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1.
Br J Cancer ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31919406

RESUMO

BACKGROUND: Chemoresistance remains a critical event that accounts for colorectal cancer (CRC) lethality. The aim of this study is to explore the ability of dichloroacetate (DCA) to increase chemosensitivity in CRC and the molecular mechanisms involved. METHODS: The effects of combination treatment of DCA and oxaliplatin (L-OHP) were analysed both in vitro and in vivo. The DCA-responsive proteins in AMPK pathway were enriched using proteomic profiling technology. The effect of DCA on CAB39-AMPK signal pathway was analysed. In addition, miRNA expression profiles after DCA treatment were determined. The DCA-responsive miRNAs that target CAB39 were assayed. Alterations of CAB39 and miR-107 expression were performed both in vitro and on xenograft models to identify miR-107 that targets CAB39-AMPK-mTOR signalling pathway. RESULTS: DCA increased L-OHP chemosensitivity both in vivo and in vitro. DCA could upregulate CAB39 expression, which activates the AMPK/mTOR signalling pathway. CAB39 was confirmed to be a direct target of miR-107 regulated by DCA. Alterations of miR-107 expression were correlated with chemoresistance development in CRC both in vitro and in vivo. CONCLUSION: These findings suggest that the miR-107 induces chemoresistance through CAB39-AMPK-mTOR pathway in CRC cells, thus providing a promising target for overcoming chemoresistance in CRC.

2.
Cell Prolif ; : e12758, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922317

RESUMO

OBJECTIVE: The aim of this study is to investigate the role and potential mechanism of p75NTR in mineralization in vivo using p75NTR-knockout mice and in vitro using ectomesenchymal stem cells (EMSCs). MATERIALS AND METHODS: Femur bone mass and daily incisor mineralization speed were assessed in an in vivo p75NTR-knockout mouse model. The molecular signatures alkaline phosphatase (ALP), collagen type 1 (Col1), melanoma-associated antigen (Mage)-D1, bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), distal-less homeobox 1 (Dlx1) and Msh homeobox 1 (Msx1) were examined in vitro in EMSCs isolated from p75NTR+/+ and p75NTRExIII-/- mice. RESULTS: p75NTR-knockout mice were smaller in body size than heterozygous and wild-type mice. Micro-computed tomography and structural quantification showed that the osteogenic ability of p75NTRExIII -knockout mice was significantly decreased compared with that of wild-type mice (P < .05). Weaker ALP and alizarin red staining and reduced expression of ALP, Col1, Runx2, BSP, OCN and OPN were also observed in p75NTRExIII-/- EMSCs. Moreover, the distance between calcein fluorescence bands in p75NTRExIII -knockout mice was significantly smaller than that in wild type and heterozygous mice (P < .05), indicating the lower daily mineralization speed of incisors in p75NTRExIII -knockout mice. Further investigation revealed a positive correlation between p75NTR and Mage-D1, Dlx1, and Msx1. CONCLUSION: p75NTR not only promotes osteogenic differentiation and tissue mineralization, but also shows a possible relationship with the circadian rhythm of dental hard tissue formation.

3.
Integr Zool ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31912943

RESUMO

Spatial patterns in heterogeneity are generally deemed a central causal factor influencing the physiology and behavior of animals in ecological systems. However, knowledge remains limited about how such patterns influence food discovery and locating by animals. We inferred that spatial heterogeneity plays a key role on animal food discovery and locating. To prove this inference, we tested food locating parameters by two rodent species Apodemus agrarius and Lasiopodomys brandtii, in different heterogeneous environments. Our results showed that spatial heterogeneity significantly influenced the food locating time of rodents, with food locating time increasing with increasing spatial heterogeneity. Furthermore, spatial heterogeneity significantly influenced invalid excavations (digging in the wrong place). Finally, spatial heterogeneity significantly influenced the frequency that heterogeneous objects were explored. Supporting our inference, our results indicate that spatial heterogeneity significantly influences the foraging behavior of animals. Consequently, increased spatial heterogeneity will impair the food locating success of rodents. We believe that this work will broaden our understanding on plant-animal interactions. This article is protected by copyright. All rights reserved.

4.
FASEB J ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912591

RESUMO

Immunologic changes in the hematoma of patients with intracerebral hemorrhage (ICH) and the contribution of these changes to prognosis are unknown. We collected the blood samples and hematoma fluid from 35 patients with acute ICH (<30 hours from symptom onset) and 55 age-matched healthy controls. Using flow cytometry and ELISA, we found that the percentages of granulocytes, regulatory T cells, helper T (Th) 17 cells, and dendritic cells were higher in the peripheral blood of patients with ICH than in healthy controls, whereas the percentages of lymphocytes, M1-like macrophages, and M2-like macrophages were lower. Levels of IL-6, IL-17, IL-23, TNF-α, IL-4, IL-10, and TGF-ß were higher in the peripheral blood of patients with ICH. The absolute counts of white blood cells, lymphocytes, monocytes, and granulocytes in the hematoma tended to be greater at 12-30 hours than they were within 12 hours after ICH, but the percentage of Th cells decreased in peripheral blood. Increased levels of IL-10 in the serum and hematoma, and a reduction in M1-like macrophages in hematoma were independently associated with favorable outcome on day 90. These results indicate that immunocytes present in the hematoma may participate in the acute-phase inflammatory response after ICH.

5.
Chemosphere ; 238: 124695, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545215

RESUMO

As the effective adsorbents, carbon materials (CMs) are typically used in the removal of disinfection byproduct (DBP) precursors during the water treatment by adding CMs before disinfection procedure. However, after the separation of CMs from the treated water by flocculation, sedimentation, and filtration, a small amount of loaded activated carbon could be released into the water treatment system and affect the DBP formation in the following disinfection. In this study, three CMs, including coal-made activated carbon (CAC), sawdust charcoal (SCC), and hydroxylated multiwall carbon nanotubes (OH-MWCNT), were used to explore the effects of residual CMs in the formation of DBPs. The results indicated that some DBP precursors could be irreversibly adsorbed into the pore structure of CMs and hardly to be extracted and determined, then affected the DBP formation in the water system. In the chlorination process of surface water samples, CMs have similar effects on the formation of DBPs. However, given that water samples contain a variety of complex substances, the effects of residual CMs on the formation of DBPs were also slightly changed.


Assuntos
Carvão Vegetal/química , Cloro/análise , Nanotubos de Carbono/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Desinfecção/métodos , Floculação , Halogenação
6.
Zhongguo Zhen Jiu ; 39(12): 1255-61, 2019 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-31820598

RESUMO

OBJECTIVE: To evaluate the clinical effect of acupuncture on smoking cessation and withdrawal symptoms and to explore the influence factors of acupuncture on smoking cessation. METHODS: A total of 500 subjects with tobacco dependence were randomized into an acupuncture group, an auricular therapy group, an acupuncture plus auricular therapy group, a TENS group and a nicotine replacement therapy group (NRT group), 100 cases in each one. In the acupuncture group, acupuncture was applied at Baihui (GV 20), Lieque (LU 7), Hegu (LI 4) and Zusanli (ST 36). The treatment was given 5 times a week, once a day in the first 2 weeks. The treatment was given once every 2 days in the week 3 and 4, 3 times a week, and twice a week, once every 3 days in the week 5 to 8. In the auricular therapy group, the ear point pressure therapy was used at shenmen (TF4), neifenmi (CO18), pizhixia (AT4) and jiaogan (AH6a), 3 times a week. In the acupuncture plus auricular therapy group, acupuncture and auricular therapy were adopted with the same points and manipulation as the previous two groups. Acupuncture was given 3 times a week and the auricular therapy was given twice a week. In the TENS group, SDZ-Ⅱ B type electric acupuncture apparatus was used to stimulate Lieque (LU 7) and Zusanli (ST 36), once a day. In the NRT group, the nicotine patch was used on the chest, back and the upper arms of the subjects, once a day. The duration of treatment was 8 weeks as one course in every group. Afterwards, the 16-week follow-up was conducted. The time-point withdrawal rate was evaluated by the level of urine cotinine in 8 weeks of treatment and in the follow-up in the subjects of 5 groups. The persistent withdrawal rate was evaluated by the self-report of the subjects in 8 weeks of treatment as well as in the follow-up in the 5 groups. The withdrawal effect, the score of the fagerstrom test for nicotine dependence (FTND) and the score of the heaviness of smoking index (HSI) were compared among the groups. Twenty indexes were selected as the potential influence factors, the 72 h withdrawal rate based on the level of urine cotinine in 8 weeks of treatment and in the follow-up was taken as the dependent variable. Using the two categories of Logistic regression analysis, the influence factors of therapeutic effect of acupuncture were screened for smoking cessation. RESULTS: After 8 weeks of treatment, the time-point withdrawal rate in the subjects among the groups was NRT group > acupuncture plus auricular therapy group > auricular therapy group > acupuncture group > TENS group. In the follow-up, the time-point withdrawal rate was acupuncture plus auricular therapy group > NRT group > acupuncture group > TENS group > auricular therapy group, but without statistical significance in comparison (P>0.05). After 8 weeks of treatment, the persistent withdrawal rate in the subjects among the groups was auricular therapy group > TENS group > acupuncture group > acupuncture plus auricular therapy group > NRT group. In the follow-up visit, the persistent withdrawal rate was auricular therapy group > TENS group > acupuncture plus auricular therapy group > acupuncture group > NRT group. The result in the auricular therapy group was better than all of the other 4 groups (P<0.05). Except in the follow-up visit, FTND score in the acupuncture group was lower than the auricular therapy group (P<0.05), FTND score and HSI score were not different significantly in statistics among the groups either in 8 weeks of treatment or in the follow-up (P>0.05). The regression analysis showed that the factors, i.e. nationality, educational background, drinking frequency, pre-treatment FTND score, pre-treatment HSI score and smoking cessation for physical reason in family, were correlated significantly with the withdrawal result after 8-week treatment (P<0.05). The factors, i.e. education background, smoking age, pre-treatment FTND score and different therapeutic methods, were correlated significantly with the withdrawal result in the follow-up (P<0.05). CONCLUSION: Acupuncture combined with auricular therapy effectively reduce nicotine dependence and smoking intensity and relieve withdrawal symptoms. There are many factors that affect the withdrawal effect in smoking cessation. Hence, the influence factors in smoking cessation with acupuncture should be clearly determined so as to develop the individual regimen for smoking cessation and improve the clinical therapeutic effect of acupuncture on smoking cessation.

7.
BMC Nephrol ; 20(1): 444, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791262

RESUMO

OBJECTIVE: To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN). METHODS: A literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis. RESULTS: Eighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (- 1.82, - 0.40), P < 0.00001], higher age [MD = 2.71, 95% CI (1.94, 3.48), P < 0.00001], and lower estimated glomerular filtration rate (eGFR) [MD = -10.34, 95% CI (- 12.09, - 8.60), P < 0.00001]; no significant between-group difference was observed with respect to 24-h urine protein and serum creatinine. However, no significant difference was observed between renal tissues PLA2R -positive and -negative groups with respect to serum albumin, eGFR, serum creatinine, and 24-h urine protein. Remission rate in the serum anti-PLA2R antibody -positive group was lower than that in the -negative group [OR = 0.41, 95% CI (0.28, 0.61),P < 0.00001]; however, no significant between-group difference in this respect was observed between the renal tissue PLA2R-positive and -negative groups. In the serum anti-PLA2R antibody -positive group, the higher titer subgroup had lower remission rate [OR = 0.19, 95% CI (0.07, 0.55),P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate. CONCLUSION: As compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.

9.
Ann Biomed Eng ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31807926

RESUMO

Clinical trials with mesenchymal stem cells (MSCs) have demonstrated potential to treat osteoarthritis, a debilitating disease that affects millions. However, these therapies are often less effective due to heterogeneous MSC differentiation. Kartogenin (KGN), a synthetic small molecule that induces chondrogenesis, has recently been explored to decrease this heterogeneity. KGN has been encapsulated in nanoparticles due to its hydrophobicity. To explore the effect of nanoparticle properties on KGN and MSC interactions, here we fabricated three nanoparticle formulations that vary in hydrophobicity, size, and surface charge using nanoprecipitation: KGN-loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (hydrophobic surface, negative charge, ~ 167 nm), PLGA-poly(ethylene glycol) (PEG) nanoparticles (hydrophilic surface, positive charge, ~ 297 nm), and PLGA-PEG-hyaluronic acid (HA) nanoparticles (hydrophilic surface, negative charge, ~ 507 nm). We observed differences in KGN loading, release, and suspension stability, with the PLGA particles exhibiting ~ 50% drug loading and PLGA-PEG-HA particles releasing the most KGN. All nanoparticles were found to interact with MSCs with evidence of increased uptake in PLGA-PEG and PLGA-PEG-HA compared with surface association of PLGA particles. Over short times (~ 7 days), MSCs incubated with all KGN-loaded formulations exhibited a similar increase in sulfated glycosaminoglycans, characteristic of chondrogenic differentiation, compared with non-KGN loaded formulations.

10.
Huan Jing Ke Xue ; 40(7): 3208-3215, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854720

RESUMO

To study the effect of on-line NaClO backwashing on the microbial community structure of membrane bioreactor (MBR) systems, a reversed A2O-MBR reactor was used to monitor system performance, membrane fouling, and microbial community structure. Measurements were made during the stabilization stage, the on-line pure water backwashing stage, and the on-line NaClO backwashing stage. The results showed that key system performance indicators during NaClO backwashing stage, such as COD, ammonia nitrogen, and TN treatment efficiency, were similar to previous stages. The average membrane fouling rate during the on-line pure water backwashing period was lower than that of the stable stage, while the membrane fouling rate increased during the on-line NaClO backwashing stage, and EPS concentration was the highest and membrane fouling was aggravated. The results of the Chao index, Simpson index, and Shannon index showed that the microbial diversity in the aerobic tank sludge remained almost stable after on-line NaClO backwashing, while the abundance of cake layer sludge increased slightly, but the microbial diversity decreased significantly. Proteobacteria was the main microbial phylum in both the aerobic tank and cake layer sludge, followed by Bacteroidetes. After on-line NaClO backwashing, the relative abundance of Proteobacteria and Bacteroides in the aerobic tank sludge did not change notably, but the composition of filter cake sludge changed significantly. Proteobacteria that possess resistance to chlorine disinfectant increased from 53.4% to 77.8%, while Bacteroides decreased from 33.44% to 14.5%. After on-line NaClO backwashing, the composition of the microbial community in aerobic tank and cake layer was similar. Azospira and Comamonadaceaea also increased significantly after NaClO backwashing. Microbial species that can tolerate NaClO treatment may be the main cause of membrane fouling.


Assuntos
Bacteroidetes , Reatores Biológicos/microbiologia , Proteobactérias , Hipoclorito de Sódio/química , Membranas Artificiais , Nitrogênio , Esgotos/microbiologia
11.
Mol Cell Probes ; : 101494, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31863825

RESUMO

Spring viremia of carp virus (SVCV) is a significant pathogenic agent that can cause large-scale outbreaks of spring viremia of carp (SVC) in many types of fish and bring huge economic losses to the aquaculture industry. A simple and convenient detection method is imperative for SVCV diagnosis. In this study, the real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed and validated. Primers and probe targeting the conserved region of M gene were designed and applied to the real-time RT-RPA assay that performed at 39 °C for 20 min. The specificity analysis showed that no cross-reaction with other pathogenic viruses of fish was found, indicating appropriate specificity of the assay. In vitro transcribed RNA standards were used to estimate the sensitivity of the assay and the detection limit was 102copies/reaction. To further evaluate the assay, 65 clinical samples were tested using both real-time RT-RPA assay and real-time RT-PCR method. The same detection results were observed, suggesting the potential application of real-time RT-RPA assay in clinical sample detection. This is the first report on RPA assay for SVCV detection and this new developed assay would be useful in both laboratory and in the field for diagnosis of SVCV.

12.
Microb Pathog ; 139: 103859, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31707078

RESUMO

Grass carp hemorrhagic disease caused by grass carp reovirus (GCRV) is the most important disease for grass carp aquaculture. Its typical clinical symptom is haemorrhaging, although the mechanism was remained unclear. In this study, we investigated the differences in blood parameters and histopathological features between grass carp infected with a virulent and avirulent isolates of genotype II GCRV. Infection with the virulent isolate resulted in increases in 8 routine blood and 2 serum biochemical parameters (P < 0.05); while 9 routine blood and 5 biochemical parameters were significantly decreased (P < 0.05) compared with fish infected with the avirulent isolate. The majority of these alterations were related to hemorrhage, inflammatory reactions and organic damage. The histopathologic changes were primarily vasodilation and hyperaemia in multiple organs, lymphocyte and macrophage infiltration as well as severe vacuolar degeneration in spleen, kidney and liver. The histopathology changes in fish infected with the avirulent isolate were minimal. These results indicated that the pathogenicity of GCRV was primarily reflected in destruction of the blood circulatory system and parenchymatous organs. This study lays the foundation for further research on the pathogenesis of bleeding caused by GCRV infection and the use of blood parameters and histopathology as tools for disease diagnosis.

13.
Anal Chim Acta ; 1092: 117-125, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31708024

RESUMO

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H+-triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pKa is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects.

14.
Front Microbiol ; 10: 2428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708899

RESUMO

Lincomycin is one of the most important antibiotics in clinical practice. To further understand the regulatory mechanism on lincomycin biosynthesis, we investigated a pleiotropic transcriptional regulator AdpAlin in the lincomycin producer Streptomyces lincolnensis NRRL 2936. Deletion of adpA lin (which generated ΔadpA lin ) interrupted lincomycin biosynthesis and impaired the morphological differentiation. We also found that putative AdpA binding sites were unusually scattered in the promoters of all the 8 putative operons in the lincomycin biosynthetic gene cluster (BGC). In ΔadpA lin , transcript levels of structural genes in 8 putative operons were decreased with varying degrees, and electrophoretic mobility shift assays (EMSAs) confirmed that AdpAlin activated the overall putative operons via directly binding to their promoter regions. Thus, we speculated that the entire lincomycin biosynthesis is under the control of AdpAlin. Besides, AdpAlin participated in lincomycin biosynthesis by binding to the promoter of lmbU which encoded a cluster sited regulator (CSR) LmbU of lincomycin biosynthesis. Results of qRT-PCR and catechol dioxygenase activity assay showed that AdpAlin activated the transcription of lmbU. In addition, AdpAlin activated the transcription of the bldA by binding to its promoter, suggesting that AdpAlin indirectly participated in lincomycin biosynthesis and morphological differentiation. Uncommon but understandable, AdpAlin auto-activated its own transcription via binding to its own promoter region. In conclusion, we provided a molecular mechanism around the effect of AdpAlin on lincomycin biosynthesis in S. lincolnensis, and revealed a cascade regulation of lincomycin biosynthesis by AdpAlin, LmbU, and BldA.

15.
Drug Des Devel Ther ; 13: 3117-3126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695328

RESUMO

Aim: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Silibinin is a flavonoid compound which has medicinal value. Previous studies revealed that silibinin exhibited an anti-fibrotic effect. However, whether silibinin could attenuate high-fat diet (HFD)-induced renal fibrosis remains unclear. Therefore, this study aimed to explore the molecular mechanism by which silibinin regulated renal fibrosis induced by HFD. Methods: In the present study, human renal glomerular endothelial cells (HRGECs) were treated with various concentrations of silibinin. Then, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. In addition, HRGECs were exposed to 100 nM TGF-ß1 for mimicking in vitro renal fibrosis. The expressions of collagen I, fibronectin, and α-SMA were detected by reverse transcription-quantitative polymerase chain reaction and Western blot. Protein levels of p-IκB and p-p65 were examined by Western blot; meanwhile, level of NF-κB was measured by immunofluorescence staining. Furthermore, HFD-induced mouse model of renal fibrosis was established. The mouse body weight, fasting glucose, kidney weight/body weight, microalbuminuria, kidney histopathology, and fibrotic area were measured to assess the severity of renal fibrosis. Results: Low concentration of silibinin (≤50 µM) had no cytotoxicity, while high concentration of silibinin (≥75 µM) exhibited significant cytotoxicity. Additionally, TGF-ß1 increased the expressions of collagen I, fibronectin, α-SMA, p-IκB, and p-p65 and decreased the level NF-κB, while these effects were notably reversed by 50 µM silibinin. Moreover, both 50 and 100 mg/kg silibinin greatly decreased HFD-induced the upregulation of kidney weight/body weight, microalbuminuria, and fibrotic area. 100 mg/kg silibinin markedly reduced collagen I, fibronectin, and p-p65 expressions in mice renal tissues. Conclusion: Silibinin was able to attenuate renal fibrosis in vitro and in vivo via inhibition of NF-κB. These data suggested that silibinin may serve as a potential agent to alleviate the renal fibrosis of DN.

16.
Front Pharmacol ; 10: 1135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680945

RESUMO

Backgrounds: Salsolinol (SAL), a plant-based isoquinoline alkaloid, was initially isolated from Aconiti Lateralis Radix Praeparata (ALRP) and identified as the active cardiotonic component of ALRP. This study was aimed to explore the therapeutic effect and mechanism by which SAL attenuates doxorubicin (DOX)-induced chronic heart failure (CHF) in rats and improves mitochondrial function in H9c2 cardiomyocytes. Methods: Rats were intraperitoneally injected with DOX to establish CHF model. Therapeutic effects of SAL on hemodynamic parameters, serum indices, and the histopathology of the heart were analyzed in vivo. Moreover, H9c2 cardiomyocytes were pretreated with SAL for 2 h before DOX treatment in all procedures in vitro. Cell viability, cardiomyocyte morphology, proliferation, and mitochondrial function were detected by a high-content screening (HCS) assay. In addition, a Seahorse Extracellular Flux (XFp) analyzer was used to evaluate the cell energy respiratory and energy metabolism function. To further investigate the potential mechanism of SAL, relative mRNA and protein expression of key enzymes in the tricarboxylic acid cycle in vivo and mitochondrial calcium uniporter (MCU) signaling pathway-related molecules in vitro were detected. Results: The present data demonstrated the pharmacological effect of SAL on DOX-induced CHF, which was through ameliorating heart function, downregulating serum levels of myocardial injury markers, alleviating histological injury to the heart, increasing the relative mRNA expression levels of key enzymes downstream of the tricarboxylic acid cycle in vivo, and thus enhancing myocardial energy metabolism. In addition, SAL had effects on increasing cell viability, ameliorating DOX-induced mitochondrial dysfunction, and increasing mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in H9c2 cardiomyocyte. Moreover, we found that SAL might have an effect on improving mitochondrial respiratory function and energy metabolism via inhibiting excessive activation of MCU pathway in H9c2 cells. However, the protective effect could be ameliorated by ruthenium red (an MCU inhibitor) and abrogated by spermine (an MCU activator) in vitro. Conclusion: The therapeutic effects of SAL on CHF are possibly related to ameliorating cardiomyocyte function resulting in promotion of mitochondrial respiratory and energy metabolism. Furthermore, the potential mechanism might be related to downregulating MCU pathway. These findings may provide a potential therapy for CHF.

17.
Opt Express ; 27(21): 30798-30809, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684323

RESUMO

Ultrashort laser pulses, featuring remarkable spectral tunability, are highly demanded for nonlinear light-matter interactions in a variety of molecules. Here, we report on the generation of soliton-plasma-driven ultrashort pulses with both bandwidth- and wavelength-tunability in the visible spectral region. Using He-filled single-ring photonic crystal fiber (SR-PCF), we demonstrate in the experiments that the spectral bandwidths of blueshifting solitons can be manipulated by adjusting the input pulse energy, gas pressure and core diameter of the SR-PCF, while the central wavelengths of these solitons can be continuously tuned over 200 nm. We found that in a large-core SR-PCF (24.6-µm core diameter), the bandwidths of blueshifting solitons can be effectively broaden to near 100 nm, pointing out the possibility of generating few-cycle, wavelength-tunable visible pulses using this set-up. In addition, we observed in the experiments that in a small-core SR-PCF (with a core diameter of 17 µm), the blueshifting solitons show little residual light near the pump wavelength, resulting in a high-efficiency frequency up-conversion process. These experimental results, confirmed by numerical simulations, pave the way to a new generation of compact, ultrashort light sources with excellent tunability at visible wavelengths, which may have many applications in the fields of time-resolved spectroscopy and ultrafast nonlinear optics.

18.
J Phys Chem Lett ; 10(23): 7374-7382, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31725303

RESUMO

We report that heterostructured NiO/Ni nanoparticles remarkably promote the catalytic H2 production of platinum (Pt) nanoclusters toward the hydrolysis of ammonia borane (AB). A hybrid nanocatalyst composed ultrasmall Pt nanoclusters, heterostructured NiO/Ni nanoparticles, and a carbon nanotube support (defined as Pt@NiO/Ni-CNT) is fabricated. The resultant Pt@NiO/Ni-CNT is highly efficient for room-temperature H2 production toward catalytic hydrolysis of AB, better than the Pt@NiO-CNT and Pt@Ni-CNT with NiO or Ni alone, and the Pt@NiO/Ni without CNT support. Optimal Pt@NiO/Ni-CNT catalyst exhibits a good catalytic activity with a high TOF of 2665 molH2 molPt-1 min-1 under ambient conditions, overtaking the activities of previously reported catalysts for AB hydrolysis. Catalytic kinetic studies indicate that compositional and structural features of the Pt@NiO/Ni-CNT synergistically accelerate the oxidative clearage of the H-OH bond from attacked H2O (the rate-determining step), thus boosting catalytic hydrolysis of AB kinetically.

19.
Food Chem ; : 125824, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31732245

RESUMO

In this work, a home-made portable dielectric barrier discharge-atomic emission spectrometer (DBD-AES) was explored to the determination of heavy metal in foodstuffs. A rapid and simple method was developed for Cd determination in rice based on this instrument. Rice was pretreated with diluted acid dissolution without complex operations and apparatus. The detection time by DBD-AES is about 3 min and the total analysis time for rice sample is within 11 min. The effects of some key experiment parameters were investigated. The limit of detection was 11.9 µg kg-1 for Cd in rice, much lower than the maximum allowable level established by EC (200 µg kg-1). The practical performance of this method was demonstrated by analyzing real and CRM rice samples. With the portability of DBD-AES, the method is suitable for rapid and in-field analysis of Cd in rice. It will be a useful tool for the routine analysis of rice.

20.
Front Mol Neurosci ; 12: 260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736707

RESUMO

Anxiety and depression are major public health concerns worldwide. Although genome-wide association studies have identified several genes robustly associated with susceptibility for these disorders, the molecular and cellular mechanisms associated with anxiety and depression is largely unknown. Reduction of microRNA-137 (miR-137) level has been implicated in the etiology of major depressive disorder. However, little is known about the in vivo impact of the loss of miR-137 on the biology of anxiety and depression. Here, we generated a forebrain-specific miR-137 knockout mouse line, and showed that miR-137 is critical for dendritic and synaptic growth in the forebrain. Mice with miR-137 loss-of-function exhibit anxiety-like behavior, and impaired spatial learning and memory. We then observe an elevated expression of EZH2 in the forebrain of miR-137 knockout mice, and provide direct evidence that knockdown of EZH2 can rescue anxious phenotypes associated with the loss of miR-137. Together our results suggest that loss of miR-137 contributes to the etiology of anxiety, and EZH2 might be a potential therapeutic target for anxiety and depressive phenotypes associated with the dysfunction of miR-137.

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