Nanomechanics of Blood Clot and Thrombus Formation

Mechanical properties have been extensively studied in pure elastic or viscous materials; however, most biomaterials possess both physical properties in a viscoelastic component. How the biomechanics of a fibrin clot is related to its composition and the microenvironment where it is formed is not yet fully understood. This review gives an outline of the building mechanisms for blood clot mechanical properties and how they relate to clot function. The formation of a blood clot in health conditions or the formation of a dangerous thrombus go beyond the mere polymerization of fibrinogen into a fibrin network. The complex composition and localization of in vivo fibrin clots demonstrate the interplay between fibrin and/or fibrinogen and blood cells. Studying these protein–cell interactions and clot mechanical properties may represent new methods for the evaluation of cardiovascular diseases (the leading cause of death worldwide), creating new possibilities for clinical diagnosis, prognosis, and therapy. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Can Serum Thymidine Kinase 1 Detect Small Invisible Malignant Tumours?

Objectives. Early detection of malignant tumour is a prerequisite for a successful treatment. Here we investigate if thymidine kinase 1 is more sensitive than imaging technology to discover small invisible malignant tumours.Material and Methods. The cellular concentration of TK1 was determined by a novel automatic chemiluminescence analyzer of magnetic particle immune sandwich minimum. The primary and secondary antibodies linked to the magnetic beads were chicken anti-human thymidine kinase 1 IgY-polyclonal antibodies (IgY pAb). The minimum number of cells able to be detected by the novel detection technology using an automatic chemiluminescence analyzer were determined based on the cellar TK1 concentration of low and high TK1 cell lines of known cell count.Results. The TK1 concentration of malignant cell was found to be 0.021 pg/cell. Assuming 200 pg of total protein/cell, TK1 corresponds to 0.01 % of the total protein/cell. The concentration of TK1 in human blood serum of malignant patients is in the range of 2-10 pmol/l (pM), corresponding to about 50 x106 growing cells in the body that release TK1 into 5 litre blood. The limit visibility by imaging of a tumour is about 1 mm in diameter, corresponding to about 109cells of a cell diameter of 1µm. Conclusion. TK1 is more sensitive than imaging.

Can Thymidine Kinase 1 Detect Small Invisible Malignant Tumours?

Objectives. Early detection of malignant tumour is a prerequisite for a successful treatment. Here we investigate if thymidine kinase 1 is more sensitive than imaging technology to discover small invisible malignant tumours.Material and Methods. The cellular concentration of TK1 was determined by an automatic chemiluminescence analyzer of magnetic particle immune sandwich minimum. The primary and secondary antibodies linked to the magnetic beads were chicken anti-human thymidine kinase 1 IgY-polyclonal antibodies (IgY). The minimum number of cells able to detect by the automatic chemiluminescence analyzer were determined based on the cellar TK1 concentration of low and high TK1 cell lines of known cell count.Results. The TK1 concentration of malignant cell was found to be 0.021 pg/cell. Assuming 200 pg of total protein/cell, TK1 corresponds to 0.01 % of the total protein/cell. The concentration of TK1 in human blood serum of malignant patients is in the range of 2-10 pmol/l (pM), corresponding to about 50 x106 growing cells that release TK1 into 5 litre blood. The limit visibility by imaging of a tumour is about 1 mm in diameter, corresponding to about 109cells of a cell diameter of 1µm. Conclusion. TK1 is more sensitive than imaging.

A Rare Case of Pseudotumoral Ureteric Tuberculosis Causing Forniceal Rupture

A 55-year-old woman, with no medical history, presented with acute right flank pain. She had no history of other urinary complaints. On physical examination, the patient was tachycardic (pulse rate: 100bpm) and tachypneic (respiratory rate: 24 breaths/min), blood pressure was11/6 and temperature was 37.4°. The abdominal examination showed severe tenderness in the right flank and the right iliac fossa. All blood reports were normal, including C-reactive protein, cell blood count and serum creatinine. Computed Tomography of the abdomen revealed a right hydronephrosis with delayed phase contrast leak and a retroperitoneal mass of 48x36mm of unknown nature, enhanced after contrast injection, which seemed to compress the right ureter causing the forniceal rupture. A double J ureteral stent was insterted into the right renal cavities with favorable evolution and immediate resolution of pain. Surgical management of the mass was scheduled one month later after the inflammatory phase and resorption of the urinoma. The patient underwent an exploratory laparotomy. Intraoperatively, a tissular retroperitoneal mass of 4 cm was discovered which invadedthe right proximal ureter as well asthe duodenum and the ileocecal pedicle (Figure 1). Resection of the tumor was performed as well as a segmental ureterectomy, right colectomy, and resection of a small portion of the duodenum. Both ureteric and colic anastomosis were then performed along with duodenal suture. The post operative course was uneventful.

Two 20-Residue-Long Peptides Derived from Plasmodium vivax Merozoite Surface Protein 10 EGF-Like Domains Are Involved in Binding to Human Reticulocytes

Plasmodium parasites’ invasion of their target cells is a complex, multi-step process involving many protein-protein interactions. Little is known about how complex the interaction with target cells is in Plasmodium vivax and few surface molecules related to reticulocytes’ adhesion have been described to date. Natural selection, functional and structural analysis were carried out on the previously described vaccine candidate P. vivax merozoite surface protein 10 (PvMSP10) for evaluating its role during initial contact with target cells. It has been shown here that the recombinant carboxyl terminal region (rPvMSP10-C) bound to adult human reticulocytes but not to normocytes, as validated by two different protein-cell interaction assays. Particularly interesting was the fact that two 20-residue-long regions (388DKEECRCRANYMPDDSVDYF407 and 415KDCSKENGNCDVNAECSIDK434) were able to inhibit rPvMSP10-C binding to reticulocytes and rosette formation using enriched target cells. These peptides were derived from PvMSP10 epidermal growth factor (EGF)-like domains (precisely, from a well-defined electrostatic zone) and consisted of regions having the potential of being B- or T-cell epitopes. These findings provide evidence, for the first time, about the fragments governing PvMSP10 binding to its target cells, thus highlighting the importance of studying them for inclusion in a P. vivax antimalarial vaccine.

CC Chemokine Ligand 17 Promoted Cell Metastasis via Tumor Necrosis Factorα/Nuclear Factor Kappa-B Signaling Pathway

Hepatocellular carcinoma (HCC) consist in a proinflammatory tumor environment that is characterized by the presence of many chemokines and cytokines. Expression of CCL17 associated with diagnoses and poor prognosis in different cancers. There are few investigations indicated the relationship between CCL17 and HCC. Thus, this study aims to investigate the role of CCL17 in HCC progression. qRT-PCR and Western Blot were performed to detect expression of CCL17 in HCC cell lines and normal hepatocyte. Elisa was used to determine TNFα, IL-6 and IL-1β. Wound-healing assay and Transwell assay were performed to assed cell metastasis. CCL17 signaling was examined utilizing Western Blot. Here, we showed that CCL17 levels markedly increased in HCC cell lines. At the same time, TNFα, IL-6 and IL-1 β were increased time-dependent after treating human recombinant CCL17 protein. Cell metastasis was significantly promoted by CCL17 while TNFa inhibitor (Lenalidomide) reversed the effects of CCL17. NF-κB signaling pathway was activated by CCL17 and TNFα inhibitor suppressed the effects of CCL17. In conclusion, CCL17 promoted cell metastasis via TNFα/NF-κB signaling pathway. CCL17 may be a potential biomarker for HCC progression.

Remifentanil Protects PC-12 Cells From OGD Damage by Up-Regulating miR-124

The purpose of the study was to clarify the function and mechanism of Remifentanil, in PC-12 cells stimulated by oxygen-glucose deprivation (OGD). An OGD environment was constructed to induce PC-12 cells, and Remifentanil (0-2.5 μM) was used to pre-treat cells; cell viability was determined by CCK-8 assay; cell apoptosis was tested via flow cytometry; knock down of miR-124 was achieved by constructing an miR-124 inhibitor and cell transfection; miR-124 expression and the transfection efficiency were tested via quantitative real-time PCR (RT-qPCR); Western blot was used to detect the expression of Bax/Bcl-2 / cleaved-caspase 3 / cleaved-caspase 9 apoptosis protein, as well as p62/LC3-I/LC3-II and JAK2/mTOR protein. Cell viability was not affected by the low concentration of Remifentanil, but was inhibited by the high concentration of Remifentanil. OGD induction reduced cell viability, enhanced apoptosis and autophagy, and activated the JAK2/mTOR pathway. The above processes were reversed by Remifentanil, alleviating the influences of OGD stimulation on PC-12 cells. Meanwhile, miR-124 was positively regulated by Remifentanil, and miR-124 silencing reversed the effects of Remifentanil on cell viability, apoptosis, autophagy and the JAK2/mTOR pathway. In conclusion, Remifentanil protected PC-12 cells from OGD damage, which was mediated by up-regulation of miR-124 and activation of the JAK2/mTOR pathway.