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1.
J Epidemiol ; 2020 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-32224596

RESUMEN

BACKGROUND: The diagnosis of hypertension should be based on the mean of two or more properly measured BP readings on each of two visits for clinical practice, but one-visit strategy was applied in most epidemiological surveys. The impact of hypertension definition based on two visits on estimates of hypertension burden is unknown. This study aims to assess the impact of hypertension diagnosis based on a two-visit strategy for estimating hypertension burden in China. METHODS: The one-visit and two-visit strategies were applied to investigate the incidence of hypertension in a cohort study based on the China Health and Nutrition Survey (CHNS) 1989-2011. Additionally the prevalence of hypertension was investigated in a cross-sectional study based on the CHNS 2006-2009/2011 and the hypertension burden in China was estimated with data from the 2012-2015 China hypertension survey. RESULTS: Overall, the age-adjusted incidence of hypertension based on the two-visit strategy (1.82%; 95% confidence interval [Cl] = 1.74%, 1.90%) was 62.1% lower than estimation based on the one-visit strategy (4.80%; 95% Cl = 4.68%, 4.93%). Similar results were found in the prevalence of hypertension (the one-visit: 18.13% [17.34, 18.92]; the two-visit: 9.47% [8.87, 10.07]). When the two-visit strategy was applied to the 2012-2015 China hypertension survey, the hypertension burden was predicted to be overestimated by 25.5%-47.8% (based on JNC 7) and 23.5%-48.2% (based on the 2017 ACC/AHA). CONCLUSION: The hypertension burden would decrease from 244.5 million persons to 127.5-182.3 million persons in China if the two-visit strategy was applied.

2.
J Vis Exp ; (157)2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32225145

RESUMEN

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

3.
Math Biosci Eng ; 17(3): 2418-2431, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32233545

RESUMEN

Background: Constructing a three-dimensional (3D) model through non-invasive techniques will greatly benefit the diagnosis and treatment of otitis media. However, such a model should reflect the physiological characteristics of the middle ear; in particular, the pressure-flow responses determine the validity of the model. Objectives: A 3D model of the middle ear was constructed by digital scanning and simulation. The pressure-flow properties in the model were measured to evaluate whether the model could reflect the real middle ear under physiological and pathological conditions. Materials and methods: Computed tomography (CT) scanning data from a healthy woman were input into Mimics 20.0 to construct 3D images of the middle ear. The 3D images were treated with Ansys 15.0 for finite element mesh generation. Msc Nastran 2014 were used for the fluid-solid coupling calculations. Results: The pressure-flow rate in the model resembled a Venturi tube, namely, the pressure decreased with increasing flow velocity, especially in the Eustachian tube. In the absence of the right mastoid process, the differences in air pressure and the maximal velocity in the model were reduced. Conclusions: This numerical model based on CT images of the middle ear recapitulates the biomechanical characteristics of the real middle ear. Significance: This study provides an easy and rapid approach to constructing a middle ear model for diagnosis and treatment of otitis media.

4.
Environ Res ; 185: 109391, 2020 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-32240841

RESUMEN

Denitrifying microbial community can be utilized for eliminating nitrate and Fe(II) combined contamination in groundwater, while excessive amount of Fe(II) limit the process. Natural mineral can be additional substrate for the microbial growth, whereas how it influences the microbial community that mediating the denitrification coupling with Fe(II) oxidation and balancing inhibition of excessive Fe(II) on denitrification remain unclear. In the present study, we conducted a series of microcosm experiments to explore the denitrification and Fe(II) oxidation kinetic, and used RNA-based qPCR and DNA-based high-throughput sequencing to elucidate microbial diversity, co-occurrence and metabolic profiles amended by wheat-rice stone and rock phosphate. The results showed that both minerals could extensively improve and double the denitrification rates (2.0 ± 0.03 to 2.12 ± 0.13 times), decrease the nitrite accumulation and trigger the high resistance of the denitrifiers from the stress of Fe(II), whereas only wheat-rice stone with higher surface area increased the oxidation of Fe(II) (<10%). The addition of both minerals enhanced the microbial alpha-diversity, shaped the beta-diversity and co-occurrence network, and recovered the transcription of nitrate and nitrite reductase (Nar, Nap, NirS, NirK) from the Fe(II) inhibition. Accordingly, heterotroph Methyloversatilis sp., Methylotenra sp. might contribute to the denitrification under wheat-rice stone amendment, Denitratisoma sp. contribute to the denitrification for rock phosphate, and Fe oxidation was partially catalyzed by Dechloromonas sp. or abiotically by the nitrite/nitrous oxide. These findings would be helpful for better understanding the bioremediation of nitrate and Fe contaminated groundwater.

5.
J Colloid Interface Sci ; 570: 402-410, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-32224321

RESUMEN

Controlled synthesis of hierarchical hydroxyapatite materials is a hot research topic because of the excellent biocompatibility and bioactivity of the materials. In this study, flower-like hydroxyapatite spheres (FHAPS) were facile synthesized in one pot using Al(OH)3 as a structure-directing agent. The prepared FHAPS comprised nanosheets possessing a uniform diameter of approximately 4 µm. Notably, the FHAPS can be degraded in solutions with a pH of 5.5 for 144 h or incubated with cells for 48 h. In addition, the FHAPS have rough surfaces, which exhibit high loading contents for the anticancer drug doxorubicin (DOX, 9.1%) and siRNA (2.0%). Thus, the FHAPS can effectively deliver DOX into drug-resistant breast cancer cells to exert an excellent killing effect compared with free DOX and transfect siRNA into tumor cells to interfere with the expression of the target protein. Taken together, this work successfully prepared FHAPS via a convenient synthesis route that shows high delivery efficiency for anticancer drugs and siRNA.

6.
Integr Cancer Ther ; 19: 1534735420906463, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32248718

RESUMEN

Chemotherapy is an effective treatment for invasive breast cancer. Paradoxically, many recently published findings showed that the first-line chemotherapeutic agent paclitaxel (PTX) showed pro-metastatic effects in the progress of treating breast cancer. Xiao-Ai-Ping (XAP) injection, composed of a traditional herbal medicine, Marsdenia tenacissimae extract, is known to exert antitumor effects on various cancers. However, there are few experimental studies on breast cancer. The underlying mechanism of the antitumor effect of XAP combined with chemotherapy agents has not been fully understood. In the present study, we sought to find the antitumor effects of XAP combined with PTX in vitro and in vivo. The data demonstrated that the combination of XAP with PTX resulted in remarkable enhancement of the pro-apoptotic, migration-inhibiting, and anti-invasive effects of PTX in vitro. Significantly, further study showed the overexpression of ATF3 in PTX-treated cell, while XAP counteracted the change of ATF3 induced by PTX. Moreover, it showed that combination treatment could promote the inhibition of tumor growth in MDA-MB-231 cell xenograft mouse model. Compared with PTX treatment, the downregulation of ATF3 indicated that ATF3 played a pivotal role in the combination of XAP with PTX to exert a synergistic effect. Overall, it is expected that PTX combined with XAP may serve as an effective agent for antitumor treatment, and dampening ATF3 maybe a potential strategy to improve the efficacy of PTX.

7.
J Cell Mol Med ; 2020 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-32249539

RESUMEN

As a class of covalently closed non-coding RNAs, circular RNAs (circRNAs) are key regulators in various malignancies including osteosarcoma (OS). In the present study, we found that circular RNA PVT1 (circPVT1) was up-regulated in OS and correlated with poor prognosis of patients with OS. Functionally, we showed that knockdown of circPVT1 suppressed OS cells metastasis. In addition, we found that (forkhead box C2) FOXC2 was a downstream gene in circPVT1-mediated metastasis in OS cells. We demonstrated that circPVT1 promoted OS cells metastasis via post-transcriptionally regulating of FOXC2. Furthermore, we revealed that microRNA 526b (miR-526b) was a key bridge which connected circPVT1 and FOXC2. We showed that miR-526b was down-regulated in OS tissue and cell lines. Through a transwell assay, we found that miR-526b suppressed OS cells metastasis by targeting of FOXC2. We also showed that miR-526b targeted circPVT1 via similar mircoRNA response elements (MREs) as it did for FOXC2. Finally, we proved that circPVT1 decoyed miR-526b to promote FOXC2-mediated metastasis in OS cells. In brief, our current study demonstrated that circPVT1, functioning as an oncogene, promotes OS cells metastasis via regulation of FOXC2 by acting as a ceRNA of miR-526b. CircPVT1/miR-526b/FOXC2 axis might be a novel target in molecular treatment of OS.

8.
Zhongguo Zhong Yao Za Zhi ; 45(1): 7-13, 2020 Jan.
Artículo en Chino | MEDLINE | ID: mdl-32237405

RESUMEN

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1ß and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.

9.
J Environ Manage ; 261: 110231, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32148301

RESUMEN

Owing to uneven development and unbalanced resource endowments within China, ensuring reliable energy, water and food supply is a core challenge to regional socio-economic development. This study makes a first attempt to examine and compare demand-driven energy, water and arable land (E-W-L) resource outsourcings within China based on the latest multi-regional input-output model. Results show that interprovincial trade reallocated 73.4%, 33.9% and 38.1% of the national total E-W-L resource inputs in 2012, respectively. Investment was the dominant final demand category for driving energy requirements, while consumption was the leading final demand category for water and arable land requirements. Important provincial regions and critical transmission sectors for the trade of embodied E-W-L resources are identified. Substantial E-W-L resources were transferred from the central and western regions to the eastern regions. Especially, Inner Mongolia was the top interregional net exporter of embodied energy, while Jiangsu topped the net importer list. Regarding virtual water transfer, Xinjiang and Shandong were the biggest interregional net exporters and net importers, respectively, while Heilongjiang and Guangdong stood out in the net trade of embodied arable land. Owing to the impact of interprovincial trade, the resource occupancy levels of the eastern developed area were much higher than those of the northeastern, central and western areas. The imbalances in the levels of socio-economic development amongst provincial regions are mirrored by their patterns of E-W-L uses and related trade transfer. Understanding the synchronal outsourcings of E-W-L resource requirements provides important implications for targeted resource management in Chinese interprovincial supply chains.


Asunto(s)
Abastecimiento de Agua , Agua , China , Desarrollo Económico , Abastecimiento de Alimentos
10.
JCO Oncol Pract ; : JOP1900525, 2020 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-32155109

RESUMEN

PURPOSE: Cancer care has increasingly shifted from physician offices (MDOs) to hospital-based outpatient departments (HOPDs). This study compared the proportion of patients receiving optimal, evidence-based anticancer drug regimens and the cost of care when administered in these sites. METHODS: Patients with breast, lung, or colorectal cancer were identified from a large health insurance database. Anticancer drug regimens were considered on pathway when they were on the payer's program list of optimal regimens when administered. Anticancer drug-related costs included all patient- and plan-paid costs on claims for anticancer drugs over the 6-month postindex period; total per-patient costs were summed over all claims in that period. RESULTS: A total of 38,140 patients (MDO, n = 18,998; HOPD, n = 19,142) were included. On-pathway status was similar in HOPDs (59.5%; 95% CI, 58.6% to 60.4%) versus MDOs (60.8%; 95% CI, 59.8% to 61.8%; P = .069). HOPDs had substantially higher costs. Adjusted cancer drug-related costs were $63,763 (95% CI, $62,301 to $65,224) for HOPDs versus $36,500 (95% CI, $35,729 to $37,271) for MDOs (P < .001); adjusted total costs were $115,843 (95% CI, $113,642 to $118,044) for HOPDs versus $77,346 (95% CI, $76,072 to $78,620) for MDOs (P < .001). For Medicare Advantage, adjusted total costs were $61,812 for HOPDs compared with $62,769 for MDOs; adjusted drug-related costs were $31,610 for HOPDs compared with $33,168 for MDOs. For commercial insurance, total costs were $119,288 for HOPDs compared with $77,613 for MDOs; drug-related costs were $65,930 for HOPDs compared with $36,366 for MDOs. CONCLUSION: Total and cancer drug-related per-patient costs were higher in HOPDs versus MDOs, but on-pathway status was similar. The cost differential between HOPDs and MDOs was driven by commercially insured members rather than Medicare Advantage members.

11.
Bosn J Basic Med Sci ; 2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32156251

RESUMEN

Inhibition of amyloid ß (Aß)-induced mitochondrial damage is considered crucial for reducing the pathological damage in Alzheimer's disease (AD). We evaluated the effect of neural stem cell-conditioned medium (NSC-CDM) on Aß25-35-induced damage in SH-SY5Y cells. An in vitro model of AD was established by treating SH-SY5Y cells with 40 µM Aß25-35 for 24 h. SH-SY5Y cells were divided into control, Aß25-35 (40 µM), Aß25-35 (40 µM) + NSC-CDM, and Aß25-35 (40 µM) + neural stem cell-complete medium (NSC-CPM) groups. Cell viability was detected by CCK-8 assay. Apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) were detected by flow cytometry. Malondialdehyde (MDA) content was detected by ELISA assay. Western blot analysis was used to detect cytochrome c release and apoptosis-related proteins. Transmission electron microscopy (TEM) was used to observe mitochondrial morphology. Cell viability significantly decreased and apoptosis significantly increased in SH-SY5Y cells treated with Aß25-35, and both effects were rescued by NSC-CDM. In addition, NSC-CDM reduced ROS production and significantly inhibited the reduction of MMP caused by Aß25-35. Furthermore, NSC-CDM ameliorated Aß25-35-induced reduction in Bcl-2 expression levels and increased the expression levels of cytochrome c, caspase-9, caspase-3, and Bax. Moreover, Aß25-35 induced the destruction of mitochondrial ultrastructure and this effect was reversed by NSC-CDM. Collectively, our findings demonstrated the protective effect of NCS-CDM against Aß25-35-induced SH-SY5Y cell damage and clarified the mechanism of action of Aß25-35 in terms of mitochondrial maintenance and mitochondria-associated apoptosis signaling pathways, thus providing a theoretical basis for the development of novel anti-AD treatments.

12.
Org Lett ; 22(6): 2437-2441, 2020 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-32142302

RESUMEN

Enantioselective incorporation of trifluoromethyl (-CF3) and trifuoromethylthio (-SCF3) groups in small molecules is of high interest to modulate the potency and pharmacological properties of drug candidates. Herein, we report a Zn-ProPhenol catalyzed diastereo- and enantioselective Mannich addition of α-trifluoromethyl- and α-trifuoromethylthio-substituted ketones. This transformation uses cyclic and acyclic ketones and generates quaternary trifluoromethyl and tetrasubstituted trifuoromethylthio stereogenic centers in excellent yields and selectivities.

13.
Thorac Cancer ; 2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-32134200

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). While rapid progression (RP) has been proposed as a non-negligible pattern of response to ICIs, its definition and related factors remain unclear. This study aimed to develop a clinical definition of RP and to identify related factors. METHODS: We retrospectively evaluated Chinese patients who had received an ICI as second-line or later treatment for locally advanced or metastatic NSCLC at a single center. We defined RP as radiological progression at the first response assessment (<2 months after starting the ICI), as well as confirmation of progressive disease or cancer-related death occurring at <3 months. The clinical outcomes were compared for patients with RP or non-RP to identify prognostic factors. RESULTS: The study evaluated 74 eligible patients with detailed records regarding their ICI therapy, including 25 patients (33.8%) who had experienced RP. Relative to patients with non-RP, patients with RP had significantly shorter median progression-free survival (1.7 months [95% CI: 1.4-2.0 months] vs. 6.3 months [95% CI 5.2-7.3 months], P < 0.001; hazard ratio: 0.14, 95% CI: 0.08-0.25) and significantly shorter median overall survival (8.2 months [95% CI 3.0-13.4 months] vs. 22.6 months [95% CI 17.0-28.1 months], P < 0.001; hazard ratio: 0.27, 95% CI: 0.15-0.49). Multivariate analysis revealed that RP was independently predicted by the presence of ≥3 metastatic sites (P = 0.039) and a neutrophil-to-lymphocyte ratio of ≥3 (P = 0.044). CONCLUSIONS: Among NSCLC patients, RP was a common response to ICI monotherapy and was associated with dramatically reduced progression-free and overall survival. Care is needed when selecting ICI monotherapy for these patients, especially if they have ≥3 metastatic sites or a neutrophil-to-lymphocyte ratio of ≥3.

14.
Microbiologyopen ; : e1013, 2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32166910

RESUMEN

Microbially mediated decomposition of particulate organic carbon (POC) is a central component of the oceanic carbon cycle, controlling the flux of organic carbon from the surface ocean to the deep ocean. Yet, the specific microbial taxa responsible for POC decomposition and degradation in the deep ocean are still unknown. To target the active microbial lineages involved in these processes, 13 C-labeled particulate organic matter (POM) was used as a substrate to incubate particle-attached (PAM) and free-living microbial (FLM) assemblages from the epi- and bathypelagic zones of the New Britain Trench (NBT). By combining DNA stable-isotope probing and Illumina Miseq high-throughput sequencing of bacterial 16S rRNA gene, we identified 14 active bacterial taxonomic groups that implicated in the decomposition of 13 C-labeled POM at low and high pressures under the temperature of 15°C. Our results show that both PAM and FLM were able to decompose POC and assimilate the released DOC. However, similar bacterial taxa in both the PAM and FLM assemblages were involved in POC decomposition and DOC degradation, suggesting the decoupling between microbial lifestyles and ecological functions. Microbial decomposition of POC and degradation of DOC were accomplished primarily by particle-attached bacteria at atmospheric pressure and by free-living bacteria at high pressures. Overall, the POC degradation rates were higher at atmospheric pressure (0.1 MPa) than at high pressures (20 and 40 MPa) under 15°C. Our results provide direct evidence linking the specific particle-attached and free-living bacterial lineages to decomposition and degradation of diatomic detritus at low and high pressures and identified the potential mediators of POC fluxes in the epi- and bathypelagic zones.

15.
Int J Nanomedicine ; 15: 1481-1498, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32189964

RESUMEN

Purpose: It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the subsequent cell interactions. Magnetosomes are protein-rich membrane nanoparticles which are synthesized by magnetic bacteria; these have gained a lot of attention owing to their unique magnetic and biochemical characteristics. Nevertheless, whether bacterial magnetosomes have a corona after interacting with the plasma, and how such a corona affects nanoparticle-cell interactions is yet to be elucidated. The aim of this study was to characterize corona formation around a bacterial magnetosome and to assess the functional consequences. Methods: Magnetosomes were isolated from the magnetotactic bacteria, M. gryphiswaldense (MSR-1). Size, morphology, and zeta potential were measured by transmission electron microscopy and dynamic light scattering. A quantitative characterization of plasma corona proteins was performed using LC-MS/MS. Protein absorption was further examined by circular dichroism and the effect of the corona on cellular uptake was investigated by microscopy and spectroscopy. Results: Various serum proteins were found to be selectively adsorbed on the surface of the bacterial magnetosomes following plasma exposure, forming a corona. Compared to the pristine magnetosomes, the acquired corona promoted efficient cellular uptake by human vascular endothelial cells. Using a protein-interaction prediction method, we identified cell surface receptors that could potentially associate with abundant corona components. Of these, one abundant corona protein, ApoE, may be responsible for internalization of the magnetosome-corona complex through LDL receptor-mediated internalization. Conclusion: Our findings provide clues as to the physiological response to magnetosomes and also reveal the corona composition of this membrane-coated nanomaterial after exposure to blood plasma.

16.
Biomed Res Int ; 2020: 8780253, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32190685

RESUMEN

Objective: The relationship between serum progesterone and the first trimester pregnancy outcome of threatened abortion is still controversial. Therefore, we aimed to further study the association between these two parameters. Methods: The present study is an observational retrospective cohort study. A total of 726 participants who had threatened abortion from a hospital in Guangdong, China, were included in this study from 17th August 2011 to 30th October 2018. The exposure variable and the outcome variable were serum progesterone measured at baseline and early pregnancy outcome, respectively. Covariates involved in this study included patients' basic demographics, obstetric history, and clinical information. Results: A negative association and a saturation effect were detected between serum progesterone and the first trimester pregnancy outcome. When progesterone <90.62 nmol/L, an increase in 1 nmol/L of serum progesterone was associated with 3% decrease of the risk of miscarriage (OR: 0.97, 95% CI: 0.95-0.98). Conclusion: There was a greater risk of abortion when the serum progesterone level was less than 90.62 nmol/L. Our findings can better assist the clinician in understanding patients' conditions and making medical decisions.

17.
BMC Microbiol ; 20(1): 48, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-32126973

RESUMEN

BACKGROUND: The root-knot nematode Meloidogyne graminicola has become a serious threat to rice production as a result of the cultivation changes from transplanting to direct seeding. The nematicidal activity of Aspergillus welwitschiae have been investigated in vitro, and the disease control efficacy of the active compound has been evaluated under greenhouse and field conditions. RESULTS: The active compound αß-dehydrocurvularin (αß-DC), isolated by nematicidal assay-directed fractionation, showed significant nematicidal activity against M. graminicola, with a median lethal concentration (LC50) value of 122.2 µg mL- 1. αß-DC effectively decreased the attraction of rice roots to nematodes and the infection of nematodes and also suppressed the development of nematodes under greenhouse conditions. Moreover, αß-DC efficiently reduced the root gall index under field conditions. CONCLUSIONS: To our knowledge, this is the first report to describe the nematicidal activity of αß-DC against M. graminicola. The results obtained under greenhouse and field conditions provide a basis for developing commercial formulations from αß-DC to control M. graminicola in the future.

18.
Biomed Res Int ; 2020: 1706168, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32149083

RESUMEN

Movement and phagocytosis characterize the fundamental actions of macrophages. Although it is known that the free fatty acid receptor GPR120 is expressed in macrophages and regulates cytokine expression to exert anti-inflammatory activities, the effects of GPR120 activation on the motility and phagocytosis of macrophages are not clear. In this study, mouse alveolar macrophages (AM) were stimulated with the GPR120 agonist TUG-891, and the changes in cell motility, intracellular Ca2+ concentration ([Ca2+]i), and the ability of phagocytosis were measured. Mouse AM in controls exhibited active movement in vitro, and TUG-891 significantly restrained AM movement. Meanwhile, TUG-891 stimulated a quick increase in [Ca2+]i in AM, which was blocked separately by the Gq protein inhibitor YM-254890, the phospholipase C (PLC) inhibitor U73122, or depletion of endoplasmic reticulum (ER) Ca2+ store by thapsigargin. The inhibition of AM movement by TUG-891 was eliminated by YM-254890, U73122, thapsigargin, and chelation of cytosolic Ca2+ by BAPTA. Moreover, TUG-891 inhibited AM phagocytosis of fluorescent microspheres, which was also blocked by YM-254890, U73122, thapsigargin, and BAPTA. In conclusion, GPR120 activation in mouse AM increases [Ca2+]i but inhibits the motility and phagocytosis via Gq protein/PLC-mediated Ca2+ release from ER Ca2+ store.

19.
ACS Nano ; 2020 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-32167741

RESUMEN

Deep Candida albicans infection is one of the major causes of death in immunosuppressed hosts. Remodeling macrophages to phenotype M1 can decrease fungus burden and facilitate combating C. albicans under an immunosuppressive state. In this study, a nanotrinity was exploited to direct fungicidal macrophage polarization by leveraging the regulation pathways in macrophage redifferentiation. Conventional chemotherapeutic imatinib, which can abrogate M2 macrophage polarization via "shutting off" the STAT6 phosphorylation pathway, was encapsulated in biodegradable polymeric nanoparticles. In house-customized dual functional mannosylated chitosan oligosaccharides were then coated on the surface of the imatinib-laden nanoparticles, and thus, a mannosylated nanotrinity was achieved with ternary functions for macrophage remodeling: (i) imatinib-blocked STAT6 phosphorylation pathway for decreasing M2 macrophage population; (ii) chitosan oligosaccharides-mediated TLR-4 pathway activation that could promote macrophage redifferentiation to M1 phenotype; (iii) mannose motif-enhanced macrophage targeting. After physiochemical characterization, regulatory effects of the mannosylated nanotrinity on macrophages and the anti-C. albicans efficacy were evaluated at the cellular level and animal level, respectively. The results demonstrated that our mannosylated nanotrinity could efficiently induce macrophage polarization toward the M1 phenotype, decrease M2 phenotype production, and markedly lessen fungus burden and increased the median survival time of mice infected with C. albicans. Therefore, the mannosylated nanotrinity developed in this study could significantly induce macrophage remodeling in situ by the two-pronged process, "turning on" M1 phenotype polarization meanwhile "shutting off" M2 phenotype polarization, and thus allowed to eradicate C. albicans infection.

20.
N Engl J Med ; 2020 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-32187464

RESUMEN

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

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