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1.
J Acoust Soc Am ; 150(3): 1997, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598622

RESUMO

Calibration methods and facilities have been employed to directly obtain sensitivities of an underwater acoustic vector receiver using two methods based on laser Doppler vibrometry. The vector receiver was first calibrated in a standing wave tube over the frequency range 20 Hz to 2 kHz, where the oscillatory velocity of the water-air interface was measured to determine the sound particle velocity at the position of vector receiver based on waveguide theory. In the frequency range 2.5-10 kHz, the vector receiver was calibrated in an anechoic vessel with dimensions of 1.2 m diameter × 1.8 m length using wideband signals, with a laser Doppler vibrometer used to detect the oscillatory motion of a plastic pellicle, which was sufficiently thin to follow the acoustic particle motion. The uncertainties of the calibration using the optical method were estimated to be 0.7-0.8 dB at 95% confidence interval. The calibration results were compared with those obtained using a reciprocity method in a 50 m × 15 m × 10 m water tank and using a comparison method in a standing wave tube, and the largest deviation did not exceed 1.0 dB over the frequency range 20 Hz to 10 kHz.

2.
Can J Gastroenterol Hepatol ; 2021: 9996358, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513751

RESUMO

Background: The performance of risk prediction models for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) was uncertain. The aim of the study was to critically evaluate the reports of transparent and external validation performances of these prediction models based on system review and meta-analysis. Methods: A systematic search of the Web of Science and PubMed was performed for studies published until October 17, 2020. The transparent reporting of a multivariable prediction model for the individual prognosis or diagnosis (TRIPOD) tool was used to critically evaluate the quality of external validation reports for six models (CU-HCC, GAG-HCC, PAGE-B, mPAGE-B, REACH-B, and mREACH-B). The area under the receiver operator characteristic curve (AUC) values was to estimate the pooled external validating performance based on meta-analysis. Subgroup analysis and metaregression were also performed to explore heterogeneity. Results: Our meta-analysis included 22 studies published between 2011 and 2020. The compliance of the included studies to TRIPOD ranged from 59% to 90% (median, 74%; interquartile range (IQR), 70%, 79%). The AUC values of the six models ranged from 0.715 to 0.778. In the antiviral therapy subgroups, the AUC values of mREACH-B, GAG-HCC, and mPAGE-B were 0.785, 0.760, and 0.778, respectively. In the cirrhosis subgroup, all models had poor discrimination performance (AUC < 0.7). Conclusions: A full report of calibration and handling of missing values would contribute to a greater improvement in the quality of external validation reports for CHB-related HCC risk prediction. It was necessary to develop a specific HCC risk prediction model for patients with cirrhosis.

3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 821-827, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533130

RESUMO

Objective To investigate the inflammatory induction effect of HCT-116 colorectal cancer cells on normal fibroblasts (NFs) extracted from para-cancerous tissues and the effect of cancer associated fibroblasts (CAFs) on cancer cell migration and its potential mechanism. Methods The enzyme digestive method was used to extract NFs and CAFs from tissues. Spatial Gene Expression Dataset was downloaded to analyze transcriptional expression levels of inflammatory factors including transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α), C-X-C motif chemokine ligand 2 (CXCL2), interleukin-1ß (IL-1ß), and stromal cell-derived factor-1 (SDF-1). In vitro direct and indirect co-culture models were used to study the interaction between fibroblasts and cancer cells. Flow cytometry was used to detect expressions of fibroblast activated protein (FAP) and α-smooth muscle actin (α-SMA). Inflammatory factors TGF-ß, TNF-α, CXCL2, IL-1ß, and SDF-1 secreted in medium were measured by ELISA. Three co-culture groups were set up in which HCT-116 cells were co-cultured respectively with NFs, CAFs, and CAFs pretreated with AMD3100, an inhibitor of SDF-1. Cell migration ability was evaluated by the cell scratch-wound assay and the TranswellTM migration assay. Results CAFs expressed higher levels of FAP and α-SMA than NFs, and HCT-116 cancer cells induced the transformation of NFs to CAFs. Compared to NFs, CAFs secreted higher levels of inflammatory factors TGF-ß, TNF-α, CXCL2, IL-1ß, and SDF-1, while in the in vitro co-culture models cancer cells induced the secretion of SDF-1 but had no effect on secretions of TGF-ß, TNF-α, CXCL2, and IL-1ß from NFs. CAFs significantly stimulated cancer cell migration compared to NFs, which was weakened by AMD3100, an inhibitor of SDF-1. Conclusion Colorectal cancer cells induce the transformation of NFs to CAFs, and CAFs stimulated cancer cell migration with the SDF-1 secreted.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CXCL12/genética , Neoplasias Colorretais/genética , Fibroblastos , Humanos
4.
Science ; 373(6555): 662-673, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34353949

RESUMO

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc-HULC mimics reduced excessive Phe in Pair -/- and Pah R408W/R408W mice and improved the Phe tolerance of these mice.


Assuntos
Fenilalanina Hidroxilase/metabolismo , Fenilalanina/metabolismo , Fenilcetonúrias/genética , RNA Longo não Codificante/genética , Acetilgalactosamina , Animais , Biopterina/análogos & derivados , Biopterina/metabolismo , Biopterina/uso terapêutico , Dieta , Modelos Animais de Doenças , Feminino , Hepatócitos/metabolismo , Humanos , Fígado/embriologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Conformação de Ácido Nucleico , Fenilalanina/administração & dosagem , Fenilalanina Hidroxilase/deficiência , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/tratamento farmacológico , Fenilcetonúrias/metabolismo , Ligação Proteica , RNA Longo não Codificante/química , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/uso terapêutico
5.
Anal Chem ; 93(36): 12409-12416, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34464100

RESUMO

Mechanisms of emissions, especially electrochemiluminescence (ECL), for graphene quantum dots (GQDs) are poorly understood, which makes near-infrared (NIR)-emitting GQDs difficult to create. To explore this poorly understood NIR ECL, two GQDs, nitrogen-doped GQDs (GQD-1) and nitrogen- and sulfur-doped ones (GQD-2), were prepared by a simple one-step solvothermal reaction with similar core structures but different surface states. The GQDs were analyzed by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. Photoluminescence results, with a comparable quantum efficiency of 13% to strong luminophores in aqueous media, suggested a mechanism that the emission mainly depends on the core structure while slightly adjusted by the heteroatom doping. ECL of GQD-2 dispersed in aqueous media with K2S2O8 as the coreactant was measured by means of ECL-voltage curves and ECL spectroscopy, demonstrating strong NIR emissions between 680 and 870 nm, with a high ECL efficiency of 13% relative to that of the Ru(bpy)32+/K2S2O8 system. Interestingly, ECL is generated by surface excited states emitting light at a much longer wavelength in the NIR region. The easily prepared GQD-2 has several advantages such as low cost and quite strong NIR-ECL in aqueous media, with which wide applications in biodetection are anticipated.


Assuntos
Grafite , Pontos Quânticos , Medições Luminescentes , Nitrogênio , Água
6.
Food Chem ; 368: 130816, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34416489

RESUMO

Acrylamide (AA), a potential carcinogen, is commonly formed in foods rich in carbohydrates at high heat. It is known that AA-induced mitochondrial dysfunction is responsible for its toxicity. Previously we found AA exposure increased miR-27a-5p expression in livers of SD rats. Here, the regulation mechanism of miR-27a-5p in mitochondrial dysfunction was investigated in rat liver cell lines (IAR20) and SD rats. The results showed that the overexpressed miR-27a-5p contributes to modulating mitochondrial dysfunction and Btf3 is identified as its target gene. The knockdown of Btf3 increases the cleaved PARP1 level and the phosphorylation of ATM and p53, which results in mitochondria-dependent apoptosis. Therefore, the miR-27a-5p-Btf3-ATM-p53 axis might play a vital role in the promotion of AA-induced cell apoptosis through disrupting mitochondrial structure and function. This would provide a potential target for the assessment and intervention of AA toxicity.

7.
Genome Med ; 13(1): 137, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454586

RESUMO

BACKGROUND: Exercise training is well established as the most effective way to enhance muscle performance and muscle building. The composition of skeletal muscle fiber type affects systemic energy expenditures, and perturbations in metabolic homeostasis contribute to the onset of obesity and other metabolic dysfunctions. Long noncoding RNAs (lncRNAs) have been demonstrated to play critical roles in diverse cellular processes and diseases, including human cancers; however, the functional importance of lncRNAs in muscle performance, energy balance, and obesity remains elusive. We previously reported that the lncRNA H19 regulates the poly-ubiquitination and protein stability of dystrophin (DMD) in muscular dystrophy. METHODS: Here, we identified mouse/human H19-interacting proteins using mouse/human skeletal muscle tissues and liquid chromatography-mass spectrometry (LC-MS). Human induced pluripotent stem-derived skeletal muscle cells (iPSC-SkMC) from a healthy donor and Becker Muscular Dystrophy (BMD) patients were utilized to study DMD post-translational modifications and associated proteins. We identified a gain-of-function (GOF) mutant of H19 and characterized the effects on myoblast differentiation and fusion to myotubes using iPSCs. We then conjugated H19 RNA gain-of-function oligonucleotides (Rgof) with the skeletal muscle enrichment peptide agrin (referred to as AGR-H19-Rgof) and evaluated AGR-H19-Rgof's effects on skeletal muscle performance using wild-type (WT) C57BL/6 J mice and its anti-obesity effects using high-fat diet (HFD)- and leptin deficiency-induced obese mouse models. RESULTS: We demonstrated that both human and mouse H19 associated with DMD and that the H19 GOF exhibited enhanced interaction with DMD compared to WT H19. DMD was found to associate with serine/threonine-protein kinase MRCK alpha (MRCKα) and α-synuclein (SNCA) in iPSC-SkMC derived from BMD patients. Inhibition of MRCKα and SNCA-mediated phosphorylation of DMD antagonized the interaction between H19 and DMD. These signaling events led to improved skeletal muscle cell differentiation and myotube fusion. The administration of AGR-H19-Rgof improved the muscle mass, muscle performance, and base metabolic rate of WT mice. Furthermore, mice treated with AGR-H19-Rgof exhibited resistance to HFD- or leptin deficiency-induced obesity. CONCLUSIONS: Our study suggested the functional importance of the H19 GOF mutant in enhancing muscle performance and anti-obesity effects.

8.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360951

RESUMO

Epidemiological studies have implied that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the development and progression of Alzheimer's disease (AD). However, the underlying mechanisms are notably understudied. Using a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) (APP/PS1) expressing transgenic (Tg) mice and neuroblastoma (N) 2a cells as in vivo and in vitro models, we revealed the mechanisms of indomethacin in ameliorating the cognitive decline of AD. By screening AD-associated genes, we observed that a marked increase in the expression of α2-macroglobulin (A2M) was markedly induced after treatment with indomethacin. Mechanistically, upregulation of A2M was caused by the inhibition of cyclooxygenase-2 (COX-2) and lipocalin-type prostaglandin D synthase (L-PGDS), which are responsible for the synthesis of prostaglandin (PG)H2 and PGD2, respectively. The reduction in PGD2 levels induced by indomethacin alleviated the suppression of A2M expression through a PGD2 receptor 2 (CRTH2)-dependent mechanism. Highly activated A2M not only disrupted the production and aggregation of ß-amyloid protein (Aß) but also induced Aß efflux from the brain. More interestingly, indomethacin decreased the degradation of the A2M receptor, low-density lipoprotein receptor-related protein 1 (LRP1), which facilitated the brain efflux of Aß. Through the aforementioned mechanisms, indomethacin ameliorated cognitive decline in APP/PS1 Tg mice by decreasing Aß production and clearing Aß from the brains of AD mice.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Indometacina/farmacologia , Placa Amiloide/tratamento farmacológico , alfa-Macroglobulinas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Humanos , Indometacina/uso terapêutico , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placa Amiloide/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Regulação para Cima , alfa-Macroglobulinas/genética
9.
Hum Vaccin Immunother ; : 1-9, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34357833

RESUMO

This study evaluated different varicella vaccination strategies in Jiangsu province, China. A decision-tree Markov model was used to evaluate the cost effectiveness of various varicella vaccination strategies for children, including direct and selective vaccination (serotesting pre-vaccination). A cohort of one-year-old children was followed through 60 one-year Markov cycles. The parameter estimation was based on field work, the literature, and statistical yearbooks. We calculated the incremental cost-utility ratio (ICUR) using the saved quality-adjusted life year (QALY). One-way and probability sensitivity analyses were performed to assess uncertainty. Among 100,000 cohort members, one-dose and two-dose direct vaccination averted 8061 and 10,701 varicella cases, respectively, compared with no vaccination. Furthermore, compared with no vaccination, one-dose and two-dose direct vaccination saved one QALY at the ICUR of USD 21,401.33 and USD 35,420.81, respectively, at less than three times the per capita gross domestic product (USD 47,626.86) of Jiangsu. The ICURs of the one-dose and two-dose selective strategies versus no vaccination were USD 42,623.62 and USD 51,406.35 per QALY gained, respectively. The cost effectiveness results were most sensitive to the QALY loss of outpatients and vaccine prices. Thus, in Jiangsu, one-dose and two-dose direct varicella vaccination in children could be cost effective at the willingness to pay threshold of three times provincial GDP per capita from a societal perspective. The findings were sensitive to the vaccine price and health utility of varicella cases.

10.
Methods Mol Biol ; 2372: 1-10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34417737

RESUMO

Long non-coding RNAs (LncRNAs) are non-protein coding transcripts longer than 200 nucleotides. Recent studies have revealed that nearly 80% of transcripts in human cells are lncRNA species. Based on their genomic location, most lncRNAs can be characterized as large intergenic non-coding RNAs, natural antisense transcripts, pseudogenes, and long intronic ncRNAs, as well as other divergent transcripts. However, despite mounting evidence suggesting that many lncRNAs are likely to be functional, only a small proportion has been demonstrated to be biologically and physiologically relevant due to their lower expression levels and current technique limitations. Thus, there is a greater need to design and develop new assays to investigate the real function of lncRNAs in depth in various systems. Indeed, several methods such as genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA immunoprecipitation followed by sequencing (RIP-seq) have been developed to examine the genome localization of lncRNAs and their interacting proteins in cells. Here, we describe an open-ended method, LncRNA pulldown assay, which has been frequently used to identify lncRNA interacting protein partners in a cellular context. We provide a detailed protocol for this assay with hands-on tips based on our own experience working in the lncRNA field.

11.
J Gen Psychol ; : 1-18, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34328410

RESUMO

Myopic loss aversion (MLA)-a combination of myopic loss and a greater sensitivity to losses than gains-has been proposed to explain the equity premium puzzle and then extended to myopic prospect theory (MPT). However, such an expected-value/utility-based theory has been challenged and the underlying mechanism remains debatable. In the current study, we applied the modified equate-to-differentiate model to address this phenomenon. In Experiment 1, we first directly explored the relationship between individuals' degree of loss aversion and their investment amounts in risky lotteries for both single and repeated plays. We found no correlations between these variables; this was inconsistent with the MLA/MPT prediction. Experiment 2 showed that individuals' evaluation scores of the differences within the dimension (probability or outcome) that has larger differences highly predicted their investment behavior, which supported the equate-to-differentiate model.

14.
Anim Biotechnol ; : 1-13, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34310260

RESUMO

The corpus luteum (CL) is a temporary organ that plays a critical role for female fertility by maintaining the estrous cycle. MicroRNA (miRNA) is a class of non-coding RNAs involved in various biological processes. However, there exists limited knowledge of the role of miRNA in yak CL. In this study, we used high-throughput sequencing to study the transcriptome dynamics of miRNA in yak early (eCL), middle (mCL) and late-stage CL (lCL). A total of 6,730 miRNAs were identified, including 5,766 known and 964 novels miRNAs. Three miRNAs, including bta-miR-126-3p, bta-miR-143 and bta-miR-148a, exhibited the highest expressions in yak CLs of all the three stages. Most of the miRNAs were 20-24 nt in length and the peak was at 22 nt. Besides, most miRNAs with different lengths displayed significant uracil preference at the 5'-end. Furthermore, 1,067, 280 and 112 differentially expressed (DE) miRNAs were found in eCL vs. mCL, mCL vs. lCL, and eCL vs. lCL, respectively. Most of the DE miRNAs were down-regulated in the eCL vs. mCL and eCL vs. lCL groups, and up-regulated in the mCL vs. lCL group. A total of 18,904 target genes were identified, with 18,843 annotated. Pathway enrichment analysis of the DE miRNAs target genes illustrated that the most enriched cellular process in each group included pathways in cancer, PI3K-Akt pathway, endocytosis, and focal adhesion. A total of 20 putative target genes in 47 DE miRNAs were identified to be closely associated with the formation, function or regression of CL. Three DE miRNAs, including bta-miR-11972, novel-miR-619 and novel-miR-153, were proved to directly bind to the 3'-UTR of their predicated target mRNAs, including CDK4, HSD17B1 and MAP1LC3C, respectively. Both of these DE miRNAs and their target mRNAs exhibited dynamic expression profiles across the lifespan of yak CL. This study presents a general basis for understanding of the regulation of miRNA on yak CL and also provides a novel genetic resource for future analysis of the gene network during the estrous cycle in the yak.

15.
Parasitol Res ; 120(8): 2827-2837, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34272998

RESUMO

Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA3) was synthesized and further prepared as self-assembled nanoparticles (DHA3NPs) by a one-step nanoprecipitation method. The pharmacokinetics and antimalarial pharmacodynamics of DHA3NPs were studied in rats and mice infected with Plasmodium yoelii BY265 (PyBY265). DHA3NPs had a regular spherical shape with a uniform size distribution of 140.27 ± 3.59 nm, entrapment efficiency (EE) of 99.63 ± 0.17%, and drug loading efficiency (DL) of 79.62 ± 0.11%. The in vitro release characterization revealed that DHA3NPs were easily hydrolysed into DHA in an esterase environment. The pharmacokinetics study demonstrated that the area under the concentration-time curve (AUC0-t) of DHA in DHA3NPs group was 2070.52 ± 578.76 h×ng×mL-1, which was higher than that of DHA and artesunate (AS) control groups (AUC0-t values of 724.18 ± 94.32 and 448.40 ± 94.45 h×ng×mL-1, respectively) (P < 0.05). The antimalarial pharmacodynamics in vivo suggested that DHA3NPS (ED90 7.82 ± 1.16 µmol×(kg×day)-1) had a superior antimalarial effect compared with that of control groups (ED90 values of 14.68 ± 0.98 (DHA) and 14.34 ± 1.96 (AS) µmol×(kg×day)-1) (P < 0.05). In addition, DHA3NPS reduced the recurrence ratio and improved the cure ratio and survival time. In summary, DHA3NPs exhibited promising pharmacokinetic characteristics and antimalarial pharmacodynamics in vivo.

16.
Prev Med ; 150: 106694, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34171345

RESUMO

We aimed to estimate the coronavirus disease 2019 (COVID-19) vaccine acceptance rate and identify predictors associated with acceptance. To this end, we searched PubMed, Web of Science, Cochrane Library, and Embase databases until November 4, 2020. Meta-analyses were performed to estimate the rate with 95% confidence intervals (CI). Predictors were identified to be associated with vaccination intention based on the health belief model framework. Thirty-eight articles, with 81,173 individuals, were included. The pooled COVID-19 vaccine acceptance rate was 73.31% (95%CI: 70.52, 76.01). Studies using representative samples reported a rate of 73.16%. The pooled acceptance rate among the general population (81.65%) was higher than that among healthcare workers (65.65%). Gender, educational level, influenza vaccination history, and trust in the government were strong predictors of COVID-19 vaccination willingness. People who received an influenza vaccination in the last year were more likely to accept COVID-19 vaccination (odds ratio: 3.165; 95%CI: 1.842, 5.464). Protecting oneself or others was the main reason for willingness, and concerns about side effects and safety were the main reasons for unwillingness. National- and individual-level interventions can be implemented to improve COVID-19 vaccine acceptance before large-scale vaccine rollout. Greater efforts could be put into addressing negative predictors associated with willingness.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Estudos Transversais , Humanos , SARS-CoV-2 , Vacinação
17.
J Agric Food Chem ; 69(27): 7765-7776, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34191505

RESUMO

Acrylamide, a well-documented neurotoxicant, is commonly found as a byproduct of the Maillard reaction in carbohydrate-rich foods. Numerous studies have indicated that acrylamide-induced apoptosis accompanied by mitochondrial dysfunction contributes to its neurotoxicity. However, the mechanisms of how acrylamide causes mitochondrial impairment is not well understood. In this study, we observed destroyed redox balance, accumulated mitochondrial reactive oxygen species (ROS), damaged mitochondrial structures, and activated apoptosis in astrocytes following acrylamide treatment. Furthermore, acrylamide decreased the expression of mitochondrial biogenesis- and dynamics-related genes, including PGC-1α, TFAM, Mfn2, and Opa1, and altered the expression of mitochondrial DNA (mtDNA)-encoded mitochondrial respiratory chain complexes, along with the inhibited mitochondrial respiration. Pretreatment with a mitochondrial ROS scavenger mitoquinone dramatically restored the expressions of PGC-1α, TFAM, Mfn2, and Opa1; protected the mitochondrial structure; and decreased acrylamide-induced apoptosis. Further in vivo experiments confirmed that acrylamide decreased the expressions of PGC-1α, TFAM, Mfn2, and Opa1 in rat brain tissues. These results revealed that acrylamide triggered the mitochondrial ROS accumulation to interfere with mitochondrial biogenesis and dynamics, causing mtDNA damage and finally resulting in mitochondrial dysfunction and apoptosis.


Assuntos
Acrilamida , DNA Mitocondrial , Acrilamida/toxicidade , Animais , DNA Mitocondrial/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
18.
Environ Sci Pollut Res Int ; 28(35): 49153-49165, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33932205

RESUMO

To explore the comprehensive utilization of agricultural wastes, solid-state fermentation was applied to residues of Flammulina velutipes (F. velutipes) and vinegar for use in culturing earthworms. Fermentation technology and earthworm culture technology were optimized by response surface methodology in this study. The optimal fermentation product for earthworm culture was obtained under an inoculum amount of 7.5%, fermentation temperature of 25.6 °C, pH 7.7 and protein content of 18.23%. The optimum culture conditions were a culture density of 18.4 individuals/dm3, an initial pH of 7.2 and a fermentation temperature of 26.8 °C. The daily weight gain multiplier of earthworms was 0.0387 units, and it increased significantly compared with that of the unfermented and cow dung groups. The fermented product of F. velutipes and vinegar residues could be used to culture earthworms and improve the metabolism and antioxidant capacities of earthworms. This provides a new way to comprehensively utilize agricultural waste resources.


Assuntos
Flammulina , Oligoquetos , Ácido Acético , Agricultura , Animais , Bovinos , Feminino , Fermentação , Humanos
19.
Front Endocrinol (Lausanne) ; 12: 630504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959095

RESUMO

Background: Diminished ovarian reserve (DOR) significantly increases the risk of female infertility and contributes to reproductive technology failure. Recently, the role of melatonin in improving ovarian reserve (OR) has attracted widespread attention. However, details on the pharmacological targets and mechanisms of melatonin-improved OR remain unclear. Objective: A systems pharmacology strategy was proposed to elucidate the potential therapeutic mechanism of melatonin on DOR at the molecular, pathway, and network levels. Methods: The systems pharmacological approach consisted of target identification, data integration, network construction, bioinformatics analysis, and molecular docking. Results: From the molecular perspective, 26 potential therapeutic targets were identified. They participate in biological processes related to DOR development, such as reproductive structure development, epithelial cell proliferation, extrinsic apoptotic signaling pathway, PI3K signaling, among others. Eight hub targets (MAPK1, AKT1, EGFR, HRAS, SRC, ESR1, AR, and ALB) were identified. From the pathway level, 17 significant pathways, including the PI3K-Akt signaling pathway and the estrogen signaling pathway, were identified. In addition, the 17 signaling pathways interacted with the 26 potential therapeutic targets to form 4 functional modules. From the network point of view, by regulating five target subnetworks (aging, cell growth and death, development and regeneration, endocrine and immune systems), melatonin could exhibit anti-aging, anti-apoptosis, endocrine, and immune system regulation effects. The molecular docking results showed that melatonin bound well to all hub targets. Conclusion: This study systematically and intuitively illustrated the possible pharmacological mechanisms of OR improvement by melatonin through anti-aging, anti-apoptosis, endocrine, and immune system regulation effects.

20.
Neuromodulation ; 24(6): 983-991, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34008282

RESUMO

OBJECTIVES: Implantable peripheral nerve stimulation has been increasingly used to treat neuropathic pain. This neuromodulation strategy may be an alternative option for intractable trigeminal neuropathic pain; however, evidence for this treatment approach remains limited. A systematic review was conducted to identify studies of patients that underwent peripheral nerve stimulation implantation for trigeminal neuropathic pain. MATERIALS AND METHODS: Databases including, PubMed, EMBASE, and Cochrane Library were searched up to October 5, 2020. The primary outcomes were changes in pain scores and response rates of neuromodulation therapy. A random effects model was used for meta-analysis. Subgroup analysis was performed to examine the source of heterogeneity. RESULTS: Thirteen studies including 221 participants were evaluated. The estimated response rate of neuromodulation treatment was 61.3% (95% CI: 44.4-75.9%, I2  = 70.733%, p < 0.0001) at the last follow-up. The overall reduction in pain scores was 2.363 (95% CI: 1.408-3.319, I2  = 85.723%, p < 0.0001). Subgroup analysis further confirmed that stimulation target (peripheral branch vs. trigeminal ganglion vs. trigeminal nerve root) contributed the heterogeneity across enrolled studies. Better clinical outcome was associated with stimulation of the trigeminal peripheral branch (p < 0.0001). CONCLUSION: Peripheral nerve stimulation may be a promising approach in the management of trigeminal neuropathic pain, especially for patients intractable to conventional therapy.


Assuntos
Terapia por Estimulação Elétrica , Neuralgia , Neuralgia do Trigêmeo , Eletrodos Implantados , Humanos , Neuralgia/terapia , Nervo Trigêmeo , Neuralgia do Trigêmeo/terapia
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