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1.
Exp Mol Pathol ; 114: 104416, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32165091

RESUMO

Mesenchymal stromal injection is a promising therapy for traumatic brain injury (TBI). The aim of this study was to explore the effects of the HIF-1α/SDF-1/CXCR4 axis on neuron repair in TBI rats through improving the bone marrow-derived mesenchymalstromal cells (BMSCs) migration. TBI rat models were established. The rats were treated with exogenous SDF-1, and then the neuronal apoptosis in TBI rats was measured. BMSCs from rats were collected, and the roles of NF-κB p65 expression in nuclei, overexpression of SDF-1 and HIF-1α, as well as downregulation of CXCR4 in BMSC migration were identified. HIF-1α- and SDF-1- treated BMSCs were transplanted into TBI rats, after which the neuronal apoptosis and activity of the HIF-1α/SDF-1/CXCR4 axis were detected. Consequently, we found SDF-1 elevated the HIF-1α/SDF-1/CXCR4 activity and presented protective roles in TBI rat hippocampal neurons with reduced neuronal apoptosis. SDF-1 promoted BMSC migration in vitro, and co-effects of SDF-1 and HIF-1α showed strong promotion, while CXCR4 inhibition suppressed BMSC migration. BMSC transplantation activated the HIF-1α/SDF-1/CXCR4 axis and reduced neuronal apoptosis in TBI rats. To conclude, our study demonstrated that the HIF-1α/SDF-1/CXCR4 axis could enhance BMSC migration and alleviate neuronal damage and apoptosis in TBI rats. This study provided novel options for TBI therapy.

2.
Endocr Pract ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160039

RESUMO

Objective: In a cohort of medullary thyroid cancer (MTC) patients with biochemical incomplete responses, 37-48% developed structural persistent disease; however, few indictors were available to distinguish those patients who were more likely to develop structural disease. We hypothesized that the relationship between preoperative calcitonin (Ctn) and postoperative Ctn (within 3 days after surgery) could be used to predict early prognosis of these patients. Methods: A total of 92 sporadic MTC patients were enrolled in this study. Our team proposed a novel indicator of structural persistent MTC called the Calcitonin Ratio (CR, CR = postoperative Ctn / preoperative Ctn). Cox regression models and the Kaplan-Meier method were used to evaluate the prognostic capability of CR. The area under the time-dependent receiver-operating characteristic curves (AUC) and the Harrell concordance index (C-index) were used for analysis. Results: The cutoff CR value used to determine MTC prognosis was 0.15. Multivariate Cox analysis revealed that CR (HR: 22.974, 95% CI: 3.259-161.959, P = 0.002), TNM (HR: 3.968, 95% CI: 1.360-21.857, P = 0.031) and multifocality (HR: 8.466, 95% CI: 1.286-55.716, P = 0.026) independently correlated with MTC prognosis. Kaplan-Meier survival curves demonstrated a lower proportion with structural persistent disease in patients with CR < 0.15 (P < 0.001). The 3, 5 and 10-year AUC values were 0.798, 0.752, and 0.743 respectively. The C-index of CR was 0.788 (95% CI: 0.763-0.813). Conclusion: In this study, CR was identified as a sensitive and specific risk stratification marker for patients with biochemical incomplete responses in sporadic MTC.

3.
J Org Chem ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202107

RESUMO

Two sesterterpenoids possessing an unusual 10,11-seco-gentianellane skeleton, gentianelloids A and B, were isolated from a traditional Uighur medicine Gentianella turkestanorum. Through extensive spectroscopic analysis and single-crystal X-ray diffraction, their structures including absolute configurations were unambiguously determined. A plausible biosynthetic pathway for the two compounds was proposed. Both compounds showed remarkable immunosuppressive activity, including inhibition of the proliferation, activation, and cytokine IFN-γ production of T cells. The findings suggested that sesterterpenoids could contribute positively to the therapeutic effects of this popular traditional Uighur medicine.

4.
Biochim Biophys Acta Gen Subj ; : 129595, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173376

RESUMO

Recombinant DNA technologies have enabled the development of transgenic animal models for use in studying a myriad of diseases and biological states. By placing fluorescent reporters under the direct regulation of the promoter region of specific marker proteins, these models can localize and characterize very specific cell types. One important application of transgenic species is the study of the cytoarchitecture of the nervous system. Neurofluorescent reporters can be used to study the structural patterns of nerves in the central or peripheral nervous system in vivo, as well as phenomena involving embryologic or adult neurogenesis, injury, degeneration, and recovery. Furthermore, crucial molecular factors can also be screened via the transgenic approach, which may eventually play a major role in the development of therapeutic strategies against diseases like Alzheimer's or Parkinson's. This review describes currently available reporters and their uses in the literature as well as potential neural markers that can be leveraged to create additional, robust transgenic models for future studies.

5.
Food Funct ; 11(2): 1856-1868, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32068207

RESUMO

Cadmium (Cd) is a toxic pollutant with high nephrotoxicity in the agricultural environment. Resveratrol has been found to have a renoprotective effect but the underlying mechanisms of this have not yet been fully elucidated. The aim of this study is to illustrate the antagonism of resveratrol against Cd-induced nephrotoxicity. A total of 80 birds were divided randomly into 4 groups and treated via diet for 90 days as follows: control group (Con); 400 mg kg-1 resveratrol group (Resv); 140 mg kg-1 Cd group (Cd 140); and 140 mg kg-1 Cd + 400 mg kg-1 resveratrol group (Cd + Resv). It was observed that resveratrol treatment dramatically alleviated Cd-induced histopathological lesions of the kidney. Simultaneously, resveratrol mitigated Cd-induced oxidative stress by reducing MDA and H2O2 production, alleviating GSH depletion and restoring the activity of antioxidant enzymes (T-SOD, Cu-Zn SOD, CAT, GST and GSH-Px). Resveratrol activated NXRs (CAR/PXR/AHR/Nrf2) signaling pathways and exerted antidotal roles by enhancing the phase I and II detoxification systems to relieve oxidative damage. Moreover, resveratrol ameliorated Cd-induced ultrastructural abnormality and mitochondria dysfunction by recovering mitochondrial function-related factors VDAC1, Cyt C and Sirt3 upregulation and Sirt1, PGC-1α, Nrf1 and TFAM transcription restrictions. Resveratrol attenuated Cd-induced excessive mitochondrial fission and promoted mitochondrial fusion, which reversed PINK1/Parkin-mediated mitophagy initiation. Collectively, our findings explicate the potential protection against Cd-induced nephrotoxicity and mitochondria damage.

6.
Nanoscale ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32096532

RESUMO

Correction for 'Effect of aspect ratios of rutile TiO2 nanorods on overall photocatalytic water splitting performance' by Bing Fu et al., Nanoscale, 2020, DOI: 10.1039/c9nr10870j.

7.
Cell Host Microbe ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32109369

RESUMO

Artemisin combination therapy (ACT) is the main treatment option for malaria, which is caused by the intracellular parasite Plasmodium. However, increased resistance to ACT highlights the importance of finding new drugs. Recently, the aspartic proteases Plasmepsin IX and X (PMIX and PMX) were identified as promising drug targets. In this study, we describe dual inhibitors of PMIX and PMX, including WM382, that block multiple stages of the Plasmodium life cycle. We demonstrate that PMX is a master modulator of merozoite invasion and direct maturation of proteins required for invasion, parasite development, and egress. Oral administration of WM382 cured mice of P. berghei and prevented blood infection from the liver. In addition, WM382 was efficacious against P. falciparum asexual infection in humanized mice and prevented transmission to mosquitoes. Selection of resistant P. falciparum in vitro was not achievable. Together, these show that dual PMIX and PMX inhibitors are promising candidates for malaria treatment and prevention.

8.
New Phytol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017125

RESUMO

The cotton fibre serves as a valuable experimental system to study cell wall synthesis in plants, but our understanding of the genetic regulation of this process during fibre development remains limited. We performed a genome-wide association study (GWAS) and identified 28 genetic loci associated with fibre quality in allotetraploid cotton. To investigate the regulatory roles of these loci, we sequenced fibre transcriptomes of 251 cotton accessions and identified 15 330 expression quantitative trait loci (eQTL). Analysis of local eQTL and GWAS data prioritised 13 likely causal genes for differential fibre quality in a transcriptome-wide association study (TWAS). Characterisation of distal eQTL revealed unequal genetic regulation patterns between two subgenomes, highlighted by an eQTL hotspot (Hot216) that established a genome-wide genetic network regulating the expression of 962 genes. The primary regulatory role of Hot216, and specifically the gene encoding a KIP-related protein, was found to be the transcriptional regulation of genes responsible for cell wall synthesis, which contributes to fibre length by modulating the developmental transition from rapid cell elongation to secondary cell wall synthesis. This study uncovered the genetic regulation of fibre-cell development and revealed the molecular basis of the temporal modulation of secondary cell wall synthesis during plant cell elongation.

9.
Oncotarget ; 11(4): 490-491, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32064053

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.23249.].

10.
Nanoscale ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053128

RESUMO

The spatial separation of reduction and oxidation reaction sites on the different facets of a semiconductor is an ideal and promising route for overall photocatalytic water splitting due to efficient charge carrier separation. Rutile TiO2 has separate oxidation and reduction crystal facets and can be used to achieve direct splitting of pure water under ultraviolet (UV) light irradiation. In order to improve the rate of water oxidation reaction, the ratio of different crystal facets of rutile should be regulated controllably. However, the preparation of rutile TiO2 architecture has been limited by the availability of synthetic techniques. In this study, rutile TiO2 nanorods with various aspect ratios were accurately prepared in the presence of Cl- anions and H+ cations, which were found to play a crucial role in forming the morphology of rutile TiO2 nanorods. In addition, the mechanism involving the growth of rutile TiO2 nanorods with different aspect ratios is proposed. Rutile TiO2 nanorods with a high proportion of oxidative (111) facets provided higher overall water splitting reactivity.

11.
Nanoscale ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32095805

RESUMO

This work was focused on the effects of Mn doping on the phase stability and magnetic performance of SmCo7 based alloys. Particularly, the role of Mn in the improvement of the magnetization of the SmCo7 matrix, as well as its mechanisms, was examined in detail. The metastable SmCo7 single phase was well stabilized by the appropriate content of Mn doping and nanostructuring of the alloy. It was discovered that the non-ferromagnetic element Mn can enhance magnetization effectively. By tailoring the Mn content and nanostructuring, the prepared SmCo7-xMnx alloy achieved good comprehensive magnetic properties. The mechanisms for the magnetization enhancement by Mn and the coupled effect of Mn doping and nanostructuring on the magnetic properties were proposed based on the characterization of magnetic structures and the model calculations of magnetic moments.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32096609

RESUMO

BACKGROUND: Sarcopenia causes several adverse events in elderly people. Muscle fibre atrophy and interstitial fibrosis are the main histopathological changes in sarcopenia and account for decreased muscle function. Tribbles homologue 3 (TRB3) was previously reported to exhibit age-related expression and play a vital role in cell proliferation, differentiation, and fibrosis. We aimed to investigate how TRB3 affects sarcopenia. METHODS: Wild-type and TRB3 knockout C57/BL6J mice were randomly divided into young and old groups. Exercise capacity was evaluated, and single-muscle function was detected by electrophysiological techniques, after which the mice were sacrificed to collect their gastrocnemius muscles for assessment of atrophy and fibrosis by histopathological and molecular biological methods. TRB3 expression, autophagy level, and MAPK signalling pathway activity were evaluated through western blotting. The interaction of TRB3 with P62 and the association between TRB3 and the MAPK signalling pathway were detected by co-immunoprecipitation. RESULTS: In aged mice, exercise capacity and cross-sectional area of skeletal muscle fibres were decreased significantly, whereas TRB3, atrophy-related markers atrogin 1 and MuRF 1, and interstitial fibrosis, including collagen volume fraction, contents of collagens I and III, and ratio of collagens I to III, were increased significantly (P < 0.05 for all). Following TRB3 knockout, the cross-sectional area of muscle fibres, mainly fast fibres, was elevated (P < 0.05 for both), the atrogin 1 expression was decreased (P = 0.0163), and the corresponding tetanic force of fast muscles was increased (P = 0.0398). Conversely, interstitial fibrosis was substantially decreased and exercise capacity was significantly increased in the knockout mice. In terms of the underlying mechanisms, the autophagy receptor p62 was markedly increased and the MAPK signalling pathway was activated in aged skeletal muscles, which might be attributed to the interaction of TRB3 with p62 and MAPKKs, including MEK1/MEK2, MEK3/MEK6, and MEK4/MKK4. Notably, TRB3 knockout reduced the accumulation of p62 and LC3 (P < 0.05 for both), decreased the phosphorylation of JNK (P = 0.0015), and increased p38 phosphorylation (P = 0.0021). CONCLUSIONS: TRB3 knockout in mice attenuated muscle fibre atrophy and reduced skeletal muscle fibrosis by increasing autophagy and inhibiting the MAPK signalling pathway. Correspondingly, in aged knockout mice, exercise capacity was improved. Interfering with TRB3 expression in aged skeletal muscles may serve as a target for the prevention and treatment of age-related sarcopenia.

13.
ChemSusChem ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012457

RESUMO

A novel and green route has been developed for the electrochemical synthesis of spiro[4.5]trienones through radical-initiated dearomative spirocyclization of alkynes with diselenides. This metal-free and oxidant-free electrosynthesis reaction was performed in an undivided cell under mild conditions. A variety of selenation spiro[4.5]trienones products were prepared in moderate-to-good yields, showing a broad scope and functional group tolerance. Moreover, the developed continuous-flow system combined with electrosynthesis possesses the potential to achieve scaled-up reactions, overcoming the low efficiency of conventional electrochemical scaled-up reactions.

14.
Chemosphere ; 249: 125858, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32062552

RESUMO

Cadmium (Cd) has been implicated in the pathogenesis of inflammation, myocardial infarction, angiocardiopathy, even cancers. However, it is unknown that Cd-induced cardiac toxicity through Nrf2-mediate antioxidant defense and Cytochrome P450 (CYP450) system. To ascertain the chemoprevention of Cd-induced cardiac toxicity, total 60 newborn chicks were fed with different doses of Cd (0 mg/kg, 35 mg/kg and 70 mg/kg) for a period of 90 days feed administration. Results indicated Cd exposure caused cardiac histopathology changed and functions abnormal, induced NOS activities raised and cardiac inflammation, triggering inflammation factors (IL-6, IL-8, TNF-α, and NF-κb) upregulation and inhabitation of IL-10. Cd caused increase of total CYP450 and Cytochrome b5 (Cyt b5) contents, while erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR) indicated opposite situations with different degrees of reduction in microsomes. The mRNA level of most CYP450s isoforms (CYP1A1, CYP1A2, CYP1A5, CYP1B1, CYP2C18, CYP2C45, CYP3A4, CYP3A7 and CYP3A9) were significantly increase but CYP2D6 expression level changed not obvious. Furthermore, Cd treatment caused increased the peroxidation product (MDA) and H2O2 over accumulation, the decreased of T-AOC accompanied by decreased activity of antioxidant enzymes (T-SOD, GST and GPX). Over accumulation of Cd lead to oxidative stress and activated Nrf2 signal pathway through upregulating pivotal target genes (HO-1, NQO1, GCLC, GCLM and SOD). These findings suggested Cd exposure caused cardiotoxicity through CYP450s enzymes homeostasis disturbance and Nrf2-mediated oxidative stress signal pathways defense. These results may provide new evidence on molecular mechanism of Cd-induced cardiac toxicity.

15.
Org Lett ; 22(3): 795-799, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31922422

RESUMO

Herein an exogenous oxidant- and metal-free electrochemical heteroaryl migration triggered by N radicals to construct new N-C bonds was developed. This methodology features a high atom economy and utilization rate of energy, and it is insensitive to water and air. Moreover, a user-friendly undivided cell was employed. The use of an organic catalyst makes it more efficient, green, and practical.

16.
Fitoterapia ; 141: 104483, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954739

RESUMO

Three depsidones boremexins A-C (1-3), two diaryl ethers boremexins D (4) and E (5), together with four known compounds were obtained from cultures of potato endophytic fungus Boeremia exigua. Their structures with absolute configurations were established by extensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 1-4, 6, and 9 displayed anti-inflammatory properties on nitric oxide production in LPS-induced RAW264.7 macrophages with an IC50 range of 19.4-34.4 µM. Compounds 2 and 5 exhibited cytotoxicities to human breast cancer cell line (MCF-7) with IC50 values of 33.1 and 4.0 µM, respectively.

17.
J Org Chem ; 85(4): 2532-2542, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31910622

RESUMO

The copper-catalyzed [4 + 2] annulation of α,ß-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.

18.
Cancer Sci ; 111(2): 502-512, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710406

RESUMO

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow-up strategies. A total of 298 patients were analyzed for their 3-year conditional overall survival (COS3), 3-year conditional disease-specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5-year overall survival (OS) and the 5-year disease-specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%-83.0%, Δ36.6% vs ≤T2: 82.4%-85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time-dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time-dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow-up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow-up model for RGC patients of different stages, which may affect the design of future clinical trials.


Assuntos
Coto Gástrico/patologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise de Sobrevida
19.
Phytochemistry ; 170: 112198, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765875

RESUMO

Fungal endophytes from plants are an important source for discovery of novel bioactive natural products. In this study, five undescribed harziane diterpenoids with a 4/7/5/6 tetracyclic scaffold, harzianols F‒J and three known derivatives, were obtained from the liquid fermentation of an endophytic fungus Trichoderma atroviride B7, which was isolated from the healthy flower of a Lamiaceae plant Colquhounia coccinea var. mollis. Their structures were elucidated by comprehensive spectroscopic analyses and X-ray crystallographic diffraction in the case of harzianol F. Harzianol I exhibited significant antibacterial effect against the growth of Staphylococcus aureus (EC50 = 7.7 ± 0.8 µg/mL), Bacillus subtilis (EC50 = 7.7 ± 1.0 µg/mL), and Micrococcus luteus (EC50 = 9.9 ± 1.5 µg/mL). Meanwhile, cytotoxic activity of harzianol I against three cancer cell lines was also observed. A plausible biosynthetic pathway for harziane diterpenoids was proposed.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Lamiaceae/química , Compostos Fitoquímicos/farmacologia , Trichoderma/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
20.
Pest Manag Sci ; 76(2): 747-757, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31386282

RESUMO

BACKGROUND: Emamectin benzoate (EB) has recently been successfully applied as a trunk injection for preventative control of the pine wilt disease (PWD) caused by Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle. Here, a whole-organism transcriptomic analysis provides comprehensive insights into the adverse effects of EB on B. xylophilus. RESULTS: A large set of differentially expressed genes (DEGs) were found, demonstrating the antagonistic effects of EB on B. xylophilus embryonic and larval development, reproduction, nervous and motor systems, and pathogenesis. In toxicity assays with EB, the number of eggs laid, hatching rate, thrashing frequency, and developmental rate of B. xylophilus were significantly suppressed at low concentrations (0.1 µg mL-1 ). Moreover, the transcriptional changes validated by real-time quantitative PCR showed downregulated transcript levels of the genes encoding pectate lyases, ß-1,4-endoglucanases, and upregulated the genes encoding glutamate-gated chloride channel, γ-aminobutyric acid type ß receptor, uridine 5'-diphospho-glucuronosyl transferase, ATP-binding cassette transporter. The potential responses of B. xylophilus to EB included the upregulation of several genes putatively contributing to oocyte protection, stem cell renewal, and xenobiotic degradation, implying the potential for drug resistance to develop. CONCLUSION: Our findings further our understanding of the effects of EB for managing the PWD and may help to improve the pesticide-use strategies for controlling B. xylophilus. © 2019 Society of Chemical Industry.

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