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1.
Environ Manage ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606066

RESUMO

Probabilistic health risk assessment has widely been used for more realistic risk analysis of contaminants. However, the existing probabilistic modeling process may be unable to reflect the actual health risks comprehensively. In the present study, the Monte Carlo simulation was employed to assess the probabilistic health risks of exposing to arsenic (As) and cadmium (Cd) in groundwater through ingestion and dermal contact pathways. To systematically evaluate the actual health risks of residents, two scenarios of the probabilistic health risk assessment were proposed: (1) fixed exposure parameters, whereas uncertain metal concentrations, and (2) uncertain exposure parameters and metal concentrations. The results indicated that the mean hazard index (HI) for local residents was mostly accepted (HI < 1), while the non-cancer risk of infants at the 95th percentile under scenario 2 (HI = 1.42) exceeded the safe level of 1, signifying the potential non-cancer risk on infants. Meanwhile, the average total cancer risk (TCR) values were several times greater than the acceptable limit of 1E-06 for all the age groups under both scenarios 1 and 2, reflecting the unacceptable cancer risk. Moreover, sensitivity analysis identified the exposure duration (ED) and concentration factor (CW) were the most relevant parameters that affect the health risk. Overall, the results of this study will be useful for the policy makers in comprehensively understanding the actual health risks of the heavy metal(loids) contamination in groundwater on receptors, as well as setting up suitable groundwater management strategies to guarantee safe water supply and to maintain health for local residents.

2.
Chemosphere ; 274: 129787, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33540305

RESUMO

The anaerobic co-digestion (coAD) of swine manure (SM) and rice straw (RS) is appealing for renewable energy recovery and waste treatment worldwidely. Improving its performance is very important for its application. In this study, long-term semi-continuous experiments were conducted to evaluate the improving effects of digestate recirculation on the performance, energy recovery, and microbial community of two-stage thermophilic-mesophilic coAD of swine manure (SM) and rice straw (RS). The experimental results indicated that the coAD systems of SM and RS (mixing ratio of 3:1) with or without digestate recirculation could not realize phase separation. The reactors of both coAD systems were characterized by pH values ranging from 7.74 to 7.85, methane production as 0.41 ± 0.02 and 0.44 ± 0.03 L/L/d, and stable operation. Notably, digestate recirculation increased total methane production, organic matter removal, and reaction rate of the coAD system by 9.92 ± 5.08, 5.22 ± 1.94, and 9.73-12.60%, respectively. Digestate recirculation improved the performance of the coAD by significantly increasing the abundance of Methanosarcina (from 4.1% to 7.5%-10.7% and 35.7%) and decreasing that of Methanothermobacter (from 94.2% to 87.3%-83.6% and 56.8%). Thus, the main methanogenesis pathway of the coAD system was changed by digestate recirculation and the methane production was effectively improved. Although the energy input of the coAD system increased by 30.26%, digestate recirculation improved the energy balance of the total system by 6.83%.

3.
Exp Eye Res ; : 108520, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33617852

RESUMO

Short chain fatty acids (SCFAs) are produced by gut microbiota as fermentation products of digestion-resistant oligosaccharides and fibers. Their primary roles are functioning as major energy sources for colon cells and assisting in gut homeostasis by immunomodulation. Recent evidence suggests that they affect various organs both at cellular and molecular levels, and regulate functions in distance sites including gene expression, cell proliferation, cell differentiation, apoptosis and inflammation. In this study, we examined whether SCFAs are present in the mouse eye and whether SCFAs affect inflammatory responses of the eye and retinal astrocytes (RACs). We observed that intra-peritoneal injected SCFAs were detected in the eye and reduced intraocular inflammation induced by lipopolysaccharide (LPS). Moreover, SCFAs displayed two disparate effects on LPS-stimulated RACs - namely, cytokine and chemokine production was reduced, but the ability to activate T cells was enhanced. Our results support the existence of gut-eye cross talk and suggest that SCFAs can cross the blood-eye-barrier via the systemic circulation. If applied at high concentrations, SCFAs may reduce inflammation and impact cellular functions in the intraocular milieu.

4.
Exp Neurol ; 339: 113645, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600815

RESUMO

Microglia are rapidly activated after acute ischemic stroke, and the polarization of microglial is associated with the prognosis of acute ischemic stroke. Lipoxin A4 (LXA4), an anti-inflammatory agent, has a protective effect against ischemic stroke. However, the role of LXA4 on the polarization of microglial after acute ischemic stroke remains undetermined. We hypothesized that LXA4 may exert the neuroprotective effect though regulating the polarization of microglial. In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted protective effects on focal cerebral ischemia-reperfusion injury and reduced the expression of the pro-inflammatory cytokines IL-1ß and TNF-α. Furthermore, LXA4 inhibited the expression of Notch-1, Hes1, iNOS and CD32 all of which are associated with the differentiation into M1 microglia. By contrast, LXA4 upregulated the expression of Hes5, Arg-1 and CD206 all of which are associated with M2 phenotype in microglia. In addition, blocking the Notch signaling pathway with the inhibitor DAPT significantly mitigated the effect of LXA4 on microglia differentiation. These data suggest that LXA4 may regulate the polarization of microglia after cerebral ischemia-reperfusion injury through the Notch signaling pathway.

5.
Bioorg Med Chem Lett ; : 127862, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609659

RESUMO

Autoimmune and inflammatory diseases place a huge burden on the healthcare system. Small molecule (SM) therapeutics provide much needed complementary treatment options for these diseases. This digest series highlights the latest progress in the discovery and development of safe and efficacious SMs to treat autoimmune and inflammatory diseases with each part representing a class of SMs, namely: 1) protein kinases; 2) nucleic acid-sensing pathways; and 3) soluble ligands and receptors on cell surfaces. In this first part of the series, the focus is on kinase inhibitors that emerged between 2018 and 2020, and which exhibit increased target and tissue selectivity with the aim of increasing their therapeutic index.

6.
Nat Commun ; 12(1): 1144, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602909

RESUMO

Pear is a major fruit tree crop distributed worldwide, yet its breeding is a very time-consuming process. To facilitate molecular breeding and gene identification, here we have performed genome-wide association studies (GWAS) on eleven fruit traits. We identify 37 loci associated with eight fruit quality traits and five loci associated with three fruit phenological traits. Scans for selective sweeps indicate that traits including fruit stone cell content, organic acid and sugar contents might have been under continuous selection during breeding improvement. One candidate gene, PbrSTONE, identified in GWAS, has been functionally verified to be involved in the regulation of stone cell formation, one of the most important fruit quality traits in pear. Our study provides insights into the complex fruit related biology and identifies genes controlling important traits in pear through GWAS, which extends the genetic resources and basis for facilitating molecular breeding in perennial trees.

7.
Biosci Biotechnol Biochem ; 85(2): 280-286, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33604643

RESUMO

Preeclampsia (PE) is characterized by the impaired invasive ability of trophocytes, which can be modulated by microRNAs (miRs). In the current study, the effects of rhynchophylline (Rhy) on the viability and invasive ability of trophocytes were explored by focusing on miR-141-3p/ZEB1 axis. The level of miR-141-3p was modulated in human trophocytes and the changes in cell viability, apoptosis, invasive ability, and ZEB1 level were detected. Then the trophocytes with miR-141-3p overexpression were treated with Rhy and the effects on trophocyte phenotypes were assessed. The induced miR-141-3p level suppressed cell viability, induced apoptosis, and inhibited invasion and ZEB1 level in trophocytes. The treatment of Rhy restored the viability and invasive ability of trophocytes under the overexpression of miR-141-3p, indicating the protective effects of Rhy on trophocytes. The findings in the current study highlighted the protective effects of Rhy on trophocytes during PE progression, which was associated with the inhibition of miR-141-3p.

8.
Biosci Rep ; 41(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33605411

RESUMO

Liver hepatocellular carcinoma (LIHC) is one of the most frequently occurring primary malignant liver tumors and seriously harms people's health in the world. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) has been shown to be associated with colon cancer cell proliferation, colony formation and invasion. In the present study, a total of 370 LIHC and 51 normal samples data were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatics and immunohistochemistry (IHC) analysis showed that MTHFD1L is highly expressed in liver tumors. Correlation analysis suggested the differences of vital status between high- and low-expression MTHFD1L groups of LIHC. Univariate and multivariate Cox proportional hazards regression were performed to identify the relationship between clinical characteristics and overall survival (OS). In addition, to explore whether MTHFD1L has an effect on the immune infiltration of LIHC. The correlation between MTHFD1L expression and 24 immune cells were analyzed by ImmuneCellAI database. Furthermore, we combined three databases CIBERSORT, TIMER and ImmuneCellAI to do a comprehensive validation and determined that dendritic cells (DCs) resting, macrophage M0 and macrophage M2 closely related to the expression of MTHFD1L. The results showed that MTHFD1L was a potential prognostic biomarker for LIHC, and could help to elucidate that how the immune microenvironment promotes liver cancer development.

9.
Oxid Med Cell Longev ; 2021: 8865762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603953

RESUMO

Myocardial injury after cardiac arrest (CA) often results in severe myocardial dysfunction and death involving mitochondrial dysfunction. Here, we sought to investigate whether baicalin, a natural flavonoid compound, exerts cardioprotection against CA-induced injury via regulating mitochondrial dysfunction. We subjected the rats to asphyxia CA after a daily baicalin treatment for 4 weeks. After the return of spontaneous circulation, baicalin treatment significantly improved cardiac function performance, elevated survival rate from 35% to 75%, prevented necrosis and apoptosis in the myocardium, which was accompanied by reduced phosphorylation of Drp1 at serine 616, inhibited Drp1 translocation to the mitochondria and mitochondrial fission, and improved mitochondrial function. In H9c2 cells subjected to simulated ischemia/reperfusion, increased phosphorylation of Drp1 at serine 616 and subsequently enhanced mitochondrial Drp1 translocation as well as mitochondrial fission, augmented cardiomyocyte death, increased reactive oxygen species production, released cytochrome c from mitochondria and injured mitochondrial respiration were efficiently improved by baicalin and Drp1 specific inhibitor with Mdivi-1. Furthermore, overexpression of Drp1 augmented excessive mitochondrial fission and abolished baicalin-afforded cardioprotection, indicating that the protective impacts of baicalin are linked to the inhibition of Drp1. Altogether, our findings disclose for the first time that baicalin offers cardioprotection against ischemic myocardial injury after CA by inhibiting Drp1-mediated mitochondrial fission. Baicalin might be a prospective therapy for the treatment of post-CA myocardial injury.

10.
Appl Radiat Isot ; 170: 109626, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33550089

RESUMO

Future international nuclear disarmament may involve the dismantlement of nuclear warheads. In nuclear warhead dismantlement verification, the mass information of the fissile material in the pit is an important attribute of nuclear warheads, and can be used to verify that the nuclear warheads demanded by the nuclear disarmament treaty have indeed been dismantled. In this paper, a method of reconstructing the fissile material mass of the pit based on the activation effect of the explosive and the neural network is proposed, and may be applied in the future nuclear warhead dismantlement verification. Firstly, the number and average abundance of 14C produced by the neutron activation reactions in the explosive inside the nuclear warhead was calculated based on the Monte Carlo numerical simulation. Secondly, it is found that the spatial distribution of the 14C abundances in the explosive is closely related to the fissile material mass of the pit through the numerical simulation. Then, neural networks were established to reconstruct the fissile material mass of the pit through the training. The testing results show that, the fissile material mass of the pit can be reconstructed accurately based on the activation effect of the explosive and the neural network, and the reconstruction precision is better than 10%.

11.
Environ Pollut ; 275: 116648, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33581628

RESUMO

The concentrations of PBDEs, NBFRs, DP, PCBs, and OCPs were analyzed in water samples of the Yellow River Basin (YRB) and in soil and maize samples collected from basin irrigation areas to understand the status of POPs and associated health risks. The results showed: (1) the congeners of eight PBDEs and seven NBFRs were detected in 10 tributaries, with average concentrations of 1575 and 4288 pg. L-1. Thirty-three congeners of PCBs were detected, and the average concentration of PCB was 232 pg. L-1. Five HCHs were the primary congeners among twenty-three congeners of OCPs in the ten tributaries, accounting for 79% of the total. The average concentration of OCPs was 8287 pg. L-1. (2) Similar congeners of HFRs, PCBs, and OCPs were found in the trunk water. The ranking based on the HFR concentration was upstream > downstream > midstream, and that of the PCB and OCP concentration was downstream > upstream > midstream. (3) PCBs and OCPs in the trunk water of the YRB and in the soil and maize irrigated with river water pose potential carcinogenic and non-carcinogenic risks. The results indicate considerable organic pollution in the YRB, suggesting that national emission standards for POPs should be implemented soon.

12.
J Hazard Mater ; 413: 125370, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33609862

RESUMO

Microplastics (MPs) have frequently been detected in freshwater environments, and there is growing concern about their ecological effects, especially the influence of the "plastisphere" on the freshwater ecosystems. The colonization of microbes on MPs would significantly alter their transport behavior, i.e., buoyancy, in fresh water. In this research, we studied the effects of biofilm colonization on the sinking and floating of three MPs, i.e., polyethylene terephthalate (PET), polypropylene (PP), and polyvinyl chloride (PVC), after 44 days of incubation in three freshwater systems (the Niushoushan River, the Qinhuai River, and East Lake) in China. The results showed that the biofilms attached to the three MPs contained different biomass and chlorophyll-a levels were related to water environmental conditions and physicochemical properties of MPs, based on redundancy analysis. Generally, PET and PVC sinking, with density higher than water, tended to increase after biofilm formation. Thereafter, the settling velocity of biofouled PET and PVC squares became faster than that of the virgin ones. In summary, our study suggested that biofouling does affect the sinking of MPs in fresh water and consequently influences the transport behavior and the distribution characteristics of MPs in freshwater environments, and this issue deserves more scientific attention.

13.
Fitoterapia ; 150: 104835, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33524516

RESUMO

Seven new limonoids, named krishnolides E-K (1-7), including three khayanolides, two mexicanolides, a derivative of trangmolin A, and an andirobin, were isolated from seeds of the Indian Krishna mangrove, Xylocarpus moluccensis. The structures of these limonoids were established by HRESIMS, extensive NMR investigations, and X-ray crystallography. Most notably, the absolute configurations of 1, 5, 6, and 7 were unequivocally determined by single-crystal X-ray diffraction analyses (Cu Kα). Krishnolide F (2) exhibited significant agonistic effects on human pregnane-X-receptor (hPXR) at the concentration of 10.0 µM. Molecular docking revealed that 2 could bind a helix near the region of the Helix 12 of hPXR. Polar contribution could be electrostatic effects from the formation of two stable protein-ligand hydrogen bonds between Gln285/1-OH and His407/1-OH, respectively. This is the first report of agonistic effects of a khayanolide-type limonoid on hPXR.

14.
Proc Natl Acad Sci U S A ; 118(6)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33547233

RESUMO

Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.

15.
Postgrad Med J ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541928

RESUMO

BACKGROUND: Increasing evidence indicated that infection factors play important roles in stroke development. Human cytomegalovirus (HCMV) infection was positively associated with atherosclerosis and hypertension which are stroke risk factors. Therefore, we aimed to explore the relationship between HCMV infection and stroke using the data of US National Health and Nutrition Examination Survey (NHANES). METHODS: We analysed data on 2844 men and 3257 women in the NHANES 1999-2004. We included participants aged 20-49 years who had valid data on HCMV infection and stroke. RESULTS: 54.1% of participants had serological evidence of HCMV infection and 0.8% of them had a previous diagnosis of stroke. There were ethnic differences in the prevalence of HCMV seropositivity (p<0.001). There was no significant association between HCMV seropositivity and stroke in men in any of the models. In women, HCMV seropositivity was associated with stroke before adjustment (OR=3.45, 95% CI 1.09 to 10.95, p=0.036). After adjusting for race/ethnicity, the association remained significant (OR=4.40, 95% CI 1.37 to 14.09, p=0.014). After further adjustment for body mass index, diabetes, hypercholesterolaemia, hypertension, alcohol consumption, smoking and physical activity, the association still existed (OR=3.58, 95% CI 1.14 to 11.25, p=0.030). The association was significant consistently in adjusted model for age (OR=3.39, 95% CI 1.08 to 10.64, p=0.037). CONCLUSIONS: We found a strong association between HCMV and stroke in women from the nationally representative population-based survey. This provide additional motivation for undertaking the difficult challenge to reduce the prevalence of stroke.

16.
Biomater Sci ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537687

RESUMO

Methionine (Met), an essential amino acid in the human body, possesses versatile features based on its chemical modification, cell metabolism and metabolic derivatives. Benefitting from its multifunctional properties, Met holds immense potential for biomedical applications. In this review, we systematically summarize the recent progress in Met-based strategies for biomedical applications. First, given the unique structural characteristics of Met, two chemical modification methods are briefly introduced. Subsequently, due to the disordered metabolic state of tumor cells, applications of Met in cancer treatment and diagnosis are summarized in detail. Furthermore, the efficacy of S-adenosylmethionine (SAM), as the most important metabolic derivative of Met, for treating liver diseases is mentioned. Finally, we analyze the current challenges and development trends of Met in the biomedical field, and suggest that Met-restriction therapy might be a promising approach to treat COVID-19.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33538056

RESUMO

Near-infrared (NIR) organic solid-state lasers play an essential role in applications ranging from laser communication to infrared night vision, but progress in this area is restricted by the lack of effective excited-state gain processes. Herein, we originally proposed and demonstrated the cascaded occurrence of excited-state intramolecular proton transfer for constructing the completely new energy systems. Cascading by the first ultrafast proton transfer of <430 fs and the subsequent irreversible second proton transfer of ~1.6 ps, the stepwise proton transfer process favors the true six-level photophysical cycle, which supports efficient population inversion and thus NIR single-mode lasing at 854 nm. This work realizes longest wavelength beyond 850 nm of organic single-crystal lasing to date and originally exploits the cascaded excited-state molecular proton transfer energy level systems for organic solid-state lasers.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 56-61, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554797

RESUMO

OBJECTIVE: To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). METHODS: The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed.The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. RESULTS: Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. CONCLUSION: NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.


Assuntos
Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Fatores de Ligação ao Core , Intervalo Livre de Doença , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos
19.
Acta Biomater ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33540061

RESUMO

Hepatitis B virus (HBV) is a global health issue, but currently available anti-HBV drugs have limited success. Previously, introduction of the Toll-like receptor (TLR)-3 ligand poly(I:C) to the liver via hydrodynamic injection (HI) was shown to effectively suppress HBV replication in a chronic HBV replication mouse model. However, this method cannot be applied in human beings. To improve the liver targeting of poly(I:C) via intravenous injection, calcium phosphate nanoparticles (CPNs) carrying poly(I:C) with or without antibodies were constructed, and their anti-HBV effects were investigated. We found that significantly more anti-F4/80-conjugated and IgG2α-conjugated nanoparticles were taken up in liver cells both in vivo and in vitro. In addition, these nanoparticles produced pronounced immunostimulatory effects in vitro in primary liver cells. Importantly, treatment with nanoparticles carrying poly(I:C) increased the production of intrahepatic cytokines and chemokines and enhanced T cell responses, significantly reducing HBsAg, HBeAg and HBV DNA levels in the mice. Compared to nonconjugated and isotype-antibody-conjugated nanoparticles, the anti-F4/80-conjugated nanoparticles demonstrated the strongest anti-HBV effects. In summary, nanoparticles carrying poly(I:C) conjugated with an F4/80 antibody promoted liver targeting, and they may represent a suitable alternative to HI for future anti-HBV treatment. Statement of Significance: HBV chronically infects approximately 250 million individuals worldwide but current anti-HBV drugs have limited success. Introduction of toll-like receptor 3 ligand poly(I:C) into liver by hydrodynamic injection has been proven to promote HBV clearance in mouse model. However, this technique is not clinically suitable for human patients. We have constructed calcium phosphate nanoparticles carrying poly(I:C) with specific antibody targeting liver nonparenchymal cells. The uptake into relevant liver cells and the anti-HBV effects were studied. After intravenous injection into mice, the uptake rate of anti-F4/80-conjugated nanoparticels was enhanced in liver, and these nanoparticles exert effective anti-HBV effects in vivo. This may provide important insight into future HBV immunotherapy based on nanoparticle-mediated drug delivery.

20.
Zhen Ci Yan Jiu ; 46(1): 14-20, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33559420

RESUMO

OBJECTIVE: To observe the effects of acupuncture on the behavior, serum inflammatory cytokines, hippocampal Nod-like receptor protein 3(NLRP3) inflammasome-related proteins and microglia activation in rats with intrauterine distress induced ischemia-hypoxic brain injury (HIBD), so as to explore the mechanism of acupuncture underlying treatment of HIBD by regulating hippocampal inflammation. METHODS: The HIBD model was established by clipping bilateral uterine arteries for 10 min and delaying caesarean delivery. HIBD rats were randomly divided into model group and acupuncture group according to body weight and litter factors, with 12 rats in each group. Twelve rats delivered normally were regarded as the normal group. Acupuncture was applied to bilateral "Benshen"(GB13) for 10 min, once a day for 14 consecutive days. H.E. staining was used to observe the pathological changes of hippocampus. The three chamber sociability test was used to determine the rat's social ability. The serum IL-1ß and IL-18 levels, the hippocampal expressions of NLRP3, apoptosis associated speck like protein containing CARD(ASC) and cysteinyl aspartate specific proteinase-1(Caspase-1), andionized calcium bindingadaptor molecule-1(IBA-1) were detected by ELISA,Western blot and Immunofluorescence, separately. RESULTS: Compared with the normal group, The hippocampal neurons in the model group are arranged loosely, and the cells are solidified and shrunk and the whole cells are deeply stained. The time of exploring the stranger rat in the model group was significantly reduced (P<0.01). The contents of IL-1ß and IL-18, the expressions of NLRP3, ASC, Caspase-1 and IBA-1 of the model group were higher than those of the normal group (P<0.01, P<0.05, P<0.001). Following acupuncture intervention, the cell structure of hippocampal neurons was improved, and there were fewer cases of cell solidification, atrophy, and deep staining. In comparison with the model group, the time of exploring stranger rat in the acupuncture group was significantly increased (P<0.01). The contents of IL-1ß and IL-18, the expressions of NLRP3, ASC and Caspase-1, and IBA-1 of the acupuncture group were significantly down-regulated than those of the model group (P<0.01, P<0.05). CONCLUSION: Acupuncture can effectively improve the social behavior deficits of HIBD rats,which may be related to inhibition of the expression of inflammatory response proteins NLRP3, ASC and Caspase-1 in the hippocampus, decrease the activation of microglia in the hippocampus, and reduce serum IL-1ß and IL-18, thereby alleviating inflammation.


Assuntos
Terapia por Acupuntura , Lesões Encefálicas , Animais , Feminino , Hipocampo/metabolismo , Inflamação/genética , Inflamação/terapia , Interleucina-1beta/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley
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