clinical application
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Zhangkai J. Cheng ◽  
Bizhou Li ◽  
Zhiqing Zhan ◽  
Zifan Zhao ◽  
Mingshan Xue ◽  

2022 ◽  
Vol 12 ◽  
Xiaoxue Li ◽  
Ying Wang ◽  
Haiyuan Yang ◽  
Yifan Dai

About one-fifth of the population suffers from liver diseases in China, meaning that liver disorders are prominent causative factors relating to the Chinese mortality rate. For patients with end-stage liver diseases such as hepatocellular carcinoma or acute liver diseases with life-threatening liver dysfunction, allogeneic liver transplantation is the only life-saving treatment. Hepatocyte transplantation is a promising alternative for patients with acute liver failure or those considered high risk for major surgery, particularly for the bridge-to-transplant period. However, the lack of donors has become a serious global problem. The clinical application of porcine xenogeneic livers and hepatocytes remains a potential solution to alleviate the donor shortage. Pig grafts of xenotransplantation play roles in providing liver support in recipients, together with the occurrence of rejection, thrombocytopenia, and blood coagulation dysfunction. In this review, we present an overview of the development, potential therapeutic impact, and remaining barriers in the clinical application of pig liver and hepatocyte xenotransplantation to humans and non-human primates. Donor pigs with optimized genetic modification combinations and highly effective immunosuppressive regimens should be further explored to improve the outcomes of xenogeneic liver and hepatocyte transplantation.

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Zhe Li ◽  
Tingting Zhao ◽  
Jiaxin Li ◽  
Qingying Yu ◽  
Yu Feng ◽  

Natural products have antitumor, anti-inflammatory, antioxidant, and other pharmacological activities and are an important source of drugs for prevention and treatment of various diseases. However, the inherent defects of natural products in physiological media such as poor solubility and stability and short biological half-life limit their clinical application. In recent years, more and more attention has been paid to the science of drug delivery by nanoscale materials. A large number of in vitro and in vivo studies have further confirmed the efficacy and safety of nanomedicine based on natural products in preclinical models of various diseases. In this review, we summarized the achievements of nanomaterials in improving the efficacy of natural products, introduced the research progress in several key fields of natural product-based nanomedicine in medical application, and discussed the challenges and prospects of clinical transformation of nanomedicine.

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Matteo Sobrero ◽  
Fabrizio Montecucco ◽  
Federico Carbone

Venous thromboembolism (VTE) represents the third most frequent cause of acute cardiovascular syndrome. Among VTE, acute pulmonary embolism (APE) is the most life-threatening complication. Due to the low specificity of symptoms clinical diagnosis of APE may be sometimes very difficult. Accordingly, the latest European guidelines only suggest clinical prediction tests for diagnosis of APE, eventually associated with D-dimer, a biomarker burdened by a very low specificity. A growing body of evidence is highlighting the role of miRNAs in hemostasis and thrombosis. Due to their partial inheritance and susceptibility to the environmental factors, miRNAs are increasingly described as active modifiers of the classical Virchow’s triad. Clinical evidence on deep venous thrombosis reported specific miRNA signatures associated to thrombosis development, organization, recanalization, and resolution. Conversely, data of miRNA profiling as a predictor/diagnostic marker of APE are still preliminary. Here, we have summarized clinical evidence on the potential role of miRNA in diagnosis of APE. Despite some intriguing insight, miRNA assay is still far from any potential clinical application. Especially, the small sample size of cohorts likely represents the major limitation of published studies, so that extensive analysis of miRNA profiles with a machine learning approach are warranted in the next future. In addition, the cost-benefit ratio of miRNA assay still has a negative impact on their clinical application and routinely test.

2022 ◽  
Vol 23 (2) ◽  
pp. 715
Ji Yeon Kim ◽  
Saeyoung Park ◽  
Se-Young Oh ◽  
Yu Hwa Nam ◽  
Young Min Choi ◽  

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

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