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1.
J Control Release ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798666

RESUMO

Breast cancer metastasis and recurrence accounts for vast majority of breast cancer-induced mortality. Tumor microenvironment (TME) plays an important role at each step of metastasis, evasion of immunosurveillance, and therapeutic resistance. Consequently, TME-targeting alternatives to traditional therapies focused on breast cancer cells are gaining increasing attention. These new therapies involve the use of tumor cells, and key TME components or secreted bioactive molecules as therapeutic targets, alone or in combination. Recently, TME-related nanoparticles have been developed to deliver various agents, such as bioactive ingredients extracted from natural sources or chemotherapeutic agents, genes, proteins, small interfering RNAs, and vaccines; they have shown great therapeutic potential against breast cancer metastasis. Among various types of nanoparticles, biomimetic nanovesicles are a promising means of addressing the limitations of conventional nanocarriers. This review highlights various nanoparticles related to or mediated by TME according to the key TME components responsible for metastasis. Furthermore, TME-related biomimetic nanoparticles against breast cancer metastasis have garnered attention owing to their promising efficiency, especially in payload delivery and therapeutic action. Here, we summarize recent representative studies on nanoparticles related to cancer-associated fibroblasts, extracellular matrix, endothelial cells, angiogenesis, and immune cells, as well as advanced biomimetic nanoparticles. Future challenges and opportunities in the field are also discussed.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33806311

RESUMO

Accurate monitoring of grassland vegetation dynamics is essential for ecosystem restoration and the implementation of integrated management policies. A lack of information on vegetation changes in the Wulagai River Basin restricts regional development. Therefore, in this study, we integrated remote sensing, meteorological, and field plant community survey data in order to characterize vegetation and ecosystem changes from 1997 to 2018. The residual trend (RESTREND) method was utilized to detect vegetation changes caused by human factors, as well as to evaluate the impact of the management of pastures. Our results reveal that the normalized difference vegetation index (NDVI) of each examined ecosystem type showed an increasing trend, in which anthropogenic impact was the primary driving force of vegetation change. Our field survey confirmed that the meadow steppe ecosystem increased in species diversity and aboveground biomass; however, the typical steppe and riparian wet meadow ecosystems experienced species diversity and biomass degradation, therefore suggesting that an increase in NDVI may not directly reflect ecosystem improvement. Selecting an optimal indicator or indicator system is necessary in order to formulate reasonable grassland management policies for increasing the sustainability of grassland ecosystems.

3.
Medicine (Baltimore) ; 100(9): e25053, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655984

RESUMO

RATIONALE: With the easy access, rodenticide poisoning has been a public health problem in many countries. Characteristics of central nervous system (CNS) lesions induced by rodenticides are scarcely reported. PATIENT CONCERNS: We presented a case of a 40-year-old man with seizure and consciousness disorder, coagulation dysfunction, and symmetric lesions in white matter and corpus callosum. DIAGNOSIS: He was diagnosed with rodenticide poisoning due to bromadiolone and fluoroacetamide. INTERVENTIONS: He was treated with vitamin K, hemoperfusion, acetamide, and calcium gluconate. OUTCOMES: His leukoencephalopathy was reversed rapidly with the improvement of clinical symptoms. LESSONS: This report presented the impact of rodenticide poisoning on CNS and the dynamic changes of brain lesions, and highlighted the importance of timely targeted treatments.


Assuntos
4-Hidroxicumarinas/envenenamento , Coagulação Sanguínea/efeitos dos fármacos , Fluoracetatos/envenenamento , Leucoencefalopatias/induzido quimicamente , Adulto , Humanos , Leucoencefalopatias/sangue , Masculino , Rodenticidas/envenenamento
4.
J Agric Food Chem ; 69(11): 3390-3400, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33703896

RESUMO

Land degraded by salinization and alkalization is widely distributed globally and involves a wide range of ecosystem types. However, the knowledge of the indigenous microbial assemblages and their roles in various saline-alkaline soils is limited. This study demonstrated microbial assemblages in various saline-alkaline soils from different regions of Inner Mongolia and revealed the key driving factors to influence microbiome. The correlation network analysis indicates the difference in adaptability of bacterial and fungal communities under stimulation by saline-alkaline stress: fungal community shows higher tolerance, stability, and resilience to various saline-alkaline soils than a bacterial community. The keystone bacteria and fungi that have potential adaptability to various saline-alkaline environments are further identified, and they may confer benefits in restoring saline-alkaline soils by their own effects or assisting plants. For salt-rich soils in different regions, the soluble salt ion components are the major determinant to drive microbial assemblages of different saline-alkaline soils, rather than salinity. Thus, these saline-alkaline soils are clustered into sulfated, chlorinated, and soda-type saline-alkaline soils. Multivariate analysis reveals unique, dominant, and common microbial taxa in three saline-alkaline soils. This result of the conceptual mode indicates that potential roles of unique and dominant microbial taxa on regulating saline-alkaline functions are more vital.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33725303

RESUMO

The phthalate concentrations in dust from undergraduate dormitories, classrooms, and homes in Beijing, China, were measured in April 2017. We analyzed the characteristics of phthalates in dust from three environments. In addition, we estimated the daily intake of phthalates via three pathways using Monte Carlo simulations. The detection frequency of eight phthalates in dust ranges from 74.5 to 100%. Di (2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) are the most abundant phthalates. The median proportion of DEHP in dust is the highest, ranging from 67.1 to 72.9%. The PMF results indicated that two, four, and three types of phthalate sources exist in home, dormitory, and classroom, respectively. The differences in the phthalate concentrations between sunny and shaded rooms and urban and suburban classrooms are insignificant, whereas that between male and female dormitories is significant. The total daily intake of DEHP, DnBP, and DiBP ranges from 97.3 to 336 ng/ (kg·day). The oral intake for DEHP in classrooms and the dermal intake of DnBP and DiBP in homes are the highest. The carcinogenic risk of DEHP to university students is the highest in classrooms and the total carcinogenic risk of the three environments is 4.70 × 10-6.

6.
Org Lett ; 23(6): 2227-2231, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33656901

RESUMO

A new and crucial synthon of 3-((diphenylmethylene)-amino)-oxindole was designed and synthesized, for which an organocatalytic and enantioselective Michael/cyclization reaction with a terminal vinyl ketone catalyzed by a cinchona base was disclosed. A wide variety (28 examples) of almost all new chiral spiro[oxindol-3,2'-pyrrols] were prepared in excellent yields (up to 99%) with excellent enantioselectivities (95-99% ee), of which a typical chiral spiro product was further reduced to chiral spiro[oxindole-3,2'-pyrrolidine].

7.
J Clin Lab Anal ; : e23760, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724522

RESUMO

BACKGROUND: Identifying new molecular diagnostic markers for Mycoplasma Pneumoniae Pneumonia (MPP) has always been an essential topic since MPP cases have increased every year, especially among children. Here, we examined the correlation between serum level of Purinergic receptor P2X7, vitamin A, and 25-hydroxy vitamin D (25(OH)D) and the severity of MPP, aiming to identify molecules that have the potential to become diagnostic markers. METHODS: This study was conducted on 186 cases aged 1-14 (136 MPP and 50 non-MPP patients). Serum levels of Purinergic receptor P2X7, vitamin A, 25(OH)D, and multiple inflammatory and immune factors were measured, compared, and tested for statistical significance. RESULTS: Serum P2X7, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels were significantly increased in severe MPP patients, while serum vitamin A, 25(OH)D, IgA, and IgG levels were significantly decreased. CONCLUSION: Our results demonstrated a positive correlation between serum P2X7 level and the severity of MPP, and negative correlations between serum levels of vitamin A and 25(OH)D and the severity of MPP, suggesting that high serum levels of P2X7 and low serum levels of vitamin A and 25(OH)D may indicate relatively severer MPP.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33759563

RESUMO

Genetic knockout (KO) of peptide transporter-1 (PepT1) protein is known to provide resistance to acute colitis and colitis-associated cancer (CAC) in mouse models. However, it was unclear which molecule(s) or pathway(s) formed the basis for these protective effects. Recently, we demonstrated that the PepT1-/- microbiota is sufficient to protect against colitis and CAC. Given that PepT1 KO alters the gut microbiome and thereby changes the intestinal metabolites that are ultimately reflected in the feces, we investigated the fecal metabolites of our PepT1 KO mice. Using a liquid chromatography-mass spectrometry (LC-MS)-based untargeted-metabolomics technique, we found that the fecal metabolites were significantly different between the KO and normal wild-type (WT) mice. Among the altered fecal metabolites, tuberonic acid (TA) was seven-fold higher in KO mouse feces than in WT mouse feces. Accordingly, we studied whether the increased TA could direct an anti-inflammatory effect. Using in vitro models, we discovered that TA not only prevented lipopolysaccharide (LPS)-induced inflammation in macrophages but also improved the epithelial cell healing processes. Our results suggest that TA, and possibly other fecal metabolites, play a crucial role in the pathway(s) associated with the anti-colitis effects of PepT1 KO.

9.
J Diabetes Investig ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33651448

RESUMO

AIMS/INTRODUCTION: Most studies have shown that aldehyde dehydrogenase 2 (ALDH2) mutations were associated with cardio-cerebrovascular complications of diabetes based on cross-sectional investigations, but few studies based on cohorts were carried out. The aim of this study was to explore the correlation between the ALDH2 gene and the occurrence of and death from cardio-cerebrovascular complications in type 2 diabetes patients through a prospective cohort study. MATERIALS AND METHODS: According to a community-based and disease-based prospective cohort study design, a baseline cohort of 10,339 persons with type 2 diabetes was established in 2016, and the occurrence of and death from cardio-cerebrovascular complications were followed up until December 2018. A total of 2,500 diabetes patients without cardio-cerebrovascular complications were randomly selected from the baseline cohort to detect the rs671 polymorphism of the ALDH2 gene. Cox regression analysis was carried out on the effect of different ALDH2 rs671 single-nucleotide polymorphisms on the risk and survival time of cardio-cerebrovascular complications among diabetes patients. RESULTS: There were 215 cardio-cerebrovascular complications, including 10 deaths, that occurred in the 2,500 diabetes patients during the follow-up period. Cox regression analysis showed that rs671 GA/AA genotype, sex (male), poor control of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, blood pressure and glycated were risk factors, whereas drinking alcohol was a protective factor for cardio-cerebrovascular complications (P < 0.05). After adjusting for age and sex, the risk of the rs671 GA/AA genotype was 1.314-fold (95% confidence interval 1.000-1.727) that of the GG genotype. CONCLUSION: The G-A mutation of ALDH2 rs671 is a risk factor for the occurrence of and death from cardio-cerebrovascular complications in type 2 diabetes patients. Further studies with larger cohorts and longer follow up will be necessary to reveal a consensus.

10.
J Vasc Surg ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548423

RESUMO

OBJECTIVE: To compare the surgical outcomes of benign and malignant carotid body tumor (CBT), and to evaluate the associated factors of malignant CBT. METHODS: Patients who underwent surgical resection of CBT from 2005 to 2018 in a tertiary center were reviewed retrospectively. The common study follow-up end date was December 31, 2019. The tumor size was measured as the maximum transverse diameter on computed tomography scan. Surgical outcomes of benign and malignant CBT were compared. Associated factors of malignancy were analyzed by multivariate logistic analysis. RESULTS: There were 229 patients undergoing CBT resection. Sixteen patients were diagnosed with malignant CBT. The median follow-up time was 66 months (range, 6-142 months). Basic information including age, sex, course of disease, family history, lesion side, tumor size, and Shamblin classification showed no significant differences between the benign and malignant CBT groups. Patients with malignant CBTs showed a higher rate of preoperative symptoms (31.3% vs 12.2%; P < .05). The rates of vascular reconstruction or repair (P < .01) and neurologic complications (P < .05) were significantly higher in the malignant CBT group. In addition, a significantly longer average procedural time was required for malignant CBTs (P < .05). However, the estimated blood loss and length of hospital stay showed no significant difference. Multivariate logistic regression analysis revealed that the malignant odds of CBT with bilateral lesions (P = .0042; odds ratio, 8.30; 95% confidence interval, 1.84-35.88) or CBT with preoperative symptoms (P = .0016; odds ratio, 7.59; 95% confidence interval, 2.13-27.89) were high. CONCLUSIONS: Compared with benign CBT, malignant CBT is prone to invasive clinical behaviors, resulting in an increased possibility of vascular reconstruction or repair during the surgery as well as postoperative neurologic complications. In addition, the malignant odds of CBT with bilateral lesions or CBT with preoperative symptoms are high.

11.
Cancer Res ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531372

RESUMO

Cancer evolves from premalignant clones that accumulate mutations and adopt unusual cell states to achieve transformation. We previously pinpointed the oligodendrocyte precursor cell (OPC) as a cell-of-origin for glioma, but the early changes of mutant OPCs during premalignancy remained unknown. Using mice engineered for inducible Nf1-Trp53 loss in OPCs, we acutely isolated labeled mutant OPCs by laser-capture microdissection and determined gene expression changes by bulk RNA sequencing and a fluctuation analysis called stochastic profiling, which uses RNA-sequencing measurements from random pools of 10 mutant cells. At 12 days after Nf1-Trp53 deletion, bulk differences were mostly limited to mitotic hallmarks and genes for ribosome biosynthesis, and stochastic profiling revealed a spectrum of stem-progenitor (Axl, Aldh1a1), proneural, and mesenchymal states as potential starting points for gliomagenesis. At 90 days, bulk sequencing detected few differentially expressed transcripts, whereas stochastic profiling revealed cell states for neurons and mural cells that do not give rise to glial tumors, suggesting cellular dead-ends for gliomagenesis. Importantly, mutant OPCs that strongly expressed key effectors of nonsense-mediated decay (Upf3b) and homology-dependent DNA repair (Rad51c, Slx1b, Ercc4) were identified along with DNA-damage markers, suggesting transcription-associated replication stress. Analysis of 10-cell transcriptomes at 90 days identified a locus of elevated gene expression containing an additional repair endonuclease (Mus81) and Rin1, a Ras-Raf antagonist and possible counterbalance to Nf1 loss. At 150 days, Rin1 was microdeleted in some gliomas and downregulated in all others. In summary, replication stress may pose a considerable bottleneck that must be resolved for glioma initiation.

12.
Cell Stem Cell ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33567267

RESUMO

The use of the dual recombinase-mediated intersectional genetic approach involving Cre-loxP and Dre-rox has significantly enhanced the precision of in vivo lineage tracing, as well as gene manipulation. However, this approach is limited by the small number of Dre recombinase driver constructs available. Here, we developed more than 70 new intersectional drivers to better target diverse cell lineages. To highlight their applicability, we used these new tools to study the in vivo adipogenic fate of perivascular progenitors, which revealed that PDGFRa+ but not PDGFRa-PDGFRb+ perivascular cells are the endogenous progenitors of adult adipocytes. In addition to lineage tracing, we used members of this new suite of drivers to more specifically knock out genes in complex tissues, such as white adipocytes and lymphatic vessels, that heretofore cannot be selectively targeted by conventional Cre drivers alone. In summary, these new transgenic tools expand the intersectional genetic approach while enhancing its precision.

13.
Plant Sci ; 304: 110589, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33568282

RESUMO

Signal transductions require calcium (Ca2+) or reactive oxygen species (ROS) signatures, which act as chemical and electrical signals in response to various biotic and abiotic stresses. Calcium as an ion or second messenger affects the membrane potential and microtubules (MTs) dynamicity, while MTs can modulate auto-propagating waves of calcium and ROS signatures in collaboration with ion channels depending on the stimulus type. Thus, in the current review, we highlight advances in research focused on the relationship between dynamic MTs and calcium and ROS signatures in short-distance transmission. The challenges of Ca2+-MTs-ROS crosstalk in cold sensing are addressed, which could suggest the prioritization of ROS or Ca2+ in signalling.

14.
Crit Rev Eukaryot Gene Expr ; 31(1): 1-9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639050

RESUMO

We investigated expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and endoglin (CD105) in renal cell carcinoma (RCC), and its potential role in predicting tumor growth and progression. A total of 47 RCC specimens and 15 adjacent normal kidney tissues were obtained. Expression of CEACAM1 and CD105 was assessed by immunohistochemistry. Microvessel density (MVD) was counted under the microscope by labeling the endothelial cells with biomarker CD34. The positivity of CEACAM1 expression in RCC (42.6%) was significantly lower than that in the normal kidney (73.%, P = 0.038). In contrast, the positivity of CD105 expression was significantly higher in RCC (78.7%) compared to that in the normal kidney (46.7%, P = 0.017). The expression level of CD105 in 47 RCC patients was significantly associated with the clinical stages of RCC (P < 0.05) but not with gender, age, tumor size, or histologic grade. Average MVD in RCC (78.05 ± 16.57) was significantly higher than that in normal tissue (43.62 ± 12.37, P < 0.05), and was significantly higher in RCC patients with advanced histologic grades (P < 0.05) or clinical stages (P < 0.01). In addition, MVD was significantly correlated with CD105 but negatively correlated with CEACAM1. Our findings suggest that down-regulation of CEACAM1 may promote angiogenesis in RCC, and that up-regulation of CD105 may promote RCC progress. MVD may be an indicator of RCC malignancy.

15.
Biochem Pharmacol ; 186: 114466, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610591

RESUMO

Cardiac microvascular endothelial cells (CMECs), derived from coronary circulation microvessel, are the main barrier for the exchange of energy and nutrients between myocardium and blood. However, microvascular I/R injury is a severely neglected topic, and few strategies can reverse this pathology. In this study, we investigated the mechanism of shear stress in microvascular I/R injury, and try to elucidate the downstream signaling pathways that inhibit CMECs apoptosis to reduce I/R injury. Our results demonstrated that shear stress inhibited the apoptosis protein, increased PECAM-1 expression and eNOS phosphorylation in hypoxia reoxygenated (H/R) CMECs. The mechanism of shear stress was related to up-regulated expression of YAP, the increased number of YAP entering the nucleus by dephosphorylation, the reduced number of TUNEL positive cells, increased miR-206 and inhibited protein level of PDCD4 in CMECs. However, siRNA-mediated knockdown of YAP abolished the protective effects of shear stress on CMECs apoptosis, similar results obtained from administration with AMO-miR-206, and also prevented PDCD4 (target gene of miR-206) increasing when treatment with both AMO-miR-206 and mimics-miR-206. In vivo, restoring the blood fluid with nitroglycerin (NTG) to mimic in vitro shear stress levels, which subsequently improved cardiac function, reduced infarcted area, lowered microvascular perfusion defects. Functional investigations clearly illustrated that increased the protein expression of PECAM-1 and eNOS phosphorylation, activated YAP, strengthened miR-206 expression, and suppressed PDCD4 expression. In summary, this study confirmed that shear stress reversed CMECs apoptosis, relieved microvascular I/R injury, the mechanism of which involving through YAP/miR-206/PDCD4 signaling pathway to finally suppress myocardial I/R injury.

16.
Health Qual Life Outcomes ; 19(1): 4, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407547

RESUMO

BACKGROUND: Pediatric Tuina has been widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0-6-year-old children with acute diarrhea. METHODS: Eighty-six participants aged 0-6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed. RESULTS: Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59-0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53-0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics. No significant difference was found between groups in days of diarrhea, global change rating, or number of days when the stool characteristics returned to normal. CONCLUSIONS: In children aged 0-6 years with acute diarrhea, pediatric Tuina showed significant effects in terms of reducing times of diarrhea compared with sham Tuina. Studies with larger sample sizes and adjusted trial designs are warranted to further evaluate the effect of pediatric Tuina therapy. TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT03005821 , Data of registration: 2016-12-29.


Assuntos
Terapias Complementares , Diarreia Infantil/terapia , Diarreia/terapia , Medicina Tradicional Chinesa/métodos , Doença Aguda/terapia , Criança , Pré-Escolar , China/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
17.
J Cell Mol Med ; 25(6): 2900-2908, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33506637

RESUMO

Lung cancer is the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer diagnoses. As an ancient therapy, moxibustion has been used to treat cancer-related symptoms in clinical practice. However, its antitumour effect on NSCLC remains largely unexplored. In the present study, a Lewis lung cancer (LLC) xenograft tumour model was established, and grain-sized moxibustion (gMoxi) was performed at the acupoint of Zusanli (ST36). Flow cytometry and RNA sequencing (RNA-Seq) were used to access the immune cell phenotype, cytotoxicity and gene expression. PK136, propranolol and epinephrine were used for natural killer (NK) cell depletion, ß-adrenoceptor blockade and activation, respectively. Results showed that gMoxi significantly inhibited LLC tumour growth. Moreover, gMoxi significantly increased the proportion, infiltration and activation of NK cells, whereas it did not affect CD4+ and CD8+ T cells. NK cell depletion reversed gMoxi-mediated tumour regression. LLC tumour RNA-Seq indicated that these effects might be related to the inhibition of adrenergic signalling. Surely, ß-blocker propranolol clearly inhibited LLC tumour growth and promoted NK cells, and gMoxi no longer increased tumour regression and promoted NK cells after propranolol treatment. Epinephrine could inhibit NK cell activity, and gMoxi significantly inhibited tumour growth and promoted NK cells after epinephrine treatment. These results demonstrated that gMoxi could promote NK cell antitumour immunity by inhibiting adrenergic signalling, suggesting that gMoxi could be used as a promising therapeutic regimen for the treatment of NSCLC, and it had a great potential in NK cell-based cancer immunotherapy.

18.
Ann Palliat Med ; 10(1): 16-28, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33474949

RESUMO

BACKGROUND: Cancer patients who receive anthracycline-based chemotherapy regimens often discontinue chemotherapy due to cardiotoxicity. Preventing and reducing anthracycline-induced cardiotoxicity (ACT) is a hot topic in cardio-oncology research. Network pharmacology is a new discipline that integrates pharmacology, bioinformatics, and systems biology. It can be used to analyze the mechanism of action of drugs in the body from a holistic perspective by constructing a "disease-gene-drug" network, providing a new method to explore compounding mechanisms of Chinese medicine. Based on network pharmacology, this study explored the mechanism of the reduction of cardiotoxicity of anthracyclines by Qishen Huanwu Capsule. METHODS: The active ingredients of Qishen Huanwu Capsule and their targets were screened based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Chemistry Database. The target genes of ACT were screened through the PharmGkb, GeneCards, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). The Venny2.1 online analysis tool was used to construct a Venn diagram to obtain the common targets of ACT and Qishen Huanwu Capsule. The STRING platform was used to construct the protein-protein interactions (PPI) among the common targets; ClueGO software was used to perform Gene Ontology (GO) biological process enrichment analysis for the common targets; the R language was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; and the results were visualized using Cytoscape software. RESULTS: The predictions indicate that Qishen Huanwu Capsule has 35 main active ingredients capable of reducing the cardiotoxicity of anthracyclines and that there are 36 common targets of ACT and Qishen Huanwu Capsule that are enriched in 133 biological processes and 27 signaling pathways. CONCLUSIONS: Qishen Huanwu Capsule regulates phosphatidylinositol 3­kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), forkhead box class O (FoxO) and other signaling pathways by regulating targets such as RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 1 (MAPK1), and mitogen-activated protein kinase 8 (MAPK8) and thereby inhibits oxidative stress and regulates apoptosis and autophagy to reduce the cardiotoxicity of anthracyclines.

19.
Environ Monit Assess ; 193(1): 43, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410991

RESUMO

Desert lakes are unique ecosystems found in oases within desert landscapes. Despite the numerous studies on oases, there are no reports regarding the spatiotemporal distribution and causes of eutrophication in the desert lakes that are located at the edge of the Linze Oasis in northwestern China. In this study, the seasonal shoreline and eutrophication of a desert lake were monitored using an unmanned aerial vehicle (UAV) and water sampling during three crop growth stages. The spatial extents of the shoreline and algal blooms and the chromophoric dissolved organic matter (CDOM) absorption coefficient were derived through UAV images. The desert lake shoreline declined during the crop growing stage, which exhibited the largest water demand and began to expand after this stage. The estimated CDOM absorption coefficient measurements and classified algal bloom area showed seasonal variations that increased from spring to late summer and then decreased in autumn. The first two crop growth stages accounted for most of the water and fertilizer requirements of the entire growth period, which may have contributed to large amounts of groundwater consumption and pollution and resulted in peak eutrophication of the lake in the second growth stage. However, the CDOM absorption coefficient of the third stage was not well correlated with that of the first two stages, suggesting that the lake may be affected by the dual effects of groundwater and precipitation recharge in the third stage. These results indicate that the water quality of desert lakes may be affected by agricultural cultivation. The agricultural demands for water and fertilizer may change the spatiotemporal changes in water quality in the lake, especially in the middle and early stages of crop growth.


Assuntos
Ecossistema , Lagos , China , Monitoramento Ambiental , Eutrofização
20.
Pharm Biol ; 59(1): 47-53, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33399495

RESUMO

CONTEXT: Therapeutic benefits of immunotherapy are restricted by cancer immune-resistance mechanisms. Rediocide-A (Red-A), a natural product extracted from Traditional Chinese Medicine, is a promising agent to battle against cancer which acts as an immune checkpoint inhibitor. OBJECTIVE: To investigate the effect of Red-A on NK-cell tumouricidal activity. MATERIALS AND METHODS: NK cells were co-cultured with A549 or H1299 cells and treated with 10 or 100 nM Red-A for 24 h. Cells treated with 0.1% dimethyl sulphoxide (DMSO) was employed as vehicle control. NK cell-mediated cytotoxicity was detected by biophotonic cytotoxicity and impedance assay. Degranulation, granzyme B, NK cell-tumour cell conjugates and ligands profiling were detected by flow cytometry. Interferon-γ (IFN- γ) production was assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Red-A increased NK cell-mediated lysis of A549 cells by 3.58-fold (21.86% vs. 78.27%) and H1299 cells by 1.26-fold (59.18% vs. 74.78%), compared to vehicle control. Granzyme B level was increased by 48.01% (A549 cells) and 53.26% (H1299 cells) after 100 nM Red-A treatment. INF-γ level was increased by 3.23-fold (A549 cells) and 6.77-fold (H1299 cells) after 100 nM Red-A treatment. Red-A treatment down-regulated the expression level of CD155 by 14.41% and 11.66% in A549 cells and H1299 cells, respectively, leading to the blockade of tumour immuno-resistance to NK cells. CONCLUSIONS: Red-A overcomes immuno-resistance of NSCLCs to NK cells by down-regulating CD155 expression, which shows the possibility of developing checkpoint inhibitors targeting TIGIT/CD155 signalling to overcome immuno-resistance of cancer cells.

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