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1.
J Transl Med ; 19(1): 135, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794921

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as "microRNA sponges". However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. METHODS: 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. RESULTS: A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. CONCLUSIONS: This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

2.
J Transl Med ; 19(1): 143, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827606

RESUMO

BACKGROUND: Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice METHODS: The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured RESULTS: There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) CONCLUSIONS: This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.

3.
Asia Pac J Clin Nutr ; 30(1): 1-6, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787034

RESUMO

BACKGROUND AND OBJECTIVES: Malnutrition in elderly individuals is extremely common. In China, Nutritional Risk Screening 2002 (NRS-2002) is often used to assess malnutrition in hospitalized elderly patients, although a gold standard for elderly outpatients is lacking. The Nutrition Screening Initiative Checklist (NSI) and Malnutrition Screening Tool (MST) have seldom been validated in elderly outpatients. This open, parallel, multi-center, cross-sectional study evaluated the performance of NRS-2002, the NSI, and the MST in estimating malnutrition risk in elderly outpatients. METHODS AND STUDY DESIGN: This study included 986 elderly outpatients, with 53.2% being women, from five clinical teaching hospitals in Beijing. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the tools were estimated using a body mass index (BMI) of <18.5 kg/m2 as a reference. RESULTS: The mean (range) age of the patients was 69.6±6.8 (60-100) years. Overall, 4.3% had BMI <18.5 kg/m2, 16.8% scored ≥3 points in NRS-2002, 9.8% scored ≥2 points in the MST, and 37.0% scored ≥3 points in the NSI. NRS-2002 had the highest sensitivity and the best AUC (0.934 vs. 0.642 for the NSI and 0.660 for the MST, p<0.05), and the MST had the highest specificity. The sensitivity and specificity of the NSI were 0.64 and 0.64, respectively. CONCLUSIONS: NRS-2002 had the highest validity, and the MST had the highest specificity in estimating the risk of malnutrition in elderly outpatients. However, the accuracy of the NSI should be further verified with large samples.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33704429

RESUMO

OBJECTIVE: To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. METHODS: 983 gout patients with fenofibrate treatment were retrospectively enrolled from the electronic record system who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dL within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during treatment period were assessed by generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. RESULTS: 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dL within 6 months after fenofibrate initiation. The median (quartile) change of SCr in the whole cohort was 0.11 (0.03-0.20) mg/dL, whereas it was 0.36 (0.33-0.45) mg/dL in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) (OR, 2.39, 95% CI,1.48-3.86) and tophus (OR, 2.29, 95% CI, 1.39-3.78) were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily elevated, serum urate and triglyceride concentrations decreased resulted from the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, 65% of patients' SCr was reversible after an average of 49 days off the drug. CONCLUSIONS: This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout need additional focus.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33534708

RESUMO

Successful epilepsy surgeries depend highly on pre-operative localization of epileptogenic zones. Stereoelectroencephalography (SEEG) records interictal and ictal activities of the epilepsy in order to precisely find and localize epileptogenic zones in clinical practice. While it is difficult to find distinct ictal onset patterns generated the seizure onset zone from SEEG recordings in a confined region, high frequency oscillations are commonly considered as putative biomarkers for the identification of epileptogenic zones. Therefore, automatic and accurate detection of high frequency oscillations in SEEG signals is crucial for timely clinical evaluation. This work formulates the detection of high frequency oscillations as a signal segment classification problem and develops a hypergraph-based detector to automatically detect high frequency oscillations such that human experts can visually review SEEG signals. We evaluated our method on 4,000 signal segments from clinical SEEG recordings that contain both ictal and interictal data obtained from 19 patients who suffer from refractory focal epilepsy. The experimental results demonstrate the effectiveness of the proposed detector that can successfully localize interictal high frequency oscillations and outperforms multiple peer machine learning methods. In particular, the proposed detector achieved 90.7% in accuracy, 80.9% in sensitivity, and 96.9% in specificity.

6.
Curr Med Sci ; 41(1): 108-117, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582914

RESUMO

Microtubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Therefore, aberrant MASTL expression is commonly implicated in various human cancers. This study analyzed MASTL expression in gastric cancer vs. adjacent normal tissue for elucidating the association with clinicopathological data from patients. This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro. The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN, GEPIA, and Oncomine online databases. Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells. RT-qPCR, Western blotting, cell viability, cell counting, flow cytometric apoptosis and cell cycle, and colony formation assays were performed. MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue, and the MASTL expression was associated with advanced tumor stage, Helicobacter pylori infection and histological subtypes. On the other hand, knockdown of MASTL expression significantly reduced tumor cell viability and proliferation, and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis. At protein level, knockdown of MASTL expression enhanced levels of cleaved PARP1, cleaved caspase-3, Bax and p-ERK1/2 expression, but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells. MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression, whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis. Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.

7.
Hum Brain Mapp ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33566375

RESUMO

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non-traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma-exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head-body-tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma-related than PTSD-specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD-specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.

8.
Gut ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558272

RESUMO

OBJECTIVE: Stroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown. DESIGN: We performed two clinical cohort studies to capture the gut dysbiosis dynamics after stroke and their relationship with stroke prognosis. Then, we used a middle cerebral artery occlusion model to explore gut dysbiosis post-stroke in mice and address the causative relationship between acute ischaemic stroke and gut dysbiosis. Finally, we tested whether aminoguanidine, superoxide dismutase and tungstate can alleviate post-stroke brain infarction by restoring gut dysbiosis. RESULTS: Brain ischaemia rapidly induced intestinal ischaemia and produced excessive nitrate through free radical reactions, resulting in gut dysbiosis with Enterobacteriaceae expansion. Enterobacteriaceae enrichment exacerbated brain infarction by enhancing systemic inflammation and is an independent risk factor for the primary poor outcome of patients with stroke. Administering aminoguanidine or superoxide dismutase to diminish nitrate generation or administering tungstate to inhibit nitrate respiration all resulted in suppressed Enterobacteriaceae overgrowth, reduced systemic inflammation and alleviated brain infarction. These effects were gut microbiome dependent and indicated the translational value of the brain-gut axis in stroke treatment. CONCLUSIONS: This study reveals a reciprocal relationship between stroke and gut dysbiosis. Ischaemic stroke rapidly triggers gut microbiome dysbiosis with Enterobacteriaceae overgrowth that in turn exacerbates brain infarction.

9.
J Vis Exp ; (167)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33554966

RESUMO

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV). First, the lentiviral construct of EcoHIV was packaged in cultured 293 FT cells for 48 hours. Then, the conditional medium was concentrated and titered. Next, we performed bilateral stereotaxic injections of the EcoHIV-EGFP into F344/N rat brain tissue. One week after infection, EGFP fluorescence signals were detected in the infected brain tissue, indicating that EcoHIV successfully induces an active HIV infection in rats. In addition, immunostaining for the microglial cell marker, Iba1, was performed. The results indicated that microglia were the predominant cell type harboring EcoHIV. Furthermore, EcoHIV rats exhibited alterations in temporal processing, a potential underlying neurobehavioral mechanism of HAND as well as synaptic dysfunction eight weeks after infection. Collectively, the present study extends the EcoHIV model of HIV-1 infection to the rat offering a valuable biological system to study HIV-1 viral reservoirs in the brain as well as HAND and associated comorbidities such as drug abuse.


Assuntos
Encéfalo/patologia , Encéfalo/virologia , Infecções por HIV/patologia , HIV-1/fisiologia , Animais , Quimera , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Infecções por HIV/complicações , Humanos , Masculino , Camundongos , Ratos Endogâmicos F344 , Técnicas Estereotáxicas , Sinapses/patologia , Fatores de Tempo , Replicação Viral
10.
Artigo em Inglês | MEDLINE | ID: mdl-33548492

RESUMO

OBJECTIVE: Amygdala-ventrolateral prefrontal cortex (VLPFC) circuitry is disrupted in pediatric anxiety disorders, yet how selective serotonin reuptake inhibitors (SSRIs) affect this circuitry is unknown. We examined the impact of the SSRI escitalopram on functional connectivity (FC) within this circuit, and whether early FC changes predicted treatment response in adolescents with generalized anxiety disorder (GAD). METHOD: Resting-state functional magnetic resonance (MR) images were acquired before and after 2 weeks of treatment in 41 adolescents with GAD (12-17 years of age) who received double-blind escitalopram or placebo for 8 weeks. Change in amygdala-based whole-brain FC and anxiety severity were analyzed. RESULTS: Controlling for age, sex, and pretreatment anxiety, escitalopram increased amygdala-VLPFC connectivity compared to placebo (F = 17.79, p = .002 FWE-corrected). This early FC change predicted 76.7% of the variability in improvement trajectory in patients who received escitalopram (p < .001) but not placebo (p = .169); the predictive power of early amygdala-VLPFC FC change significantly differed between placebo and escitalopram (p = .013). Furthermore, this FC change predicted improvement better than baseline FC or clinical/demographic characteristics. Exploratory analyses of amygdala subfields' FC revealed connectivity of left basolateral amygdala (BLA) -VLPFC (F = 19.64, p < .001 FWE-corrected) and superficial amygdala-posterior cingulate cortex (F = 22.92, p = .001 FWE-corrected) were also increased by escitalopram, but only BLA-VLPFC FC predicted improvement in anxiety over 8 weeks of treatment. CONCLUSION: In adolescents with GAD, escitalopram increased amygdala-prefrontal connectivity within the first 2 weeks of treatment, and the magnitude of this change predicted subsequent clinical improvement. Early normalization of amygdala-VLPFC circuitry might represent a useful tool for identifying future treatment responders as well as a promising biomarker for drug development. CLINICAL TRIAL REGISTRATION INFORMATION: Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety; https://www.clinicaltrials.gov/; NCT02818751.

11.
Clin Nutr ; 40(2): 657, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33413915
12.
Sci Total Environ ; 763: 144204, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385838

RESUMO

Surface area and porosity are important physical properties of biochar, playing a crucial role in many biochar applications, such as wastewater treatment and soil remediation. The production of engineered biochar with highly porous structure and large surface area has received extensive attention. This paper comprehensively reviewed the effects of biomass and pyrolysis parameters on the surface area and porosity of biochar. The composition of biomass feedstock and pyrolysis temperature are the major influencing factors. It is suggested that the lignocellulosic biomass is an outstanding candidate, wood and woody biomass in particular. Besides, moderate temperatures (400-700 °C) are suitable for the development of the pore structure. Further improvement can be implemented by additional treatments. Activation is the most widely used and effective way to promote biochar surface area and porosity, especially the chemical activation. Enhancement can also be achieved by using other treatment methods, such as carbonaceous materials coating, ball milling, and templating. Future research should focus on upgrading or developing treatment technology to achieve enhanced functionality and porous structure of biochar simultaneously.


Assuntos
Carvão Vegetal , Pirólise , Biomassa , Porosidade , Solo
13.
Artigo em Inglês | MEDLINE | ID: mdl-33506418

RESUMO

High-siliceous/calcareous mineral granules may cause cytotoxicity by attaching to cell membranes. In this research, giant (GUVs) and small unilamellar vesicles (SUVs) were used as model membranes for studying the interaction between high-siliceous/calcareous mineral granules (micro calcite, micro quartz, nano calcium carbonate, and nano silica) and artificial membranes. Confocal laser scanning microscopy (CLSM) and fluorescence labeling experiments suggest that nano calcium carbonate (nano CaCO3) and nano silica (nano SiO2) induce gelation by disrupting the oppositely charged membranes, indicating the important role of electrostatic forces. Thereby, the mineral granule size affects the electrostatic interactions and thus leading to the damage of the membranes. FTIR spectra and molecular dynamics reveal that mineral granules mainly interact with -PO2-, -OH, and -C-N(CH3)3+ groups in phospholipids. The electrostatic force between nano minerals and phospholipids is greater in the case SiO2 when compared to CaCO3. Moreover, nano SiO2 forms the strongest hydrogen bond with the -PO2- group as confirmed by FTIR. Thus, nano SiO2 causes the greatest damage to membranes. This research provides a deeper understanding of the mechanism regarding the interaction between inhalable mineral granules and cell membranes.

14.
PLoS One ; 16(1): e0245317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33428672

RESUMO

BACKGROUND: Intolerance to gastric feeding tubes is common among critically ill adults and may increase morbidity. Administration of prokinetics in the ICU is common. However, the efficacy and safety of prokinetics are unclear in critically ill adults with gastric feeding tubes. We conducted a systematic review to determine the efficacy and safety of prokinetics for improving gastric feeding tube tolerance in critically ill adults. METHODS: Randomized controlled trials (RCTs) were identified by systematically searching the Medline, Cochrane and Embase databases. Two independent reviewers extracted the relevant data and assessed the quality of the studies. We calculated pooled relative risks (RRs) for dichotomous outcomes and the mean differences (MDs) for continuous outcomes with the corresponding 95% confidence intervals (CIs). We assessed the risk of bias using the Cochrane risk-of-bias tool and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to rate the quality of the evidence. RESULTS: Fifteen RCTs met the inclusion criteria. A total of 10 RCTs involving 846 participants were eligible for the quantitative analysis. Most studies (10 of 13, 76.92%) showed that prokinetics had beneficial effects on feeding intolerance in critically ill adults. In critically ill adults receiving gastric feeding, prokinetic agents may reduce the ICU length of stay (MD -2.03, 95% CI -3.96, -0.10; P = 0.04; low certainty) and the hospital length of stay (MD -3.21, 95% CI -5.35, -1.06; P = 0.003; low certainty). However, prokinetics failed to improve the outcomes of reported adverse events and all-cause mortality. CONCLUSION: As a class of drugs, prokinetics may improve tolerance to gastric feeding to some extent in critically ill adults. However, the certainty of the evidence suggesting that prokinetics reduce the ICU or hospital length of stay is low. Prokinetics did not significantly decrease the risks of reported adverse events or all-cause mortality among critically ill adults.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33512508

RESUMO

Anxiety and depressive symptoms may predispose individuals to sleep disturbance. Understanding how these emotional symptoms affect sleep quality, especially the underlying neural basis, could support the development of effective treatment. The aims of the present study were therefore to investigate potential changes in brain morphometry associated with poor sleep quality and whether this structure played a mediating role between the emotional symptoms and sleep quality. 141 healthy adults (69 women, mean age 26.06 years, SD = 6.36 years) were recruited. A structural Magnetic Resonance Imaging (MRI) investigation was performed and self-reported measures of anxiety, depressive symptoms and sleep quality obtained for each participant. Whole-brain regression analysis revealed that worse sleep quality was associated with thinner cortex in left Superior Temporal Sulcus (STS). Furthermore, the thickness of left STS mediated the association between the emotional symptoms and sleep quality. A subsequent commonality analysis showed that physiological component of the depressive symptoms had the greatest influence on sleep quality. In conclusion, thinner cortex in left STS may represent a neural substrate for the association between anxiety and depressive symptoms and poor sleep quality and may thus serve as a potential target for neuromodulatory treatment of sleep problems.

16.
Transl Oncol ; 14(4): 101018, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33493800

RESUMO

Absent in melanoma 2 (AIM2) as an immune regulator for the regulation of tumor-associated macrophages (TAMs) function is unclear in tumor development. Here, the AIM2 function was investigated in TAMs-mediated malignant behaviors of renal carcinoma. The correlation analysis result showed that the AIM2 expression in TAMs was negatively correlated with the percentages of M2-like polarization phenotype in human or murine renal cancer specimens. By the cocultured assay with bone marrow-derived macrophages (BMDMs) and Renca cells, overexpression of AIM2 in macrophages enhanced the inflammasome activation and reversed the phenotype from M2 to M1. Compared with BMDMs-Ctrl cocultured group, BMDMs-AIM2 cocultured group showed reduced tumor cell proliferation and migration. The blockade of inflammasome activation by the inhibitor Ac-YVAD-CMK abrogated AIM2-mediated M1 polarization and the inhibition of tumor cell growth. To evaluate the therapeutic efficacy of AIM2-mediated M1 macrophages in vivo, BMDMs-AIM2 were intravenously injected into subcutaneous Renca-tumor mice. The results showed that the infiltration of M1 TAMs was increased and tumor growth was suppressed in BMDMs-AIM2-treated mice when compared with BMDMs-Ctrl-treat mice. Accordingly, the blockade of inflammasome activation reduced the anti-tumor activities of BMDMs-AIM2. Moreover, the lung metastases of renal carcinoma were suppressed by the administration of BMDMs-AIM2 accompanied with the reduced tumor foci. These results demonstrated that AIM2 enhanced TAMs polarization switch from anti-inflammatory M2 phenotypy to pro-inflammatory M1 through inflammasome signaling activation, thus exerting therapeutic intervention in renal carcinoma models. Our results provide a possible molecular mechanism for the modulation of TAMs polarization in tumor microenvironment and open a new potential therapeutic approach for renal cancer.

17.
Sci Total Environ ; 763: 144616, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385844

RESUMO

The quantitative evaluations of nutrients delivered by submarine groundwater discharge (SGD) have been widely conducted worldwide, but sources of nutrients in the discharged submarine groundwater remain unclear. Identifying these sources of nutrients is essential to the protection and management of marine ecological environments. This study aims to evaluate the magnitudes of SGD and the associated nitrate in the Guangdong-Hongkong-Macao Greater Bay Area (GHM Greater Bay Area), China, and identify the sources of SGD-driven nitrate in this region using radioactive radium (Ra) isotopes (223Ra, 224Ra, and 228Ra) and stable nitrogen (N) and oxygen (O) isotope composition of nitrate (δ15N-NO3- and δ18O-NO3-). The results of the Ra mixing model show that the estimated SGD and the associated nitrate fluxes into the Greater Bay Area are (9.15 ± 1.26) × 108 m3/d and (3.77 ± 0.52) × 107 mol/d, respectively, both of which are comparable to the contributions from the Pearl River. Combing NO3- dual isotopic signatures of sampled coastal groundwater and five kinds of potential nitrate sources, we found that ammonium (NH4+) fertilizer and natural soil N are the two main sources of nitrate in discharged submarine groundwater and rivers. No anthropogenic inputs from manure or sewage waste were identified. This study provides significant insights into the establishment of effective management strategies for controlling SGD-nutrients into the bay and protecting the marine ecological environment.

18.
Scand J Gastroenterol ; 56(2): 137-144, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33307879

RESUMO

OBJECTIVE: The aim of this study was to compare the effects of colonic electrical stimulation (CES) and prucalopride on gastrointestinal transit and defecation and to verify the safety of CES in a canine model of constipation. METHODS: Eight beagles received CES implantation and induction drugs for slow transit constipation (STC). In the STC model, the gastrointestinal transit time (GITT), colonic transit time (CTT), stool frequency and stool consistency were assessed to compare the effects of CES and prucalopride on gastrointestinal transit and defecation. The histocompatibility of the implantable device was evaluated. RESULTS: The individualized parameters for CES varied greatly among the animals, and the GITTs were not significantly shortened by CES or prucalopride; however, both the CES and prucalopride treatment significantly accelerated CTT and improved stool consistency compared with sham stimulation. CES treatment also resulted in significantly higher stool frequency than prucalopride treatment, which did not significantly change the stool frequency. No severe inflammation response was detected in the gross and microscopic appearance around the implants. CONCLUSION: CES and prucalopride treatment may yield similar short-term effects for improving gastrointestinal transit and stool consistency, and CES outperformed prucalopride treatment in terms of defecation inducement in the short term. There were ideal levels of endurance and histocompatibility for the animals that underwent CES.

19.
Phytomedicine ; 81: 153428, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33341025

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive fibrotic lung disease lacking a validated and effective therapy. Aberrant activation of the Wnt/ß-catenin signaling cascade plays the key role in the pathogenesis of IPF. Betulinic acid is a natural pentacyclic triterpenoid molecule that has excellent antitumor and antiviral activities. HYPOTHESIS: We hypothesized that BA has an anti-pulmonary fibrosis effect mediated by the suppression of the Wnt/ß-catenin pathway. Study design Pulmonary fibrosis markers were detected in vitro and in vivo to confirm the antifibrotic effect of BA. The Wnt/ß-catenin pathway-related proteins were overexpressed to determine the effect of BA on Wnt signaling. METHODS AND RESULTS: BA dose-dependently inhibited Wnt3a-induced fibroblast activation in vitro. Moreover, BA decreased Wnt3a- and LiCl-induced transcriptional activity, as assessed by the TOPFlash assay in fibroblasts, and repressed the expression of the Wnt target genes cyclin D1, axin 2, and S100A4. Further investigation indicated that BA restrained the nuclear accumulation of ß-catenin, mainly by increasing the phospho-ß-catenin ratio (S33/S37/T41 and S45), inhibited the phosphorylation of DVL2 and LRP, and decreased the levels of Wnt3a and LRP6. In agreement with the results of the in vitro assays, the in vivo experiments indicated that BA significantly decreased bleomycin-induced pulmonary fibrosis in mice and suppressed myofibroblast activation by inhibiting Wnt/ß-catenin signaling. CONCLUSION: BA may directly interfere with the Wnt/ß-catenin pathway to subsequently repress myofibroblast activation and pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Bleomicina/toxicidade , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Masculino , Camundongos Endogâmicos C57BL , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
20.
ACS Nano ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284574

RESUMO

High entropy alloy nanoparticles (HEA-NPs) are expanding their influence in many fields. To explore the electronic structures in such multielemental systems, HEA-NPs were synthesized on two different carbon substrates through carbothermal shock and in situ reduction methods. The relationship between the apparent core level energy shifts (negative or positive) and the electron density changes among the components of quinary-metal HEA-NPs was investigated by X-ray photoelectron spectroscopy (XPS) analysis and first-principles electronic structure calculations. It was found that Cu displays a negative core level shift while Fe, Co, Mg, Cr, and Mn display a positive core level shift. While experiments show an apparent positive core level shift for Ni, electronic structure calculations reveal that this arises from shifts in the Fermi level and that the electron density redistribution in Ni behaves more like Cu than the other elements. The findings show that the electron density redistribution in the NPs occurs from less electronegative elements to more electronegative ones. This work should guide the design of HEA-NPs to expand their potential applications in mechanical structures, medicine, catalysis, and energy storage/conversion.

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