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1.
Chem Commun (Camb) ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32497159

RESUMO

We evaluate experimentally the force exerted by flexible metal-organic frameworks through expansion for a representative model system, namely MIL-53(Al). The results obtained are compared with data collected from intrusion experiments while molecular simulations are performed to shed light on the re-opening of the guest-loaded structure. The critical impact of the transition stimulating medium on the magnitude of the expansion force is demonstrated.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32539429

RESUMO

Backgroud The role of HIV infection in precipitating different clinical features in Cryptococcal meningitis (CM) patients remains controversial. Methods One hundred and twelve CM patients living with HIV/AIDS (CM+HIV+ patients) and 112 CM patients living without HIV/AIDS (CM+HIV- patients) were enrolled after propensity score matching. Demographic characteristics, symptoms, routine blood tests, biochemical and cerebrospinal fluid (CSF) profiles were compared between the two groups. Kaplan-Meier analysis and Cox proportional hazards model was used to assess 10-week mortality. Results CM+HIV+ patients frequently occurred in young (mean age 40.3±10.5) and male (89.3%) populations who also experienced leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, and hypoalbuminemia, less headaches (66.9%) and higher cryptococcemia (23.2%) (all P < 0.050); they also had higher glucose (2.6±1.1 mmol/L), increased smear positivity (78.8%) and decreased white blood cells [8.0 (2.0-28.0)×106/L] in initial CSF assay (all P< 0.050). The 10-week cumulative survival rate was 84.6% for CM+HIV+ patients and 88.5% for CM+HIV- patients (P = 0.345). Age < 35.0 years old (Hazard ratio (HR) 3.0 (1.0-8.9), P=0.046), intracranial pressure (ICP) > 250.0 mmH2O (HR: 4.8(1.1-21.6), P=0.041) and treatment lacking amphotericin B [HR: 6.5(1.9-21.4), P=0.003] were independent risk factors for 10-week mortality in CM+HIV+ patients. Conclusions There are significant clinical differences in cryptococcal meningitis patients living with or without HIV/AIDS. However, the 10-week survival rate was similar between the two groups. Younger population, high ICP and treatment lacking amphotericin B were independent risk factors for 10-week mortality of Chinese CM+HIV+ patients.

3.
Drug Des Devel Ther ; 14: 1921-1931, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546959

RESUMO

Purpose: Arsenic trioxide (ATO) has been shown to induce hepatic injury. Crocetin is a primary constituent of saffron, which has been verified to have antioxidant and anti-inflammatory effects. In the current experiment, we evaluated the efficacy of crocetin against ATO-induced hepatic injury and explored the potential molecular mechanisms in rats. Methods: Rats were pretreated with 25 or 50 mg/kg crocetin 6 h prior to treating with 5 mg/kg ATO to induce hepatic injury daily for 7 days. Results: Treatment with crocetin attenuated ATO-induced body weight loss, decreases in food and water consumption, and improved ATO-induced hepatic pathological damage. Crocetin significantly inhibited ATO-induced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) increases. Crocetin prevented ATO-induced liver malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Crocetin abrogated the ATO-induced decrease of catalase (CAT) and superoxide dismutase (SOD) activity. Crocetin was found to significantly restore the protein levels of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Furthermore, crocetin promoted the expression of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADP(H): quinone oxidoreductase 1 (NQO1). Conclusion: These findings suggest that crocetin ameliorates ATO-induced hepatic injury in rats. In addition, the effect of crocetin might be related to its role in antioxidant stress, as an anti-inflammatory agent, and in regulating the Nrf2 signaling pathway.

4.
ACS Nano ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32579339

RESUMO

Toehold-mediated strand displacement reaction, the fundamental basis in dynamic DNA nanotechnology, has proven its extraordinary power in programming dynamic molecular systems. Programmed activation of the toehold in a DNA substrate is crucial for building sophisticated DNA devices with digital and dynamic behaviors. Here we developed a detachable DNA circuit by embedding a pH-controlled intermolecular triplex between the toehold and branch migration domain of the traditional "linear substrate". The reaction rate and the "on/off" state of the detachable circuit can be regulated by varying the pHs. Similarly, a two-input circuit composed of three pH-responsive DNA modules was then constructed. Most importantly, a resettable self-assembly system of spherical nucleic acids was built by utilizing the high detachability of the intermolecular triplex structure-based DNA circuit. This work demonstrated a dynamic DNA device that can be repeatedly operated at constant temperature without generating additional waste DNA products. Moreover, this strategy showed an example of recycling waste spherical nucleic acids from a self-assembly system of spherical nucleic acids. Our strategy will provide a facile approach for dynamic regulation of complex molecular systems and reprogrammable nanoparticle assembly structures.

5.
Adv Parasitol ; 110: 107-144, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563323

RESUMO

As a zoonotic parasitosis caused by the parasitism of Echinococcus larvae, echinococcosis imposes serious disease and economic burdens on human beings and society, and is thus a global public health issue. Its complex life history, wide distribution, the combined influence of various epidemic factors, coupled with the unique natural environment, customs, and religious beliefs in endemic areas, pose a huge challenge to the national echinococcosis control programme in China. Accurate early detection and confirmation of diagnosis of echinococcosis, the use of effective drugs, real-time surveillance of the infection status of populations and various hosts, controlling the source of infection, and blocking the route of transmission are of enormous significance for control. In this paper, the work by NIPD-CTDR on the prevention and control of echinococcosis in China is reviewed, with a view to providing reference for the further promotion of the national echinococcosis control programme.

6.
Adv Parasitol ; 110: 185-216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563325

RESUMO

Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne disease prevalent in China. VL was rampant in the vast area of China north of the Yangtze River before the founding of the People's Republic of China in 1949. As a result of strenuous interventions, the disease was basically eliminated in most of the former epidemic areas in 1958-60. At present, only sporadic cases occur in the western regions of China. In the process, National Institute of Parasitic Diseases at China CDC and the Chinese Center for Tropical Diseases Research (NIPD-CTDR) have achieved great impact in controlling the diseases as well as in research on Leishmania spp. This review summarized the contribution of experts from NIPD-CTDR to the control and elimination of VL in various aspects, such as understanding the epidemiological features of VL, confirmation of VL vectors and their distribution, development of control tools including diagnostics and insecticides, monitoring and evaluation supported by information management, technical supports to the control programmes, as well as analysis of the challenges faced. At the same time, it puts forward constructive suggestions for the ultimate interruption of VL transmission in China.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32564469

RESUMO

Studies on the effectiveness and mechanisms of reducing scar formation by interfering with the renin-angiotensin-aldosterone-system (RAAS) have been demonstrated in animals, but not in humans due to the lack of clinical support. Our aim was to investigate whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) could inhibit scar formation in humans. Thus, an observational and hypothesis-generating study using a designed questionnaire was carried out. 347 patients with postoperative scars secondary to thyroid tumours were enrolled. They were divided into four groups: ACEI group, ARB group, other antihypertensive drugs control group and blank control group according to the administration of anti-hypertensive drugs. The width of scar was measured, and the Scar Cosmesis Assessment and Rating (SCAR) Scale was filled out. Results showed that patients of ACEI group (mean scar width 1.60 mm) and ARB group (mean scar width 1.57 mm) formed smaller scars than those of other anti-hypertensive drugs control group (mean scar width 2.09 mm) and blank control group (mean scar width 2.0 mm). Oral administration of ACEI and ARB may be associated with better post-surgical scar formation in humans. These two kinds of anti-hypertensive drugs may be active components of anti-scar medicine.

9.
J Comp Eff Res ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419473

RESUMO

Aim: To investigate the cost-effectiveness of lenvatinib and sorafenib in the treatment of patients with nonresected hepatocellular carcinoma in China. Materials & methods: Markov model was used to simulate the direct medical cost and quality-adjusted life years (QALY) of patients with hepatocellular carcinoma. Clinical data were derived from the Phase 3 randomized clinical trial in a Chinese population. Results: Sorafenib treatment resulted in 1.794 QALYs at a cost of $43,780.73. Lenvatinib treatment resulted in 2.916 QALYs for patients weighing <60 and ≥60 kg at a cost of $57,049.43 and $75,900.36, The incremental cost-effectiveness ratio to the sorafenib treatment group was $11,825.94/QALY and $28,627.12/QALY, respectively. Conclusion: According to WHO's triple GDP per capita, the use of lenvatinib by providing drugs is a cost-effective strategy.

10.
Eur J Pharmacol ; 880: 173140, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32387370

RESUMO

The inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the basic pathological feature of proliferative vascular diseases. Tanshinone ⅡA (Tan ⅡA), which is the most abundant fat-soluble element extracted from Salvia miltiorrhiza, has potent protective effects on the cardiovascular system. However, the underlying mechanism is still not fully understood. Here, we show that Tan ⅡA significantly inhibits neointimal formation and decreases VSMC inflammation by upregulating the expression of KLF4 and inhibiting the activation of NFκB signaling. Using a microRNA array analysis, we found that miR-712-5p expression is significantly upregulated in tumor necrosis factor alpha (TNF-α)-treated VSMCs. Loss- and gain-of-function experiments revealed that transfection of miR-712-5p mimic promotes, whereas depletion of miR-712-5p suppresses TNF-α-induced VSMC inflammation, leading to amelioration of intimal hyperplasia induced by carotid artery ligation. Moreover, depletion of miR-712-5p by its antagomir largely abrogates TNF-α-induced VSMC proliferation. Our findings suggest that miR-712-5p mediates the stimulatory effect of TNF-α on VSMC inflammation, and that Tan ⅡA inhibits VSMC inflammation and proliferation in vivo and in vitro by suppression of miR-712-5p expression. Targeting miR-712-5p may be a novel therapeutic strategy to prevent proliferative vascular diseases.

12.
Mater Sci Eng C Mater Biol Appl ; 111: 110749, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279810

RESUMO

Bone tissue engineering using osteoinductive scaffolds has evolved into a promising approach for bone regeneration. Pearl powder has recently gained interest in bone regeneration due to their bioactive characteristics and favorable mechanical properties. In order to mimic bone tissue structurally and compositionally, chitosan-hyaluronic acid (C-HA) scaffolds containing nano-pearl powder (NPP) were fabricated in current study by using freeze-drying method. The microstructure, porosity, hydrophilia, and mechanical property of scaffolds were studied by scanning electron microscopy (SEM), mercury porosimeter, contact angles, and universal material experiment machine respectively. The crystal form of NPP, which was packed in scaffolds, was tested by X-ray diffraction (XRD), and the interaction between three constituents was studied by Fourier transformed infrared (FTIR). In the other hand, the biocompatibility, osteogenic characteristics, and osteogenic related gene expression of scaffolds were examined by cell counting kit-8 (CCK-8), alkaline phosphatase activity (ALP), RT-qPCR, and Western blotting. The results revealed that the NPP was successfully incorporated in the C-HA scaffolds. The hydrophilia and mechanical properties of scaffolds increased with NPP content, whereas the pore morphology was disturbed, especially for 25% scaffold. The scaffolds had a high porosity between 89% and 93%, and decreased slightly with the increase of NPP. Cell culture tests indicated that scaffolds with higher NPP proportion were beneficial for the proliferation and differentiation of MC3T3-E1 cells, and scaffolds with 10 wt% and 25 wt% nano-pearl powder were most effective. The differentiation might be promoted by upregulating the expression of Col αI, OCN, OPN and Runx2 genes. Therefore, the nano-pearl powder/chitosan-hyaluronic acid (NPP/C-HA) scaffolds may serve as a promising biomaterial for bone tissue engineering.

13.
Cell Cycle ; 19(10): 1122-1131, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32286142

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with high metastasis, poor prognosis and conventional chemotherapy resistance. Prostate cancer associated transcript 1 (PCAT1) is an important lncRNA that was reported to be involved in cell proliferation, migration and invasion of several types of cancer cells. However, its role in ccRCC is still undetermined. This study found that PCAT1 levels were elevated in ccRCC tumors as well as several ccRCC cells, and knockdown of PCAT1 with siRNA (si-PCAT1) alleviated cell proliferation, migration and invasion of Caki-2 and ACHN cells. With bioinformatics analysis, dual-luciferase reported assay, RNA pull-down assay and Spearman's correlation analysis, we demonstrated that PCAT1 acted as a sponge for miR-656 and miR-539. Moreover, we found dual competitive interaction of miR-656/539 with PCAT1 and yes-associated protein (YAP), resulting in the identification of PCAT1-miR-656/539-YAP axis in Caki-2 and ACHN cells. With CCK-8 assay and transwell assay, miR-656/539 inhibitor or YAP overexpression could alleviate the effects of si-PCAT1 on the proliferation, migration and invasion of Caki-2 and ACHN cells. Our data indicated that PCAT1 promotes proliferation, migration and invasion of ccRCC cells by upregulating YAP via sponging miR-656 and miR-539. Taken together, this study provided a novel therapeutic target for ccRCC treatment.

14.
Chem Commun (Camb) ; 56(28): 3943-3946, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32195505

RESUMO

Sortase is one of the most widely used enzymes for covalent protein conjugation that links protein and protein/small molecules together in a site-specific way. It typically recognizes the "GGG" and "LPXTG" peptide sequences and conjugates them into an "LPXTGGG" linker. As a non-natural linker with several flexible glycine residues, it is unknown whether it affects the properties of the conjugated protein. To verify the use of sortase for protein-protein conjugation, we combined single-molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulations to characterize sortase-conjugated polyprotein I27 with three different linkers. We found that the I27 with classic linkers "LPETGGG" and "LPETG" from sortase ligation were of normal stability. However, a protein with a longer artificial linker "LPETGGGG" showed a 15% lower unfolding force. MD simulations revealed that the 4G linker showed a high probability of a closed conformation, in which the adjacent monomer has transient protein-protein interaction. Thus, we verify the use of sortase for protein conjugation, and a longer linker with a higher glycine content should be used with caution.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32207334

RESUMO

The availability of blood transfusion has been a recurrent concern for medical institutions and patients. Efficient management of this resource represents an important challenge for many hospitals. Likewise, rapid reaction during transfusion decisions and planning is a critical factor to maximize patient care. This paper proposes a novel strategy for predicting the blood transfusion need, based on available information, by means of Restricted Boltzmann Machines (RBM). By extracting and analyzing high-level features from 4831 patient records, RBM can deal with complex patterns recognition, helping supervised classifiers in the task of automatic identification of blood transfusion requirements. Results show that a successfully classification is obtained (96.85%), based only on available information from the patient records.

16.
BMC Genomics ; 21(1): 245, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188400

RESUMO

BACKGROUND: Sheath blight (SB), caused by Rhizoctonia solani, is a common rice disease worldwide. Currently, rice cultivars with robust resistance to R. solani are still lacking. To provide theoretic basis for molecular breeding of R. solani-resistant rice cultivars, the changes of transcriptome profiles in response to R. solani infection were compared between a moderate resistant cultivar (Yanhui-888, YH) and a susceptible cultivar (Jingang-30, JG). RESULTS: In the present study, 3085 differentially express genes (DEGs) were detected between the infected leaves and the control in JG, with 2853 DEGs in YH. A total of 4091 unigenes were significantly upregulated in YH than in JG before infection, while 3192 were significantly upregulated after infection. Further analysis revealed that YH and JG showed similar molecular responses to R. solani infection, but the responses were earlier in JG than in YH. Expression levels of trans-cinnamate 4-monooxygenase (C4H), ethylene-insensitive protein 2 (EIN2), transcriptome factor WRKY33 and the KEGG pathway plant-pathogen interaction were significantly affected by R. solani infection. More importantly, these components were all over-represented in YH cultivar than in JG cultivar before and/or after infection. CONCLUSIONS: These genes possibly contribute to the higher resistance of YH to R. solani than JG and were potential target genes to molecularly breed R. solani-resistant rice cultivar.

17.
Cancer Biother Radiopharm ; 35(4): 307-312, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32191497

RESUMO

Background: Long noncoding RNA (lncRNA) LUADT1 is a known oncogenic lncRNA in lung cancer. This study aimed to explore the roles of LUADT1 in melanoma. Materials and Methods: Sixty pairs of melanoma and nontumor tissues were obtained from 60 melanoma patients (37 men and 23 women, 38-68 years, 52.1 ± 4.9 years) at the First Affiliated Hospital of Zhejiang University School of Medicine. Gene expression was analyzed by quantitative polymerase chain reaction and western blot. Cell transfections were performed to analyze gene expression. Results: We found that LUADT1 was upregulated in melanoma and high levels of LUADT1 predicted poor survival. RNA interaction prediction showed that LUADT1 can form base pairing with miR-28-5p. In melanoma cells, LUADT1 overexpression mediated the upregulated Ras-related protein Rap-1b (RAP1B). Cell proliferation assay showed that LUADT1 and RAP1B overexpression mediated the increased proliferation rate of melanoma cells. In addition, miR-28-5p overexpression played opposite roles attenuating the effects of LUADT1 overexpression on both RAP1B expression and cancer cell proliferation. Conclusions: LUADT1 in melanoma and may sponge miR-28-5p to upregulate RAP1B, thereby promoting cancer cell proliferation.

18.
J Am Chem Soc ; 142(12): 5785-5792, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32109356

RESUMO

Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is required-the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.

19.
J Vis Exp ; (156)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32091003

RESUMO

Chemical and bio-conjugation techniques have been developed rapidly in recent years and allow the building of protein polymers. However, a controlled protein polymerization process is always a challenge. Here, we have developed an enzymatic methodology for constructing polymerized protein step by step in a rationally-controlled sequence. In this method, the C-terminus of a protein monomer is NGL for protein conjugation using OaAEP1 (Oldenlandia affinis asparaginyl endopeptidases) 1) while the N-terminus was a cleavable TEV (tobacco etch virus) cleavage site plus an L (ENLYFQ/GL) for temporary N-terminal protecting. Consequently, OaAEP1 was able to add only one protein monomer at a time, and then the TEV protease cleaved the N-terminus between Q and G to expose the NH2-Gly-Leu. Then the unit is ready for next OaAEP1 ligation. The engineered polyprotein is examined by unfolding individual protein domain using atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS). Therefore, this study provides a useful strategy for polyprotein engineering and immobilization.

20.
Immunol Cell Biol ; 98(4): 318-331, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31950542

RESUMO

Pre-exposure to volatile anesthetics inhibits inflammation induced by various stimuli, including surgical procedures and ischemia. We hypothesize that volatile anesthetics may induce anti-inflammatory effects via a mechanism involving regulation of histone deacetylases (HDACs). Pre-exposure of 1.5% isoflurane for 0.5 h induced anti-inflammatory effects [measured by cytokine production of tumor necrosis factor-ɑ, interleukin-8 (IL-8) and IL-1ß] in both human THP-1 cells and primary human peripheral blood monocytes stimulated by lipopolysaccharide. In human THP-1 cells, coadministration of the HDAC inhibitor trichostatin A (TSA) blocked the isoflurane-induced anti-inflammatory effects. TSA also blocked isoflurane-upregulated HDAC1-3 expression and isoflurane-reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB). The ability of isoflurane to reduce NF-κB nuclear translocation and proinflammatory responses in the cell line was blocked by gene silencing of HDAC1 and HDAC2, but not by gene silencing of HDAC3. A coimmunoprecipitation assay demonstrated that the decreased interaction between HDAC1 and HDAC2 through lipopolysaccharide was restored by isoflurane pretreatment. These findings were validated in primary human peripheral blood monocytes  wherein gene silencing of HDAC1 and HDAC2 resulted in increased cytokine production and NF-κB nuclear translocation induced by isoflurane pre-exposure and lipopolysaccharide stimulation. These results indicate that anti-inflammatory effects of the volatile anesthetic isoflurane in human monocytes involve regulation of HDAC1 and HDAC2.

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