Dissolvable Gelatin-Based Microcarriers Generated through Droplet Microfluidics for Expansion and Culture of Mesenchymal Stromal Cells

Microcarriers are synthetic particles used in bioreactor-based cell manufacturing of anchorage-dependent cells to promote proliferation at efficient physical volumes, mainly by increasing the surface area-to-volume ratio. Mesenchymal stromal cells (MSCs) are adherent cells that are used for numerous clinical trials of autologous and allogeneic cell therapy, thus requiring avenues for large-scale cell production at efficiently low volumes and cost. Here, a dissolvable gelatin-based microcarrier is developed for MSC expansion. This novel microcarrier shows comparable cell attachment efficiency and proliferation rate when compared to several commercial microcarriers, but with higher harvesting yield due to the direct dissolution of microcarrier particles and thus reduced cell loss at the cell harvesting step. Furthermore, gene expression and in vitro differentiation suggest that MSCs cultured on gelatin microcarriers maintain trilineage differentiation with similar adipogenic differentiation efficiency and higher chondrogenic and osteogenic differentiation efficiency when compared to MSCs cultured on 2D planar polystyrene tissue culture flask; on the contrary, MSCs cultured on conventional microcarriers appear to be bipotent along osteochondral lineages whereby adipogenic differentiation potential is impeded. These results suggest that these gelatin microcarriers are suitable for MSC culture and expansion, and can also potentially be extended for other types of anchorage-dependent cells.     

Knowledge and attitudes regarding genetic testing among Jordanians: An approach towards genomic medicine

BackgroundThe twenty first century can be called the genomic era referring to the rapid development of genetics, and the beginning of genomic medicine. An initial step towards genomic medicine is to evaluate the knowledge and attitude towards genetic testing among different populations. The aims of this study were to assess the genetic knowledge and attitude towards genetic testing among the Jordanian population and patients with immune diseases. In addition, we evaluated the association between knowledge, attitude and several demographic factors of the population.MethodsThis study was performed using an online questionnaire that was distributed to respondents from different regions of Jordan.ResultsA total of 1149 participants were recruited from the Jordanian population. Overall factual genetic knowledge of the participants was good (65.4%), with education level, working or studying in a health-related field and household average monthly income being significant predictors of factual knowledge scores (P = 0.03, P < 0.001 and P < 0.001, respectively). However, factual knowledge results revealed that scores of questions related to diseases were significantly higher than scores of gene-related scientific facts (P < 0.01). Participants of our study reported to have low perceived knowledge on medical uses (39.5%) and social consequences (23.9%) of genetic testing. Regarding the participants’ attitudes, favorable attitudes towards genetic testing were prevailing (91.5%). Favorable attitudes were more prominent among higher educated participants, and participants with higher scores of factual knowledge.ConclusionDespite the fact that our Jordanian-based study revealed a good level of genetic knowledge as well as a favorable attitude towards genetic testing, we realized an imbalance of knowledge between gene-related scientific facts and disease-related concepts as well as between factual and perceived genetic knowledge, which indicates the necessity of increasing the awareness about genetic testing in order to ensure that individuals can take informed decisions that help in the employment of personalized medicine.     

中药调节肠道菌群防治高血压的研究进展

肠道菌群是人体内环境的重要组成部分,可影响机体的代谢、免疫和炎症反应,与原发性高血压的发生发展密切相关,已成为防治高血压的研究热点。中药在临床用于原发性高血压的治疗且疗效显著。研究表明中药可被肠道菌群分解代谢为易于吸收的活性物质,而这些活性物质又可通过调节肠道菌群结构及其代谢产物防治高血压。本文以肠道菌群作为切入点,通过分析肠道菌群与原发性高血压发生发展的关系和中药在调节原发性高血压肠道菌群方面的研究,总结中药通过调节肠道菌群防治原发性高血压的作用和机制,以期为中药防治高血压及药物研发提供新的研究思路。     

基于新型冠状病毒S蛋白结构及入胞机制的抗体与药物研发

新型冠状病毒肺炎,世界卫生组织命名为“2019冠状病毒病”（corona virus disease 2019, COVID-19）,是一种由2019新型冠状病毒（2019 nCov）感染导致的肺炎。目前新冠肺炎在全球广泛流行,且疫情尚未得到全部控制。由于新型冠状病毒表面的刺突蛋白（spike protein,S）介导病毒与细胞膜受体结合并参与入胞过程,S蛋白在病毒的传播过程中发挥着重要作用。针对S蛋白的研究不仅可以解析病毒相关蛋白质结构与功能,阐释其入胞机制,同时也为新冠肺炎的预防、诊断与治疗提供相关信息,有着重要的应用价值。S蛋白与特异性受体--血管紧张素酶II（angiotensin converting enzyme II, ACE2）结合,相较于SARS病毒,新型冠状病毒S蛋白的RBD区域（receptor binding domain）与ACE2亲和力更高,但其S蛋白与ACE2结合能力整体上弱于SARS病毒。S蛋白结合ACE2受体 介导的新型冠状病毒入胞机制包括胞吞和非胞吞途径。丝氨酸蛋白酶2（transmembrane protease serine 2, TMPRSS2）、溶酶体组织蛋白酶（lysosomal cathepsin）和Furin蛋白酶可切割S蛋白S1和S2亚基间的酶切位点,促进病毒和靶膜的融合。基于S蛋白的结构,本文从抗体的结合位点、来源与类型等方面对靶向新型冠状病毒S蛋白的抗体进行了比较分析,对相关药物作用机制与进展进行了综述。虽然靶向冠状病毒S蛋白的抗体和药物特异性高,治疗效果较好,但部分试剂的作用机制、安全性、适用性和稳定性等性质仍未研究透彻,需要严格评估,因此其研发与应用也存在着一定挑战。     

生防菌株HG18基因组信息分析与抗菌功能基因挖掘

贝莱斯芽胞杆菌（Bacillus velezensis）HG18是1株低温生防菌株,能够分泌抗菌物质。为挖掘和利用其抗菌功能基因,服务农业生产,采用二、三代相结合测序技术,对其进行全基因组测序,获得菌株完整基因组序列。基因组全长4 461 844 bp,包含一个染色体和一个质粒,GC含量44.06%,编码4 643个基因,编码基因总长度3 893 994 bp,占基因组87.27%。发现6个几丁质降解相关基因,2个葡聚糖酶基因和1个壳聚糖酶基因,2个脂肽类抗菌物质芬芥素与表面活性素合成基因簇,2个细菌素subtilin和bacillolysin合成基因。研究为提高抗菌物质产量的菌株定向遗传改造以及植物抗病育种提供基因资源。     

福建省福州市马尾区药用植物资源研究

依托第四次全国中药资源普查工作,摸清马尾区药用植物资源种类、分布、重点中药材品种以及药材栽培等情况。根据第四次全国中药资源普查要求,通过实地调查、走访以及栽培基地调查等方法对马尾区药用植物资源进行调查,查阅相关资料确定野生药用植物的药用部位、生活型等。马尾区野生药用植物种类共计506种,隶属于132科360属,含2～5种的寡种科占绝对优势地位;草本为主要生活型,药用部位集中在根类和全草类;有福建省重点药材50种、特色药材22种。由于长期受人为干扰,马尾区原生植被破坏严重,药用植物种类较为贫乏。因此,可考虑林下种植中药改善土壤环境,实现中药资源可持续发展。     

Progress of Gastric Cancer Surgery in the era of Precision Medicine

With the development of genomics, the update of modern imaging technology and the advent of artificial intelligence and big data, the surgical treatment of gastric cancer has gradually stepped into precision medicine. Precision surgery treatment of gastric cancer is based on accurate molecular typing and staging using modern molecular diagnostic technology and imaging, and the formulation of precise and individualized surgical treatment plans, with the concept of minimally invasive and accelerated rehabilitation surgery running through it. For intermediate-stage gastric cancer, we have adopted a comprehensive treatment approach including traditional radiotherapy and chemotherapy, targeted therapy and immunotherapy. Utilize artificial intelligence and big data technology to improve the standardization and interconnectivity of specialty data and realize the transformation of evidence-based medicine. Promoting the standardization, standardization and individualization of gastric cancer surgical treatment, providing patients with precise diagnosis and treatment, and further improving patients'' prognosis are the opportunities and challenges in the development of gastric cancer surgery.     

Predicting the structural integrity of bone defects repaired using bone graft materials

Bone defects create stress concentrations which can cause fracture under impact or cyclic loading. Defects are often repaired by filling them with a bone graft material; this will reduce the stress concentration, but not completely, because these materials have lower stiffness than bone. The fracture risk decreases over time as the graft material is replaced by living bone. Many new bone graft materials are being developed, using tissue engineering and other techniques, but currently there is no rational way to compare these materials and predict their effectiveness in repairing a given defect. This paper describes, for the first time, a theoretical model which can be used to predict failure by brittle fracture or fatigue, initiating at the defect. Preliminary results are presented, concentrating on the prediction of stress fracture during the crucial post-operative period. It is shown that the likelihood of fracture is strongly influenced by the shape of the defect as well as its size, and also by the level of post-operative exercise. The most important finding is that bone graft materials can be successful in preventing fracture even when their mechanical properties are greatly inferior to those of bone. Future uses of this technique include pre-clinical assessment of bone replacement materials and pre-operative planning in orthopaedic surgery.     

Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging

Recent genome‐wide association studies have linked type‐2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up‐regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type‐2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age‐dependent alterations of insulin and glucose homeostasis using Super‐Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age‐matched wild‐type controls, Super‐Ink4/Arf mice do not develop glucose intolerance with aging. Insulin tolerance tests demonstrated increased insulin sensitivity in Super‐Ink4/Arf compared with wild‐type mice, which was accompanied by higher activation of the insulin receptor substrate (IRS)‐PI3K‐AKT pathway in liver, skeletal muscle and heart. Glucose uptake studies in Super‐Ink4/Arf mice showed a tendency toward increased ¹⁸F‐fluorodeoxyglucose uptake in skeletal muscle compared with wild‐type mice (P = 0.079). Furthermore, a positive correlation between glucose uptake and baseline glucose levels was observed in Super‐Ink4/Arf mice (P < 0.008) but not in wild‐type mice. Our studies reveal a protective role of the Ink4/Arf locus against the development of age‐dependent insulin resistance and glucose intolerance.     

Role of oncoproteomics in the personalized management of cancer

Oncoproteomics is the term used to describe the application of proteomic technologies in oncology and parallels the related field of oncogenomics. It is now contributing to the development of personalized management of cancer. Proteomic technologies are used for the identification of biomarkers in cancer, which will facilitate the integration of diagnosis and therapy of cancer. Molecular diagnostics, laser capture microdissection and protein biochips are among the technologies that are having an important impact on oncoproteomics. The discovery of protein patterns developed by the US Food and Drug Administration/National Cancer Institute Clinical Proteomics Program is capable of distinguishing cancer and disease-free states with high sensitivity and specificity and will also facilitate the development of personalized therapy of cancer. Examples of application are given for breast and prostate cancer and a selection of companies and their collaborations that are developing application of proteomics to personalized treatment of cancer are discussed. Continued refinement of techniques and methods to determine the abundance and status of proteins in vivo holds great promise for the future study of normal cells and the pathology of associated neoplasms. Personalized cancer therapy is expected to be in the clinic by the end of the first decade of the 21st century.