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1.
Clin Respir J ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942518

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one third of the adult population are hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension. METHODS AND RESULTS: 148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/mL (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/mL (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg for more than once (≥ 2 times) during hospitalization, were more likely to have ICU admission (P=0.037), invasive mechanical ventilation (P=0.028), and renal injury (P=0.005). A stricter BP control with the threshold of 130/80 mmHg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB) and spironolactone, was associated with lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) Vs. 25 (43.1%), P=0.048). CONCLUSION: Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need of ICU admission.

2.
Shock ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33882516

RESUMO

ABSTRACT: During sepsis the normal induction of circulating insulin-like growth factor-I (IGF-I) by growth hormone (GH) action on liver is attenuated, a phenomenon called hepatic GH resistance. Hepatic GH resistance can be caused by cytokine-mediated activation of the NF-κB pathway which interferes with normal GH-signaling. The afferent and efferent fibers of the vagus nerve are integral to the cholinergic anti-inflammatory pathway (CAP) which attenuates hepatic TNFα production by activating the α7 nicotinic acetylcholine receptor (α7nAChR). We examined the effects of selective afferent vagotomy and α7nAChR activation on sepsis-induced mortality, hepatic and systemic inflammation, the GH/IGF system and hepatic GH resistance using Sprague Dawley (SD) rats, C57BL/6 wild type (WT) mice and α7nAChR knockout (KO) mice. Capsaicin was used to perform SAV and GTS-21 (α7nAChR agonist) was used to activate the α7nAChR. Sepsis-induced mortality, hepatic NF-κB activation and plasma cytokine levels were increased in SAV rats and reduced in GTS-21 treated mice. The effects of sepsis on the GH/IGF-I system plasma IGF-I, IGF binding protein-1 (IGFBP-1), hepatic IGF-I, IGFBP-1 and GH receptor (GHR) mRNA) and rhGH-responsiveness in mice were improved by GTS-21. Collectively these results confirm the protective effects of the anti-inflammatory CAP pathway and α7nAChR activation in sepsis. They also provide evidence the CAP and α7nAChR activation could be used to attenuate hepatic GH resistance and anabolic failure in sepsis.

3.
Nanoscale Res Lett ; 16(1): 54, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826006

RESUMO

Bacterial infection especially caused by multidrug-resistant bacteria still endangers human life. Photodynamic therapy (PDT) can effectively kill bacteria, and nanofiber-based PDT can effectively reduce damage to normal tissues. However, current photosensitizers coated on the surfaces of fibers would release to the wound, causing some side effects. And nanofibers prepared by traditional method exhibit poor adhesion on the wound, which severely reduces the PDT effect due to its short-range effect. Herein, core-shell curcumin composite nanofibers are prepared by in situ electrospinning method via a self-made portable electrospinning device. The obtained composite nanofibers show superior adhesiveness on different biological surface than that of traditional preparation method. Upon 808-nm irradiation, these composite nanofibers effectively produced singlet oxygen (1O2) without curcumin falling off. After these composite nanofibers' exposure to drug-resistant bacteria, they exhibit dual antibacterial behaviors and efficiently kill the drug-resistant bacteria. These dual antibacterial nanofiber membranes with excellent adhesiveness may benefit the application of wound infection as antibacterial dressing.

4.
Sci Total Environ ; 784: 147100, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33892322

RESUMO

High-alumina coal fly ash (HAFA) is a special solid waste since its alumina content can reach 40-50 wt%, which is seen as a potential resource for mullite material production. However, obtaining an ideal mullite material from HAFA is difficult because of its low Al2O3/SiO2 mass ratio. In this work, the microstructure characteristics of HAFA were systematically analyzed by combining multiple characterization techniques. It was found that HAFA had a core-shell structure with a mullite/corundum crystal core and a silica-rich amorphous phase shell. The novel mechanochemical activation-desilication process was used to remove amorphous phase from HAFA and elevate the Al2O3/SiO2 mass ratio. In particular, the effect of particle size after mechanical treatment and mechanism of the desilication process were extensively investigated. On decreasing the particle size, a high leaching rate of alumina was achieved during mechanochemical activation, thus generating a hydroxysodalite coating layer as desilication was suppressed, and the amorphous phase was effectively removed. The mineralogical phase of the desilicated HAFA is mainly mullite and corundum, and the Al2O3/SiO2 mass ratio was elevated from 1.29 to 3.02. Mullite refractory obtained from the desilicated HAFA exhibited excellent physical properties. This study provides insights into further high-valued utilization of HAFA.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33838149

RESUMO

The functional connectivity of the auditory network is considered to be important in the development of tinnitus. We hypothesized that sound therapy, as a commonly used effective treatment for tinnitus, can modulate the functional connectivity of the auditory network. In this prospective observational study, we recruited 27 tinnitus patients who had undergone 12 weeks of sound therapy and 27 matched healthy controls. For the two groups of subjects, resting-state functional magnetic resonance imaging was acquired both at baseline and at the 12th week. We utilized independent component analysis and seed-based functional connectivity analysis to characterize the connectivity features of the auditory network. Interaction effects between the two groups and the two scans within the auditory network were observed, which were driven by increased functional connectivity in the left primary auditory cortex (PAC) and decreased values in the secondary auditory cortex (SAC) in tinnitus patients after treatment. Increased connections between the auditory network and limbic network, as well as decreased values with the bilateral thalami, were identified. The effects were mainly driven by the functional connectivity alterations of the SAC rather than that of the PAC. Significant positive correlations between the percent improvement in the Tinnitus Handicap Inventory (THI) score and the percentage change rates of functional connectivity between the SAC and bilateral thalami were observed. Our study contributes to the understanding of the mechanism of tinnitus and effective sound therapy, providing evidence to support the theory of a gain adaptation mechanism that quantifies the recovered gating function of the thalamus in tinnitus patients.

6.
Nanoscale ; 13(12): 6105-6116, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33729238

RESUMO

Bleeding in outdoor environments is often accompanied by bacterial infection. Due to poor outdoor conditions, it is essential to use the same materials to achieve one-stop treatment of fast hemostasis and simultaneously sterilizing bacteria, especially multidrug-resistant bacteria. Photodynamic therapy (PDT) can kill superbacteria, and local PDT through a nanofiber platform can effectively reduce damage to normal tissue. However, current photosensitizers whether in the interior or on the surface of fibers would leak into the wound and inhibit collagen regeneration. Herein, we use a battery-powered handheld electrospinning device that can work outdoors. It directly spins fibers onto the wound, which facilitates fast hemostasis due to its excellent adhesion to the wound. Eluting holes in the hydrophobic fibers by wound tissue fluid are also proposed to accelerate the escape of reactive oxygen species (ROS) from the interior of the fibers to the wound. After photosensitizers were coated on upconverting nanoparticles (UCNPs), they formed clusters whose size (∼55 nm) was much larger than the uniform elution hole (∼4 nm), which prevented photosensitizers from leaking out into the wound tissue. This cluster structure can also tailor the photosensitizers to be triggered by near infrared (NIR) light, whose deeper penetration depth in tissue can facilitate treating deep infections. Because of the combination of the in situ fiber deposition method with the designed elution mode, ROS is effectively poured out onto the fiber surface and is quickly delivered to the wound. Thus, after rapid hemostasis (<7 s), this one-stop treatment followed by photodynamic sterilizing of superbacteria can promote collagen regeneration and reduce wound healing time from 24 to 16 days.

7.
Sleep ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769549

RESUMO

STUDY OBJECTIVES: This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA). METHODS: We conducted a systematic search through PubMed, Medline, the Cochrane Library, EMBASE, Scopus and ClinicalTrials (all searched from inception to 15 August 2020). Publications were limited to articles, clinical conferences and letters, including randomized controlled trials and retrospective studies. We used a random-effects model to calculate the odds ratio (OR) and mean difference (MD) with corresponding confidence interval (CI). Subgroup analyses were conducted to analyze the sources of heterogeneity. RESULTS: Eight studies fulfilled the inclusion and exclusion criteria for patients newly diagnosed with obstructive sleep apnea. Overall, the use of NBSH was associated with increased use of CPAP per night (MD = 0.62 h; 95% CI = 0.26-0.98) and use for more nights (MD = 12.08%; 95% CI = 5.27-18.88). When a study seriously affecting heterogeneity was removed, more patients adhered well with CPAP use (pooled OR = 2.48; 95% CI = 1.75-3.52) with good adherence defined as CPAP use for>4 h/night on>70% of nights. Among prescribed NBSHs, eszopiclone showed the most significant effect on CPAP adherence. CONCLUSION: CPAP adherence may increase in OSA patients treated with non-benzodiazepine sedative hypnotics especially eszopiclone. The effect of zolpidem and zaleplon on CPAP adherence requires further investigation by larger scale, randomized, controlled trials.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33650711

RESUMO

In this work, Fe3 O4 nanoparticles (NPs) were coated with polydopamine (PDA) to structure Fe3 O4 @PDA NPs by the spontaneous oxygen-mediated self-polymerization of dopamine (DA) in an aqueous solution of pH = 8.5. The fabricated Fe3 O4 @PDA NPs were grafted by glutaraldehyde to realize the immobilization of penicillin G acylase (PGA) under mild conditions. The carriers of each stage were characterized and investigated by transmission electron microscopy, X-ray diffraction, Fourier transform infrared, and vibrating sample magnetometry. To improve the catalytic activity and stability of immobilized PGA, the immobilization conditions were investigated and optimized. Under the optimal immobilization conditions, the enzyme loading capacity, enzyme activity, and enzyme activity recovery of immobilized PGA were 114 mg/g, 26,308 U/g, and 78.5%, respectively. In addition, the immobilized PGA presented better temperature and pH stability compared with free PGA. The reusability study ensured that the immobilized PGA showed an excellent repeating application performance. In particular, the recovery rate of immobilized PGA could reach 94.8% and immobilized PGA could retain 73.0% of its original activity after 12 cycles, indicating that the immobilized PGA exhibited a high operation stability and broad application potential in the biocatalysis field.

9.
Shock ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33555843

RESUMO

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving technique for the management of lethal torso hemorrhage. Its benefit, however, must be weighed against the lethal distal organ ischemia-reperfusion injury (IRI). This study uses a novel direct gut cooling technique to manage the distal organ IRI. METHODS: A rat lethal hemorrhage model was established by bleeding of 50% of the estimated total blood volume via inferior vena cava. A novel TransRectal Intra-Colon (TRIC) temperature management device was positioned in the descending colon either to maintain intra-colon temperature at 37°C or 12°C. The upper body temperature was maintained at as close to 37°C as possible in both groups. A 2F Fogarty balloon catheter was inserted via the femoral artery into the descending thoracic aorta for the implementation of REBOA. After REBOA, the balloon was deflated, and the shed blood was returned. The temperature managements were continued for additional 180-270 min during the post-REBOA period. RESULTS: All rats subjected to REBOA management of lethal hemorrhage at 37°C had severe histopathological gut and abdominal organ IRI, severe functional deficits, and died within 24 h with 100% mortality. By contrast, directly cooling the colon to 10-12°C with the novel TRIC device abolished mortality, and dramatically improved ABG parameters, prevented the abdominal organ injury, and reduced the functional deficits during the 7-day post-REBOA period. CONCLUSIONS: Directly trans-rectal colon cooling during REBOA management of lethal hemorrhage offers extraordinary functional improvement and amazing tissue protection, and abolishes mortality.

10.
J Mater Chem B ; 9(4): 1089-1095, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33427258

RESUMO

Near-infrared fluorophores are emerging as promising molecular tools for cancer theranostics because of their inherent biodegradability, low toxicity, and synthetic flexibility. However, they still suffer from several limitations, such as poor photostability and insufficient organelle-targeting stability during photothermal therapy. In this work, we introduce an "aldehyde functionalization" strategy for simultaneously enhancing photostability and mitochondria-immobilization of near-infrared fluorophores for the first time. Based on the proposed strategy, representative near-infrared organic molecules, namely AF-Cy, were rationally designed and synthesized. Upon aldehyde modification, the AF-Cy dyes displayed both remarkable photostability and mitochondrial-targeting stability. The strong absorption in the near-infrared region confers the AF-Cy dyes with outstanding fluorescent/photoacoustic imaging and photothermal therapy capabilities. Finally, in vitro and in vivo studies revealed the enhanced performance in inhibiting the growth of breast tumors under NIR laser radiation, and these results suggested the strong potential of AF-Cy dyes as efficient multimodal imaging-guided photothermal therapy agents, further highlighting the value of this simple strategy in the design high performance near-infrared fluorophores for tumor theranostics.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Corantes Fluorescentes/farmacologia , Mitocôndrias/efeitos dos fármacos , Imagem Multimodal , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de Superfície
11.
Sci Total Environ ; 768: 144174, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33453530

RESUMO

The mobility and environmental risk of colloids and associated pollutants are dependent on their dispersion stability under various conditions. In this work, the stability and correlated migration of illite colloids (IC) were systematically investigated over a wide range of aquatic chemistry conditions. The results showed that IC was aggregation favorable at low pH, low temperature and high ionic strength. The critical coagulation concentration (CCC) of IC increased exponentially with increasing values of r/Z3, following the Schulze-Hardy and Hofmeister series. Humic acid (HA) greatly mitigated colloid aggregation since the attachment of HA on IC surface increased the steric hindrance and electrostatic potential, and the enhancement of stability was linearly correlated with the HA concentration. The Derjaguin-Landau-Verwey-Overbeek (DLVO) model revealed that the interaction force deriving from van der Waals forces and electrostatic double-layer energy evolved as the aquatic chemistry varied, and the reduction in repulsion force between particles facilitated the colloid collision and then aggregation. The migration of IC in the porous sand column was highly correlated with the dispersion stability and filtration effect, the agglomerated colloids were redispersed and released when conditions favored dispersion. The illite colloids acted as efficient carriers for Eu(III) transport. These findings are essential for improving the understanding of the geological fate of environmental colloids and associated radionuclides.

12.
Am J Orthod Dentofacial Orthop ; 159(2): 202-209.e2, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33388198

RESUMO

INTRODUCTION: This study aimed to establish mathematical equations to describe the dental and basal arch forms in skeletal Class II malocclusion and to investigate correlations between these forms to facilitate clinical diagnosis and treatment design. METHODS: Cone-beam computed tomography images of 60 patients (30 each with skeletal Class II malocclusion and normal occlusion) were subjected to 3-dimensional volume rendering, image reconstruction, and measurement. Using a computer program written in Java on the Eclipse platform (Eclipse Foundation, Ottawa, Canada), a beta function was used to establish mathematical models of dental and basal bone arch forms, and model-fitting was performed. RESULTS: A mathematical model was developed to describe the dental and basal arch forms in skeletal Class II malocclusion. The maxillary and mandibular dental arch lengths were significantly longer in skeletal Class II malocclusion than in normal occlusion, whereas the width of the maxillary molar segment was smaller. The maxillary molar and mandibular intercranial segments in the basal arch were significantly longer in skeletal Class II malocclusion than in normal occlusion, whereas the mandibular intercranial segment width was smaller. CONCLUSIONS: The dental arch and basal bone arch forms in the maxilla and mandible follow individual curves, described by a beta function. In skeletal Class II malocclusion, the dental and basal arches are discrepant in horizontal and anteroposterior dimensions, which should be considered during orthodontic treatment planning to improve arch matching.


Assuntos
Arco Dental , Má Oclusão de Angle Classe II , Canadá , Cefalometria , Arco Dental/diagnóstico por imagem , Humanos , Má Oclusão de Angle Classe II/diagnóstico por imagem , Má Oclusão de Angle Classe II/terapia , Mandíbula/diagnóstico por imagem , Maxila/diagnóstico por imagem
14.
Redox Rep ; 25(1): 104-111, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269646

RESUMO

Objectives: Inflammation is an important predisposing and progressive factor in chronic kidney disease (CKD). Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is associated with many fundamental cellular processes, but in chronic inflammatory pathologies remains unclear. Methods: An in vitro peripheral inflammation model was established using lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages, followed by inflammasome activation by ATP treatment. Knockdown of hnRNPK by sihnRNPK and FLICE-like inhibitory protein (FLIP) by siFLIP transfection were achieved in Raw264.7 macrophages. ELISA was used to determine the expression of IL-1ß, IL-18 and TNF-α. Real time PCR was applied to detect the mRNA levels of hnRNPK, NOD-like receptors family pyrin domain-containing 3 (NLRP3), FLIP, Caspase-1, IL-1ß and IL-18. Western blot and immunofluorescence were performed to detect relevant protein expressions. Co-immunoprecipitation (Co-IP) was used to assess the interaction of hnRNPK with FLIP. Results: Results showed that LPS plus ATP activated NLRP3 inflammasome, which evidenced by the up-regulation of TNF-α, IL-1ß and IL-18. Notably, hnRNPK and FLIP were significantly up-regulated in activated NLRP3 inflammasome of macrophages. HnRNPK or FLIP knockdown significantly suppressed the activation of NLRP3 inflammasome, as reflected by down-regulation of Caspase-1, IL-1ß and IL-18. Importantly, hnRNPK could directly bind to FLIP in activated NLRP3 inflammasome. Discussion: Our findings suggest that hnRNPK could promote the activation of NLRP3 inflammasome by directly binding FLIP, which might provide potential new therapeutic targets for CKD.

15.
Br J Pharmacol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140842

RESUMO

BACKGROUND AND PURPOSE: Pulmonary veno-occlusive disease (PVOD) is a rare disease characterized by the obstruction of small pulmonary veins leading to pulmonary hypertension. However, the mechanisms underlying pulmonary vessel occlusion remain largely unclear. EXPERIMENTAL APPROACH: A mitomycin C (MMC)-induced PVOD rat model was used as in vivo animal model; and primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as in vitro cell model. RESULTS: Our data suggested an endothelial-to-mesenchymal transition (EndoMT) may be present in the pulmonary microvessels isolated from either PVOD patients or MMC-induced PVOD rats. In compare to the control vessels, vessels from both PVOD patients and PVOD rats represented co-localized staining of specific endothelial marker von Willebrand factor (vWF) and mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the presence of cells that co-express endothelial and mesenchymal markers. Then, in both the lung tissues of MMC-induced PVOD rats and MMC-treated rat PMVECs, decreased levels of endothelial markers (e.g. VE-cadherin, CD31) and increased mesenchymal markers (e.g. Vimentin, Fibronectin, α-SMA) were detected, also indicating EndoMT. Moreover, MMC induced activation of the TGFß/Smad3/Snail axis, while blockage of this pathway with either specific Smad3 inhibitor (SIS3) or small interfering RNA (siRNA) against Smad3, both dramatically abolished the MMC-induced EndoMT. Notably, treatment with SIS3 remarkably prevented the pathogenesis of MMC-induced PVOD in rats. CONCLUSIONS: Our data indicated that targeted inhibition of Smad3 leads to a potential, novel strategy for PVOD therapy, likely by inhibiting the EndoMT in pulmonary microvasculature.

16.
Front Neurosci ; 14: 911, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013302

RESUMO

According to previous studies, many neuroanatomical alterations have been detected in patients with tinnitus. However, few studies have reported on the morphological changes observed following sound therapy. To explore the brain anatomical alterations in patients with idiopathic tinnitus using voxel-based morphometry (VBM) analysis before and after effective 12 weeks sound therapy. The protocol was registered on ClinicalTrials.gov, ID: NCT02774122. In this study, we collected data from 27 matched healthy control (HC) individuals and 27 idiopathic tinnitus patients before and after 12 weeks of sound therapy by using adjusted narrow band sound. 3.0T MRI system and high-resolution 3D structural images were acquired with a 3D-BRAVO pulse sequence. Structural image data preprocessing was performed using the VBM8 toolbox. The Tinnitus Handicap Inventory (THI) score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Mann-Whitney U Test, Wilcoxon Signed-Ranks test, and Pearson's correlation analysis were used in the statistical analysis. We found significantly decreased gray matter (GM) volume in the left thalami, right thalami, and cochlear nucleus among the tinnitus patients before sound therapy (baseline) compared to the HC group. However, we did not find significant differences in brain regions between the 12-week treatment and HC groups. According to the results of Wilcoxon Signed-Ranks test, the 12-week sound therapy group demonstrated significant greater brain volume compared with the baseline group among these brain regions. Decreased THI score and changed GM volume were not correlated. This is a useful study for observing the characteristics of neuroanatomical changes in patients with idiopathic tinnitus before and after sound treatment. The study characterized the effect of sound therapy on brain volume. It found that sound therapy had a normalizing effect on the bilateral thalami and cochlear nucleus. Clinical Trial Registration: www.ClinicalTrials.gov, NCT02774122.

17.
Enzyme Microb Technol ; 141: 109651, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33051010

RESUMO

Corynebacterium glutamicum is an important industrial organism for the production of a variety of biological commodities. We discovered a promoter encoded by the gene NCgl2319 in C. glutamicum, which could be induced by benzyl alcohol, could be used as an efficient tunable expression system. In initial attempts, this promoter failed to function in a recombinant expression system. This was remedied by extending the original genetic context of the promoter, generating a new version Pcat-B. The Pcat-B transcription initiation site, its critical active regions, and its effect of inducers were fully characterized resulting in tunable expression. This approach proved to be very efficient in producing a pharmaceutical protein, N-terminal pro-brain natriuretic peptide (NT-proBNP). Production of approximately 440.43 mg/L NT-proBNP was achieved with the Pcat-B expression system demonstrating its application for controllable pharmaceutical protein production in C. glutamicum.

18.
Br J Pharmacol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33080042

RESUMO

BACKGROUND AND PURPOSE: Pulmonary hypertension related to pulmonary fibrosis is classed as WHO Group III, one of the most common groups which lacks effective treatment options. In this study, we aimed to uncover the underlying mechanisms, particularly the involvement of the BMP9/BMPR2/SMAD signalling pathway, in this subtype of pulmonary hypertension. EXPERIMENTAL APPROACH: Male Sprague Dawley rats were used to establish a model of pulmonary hypertension with pulmonary fibrosis, induced by bleomycin. Haemodynamic and lung functions were measured, along with histological and immunohistochemical examinations. Primary cultures of rat pulmonary microvascular endothelial cells (PMVECs) were analysed with western blots, apoptosis assays and immunohistochemistry. KEY RESULTS: Early (7 days) after bleomycin treatment of rats, pulmonary arterial thickening and severe loss of pulmonary arterial endothelium were observed, followed (14 days) by increased right ventricular systolic pressure and right ventricular hypertrophy. Marked down-regulation of the BMP9/BMPR2/SMAD signalling pathway was markedly down-regulated in lung tissues from bleomycin-treated rats (throughout the 7- to 35-day treatment period) and bleomycin-treated rat PMVECs, along with excessive cell apoptosis and loss of pulmonary arterial endothelium. Treatment with recombinant human bone morphogenetic protein 9 (rhBMP9) attenuated these aspects of bleomycin-induced pulmonary hypertension, by restoring disrupted BMP9/BMPR2/SMAD signalling. CONCLUSION AND IMPLICATIONS: In bleomycin-treated rats, early and persisting suppression of the BMP9/BMPR2/SMAD signalling pathway triggered severe loss of pulmonary arterial endothelium and subsequent pulmonary arterial vascular remodelling, contributing to the development of pulmonary hypertension. Therapeutic approaches reinforcing BMP9/BMPR2/SMAD signalling might be ideal strategies for this subtype of pulmonary hypertension.

20.
ACS Omega ; 5(38): 24356-24366, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33015452

RESUMO

In this work, an ion imprinted polymer (ReO4 --IIP) of the perrhenate ion based on acrylamide (AM) and acrylic acid (AA) was prepared by solution polymerization using ReO4 - as a template ion, N,N-methylenebisacrylamide (NMBA) as cross-linkers, hydrogen peroxide-vitamin C (H2O2-Vc) as an initiator, and a mixed solution of water (H2O) and methanol (CH3OH) with volume ratio v(H2O)/v(CH3OH) = 3:7 as a solvent. During the process of synthesis condition investigation and optimization, the adsorption capacity (Q) and the separation degree (R) in the equimolar concentration mixture solutions of NH4ReO4 and KMnO4 were adopted as indexes, and the obtained optimal conditions were as follows: the molar ratios of NMBA, NH4ReO4, AA, H2O2, and Vc to AM were 5.73, 0.052, 1.29, 0.02, and 0.003, and the temperature and time of polymerization were 40 °C and 28 h, respectively. Under optimal conditions, the sample with indexes, Q and R of 0.064 mmol/g and 3.20, were harvested. What is more, a further reusability study found that good adsorption selectivity was maintained after repeating the experiment 9 times. Taking the non-IP prepared under the same conditions as a control, Fourier transform infrared spectroscopy, transmission electron microscopy, and Brunauer Emmett Teller were used to characterize the structure of the ReO4 --IIP prepared under the optimal conditions. Finally, the kinetic study results showed that the zero-order kinetic model could better describe the adsorption process. The thermodynamic study results showed that the Langmuir model was more suitable for describing the isotherm adsorption process of the IIP.

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