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1.
Biochim Biophys Acta Mol Basis Dis ; 1864(4 Pt A): 1086-1103, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29353068

RESUMO

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. Mitochondrial dysfunction has been the focus of the pathogenesis of PD. The mitochondrial ATP-sensitive potassium channel (mitoKATP) plays a significant role in mitochondrial physiology and has been extensively shown to protect against ischemic and brain reperfusion injury. However, there have long been controversies regarding its role in Parkinson's disease. We investigated the role of mitoKATP channels in rotenone-induced PD model in vivo and vitro and the interactions of mitoKATP channels, mitochondrial dynamics and PD. The results indicated that the use of diazoxide to activate mitoKATP channels resulted in the aggravation of rotenone-induced dopamine neurodegeneration in PC12 cells and SD rats. In contrast, the use of 5-hydroxydecanoate (5-HD) to inhibit mitoKATP channels improved rotenone-induced dopamine neurodegeneration, which was not consistent with mitoKATP channels in ischemic and brain reperfusion injury. Further analysis determined that the mitoKATP channel was involved in PD mainly via the regulation of mitochondrial biogenesis and fission/fusion. And the pore subunits of Kir6.1, the major component of mitoKATP channels, was the key contributor in its interaction with mitochondrial dynamics in rotenone-induced dopamine neurodegeneration. Therefore, it can be concluded that mitoKATP channels regulate mitochondrial dynamics to participate in rotenone-induced PD mainly attributes to the pore subunits of Kir6.1. And additionally, though mitoKATP channels may represent a direction of one potential target for neuroprotection, it should be noted that the effects are different in the activation or inhibition of mitoKATP channels in different models.


Assuntos
Canais KATP/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Doença de Parkinson Secundária/metabolismo , Animais , Masculino , Mitocôndrias/patologia , Células PC12 , Doença de Parkinson Secundária/patologia , Ratos , Ratos Sprague-Dawley , Rotenona/efeitos adversos , Rotenona/farmacologia
2.
Psychosom Med ; 80(6): 564-572, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794946

RESUMO

OBJECTIVE: Behavioral and psychosocial factors have been associated with a decline of the quality of semen. However, the relationship of depression and physical activity (PA) with semen quality remains unclear. METHODS: Data were obtained from 587 young male Chinese college students in June 2013. Participants completed a questionnaire assessing life-style factors, the Zung self-rated depression scale, and three items related to PA. They underwent a physical examination and provided a semen sample and a blood sample for reproductive hormones (testosterone, estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and prolactin). RESULTS: Men with high depression scores (n = 63, 10.7%) had lower sperm concentration (M (SD) = 66.9 (74.5) versus 72.6 (56.9) [10/ml], p = .043) and total sperm count (M (SD) = 241.6 (299.7) versus 257.0 (204.0) [10], p = .024) than nondepressed men. Participants with low PA levels (n = 99, 16.9%) had lower total sperm count (M (SD) = 204.4 (153.7) versus 265.8 (225.8) [10/ml], p = .017) than participants with higher activity levels. After adjusting for potential confounders, depressed men had 18.90% (95% confidence interval [CI] = 1.14%-33.47%) lower sperm concentration and 21.84% (95% CI = 3.39%-36.90%) lower total sperm count than nondepressed men. Men with low PA levels had 23.03% (95% CI = 2.80%-46.89%) lower total sperm count than physically active participants. An interaction effect between depression and PA on sperm concentration was detected (p = .033). There were no significant associations of depression and PA with reproductive hormones (p > .05). CONCLUSIONS: Depression and low levels of PA are associated with lower levels of semen quality, which may have implications for reproductive health.


Assuntos
Transtorno Depressivo/sangue , Exercício Físico/fisiologia , Hormônios Esteroides Gonadais/sangue , Gonadotropinas Hipofisárias/sangue , Sêmen , Adolescente , Adulto , China/epidemiologia , Transtorno Depressivo/epidemiologia , Humanos , Masculino , Contagem de Espermatozoides , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos , Adulto Jovem
3.
J Sleep Res ; 27(4): e12615, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28994211

RESUMO

This study explores whether sleep duration is associated with sperm chromatin integrity. To do so, we conducted a three-phase panel study of 796 male volunteers from colleges in Chongqing (China) from 2013 to 2015. Sleep duration was measured using a modified Munich Chronotype Questionnaire. Sperm DNA integrity was examined via Sperm Chromatin Structure Assay and Comet assay. Setting 7-7.5 h day-1 of sleep duration as a reference, either longer or shorter sleep duration was associated negatively with high DNA stainability (HDS) (P = 0.009), which reflected the immaturity of sperm chromatin. The volunteers with > 9.0 h day-1 sleep and those with ≤ 6.5 h day-1 sleep had 40.7 and 30.3% lower HDS than did volunteers with 7-7.5 h day-1 sleep. No association was found between sleep duration and DNA fragmentation index or Comet assay parameters. This study suggests that sleep duration is associated with sperm chromatin integrity. Further studies are required to validate these findings and investigate the mechanism underlying this association.


Assuntos
Cromatina/fisiologia , Sono/fisiologia , Espermatozoides/fisiologia , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Humanos , Masculino , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
4.
Hum Reprod ; 31(5): 958-67, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27052617

RESUMO

STUDY QUESTION: Is anogenital distance associated with semen parameters and serum reproductive hormone levels in males? SUMMARY ANSWER: Anogenital distance is associated with serum reproductive hormones, but not with semen quality. WHAT IS KNOWN ALREADY: Epidemiological studies have suggested that anogenital distance (AGD) may be associated with testicular dysfunction in adult men. However, the role of AGD in estimating male reproductive function remains unclear. STUDY DESIGN, SIZE, DURATION: We examined the associations between AGD and semen parameters and reproductive hormones levels in 656 young college students in a Male Reproductive Health in Chongqing College Students (MARHCSs) cohort study in June of 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: In this study, two variants of AGD (AGDAP and AGDAS) were measured in 656 university students. Serum levels of testosterone (T), estradiol (E2), progesterone (P), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG) and inhibin-B; and semen quality outcomes, including semen volume, sperm concentration, total sperm number, sperm progressive motility, total motility and morphology, were assessed. The associations between AGD and semen parameters/reproductive hormones levels were analyzed using multiple regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Both AGDAS and AGDAP were not associated with any semen parameters. In the non-parametric correlation analysis, AGDAP were correlated with sperm progressive motility and reproductive hormones of E2, testosterone, SHBG and the testosterone/LH ratio. However, body mass index (BMI) also significantly correlated with serum testosterone ( ITALIC! r = -0.216, ITALIC! P = <0.0001) and SHBG ( ITALIC! r = -0.229, ITALIC! P = <0.001). In the multiple regression models, AGDAP was negatively associated with the serum E2 level (95% CI, -0.198 to -0.043; ITALIC! P = 0.002) and positively associated with the ratio of T/E2 (95% CI, 0.004-0.011; ITALIC! P = 0.001) after an adjustment for BMI and other confounders. LIMITATIONS, REASONS FOR CAUTION: Using only a single semen sample to predict male reproductive function over a longer period is a potential limitation of the present study. The other limitation is the cross-sectional nature of the study design. Longitudinal data from an extended follow-up on a large cohort would be more definitive. WIDER IMPLICATIONS OF THE FINDINGS: Our results do not support previous studies where AGD is associated with male semen quality. The utility of AGD in predicting reproductive outcomes in adult males should thus be considered prudently. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Key Program of Natural Science Funding of China (no. 81130051), Young Scientist Program of NSFC (no. 81502788) and the National Scientific and Technological Support Program of China (no. 2013BAI12B02). None of authors had any competing interests to declare.


Assuntos
Hormônios Esteroides Gonadais/sangue , Períneo/anatomia & histologia , Análise do Sêmen , Adulto , Canal Anal , Biometria , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pênis/anatomia & histologia , Progesterona/sangue , Prolactina/sangue , Testosterona/sangue
5.
Int J Mol Sci ; 16(8): 17018-28, 2015 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-26225959

RESUMO

BACKGROUND: MiR-198 has been considered as an inhibitor of cell proliferation, invasion, migration and a promoter of apoptosis in most cancer cells, while its effect on non-cancer cells is poorly understood. METHODS: The effect of miR-198 transfection on HaCaT cell proliferation was firstly detected using Cell Count Kit-8 and the cell cycle progression was analyzed by flow cytometry. Using bioinformatics analyses and luciferase assay, a new target of miR-198 was searched and identified. Then, the effect of the new target gene of miR-198 on cell proliferation and cell cycle was also detected. RESULTS: Here we showed that miR-198 directly bound to the 3'-UTR of CCND2 mRNA, which was a key regulator in cell cycle progression. Overexpressed miR-198 repressed CCND2 expression at mRNA and protein levels and subsequently led to cell proliferation inhibition and cell cycle arrest in the G1 phase. Transfection ofSiCCND2 in HaCaT cells showed similar inhibitory effects on cell proliferation and cell cycle progression. CONCLUSION: In conclusion, we have identified that miR-198 inhibited HaCaT cell proliferation by directly targeting CCND2.


Assuntos
Ciclina D2/genética , Queratinócitos/citologia , Queratinócitos/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Sequência de Bases , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular , Proliferação de Células , Ciclina D2/metabolismo , Ensaios Enzimáticos , Fase G1/genética , Humanos , Luciferases/metabolismo , MicroRNAs/genética , Dados de Sequência Molecular , Ligação Proteica/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transfecção
6.
Foods ; 13(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38540878

RESUMO

A bacteria capable of degrading aflatoxin M1 (AFM1) was isolated from African elephant manure. It was identified as Bacillus pumilus by 16s rDNA sequencing and named B. pumilusE-1-1-1. Compared with physical and chemical methods, biological methods have attracted much attention due to their advantages, such as thorough detoxification, high specificity, and environmental friendliness. This work aimed to study the effects of a recombinant catalase (rCAT) from B. pumilusE-1-1-1 on the degradation of AFM1 in pattern solution. The degradation mechanism was further explored and applied to milk and beer. Kinetic Momentum and Virtual Machine Maximum values for rCAT toward AFM1 were 4.1 µg/mL and 2.5 µg/mL/min, respectively. The rCAT-mediated AFM1 degradation product was identified as C15H14O3. Molecular docking simulations suggested that hydrogen and pi bonds played major roles in the steadiness of AFM1-rCAT. In other work, compared with identical density of AFM1, survival rates of Hep-G2 cells incubated with catalase-produced AFM1 degradation products increased by about 3 times. In addition, degradation rates in lager beer and milk were 31.3% and 47.2%, respectively. Therefore, CAT may be a prospective substitute to decrease AFM1 contamination in pattern solution, milk, and beer, thereby minimizing its influence on human health.

7.
Int J Biol Macromol ; 277(Pt 1): 134094, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39059525

RESUMO

Leuconostoc citreum JZ-002 was extracted from artisanal orange wine. This strain was used to synthesize dextran with a purification extraction of 27.9 g/L. The resulting dextran had a molecular weight of 2.45 × 106 Da. A significant portion, amounting to 64 % of the structure, is constituted by the main chain, with α-(1,6) glycosidic bonds acting as the linkages. In contrast, the branched chain, comprising 34 % of the entire molecule, is characterized by the presence of α-(1,3) glycosidic bonds. The dextransucrase DsrB, believed to be accountable for the formation of the dextran backbone, was successfully cloned into the pET-28a-AcmA vector. The recombinant expression of the enzyme was achieved. Purified recombinant enzymes and immobilized in a single go using the gram-positive enhancer matrix (GEM). The maximum yield of dextran produced by suchimmobilized enzyme was 191.9 g/L. The composition featured a dextran connected via α-(1,6) glycosidic linkages. Molecular weight controlled synthesis was achieved with sucrose concentrations of 100-2000 mM and enzyme concentrations of 320-1280 U. The Mw of the synthesized dextran extended from 4680 to 1,320,000 Da. By controlling the ratio between enzyme concentration and sucrose concentration, dextrans with diverse Mw can be enzymatically generated.


Assuntos
Dextranos , Glucosiltransferases , Leuconostoc , Dextranos/química , Dextranos/biossíntese , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Glucosiltransferases/química , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Leuconostoc/enzimologia , Peso Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Sacarose/química
8.
Biosens Bioelectron ; 252: 116139, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38412686

RESUMO

Micro/nanomaterials display considerable potential for increasing the sensitivity of lateral flow immunoassay (LFIA) by acting as 3D carriers for both antibodies and signals. The key to achieving high detection sensitivity depends on the probe's orientation on the material surface and its multivalent biomolecular interactions with targets. Here, we engineer Lactococcus lactis as the bacterial microcarrier (BMC) for a multivalent immunorecognition probe that was genetically programmed to display multifunctional components including a phage-screened single-chain variable fragment (scFv), an enhanced green fluorescent protein (eGFP), and a C-terminal peptidoglycan-binding domain (AcmA) anchored on BMC through the cell wall peptidoglycan. The innovative design of this biocarrier system, which incorporates a lab-on-a-chip microfluidic device, allows for the rapid and non-destructive self-assembly of the multivalent scFv-eGFP-AcmA@BMC probe, in which the 3D structure of BMC with a large peptidoglycan surface area facilitates the precisely orientated attachment and immobilization of scFv-eGFP-AcmA. This leads to a remarkable fluorescence aggregation amplification effect in LFIA, outperforming a monovalent 2D scFv-eGFP-AcmA probe for florfenicol detection. By designing a portable sensing device, we achieved an exceptionally low detection limit of 0.28 pg/mL and 0.21 pg/mL for florfenicol in lake water and milk sample, respectively. The successful microfabrication of this biocarrier holds potential to inspire innovative biohybrid designs for environment and food safety biosensing applications.


Assuntos
Técnicas Biossensoriais , Lactococcus lactis , Tianfenicol/análogos & derivados , Animais , Antibacterianos/metabolismo , Lactococcus lactis/genética , Lactococcus lactis/química , Peptidoglicano/metabolismo , Microtecnologia , Leite , Lagos , Imunoensaio , Água
9.
Cell Mol Neurobiol ; 33(8): 1109-21, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24002177

RESUMO

14-3-3 proteins have been confirmed to be involved in Parkinson's disease. It has been reported that an increase of 14-3-3 (theta, epsilon, and gamma) expression has neuroprotective effect in response to rotenone and MPP(+) in dopaminergic cell culture and transgenic C. elegans with alpha-synuclein overexpression. To further investigate the detail mechanism of 14-3-3 proteins in rotenone-induced dopamine neurotoxicity, we observed the expression of 14-3-3 isoforms, and the influence of 14-3-3epsilon knockdown on autophagic activity and cell function. The results showed that rotenone led to a decrease in expression of 14-3-3 protein and mRNA, and an increase in expression and aggregation of alpha-synuclein protein. Knockdown of 14-3-3epsilon expression in turn further aggravated PC12 cell damage, such as an enhancement of ROS formation, and a reduction of cell viability and ATP production. Further experiments confirmed that the autophagic activity was promoted with 14-3-3epsilon siRNA transfection, including an enhancement of autophagosome formation and the ratio of LC3-II/LC3-I. Therefore, we concluded that the regulation of 14-3-3 proteins in rotenone-induced neurotoxicity might be associated with its isoform 14-3-3epsilon's involvement in autophagy, which might be considered a mechanism in addition to the currently known function of 14-3-3 proteins in neurodegenerative disease pathogenesis.


Assuntos
Proteínas 14-3-3/metabolismo , Autofagia/efeitos dos fármacos , Neurotoxinas/toxicidade , Rotenona/toxicidade , Proteínas 14-3-3/genética , Trifosfato de Adenosina/metabolismo , Animais , Autofagia/genética , Forma Celular/efeitos dos fármacos , Forma Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Células PC12 , Fagossomos/efeitos dos fármacos , Fagossomos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Quaternária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transfecção , alfa-Sinucleína/metabolismo
10.
World J Clin Cases ; 9(25): 7358-7364, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616802

RESUMO

BACKGROUND: Coronary heart disease (CHD) is a type of coronary atherosclerotic heart disease. In recent years, the incidence of CHD has been increasing annually, with an increasing number of young patients. Severe CHD may cause severe myocardial ischemia or myocardial necrosis, which in turn may cause myocardial infarction and related complications that seriously affect the life and health of the patient. AIM: To examine the coronary arteries and clinical features of young and middle-aged male patients with CHD. METHODS: From February 2019 to January 2020, 110 male CHD patients admitted to our hospital were selected as research subjects and were divided into two groups by age: middle-aged group (n = 55) and young group (n = 55). The coronary arteries and clinical features of the patients were compared. RESULTS: There were no significant differences in dyslipidemia, stroke history, high-density lipoprotein cholesterol, or triacylglycerol (P > 0.05) between the two groups. In the young group, age, diabetes, hypertension, smoking history, body mass index, family history of CHD, drinking history, fibrinogen, low-density lipoprotein cholesterol, total cholesterol, and single-vessel disease were higher than those in the middle-aged group. Correspondingly, serum uric acid, hyperuricemia, myocardial infarction, Gensini score > 50, collateral circulation, multivessel disease, double vessel disease, involvement of the right coronary artery, and involvement of the left main coronary artery were lower in the young group than in the middle-aged group. The middle-aged group mainly suffered from a high Gensini score, implicating multiple arteries, whereas the young group was mainly affected by single-vessel disease. The between-group difference was significant (P < 0.05). CONCLUSION: In CHD attacks, multiple coronary arteries are implicated in middle-aged male patients and single-vessel disease in young male patients.

11.
J Mol Neurosci ; 71(11): 2336-2352, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33515431

RESUMO

Mitochondria harbor small circular genomes (mtDNA) that encode 13 oxidative phosphorylation (OXPHOS) proteins, and types of damage to mtDNA may contribute to neuronal damage. Recent studies suggested that regulation of mtDNA repair proteins may be a potential strategy for treating neuronal damage. The mtDNA repair system contains its own repair enzymes and is independent from the nuclear DNA repair system. Endo/exonuclease G-like(EXOG) is a mitochondria-specific 5-exo/endonuclease required for repairing endogenous single-strand breaks (SSBs) in mtDNA. However, whether EXOG plays a key role in neuronal damage induced by rotenone remains unknown. Thus, in this study, we aimed to investigate the effect of EXOG on mtDNA repair and mitochondrial functional maintenance in rotenone-induced neurotoxicity. Our results indicated that rotenone influenced the expression and location of EXOG in PC12 cells. Meanwhile, after rotenone exposure, the expression was reduced for proteins responsible for mtDNA repair, including DNA polymerase γ (POLG), high-temperature requirement protease A2 (HtrA2), and the heat-shock factor 1-single-stranded DNA-binding protein 1 (HSF1-SSBP1) complex. Further analysis demonstrated that EXOG knockdown led to reduced mtDNA copy number and mtDNA transcript level and increased mtDNA deletion, which further aggravated the mtDNA damage and mitochondrial dysfunction under rotenone stress. In turn, EXOG overexpression protected PC12 cells from mtDNA damage and mitochondrial dysfunction induced by rotenone. As a result, EXOG knockdown reduced cell viability and tyrosine hydroxylase expression, while EXOG overexpression alleviated rotenone's effect on cell viability and tyrosine hydroxylase expression in PC12 cells. Further, we observed that EXOG influenced mtDNA repair by regulating protein expression of the HSF1-SSBP1 complex and POLG. Furthermore, our study showed that PGC-1α upregulation with ZLN005 led to increased protein levels of EXOG, POLG, HSF1, and SSBP1, all of which contribute to mtDNA homeostasis. Therefore, PGC-1α may be involved in mtDNA repair through interacting with multiple mtDNA repair proteins, especially with the help of EXOG. In summary, EXOG regulation by PGC-1α plays an essential role in rotenone-induced neurotoxicity in PC12 cells. EXOG represents a protective effect strategy in PC12 cells exposed to rotenone.


Assuntos
Reparo do DNA , Endonucleases/metabolismo , Mitocôndrias/metabolismo , Rotenona/toxicidade , Desacopladores/toxicidade , Animais , Dano ao DNA , DNA Polimerase gama/metabolismo , DNA Mitocondrial/genética , Proteínas de Ligação a DNA/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células PC12 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Fatores de Processamento de Serina-Arginina/metabolismo
12.
Front Cell Infect Microbiol ; 11: 739429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722335

RESUMO

Background: The severities of human adenovirus (HAdV) infection are diverse in different areas of Tibet, China, where a large altitude span emerges. Serious consequences may be caused by medical staff if the clinical stages and immunological conditions of patients in high-altitude areas are misjudged. However, the clinical symptoms, immunological characteristics, and environmental factors of HAdV infection patients at different altitude areas have not been well described. Methods: In this retrospective, multicenter cohort study, we analyzed the data of patients who were confirmed HAdV infection by PCR tests in the General Hospital of Tibet Military Command or CDC (the Center for Disease Control and Prevention) of Tibet Military Command from January 1, 2019, to December 31, 2020. Demographic, clinical, laboratory, radiological, and epidemiological data were collected from medical records system and compared among different altitude areas. The inflammatory cytokines as well as the subsets of monocytes and regulatory T cells of patients were also obtained and analyzed in this study. Results: Six hundred eighty-six patients had been identified by laboratory-confirmed HAdV infection, including the low-altitude group (n = 62), medium-altitude group (n = 206), high-altitude group (n = 230), and ultra-high-altitude group (n = 188). Referring to the environmental factors regression analysis, altitude and relative humidity were tightly associated with the number of infected patients (P < 0.01). A higher incidence rate of general pneumonia (45.7%) or severe pneumonia (8.0%) occurred in the ultra-high-altitude group (P < 0.05). The incubation period, serial interval, course of the disease, and PCR-positive duration were prolonged to various extents compared with the low-altitude group (P < 0.05). Different from those in low-altitude areas, the levels of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, TNF-α, TNF-ß, and VEGF in the plasma of the ultra-high-altitude group were increased (P < 0.05), while the proportion of non-classical monocytes and regulatory T cells was decreased (P < 0.05). Conclusions: The findings of this research indicated that patients with HAdV infection in high-altitude areas had severe clinical symptoms and a prolonged course of disease. During clinical works, much more attention should be paid to observe the changes in their immunological conditions. Quarantine of patients in high-altitude areas should be appropriately extended to block virus shedding.


Assuntos
Infecções por Adenoviridae , Adenovírus Humanos , Adenovírus Humanos/genética , Altitude , China/epidemiologia , Estudos de Coortes , Humanos , Estudos Retrospectivos , Tibet
13.
Neurotox Res ; 35(2): 331-343, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30242625

RESUMO

Parkinson's disease (PD) is a progressive, selective, and age-related neurodegenerative disease. The pathogenic focus of PD is mitochondrial dysfunction. When mitochondrial homeostasis was damaged, it can lead to reactive oxygen species formation to further accelerate the accumulation of dysfunctional mitochondria, resulting in a vicious cycle harmful to the neuron. PINK1 and Parkin, two proteins that are linked to PD, play vital roles in mitophagy, which was very important in maintaining mitochondrial homeostasis. Thus, at present, we explored mitochondrial biogenesis, mitophagy, and fission/fusion in rotenone-induced dopamine neurotoxicity. In particular, we focused on interactions between the PINK1/Parkin pathway and PGC-1α in the regulation of mitochondrial homeostasis impairment. The results indicated that both the autophagy and mitophagy levels increased significantly and were accompanied by altered levels of PINK1/Parkin proteins in rotenone-induced neurotoxicity. PINK1 influenced mitochondrial biogenesis by inhibiting PGC-1α and mtTFA protein expression as well as the mtDNA copy number. PGC-1α, in turn, inhibited PINK1/Parkin protein expression and the mitophagy levels. Furthermore, the results demonstrated that PINK1 influenced mitochondrial fission/fusion by regulating MFN2 and phosphorylating Drp1. In summary, mutual antagonism of the PINK1/Parkin pathway and PGC-1α formed a balance that regulated mitochondrial biogenesis, fission/fusion, and mitophagy. These effects contributed to the maintenance of mitochondrial homeostasis in rotenone-induced neurotoxicity.


Assuntos
Homeostase/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/antagonistas & inibidores , Proteínas Quinases , Rotenona/toxicidade , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Homeostase/fisiologia , Mitocôndrias/fisiologia , Células PC12 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Quinases/metabolismo , Ratos , Ubiquitina-Proteína Ligases/metabolismo
14.
Environ Pollut ; 235: 836-849, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29353801

RESUMO

Increasing evidence shows that impaired telomere function is associated with male infertility, and various environmental factors are believed to play a pivotal role in telomerase deficiency and telomere shortening. Benzo[a]pyrene (B[a]P), a ubiquitous pollutant of polycyclic aromatic hydrocarbons (PAHs), can act as a reproductive toxicant; however, the adverse effect of B[a]P on telomeres in male reproductive cells has never been studied, and the related mechanisms remain unclear. In this study, we explored the effects of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the active metabolite of B[a]P, on telomere dysfunction in mouse spermatocyte-derived cells (GC-2) and also the potential role of telomerase in BPDE-induced spermatogenic cell damage. The results showed that BPDE induced cell viability inhibition, senescence, and apoptosis in GC-2 cells in a dose-dependent manner. Shortened telomeres, telomere-associated DNA damage, reduced telomerase activity, and TERT expression were also observed in BPDE-treated cells, accompanied with the activation of DNA damage response pathway (ATM/Chk1/p53/p21). Moreover, by establishing the TERT knockdown and re-expression cell models, we found that TERT regulated telomere length and the expression of DNA damage response-related proteins to influence senescence and apoptosis in GC-2 cells. These in vitro findings were further confirmed in vivo in the testicular cells of rats orally administrated with B[a]P for 7 days. B[a]P treatment resulted in histological lesions, apoptosis, and senescence in the testes of rats, which were accompanied by shortened telomeres, reduced levels of TERT protein, and increased expression of DNA damage response-related proteins. In conclusion, it can be concluded that TERT-mediated telomere dysfunction contributes to B[a]P- and BPDE-induced senescence and apoptosis through DNA damage response in male reproductive cells.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Benzo(a)pireno/toxicidade , Dano ao DNA , Espermatócitos/efeitos dos fármacos , Telômero/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Ratos , Telomerase/genética , Telomerase/metabolismo
15.
Mol Neurobiol ; 54(5): 3783-3797, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27271125

RESUMO

Parkinson's disease is a common neurodegenerative disease in the elderly, and mitochondrial defects underlie the pathogenesis of PD. Impairment of mitochondrial homeostasis results in reactive oxygen species formation, which in turn can potentiate the accumulation of dysfunctional mitochondria, forming a vicious cycle in the neuron. Mitochondrial fission/fusion and biogenesis play important roles in maintaining mitochondrial homeostasis. It has been reported that PGC-1α is a powerful transcription factor that is widely involved in the regulation of mitochondrial biogenesis, oxidative stress, and other processes. Therefore, we explored mitochondrial biogenesis, mitochondrial fission/fusion, and especially PGC-1α as the key point in the signaling mechanism of their interaction in rotenone-induced dopamine neurotoxicity. The results showed that mitochondrial number and mass were reduced significantly, accompanied by alterations in proteins known to regulate mitochondrial fission/fusion (MFN2, OPA1, Drp1, and Fis1) and mitochondrial biogenesis (PGC-1α and mtTFA). Further experiments proved that inhibition of mitochondrial fission or promotion of mitochondrial fusion has protective effects in rotenone-induced neurotoxicity and also promotes mitochondrial biogenesis. By establishing cell models of PGC-1α overexpression and reduced expression, we found that PGC-1α can regulate MFN2 and Drp1 protein expression and phosphorylation to influence mitochondrial fission/fusion. In summary, it can be concluded that PGC-1α-mediated cross talk between mitochondrial biogenesis and fission/fusion contributes to rotenone-induced dopaminergic neurodegeneration.


Assuntos
Neurônios Dopaminérgicos/patologia , Dinâmica Mitocondrial , Neurotoxinas/toxicidade , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Rotenona/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , DNA Mitocondrial/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Dinâmica Mitocondrial/efeitos dos fármacos , Células PC12 , Fosforilação/efeitos dos fármacos , Ratos
16.
Environ Pollut ; 220(Pt A): 680-687, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27751638

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants that have adverse effects on the male reproductive function. Many studies have confirmed that PAHs preferentially accumulate in mitochondria DNA relative to nuclear DNA and disrupt mitochondrial functions. However, it is rare whether exposure to PAHs is associated with mitochondrial damage and dysfunction in sperm. To evaluate the effects of PAHs on sperm mitochondria, we measured mitochondrial membrane potential (MMP), mitochondrial DNA copy number (mtDNAcn) and mtDNA integrity in 666 individuals from the Male Reproductive Health in Chongqing College Students (MARHCS) study. PAHs exposure was estimated by measuring eight urinary PAH metabolites (1-OHNap, 2-OHNap, 1-OHPhe, 2-OHPhe, 3-OHPhe, 4-OHPhe, 2-OHFlu and 1-OHPyr). The subjects were divided into low, median and high exposure groups using the tertile levels of urinary PAH metabolites. In univariate analyses, the results showed that increased levels of 2-OHPhe, 3-OHPhe, ∑Phe metabolites and 2-OHFlu were found to be associated with decreased sperm mtDNAcn. After adjusting for potential confounders, significantly negative associations of these metabolites remained (p = 0.039, 0.012, 0.01, 0.035, respectively). Each 1 µg/g creatinine increase in 2-OHPhe, 3-OHPhe, ∑Phe metabolites and 2-OHFlu was associated with a decrease in sperm mtDNAcn of 9.427%, 11.488%, 9.635% and 11.692%, respectively. There were no significant associations between urinary PAH metabolites and sperm MMP or mtDNA integrity. The results indicated that the low exposure levels of PAHs can cause abnormities in sperm mitochondria.


Assuntos
Variações do Número de Cópias de DNA/efeitos dos fármacos , DNA Mitocondrial/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Mitocôndrias/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/urina , Espermatozoides/efeitos dos fármacos , Adulto , China , Estudos Transversais , DNA Mitocondrial/genética , Exposição Ambiental , Poluição Ambiental/análise , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/genética , Adulto Jovem
17.
Environ Int ; 104: 58-68, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28441547

RESUMO

BACKGROUND: Environment-Protection-Agency Reference Doses (EPA RfDs) for phthalate intakes are based on limited evidence, especially regarding low-dose male-reproductive toxicity. This study investigates the association between phthalate exposure and semen parameters and reproductive hormones in a general population with low phthalate exposure compared to the EPA RfDs. METHODS: The MARHCS (Male-Reproductive-Health-in-Chongqing-College-Students) cohort recruited 796 male students, who experienced a relocation of campuses and shifting environmental exposure. Urine, semen and blood before and after the relocation was collected and investigated for: (1) the associations between 13 urinary phthalate metabolites and 11 semen/hormone outcomes (five semen parameters including semen volume, sperm concentration, total sperm number, progressive motility, normal morphology) and six serum reproductive hormones including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, testosterone; (2) re-analysis of the metabolite-outcome associations in the subjects with estimated phthalate intakes below the RfDs; (3) a change in phthalate metabolites and change in semen/hormone outcomes after the relocation; (4) the association between these changes. RESULTS: (1) All but two semen/hormone outcomes were associated with at least one phthalate metabolite, e.g., each quartile monoethyl phthalate was associated with a 5.3%, 5.7% and 2.6% decrease of sperm concentration, total sperm number and progressive motility respectively. (2) In the subjects with phthalate intakes below the RfDs, these metabolite-outcome associations remained significant. (3) All metabolites except mono(2-ethylhexyl) phthalate declined after relocation (P<0.001 respectively); at the same time, semen volume, normal morphology, estradiol and luteinizing hormone increased (by 5.9%, 25.0%, 34.2% and 10.0%) and testosterone decreased (by 7.0%). (4) The changes in semen volume, normal morphology, estradiol and testosterone, but not the change in luteinizing hormone after relocation, were associated with the changes in the phthalate metabolites. CONCLUSIONS: Phthalate exposure is associated with interrupted semen quality and reproductive hormones in the human population even with a dose given below the RfDs. These effects, however, may only partially revert back when exposure decreases, thus emphasizing the urgency of stricter phthalate administration.


Assuntos
Poluentes Ambientais/urina , Hormônios/sangue , Ácidos Ftálicos/urina , Sêmen , Adulto , Monitoramento Ambiental , Humanos , Masculino , Estudos Prospectivos , Análise do Sêmen , Contagem de Espermatozoides , Espermatozoides/fisiologia , Estados Unidos , United States Environmental Protection Agency , Adulto Jovem
18.
Oxid Med Cell Longev ; 2016: 6705621, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26770656

RESUMO

It has been confirmed that mitochondrial impairment may underlie both sporadic and familial Parkinson's disease (PD). Mitochondrial fission/fusion and biogenesis are key processes in regulating mitochondrial homeostasis. Therefore, we explored whether the protective effect of resveratrol in rotenone-induced neurotoxicity was associated with mitochondrial fission/fusion and biogenesis. The results showed that resveratrol could not only promote mitochondrial mass and DNA copy number but also improve mitochondrial homeostasis and neuron function in rats and PC12 cells damaged by rotenone. We also observed effects with alterations in proteins known to regulate mitochondrial fission/fusion and biogenesis in rotenone-induced neurotoxicity. Therefore, our findings suggest that resveratrol may prevent rotenone-induced neurotoxicity through regulating mitochondrial fission/fusion and biogenesis.


Assuntos
Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Neurotoxinas/toxicidade , Biogênese de Organelas , Rotenona/toxicidade , Estilbenos/farmacologia , Trifosfato de Adenosina/biossíntese , Animais , Apoptose/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA Mitocondrial/genética , Dosagem de Genes , Masculino , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células PC12 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Teste de Desempenho do Rota-Rod , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos
19.
Sleep ; 39(1): 79-86, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26350472

RESUMO

STUDY OBJECTIVES: To investigate the association between sleep duration and semen parameters as well as reproductive hormone levels. METHODS: We designed a cohort of male college students in Chongqing, China. A total of 796 subjects were recruited in 2013 and 656 (82.4%) were followed up in 2014. Each time, semen and peripheral blood samples were collected for semen quality and reproductive hormone measurement. Sleep duration was estimated by revised Munich Chronotype Questionnaire. In 2014, sleep quality was also measured by Pittsburgh Sleep Quality Index (PSQI). RESULTS: There was a substantial inverse U-shaped association between sleep duration and two semen parameters (semen volume and total sperm number), with 7.0-7.5 h/day of sleep showing highest parameters. Either longer or shorter sleep was associated with decreased semen parameters in a dose-response manner (P = 0.002 and 0.001, respectively). Sleeping > 9.0 h was associated with a 21.5% (95% confidence interval 9.2, 32.2) reduction in semen volume and 39.4% (23.3, 52.1) reduction in total sperm number; sleeping ≤ 6.5 h was associated with 4.6% (-10.5, 22.3) and 25.7% (-1.2, 60.1) reduction. Increase of the two parameters was found in those who changed sleep duration toward 7.0-7.5 h/day from 2013 to 2014. The U-shaped association was independent from PSQI and was replicated in another dataset of 1,346 males. No association found between sleep duration and reproductive hormone. CONCLUSIONS: Either restricted or excessive sleep may impair semen quality. Further research is needed to validate this finding.


Assuntos
Análise do Sêmen , Sêmen/citologia , Sêmen/fisiologia , Sono/fisiologia , China , Seguimentos , Hormônios/sangue , Humanos , Estudos Longitudinais , Masculino , Reprodução , Contagem de Espermatozoides , Fatores de Tempo , Adulto Jovem
20.
Medicine (Baltimore) ; 94(28): e1166, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26181561

RESUMO

Decline of semen quality in past decades is suggested to be potentially associated with environmental and sociopsychobehavioral factors, but data from population-based cohort studies is limited. The male reproductive health in Chongqing College students (MARHCS) study was established in June 2013 as a perspective cohort study that recruited voluntary male healthy college students from 3 universities in Chongqing. The primary objectives of the MARHCS study are to investigate the associations of male reproductive health in young adults with sociopsychobehavioral factors, as well as changes of environmental exposure due to the relocation from rural campus (in University Town) to metro-campus (in central downtown). A 93-item questionnaire was used to collect sociopsychobehavioral information in manner of interviewer-interviewing, and blood, urine and semen samples were collected at the same time. The study was initiated with 796 healthy young men screened from 872 participants, with a median age of 20. About 81.8% of this population met the WHO 2010 criteria on semen quality given to the 6 routine parameters. Decreases of 12.7%, 19.8%, and 17.0%, and decreases of 7.7%, 17.6%, and 14.7% in total sperm count and sperm concentration, respectively, were found to be associated with the tertiles of accumulated smoking amount. Fried food consumption (1-2  times/wk or ≥3  times/wk vs nonconsumers) was found to be associated with decreased total sperm count (10.2% or 24.5%) and sperm concentration (13.7% or 17.2%), respectively. Coffee consumption was found to be associated with increased progressive and nonprogressive motility of 8.9% or 15.4% for subjects consuming 1-2  cups/wk or ≥3  cups/wk of coffee, respectively. Cola consumption appeared an association with decreased semen volume at 4.1% or 12.5% for 1-2  bottles/wk or ≥3  bottles/wk. A cohort to investigate the effects of environmental/sociopsychobehavioral factors act on semen quality was successfully set up. We found smoking, coffee/cola/fried foods consumption to be significantly associated with semen quality from the baseline investigation.


Assuntos
Estilo de Vida , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Análise do Sêmen , Sêmen/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Bebidas/efeitos adversos , Dieta/efeitos adversos , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos , Fumar/efeitos adversos , Motilidade dos Espermatozoides , Adulto Jovem
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