1.Research Progress and Forensic Application of Human Vascular Finite Element Modeling and Biomechanics.
Yong ZENG ; Dong-Hua ZOU ; Ying FAN ; Qing XU ; Lu-Yang TAO ; Yi-Jiu CHEN ; Zheng-Dong LI
Journal of Forensic Medicine 2023;39(5):471-477
The finite element method (FEM) is a mathematical method for obtaining approximate solutions to a wide variety of engineering problems. With the development of computer technology, it is gradually applied to the study of biomechanics of human body. The application of the combination of FEM and biomechanics in exploring the relationship between vascular injury and disease, and pathological mechanisms will be a technological innovation for traditional forensic medicine. This paper reviews the construction and development of human vascular FEM modeling, and its research progress on the vascular biomechanics. This paper also looks to the application prospects of FEM modeling in forensic pathology.
Humans
;
Computer Simulation
;
Models, Biological
;
Biomechanical Phenomena
;
Finite Element Analysis
;
Forensic Medicine
2.Quantitative proteomics reveal the potential biological functions of the deubiquitinating enzyme Ubp14 in Saccharomyces cerevisiae.
Zhaodi LI ; Qiuyan LAN ; Yanchang LI ; Cong XU ; Lei CHANG ; Ping XU ; Changzhu DUAN
Chinese Journal of Biotechnology 2022;38(10):3901-3913
Ubiquitination is one of the reversible protein post-translational modifications, in which ubiquitin molecules bind to the target protein in a cascade reaction of ubiquitin activating enzymes, ubiquitin conjugating enzymes, and ubiquitin ligases. The deubiquitinating enzymes (DUBs) remove ubiquitin residues from the substrates, which play key roles in the formation of mature ubiquitin, the removal and trimming of ubiquitin chains, as well as the recycling of free ubiquitin chains. Ubp14, a member of the ubiquitin specific proteases family in Saccharomyces cerevisiae, is mainly responsible for the recycling of intracellular free ubiquitin chains. To investigate its global biological function, a ubp14∆ mutant was constructed by homologous recombination technique. The growth rate of ubp14∆ mutant was lower than that of the wild-type (WT) strain. Using stable isotope labeling by amino acids in cell culture (SILAC) combined with deep coverage proteomics analysis, the differentially expressed proteins of ubp14∆ mutant relative to the wild-type strain were systematically analyzed. A total of 3 685 proteins were identified in this study, and 109 differentially expressed proteins were filtered out by statistical analysis. Gene ontology analysis found that differentially expressed proteins caused by Ubp14 loss were mainly involved in amino acid metabolism, REDOX, heat shock stress and etc, which shed light on the broad biological function of this DUB. This study provides highly reliable proteomic data for further exploring the biological functions of the deubiquitination enzyme Ubp14, and further understanding the relationship between the free ubiquitin homeostasis and biological process regulation.
Saccharomyces cerevisiae/metabolism*
;
Proteomics
;
Endopeptidases/metabolism*
;
Ubiquitin/metabolism*
;
Ubiquitination
;
Proteins/metabolism*
;
Deubiquitinating Enzymes/metabolism*
;
Biological Phenomena
3.HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression.
Cancan LUO ; Tiantian YU ; Ken H YOUNG ; Li YU
Journal of Zhejiang University. Science. B 2022;23(8):666-681
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin's lymphoma. A total of 10%‒15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2 (BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL; however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase (HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.
Aminopyridines
;
Animals
;
Benzamides
;
Biological Phenomena
;
Bridged Bicyclo Compounds, Heterocyclic
;
Down-Regulation
;
Histone Deacetylase Inhibitors/therapeutic use*
;
Humans
;
Lymphoma, Large B-Cell, Diffuse/pathology*
;
Mice
;
Neoplasm Recurrence, Local
;
Proto-Oncogene Proteins c-bcl-2/metabolism*
;
Proto-Oncogene Proteins c-myc/therapeutic use*
;
Sulfonamides
;
Tumor Suppressor Protein p53/metabolism*
4.Effects of different alveolar bone finite element models on the biomechanical responses of periodontal ligament.
Jianlei WU ; Yunfeng LIU ; Boxiu LI ; Dongcai WANG ; Xingtao DONG ; Jiali ZHOU
Journal of Biomedical Engineering 2021;38(2):295-302
In the study of oral orthodontics, the dental tissue models play an important role in finite element analysis results. Currently, the commonly used alveolar bone models mainly have two kinds: the uniform and the non-uniform models. The material of the uniform model was defined with the whole alveolar bone, and each mesh element has a uniform mechanical property. While the material of the elements in non-uniform model was differently determined by the Hounsfield unit (HU) value of computed tomography (CT) images where the element was located. To investigate the effects of different alveolar bone models on the biomechanical responses of periodontal ligament (PDL), a clinical patient was chosen as the research object, his mandibular canine, PDL and two kinds of alveolar bone models were constructed, and intrusive force of 1 N and moment of 2 Nmm were exerted on the canine along its root direction, respectively, which were used to analyze the hydrostatic stress and the maximal logarithmic principal strain of PDL under different loads. Research results indicated that the mechanical responses of PDL had been affected by alveolar bone models, no matter the canine translation or rotation. Compared to the uniform model, if the alveolar bone was defined as the non-uniform model, the maximal stress and strain of PDL were decreased by 13.13% and 35.57%, respectively, when the canine translation along its root direction; while the maximal stress and strain of PDL were decreased by 19.55% and 35.64%, respectively, when the canine rotation along its root direction. The uniform alveolar bone model will induce orthodontists to choose a smaller orthodontic force. The non-uniform alveolar bone model can better reflect the differences of bone characteristics in the real alveolar bone, and more conducive to obtain accurate analysis results.
Biomechanical Phenomena
;
Computer Simulation
;
Finite Element Analysis
;
Humans
;
Models, Biological
;
Periodontal Ligament
;
Stress, Mechanical
;
Tooth Movement Techniques
5.Research progress on the biological regulatory function of lysophosphatidic acid in bone tissue cells.
Xiang-Nan WU ; Yuan-Yuan MA ; Zhi-Chao HAO ; Hang WANG
West China Journal of Stomatology 2020;38(3):324-329
Lysophosphatidic acid (LPA) is a small phospholipid that is present in all eukaryotic tissues and blood plasma. As an extracellular signaling molecule, LPA mediates many cellular functions by binding to six known G protein-coupled receptors and activating their downstream signaling pathways. These functions indicate that LPA may play important roles in many biological processes that include organismal development, wound healing, and carcinogenesis. Recently, many studies have found that LPA has various biological effects in different kinds of bone cells. These findings suggest that LPA is a potent regulator of bone development and remodeling and holds promising application potential in bone tissue engineering. Here, we review the recent progress on the biological regulatory function of LPA in bone tissue cells.
Biological Phenomena
;
Bone and Bones
;
Lysophospholipids
;
Receptors, Lysophosphatidic Acid
6.Muscle activity during low-speed rear impact.
O'Driscoll OLIVE ; Magnusson MARIANNE ; Pope Malcolm HENRY ; Chow Daniel HUNG-KAY
Chinese Journal of Traumatology 2019;22(2):80-84
PURPOSE:
Whiplash associated disorders remain a major health problem in terms of impact on health care and on societal costs. Aetiology remains controversial including the old supposition that the cervical muscles do not play a significant role. This study examined the muscle activity from relevant muscles during rear-end impacts in an effort to gauge their influence on the aetiology of whiplash associated disorders.
METHODS:
Volunteers were subjected to a sub-injury level of rear impact. Surface electromyography (EMG) was used to record cervical muscle activity before, during and after impact. Muscle response time and EMG signal amplitude were analysed. Head, pelvis, and T1 acceleration data were recorded.
RESULTS:
The activities of the cervical muscles were found to be significant. The sternocleidomastoideus, trapezius and erector spinae were activated on average 59 ms, 73 ms and 84 ms after the impact stimulus, respectively, prior to peak head acceleration (113 ms).
CONCLUSION
The cervical muscles reacted prior to peak head acceleration, thus in time to influence whiplash biomechanics and possibly injury mechanisms. It is recommended therefore, that muscular influences be incorporated into the development of the new rear-impact crash test dummy in order to make the dummy as biofidelic as possible.
Acceleration
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Accidents, Traffic
;
Biomechanical Phenomena
;
Electromyography
;
Head
;
physiopathology
;
Humans
;
Models, Biological
;
Neck Muscles
;
physiopathology
;
Reaction Time
;
Whiplash Injuries
;
etiology
;
physiopathology
7.Human ex vivo and in vitro disease models to study food allergy
Lisa HUNG ; Helena OBERNOLTE ; Katherina SEWALD ; Thomas EIWEGGER
Asia Pacific Allergy 2019;9(1):e4-
Food allergy is a growing global public health concern. As treatment strategies are currently limited to allergen avoidance and emergency interventions, there is an increasing demand for appropriate models of food allergy for the development of new therapeutics. Many models of food allergy rely heavily on the use of animals, and while useful, many are unable to accurately reflect the human system. In order to bridge the gap between in vivo animal models and clinical trials with human patients, human models of food allergy are of great importance. This review will summarize the commonly used human ex vivo and in vitro models of food allergy and highlight their advantages and limitations regarding how accurately they represent the human in vivo system. We will cover biopsy-based systems, precision cut organ slices, and coculture systems as well as organoids and organ-on-a-chip. The availability of appropriate experimental models will allow us to move forward in the field of food allergy research, to search for effective treatment options and to further explore the cause and progression of this disorder.
Allergens
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Anaphylaxis
;
Animals
;
Biological Phenomena
;
Coculture Techniques
;
Emergencies
;
Food Hypersensitivity
;
Humans
;
In Vitro Techniques
;
Models, Animal
;
Models, Theoretical
;
Organoids
;
Public Health
8.Progress in finite element analysis of meniscus.
Bo JIN ; Yun-Gen HU ; Lei HAN
China Journal of Orthopaedics and Traumatology 2019;32(5):485-488
The meniscus biomechanics is one of the hottest areas in medical research. Finite element analysis(FEA) provides a new method for biomechanical studies. Using the FEA, the stress force and strain distribution characteristics of the normal meniscus can be analysed by establishing the finite element model of the meniscus and utilizing finite element softwares. In addition, the finite simulation of the meniscus tears, meniscectomy, and knee tissue injury can assess the changes of meniscus biomechanical properties. These research results provide theoretical basis of biomechanics to prevent and treat knee joint injuries. However, the finite element analysis method has its limitations, future research will be aimed at establishing high quality finite element models, making the models offer more authentic simulations of the meniscus anatomy, and ensuring the FEA could be applied to research a variety of knee injuries.
Biomechanical Phenomena
;
Finite Element Analysis
;
Humans
;
Knee Injuries
;
Menisci, Tibial
;
Meniscus
;
Models, Biological
;
Tibial Meniscus Injuries
9.miR-148b-3p, miR-190b, and miR-429 Regulate Cell Progression and Act as Potential Biomarkers for Breast Cancer
Wenzhu DAI ; Jixiang HE ; Ling ZHENG ; Mingyu BI ; Fei HU ; Minju CHEN ; Heng NIU ; Jingyu YANG ; Ying LUO ; Wenru TANG ; Miaomiao SHENG
Journal of Breast Cancer 2019;22(2):219-236
PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.
Apoptosis
;
Biological Phenomena
;
Biological Processes
;
Biomarkers
;
Breast Neoplasms
;
Breast
;
Diagnosis
;
Female
;
Gene Ontology
;
Genome
;
Humans
;
In Vitro Techniques
;
Kaplan-Meier Estimate
;
MicroRNAs
;
ROC Curve
;
Sensitivity and Specificity
10.Zn metabolism of monogastric species and consequences for the definition of feeding requirements and the estimation of feed Zn bioavailability.
Daniel BRUGGER ; Wilhelm M WINDISCH
Journal of Zhejiang University. Science. B 2019;20(8):617-627
A major goal of mineral nutrition research is to provide information of feed zinc (Zn) utilization efficiency and gross Zn requirements as affected by changing rearing conditions. This can be achieved only by applying precise experimental models that acknowledge the basic principles of Zn metabolism. This review article summarizes the most important aspects of Zn homeostasis in monogastric species, including molecular aspects of Zn acquisition and excretion. Special emphasis is given to the role of the skeleton as well as the exocrine pancreas for animal Zn metabolism. Finally, we discuss consequences arising from these physiological principles for the experimental design of trials which aim to address questions of Zn requirements and bioavailability.
Animal Feed
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Animal Nutritional Physiological Phenomena
;
Animals
;
Biological Availability
;
Diet
;
Genotype
;
Homeostasis
;
Humans
;
Minerals/metabolism*
;
Pancreas, Exocrine/metabolism*
;
Trace Elements
;
Zinc/metabolism*

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