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1.
Artigo em Inglês | MEDLINE | ID: mdl-33048677

RESUMO

The images used in various practices are often disturbed by noise, such as Gaussian noise, speckled noise, and salt and pepper noise. Images with noise are one of the challenges for segmentation, since the noise may cause inaccurate segmented results. To cope with the effect of noise on images during segmentation, a novel active contour model is proposed in this paper. The newly proposed model consists of fitting term, regularization term and penalty term. The fitting term is designed using a Gaussian kernel function and fractional order differentiation with an adaptively defined fractional order, which applies different orders to different pixels. The regularization term is applied to maintain the smoothness of curves. In order to ensure stable evolution of curves, a penalty term is added into the proposed model. Comparison experiments are conducted to show the effectiveness and efficiency of the proposed model.

2.
Plant Genome ; 13(2): e20022, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33016607

RESUMO

The maize C system of cytoplasmic male sterility (CMS) and its fertility restoration gene Rf4 have been widely used for maize hybrid production; however, the underlying mechanism is still uncertain. The sterility factor functions in mitochondria, where it interacts directly or indirectly with the restorer. Mitoproteomics can capture all participants involved in CMS and restoration at the organelle level. In the present study, we identified and quantified anther mitochondrial proteins from CMS, maintainer and restorer lines. We obtained 14,528 unique peptides belonging to 3,369 proteins. Comparative analysis of 1840 high-confidence proteins revealed 68 were differentially accumulated proteins likely involved in CMS or its restoration within mitochondria. These proteins were mainly associated with fatty acid metabolism, amino acid metabolism and protein-processing pathways. These results suggest that an energy deficiency caused by the sterility factor hinders other proteins or protein complexes required for pollen development through nuclear-mitochondrial interaction. The restorer factor may boost the energy generation by activating alternative metabolic pathways and by improving the post-translation processing efficiency of proteins in energy-producing complexes to restore pollen fertility. Our findings may aid detailed molecular analysis and contribute to a better understanding of maize CMS-C restoration and sterility.

3.
Chin J Integr Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000415

RESUMO

OBJECTIVE: To observe the effects and safety of Tongyan Spray () on the range and time of hyoid motion in patients with ischemic post-stroke dysphagia. METHODS: Seventy-two patients with ischemic post-stroke dysphagia were selected and randomly assigned to a treatment group (36 cases) and a control group (36 cases) by a random number table from January 2013 to October 2014. All patients swallowed 4 kinds of barium meals with different traits respectively, and each patient underwent video fluoroscopy (VF) examination twice. In the treatment group, Tongyan Spray was sprayed to the pharynx on both sides and the middle part once respectively. The spray was applied 30 min before the second examination. Purified water at room temperature was used as placebo in the control group. The changes in the range and time of hyoid motion in both groups were observed before and after treatment. RESULTS: Six patients dropped out in each group, and 60 patients completed the study and were included in the final analysis. Significant improvement was observed in the range of superior hyoid excursion distance and the time of hyoid motion in the treatment group compared with the control group (P<0.05). There were no obvious adverse reactions observed in oral mucosa in both groups during the whole study. CONCLUSION: Tongyan Spray was an effective and safe medicine for improving swallowing function in patients with ischemic post-stroke dysphagia.

4.
Biomed Res Int ; 2020: 9451596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33015188

RESUMO

Hair loss is a common disease in dermatology, while the approved drugs may have unpredictable side effects. In this study, the effect of timosaponin BII extracted from Anemarrhena asphodeloides on hair growth of C57BL/6 mice was investigated by measuring the hair follicle morphology, hair growth length and area in C57BL/6 male mice, and the immunohistochemical analysis of ß-catenin, Wnt3a, and Wnt10b in the dorsal skins of mice after topical application with minoxidil and timosaponin BII for 15 days. The decrease in skin brightness, the increase in the regrowing area of hair and hair follicles numbers, and the improvement of hair follicle morphology in the group applied with 0.5% timosaponin BII indicated an induction of the anagen phase in telogenic mice skin, which were comparative to the 2% minoxidil treatment. The immunohistochemical analysis detected an increase in the expression of ß-catenin and Wnt10b, supporting the theory of the activation of the ß-catenin/Wnt pathway was one of the pathways that are related to anagen phase induction. Anemarrhena asphodeloides is a herb commonly used for metabolic disorders in China. The present study is the first to show that the timosaponin BII, which is present at a high concentration in A. asphodeloides, promotes hair growth in C57BL/6 male mice. The results indicate that timosaponin BII may be a potential promoting agent for hair growth.

5.
Emerg Microbes Infect ; : 1-31, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048025

RESUMO

Balamuthia mandrillaris infection is a rare and fatal disease. It has been reported globally, with most cases reported in the US. We have recorded 28 cases of Balamuthia mandrillaris infection during the past 20 years. The diagnosis was confirmed by immunohistochemical staining with polyclonal anti-Balamuthia antibody and polymerase chain reaction amplification with specific primers. Eighteen patients (64%) were male and 10 (36%) were female. Patient age ranged from 3 to 74 (mean, 27) years; 14 (50%) patients were children. Patient locations were distributed among 12 separate Provinces in China. Twenty-seven (96%) patients lived in rural areas, and 17 (61%) patients reported a history of trauma before the appearance of skin lesions. All cases presented with skin lesions as the primary symptom, and 16 (57%) cases developed encephalitis. Histopathology of skin lesions revealed granulomatous changes with histiocytes, lymphocytes, and plasma cells infiltration. Amebas were identified in all cases with immunohistochemical staining. Follow-up information was available in 27 (96%) cases. Fifteen (56%) patients died due to encephalitis and 12 (44%) were free of disease after treatment. Our results show that the clinical characteristics of Balamuthia mandrillaris infection in China are very different from those in the US. Infection of traumatized skin may play an important role in the pathogenesis of the disease in China. Encephalitis usually develops 3-4 years after skin lesions in Chinese cases. Patients with only skin lesions have a higher cure rate than patients with encephalitis.

6.
J Mech Behav Biomed Mater ; 113: 104147, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33096450

RESUMO

Silk is widely used in the biomedical field (e.g., surgical sutures) for its excellent mechanical properties and biocompatibility. The properties of silk can be further enhanced by a multitude of methods, including nano particle feeding, which is convenient and green. Generally, the filament length of a silkworm cocoon ranges from 1300 to 1700 m. Despite the fact that the filament size, a key factor affecting the mechanical properties of silk, varies along the length, evaluation of strengthened silk by segment and the specific distribution along the length has not been reported. Therefore, in the present study, we fed silkworms with graphene oxide-sprayed mulberry leaves and evaluated the silk properties segment by segment. The silk's strength and elongation were significantly enhanced, with more α-helical/random coils and thicker mesophase regions. Specifically, the silk from 2‰ GO-treated group had higher strength in the first 60% of the length, whereas the silk from 1‰ GO-treated group was stronger in the last 40% of the length. Notably, the silk from 1‰ GO-treated group had the highest strength and Young's modulus in the last 20% of the length, indicating that this segment is more suitable for use as a surgical suture. Our findings demonstrate that different silk segments offer a great range of desirable assets, and the feasibility to select a specific segment with the desired properties for a specific application.

7.
BMC Genomics ; 21(1): 719, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33069230

RESUMO

BACKGROUND: Flammulina filiformis (previously known as Asian F. velutipes) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicted its biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis. RESULTS: We found that the genome of the F. filiformis was 35.01 Mb in length and harbored 10,396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain. CONCLUSIONS: F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.

8.
J Biol Dyn ; 14(1): 802-825, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33084532

RESUMO

In this paper, we propose and analyse a delayed HIV-1 model with both viral and cellular transmissions and virus waning. We obtain the threshold dynamics of the proposed model, characterized by the basic reproduction number R 0 . If R 0 < 1 , the infection-free steady state is globally asymptotically stable; whereas if R 0 > 1 , the system is uniformly persistent. When the delays are positive, we show that the intracellular delays in both viral and cellular infections may lead to stability switches of the infected steady state. Both analytical and numerical results indicate that if the effect of cell-to-cell transmission is ignored, then the risk of HIV-1 infection will be underestimated. Moreover, the viral load of model without virus waning is higher than the one of model with virus waning. These results highlight the important role of two ways of viral transmission and virus waning on HIV-1 infection.

9.
Aging (Albany NY) ; 12(19): 18878-18888, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031060

RESUMO

In this retrospective study we assessed the efficacy and safety of tocilizumab in patients with critical or severe coronavirus disease 2019 (COVID-19). We enrolled 181 patients admitted to Huoshenshan Hospital (Wuhan, China) with confirmed COVID-19 between January 2020 and February 2020. Ninety-two patients were treated with tocilizumab, and 89 patients were treated conventionally. We analyzed the clinical manifestations, changes in CT scan images, and laboratory tests before and after tocilizumab treatment, and compared these results with the conventionally treated group. A significant reduction in the level of C-reactive protein was observed 1 week after tocilizumab administration. In some cases this meant the end of the IL-6-related cytokine storm. In addition, tocilizumab relieved fever, cough, and shortness of breath with no reported adverse drug reactions. These findings suggest tocilizumab improves clinical outcomes and is effective for treatment of patients with critical or severe COVID-19. However, future clinical trials are needed to better understand the impact of tocilizumab interference with IL-6 and provide a therapeutic strategy for treatment of COVID-19.

10.
Sci Total Environ ; 755(Pt 2): 142632, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045611

RESUMO

High concentrations of antibiotics can exert strong selection pressures on the microbial community and promote the emergence and dissemination of antibiotic resistance genes (ARGs). The activated sludge reactors treating ampicillin, cephalexin and chloramphenicol production wastewater were established to investigate the responses of microbial community, ARGs and mobile genetic elements (MGEs) to antibiotics. Antibiotic selection pressures significantly declined the microbial diversity and changed microbial community structures. Based on metagenomic analysis, a total of 500 ARG subtypes affiliated with 18 ARG types were identified and 63 ARGs were shared by all samples. The substantial increase of ARG abundance and the shifts of ARG profiles were significantly correlated with antibiotic types and concentrations. The evident enrichment of non-corresponding ARG types suggested the strong co-selection effects of the target antibiotics. Additionally, metagenomic analysis revealed the occurrence of 104 MGEs belonging to various types and the five dominant MGEs were tnpA, intI1, tniA, tniB and IS91. The ARG-MGE co-occurrence associations implied the potential mobility of ARGs. Network analysis also demonstrated that five ARG types (aminoglycoside, beta-lactam, chloramphenicol, multidrug and tetracycline resistance genes) tended to co-occur internally and the obvious co-occurrence patterns among different ARG types indicated the potential for resistance co-selection. Moreover, 15 bacterial genera were speculated as the hosts of diverse ARGs. This study provides a comprehensive overview of the occurrence of ARGs and MGEs and is valuable for the risk assessment and management of antibiotic resistance.

11.
IEEE Trans Cybern ; PP2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079691

RESUMO

In this article, the problem of consensus control is investigated for a class of multiagent systems (MASs) with both stochastic noises and nonidentical exogenous disturbances. The signal transmission among agents is implemented through a digital communication network subject to both uniform quantization and round-robin protocol as a reflection of network constraints. The consensus strategy is designed by adopting the estimates of the relative states of the agent to its neighbors, which renders the distributed nature of the controller. A new consensus concept, namely, quasiconsensus in probability, is employed to evaluate the state response of the agents to the stochastic noises, the exogenous disturbances, and the quantization error. An augmented system is first formed that relies on the deviations of the individual state from the average state, the observer error of the relative state, as well as the relative measurement output. Based on the augmented model, an analysis approach on dynamical behaviors is developed to facilitate the consensus analysis of MASs by means of the switching Lyapunov function technique and the stochastic analysis methods. Then, the existence condition and the explicit expression of the time-varying gain matrices are proposed for the expected controller by resorting to the feasibility of several matrix inequalities. Numerical simulation results are presented to demonstrate the applicability of the theoretical results.

12.
Plant Pathol J ; 36(5): 385-397, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33082723

RESUMO

The ascomycete fungus Colletotrichum gloeosporioides infects a wide range of plant hosts and causes enormous economic losses in the world. The transcription factors (TFs) play an important role in development and pathogenicity of many organisms. In this study, we found that the C2H2 TF CgCrzA is localized in both cytoplasm and nucleus under standard condition, and it translocated from cytoplasm to nucleus in a calcineurin-dependent manner. Moreover, the ΔCgCrzA was hypersensitive to cell wall perturbing agents and showed severe cell wall integrity defects. Deletion of the CgCRZA inhibited the development of invasive structures and lost pathogenicity to plant hosts. Our results suggested that calcineurin-responsive TF CgCrzA was not only involved in regulating cell wall integrity, but also in morphogenesis and virulence in C. gloeosporioides.

13.
J Environ Manage ; 277: 111386, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049610

RESUMO

In this study, nano α-FeOOH (nFeOOH, 100-500 nm) was coated onto activated carbon (nFeOOH@AC) through a dipping means for enhanced Cr(VI) immobilization from drinking water. The nFeOOH@AC significantly improved the Cr(VI) removal from 19.9% (AC control) to 93.4%. XPS spectra and chromium speciation demonstrated that about 90% of adsorbed Cr(VI) was converted to Cr(III) by the nFeOOH@AC, accompanying with a reduction-oxidation of Fe3+/Fe2+ in the nFeOOH matrix due to electrons delivering between AC and surface-bound Cr(VI). The resultant Cr(III) subsequently reacted with Fe(III) to generate stable (CrχFe1-χ)(OH)3 precipitates, leading to a much lower Cr(III) release of 7.5% back to solution by the nFeOOH@AC as compared to the AC control of 33.8%, indicating that the nFeOOH@AC had a prospective potential for Cr(VI) immobilization and decreased Cr residue in treated drinking water. Results from column experiment also showed that the nFeOOH@AC afforded a 3.5 times higher capacity for Cr(VI) immobilization and a 3.4 times longer life-span than the pristine AC. Besides, Cr(VI) immobilization by the nFeOOH@AC was a pH-dependent process and the adsorbed Cr on the nFeOOH@AC could be readily desorbed with acetic acid. The disabled nFeOOH@AC could be refreshed by recoating nFeOOH particles with the above dipping method after stripping all the iron oxides with hydrochloric acid. This study demonstrated that nFeOOH coating is an efficient approach to enhance Cr(VI) elimination by AC during drinking water treatments.

14.
Chemosphere ; 264(Pt 2): 128452, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33049506

RESUMO

Inorganic arsenic, a well-known human carcinogen, poses a major threat to global health. Given the immunosuppressive potentials of inorganic arsenic as well as limited understanding of this metalloid on antigen-presenting dendritic cells (DCs), we systematically screened the immune targets in response to arsenic treatment, as well as its possible molecular mechanism in cultured murine DCs. Our results denoted that arsenite (As) significantly induced immune tolerance by down-regulating the expression of phenotypic molecules, pro-inflammatory factors and T-lymphocyte helper (Th)1/Th17-inducible cytokines in lipopolysaccharides (LPS)-stimulated myeloid-derived dendritic cells (BMDCs). Inconsistent with dampened phosphorylation of immune-related proteins (nuclear factor kappa-B) NF-κB, p38 and JNK, the metalloid drastically induced the expression of Heme oxygenase-1 (HO-1) protein, which enlightened us to continuously explore the possible roles of HO-1 pathway in As-induced immune tolerance in BMDCs. In this respect, immunosuppressive properties of HO-1 pathway in BMDCs were firstly confirmed through pharmacological overexpression of HO-1 by both CoPP and CORM-2. By contrast, limited HO-1 expression by HO-1 inhibitor ZnPP specifically alleviated As-mediated down-regulation of CD80, chemokine factor C-C chemokine receptor 7 (CCR7), tumor necrosis factor (TNF) -α, Interleukin (IL)-23 and IL-6, which reminds us the peculiarity of HO-1 in As-induced immune tolerance in murine DCs. Based on these experimental findings, we postulated the immunosuppressive property of inorganic arsenic might be mediated partially by HO-1 in DCs, thus contributing to the interactions of DCs-polarized differentiation of T-lymphocyte subtype as well as the development of infections and malignant diseases.

15.
Respir Res ; 21(1): 271, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076910

RESUMO

BACKGROUND: The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown. METHODS: Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks. We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure. Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing. Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified. RESULTS: After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD. The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung. However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide. CONCLUSION: Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease.

16.
Vet Parasitol ; 287: 109267, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091629

RESUMO

Adonis coerulea Maxim. as a folk medicine, presented acaricidal acitvity. However, the mode of action and active compounds were unclear. In this study, using proteomics and surface plasmon resonance (SPR) technology the mode of action and active compounds of A. coerulea were investigated, as well as a sensitive and environmentally friendly analytical method developed. Proteomics analysis results showed that after treatment of mites with A. coerulea methanol extract (MEAC), 135 proteins were differentially expressed, most of them enriched in the myocardium pathway and participated in the function of the inflated cystic organ. Na+-K+-ATPase may be a potential target. Then, it was used as a target to capture the compounds from the extract using a SPR test. Twelve compounds were found, five compounds, namely ellagic acid, ouabain, convallatoxin, strophanthidin and cymarin presented the higher affinity with Na+-K+-ATPase in molecular docking test. Further study showed that the latter four compounds presented the stronger cytotoxicity and the inhibitory effect on Na+-K+-ATPase with IC50 values ranging with 2.38-0.56 µg/mL, and also showed toxicity against Psoroptes cuniculi. These results indicated that MEAC presented toxicity against mites by inhibiting Na+-K+-ATPase, and cardiac glycosides may be active compounds of this plant in terms of its acaricidal activity. Only 10 g of plant was used to investigate its active compounds. This study lays the foundation for developing sensitive methods for active compound detection.

17.
Medicine (Baltimore) ; 99(40): e22564, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019468

RESUMO

BACKGROUND: At present, the prevalence of type 2 diabetes mellitus (T2DM) has become a major public health issue throughout the world, especially in developing countries. Notably, traditional Chinese patent medicines (TCPMs) are of great significance in the treatment of T2DM combined with conventional Western medicine therapy. However, there is a lack of comparison among all the current common TCPMs for treating T2DM. Therefore, this study intends to explore the efficacy and safety of different TCPMs against T2DM through the Bayesian network meta-analysis (NMA). METHODS: We will conduct a comprehensive and systematic search for randomized controlled trials (RCTs) of TCPM for the treatment of T2DM in both Chinese and English databases published till August 2020. Two researchers will be responsible for screening eligible literature, extracting data, and assessing the risk of bias of included studies independently. Then, pairwise meta-analyses and Bayesian network meta-analyses will be conducted to assess all available evidence. In the end, data will be analyzed using STATA15.0 and WinBUGS1.4.3 software. CONCLUSION: This study will compare the efficacy and safety of different TCPMs against T2DM in detail. Our findings will provide a reliable evidence for selecting clinical treatment program and guideline development of T2DM.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Medicina Tradicional Chinesa/métodos , Medicamentos sem Prescrição/efeitos adversos , Teorema de Bayes , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Metanálise em Rede , Medicamentos sem Prescrição/uso terapêutico , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
18.
Genet Epidemiol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063887

RESUMO

In silico simulations play an indispensable role in the development and application of statistical models and methods for genetic studies. Simulation tools allow for the evaluation of methods and investigation of models in a controlled manner. With the growing popularity of evolutionary models and simulation-based statistical methods, genetic simulations have been applied to a wide variety of research disciplines such as population genetics, evolutionary genetics, genetic epidemiology, ecology, and conservation biology. In this review, we surveyed 1409 articles from five journals that publish on major application areas of genetic simulations. We identified 432 papers in which genetic simulations were used and examined the targets and applications of simulation studies and how these simulation methods and simulated data sets are reported and shared. Whereas a large proportion (30%) of the surveyed articles reported the use of genetic simulations, only 28% of these genetic simulation studies used existing simulation software, 2% used existing simulated data sets, and 19% and 12% made source code and simulated data sets publicly available, respectively. Moreover, 15% of articles provided no information on how simulation studies were performed. These findings suggest a need to encourage sharing and reuse of existing simulation software and data sets, as well as providing more information regarding the performance of simulations.

19.
J Ethnopharmacol ; 266: 113430, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33011366

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.

20.
Int J Mol Sci ; 21(19)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33028029

RESUMO

In response to hypoxia under submergence, plants switch from aerobic respiration to anaerobic fermentation, which leads to the accumulation of the end product, ethanol. We previously reported that Arabidopsis thaliana autophagy-deficient mutants show increased sensitivity to ethanol treatment, indicating that ethanol is likely involved in regulating the autophagy-mediated hypoxia response. Here, using a transcriptomic analysis, we identified 3909 genes in Arabidopsis seedlings that were differentially expressed in response to ethanol treatment, including 2487 upregulated and 1422 downregulated genes. Ethanol treatment significantly upregulated genes involved in autophagy and the detoxification of reactive oxygen species. Using transgenic lines expressing AUTOPHAGY-RELATED PROTEIN 8e fused to green fluorescent protein (GFP-ATG8e), we confirmed that exogenous ethanol treatment promotes autophagosome formation in vivo. Phenotypic analysis showed that deletions in the alcohol dehydrogenase gene in adh1 mutants result in attenuated submergence tolerance, decreased accumulation of ATG proteins, and diminished submergence-induced autophagosome formation. Compared to the submergence-tolerant Arabidopsis accession Columbia (Col-0), the submergence-intolerant accession Landsberg erecta (Ler) displayed hypersensitivity to ethanol treatment; we linked these phenotypes to differences in the functions of ADH1 and the autophagy machinery between these accessions. Thus, ethanol promotes autophagy-mediated submergence tolerance in Arabidopsis.

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