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1.
Zhongguo Zhong Yao Za Zhi ; 46(4): 894-901, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645094

RESUMO

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.


Assuntos
Medicamentos de Ervas Chinesas , Eczema , Ephedra sinica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Tecnologia
2.
Adv Healthc Mater ; : e2002200, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33644993

RESUMO

Gliomas remain difficult to treat because of their metastatic and recurrent nature and the existence of the blood-brain barrier (BBB), which impedes drug delivery. Microglia, the resident macrophages in the CNS, can be recruited by gliomas and can penetrate the tumor. In this study, microglia (BV2 cells) are used as transport vectors to deliver paclitaxel for the treatment of glioma. To avoid paclitaxel toxicity in microglia, liposomes are first employed to isolate the drug from BV2 cells. Dipalmitoyl phosphatidylserine (DPPS), as an "eat me" signal, is doped into liposomes to amplify their phagocytosis by microglia. This study demonstrates that engineered microglia can cross the BBB, independently migrate toward gliomas, and transfer cargo to glioma cells. Of note, extracellular vesicles and tunneling nanotubes are found to offer unique modes of cargo transportation between microglia and glioma cells. In vivo, the engineered drug-loaded microglia has a high ability to target the brain, penetrate glioma, and suppress tumor progression, supporting the notion that the use of engineered microglia is a potential strategy for the treatment of glioma. These findings present new opportunities for exploration into the use of microglia as transport vectors to deliver therapeutic agents through specific membrane nanotubes and vesicles.

3.
PLoS Negl Trop Dis ; 15(2): e0009119, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33524050

RESUMO

BACKGROUND: Health promotion is essential to the SAFE strategy for trachoma elimination. Schools are a valuable venue for health promotion. However, there is little literature about the impact of health education and water infrastructure in schools on facial cleanliness and trachoma in the community. Our study aimed to describe the current state of school health promotion in Kongwa, Tanzania, and to examine the transferability of health messages from schools to the community at large. METHODOLOGY/FINDINGS: A cross-sectional survey was carried out in all 92 villages in Kongwa district, which included 85 primary schools. Data were collected on health messages and water infrastructure in the schools. A random sample of 3084 children aged 0-5 were examined for facial cleanliness in all villages. In 50 villages, a random sample of 50 children aged 1-9 per village were examined for follicular trachoma (TF). Thirty-seven (44.6%) schools had educational materials on face-washing. Fifty (60.2%) schools had a washing station. The presence of a health teacher was correlated with having posters on face washing in classrooms. The presence of face-washing materials was correlated with the availability of washing stations. Neither teachers mentioning face-washing in health curricula nor educational materials in classrooms were associated with clean faces or trachoma in the community. Having a washing station in the school was associated with lower community rates of trachoma. CONCLUSIONS: Primary school health messages and materials on trachoma were not associated with clean faces or lower rates of trachoma in the community. The target audience for primary school health promotion is likely the students themselves, without immediate rippling effects in the community. A long-term perspective should be considered during the implementation of health promotion in schools. The goal of school health promotion should be training the next generation of parents and community health leaders in combatting trachoma.

4.
Mol Cancer ; 20(1): 36, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608029

RESUMO

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.

5.
FEMS Microbiol Ecol ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33605997

RESUMO

The whitefly Bemisia tabaci is a destructive agricultural pest that frequently harbours various species of secondary symbionts including Rickettsia. Previous studies have revealed that the infection of Rickettsia can improve whitefly performance on food plants, however, to date no evidence has shown if, and how Rickettsia manipulates the plant-insect interactions. In the current study, the effects of Rickettsia persistence on the induced plant defenses, and the consequent performance of whitefly B. tabaci were investigated. Results revealed that Rickettsia can be transmitted into plants via whitefly feeding, and remain alive within the cotton plants at least two weeks. The different expression genes of cotton plants were mostly concentrated in the phytohormone signaling pathways, the marker genes of jasmonic-acid signaling pathway (AOC, AOS, LOX, MYC2) were significantly down-regulated, while the marker genes of the salicylic-acid signaling pathway (WRKY70, PR-1) were up-regulated. Biological experiments revealed that the fecundity of Rickettsia negative B. tabaci significantly increased when they fed on Rickettsia persistent cotton plants. Taken together, we provided experimental evidences that the persistence of Rickettsia and it induced defense responses in cotton plants can increase the fitness of whitefly, and by this, Rickettsia may increase its infection and spread within its whitefly host.

6.
Ann Palliat Med ; 10(1): 156-168, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33440960

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease characterized by platelet destruction. In previous studies, Jianpi Yiqi Shexue (JPYQSX) was shown to increase the peripheral platelet (PLT) counts in patients with ITP. In addition, JPYQSX also dramatically alleviated weakness and fatigue. This study aimed to investigate the effect of JPYQSX on ITP related fatigue and to illuminate the underlying mechanisms of its therapeutic effects. METHODS: Prednisone and different doses of JPYQSX were orally administered to mice with ITP. Post-treatment, all mice were subjected to a forced swimming test. In addition, blood samples were analyzed using an automated hematology analyzer. Spleen, liver, lungs, heart, kidneys, and colon tissues were collected to determine the expressions of reactive oxygen species (ROS), adenosine triphosphate (ATP), mitochondrial DNA (mtDNA), succinate dehydrogenase complex flavoprotein subunit A (SDHA), caseinolytic mitochondrial matrix peptidase proteolytic subunit (ClpP), and Lon peptidase 1 (Lonp1). RESULTS: Compared with the vehicle group, JPYQSX prolonged the forced swimming time, increased the PLT counts, and reduced the liver and spleen indices {calculated as follows: organ index (%) = [organ weight (mg)/body weight (g)] ×100%}. In addition, the levels of ROS were upregulated, while the ATP and mtDNA contents were downregulated in ITP model mice. Administration of JPYQSX restored the expression of these mitochondrial molecules to normal levels. Furthermore, JPYQSX also decreased the expressions of SDHA, ClpP, and Lonp1, which are closely related to mitochondrial activity. CONCLUSIONS: These findings suggest that JPYQSX prevents antiplatelet sera-mediated platelet destruction in ITP mice and ameliorates fatigue possibly through its effect on mitochondrial function. This study revealed JPYQSX as a potential alternative approach for ITP therapy.

7.
J Med Internet Res ; 23(2): e22427, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493124

RESUMO

BACKGROUND: During the outbreak of COVID-19, numerous rumors emerged on the internet in China and caused confusion among the public. However, the characteristics of these rumors in different phases of the epidemic have not been studied in depth, and the official responses to the rumors have not been systematically evaluated. OBJECTIVE: The aims of this study were to evaluate the rumor epidemic and official responses during the COVID-19 outbreak in China and to provide a scientific basis for effective information communication in future public health crises. METHODS: Data on internet rumors related to COVID-19 were collected via the Sina Weibo Official Account to Refute Rumors between January 20 and April 8, 2020, extracted, and analyzed. The data were divided into five periods according to the key events and disease epidemic. Different classifications of rumors were described and compared over the five periods. The trends of the epidemic and the focus of the public at different stages were plotted, and correlation analysis between the number of rumors and the number of COVID-19 cases was performed. The geographic distributions of the sources and refuters of the rumors were graphed, and analyses of the most frequently appearing words in the rumors were applied to reveal hotspots of the rumors. RESULTS: A total of 1943 rumors were retrieved. The median of the response interval between publication and debunking of the rumors was 1 day (IQR 1-2). Rumors in text format accounted for the majority of the 1943 rumors (n=1241, 63.9%); chat tools, particularly WeChat (n=1386, 71.3%), were the most common platform for initial publishing of the rumors (n=1412, 72.7%). In addition to text rumors, Weibo and web pages were more likely to be platforms for rumors released in multimedia formats or in a combination of formats, respectively. Local agencies played a large role in dispelling rumors among social media platforms (1537/1943, 79.1%). There were significant differences in the formats and origins of rumors over the five periods (P<.001). Hubei Province accounted for most of the country's confirmed rumors. Beijing and Wuhan City were the main centers for debunking of disinformation. The words most frequently included in the core messages of the rumors varied by period, indicating shifting in the public's concern. CONCLUSIONS: Chat tools, particularly WeChat, became the major sources of rumors during the COVID-19 outbreak in China, indicating a requirement to establish rumor monitoring and refuting mechanisms on these platforms. Moreover, targeted policy adjustments and timely release of official information are needed in different phases of the outbreak.


Assuntos
/epidemiologia , Comunicação , Mídias Sociais , China/epidemiologia , Surtos de Doenças , Humanos , Saúde Pública
8.
Sci Rep ; 11(1): 2519, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510252

RESUMO

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb's ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.

9.
Bioorg Med Chem Lett ; 33: 127739, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316408

RESUMO

A series of pyrano[3,2-a]carbazole alkaloids were designed and synthesized as derivatives of Girinimbine. The anticancer activities of these derivatives (3, 4a-j, 5a, 5c, 5f, 5i, 6c, 7a, 7c, 7f, 7i) against 10 cancer cell lines were studied. Among them, compounds 3 and 7i with N-methyl piperazine showed significant anticancer activity against MCF-7 cell lines with the IC50 values of 1.77 and 4.32 µM, respectively. Furthermore, their effects on altering cell morphology, inducing cell cycle arrest and apoptosis in MCF-7 cells were studied in vitro. In addition, the molecular docking study was carried out by using Discovery Studio software to predict the interactions between these derivatives and tubulin. All in all, these consequences reveal that pyranocarbazole derivatives with N-methyl piperazine can be used as potential anticancer lead compounds and provide useful points for the further optimization of pyranocarbazole alkaloids.

10.
Nucleic Acids Res ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270889

RESUMO

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 2039-2045, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283739

RESUMO

OBJECTIVE: To compare the effect of Sheng-Xue-Xiao-Ban Capsule (SXXBC) and indirubin to the peripheral platelets of the Idiopathic thrombocytopenic purpura (ITP) model mouse. METHODS: The ITP mouse model was established by the method of passive immunization. SXXBC and indirubin were used for intervention treatment. Then the hemorrhagic phenomena of ITP mice were observed and the numbers of peripheral platelets, hemoglobin and white blood cells, bone marrow megakaryocytes and their classification and coagulation function were detected and compared. RESULTS: The improvement rate of hemorrhage in SXXBC group was 40% for small dose, 60% for medium dose and 80% for high dose, while the improvement rate of hemorrhage in indirubin group was 30% for small dose, 50% for medium dose and 60% for high dose. There was no statistically significant difference in the improvement rate of hemorrhage between the two groups (P>0.05). Compared with the model control group, PLT and Hb increased in different doses of SXXBC and indirubin group 4th-8th day after drug intervention (P<0.05, 0.01). However, there was no significant difference between the different doses of SXXBC group and indirubin group (P>0.05). Compared with the model control group, the WBC in each group was significantly lower (P<0.05, 0.01) on the 4th-8th day after drug intervention; However, there was no statistical significance between the two groups of SXXBC and indirubin (P>0.05). Compared with the model control group, the total number of megakaryocytes in each treatment group were decreased (P<0.05, P<0.01), in which the number of primary megakaryocytes in the large and medium dose groups of SXXBC and indirubin were decreased (P<0.05, 0.01), and the number of juvenile megakaryocytes in the large dose group of SXXBC and indirubin were also decreased (P<0.05). The number of granular megakaryocytes were decreased in each intervention groups (P<0.05, 0.01), and the number of thromocytogenic megakaryocyte was increased in the high and medium dose groups of SXXBC and indirubin (P<0.01). The time of prothrombin was shortened in the high and medium dose groups of SXXBC and indirubin (P<0.05), and the fibrinogen (FIB) content in the high and medium dose groups of SXXBC was close to that of the normal control group. CONCLUSION: Both of the SXXBC and the indirubin standard all show good hemostatic effects. Indirubin shows a positive effect on increasing the peripheral platelet and hemoglobin in ITP model mice, regulating the immune response, reducing the total number of bone marrow megakaryocytes, increasing the thromocytogenic megakaryocyte, and increasing coagulation function.

12.
Entropy (Basel) ; 22(6)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33286370

RESUMO

This paper considers an adaptive fault-tolerant control problem for a class of uncertain strict feedback nonlinear systems, in which the actuator has an unknown drift fault and the loss of effectiveness fault. Based on the event-triggered theory, the adaptive backstepping technique, and Lyapunov theory, a novel fault-tolerant control strategy is presented. It is shown that an appropriate comprise between the control performance and the sensor data real-time transmission consumption is made, and the fault-tolerant tracking control problem of the strict feedback nonlinear system with uncertain and unknown control direction is solved. The adaptive backstepping method is introduced to compensate the actuator faults. Moreover, a new adjustable event-triggered rule is designed to determine the sampling state instants. The overall control strategy guarantees that the output signal tracks the reference signal, and all the signals of the closed-loop systems are convergent. Finally, the fan speed control system is constructed to demonstrate the validity of the proposed strategy and the application of the general systems.

13.
Aging (Albany NY) ; 122020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33260154

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associated with the immune microenvironment. To identify the effective population before administering treatment, the establishment of prognostic immune biomarkers is crucial for early HCC diagnosis and treatment. RESULTS: A total of 335 IRGs identified from 788 overlapping IRGs were associated with the survival of HCC. A prognostic immunoscore model was identified. The Kaplan-Meier survival curves and time-dependent ROC analysis revealed a powerful prognostic performance of immunoscore signature via multi validation. Besides, the immunoscore signature exhibited a better predictive power compared to other prognostic signatures. Gene set enrichment analysis showed multiple signaling differences between the high and low immunoscore group. Furthermore, immunoscore was significantly associated with multiple immune cells and immune infiltration in the tumor microenvironment. CONCLUSIONS: We identified the immunoscore as a robust marker for predicting HCC patient survival. METHODS: Three sets of immune-related genes (IRGs) were integrated to identify the overlapping IRGs. Weighted gene co-expression network analysis was performed to obtain the survival-related IRGs. Further, the prognostic immunoscore model was constructed via LASSO-penalized Cox regression analysis. Then the prognostic performance of immunoscore was evaluated. In addition, ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between immunoscore and tumor immune microenvironment.

14.
Front Surg ; 7: 580203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195388

RESUMO

Background: Lymph node metastasis (LNM) status is critical to the treatment. Fewer studies has focused on LNM in patients with small-size non-small cell lung cancer (NSCLC). This study aims to investigate clinicopathological characteristics associated with skip N2 (SN2) and non-skip N2 (NSN2) metastasis, and their metastatic patterns in NSCLC with tumor size of 1-2 cm. Methods: We reviewed the records of NSCLC patients with tumor size of 1-2 cm who underwent lobectomy with systematic lymph node dissection (LND) between January 2013 and June 2019. Clinical, radiographical, and pathological characteristics were compared among N1, SN2, and NSN2 groups. Metastatic patterns of mediastinal lymph node were analyzed based on final pathology. Results: A total of 63 NSCLC patients with tumor size of 1-2 cm were staged as pN2, including 25 (39.7%) SN2 and 38 (60.3%) NSN2. The incidence rates of SN2 and NSN2 were 2.8% (25/884) and 4.3% (38/884), respectively. For all clinicopathological characteristics, no significant difference was observed among the groups of N1, SN2, and NSN2. For the tumor located in each lobe, specific nodal drainage stations were identified: 2R/4R for right upper lobe; 2R/4R and subcarinal node (#7) for right middle lobe and right lower lobe; 4L and subaortic node (#5) for left upper lobe; #7 for left lower lobe. However, there were still a few patients (10.9%, 5/46) had the involvement of lower zone for tumors of upper lobe and the involvement of upper zone for lower lobe. Conclusions: SN2 occurs frequently in patients with small-size NSCLC. Whether lobe-specific selective LND is suitable for all small-size patients deserves more studies to confirm. Surgeons should be more careful when performing selective LND for tumors located in the lower and upper lobes.

15.
Polymers (Basel) ; 12(11)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33213107

RESUMO

Ambient temperature self-blowing tannin-furanic foams have been prepared by substituting a great part-even a majority-of furfuryl alcohol with humins, a polyfuranic material derived from the acid treatment at high temperature of fructose. Closed-cell foams were prepared at room temperature and curing, while interconnected-cell foams were prepared at 80 °C and curing, this being due to the more vigorous evaporation of the solvent. These foams appear to present similar characteristics as other tannin-furanic foams based only on furfuryl alcohol. A series of tannin-humins-furfuryl alcohol oligomer structures have been defined indicating that all three reagents co-react. Humins appeared to react well with condensed tannins, even higher molecular weight humins species, and even at ambient temperature, but they react slower than furfuryl alcohol. This is due to their high average molecular weight and high viscosity, causing their reaction with other species to be diffusion controlled. Thus, small increases in solvent led to foams with less cracks and open structures. It showed that furfuryl alcohol appears to also have a role as a humins solvent, and not just as a co-reagent and self-polymerization heat generator for foam expansion and hardening. Stress-strain for the different foams showed a higher compressive strength for both the foam with the lowest and the highest proportion of humins, thus in the dominant proportions of either furfuryl alcohol or the humins. Thus, due to their slower reactivity as their proportion increases to a certain critical level, more of them do proportionally participate within the expansion/curing time of the foam to the reaction.

16.
Nanomedicine (Lond) ; 15(27): 2655-2670, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33179590

RESUMO

Aim: To investigate the effects of the different morphological characteristics of Prussian blue nanoparticles (PB NPs) on their biocompatibility and biosafety. Materials & methods: PB NPs with different sizes, shapes and charges were synthesized and their biosafety and biocompatibility performance were systematically compared in vitro and in vivo. Results: Increased size and positive charge of PB NPs adversely affected cell viability, while improving their peroxidase activity and photothermal conversion efficiency. In vivo analysis demonstrated good biocompatibility of PB NPs, without retention in the organs, but increased size retarded their metabolism. Meanwhile, increased size and positive charge adversely affected hepatic and renal function. Conclusion: This comprehensive exploration of biosafety and biocompatibility provides strong evidences for the use of PB NPs as nanodrug carrier and/or imaging agent.

17.
Zhongguo Zhen Jiu ; 40(10): 1108-12, 2020 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-33068355

RESUMO

OBJECTIVE: To observe the effect of acupuncture technique of Tiaoxin Tongdu on learning-memory ability and expressions of hippocampal vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) in rats with vascular dementia (VD), and to explore the mechanism of acupuncture technique of Tiaoxin Tongdu for VD. METHODS: A total of 24 male SD rats were randomly divided into a sham operation group, a model group, a medication group and an acupuncture group after Morris water maze test, 6 rats in each group. VD model was established by permanent ligation of bilateral common carotid arteries in the model group, the medication group and the acupuncture group. Treatment was given on the next day after successful modeling. The rats in the acupuncture group were treated with acupuncture at "Baihui" (GV 20), "Shenting" (GV 24), "Shuigou" (GV 26), "Dazhui" (GV 14), "Fengfu" (GV 16), "Mingmen" (GV 4), "Neiguan" (PC 6), "Daling" (PC 7) and "Laogong" (PC 8) for 30 min; the rats in the medication group were treated with nimodipine solution (0.0625 g/kg) by gavage, once a day, for 2 weeks. Morris water maze test was used to detect the behavior of rats before modeling, 2 weeks after modeling and after intervention; after intervention, the expressions of VEGF and Ang-1 protein in hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the average escape latency of rats in the model group was prolonged (P<0.01), and the times of crossing the original platform were reduced (P<0.01). Compared with the model group, the average escape latency of rats in the medication group and acupuncture group was significantly shortened (P<0.01), and the times of crossing the original platform were increased (P<0.01, P<0.05). Compared with the sham operation group, the expressions of VEGF and Ang-1 protein in hippocampus in the model group were increased (P<0.05, P<0.01). Compared with the model group, the expressions of VEGF and Ang-1 protein in the hippocampus in the medication group and acupuncture group were significantly increased (P<0.01, P<0.05). CONCLUSION: The acupuncture technique of Tiaoxin Tongdu can significantly improve the learning and memory ability of VD rats, and its mechanism may be related to up-regulating the expressions of VEGF and Ang-1 protein in hippocampus and inducing angiogenesis.

18.
Mol Ther Oncolytics ; 19: 8-18, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33024815

RESUMO

Liver cancer is the fastest growing cause of cancer deaths in the United States due to its aggressiveness and lack of effective therapies. The current preclinical study examines valeric acid (pentanoic acid [C5H10O2]), one of the main compounds of valerian root extract, for its therapeutic use in liver cancer treatment. Anticancer efficacy of valeric acid was tested in a series of in vitro assays and orthotopic xenograft mouse models. The molecular target of valeric acid was also predicted, followed by functional confirmation. Valeric acid has a broad spectrum of anticancer activity with specifically high cytotoxicity for liver cancer in cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation assays. Mouse models further demonstrate that systematic administration of lipid-based nanoparticle-encapsulated valeric acid significantly reduces the tumor burden and improves survival rate. Histone deacetylase (HDAC)-inhibiting functions of valeric acid are also revealed by a structural target prediction tool and HDAC activity assay. Further transcriptional profiling and network analyses illustrate that valeric acid affects several cancer-related pathways that may induce apoptosis. In summary, we demonstrate for the first time that valeric acid suppresses liver cancer development by acting as a potential novel HDAC inhibitor, which warrants further investigation on its therapeutic implications.

19.
Chem Asian J ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025769

RESUMO

An unprecedented copper-catalyzed heteroaromatization/sulfonyl transfer of propargylic alcohols with isocyanide has been developed. 3-Sulfonyl benzofurans and indoles were produced under Cu(I) catalysis in good to high yields. The developed catalytic methodology provides controlled, modular, and facile access to sulfonyl benzoheterocycle scaffolds.

20.
Acta Physiol (Oxf) ; : e13555, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32886850

RESUMO

AIM: By activating prostacyclin receptors (IP receptors), prostacyclin (PGI2 ) exerts cardiovascular protective effects such as vasodilation and inhibition of vascular smooth muscle cell (VSMC) proliferation. However, IP receptors are dysfunctional under pathological conditions, and PGI2 produces detrimental effects that are opposite to its physiological protective effects via thromboxane-prostanoid (TP) receptors. This attempted to investigate whether or not IP receptor dysfunction facilitates the shift of PGI2 action. METHODS: The effects of PGI2 and its stable analog iloprost on VSMC phenotypic transformation and proliferation were examined in A10 cells silencing IP receptors, in human aortic VSMCs (HAVSMCs) knocked down IP receptor by CRISPR-Cas9, or in HAVSMCs transfected with a dysfunctional mutation of IP receptor IPR212C . RESULTS: PGI2 /iloprost treatment stimulated cell proliferation, upregulated synthetic proteins and downregulated contractile proteins, suggesting that PGI2 /iloprost promotes VSMC phenotypic transformation in IP-deficient cells. The effect of PGI2 /iloprost was prevented by TP antagonist S18886 or TP knockdown, indicating that the VSMC detrimental effect of PGI2 is dependent on TP receptor. RNA sequencing and Western blotting results showed that RhoA/ROCKs, MEK1/2 and JNK signalling cascades were involved. Moreover, IP deficiency increased the distribution of TP receptors at the cell membrane. CONCLUSION: PGI2 induces VSMC phenotypic transformation when IP receptors are impaired. This is attributed to the activation of TP receptor and its downstream signaling cascades, and to the increased membrane distribution of TP receptors. The VSMC detrimental effect of PGI2 medicated by IP dysfunction and TP activation might probably exacerbate vascular remodelling, accelerating cardiovascular diseases.

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