Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 514
Filtrar
1.
J Stroke Cerebrovasc Dis ; 30(7): 105807, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33895428

RESUMO

BACKGROUND: Robot-assisted gait training has been confirmed to have beneficial effect on the rehabilitation of stroke patients. An exoskeleton robot, named BEAR-H1, is designed to help stroke patients with walking disabilities. METHODS: 17 subjects in experimental group and 15 subjects in control group completed the study. The experimental group received 30 minutes of BEAR-H1 assisted gait training(BAGT), and the control group received 30 minutes of conventional training, 5 times/week for 4weeks. All subjects were evaluated with 6-minute walk test (6MWT), Fugl-Meyer Assessment for lower extremity (FMA-LE), Functional Ambulatory Classification (FAC), Modified Ashworth Scale (MAS), and gait analysis at baseline and after 4 weeks intervention. RESULTS: The improvements of 6MWT, FMA-LE, gait speed, cadence, step length and cycle duration in BAGT group were more noticeable than in the control group. However, there was no difference in the assessment of MAS between two groups. CONCLUSIONS: Our results showed that BAGT is an effective intervention to improve the motor and walking ability during 4 weeks training for subacute stroke patients.

2.
Chronobiol Int ; : 1-11, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33823715

RESUMO

Europe has the lowest fertility rate in the world, and 19 European countries are already experiencing negative population growth. Previous studies have shown that light-dark cycle misalignment induces damages to semen quality in animals, but whether shift work impairs male human fertility remains controversial. The diverse types of shift work, which may have distinct health impacts, have not been differentiated in the few previous studies. The present study aims to assess the impact of different male shift work types, i.e., rotating shift work (RSW), permanent shift work (PSW), and daily split shifts (DSS), on male fertility in European countries, based on the European Working Conditions Survey of 54,734 men and 52,457 women of reproductive (15-49 years) age from 35 countries conducted between 2000 and 2015. Year-specific total fertility rate (TFR) for each country was obtained from the World Bank. Mixed linear model was used to analyze the association between the prevalence of shift work types and TFR among the countries during the 15 years span, with adjustment for latitude, per capita GDP, working duration, working frequency, median age of men or women engaged in shift work, education level of men or women, and female shift-work condition in reproductive aged participants. The results showed that the average prevalence of RSW declined from 15.6% in 2000 to 9.8% in 2010, and then rose to 11.1% by 2015, while TFR went up from 1.45 in 2000 to 1.60 in 2010, and then decreased to 1.56 in 2015. A 10% increase of RSW prevalence was associated with a 0.114 decrease of TFR (95% CI: -0.167, -0.061, P < .001), indicating 11.4 fewer births per 100 women throughout lifetime. The association remained significant (ß = -0.088, 95% CI: -0.160, -0.015, P = .020) after adjusting for confounding factors. However, no association was observed between TFR and the prevalence of male PSW (ß = -0.011, 95% CI: -0.094, 0.073, P = .801) or DSS (ß = 0.357, 95% CI: -0.171, 0.884, P = .189). In conclusion, male RSW, rather than PSW and DSS, may reduce TFR. Further studies are needed to validate our findings.

3.
Environ Pollut ; 280: 116883, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33794416

RESUMO

Exposure to outdoor fine particulate matter (PM2.5)-bound polycyclic aromatic hydrocarbons (PAHs) is linked to reproductive dysfunction. However, it is unclear which component of PAHs is responsible for the adverse outcomes. In the Male Reproductive Health in Chongqing College Students (MARHCS) cohort study, we measured the exposure levels of 16 PAHs by collecting air PM2.5 particles and assessed eight PAHs metabolites from four parent PAHs, including naphthalene, fluorene, phenanthrene, and pyrene in urine samples. We investigated compositional profiles and variation characteristics for 16 PAHs in PM2.5, and then assessed the association between PAHs exposure and semen routine parameters, sperm chromatin structure, and serum hormone levels in 1452 samples. The results showed that naphthalene (95% CI: -17.989, -8.101), chrysene (95% CI: -64.894, -47.575), benzo[a]anthracene (95% CI: -63.227, -45.936) and all the high molecular weight (HMW) PAHs in PM2.5 were negatively associated with sperm normal morphology. Most of the low molecular weight (LMW) PAHs, such as acenaphthylene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, benzo[a]anthracene, ∑LMW PAHs and ∑16 PAHs, were correlated with increased sperm motility (all corrected P < 0.05). On the other hand, sperm normal morphology was all negatively associated with urinary metabolites of ∑OH-Nap (95% CI: -5.611, -0.536), ∑OH-Phe (95% CI: -5.741, -0.957), and ∑OH-PAHs (95% CI: -5.274, -0.361). Urinary concentrations of ∑OH-PAHs were found to be negatively associated with sperm high DNA stainability (HDS) (P = 0.023), while ∑OH-Phe were negatively associated with serum testosterone level and sperm HDS (P = 0.004). Spearman correlation analysis showed that except for the urinary OH-Nap metabolites, the rest of the urinary OH-PAHs metabolites were negatively correlated with their parent PAHs in air. The results of this study suggest that various PAHs' components may affect reproductive parameters differently. Inhalation of PAHs in air, especially HMW PAHs, may be a potential risk factor for male reproductive health.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33877318

RESUMO

BACKGROUND AND AIMS: The activation of orbital fibroblasts, the prime targets in thyroid eye disease, is central to its underlying pathogenesis. We aimed to investigate the mechanism of thyroid eye disease orbital fibroblast activation from the perspective of non-coding RNA regulation. METHODS: Immunofluorescence (IF) staining was applied to evaluate the fibrotic changes in target cells. Cell proliferation were evaluated by EDU and colony formation assays. Collagen I concentration was determined by ELISA assay. Human microarray analysis was performed on three thyroid eye disease and 3 healthy control orbital tissue samples. RESULTS: Bioinformatics analysis showed that cell adhesion signaling factors were differentially expressed in thyroid eye disease tissues, including I-CAM-1, I-CAM-4, V-CAM, and CD44, which were all upregulated in diseased orbital tissues. LncRNA LPAL2 level was also upregulated in orbital tissues and positively correlated with I-CAM-1 and I-CAM-4 expression. Stimulation of the thyroid eye disease orbital fibroblasts by TGF-ß1 significantly increased the expression of I-CAM-1, I-CAM-4, and LPAL2. Knockdown of LPAL2 in orbital fibroblasts inhibited TGF-ß1-induced increases in cell adhesion factor levels and orbital fibroblast activation. Microarray profiling was performed on thyroid eye disease and normal orbital tissues to identify differentially expressed miRNAs and miR-1287-5p was remarkably reduced within diseased orbital samples. miR-1287-5p was directly bound to EGFR 3'UTR and LPAL2 and LPAL2 modulated EGFR/AKT signaling through targeting miR-1287-5p. CONCLUSIONS: The LPAL2/miR-1287-5p axis modulated TGF-ß1-induced increases in cell adhesion factor levels and thyroid eye disease orbital fibroblast activation through EGFR/AKT signaling.

6.
Int J Biol Sci ; 17(4): 995-1009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867824

RESUMO

Homoharringtonine (HHT), a natural alkaloid derived from the cephalotaxus, exhibited its anti-cancer effects in hematological malignancies clinically. However, its pesticide effects and mechanisms in treating solid tumors remain unclear. In this study, we found that HHT was capable of inhibiting tumor growth after 5-days treatment of breast cancer cells, MCF-7, in vivo. Furthemore, HHT also significantly inhibited the cancer cell growth and induced cell apoptosis in vitro. miRNA sequencing proved miR-18a-3p was noticeably downregulated in the cells after HHT treatment. Moreover, downregulating miR-18a-3p increased HHT-induced cell apoptosis; our data supported that HHT suppressed miR-18a-3p expression and inhibited tumorigenesis might via AKT-mTOR signaling pathway. In conclusion: our study proved that HHT suppressed breast cancer cell growth and promoted apoptosis mediated by regulating of the miR-18a-3p-AKT-mTOR signaling pathway, HHT may be a promising antitumor agent in breast cancer treatment.

7.
Aging Cell ; : e13343, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721419

RESUMO

Although important factors governing the meiosis have been reported in the embryonic ovary, meiosis in postnatal testis remains poorly understood. Herein, we first report that SRY-box 30 (Sox30) is an age-related and essential regulator of meiosis in the postnatal testis. Sox30-null mice exhibited uniquely impaired testis, presenting the abnormal arrest of germ-cell differentiation and irregular Leydig cell proliferation. In aged Sox30-null mice, the observed testicular impairments were more severe. Furthermore, the germ-cell arrest occurred at the stage of meiotic zygotene spermatocytes, which is strongly associated with critical regulators of meiosis (such as Cyp26b1, Stra8 and Rec8) and sex differentiation (such as Rspo1, Foxl2, Sox9, Wnt4 and Ctnnb1). Mechanistically, Sox30 can activate Stra8 and Rec8, and inhibit Cyp26b1 and Ctnnb1 by direct binding to their promoters. A different Sox30 domain required for regulating the activity of these gene promoters, providing a "fail-safe" mechanism for Sox30 to facilitate germ-cell differentiation. Indeed, retinoic acid levels were reduced owing to increased degradation following the elevation of Cyp26b1 in Sox30-null testes. Re-expression of Sox30 in Sox30-null mice successfully restored germ-cell meiosis, differentiation and Leydig cell proliferation. Moreover, the restoration of actual fertility appeared to improve over time. Consistently, Rec8 and Stra8 were reactivated, and Cyp26b1 and Ctnnb1 were reinhibited in the restored testes. In summary, Sox30 is necessary, sufficient and age-associated for germ-cell meiosis and differentiation in testes by direct regulating critical regulators. This study advances our understanding of the regulation of germ-cell meiosis and differentiation in the postnatal testis.

8.
Chronobiol Int ; : 1-12, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33715553

RESUMO

Recent studies have shown that the reduction of sperm count is associated with sleep behaviors, including restricted/excessive sleep duration, late sleep time midpoint, and shift of sleep midpoint time (social jetlag). Chronotype is suggested to regulate sleep behaviors; however, the relationship between chronotype and human sperm count is unknown. The relationship between sleep behaviors and human sperm count, when sleep behaviors as well as chronotype are controlled is also unclear. We performed a path analysis of the data obtained from 667 Chinese men recruited into the MARHCS (Male Reproductive Health in Chongqing College Students) study. Chronotype, sleep duration, sleep time midpoint, and social jetlag were estimated by the Munich Chronotype Questionnaire. Sperm count was measured by computer-aided sperm analysis. The comprehensive relationship between chronotype, all sleep behaviors, and sperm count was tested by path analysis, in which the standardized residual of sperm count was used for adjustment of age, abstinence period, body mass index, tobacco smoking, alcohol drinking, and intake of tea, cola, and coffee. Our major findings are: (1) Chronotype negatively correlated with sleep duration (correlation coefficient (R) = -0.32, P < .001) and positively correlated with sleep midpoint (R = 0.65, P < .001) and social jetlag (R = 0.37, P < .001). (2) Sleep duration (U-shape transformed; R = -0.11, P = .005), sleep midpoint (R = -0.09, P = .021), and social jetlag (R = -0.12, P = .001), respectively, correlated with sperm count in univariate analysis. The relationship between sleep midpoint and sperm count disappeared when social jetlag was controlled. (3) Path analysis showed that chronotype is connected with sperm count through two pathways: via sleep duration (standardized path coefficient = -0.09, 95% CI: -0.17 to -0.01, P = .030) and via social jetlag (standardized path coefficient = -0.09, 95% CI: -0.17 to -0.01, P = .031). For men of earlier, intermediate, and later tertile of chronotype, the sleep-duration-related decrease of sperm count was separately estimated to be 16.3%, 12.8%, and 11.6%, while the social-jetlag-related decrease of sperm count was estimated to be 9.3%, 12.8%, and 19.2%. The total effect of sleep behaviors on sperm count was estimated to be 25.7%, 25.6%, and 30.7%, with an average of 27.4% for men of different chronotypes. The present study showed that men of earlier chronotype were prone to restricted/excessive sleep duration, while men of later chronotype were prone to social jetlag, both of which correlated with reduced sperm count, suggesting that chronotype may modulate the sleep behaviors and exert dual effects on sperm count via different sleep behaviors, leading to a ubiquitous sperm decline. Men of different chronotypes should take care to avoid different types of improper sleep behaviors, so as to prevent such deleterious effect on sperm count.

9.
J Food Biochem ; : e13709, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33778958

RESUMO

The thymus regulates a specific microenvironment for the growth and maturation of naive T cells. Involution of immune function was an important factor during body aging. Preventing the senescence of immune organs has become a major medical issue. Resveratrol (RSV) has been proved to delay the aging of many organs including the thymus. However, the underlying mechanism remains indefinite and the dosages of RSV on thymus involution need to be further clarified. In the current study, the senescence-accelerated mice were produced using d-galactose for two months. RSV at different dosages (25, 50, 100 mg kg-1  day-1 ) was then administered. The alteration of the thymic morphological structure was observed. It showed that three dosages of RSV significantly decreased cellular senescence of the thymus and no dosage difference was detected. For cellular proliferation and apoptosis of the thymus, 50 and 25 mg/kg per day of RSV displayed the best effects on cellular proliferation and apoptosis in the thymus, respectively. Furthermore, 50 mg/kg per day of RSV increased the expression of FoxN1 both at transcription and translation levels. These findings indicated that RSV could delay thymus atrophy in a dosage-dependent pattern and FoxN1 might involve in the beneficial mechanism of RSV, which was of great significance for the enhancement of thymic health and organic immunity. PRACTICAL APPLICATIONS: Resveratrol has been proved to delay aging of many organs including of thymus. In the present study, we explored the dosage of resveratrol on thymus involution and the expression of transcription factors forkhead box protein N1 (FoxN1) in the senescenceaccelerated mice induced by D-galactose. The results indicated that resveratrol could delay thymus atrophy in a dosage-dependent pattern within a certain dose range, and higher RSV concentration may have drug toxicity, which suggests that the dosage of RSV requires attention, And FoxN1 might involve in the beneficial mechanism of resveratrol supplement, which was of great significance to explore the mechanism for the enhancement of thymus immunity.

10.
Sci Total Environ ; 774: 145691, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611002

RESUMO

Air pollution, which is associated with male reproductive health. However, it is unknown the acute effects of ambient air pollutants exposure on male reproductive hormones. The current study, we measured serum levels of reproductive hormone in 2030 blood samples gathered from The Male Reproductive Health in Chongqing College Students (MARHCS) cohort study. We derived a full coverage of ambient air pollutant (PM10, PM2.5, SO2, NO2, CO and O3) concentrations by employing machine learning algorithms, and used a mixed-effect model to estimate single-day and cumulative effects of air pollutants exposure on serum reproductive hormones. Our results showed that (1) PM10 and PM2.5 concentrations were positively associated with estradiol (E2) in both single and cumulative lag days, but were negatively associated with the ratio of Testosterone/E2 (the T/E2 ratio). NO2 was positively associated with estradiol at lag day 2 (95% CI: 0.290, 0.881; corrected P = 0.048) and lag 0-2 days (95% CI: 0.523, 1.337; corrected P = 0.003), with progesterone (P) at lag day 2 and lag day 3 (corrected P < 0.05). There was also a positive association between CO exposure and progesterone at lag day 2. (2) SO2 was inversely associated with E2 at lag day 3, 4 and lag 0-4 days, and progesterone at lag day 0, 1, 2 and lag 0-1, 0-2, 0-4 days, but positively associated with the T/E2 ratio at lag day 3, 4 and lag 0-4 days (corrected P < 0.05). O3 exposure was negatively associated with E2 at lag day 3 (95% CI: -0.216, -0.074, corrected P = 0.03). (3) No significant associations were found between the cumulative daily average air pollutant exposure of CO, O3 and hormone outcomes. This study suggests that short-term exposure to air pollutants may thus alter reproductive hormone levels, especially on serum estradiol, progesterone levels and the T/E2 ratio.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Hormônios , Humanos , Masculino , Material Particulado/efeitos adversos , Material Particulado/análise , Saúde Reprodutiva , Estudantes
11.
Artigo em Inglês | MEDLINE | ID: mdl-33556482

RESUMO

Cognitive and sensory deficits were considered a core feature of major depressive disorder (MDD). However, few studies investigated stereopsis integrity in patients with MDD. Thus, the objectives of this study investigated stereopsis integrity and its correlations with cognitive function and depressive symptom in patients with MDD. 90 patients with MDD and 116 healthy controls (HCs) were enrolled in this study. Their stereoacuity was evaluated using the Titmus Stereopsis Test as well as assessing their cognitive function and depressive symptom by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Hamilton Depression Scale (HAMD). Log seconds of arc was significantly higher in patients than HCs (1.92 ± 0.41 versus 1.67 ± 0.16, t = 5.35, p < 0.0001). The percentage of patients with correct stereopsis detection was markedly declined in 400 (z = 3.06, p = 0.002), 200 (z = 3.84, p < 0.001), 140 (z = 4.73, p < 0.001), 100 (z = 4.58, p < 0.001), 80 (z = 5.06, p < 0.001), 60 (z = 4.72, p < 0.001), 50 (z = 4.24, p < 0.001), and 40 (z = 4.85, p < 0.001) seconds of arc compared with HCs. Log seconds of arc was significantly correlated with the RBANS total score (r = -0.38, p < 0.0001), subscores of attention (r = -0.49, p < 0.0001) and language (r = -0.33, p = 0.001) rather than HAMD score (r = 0.03, p = 0.78) in MDD patients. In addition, log seconds of arc was significantly related to the RBANS total score (r = -0.58, p < 0.0001) and language score (r = -0.45, p = 0.006) rather than attention score (r = -0.30, p = 0.07) in HCs. Further stepwise multivariate regression analyses showed the negative correlation of log seconds of arc with attention score (ß = -0.80, t = -3.95, p < 0.0001) rather than HAMD score (ß = -0.008, t = -0.09, p = 0.93) in MDD patients. However, there was no relationship between log seconds of arc and attention score in HCs (ß = 1.52, t = 1.19, p = 0.24). Our results identified the marked deficits of stereopsis in MDD patients that were tightly correlated with their attention functioning rather than depressive symptom.

12.
Bioresour Technol ; 326: 124699, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33535150

RESUMO

Utilization of glycerol, a biodiesel byproduct, has not been well explored. In the present study, glycerol and the other carbon sources were studied for cometabolism of dibenzothiophene (DBT), a model chemical commonly used in bioremediation studies, by Paraburkholderia sp. C3. This study showed a direct association between rhamnolipids (RLs) biosynthesis and DBT biodegradation induced by different carbon sources in a Paraburkholderia specie. Glycerol can induce the strain C3 produce at least four RLs. The RL precursor is mainly derived from the fatty acid synthesis (FAS II) and ß-oxidation pathway. The genome contained two (fabF and fabG) and four (fadA, fadE, fadB and echA) genes involved in FAS II and ß-oxidation, respectively. The genome also carried the rhlA and rhlB genes involved in rhamnosyltransferase for RL biosynthesis and two DBT dioxygenase genes (nahAc and catA). The findings suggest a viable approach of using the biodiesel byproduct glycerol to remediate contaminated environments.


Assuntos
Biocombustíveis , Glicerol , Ácidos Graxos , Redes e Vias Metabólicas/genética , Tiofenos
13.
Phys Rev Lett ; 126(6): 060401, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33635691

RESUMO

An energy gap develops near quantum critical point of quantum phase transition in a finite many-body (MB) system, facilitating the ground state transformation by adiabatic parameter change. In real application scenarios, however, the efficacy for such a protocol is compromised by the need to balance finite system lifetime with adiabaticity, as exemplified in a recent experiment that prepares three-mode balanced Dicke state near deterministically [Y.-Q. Zou et al., Proc. Natl. Acad. Sci. U.S.A. 115, 6381 (2018)PNASA60027-842410.1073/pnas.1715105115]. Instead of tracking the instantaneous ground state as unanimously required for most adiabatic crossing, this work reports a faster sweeping policy taking advantage of excited level dynamics. It is obtained based on deep reinforcement learning (DRL) from a multistep training scheme we develop. In the absence of loss, a fidelity ≥99% between prepared and the target Dicke state is achieved over a small fraction of the adiabatically required time. When loss is included, training is carried out according to an operational benchmark, the interferometric sensitivity of the prepared state instead of fidelity, leading to better sensitivity in about half of the previously reported time. Implemented in a Bose-Einstein condensate of ∼10^{4} ^{87}Rb atoms, the balanced three-mode Dicke state exhibiting an improved number squeezing of 13.02±0.20 dB is observed within 766 ms, highlighting the potential of DRL for quantum dynamics control and quantum state preparation in interacting MB systems.

14.
Sci Total Environ ; 771: 144839, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545462

RESUMO

3-methylcholanthrene (3-MCA) is a typical representative PAH. It has strong toxicity and is a typical chemical carcinogen. However, the epigenetic mechanisms underlying 3-MCA-induced tumourigenesis are largely unknown. In this study, a model of the 3-MCA-induced malignant transformation of human bronchial epithelial (HBE) cells was established successfully. The profiles of gene expression and DNA methylation and hydroxymethylation were obtained and analysed with an Illumina HiSeq 4000. A total of 707 genes were found to be significantly up-regulated, and 686 genes were found to be significantly down-regulated. Compared to control cells, 8545 mRNA-associated differentially methylated regions and 15,121 mRNA-associated differentially hydroxymethylated regions in promoters were found to be significantly altered in transformed cells. By using mRNA expression and DNA methylation and hydroxymethylation interaction analysis, 99 differentially expressed genes were identified. Among them, CA9 and EGLN3 were verified to be significantly down-regulated, and CARD6 and LCP1 were shown to be significantly up-regulated, and these genes mainly participated in cell growth, migration and invasion, indicating that these genes were key genes involved in the 3-MCA-induced malignant transformation of HBE cells. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that a large number of differentially expressed genes (DEGs) were involved mainly in RNA polymerase II transcription factor activity, chemical carcinogenesis, base-excision repair (BER), cytokine-cytokine receptor interactions, glycerolipid metabolism, steroid hormone biosynthesis, cAMP signalling pathways and other signalling pathways. Our study suggested that characteristic gene alterations associated with DNA methylation and hydroxymethylation could play important roles in environmental 3-MCA-induced lung carcinogenesis.


Assuntos
Metilação de DNA , Metilcolantreno , Epigênese Genética , Expressão Gênica , Humanos , Pulmão
15.
Theranostics ; 11(5): 2395-2409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500732

RESUMO

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aß). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aß levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aß in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aß clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

16.
Int J Biol Macromol ; 173: 136-145, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33482202

RESUMO

Herbivores gastrointestinal microbiota is of tremendous interest for mining novel lignocellulosic enzymes for bioprocessing. We previously reported a set of potential carbohydrate-active enzymes from the metatranscriptome of the Hu sheep rumen microbiome. In this study, we isolated and heterologously expressed two novel glucanase genes, Cel5A-h38 and Cel5A-h49, finding that both recombinant enzymes showed the optimum temperatures of 50 °C. Substrate-specificity determination revealed that Cel5A-h38 was exclusively active in the presence of mixed-linked glucans, such as barley ß-glucan and Icelandic moss lichenan, whereas Cel5A-h49 (EC 3.2.1.4) exhibited a wider substrate spectrum. Surprisingly, Cel5A-h38 initially released only cellotriose from lichenan and further converted it into an equivalent amount of glucose and cellobiose, suggesting a dual-function as both endo-ß-1,3-1,4-glucanase (EC 3.2.1.73) and exo-cellobiohydrolase (EC 3.2.1.91). Additionally, we performed enzymatic hydrolysis of sheepgrass (Leymus chinensis) and rice (Orysa sativa) straw using Cel5A-h38, revealing liberation of 1.91 ± 0.30 mmol/mL and 2.03 ± 0.09 mmol/mL reducing sugars, respectively, including high concentrations of glucose and cellobiose. These results provided new insights into glucanase activity and lay a foundation for bioconversion of lignocellulosic biomass.


Assuntos
Proteínas de Bactérias/metabolismo , Celobiose/biossíntese , Celulose 1,4-beta-Celobiosidase/metabolismo , Endo-1,3(4)-beta-Glucanase/metabolismo , Glucose/biossíntese , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/genética , Celulose/metabolismo , Celulose 1,4-beta-Celobiosidase/genética , Clonagem Molecular , Endo-1,3(4)-beta-Glucanase/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Microbioma Gastrointestinal/fisiologia , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Glucanos/metabolismo , Hidrólise , Cinética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rúmen/microbiologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Ovinos/microbiologia , Especificidade por Substrato , Trioses/metabolismo , beta-Glucanas/metabolismo
17.
Genomics ; 113(2): 740-754, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516849

RESUMO

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.

18.
J Mol Neurosci ; 2021 Jan 30.
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.

19.
Sci Total Environ ; 767: 144380, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33450593

RESUMO

Male reproductive damage in the general population comprises different disorders in various biomarkers, which could be respectively caused by a number of exposure factors. However, researchers considering the environmental/behavioral/psychological exposures together to evaluate their contribution to male reproductive damage are still lacking. The present study investigated the comprehensive association between 138 environmental/behavioral/psychological exposures and 32 male reproductive biomarkers in 796 young Chinese men using graph-guided fused lasso (GFLASSO) and hierarchical clustering methods. All biomarkers were found to be associated with various exposures. A combination of these exposures not only predicted the levels of single biomarkers in another test dataset, but also identified the comprehensive reproductive features by clustering the men into five subgroups with distinct damages representing disrupted spermatogenesis with abnormal sperm morphology, low sperm motility with DNA fragmentation, chromatin immaturity, aberrant endocrine, or DNA strand breakage. The findings can be used to suggest a novel way to identify the males with a high risk of reproductive damage and develop personalized preventive strategies.


Assuntos
Infertilidade Masculina , Motilidade Espermática , Biomarcadores , China , Humanos , Masculino , Contagem de Espermatozoides , Espermatozoides , Estudantes
20.
Chempluschem ; 86(1): 191-197, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33502826

RESUMO

Two new polyoxometalate (POM)-based hybrid compounds modified by a Schiff base, [Fe(DAPSC)(H2 O)2 ]2 [HPMo2 V Mo10 VI O40 ] ⋅ 5H2 O (1) and [Fe(DAPSC)(H2 O)]2 [HPV3 IV Mo4 V Mo7 VI O42 ] ⋅ 6H2 O (2), (DAPSC=2,6-diacetylpyridine bis-(semicarbazone)), have been successfully constructed from typical Keggin POMs, iron ions, and DAPSC ligands under hydrothermal condition. Structural analysis demonstrates that the Fe-Schiff base ligand units are free from polyacid anions in compound 1. While in compound 2, the Fe-Schiff base ligand units are bridged with polyacid anions via Fe-O bonds to emerge a stable double-supported skeleton. Noticeably, owing to the introduction of vanadium in H5 PMo10 V2 O40 ⋅ 32.5H2 O, a divanadium-capped configuration is shaped in compound 2. Besides, the third-order nonlinear optical (NLO) properties of two compounds were explored. It should be noted that both compounds 1 and 2 have two-photon absorption properties, which indicates that the two compounds are potential nonlinear optical materials.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...