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1.
Artigo em Inglês | MEDLINE | ID: mdl-32159381

RESUMO

Objective: This study aimed at investigating the specific roles of laminarin from seaweed (Laminaria japonica) in hepatocellular carcinoma (HCC) and its potential mechanisms related to senescence marker protein-30 (SMP-30). Materials and Methods: Human HCC cell lines, including Bel-7404 and HepG2, were incubated with different concentrations of laminarin (0, 5, 15, 25, 35, and 45 mg/mL). The cell viability and apoptosis rates were detected by WST-8 cell proliferation assay and flow cytometry, respectively. Hepa 1-6 tumor-bearing mice were injected with different concentrations of laminarin (400, 800, and 1200 mg/kg·d), and tumor volume and weight were measured. The expression of SMP-30 was detected in laminarin-treated Bel-7404 and HepG2 HCC cells and LO2 normal liver cells by quantitative real-time PCR and Western blotting. Results: The treatment with laminarin (48 h) significantly decreased the viability and increased the apoptosis rates of Bel-7404 and HepG2 cells in a dose-dependent manner. The injection of laminarin also significantly decreased the tumor volumes (beginning on the 10th day) and tumor weights (30 d post-injection) of mice in a dose-dependent manner. In addition, the treatment with laminarin (35 mg/mL for 48 h) significantly upregulated SMP-30 in Bel-7404 and HepG2 cells but not in LO2 cells. Conclusion: Laminarin inhibited the proliferation of Bel-7404 and HepG2 cells and inhibited the growth of tumors in Hepa 1-6 tumor-bearing mice by upregulating SMP-30.

2.
Am J Chin Med ; : 1-23, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138532

RESUMO

Oxidative stress (OS) is the common mechanism for age-related diseases. The co-occurrence of osteoporosis (OP) and cardiovascular disease (CVD) in postmenopausal women makes it warranted to find a holistic approach for treatment of multiple diseases or conditions. The rhizome of Ligusticum chuanxiong Hort. (CX), which has high anti-oxidant properties and is widely used for CVD treatment in China, might be the potential candidate. In the present study, CX ethanol extract (CXE) was applied to H2O2 induced MG63 cells to study its effects and mechanisms on osteoblastogenesis against OS. CXE was then administered to six-month-old Sprague Dawley sham or ovariectomized (OVX) rats fed either a low saturated fat-sucrose (LFS) or a high fat-sucrose (HFS) diet for 12 weeks, to confirm its anti-osteoporotic effects. The results demonstrated that CXE directly improved proliferation and differentiation in vitro in an H2O2-induced osteoblast cell model by attenuating cellular reactive oxygen species levels and inhibiting osteoblast apoptosis via PI3K/Akt signaling pathway. CXE significantly improved bone properties as revealed by the increase in trabecular bone mineral density and decrease in trabecular separation at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats but not in LFS-fed OVX rats. CXE ameliorated dyslipidemia, greatly reduced lipid deposition and malondialdehyde levels, improved activities of superoxide dismutase, catalase and glutathione peroxidase in the livers of HFS-fed OVX rats. In conclusion, CXE could favor osteoblastogenesis against OS. The ability of CXE to reduce bone loss in HFS-fed OVX rats was associated with its abilities to correct dyslipidemia, and reduce lipid deposition and OS levels.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32144705

RESUMO

Glyphosate is the active component of several commercial formulations as in Roundup®. The present study was investigated the toxic effects of pure glyphosate or Roundup® on the liver and small intestine of chick embryos. On day 6, a total of 180 fertile eggs injected with deionized water (control group), 10 mg pure glyphosate, or 10 mg of the active ingredient glyphosate in Roundup®/kg egg mass. The results showed an increase in relative weights of the liver in embryos that treated with Roundup®. Furthermore, oxidative stress was observed in the embryos treated with glyphosate or Roundup®, increased total superoxide dismutase, and content of malondialdehyde in the liver and intestine; moreover, decrease of glutathione peroxidase in the liver with increased in the intestine compared with the control. Besides, glutamic-pyruvic transaminase was increased in Roundup® group compared with other groups. Moreover, histopathological alterations in the liver and intestine tissues were observed in treated groups. Suppression of hepatic CYP1A2, CYP1A4, CYP1B1, and MDR1 mRNA expression after exposed to Roundup®. Furthermore, inhibition of CYP1A4 in the duodenum, CYP1A4, and MRP2 in the jejunum in embryos exposed to glyphosate or Roundup®. In addition, glyphosate treatment caused an increase of CYP3A5, CYP1C1, and IFNY mRNA expression in the jejunum and CYP1A2 expression in the ileum, while IFN-Y gene increase in embryos treated with Roundup®. In conclusion, in ovo exposure to glyphosate caused histopathological alterations and induced oxidative stress in the liver and small intestines. Moreover, the expression of cytochrome P450, MDR1, and MRP2 transporters was also modulated in the liver and small intestines for chick embryos.

4.
J Hosp Infect ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32199963

RESUMO

BACKGROUND: Postoperative pneumonia is the third most common complication in surgical patients. However, little is known regarding pneumonia after craniotomy, which is the most commonly performed surgery in the neurosurgery department. AIM: To investigate the incidence of pneumonia and its association with the length of hospital stay, identify risk factors, and build a prediction model with nomogram. METHODS: The study population was based on the American College of Surgeons National Surgical Quality Improvement Program 2005-2017. Both multivariate logistic regression models and linear regression models were employed. FINDINGS: The overall incidence rate of postoperative pneumonia is 3.11% in a total of 57,201 surgeries. The risk factors include age >55, male, lower body mass index, diabetes, functional dependent, ventilator dependence, history of severe chronic obstructive pulmonary disease, hypertension, systemic sepsis, white blood cells >12,000, emergency case, American Society of Anesthesiologists class ≥3, general anesthesia, and total operation time >240 min. Ten featured factors are used in nomogram (C-statistic 0.803). Postoperative pneumonia was associated with extended hospital stay. Compared to other postoperative complications, pneumonia showed the second-highest impact on the extension of hospital stay (4.7 days). CONCLUSION: This study identified several preoperative risk factors for postoperative pneumonia after craniotomy, novel factors including male, low BMI warrants further investigation. The novel nomogram could serve as a reliable tool for evaluating postoperative pneumonia risk preoperatively.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32156109

RESUMO

Introducing an efficient method for the rapid conversion of starch into gluconic acid is desirable to solve the current problems existing in traditional gluconic acid preparation processes. In this study, a robust and easy-to-use multienzymatic cascade reaction system of coimmobilized GA@GOx hybrid nanoflowers with a specific spatial distribution of enzymes by compartmentalization was constructed and applied to catalyze starch to gluconic acid in one pot. In the preparation processes, the glucose oxidase (GOx) hybrid nanoflowers were first synthesized via a self-assembly mechanism, and then, glucoamylase (GA) was adsorbed on the surface of GOx hybrid nanoflowers through the interaction of Cu2+ and amino acids of GA. The optimum preparation conditions and reaction parameters of the GA@GOx hybrid nanoflowers had been investigated. In addition, the morphology, composition, and crystallization of the GA@GOx hybrid nanoflowers had been fully studied. Based on the lower Km, the GA@GOx hybrid nanoflowers with compartmentalization had a better effect of the substrate channeling on the catalytic efficiency. The final results indicated that the overall enzyme activity of the GA@GOx hybrid nanoflowers increased by 1.5 times, and the conversion efficiency was 92.12% within 80 min significantly superior to the free multienzyme system, which showed the outstanding conversion of starch into gluconic acid in one pot.

6.
Biochem Pharmacol ; : 113926, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32217098

RESUMO

BACKGROUND AND PURPOSE: Indoleamine 2, 3-dioxygenase 1 (IDO1) has been linked to neuropathic pain and IDO1 inhibitors have been shown to reduce pain in animals. Some studies have indicated that IDO1 expression increased after neuropathic pain in hippocampus and spinal cord, whether these changes existing in anterior cingulate cortex (ACC) and amygdala remains obscure and how IDO1 inhibition leads to analgesia is largely unknown. Here, we evaluated the antinociceptive effect of PCC0208009, an indirect IDO1 inhibitor, on neuropathic pain and examined the related neurobiological mechanisms. EXPERIMENTAL: Approach The effects of PCC0208009 on pain, cognition and anxiogenic behaviors were evaluated in a rat model of neuropathic pain. Motor disorder, sedation and somnolence were also assessed. Biochemical techniques were used to measure IDO1-mediated signaling changes in ACC and amygdala. Key Results In rats receiving spinal nerve ligation (SNL), IDO1 expression level was increased in ACC and amygdala. PCC0208009 attenuated pain-related behaviors in the formalin test and SNL model and increased cognition and anxiogenic behaviors in SNL rats at doses that did not affect locomotor activity and sleeping. PCC0208009 inhibited IDO1 expression in ACC and amygdala by inhibiting the IL-6-JAK2/STAT3-IDO1-GCN2-IL-6 pathway. In addition, PCC0208009 reversed synaptic plasticity at the functional and structural levels by suppressing NMDA2B receptor and CDK5/MAP2 or CDK5/Tau pathway in ACC and amygdala. Conclusion and Implications These results support the role of IDO1-mediated molecular mechanisms in neuropathic pain and suggest that the IDO1 inhibitor PCC0208009 demonstrates selective pain suppression and could be a useful pharmacological therapy for neuropathic pain.

7.
BMC Anesthesiol ; 20(1): 69, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213162

RESUMO

BACKGROUND: Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. METHODS: Fifteen osteoarthritis patients undergoing total knee replacement due to chronic knee pain and 15 patients without pain undergoing other surgeries with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia. CSF were added to cultured T98G cells in the presence of lipopolysaccharide. IL-6, IL-1ß and TNF-α release from T98G cells were measured using enzyme immunoassay. Antibody array and western blotting were performed using CSF-triggered T98G cell lysates to identify possible signalling targets. Age, gender and pain scores were recorded. Mann-Whitney U test was used to compare IL-6 release and protein expression between groups. Association between IL-6 and pain score was analysed using linear regression. RESULTS: Significant higher levels of IL-6 were released by T98G cells when induced by osteoarthritis patients' CSF in the presence of LPS. The IL-6 levels showed positive association with pain score (adjusted B estimate = 10.1 (95% Confidence Interval 4.3-15.9); p = 0.001). Antibody array conducted with 6 pooled T98G cell lysate induced with osteoarthritis pain patient CSF identified greater than 2-fold proteins including STE20-related kinase adaptor protein and spleen tyrosine kinase. Further validation done using western blotting of individual CSF-triggered T98G cell lysate showed non-significant increase. CONCLUSION: Higher IL-6 release from T98G when triggered by OA-CSF, in the presence of LPS, suggest the presence of "unknown molecule" in CSF that may be crucial in the maintenance phase of chronic pain in our osteoarthritis population. Further studies on the signalling pathways involved in pain and relevance of IL-6 release from T98G cells in other pain models are needed.

8.
G3 (Bethesda) ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32220954

RESUMO

Plants have a variety of strategies to avoid canopy shade and compete with their neighbors for light, collectively called the shade avoidance syndrome (SAS). Plants also have extensive systems to defend themselves against pathogens and herbivores. Defense and shade avoidance are two fundamental components of plant survival and productivity, and there are often tradeoffs between growth and defense. Recently, MYC2, a major positive regulator of defense, was reported to inhibit elongation during shade avoidance. Here, we further investigate the role of MYC2 and the related MYC3 and MYC4 in shade avoidance, and we examine the relationship between MYC2/3/4 and the PIF family of light-regulated transcription factors. We demonstrate that MYC2/3/4 inhibit both elongation and flowering. Furthermore, using both genetic and transcriptomic analysis we find that MYCs and PIFs generally function independently in growth regulation. However, surprisingly, the pif4/5/7 triple mutant restored the petiole shade avoidance response of myc2 (jin1-2) and myc2/3/4 We theorize that increased petiole elongation in myc2/3/4 could be more due to resource tradeoffs or post-translational modifications rather than interactions with PIF4/5/7 affecting gene regulation.

9.
J Magn Reson Imaging ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027071

RESUMO

BACKGROUND: The interpretation system for prostate MRI is largely based on qualitative image contrast of different tissue types. Therefore, a fast, standardized, and robust quantitative technique is necessary. Synthetic MRI is capable of quantifying multiple relaxation parameters, which might have potential applications in prostate cancer (PCa). PURPOSE: To investigate the use of quantitative relaxation maps derived from synthetic MRI for the diagnosis and grading of PCa. STUDY TYPE: Prospective. SUBJECTS: In all, 94 men with pathologically confirmed PCa or benign pathological changes. FIELD STRENGTH/SEQUENCE: T1 -weighted imaging, T2 -weighted imaging, diffusion-weighted imaging, and synthetic MRI at 3.0T. ASSESSMENT: Four kinds of tissue types were identified on pathology, including PCa, stromal hyperplasia (SH), glandular hyperplasia (GH), and noncancerous peripheral zone (PZ). PCa foci were grouped as low-grade (LG, Gleason score ≤6) and intermediate/high-grade (HG, Gleason score ≥7). Regions of interest were manually drawn by two radiologists in consensus on parametric maps according to the pathological results. STATISTICAL TESTS: Independent sample t-test, Mann-Whitney U-test, and receiver operating characteristic curve analysis. RESULTS: T1 and T2 values of PCa were significantly lower than SH (P = 0.015 and 0.002). The differences of T1 and T2 values between PCa and noncancerous PZ were also significant (P ≤ 0.006). The area under the curve (AUC) of the apparent diffusion coefficient (ADC) value was significantly higher than T1 , T2 , and proton density (PD) values in discriminating PCa from SH and noncancerous PZ (P ≤ 0.025). T2 , PD, and ADC values demonstrated similar diagnostic performance in discriminating LG from HG PCa (AUC = 0.806 [0.640-0.918], 0.717 [0.542-0.854], and 0.817 [0.652-0.925], respectively; P ≥ 0.535). DATA CONCLUSION: Relaxation maps derived from synthetic MRI were helpful for discriminating PCa from other benign pathologies. But the overall diagnostic performance was inferior to the ADC values. T2 , PD, and ADC values performed similarly in discriminating LG from HG PCa lesions. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

11.
Langmuir ; 36(9): 2474-2481, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32069412

RESUMO

Carbon dots (CDs) are highly fluorescent nanomaterials with surface carboxyl and amino groups. However, their exact structure remains under debate. In this work, we probed the surface properties of CDs by physically adsorbing them onto various nanomaterials. Three types of nanomaterials, including CeO2 nanoparticles (nanoceria), gold nanoparticles, and graphene oxide were tested. Among them, nanoceria strongly adsorbed the CDs and quenched their fluorescence. For the tested anions to compete with the CDs for adsorption, only phosphate and F- induced desorption of the CDs from nanoceria, and the phosphate-induced desorption was less compared to that by F-. This was opposite to the desorption of DNA from nanoceria, where phosphate induced more DNA desorption. Furthermore, using calcein and fluorescein as representative dyes for comparison, we conclude that the CDs might use their carboxyl groups to adsorb on nanoceria, while DNA uses its phosphate backbone for adsorption. This difference may explain their occupying different surface sites on nanoceria and different displacement by phosphate and F-. Using nanomaterials as probes to understand the surface properties of CDs is effective, and such understanding might in turn be used for building hybrid materials for applications.

12.
Biomacromolecules ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32040910

RESUMO

As a biomaterial, silk presents unique features with a combination of excellent mechanical properties, biocompatibility, and biodegradability. The biodegradability aspects of silk biomaterials, especially with options to control the rate from short (days) to long (years) time frames in vivo, make this protein-based biopolymer a good candidate for developing biodegradable devices used for tissue repairs and tissue engineering, as well as medical device implants. Silk materials, including native silk fibers and a broad spectrum of regenerated silk materials, have been investigated in vitro and in vivo to demonstrate degradation by proteolytic enzymes. In this Review, we summarize the findings on these studies on the enzymatic degradation of Bombyx mori (B. mori) silk materials. We also present a discussion on the factors that dictate the degradation properties of silk materials. Finally, in future perspectives, we highlight some key challenges and potential directions toward the future study of the degradation of silk materials.

13.
Bioorg Chem ; 96: 103615, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32007726

RESUMO

Advanced glycation end-products (AGEs), which instigate many disorders, are mostly mediated by dicarbonyl rearrangements. We studied the corresponding mechanisms of the anti-glycation effects of two anthocyanins purified from mulberry fruits, namely cyanidin 3-glucoside (C3G) and cyanidin 3-rutinoside (C3R), on glycated ß-lactoglobulins (ß-Lg). Both mulberry anthocyanins (MAs) inhibited the AGEs-formation in a dose-dependent manner, but the effect of C3R was significantly stronger than that of C3G (p < 0.05). MAs inhibited AGEs-formation by selectively trapping dicarbonyls, especially glyoxal. The UPLC-ESI-Q-TOF-MS results characterized that C3R formed mono- and di-glyoxal adducts, where C3G only created di-glyoxal adducts. Additionally, C3R could directly interact with some of the glycation sites of ß-Lg. Overall, GO-trapping and ß-Lg-MAs covalent/noncovalent binding are disclosed as the key mechanisms of the anti-AGEs activity of MAs on ß-Lg, which could be valorised as effectual AGEs inhibitors in proteins-rich matrices.

14.
Environ Pollut ; 261: 114129, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045792

RESUMO

Glyphosate is the most popular herbicide used worldwide. This study aimed to investigate the adverse effects of glyphosate on the small intestine and gut microbiota in rats. The rats were gavaged with 0, 5, 50, and 500 mg/kg of body weight glyphosate for 35 continuous days. The different segments of the small intestine were sampled to measure indicators of oxidative stress, ion concentrations and inflammatory responses, and fresh feces were collected for microbiota analysis. The results showed that glyphosate exposure decreased the ratio of villus height to crypt depth in the duodenum and jejunum. Decreased activity of antioxidant enzymes (T-SOD, GSH, GSH-Px) and elevated MDA content were observed in different segments of the small intestine. Furthermore, the concentrations of Fe, Cu, Zn and Mg were significantly decreased or increased. In addition, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MAPK3, NF-κB, and Caspase-3 were increased after glyphosate exposure. The 16 S rRNA gene sequencing results indicated that glyphosate exposure significantly increased α-diversity and altered bacterial composition. Glyphosate exposure significantly decreased the relative abundance of the phylum Firmicutes and the genus Lactobacillus, but several potentially pathogenic bacteria were enriched. In conclusion, this study provides important insight to reveal the negative influence of glyphosate exposure on the small intestine, and the altered microbial composition may play a vital role in the process.

15.
Histochem Cell Biol ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32078038

RESUMO

Serine-52 (Ser52) is the major physiologic site of keratin 18 (K18) phosphorylation. Here, we report that serine-52 phosphorylated K18 (phospho-Ser52 K18) accumulated on centrosomes in a cell cycle-dependent manner. Moreover, we found that phospho-Ser52 K18 was located at the proximal end of the mother centriole. Transfection with the K18 Ser52 → Ala (K18 S52A) mutant prevented centriole localization of phospho-Ser52 K18 and resulted in separation of the mother-daughter centrioles. Inhibition of microtubule polymerization led to the disappearance of aggregated phospho-Ser52 K18 on the centrosome; removal of inhibitors resulted in reaccumulation of phospho-Ser52 K18 in microtubule-organizing centers. Transfection with a K18 S52A mutant inhibited microtubule nucleation. These results reveal a cell cycle-dependent change in centrosome localization of phospho-Ser52 k18 and strongly suggest that the phosphorylation status of Ser52 K18 of mother centrioles plays a critical role in maintaining a tight engagement between mother and daughter centrioles and also contributes to microtubule nucleation.

16.
Anal Chim Acta ; 1104: 125-131, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32106943

RESUMO

We report on the synthesis of manganese oxide doped CDs (MnOx-CDs) by a hydrothermal strategy using manganese (III) acetylacetonate (Mn(III) (C5H7O2)3) as the only raw materials. The MnOx-CDs exhibit water solubility, favorable biocompatibility, low cytotoxicity, and show blue fluorescence with excitation/emission maxima at 326/442 nm with a quantum yield of 11.3%, allowing efficient cellular imaging. The MnOx-CDs have a reversible temperature-sensitive fluorescent property in vitro within 10-60 °C, which can also be used as a sensitive thermometer in living cells. By a scratch assay, the MnOx-CDs can restrain the migration of HepG2 cancer cells, which make the MnOx-CDs be attractive candidates for liver cancer adjuvant treatment. Besides, the fluorescence of the MnOx-CDs is quenched in the presence of Fe3+ due to the formation of a nonfluorescent MnOx-CDs-Fe3+ complex between oxygen-containing groups on the surface of MnOx-CDs and Fe3+, and the quenched fluorescence of MnOx-CDs can be turn-on by dissociation of MnOx-CDs-Fe3+ complexes by biothiols including L-cysteine, homocysteine and glutathione. Therefore, the Fe3+ and biothiols can be sequentially detected with high reliability and accuracy via exploiting the on-off-on nanosensor at room temperature, respectively. Further application to detection biothiols in human serum indicated that the probe was practicality and feasibility in medical field.

17.
Eur J Radiol ; 124: 108858, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035370

RESUMO

PURPOSE: To verify the feasibility of synthetic MRI in quantitative evaluation of lumbar intervertebral disk (IVD) degeneration, as compared to the conventional CarrPurcell-Meiboom-Gill (CPMG) T2 mapping approach. METHODS: Twenty-four patients with chronic low back pain participated in this study. Patients underwent routine lumbar MRI, CPMG T2 mapping, and synthetic MRI (MAGiC) acquisition. The degree of IVD degeneration was derived from T2-weighted images according to the Pfirrmann classification. The correlation between two T2 measurements was assessed by Pearson correlation and Bland-Altman analysis. Statistical differences of quantitative values obtained from MAGiC data across different degeneration grades were quantified by one-way ANOVA. ROC curves were used to test the sensitivity and specificity of CPMG and MAGiC T2 measurements for assessing Pfirrmann grading. RESULTS: T2 values obtained from CPMG and MAGiC data exhibited strong positive correlation (r = 0.962, p < 0.01). Significant negative correlations were found between quantitative values (p < 0.05) and the Pfirrmann grading. Quantitative values show significant difference across Pfirrmann grading groups (one-way ANOVA, p < 0.001). Additionally, post-hoc tests show significant differences of T1 and T2 between adjacent groups among grades I-IV (p < 0.05), while the significant differences of PD were only observed between adjacent groups among grades II-IV (p < 0.05). There is no significant difference between AUCs of T2 values obtained from CPMG and MAGiC data in differentiating grade I/ II, grade II/ III and grade III/IV. CONCLUSIONS: The synthetic MRI may be used to provide quantitative biomarkers for assessing the level of lumbar intervertebral disc degeneration.

18.
Elife ; 92020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985398

RESUMO

The use of genetics has been invaluable in defining the complex mechanisms of aging and longevity. Zebrafish, while a prominent model for vertebrate development, have not been used systematically to address questions of how and why we age. In a mutagenesis screen focusing on late developmental phenotypes, we identified a new mutant that displays aging phenotypes at young adult stages. We find that the phenotypes are due to loss-of-function in the non-classical cadherin celsr1a. The premature aging is not associated with increased cellular senescence or telomere length but is a result of a failure to maintain progenitor cell populations. We show that celsr1a is essential for maintenance of stem cell progenitors in late stages. Caloric restriction can ameliorate celsr1a aging phenotypes. These data suggest that celsr1a function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.

19.
Environ Pollut ; 256: 113368, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31676097

RESUMO

Particulate matter (PM) released from the processes of livestock production has a negative impact on the health of animals and workers. Herein, the concentration, major chemical components, morphology and microbiological compositions of particulate matter 2.5 (PM2.5, particles with aerodynamic diameter less than 2.5 µm) in a broiler breeding house were investigated. The results showed that the PM2.5 distribution in the chicken house was affected by the illumination, draught fans, chicken frame structure and activity of the chickens in the broiler breeding house. Component analysis showed that organic carbon (OC) accounted for the largest proportion, and followed by element carbon (EC), SO42-, NO3-, NH4+, Na+, K+ and Ca2+. Ultrastructural observations revealed that the shape of PM2.5 had a round, rectangular, chain-like and irregular shape. The concentration of endotoxin was approximately 0.3 EU/m3. Microbiological analysis showed that at the genus level, the pathogenic bacteria included Staphylococcus, Corynebacterium, Enterococcus, Parabacteroides, Escherichia and Megamonas. The abundant harmful fungi were Aspergillus, Scopulariopsis, Wallemia, and Fusarium. Through redundancy analysis (RDA) analysis, we determined that OC, EC, Na+, K+, and NH4+ had strong correlations with Brachybacterium, Brevibacterium, Corynebacterium, Escherichia, Scopulariopsis and Microascus. SO42- was closely related to Scopulariopsis and Salinicoccus. Salinicoccus was also strongly correlated with NO3-. Our results indicated that feed, faeces, and outside soot are contributed to the increase in PM2.5 concentration in the chicken house, while the sources of the dominant bacterial and fungi might be feed, faeces, suspended outside soil and cereal crops.

20.
Regul Toxicol Pharmacol ; 110: 104522, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726191

RESUMO

20(s)-ginsenoside Rg3 is a red ginseng-derived compound with the formula C42H72O13 that has been increasingly used by humans, leading to safety concerns regarding this use. In the current study, we conducted a 26-week study during which 20(S)-ginsenoside Rg3 (0, 7, 20, or 60 mg/kg) was continuously administered orally to Beagle dogs in order to explore its toxicity in these animals, with control dogs receiving a vehicle capsule. In total, 10 dogs received each dose of this compound (n = 5 male, n = 5 female per dose). Animals were continuously monitored for a 26-week administration period and a subsequent 4-week follow-up recovery period. At the end of study, we observed no evidence of 20(S)-ginsenoside Rg3 toxicity in clinical indications, body weight, food intake, ophthalmoscopy, electrocardiogram, urinalysis, hematology, serum biochemistry, gross and histopathology findings. However, the kidney relative weight of animals receiving 60 mg/kg of compound was significantly elevated relative to control animals (5.15 ±â€¯0.88‰ vs. 4.11 ±â€¯0.59‰. P < 0.05), and this effect was reversed after 4-week recovery period. Based on these results, the NOAEL value for orally administered 20(S)-ginsenoside Rg3 in dogs is 20 mg/kg.

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