ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates.Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28).Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions.Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.     

Effects of dietary fat on cholesterol movement between tissues in CBA/J and C57BR/cdJ mice.

Differences in dietary fats cause differences in cholesterol metabolism in mice. CBA/J mice are resistant to diet-induced hypercholesterolemia and atherosclerosis; they adjust hepatic hydroxymethyl-glutaryl-CoA reductase activity (HMGR) to maintain homeostasis; C57BR/cdJ mice are susceptible, but young animals are thought to maintain homeostasis by changing fecal excretion of sterols. Compartmental modelling of movement of [4-14C]cholesterol was used to analyze movement of cholesterol between serum and liver, heart, and carcass in mice fed 40 en% fat, polyunsaturated to saturated fatty acid ratio (P/S) = 0.24 (US74) or 30 en% fat, P/S = 1 (MOD). Dietary effects were quite pronounced, while strain effects were more subdued. The C57/cdJ animals appear to regulate the overall cholesterol balance by reducing synthesis, as do the CBA/J animals, even though synthesis is not reduced to the same degree as in the CBA/J animals. Both diet and strain influence the whole-animal turnover rate, with slower turnover occurring for C57BR/cdJ animals and animals fed the US74 diet.     

An improved method of light-induced pigmentation.

An improved procedure was developed whereby a primary light signal can be intensified and made visible by activation of a pre-tyrosinase (pre-phenoloxidase) enzyme [isolated from silkworm (Bombyx mori)] by alpha-chymotrypsin; this activation results from the light-activated conversion of the inactive cis-cinnamoyl-alpha-chymotrypsin.     

Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings

This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4^?/?) (n = 6 per each TLR4^?/? group) mice were categorized into sham control (SC^B6), SC^TLR4?/?, IS^B6, IS^TLR4?/?, IS^B6 + Mel (i.p. daily administration) and IS^TLR4?/? + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK‐α/p‐NF‐κB/nuclear‐NF‐κB/nuclear‐IRF‐3&7/IL‐1β/IL‐6/TNF‐α/IFN‐γ) and oxidative stress (NOX‐1/NOX‐2/ASK1/p‐MKK4&7/p‐JNK/p‐c‐JUN) downstream pathways as well as mitochondrial‐damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group IS^B6, lowest in groups SC^B6 and SC^TLR4?/?, lower in group IS^TLR4?/? + Mel than in groups IS^TLR4?/? and IS^B6 + Mel and lower in group IS^B6 + Mel than in group IS^TLR4?/? (all P < .0001). The brain infarct volume, brain infarct area and the number of inflammatory cells in brain (CD14/F4‐88) and in circulation (MPO+//Ly6C+/CD11b+//Ly6G+/CD11b+) exhibited an identical pattern, whereas the neurological function displayed an opposite pattern of inflammatory protein expression among the six groups (all P < .0001). In conclusion, TLR inflammatory and oxidative stress signallings played crucial roles for brain damage and impaired neurological function after IS that were significantly reversed by Mel therapy.     

烧伤早期伴发脓毒症患者血清PCT、hs-CRP、COR及WBC的动态变化及临床意义

目的:探讨烧伤早期伴发脓毒症患者血清降钙素原(PCT)、超敏C反应蛋白(hs-CRP)、皮质醇(COR)和白细胞计数(WBC)水平并分析其临床价值。方法:回顾性分析2014年12月至2018年1月本院收治的63例烧伤早期患者的临床资料,其中19例患者伴发脓毒症(脓毒症组),44例患者未伴发脓毒症(无脓毒症组),另选取30例于本院进行体检的志愿者作为健康对照组,依据病情严重程度将脓毒症患者分为脓毒症休克组(n=4)、严重脓毒症组(n=7)、一般脓毒症组(n=8),依据预后情况分为预后良好组(n=13)和预后不良组(n=6)。动态检测并对比所有研究对象血清PCT、hs-CRP、COR和WBC水平。结果:无脓毒症组、脓毒症组血清PCT、hs-CRP、COR和WBC水平高于健康对照组,且脓毒症组高于无脓毒症组(P<0.05)。烧伤后7 d、11 d、15 d,脓毒症组血清PCT、hs-CRP、COR和WBC水平均高于无脓毒症组(P<0.05)。脓毒症休克组血清PCT、hs-CRP、COR和WBC水平高于严重脓毒症组、一般脓毒症组,且严重脓毒症组患者高于一般脓毒症组患者(P<0.05)。预后不良组血清PCT、hs-CRP、COR和WBC水平高于预后良好组(P<0.05)。结论:血清PCT、hs-CRP、COR和WBC水平在烧伤早期伴发脓毒症患者中水平异常升高,与病情严重程度有关,上述指标对预后判断有一定的临床参考价值。     

A processing product of the Plasmodium falciparum reticulocyte binding protein RH1 shows a close association with AMA1 during junction formation

Plasmodium falciparum responsible for the most virulent form of malaria invades human erythrocytes through multiple ligand‐receptor interactions. The P. falciparum reticulocyte binding protein homologues (PfRHs) are expressed at the apical end of merozoites and form interactions with distinct erythrocyte surface receptors that are important for invasion. Here using a range of monoclonal antibodies (mAbs) against different regions of PfRH1 we have investigated the role of PfRH processing during merozoite invasion. We show that PfRH1 gets differentially processed during merozoite maturation and invasion and provide evidence that the different PfRH1 processing products have distinct functions during invasion. Using in‐situ Proximity Ligation and FRET assays that allow probing of interactions at the nanometre level we show that a subset of PfRH1 products form close association with micronemal proteins Apical Membrane Antigen 1 (AMA1) in the moving junction suggesting a critical role in facilitating junction formation and active invasion. Our data provides evidence that time dependent processing of PfRH proteins is a mechanism by which the parasite is able to regulate distinct functional activities of these large processes. The identification of a specific close association with AMA1 in the junction now may also provide new avenues to target these interactions to prevent merozoite invasion.     

Molecular Targets for the Testing of COVID‐19

The pandemic outbreaks of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), spread all over the world in a short period of time. Efficient identification of the infection by SARS‐CoV‐2 has been one of the most important tasks to facilitate all the following counter measurements in dealing with the infectious disease. In Taiwan, a COVID‐19 Open Science Platform adheres to the spirit of open science: sharing sources, data, and methods to promote progress in academic research while corroborating findings from various disciplines has established in mid‐February 2020, for collaborative research in support of the development of detection methods, therapeutics, and a vaccine for COVID‐19. Research priorities include infection control, epidemiology, clinical characterization and management, detection methods (including viral RNA detection, viral antigen detection, and serum antibody detection), therapeutics (neutralizing antibody and small molecule drugs), vaccines, and SARS‐CoV‐2 pathogenesis. In addition, research on social ethics and the law are included to take full account of the impact of the COVID‐19 virus.     

Comparison of hinge microflow fields of bileaflet mechanical heart valves implanted in different sinus shape and downstream geometry

The characterization of the bileaflet mechanical heart valves (BMHVs) hinge microflow fields is a crucial step in heart valve engineering. Earlier in vitro studies of BMHV hinge flow at the aorta position in idealized straight pipes have shown that the aortic sinus shapes and sizes may have a direct impact on hinge microflow fields. In this paper, we used a numerical study to look at how different aortic sinus shapes, the downstream aortic arch geometry, and the location of the hinge recess can influence the flow fields in the hinge regions. Two geometric models for sinus were investigated: a simplified axisymmetric sinus and an idealized three-sinus aortic root model, with two different downstream geometries: a straight pipe and a simplified curved aortic arch. The flow fields of a 29-mm St Jude Medical BMHV with its four hinges were investigated. The simulations were performed throughout the entire cardiac cycle. At peak systole, recirculating flows were observed in curved downsteam aortic arch unlike in straight downstream pipe. Highly complex three-dimensional leakage flow through the hinge gap was observed in the simulation results during early diastole with the highest velocity at 4.7 m/s, whose intensity decreased toward late diastole. Also, elevated wall shear stresses were observed in the ventricular regions of the hinge recess with the highest recorded at 1.65 kPa. Different flow patterns were observed between the hinge regions in straight pipe and curved aortic arch models. We compared the four hinge regions at peak systole in an aortic arch downstream model and found that each individual hinge did not vary much in terms of the leakage flow rate through the valves.