Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.     

Comparison of microscopic features of bone false starts produced by reciprocating saw blades and handsaws of the same class

In cases of criminal dismemberment, the analysis of saw marks helps to determine the class of the saw used. The present study compared the microscopic features of experimental false starts performed on three freshly defleshed human femurs. 150 lesions were produced using three reciprocating blades and two hand saws of similar class. Two groups of tools were created according to the class of the blades: group 1 (teeth per inch = 6, alternating set) and group 2 (teeth per inch = 24, wavy set).The minimum width of the kerf was always thicker with reciprocating blades than that of the handsaw of the same class. This fact is linked to the thickness of the blades and not necessarily to the fast forth and back motion of the blades. Shape kerf profiles and shape of the walls were very confusing, with a lot of variation of the false starts caused by the reciprocating blades and the risk of misclassification (rip teeth versus crosscut teeth, alternating set versus wavy set). Striae on the kerf floor and bone islands were more consistent.The main conclusions are, first, that usual features of false starts achieved by reciprocating saw blades used in this work vary a great deal and may lead to misclassification of the saw class, and second, that no criterion has been found to differentiate reciprocating blades and handsaws. These results demonstrate that we have to be very prudent while estimating the possible saw from a false start in a real forensic case.     

Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial

BackgroundPretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients.MethodsWe created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups.ResultsIn 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p ?< ?0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p ?< ?0.001), and using 0, 1–100 and ?> ?100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p ?= ?0.06). Similar results were found in all subanalyses.ConclusionCalcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.     

冠状病毒特征与进化优势

冠状病毒是近年来新发突发传染病的重要来源,因家族成员庞大、宿主谱广、突变株多样,在进化中展示了其优越性。本文通过回顾冠状病毒基因组特征、感染宿主动物与受体分布及基因突变等方面的研究进展,对其在进化和传播中存在的优势进行总结和讨论,以期引起对相关病毒防控的重视。     

Green tea catechins inhibit Porphyromonas gulae LPS-induced inflammatory responses in human gingival epithelial cells

ObjectivesTo determine the anti-inflammatory effects of green tea catechins in immortalized human gingival epithelial cells (Ca9-22) stimulated with Porphyromonas gulae lipopolysaccharide (LPS).MethodsCa9-22 cells were incubated with P. gulae LPS (10 μg/ml) with or without green tea catechins, epigallocatechin-3-gallate (EGCg), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) (each at 50 μM), for 6 or 24 h. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay were used to determine the induction of cyclooxygenase 2 (COX2), tumor necrosis factor alpha (TNF-ɑ), interleukin 6 (IL-6), and IL-8. Furthermore, the expression of toll-like receptors (TLRs) 2 and 4 was examined using real-time PCR and western blotting analysis, and phosphorylation of the p38 and ERK1/2 was examined using western blotting analysis.ResultsAt the mRNA and protein levels, EGCg, EGC, ECG, and EC were found to significantly inhibit COX2, TNF-ɑ, IL-6, and IL-8. Furthermore, the levels of ERK1/2 and p38 phosphorylation induced by P. gulae LPS were decreased following the addition of each of the catechins, as well as TLR2 and 4 mRNA and protein.ConclusionsThese findings indicate that green tea catechins are potent inhibitors of in?ammatory responses induced by P. gulae LPS, and may also be useful for prevention and/or attenuation of periodontitis.     

Top advances of the year: Hepatobiliary cancers

This commentary reviews top advances in hepatobiliary cancer research in 2021–2022, focusing on leveraging immunotherapeutics in combination with other therapies earlier in the disease course and targeted to patient's individualized biomarkers that may predict response or resistance to checkpoint inhibitors.     

呼吸机自动测量气道阻断压与标准测量方法的一致性

目的 验证呼吸机自动测量的气道阻断压(airway occlusion pressure,P0.1)与标准测量方法的一致性,以及不同触发形式对自动测量结果的影响。方法 选择采用非阻断自动测量P0.1的呼吸机,分别进行模拟肺和临床试验。调节全自动自主呼吸模拟肺,模拟具有不同呼吸努力和呼吸力学特征的48种状态,应用待检测呼吸机,以压力支持通气模式为模拟肺进行通气。临床研究部分纳入15例接受压力支持通气的成年患者。两部分研究均随机交叉应用压力和流量触发,采集呼吸机自动监测的P0.1后,采用标准呼气末气道阻断法进行P0.1测量,作为标准参考值。采用Bland-Altman检验分析P0.1呼吸机监测值与标准参考值的一致性,计算残差(呼吸机监测值-标准参考值)和95%一致性区间,比较不同触发形式对残差的影响。结果 在模拟肺验证中,P0.1呼吸机监测值与标准参考值之间的残差(95%一致性区间)在压力和流量触发下分别为0.04(－0.63~0.70)和－0.54(－1.44~0.36)cmH₂O(1 cmH₂O=0.098 kPa),两者相比差异具有统计学意义(P<0.001)。临床观察获得了相似的结果,压力和流量触发时的残差(95%一致性区间)分别为－0.11(－0.73~0.52)和－0.54(－1.50~0.59)cmH₂O,差异无统计学意义(P>0.05),表明呼吸机监测值与标准参考值间存在一致性。结论 压力触发时,呼吸机非阻断法自动测量的P0.1与标准方法具有良好的一致性。而流量触发明显低估P0.1,建议自动监测时切换到压力触发。