Advances and applications of organoids: a review / 生物工程学报

Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.

Research of roles of NF-κB and promote apoptosis protein Bak in ucelrative coli-tis / 中国免疫学杂志

Objective:To study the expression levels of nuclear factor kappa B, Bcl-2 associated K and TNF-αproteins to discuss the effects of NF-κB and Bak proteins in the pathogenesis of UC.Methods:Eighty clean grade of adult Sprague-Dawley( SD) rats were used,male and female in half and then rando mly selected sixty as the model group,another twenty as the control group.SD rats model were manufactured by a compound method:Trinitrobenzene sulfonic acid ( TNBS )+ethanol.We observed and assessed colonic mucosa by the general morphology and histological changes.To applicated immunohistochemistry and RT-PCR methods to detected the protein and mRNA expression levels of NF-κB,Bak and TNF-αin the model groups and the control group and to analysed their relationships.Results:The successful rate of making model was 97%.The number of inflammatory cells in the model groups more than the control(P0.05).The expression levels of NF-κB,TNF-αincreased as the histological grade increased(P<0.05),however,the expression level of Bak decreased(P<0.05).NF-κB in colonic mucosa of rats with UC had a significantly positive correlation with that of TNF-α(r=0.892,P<0.01),and negatively correlated with that of Bak(r=-0.793,P<0.01).Conclusion:The levels of NF-κB and Bak may be related to the occurrence and development of UC.

Infection with L-form of Helicobacter pylori and expressions of MIF, MMP9 and VEGF in gastric carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation between infection with L-form of Helicobacter pylori (Hp-L) and the expressions of macrophage migration inhibition factor (MIF), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor (VEGF) in gastric cancer.</p><p><b>METHODS</b>Hp-L was examined in 80 gastric carcinoma and 50 adjacent normal tissues by Gram staining and immunohistochemical staining, and the expressions of MIF, MMP9 and VEGF were detected by immunohistochemical staining; the expression of MIF mRNA was detected by RT-PCR and the expression of MIF, MMP9 and VEGF proteins were detected by Western blotting in 30 fresh gastric cancer tissues and the corresponding adjacent tissues.</p><p><b>RESULTS</b>Of the 80 gastric carcinoma tissues, 57 (71.25%) showed Hp-L positivity detected by both Gram staining and immunohistochemical staining, as compared with a rate of only 14% in the adjacent normal tissues (P<0.05). The gastric carcinoma tissues showed higher expression levels of MIF, MMP9 and VEGF proteins than the corresponding adjacent normal mucosa; the positivity MIF, MMP-9 and VEGF proteins were significantly higher in Hp-L-positive gastric carcinoma than in Hp-L-negative cases (P<0.05). Positive correlations were found between Hp-L positivity and the expressions of MIF, MMP-9 and VEGF (r=0.598, 0.292, 0.341, respectively, P<0.05). The 30 fresh gastric cancer tissues showed also significantly higher MIF mRNA expression and MIF, MMP-9 and VEGF protein expressions than the adjacent tissues (t=3.729, P<0.01). The expressions of MIF and MMP-9 were also related to the clinicopathological factors including lymph node metastasis and depth of invasion (P<0.05).</p><p><b>CONCLUSION</b>Infection with L-form of Hp-L can be an important factor that contributes to the invasion and metastasis of gastric carcinoma, the mechanism of which involves up-regulated expressions of MIF, MMP-9 and VEGF.</p>

A porcine model of congenital heart defect with decreased pulmonary blood flow established and the evaluate of immature pulmonary vascular of morphological chang / 中华胸心血管外科杂志

Objective Artificial atrial septum defect combining pulmonary artery banding to create a model of congenital heart defect with decreased pulmonary blood flow to explore the morphological changes of immature pulmonary vascular. Methods Choose twenty piglets with about one to two-month-old, which are exclusively for experiment used. The piglets were randomly divided into three groups: normal control group (group C, n = 6), Small incisions on the right chest, produced a transient reduction in pulmonary blood; low-medium pulmonary artery stenosis groups ( group T1, n = 7 ) : Did artificial room septostomy creation by self-dilators which were delivered into the surface of the right atrium and controlled Systolic trans pulmonary artery banding pressure (Trans-PABP) at pressure of 20 - 30 mmHg; severe pulmonary artery stenosis groups ( group T2, n = 7): T2 were the same surgical procedures with group T1 ,and controlled Trans-PABP ≥ 30 -50 mmHg. Monitored ultrasound after operation , carried out 64-slice computed tomography scanning after one month, to measure the proximal vessel diameter and TransPABP , after two month surgical exploration on the left chest. When the animals were sacrificed, the heart and lung tissue was cut to measure atrial septal defect, pulmonary artery and the banding diameter. By weihgt elastic fiber and van Cieson staining to observe the morphological pathological changes, three groups took lung tissue with right middle lobe lateral segment about 1.0 cm × 0.8 cm × 0.8cm at the end of surgery and 2-months after operation respectively. Results The models were all successfully in the survival animal of the two test groups. One pig died from tracheal intubation accident in the C group, there was one case died due to bowel obstruction in the T1 group, And there were two cases died result from acute right heart failure and chronic heart failure respectively in T2 group. 64-slice CT angiography showed that BD was significantly lower than the AOD in the two test groups, the proximal pulmonary vascular expansion result from stenosis, distal pulmonary vascular scarce. Histopathology showed that the pulmonary artery inside diameter of T1 and T2 was significantly higher than group C(P ＜0. 05,P ＜ 0.01), and the NAPSC of two experimental groups were significantly lower than group C 2-month after operation( P ＜0.01).Conclusion This type of Piglet model is closer to clinical pathological and physiological ,64-slice spiral CT combined with lung histopathology observed for the evaluation of pulmonary vascular hypoplasia is a reliable method. Tunica media of pulmonary arterioles hypoplasia with the number reducing, with pulmonary artery banding increased,the degree of pulmonary arterioles hypoplasia gradually increased.