ABSTRACT
Tissue has a complex three-dimensional (3D) dynamic structure, and is affected by various forms of forces. Cells sense mechanical forces from extracellular matrix (ECM), and the mechanical micro-environment constructed by ECM regulates different biological functions of cells. To prepare biomaterials which can simulate the ECM mechanical micro-environment of tissues is one of the research hot spots and difficulties in biomechanical field. Different physical and chemical properties of biomaterials endow materials with specific mechanical properties, which further affect the behavior and function of cells. Based on the latest literature of biomechanics of materials in the year 2021, this study mainly focused on the role of novel mechanical biomaterials in regulating cell biological behavior and application in tissue engineering. The future development direction in the field of biomechanics of materials was also discussed.
ABSTRACT
BACKGROUND@#Immune checkpoint inhibitors (ICIs) such as antibodies against programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1), have shown remarkable efficacies in many subtypes of cancers. However, ICIs may also cause severe immune-related adverse events in the recipient patients. Recently, ICI-associated myocarditis have been reported in hundreds of patients worldwide, with a mortality rate of approximately 50% in these cases. This study aims to recapitulate the cardiotoxicity and explore the detoxicifying approaches to attenuate mortality caused by PD-1/PD-L1 inhibitors in healthy mice.@*METHODS@#Six to eight-week-old C57BL/6 mice were inoculated with anti-PD-1 antibody (12.5 μg/g every 5 days for 6 injections), anti-PD-L1 antibody (10 μg/g once a week for 6 weeks), anti-PD-L1 antibody (with the same dosage described above) in combination with levothyroxine (0.25 μg/g, intraperitoneally injected half an hour before anti-PD-L1 antibody injection), or isotype control immunoglobulin IgG (10 μg/g once a week for 6 weeks). The ejection function of the hearts was detected by echocardiography, body temperature and blood pressure were detected by Mouse MonitorTM and non-invassive blood pressure minotor, and serum free thyroxine concentration was detected by The enzyme linked immunosorbent assay (ELISA).@*RESULTS@#PD-L1 was expressed at different levels by the cardiomyocytes of the mice. The isotype control immunoglobulin and anti-PD-1 antibody did not cause death of the mice. The 12 mice receiving 3-6 injections of anti-PD-L1 antibody showed a significant increase in the heart-to-tibial ratio and cardiomyoctye degeneration, hyalinization and extravascular inflammatory cell infiltration. In addition, the serum thyroxine was mardedly decreased to 1/3 of that in the control group mice, and the blood pressure and body temperature were abnormally decreased in mice upon treatment with PD-L1 blockade. Eight of the 12 (66.7%) mice died from multiple intravenous injection of anti-PD-L1 antibody.Intraperitoneal injection of levothyroxine 30 min before the injection of anti-PD-L1 antibody significantly attenuated the mortality rate of the anti-PD-L1 antibody-treated mice.@*CONCLUSIONS@#The anti-PD-L1 antibody is cardiotoxic and lethal, and levothyroxine is able to rescue the mice from this immune checkpoint inhibitor-caused mortality.
ABSTRACT
An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Subject(s)
Adult , Animals , Humans , Mice , COVID-19 , Epithelial Cells , Lung , Pandemics , Peptidyl-Dipeptidase A , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Ubiquitin-Protein Ligases/geneticsABSTRACT
Objective To discuss the application about the TPDS educational reform of molecular biology in the medical students. Methods Choose 2009 and 2010 7-year program students (174 person) of clinical medicine as the research object, achieve to TPDS teaching; Control group ( 2010 basic medicine and general medicine students , 2011 basic medicine and pediatric medical students (394 person) carry out general teaching model. Taking the students test scores as the main teaching effect evaluation index, the questionnaire survey as the supplement. Statistical analysis was carried out using t test analysis method. Results Molecular biology of the experimental group students scores (94.39 ±4.34)are significantly higher than that of the control group (85.1 ±8.77), and P<0.05. The questionnaire showed that more than 80%students improved themselves in the areas of self-study ability, information collecting ability, problem-solving ability, and team cooperation abilityafter the course of study. Conclusion TPDS educational reform isoptional for the cultivating applied talents, intend to stimulate students' autonomous learning ability, inspire students to independent analysis and solve problems, improve students' unity cooperation spirit and model the humanistic spirit.