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1.
Eur Respir J ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764183

RESUMO

BACKGROUND: Enlarging tuberculosis (TB) preventive treatment among at-risk populations is a critical component of the End TB Strategy. It is urgently needed to develop suitable latent tuberculosis infection (LTBI) testing and treatment tools according to local TB epidemic and available resources in worldwide. METHODS: Based on an open-labeled randomised controlled trial conducted since 2015 among rural residents aged 50-70 years with LTBI, the protective efficacy of the 6-week twice-weekly regimen of rifapentine plus isoniazid was further evaluated in a 5-year follow-up survey. RESULTS: A total of 1298 treated participants and 1151 untreated controls were included in the 5-year protective efficacy analysis. In the per-protocol analysis, the incidence rate was 0.49/100 person-years (95% confidence interval (CI): 0.30-0.67) in the untreated control group and 0.19/100 person-years (95% CI: 0.07-0.32) in the treated group, the protection rate was 61.22%. Subgroup analysis showed that the protection rate was 76.82% in the per-protocol analysis among participants with baseline IFN-γ levels in the highest quartile (≥3.25 IU·mL-1). The multiple logistic regression analysis indicated that participants with baseline BMI <18.5 kg·m-2 and with pulmonary fibrotic lesions had increased hazard of developing active disease with an adjusted hazard ratio (aHR) of 3.64 (95% CI: 1.20-11.00) and 5.99 (95% CI: 2.20-16.27), respectively. In addition, individuals with higher baseline IFN-γ levels showed an increased risk of TB occurrence (aHR 2.27, 95% CI 1.13-4.58). CONCLUSIONS: Our findings suggested the 6-week twice-weekly regimen of rifapentine plus isoniazid for LTBI treatment might be an optional tool for TB control in Chinese population.

2.
Med Mol Morphol ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796378

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrinopathy related to female infertility. We investigated the function of the microRNA-98-3p (miR-98-3p)/Yin-Yang-1 (YY1) axis to the pathophysiological processes in PCOS mice. A mouse model of PCOS was established using dehydroepiandrosterone (DHEA). Hematoxylin and eosin (HE) staining was used to assess morphologic changes of the ovaries. Hormonal serum levels were measured by ELISA. Estrogen synthesis in OGCs was measured using chemiluminescence immunoassay. The viability, cell cycle, and apoptosis of ovarian granulosa cells (OGCs) were assessed by CCK-8, flow cytometry, and western blot. Luciferase reporter assays were conducted to examine the binding of miR-98-3p to YY1. YY1 was upregulated, while miR-98-3p was downregulated both in the ovarian tissues of PCOS mice and OGCs separated from PCOS mice and patients. YY1 Knockdown promoted OGC proliferation and inhibited apoptosis as well as increased estrogen production in OGCs. YY1 was verified to be targeted by miR-98-3p. Additionally, YY1 overexpression prevented the effects of miR-98-3p overexpression on the proliferation and apoptosis of OGCs. Importantly, miR-98-3p attenuated ovarian injury in PCOS mice. MiR-98-3p targets and downregulates YY1 expression, thereby affecting the proliferation and apoptosis of OGCs in PCOS.

3.
EClinicalMedicine ; 42: 101185, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34805810

RESUMO

Background: PB-201, a partial, pancreas/liver-dual glucokinase activator, showed good tolerance and glycaemic effects in multinational studies. This study determined its optimal dose, safety, pharmacokinetics, and pharmacodynamics in Chinese patients with type 2 diabetes. Methods: In this double-blind, randomised, four-period, crossover, phase 1 trial in China, conducted at the Peking University Third Hospital, adult patients with drug-naive type 2 diabetes were randomised (1:1:1:1) to four sequence groups using a computer-generated randomisation table. In each period, they received oral placebo or PB-201 (50+50, 100+50, or 100+100 mg split doses) for 7 days. Investigators and patients were masked to treatment assignment. The primary endpoints were safety and pharmacokinetics. Continuous glucose monitoring was used to delineate the glucose excursion profile. Trial registration number: NCT03973515. Findings: Between August 27, 2019 and December 19, 2019, 16 patients were randomised. PB-201 showed a dose-proportional pharmacokinetic profile without apparent accumulation in the body and induced dose-dependent lowering of blood glucose. PB-201 at 50+50, 100+50, and 100+100 mg increased mean time in range (49·210% [standard deviation 27], 56·130% [25], and 63·330% [20] with three doses, respectively) versus placebo (49·380% [27]) and reduced estimated glycated haemoglobin from baseline (-0·5445% [1·654], -1·063% [1·236], and -1·888% [1·381] vs -0·581% [1·200]). Fifteen patients (93·8%) had treatment-emergent adverse events, which were mild. No patients had hypoglycaemia with venous/capillary glucose <3·9 mmol/L or nocturnal hypoglycaemia. Interpretation: PB-201 100 mg twice daily is identified as the optimal dose, which shows promising glucose-lowering effects and low risks of hypoglycaemia and other side effects. Further investigation of PB-201 100 mg twice daily in confirmatory trials is warranted. Funding: PegBio.

4.
Proc Natl Acad Sci U S A ; 118(46)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34772807

RESUMO

Chronic infection with liver flukes (such as Clonorchis sinensis) can induce severe biliary injuries, which can cause cholangitis, biliary fibrosis, and even cholangiocarcinoma. The release of extracellular vesicles by C. sinensis (CsEVs) is of importance in the long-distance communication between the hosts and worms. However, the biological effects of EVs from liver fluke on biliary injuries and the underlying molecular mechanisms remain poorly characterized. In the present study, we found that CsEVs induced M1-like activation. In addition, the mice that were administrated with CsEVs showed severe biliary injuries associated with remarkable activation of M1-like macrophages. We further characterized the signatures of miRNAs packaged in CsEVs and identified a miRNA Csi-let-7a-5p, which was highly enriched. Further study showed that Csi-let-7a-5p facilitated the activation of M1-like macrophages by targeting Socs1 and Clec7a; however, CsEVs with silencing Csi-let-7a-5p showed a decrease in proinflammatory responses and biliary injuries, which involved in the Socs1- and Clec7a-regulated NF-κB signaling pathway. Our study demonstrates that Csi-let-7a-5p delivered by CsEVs plays a critical role in the activation of M1-like macrophages and contributes to the biliary injuries by targeting the Socs1- and Clec7a-mediated NF-κB signaling pathway, which indicates a mechanism contributing to biliary injuries caused by fluke infection. However, molecules other than Csi-let-7a-5p from CsEVs that may also promote M1-like polarization and exacerbate biliary injuries are not excluded.

5.
Front Microbiol ; 12: 716900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484159

RESUMO

Objectives: Exploring biomarkers monitoring latent tuberculosis infection (LTBI) treatment effectiveness would benefit optimizing the therapeutic regimen. This study aims to identify potential mycobacteria-specific antigen-induced cytokines associated with host responses to preventive treatment. Methods: Based on a randomized controlled trial on LTBI treatment among individuals with chest radiography abnormalities suggestive of prior tuberculosis (TB), the dynamically changed cytokine levels in QuantiFERON-TB Gold In-Tube (QFT) supernatants were estimated during the treatment by bead-based multiplex assays and enzyme-linked immunosorbent assay. Results: In total, 63 treated participants and 32 untreated controls were included in the study. The levels of 13 background-corrected mycobacteria-specific antigen-stimulated cytokines [basic fibroblast growth factor (FGF), growth-regulated oncogene (GRO)-α, interleukin (IL)-1α, IL-1ra, IL-12 (p70), stem cell factor (SCF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), IL-8, interferon (IFN)-α2, IL-5, IL-12 (p40), leukemia inhibitory factor (LIF), and IL-17A] were found to be statistically different between before and after treatment in treated participants, while no statistically differences were observed in untreated controls. Among these 13 cytokines, the level of IL-8 was significantly lower in the QFT reversed group than that in the non-reversed group (p = 0.028) among treated participants, while such a difference was not found for untreated controls (p = 0.292). Conclusion: Our results suggested that the lower level of mycobacteria-specific antigen-induced IL-8 might be associated with the host's positive response to LTBI treatment.

6.
Front Cell Dev Biol ; 9: 663148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485272

RESUMO

Abnormal expression of circRNAs (circular RNAs), a subclass of non-coding RNAs, has been documented in numerous human diseases. Herein, we explored whether circRNAs act as ceRNAs (competing endogenous RNAs) to modulate the pathological process-insulin resistance, as well as dyslipidemia of MetS (Metabolic Syndrome). The profile of circRNAs in serume of MetS and control samples was characterized by circRNA deep sequencing. We identified circRNF111 as a key downregulated circRNA involved in MetS. The decreased expression of circRNF111 in the serum samples of MetS was directly linked to excessive insulin resistance and dyslipidemia. Loss-of-function experiments showed that circRNF111 knockdown inhibited the glucose uptake and the Akt signaling pathway, meanwhile increased the deposition of triglycerides in adipogenic differentiated hADSCs (human adipose-derived stem cells). Mechanistically, circRNF111 sponged miR-143-3p and functioned via targeting miR-143-3p along with its downstream target gene IGF2R. The role along with the mechanism of circRNF111 sponging miR-143-3p in MetS was also explored in obese mice triggered by high-fat die. Therefore, our data suggest a protective role of the novel circRNA-circRNF111 in MetS progression. CircRNF111 inhibition enhances insulin resistance and lipid deposition in MetS through regulating miR-143-3p-IGF2R cascade. This provides a promising therapeutic approach for MetS.

7.
Oncol Lett ; 22(5): 765, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34589144

RESUMO

Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Due to the complicated etiology and lack of significant early symptoms, the diagnosis and treatment of bladder cancer is difficult. Lysosome-associated transmembrane protein 4ß (LAPTM4B) was reported to be involved in the development and progression of several types of tumor, however, its potential effect on the development and metastasis of bladder cancer is still unclear. Immunohistochemistry was performed to detect the protein expression level of LAPTM4B in bladder cancer tissues and short hairpin RNAs targeting LAPTM4B were transfected into bladder cancer cells to knockdown its expression. MTT and colony formation assays were performed to detect cell proliferation, while wound healing and Transwell invasion assays were performed to detect cell migration and invasion, respectively. In addition, tumor growth assays were performed to confirm the effects of LAPTM4B in mice. The present study demonstrated that LAPTM4B was associated with the prognosis of patients with bladder cancer. In addition, LAPTM4B was associated with clinical characteristics, including tumor stage and recurrence. The results further showed that LAPTM4B knockdown could suppress the proliferation of bladder cancer cell lines. In addition, the migration and invasion of T24 and 5637 cells was suppressed following LAPTM4B knockdown in vitro. The in vivo data confirmed that knockdown of LAPTM4B markedly inhibited tumor growth and metastasis in mice. In summary, the results from the present study provide strong evidence of the effects of LAPTM4B in bladder cancer progression.

8.
Nanoscale Res Lett ; 16(1): 139, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478000

RESUMO

The application of cells as carriers to encapsulate chemotherapy drugs is of great significance in antitumor therapy. The advantages of reducing systemic toxicity, enhancing targeting and enhancing the penetrability of drugs to tumor cells make it have great potential for clinical application in the future. Many studies and advances have been made in the encapsulation of drugs by using erythrocytes, white blood cells, platelets, immune cells and even tumor cells. The results showed that the antitumor effect of cell encapsulation chemotherapy drugs was better than that of single chemotherapy drugs. In recent years, the application of cell-based vectors in cancer has become diversified. Both chemotherapeutic drugs and photosensitizers can be encapsulated, so as to achieve multiple antitumor effects of chemotherapy, photothermal therapy and photodynamic therapy. A variety of ways of coordinated treatment can produce ideal results even in the face of multidrug-resistant and metastatic tumors. However, it is regrettable that this technology is only used in vitro for the time being. Standard answers have not yet been obtained for the preservation of drug-loaded cells and the safe way of infusion into human body. Therefore, the successful application of drug delivery technology in clinical still faces many challenges in the future. In this paper, we discuss the latest development of different cell-derived drug delivery systems and the challenges it will face in the future.

9.
Biosci Rep ; 41(10)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34505627

RESUMO

Inflammatory response mediated by immune cells is either directly or indirectly regulated by mesenchymal stromal cells (MSCs). Accumulating evidence suggests that thrombospondin-1 (TSP-1) is highly expressed in response to inflammation. In this work, we isolated and identified human thymic mesenchymal stromal cells (tMSCs) and detected the expression of TSP-1. We found that tMSCs expressed TSP-1 and Poly (I:C) or LPS treatment promoted the expression of TSP-1. Further, we isolated and identified exosomes originating from tMSCs (MEXs). Notably, exosomes derived from LPS-pretreated tMSCs (MEXsLPS) promoted the polarization of macrophages to M1-like phenotype and IL-6, TNF-α secretion as well as the pro-inflammatory differentiation of CD4+T cells into Th17 cells. Upon silencing the expression of TSP-1 in tMSCs, the pro-inflammatory effects of MEXsLPS were suppressed. Therefore, these findings uncovered TSP-1 as the principal factor in MEXsLPS pro-inflammatory regulation.

10.
J Clin Tuberc Other Mycobact Dis ; 25: 100266, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34458591

RESUMO

Background: In China, rural doctors played a crucial role in TB cases referral and management. The current study aimed to evaluate the effect of WeChat-based training program on improving the rural doctors' knowledge on TB management. Methods: A One-year WeChat-based training was conducted among registered rural doctors from Zhongmu County, located in middle China, by means of releasing original contents (in forms of text, poster, video or cartoon) through WeChat subscription account (WeChat SA) once a week. Pre-and-post-training offline tests were hold using the same self-administered questionnaire to evaluate the training effect. Results: A total of 467 rural doctor were included in the study. During the training, 60 original articles were posted through WeChat SA. With respect to the two tests, the median score increased from 50 (40.0-60.0) to 60 (53.0-70.0) (p < 0.001) after training. As compared with posters, the median readings were significantly higher for released contents in forms of text, video and cartoon (p < 0.001). Female's test performance improved better than male's. In addition, a positive relation was observed between education level and the test performance regardless of training. Conclusions: Our results indicated that WeChat-based training improved the knowledge of rural doctors on TB management to a certain extent. It is worthy to explore more effective new media-based training methods to promote TB control in rural China.

11.
Front Oncol ; 11: 693234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381716

RESUMO

Background: Lung adenocarcinoma (LUAD) is a highly mortal cancer. Tertiary lymphoid structures (TLS) are ectopic lymphoid organs with similar morphological and molecular characters to secondary lymphoid organ. The aim of this study is to investigate the prognostic effect of a gene signature associated with TLSs, including B-cell-specific genes. Methods: Clinical data of 515 LUAD patients in the TGCA cohort were used to examine the relationship of TLS signature with immune microenvironment, tumor mutational burden (TMB), and driver gene mutations. Patients were divided into the TLS signature high group and TLS signature low group, and comparative analysis of survival and its influencing factors between the two groups was performed. The resulting data were then validated in the GSE37745 cohort. Results: TLS signature high group had significantly better overall survival (OS) and progression-free interval (PFI) as well as significantly higher infiltration of immune cell subsets, cancer immune cycle (CIC) signature except for immunogram score2 (IGS2), and expression of major checkpoint genes than the TLS signature low group. Notably, while TLS signature was not markedly associated with TMB and mutation frequencies of driver genes, there were significant differences in overall survival of patients with given mutation status of EGFR, KRAS, BRAF and TP53 genes between the TLS signature high and low groups. Conclusion: This study provided evidence that LUAD patients with high TLS signature had a favorable immune microenvironment and better prognosis, suggesting that TLS signature is an independent positive prognostic factor for LUAD patients.

12.
Front Med (Lausanne) ; 8: 692813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307419

RESUMO

Objective: To verify the effects of comprehensive infection prevention and control (IPC) interventions for the prevention of the cross-transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) within intensive care units (ICUs) in an epidemic region. Methods: A historical control, quasi-experimental design was performed. The study was conducted between January 2017 and December 2019, following the implementation of a multimodal IPC bundle. The baseline period was established from January 2013 to June 2013, when only basic IPC measures were applied. Results: A total of 748 patients were enrolled during the entire study. The incidence of ICU-acquired CRKP colonization/infection was 1.16 per 1,000 patient-days during the intervention period, compared with 10.19 per 1,000 patient-days during the baseline period (p = 0.002). The slope of the monthly incidence of CRKP at admission showed an increasing trend (p = 0.03). The incidence of ICU-acquired catheter-related bloodstream infections caused by CRKP decreased from 2.54 to 0.96 per 1,000 central-line-days (p = 0.08). Compliance with contact precautions and terminal room disinfection improved during the intervention period. All environmental surface culture samples acquired after terminal room disinfection were negative for CRKP. Conclusion: Our findings suggest that in epidemic settings, multimodal IPC intervention strategies and consistent monitoring of compliance, may limit the spread of CRKP in ICUs.

13.
Opt Express ; 29(13): 20063-20076, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34266104

RESUMO

Gold nanojets with various morphologies, from nanopillar to nanotip with up to 800 nm height, and finally to nanotip with droplet, are fabricated on gold thin film by a femtosecond laser irradiation. The near-field localized surface plasmon resonance (LSPR) and photothermal effects of gold nanojets are studied through finite element electromagnetic (EM) analysis, supporting in nanojets design for potential applications of high-resolution imaging, nanomanipulation and sensing. For an individual nanotip, the confined electron oscillations in LSPR lead to an intense local EM field up to three orders of magnitude stronger than the incident field strength at the end of gold tip, where the vertical resolution for the field enhancement was improved down to nanoscale due to the small size of the sharp gold tip (5-nm-radius). At specific wavelength, nanopillar can serve as an effective light-to-heat converter and its heating can be fine-tuned by external irradiation, and its dimension. The long-range periodic nanojet arrays (periods from 1.5 µm to 2.5 µm) with different geometry were printed using several pulse energy levels. By confining more light into the tip (two orders of magnitude stronger than single tip), nanotip array shows more pronounced potential to serve as a refractometric sensor due to their high sensitivity and reproducibility. These results promote fs laser printing as a high-precision tool for nanoarchitecture in optical imaging, nanomanipulation and sensing application.

14.
Malar J ; 20(1): 308, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243763

RESUMO

BACKGROUND: Vaccination with radiation-attenuated Plasmodium falciparum sporozoites is known to induce protective immunity. However, the mechanisms underlying this protection remain unclear. In this work, two recent radiation-attenuated sporozoite vaccination studies were used to identify potential transcriptional correlates of vaccination-induced protection. METHODS: Longitudinal whole blood RNAseq transcriptome responses to immunization with radiation-attenuated P. falciparum sporozoites were analysed and compared across malaria-naïve adult participants (IMRAS) and malaria-experienced adult participants (BSPZV1). Parasite dose and method of delivery differed between trials, and immunization regimens were designed to achieve incomplete protective efficacy. Observed protective efficacy was 55% in IMRAS and 20% in BSPZV1. Study vaccine dosings were chosen to elicit both protected and non-protected subjects, so that protection-associated responses could be identified. RESULTS: Analysis of comparable time points up to 1 week after the first vaccination revealed a shared cross-study transcriptional response programme, despite large differences in number and magnitude of differentially expressed genes between trials. A time-dependent regulatory programme of coherent blood transcriptional modular responses was observed, involving induction of inflammatory responses 1-3 days post-vaccination, with cell cycle responses apparent by day 7 in protected individuals from both trials. Additionally, strongly increased induction of inflammation and interferon-associated responses was seen in non-protected IMRAS participants. All individuals, except for non-protected BSPZV1 participants, showed robust upregulation of cell-cycle associated transcriptional responses post vaccination. CONCLUSIONS: In summary, despite stark differences between the two studies, including route of vaccination and status of malaria exposure, responses were identified that were associated with protection after PfRAS vaccination. These comprised a moderate early interferon response peaking 2 days post vaccination, followed by a later proliferative cell cycle response steadily increasing over the first 7 days post vaccination. Non-protection is associated with deviations from this model, observed in this study with over-induction of early interferon responses in IMRAS and failure to mount a cell cycle response in BSPZV1.


Assuntos
Vacinas Antimaláricas/uso terapêutico , Malária Falciparum/prevenção & controle , Anticorpos Antiprotozoários/sangue , Ensaios Clínicos como Assunto , Humanos , Vacinas Antimaláricas/administração & dosagem , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Proteínas de Protozoários/genética , Esporozoítos/genética , Esporozoítos/imunologia , Transcrição Genética , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/uso terapêutico
15.
J Inflamm Res ; 14: 2913-2931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239315

RESUMO

Background: Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates. Methods: First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking. Results: We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1ß, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R. Conclusion: P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia.

16.
Bioorg Chem ; 114: 105150, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34328853

RESUMO

Manoalide was studied as a potential anti-inflammatory agent for the last forty years and more than 200 publications and 180 patents were reported on this compound. However, the configurations at positions 24 and 25 and configuration-dependent bioactivity were not yet studied. In the current report, ten manoalide-like sesterterpenoids were isolated from Luffariella sp. (1-10). These stereoisomers were identified and separated for the first time since 1980 and their configurations at positions 24 and 25 were determined by analyzing their spectroscopic spectra. The configuration-dependent anti-proliferative activity of manoalide derivatives was examined by evaluating their effect on four leukemic cancer cell lines (Molt 4, K562, Sup-T1, and U937). The 24R,25S-isomers exhibited the most potent activity (IC50 0.50-7.67 µM). The anti-proliferative mechanism of action of 24R,25S-manoalide (7) was further studied on Molt 4 cells. Compound 7 exhibited apoptotic activity on Molt 4 cells through the disruption of mitochondrial membrane potential (MMP) and the generation of intracellular reactive oxygen species (ROS). It also inhibited the activity of human topoisomerase I and II. The apoptotic-inducing effect of 7 was further supported by the in vivo experiment by suppressing the volume of xenograft tumor growth (66.11%) compared with the control.

17.
Ecotoxicol Environ Saf ; 219: 112312, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33989917

RESUMO

Copper (Cu) pollution is common in the soil. Due to the widespread application of TiO2 NPs, there is a high propensity for the co-occurrence of TiO2 nanoparticles (NPs) and Cu in agricultural soils. It is therefore imperative to evaluate the joint effects of TiO2 NPs and Cu on crops. In this study, the mutual effects of TiO2 NPs and Cu on their toxicity and accumulation in soybean seedlings and on their fates in a hydroponic system were determined. When Cu was at levels of 1 and 2 mg/L, the co-occurring TiO2 NPs at a non-toxic concentration (10 mg/L) significantly enhanced the toxicity and accumulation of Cu and Ti in soybeans, and inhibited the translocation of Cu from soybean roots to shoots. However, when the Cu concentration for co-exposure was ≥ 5 mg/L, such mutual effects disappeared. The amount of Cu ions adsorbed onto TiO2 NPs after 48 h of co-exposure gradually increased from 31 to 118 mg/g when the Cu concentration was increased from 1 to 20 mg/L. The aggregation and sedimentation of TiO2 NPs were significantly increased after 48 h of co-exposure with the Cu at a concentration higher than 5 mg/L, as compared to the single TiO2 NPs exposure. The increasing aggregation and sedimentation might reduce the bioavailability of TiO2 NPs associated with the adsorbed Cu to soybeans, and consequently alleviate or even neutralize the enhanced toxicity and accumulation of Cu in soybeans exerted by the co-existing TiO2 NPs. Our results thus suggest that consideration of the impact of TiO2 NPs on the phytotoxicity of heavy metals, and specifically Cu, needs to be interpreted with care, and highlight the importance of integrating the interaction and fates of TiO2 NPs and metals into their risk assessment.


Assuntos
Cobre/metabolismo , Nanopartículas/toxicidade , Titânio/toxicidade , Adsorção , Disponibilidade Biológica , Cobre/toxicidade , Produtos Agrícolas , Fabaceae , Hidroponia , Metais Pesados/farmacologia , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Solo , Soja
18.
Pediatr Emerg Care ; 37(6): 329-333, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009897

RESUMO

ABSTRACT: Starting in 2022, the American Board of Pediatrics will launch the Maintenance of Certification Assessment for Pediatrics: Pediatric Emergency Medicine (MOCA-Peds: PEM) longitudinal assessment, which will provide an at-home alternative to the point-in-time examination. This longitudinal assessment will help engage PEM physicians participating in continuing certification in a more flexible and continuous lifelong, self-directed learning process while still providing a summative assessment of their knowledge. This commentary provides background information on MOCA-Peds and an introduction to MOCA-Peds: PEM and how it gives the PEM physician another option to participate in continuing certification.


Assuntos
Medicina de Emergência , Medicina de Emergência Pediátrica , Médicos , Certificação , Criança , Competência Clínica , Medicina de Emergência/educação , Humanos , Aprendizagem , Estados Unidos
19.
Front Neurol ; 12: 595984, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935930

RESUMO

Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.

20.
Transl Pediatr ; 10(4): 746-753, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012824

RESUMO

Background: Allergic rhinitis is one of the most common nasal inflammatory diseases among children. Assessment of clinical symptoms, skin prick test and serum immunoglobulin E (IgE) are common methods used to diagnose allergic rhinitis and assess inflammation degree in clinical settings. However, via blood tests assess eosinophils inflammation is invasive, and may cause fear in children. It makes have burden of the diagnosis of allergic rhinitis. Nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) are noninvasive, inexpensive, and can provide immediate results. These methods may therefore be preferable to assess the inflammation of allergic rhinitis. Methods: This study was a retrospective analysis. We recruited 61 children with allergic rhinitis from November 2019 to March 2020. The participants were assessed using the FeNO and nNO tests. We also administered questionnaires and carried out traditional allergen and blood tests. We analyzed the relationship between diagnosis results and FeNO and nNO levels before and after the treatment of allergic rhinitis, to investigate the clinical application of FeNO and nNO levels for assess eosinophilic inflammation of allergic rhinitis in children. Results: We observed a significant association both FeNO, nNO level with eosinophils, total IgE. In different levels of eosinophils (EOS), the correlation of detection parameters had obvious change. FeNO and nNO levels were obvious higher compared to pre-treatment. Conclusions: Using NO concentration can indicates the extent of allergic inflammation and can measure allergy treatment effects combine other influence indexes. The combined use of FeNO and nNO levels may be a useful method for assess the degree of eosinophilic inflammation of allergic rhinitis in children.

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