei coal mining collapsed lakes, and provide new insights for the subsequent ecological conservation and restoration of the coal mining collapsed lakes.


Subject(s)
Geologic Sediments , Lakes , Bacteria/genetics , Biodiversity , China , Firmicutes/genetics , Geologic Sediments/microbiology , Lakes/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics
4.
Ecotoxicol Environ Saf ; 241: 113748, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35696965

ABSTRACT

Forest ecosystems play an important role in environmental protection and maintaining ecological balance. Understanding the physiological mechanisms of tree species response to aluminum (Al) toxic is crucial to reveal the main causes of plantation decline in acid rain area. As an important afforestation tree species in tropical and subtropical areas, Eucalyptus has high economic value and plays crucial ecological roles. However, continuous fertilization and acid precipitation can exacerbate soil acidification and increase soil active Al, which has a significant negative impact on Eucalyptus growth. Hence, species and genotypes with high Al resistance are required to solve the problem of Al toxicity of acidic soils for sustainable forest production. In this study, E. urophylla was better adapted to Al stress than E. grandis or E. tereticornis; its high Al resistance was attributed to greater antioxidant enzyme activity and non-enzymatic antioxidant content, and a lower degree of membrane lipid peroxidation than E. grandis or E. tereticornis. The differences in adaptability among the three pure species were attributed to their distinct habitats. Eucalyptus urophylla × E. grandis inherited the outstanding adaptability to Al stress from its maternal species (E. urophylla), indicating that Al tolerance is highly heritable and can be selected in Eucalyptus breeding. Our results indicated that the response of Eucalyptus to Al stress may fluctuate according to the time under stress, and might be related to dynamic changes in ROS elimination and accumulation.


Subject(s)
Eucalyptus , Aluminum/toxicity , Antioxidants , Ecosystem , Eucalyptus/genetics , Oxidative Stress , Plant Breeding , Soil , Trees
5.
Arch Osteoporos ; 17(1): 52, 2022 03 22.
Article in English | MEDLINE | ID: mdl-35316429

ABSTRACT

PURPOSE: This study aimed to observe the effect of individualized nursing based on a comprehensive geriatric assessment (CGA) on improving the quality of life of elderly osteoporosis patients. METHODS: Ninety-two elderly osteoporosis patients were divided into two groups using the random number table method, with 46 patients in each group. The control group received routine nursing, while the observation group was the recipients of personalized care intervention based on a CGA. The abbreviated generic Quality of Life Scale developed through the World Health Organization and an inpatient nursing satisfaction scale were used to evaluate the quality of life and patient satisfaction scores of the two groups before and 6 months after the nursing intervention. RESULTS: There were no significant differences in the WHOQOL-BREF scores between the two groups before intervention (p > 0.05). After 6 months of intervention, the index of each domain was significantly higher than that before the intervention (p < 0.05), and the index of each domain in the observation group was significantly higher than that in the control group after 6 months of intervention (p < 0.05). There was no significant difference in patient satisfaction scores between the two groups before the intervention (p > 0.05). However, after 6 months of intervention, the patient satisfaction scores in the observation group were significantly higher than those in the control group after 6 months of intervention (p < 0.05). CONCLUSION: Individualized nursing intervention based on a CGA can effectively improve the quality of life of elderly osteoporosis patients and improve patient satisfaction.


Subject(s)
Geriatric Assessment , Osteoporosis , Aged , Geriatric Assessment/methods , Humans , Quality of Life
7.
Chem Asian J ; 15(8): 1290-1295, 2020 Apr 17.
Article in English | MEDLINE | ID: mdl-32166912

ABSTRACT

Organic electrode materials hold great potential for fabricating sustainable energy storage systems, however, the development of organic redox-active moieties for rechargeable aqueous zinc-ion batteries is still at an early stage. Here, we report a bio-inspired riboflavin-based aqueous zinc-ion battery utilizing an isoalloxazine ring as the redox center for the first time. This battery exhibits a high capacity of 145.5 mAh g-1 at 0.01 A g-1 and a long-life stability of 3000 cycles at 5 A g-1 . We demonstrate that isoalloxazine moieties are active centers for reversible zinc-ion storage by using optical and photoelectron spectroscopies as well as theoretical calculations. Through molecule-structure tailoring of riboflavin, the obtained alloxazine and lumazine molecules exhibit much higher theoretical capacities of 250.3 and 326.6 mAh g-1 , respectively. Our work offers an effective redox-active moiety for aqueous zinc batteries and will enrich the valuable material pool for electrode design.

8.
Phys Chem Chem Phys ; 22(3): 1371-1380, 2020 Jan 21.
Article in English | MEDLINE | ID: mdl-31854404

ABSTRACT

We systematically studied water adsorption and oxidation on the unreconstructed TiO2(001) surface using first-principles calculations. Water first adsorbs on the surface in a dissociative state and then in a molecular state, as water coverage increases. The geometric properties of all adsorption structures suggest that the dissociative water molecules can induce stress release of the (001) surface at low coverage, reducing reactivity of the surface and thus leading to molecular adsorption of water on the surface at high coverage. The adsorption energy (or the surface energy) monotonously increases (or decreases) with the increase of the coverage, which further confirms that water, irrespective of its dissociative or molecular state, can improve the stability of the (001) surface and reduce its activity. We deeply investigated the mechanism of the oxygen evolution reaction (OER) on the water-covered (001) surface. A new water-assisted OER pathway is identified on the (001) surface, which includes the sequential transfer of protons from molecular water and surface hydroxyls, and O-O coupling processes. During the OER pathway, the O-O coupling step exhibits the largest thermodynamic energy and highest energy barrier, clarifying that it is the rate-determining step in the whole pathway. Our findings provide new insights into the strong dependence of water adsorption modes on coverage for the anatase TiO2(001) surface and may explain the high oxidation activity of the TiO2(001) surface in aqueous environments typical of TiO2 photocatalysis.

9.
BMC Cardiovasc Disord ; 19(1): 110, 2019 05 14.
Article in English | MEDLINE | ID: mdl-31088358

ABSTRACT

BACKGROUND: This study aims to investigate the chlamydia pneumoniae infection (PC) in patients with coronary heart disease. METHODS: A total of 92 patients with coronary heart disease, who were treated with percutaneous coronary intervention (PCI), were selected as the case group. In addition, 50 healthy people were enrolled as the control group. The incidences of CP infection and serum Chlamydia pneumoniae IgA antibody (CP-IgA), high sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were compared in these two groups. The classification of coronary artery lesion, the incidence of perioperative cardiovascular events, and adverse prognosis events within six months after procedure were compared. RESULTS: The incidence of CP infection in the case group was higher (42.4% vs. 0%, P < 0.05). Furthermore, 17 patients were at grade I, 39 patients were at grade II, and 36 patients were at grade III. The incidences for these three kinds of patients were 17.6, 30.8, and 66.7%. The incidence of CP infection at grade III was higher than that of grade I or II (P < 0.05). Serum CP-IgA, hs-CRP and IL-6 levels increased with the severity of the coronary artery disease (P < 0.05), and the serum hs-CRP and IL-6 levels of patients with perioperative cardiovascular events were higher (P < 0.05). Moreover, the serum CP-IgA levels of the patients with adverse prognosis events were also higher (P < 0.05). CONCLUSIONS: Patients with coronary heart disease have a high CP infection rate. The degree of infection is relevant to the severity of the coronary artery lesions and postoperative prognosis of patients, suggesting that CP infection may be an important factor affecting the incidence and prognosis of coronary heart disease.


Subject(s)
Chlamydophila Infections/epidemiology , Chlamydophila pneumoniae/pathogenicity , Coronary Disease/epidemiology , Antibodies, Bacterial/blood , Beijing/epidemiology , Biomarkers/blood , C-Reactive Protein/analysis , Case-Control Studies , Chlamydophila Infections/blood , Chlamydophila Infections/diagnosis , Chlamydophila pneumoniae/immunology , Coronary Disease/blood , Coronary Disease/diagnosis , Coronary Disease/therapy , Female , Humans , Immunoglobulin A/blood , Incidence , Interleukin-6/blood , Male , Middle Aged , Percutaneous Coronary Intervention , Severity of Illness Index , Time Factors , Treatment Outcome
10.
Arch Gerontol Geriatr ; 83: 7-12, 2019.
Article in English | MEDLINE | ID: mdl-30921603

ABSTRACT

BACKGROUND: Frailty, featured by the presence of fatigue, weight loss, decrease in grip strength, decline gait speed and reduced activities substantially increase the risk of falls, disability, hospitalizations, and mortality of older people. Nutritional supplementation and resistance exercise may improve muscle function and reverse frailty status. OBJECTIVE: To evaluate whether whey protein supplements can improve muscle function of frail older people in addition to resistance exercise. METHODS: 115 community-dwelling older adults who met the Fried's criteria for frailty from four hospitals' out-patients clinic in Beijing, China completed the study. It's a case-control study which whey protein was used as daily supplementation for 12 weeks for active group and regular resistance exercise for active group and control group. Handgrip strength, gait speed, chair-stand test, balance score, and SPPB score were compared in both groups during the 12-week follow-up. RESULTS: Overall, 115 subjects were enrolled for study with 66 in active group and 49 in control group. Handgrip strength, gait speed, and chair-stand time were all significantly improved in both groups with significant between-group differences. The active group improved significantly in handgrip strength compared with the control group, which between-group effect (95% confidence interval) for female was 0.107 kg (0.066-0.149), p = 0.008 and for male was 0.89 kg (0.579-1.201), p = 0.007. For chair-stand time, between-group effect (95% confidence interval) was -2.875 s (-3.62 to -2.124), p = 0.004 and for gait speed, between-group effect (95% confidence interval) was 0.109 m/s (0.090 to 0.130), p = 0.003. CONCLUSIONS: The 12-week intervention of whey protein oral nutritional supplement revealed significant improvements in muscle function among the frailty elderly besides aiding with resistance exercise. These results warrant further investigations into the role of a multi-modal supplementation approach which could prevent adverse outcomes among frailty elderly at risk for various disabilities.


Subject(s)
Dietary Supplements , Frail Elderly , Sarcopenia/physiopathology , Whey Proteins/administration & dosage , Aged , Aged, 80 and over , Case-Control Studies , China , Female , Gait , Hand Strength , Humans , Independent Living , Male , Postural Balance
11.
Life Sci ; 210: 158-165, 2018 Oct 01.
Article in English | MEDLINE | ID: mdl-30189214

ABSTRACT

AIMS: The present study describes the derivation and validation of the Chronic Heart Failure Severity Index (CHFSI). MAIN METHODS: The CHFSI was derived using data obtained from a single-center prospective cohort study (2000-2014) that enrolled 756 patients. Logistic regression was used to identify independent predictors of mortality and quality of life over a 15-year follow-up period. KEY FINDINGS: The score was validated at the first 5-year (n = 644), second 5-year (n = 364), and third 5-year (n = 262). Independent predictors of mortality were older age (OR = 2.04, P < 0.001), etiology score (OR = 2.61, P < 0.001), faster heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P < 0.001), and left ventricular ejection fraction ≤45% (OR = 1.97, P = 0.018). The derived CHFSI predicted the mortality, and the AUC for the logistic model was 0.78 (95% confidence interval = 0.74-0.81, P < 0.001). Based on the logistic model, an integer scoring system was derived. Patients were classified into three groups: low risk (0-7 points), intermediate risk (8-11 points) and high risk (≥12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275), 84.0% (204/243), and 100% (99/99), respectively (P < 0.001). The 6-min walk test revealed a significant difference in quality of life among patients in the low, medium and high risk groups (all, P < 0.0001). SIGNIFICANCE: The CHFSI is a very useful clinical predictive tool that identifies patients at risk of future mortality and their quality of life across healthcare systems.


Subject(s)
Heart Failure/mortality , Quality of Life , Severity of Illness Index , Adult , Aged , Chronic Disease , Female , Follow-Up Studies , Heart Failure/therapy , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Assessment , Survival Rate
12.
Adv Sci (Weinh) ; 5(3): 1700634, 2018 03.
Article in English | MEDLINE | ID: mdl-29593966

ABSTRACT

Aqueous sodium-ion battery of low cost, inherent safety, and environmental benignity holds substantial promise for new-generation energy storage applications. However, the narrow potential window of water and the enlarged ionic radius because of hydration restrict the selection of electrode materials used in the aqueous electrolyte. Here, inspired by the efficient redox reaction of biomolecules during cellular energy metabolism, a proof of concept is proposed that the redox-active biomolecule alizarin can act as a novel electrode material for the aqueous sodium-ion battery. It is demonstrated that the specific capacity of the self-assembled alizarin nanowires can reach as high as 233.1 mA h g-1, surpassing the majority of anodes ever utilized in the aqueous sodium-ion batteries. Paired with biocompatible and biodegradable polypyrrole, this full battery system shows excellent sodium storage ability and flexibility, indicating its potential applications in wearable electronics and biointegrated devices. It is also shown that the electrochemical properties of electrodes can be tailored by manipulating naturally occurring 9,10-anthroquinones with various substituent groups, which broadens application prospect of biomolecules in aqueous sodium-ion batteries.

13.
Food Chem Toxicol ; 114: 23-33, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29432836

ABSTRACT

Quercetin (QU) is one of the most common flavonoids that are present in a wide variety of fruits, vegetables, and beverages. This compound possesses potent anti-inflammatory and anti-oxidant properties. Supplemental oxygen is routinely administered to premature infants with pulmonary insufficiency. However, hyperoxia is one of the major risk factors for the development of bronchopulmonary dysplasia (BPD), which is also termed chronic lung disease in premature infants. Currently, no preventive approaches have been reported against BPD. The treatment of BPD is notably limited to oxygen administration, ventilatory support, and steroids. Since QU has been shown to be effective in reducing inflammation and oxidative stress in various disease models, we hypothesized that the postnatal QU treatment of newborn mice will protect against hyperoxic lung injury by the upregulation of the phase I (CYP1A/B) and/or phase II, NADPH quinone reductase enzymes. Newborn C57BL/6J mice within 24 h of birth with the nursing dams were exposed to either 21% O2 (air) and/or 85% O2 (hyperoxia) for 7 days. The mice were treated, intraperitoneally (i.p.) once every other day with quercetin, at a concentration of 20 mg/kg, or saline alone from postnatal day (PND) 2-6. The mice were sacrificed on day 7, and lung and liver tissues were collected. The expression levels of CYP1A1, CYP1B1, NQO1 proteins and mRNA as well as the levels of MDA-protein adducts were analyzed in lung and liver tissues. The findings indicated that QU attenuated hyperoxia-mediated lung injury by reducing inflammation and improving alveolarization with decreased number of neutrophil and macrophage infiltration. The attenuation of this lung injury correlated with the upregulation of CYP1A1/CYP1B1/NQO1 mRNA, proteins and the down regulation of NF-kB levels and MDA-protein adducts in lung and liver tissues. The present study demonstrated the potential therapeutic value of quercetin in the prevention and/or treatment of BPD.


Subject(s)
Bronchopulmonary Dysplasia/drug therapy , Hyperoxia/drug therapy , Quercetin/administration & dosage , Animals , Animals, Newborn/metabolism , Bronchopulmonary Dysplasia/genetics , Bronchopulmonary Dysplasia/metabolism , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1B1/genetics , Cytochrome P-450 CYP1B1/metabolism , Humans , Hyperoxia/genetics , Hyperoxia/metabolism , Infant, Newborn , Lung/drug effects , Lung/metabolism , Mice , Mice, Inbred C57BL , NAD(P)H Dehydrogenase (Quinone)/genetics , NAD(P)H Dehydrogenase (Quinone)/metabolism , Oxidative Stress/drug effects , Oxygen/metabolism
14.
Toxicol Appl Pharmacol ; 339: 133-142, 2018 01 15.
Article in English | MEDLINE | ID: mdl-29180065

ABSTRACT

Exposure to supraphysiological concentrations of oxygen (hyperoxia) leads to bronchopulmonary dysplasia (BPD), one of the most common pulmonary morbidities in preterm neonates, which is more prevalent in males than females. Beta-naphthoflavone (BNF) is protective against hyperoxic lung injury in adult and neonatal wild type (WT) mice and in and mice lacking Cyp1a1gene. In this investigation, we tested the hypothesis that BNF treatment will attenuate neonatal hyperoxic lung injury in WT and Cyp1a2-/- mice, and elucidated the effect of sex-specific differences. Newborn WT or Cyp1a2-/- mice were treated with BNF (10mg/kg) or the vehicle corn oil (CO) i.p., from postnatal day (PND) 2 to 8 once every other day, while being maintained in room air or hyperoxia (85% O2) for 14days. Hyperoxia exposure lead to alveolar simplification and arrest in angiogenesis in WT as well as Cyp1a2-/- mice No significant differences were seen between WT and Cyp1a2-/- mice. Cyp1a2-/- female mice had better preservation of pulmonary angiogenesis at PND15 compared to similarly exposed males. BNF treatment attenuated lung injury and inflammation in both genotypes, and this was accompanied by a significant induction of hepatic and pulmonary CYP1A1 in WT but not in Cyp1a2-/- mice. BNF treatment increased NADPH quinone oxidoreductase (NQO1) mRNA levels in Cyp1a2-/- mouse livers compared to WT mice. These results suggest that BNF is protective in neonatal mice exposed to hyperoxia independent of CYP1A2 and this may entail the protective effect of phase II enzymes like NQO1.


Subject(s)
Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Cytochrome P-450 CYP1A2/deficiency , Hyperoxia/drug therapy , Hyperoxia/metabolism , beta-Naphthoflavone/therapeutic use , Acute Lung Injury/genetics , Animals , Animals, Newborn , Cytochrome P-450 CYP1A2/genetics , Enzyme Inhibitors/therapeutic use , Female , Hyperoxia/genetics , Male , Mice , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Treatment Outcome
15.
Biochem Biophys Res Commun ; 495(1): 408-413, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29101037

ABSTRACT

Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this study, we tested the hypothesis that newborn transgenic mice carrying the human CYP1A1-Luc promoter will display transcriptional activation of the human CYP1A1 promoter in vivo upon exposure to hyperoxia, and that these mice will be less susceptible to hyperoxic lung injury and alveolar simplification than similarly exposed wild type (WT) mice. Newborn WT (CD-1) or transgenic mice carrying a 13.2 kb human CYP1A1 promoter and the luciferase (Luc) reporter gene (CYP1A1-luc) were maintained in room air or exposed to hyperoxia (85% O2) for 7-14 days. Hyperoxia exposure of CYP1A1-Luc mice for 7 and 14 days resulted in 4- and 30-fold increases, respectively, in hepatic Luc (CYP1A1) expression, compared to room air controls. In lung, hyperoxia caused a 2-fold induction of reporter Luc at 7 days, but the induction declined after 14 days. The newborn CYP1A1-Luc mice were less susceptible to lung injury and alveolar simplification than similarly exposed wild type (WT) CD-1 mice. Also, the CYP1A1-Luc mice showed increased levels of hepatic and pulmonary CYP1A1 expression and hepatic CYP1A2 activity after hyperoxia exposure. Hyperoxia also increased NADP(H) quinone reductase (NQO1) pulmonary gene expression in both CD-1 and CYP1A1-Luc mice at both time points, but this was more pronounced in the latter at 14 days. Our results support the hypothesis that hyperoxia activates the human CYP1A1 promoter in newborn mice, and that increased endogenous expression of CYP1A1 and NADP(H) quinone reductase (NQO1) contributes to the decreased susceptibilities to hyperoxic lung injury in the transgenic animals. This is the first report providing evidence of hyperoxia-mediated transcriptional activation of the human CYP1A1 promoter in newborn mice, and this in conjunction with decreased lung injury, suggests that these phenomena have important implications for BPD.


Subject(s)
Cytochrome P-450 CYP1A1/genetics , Hyperoxia/complications , Hyperoxia/genetics , Lung Injury/etiology , Lung Injury/genetics , Lung/pathology , Transcriptional Activation , Animals , Animals, Newborn , Humans , Hyperoxia/metabolism , Hyperoxia/pathology , Lung/metabolism , Lung Injury/metabolism , Lung Injury/pathology , Mice , Mice, Transgenic , NAD(P)H Dehydrogenase (Quinone)/genetics , Oxygen/metabolism , Promoter Regions, Genetic
16.
Medicine (Baltimore) ; 96(33): e7727, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28816949

ABSTRACT

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases.A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation.WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing.Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients.


Subject(s)
Cardiomyopathy, Dilated/genetics , Exome/genetics , Potassium Channels, Inwardly Rectifying/genetics , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Polymorphism, Single Nucleotide
17.
Toxicol Sci ; 157(1): 260-271, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28201809

ABSTRACT

Prolonged hyperoxia contributes to bronchopulmonary dysplasia (BPD) in preterm infants. ß-Naphthoflavone (BNF) is a potent inducer of cytochrome P450 (CYP)1A enzymes, which have been implicated in hyperoxic injuries in adult mice. In this investigation, we tested the hypothesis that newborn mice lacking the Cyp1a1 gene would be more susceptible to hyperoxic lung injury than wild-type (WT) mice and that postnatal BNF treatment would rescue this phenotype by mechanisms involving CYP1A and/or NAD(P)H quinone oxidoreductase (NQO1) enzymes. Newborn WT or Cyp1a1-null mice were treated with BNF (10 mg/kg) or the vehicle corn oil (CO) i.p., from postnatal day (PND) 2 to 14 once every other day, while being maintained in room air or hyperoxia (85% O2) for 14 days. Both genotypes showed lung injury, inflammation, and alveolar simplification in hyperoxia, with Cyp1a1-null mice displaying increased susceptibility compared to WT mice. BNF treatment resulted in significant attenuation of lung injury and inflammation, with improved alveolarization in both WT and Cyp1a1-null mice. BNF exposed normoxic or hyperoxic WT mice showed increased expression of hepatic CYP1A1/1A2, pulmonary CYP1A1, and NQO1 expression at both mRNA and protein levels, compared with vehicle controls. However, BNF caused greater induction of hepatic CYP1A2 and pulmonary NQO1 enzymes in the Cyp1a1-null mice, suggesting that BNF protects against hyperoxic lung injury in WT and Cyp1a1-null mice through the induction of CYP1A and NQO1 enzymes. Further studies on the protective role of flavonoids against hyperoxic lung injury in newborns could lead to novel strategies for the prevention and/or treatment of BPD.


Subject(s)
Bronchopulmonary Dysplasia/etiology , Cytochrome P-450 CYP1A1/genetics , Infant, Premature , Oxygen/administration & dosage , beta-Naphthoflavone/administration & dosage , Animals , Animals, Newborn , Blotting, Western , Bronchopulmonary Dysplasia/genetics , Genetic Predisposition to Disease , Humans , Infant, Newborn , Mice , Mice, Knockout , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/enzymology
18.
J Mol Model ; 22(9): 197, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27488103

ABSTRACT

Aminothiophenol/Au(111) has been adopted as an exemplary model in plasmonics research, including surface-enhanced Raman spectroscopy, due to its high plasmonic-induced spectral-signal enhancement. The present work was aimed at clarifying whether aminothiophenol on Au(111) is chemically stable in the absence of any photo- and plasmonic-induced effects. Briefly, first-principles calculations were employed to track the detailed mechanism of oxidative coupling of p-aminothiophenol (PATP) to its azo-adduct with an N = N bond, i.e., p,p'-dimercaptoazobenzene (DMAB). Our results show the following: first, in the presence of adsorbed O2, PATP fractures its N-H bond and transfers the hydrogen to a nearby oxygen. This pathway is more favorable than the transfer of H to Au, but the activation barrier of 0.9 eV is still too high for the reaction to occur in the absence of thermal-, photo-, or plasmonic-activation. If this bar can be lifted, two such dehydrogenated PATP can couple themselves to form an adduct with a N-N bond, i.e., p,p'-dimercaptohydroazobenzene (DMHAB), and this reaction is exoergic with an energy barrier of 0.57 eV. Again, this step is slow in the absence of moderate thermal activation or photo-/plasmonic-activation. Finally, dehydrogenation of DMHAB gives the azo-adduct of DMAB, and this reaction is spontaneous, with no energy barrier.


Subject(s)
Aniline Compounds/chemistry , Gold/chemistry , Models, Theoretical , Sulfhydryl Compounds/chemistry , Oxidation-Reduction
19.
Int J Clin Exp Pathol ; 8(9): 10861-7, 2015.
Article in English | MEDLINE | ID: mdl-26617800

ABSTRACT

BACKGROUND: The principal aim of this study was to investigate the clinical, epidemiological and pathologic features for a series of 79 cases of adipositas cordis sudden death. METHODS: We analyzed clinical and autopsy pathological features of 79 patients (43 females and 36 males) with adipositas cordis who died suddenly between 1975 and 2010. Data were extracted from China National Knowledge Infrastructure and Wan Fang Database. RESULTS: The average age of the 79 cases was 36.6 ± 1.4 years old ranging from 13 to 68, and 82.3% of them were between 20 to 50 years old. Sudden death was the first symptom in 62 (78.5%) of the cases, only 17 (21.5%) had a history of chest distress or dyspnea. More than 4/5 (87.3%) of the cases had no any past medical history. At autopsy, the subjects' heart weight was mild or moderately increased, and a large amount of fatty tissues but not fibrous or fibro fatty was accumulated underneath the epicardium and infiltrated toward the right ventricle walls, and even infiltrated to all layers of the cardiac walls. Regional epidemiological data showed that about 80% of cases were living north and only 20% were living south of the Yangzi River, but not any familial heredity. CONCLUSION: Adipositas cordis sudden death is a very severe disease, it occurs mostly in youth and middle-aged and sudden death is often the first symptom. There is a significant regional difference, but not any genetic correlation. The pathogenesis of adipositas cordis sudden death should to be further explored.


Subject(s)
Adipose Tissue/pathology , Arrhythmogenic Right Ventricular Dysplasia/epidemiology , Death, Sudden, Cardiac/epidemiology , Myocardium/pathology , Adolescent , Adult , Aged , Arrhythmogenic Right Ventricular Dysplasia/mortality , Arrhythmogenic Right Ventricular Dysplasia/pathology , Autopsy , Cause of Death , China/epidemiology , Databases, Factual , Death, Sudden, Cardiac/pathology , Female , Fibrosis , Humans , Male , Middle Aged , Risk Factors , Time Factors , Young Adult
20.
J Mol Model ; 21(10): 265, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26385850

ABSTRACT

The capture of N3-chains and N5-rings on the outer surface of C60 was studied using density functional calculations. For the neutral N5-ring, it was found that a N5-ring trapped by a C60 cage becomes more stable than an isolated N5-ring radical, and a C60-N5 compound with a C-N bond at an exohedral position of C60 is more stable than an isomer with the N5-ring encapsulated in C60. Such stability arises from the reduction in molecular strain energy, and charge transfer from C60 to N5. Dynamics calculations indicate that capture of the N5-ring on the outer surface of C60 is a barrierless process. Furthermore, the trapping sites of more N5-rings on the C60 were determined using condensed Fukui functions, where the N5-rings prefer to be trapped on the surface to form addition products across 6,6-junctions. Based on the optimized geometries of C60-(N5) n (n = 2, 6, 10), their chemical stabilities were found to be comparable with that of C60 in terms of the gap between the highest occupied molecular orbitals and the lowest unoccupied molecular orbitals. Similar phenomena were found for an N3-chain wrapped on the surface of C60. However, the results of the average adsorption energies show that C60 can capture N5-rings more effectively than N3-chains.


Subject(s)
Fullerenes/chemistry , Models, Theoretical , Nitrogen/chemistry , Models, Chemical , Models, Molecular
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