Publications by authors named "Tihomir Georgiev"

Colorectal cancer is a major cause of morbidity and mortality in the world. Approximately, one of three diagnosed colorectal cancers is a rectal cancer. Recent developments in the field of rectal surgery have promoted the use of surgical robots, which are of great need when surgeons face anatomical difficulties, such as a narrowed male pelvis, bulky tumor, or obese patients.

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  • NFAT5, an osmosensitive transcription factor, plays a significant role in regulating salt and water balance in the cornea, impacting transparency and susceptibility to blindness.
  • In healthy corneas, NFAT5 is primarily found in fibroblasts, but its expression increases in corneal macrophages after perforating injury, contributing to fluid balance.
  • The study reveals that NFAT5 normally suppresses corneal edema resorption, suggesting that targeting this factor could offer new treatment options for corneal edema and related blindness.
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Aims: Pathological neovascularisation of the host bed and the transplant itself is the main risk factor for graft rejection after corneal transplantation. This study aims to prevent this process by preincubation of the corneal donor tissue ex vivo with an antivascular endothelial growth factor (VEGF) cytokine trap blocking additional postsurgical hemangiogenesis and lymphangiogenesis to promote high-risk graft survival.

Methods: The donor tissue was preincubated with a VEGFR1R2 cytokine trap for 24 hours prior to murine high-risk corneal transplantation (human IgG Fc was used as the control).

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Human induced pluripotent stem cells (hiPSCs) can serve as an unlimited source to rebuild organotypic tissues . Successful engineering of functional cell types and complex organ structures outside the human body requires knowledge of the chemical, temporal, and spatial microenvironment of their counterparts. Despite an increased understanding of mouse and human embryonic development, screening approaches are still required for the optimization of stem cell differentiation protocols to gain more functional mature cell types.

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Creating in vitro models of diseases of the pancreatic ductal compartment requires a comprehensive understanding of the developmental trajectories of pancreas-specific cell types. Here we report the single-cell characterization of the differentiation of pancreatic duct-like organoids (PDLOs) from human induced pluripotent stem cells (hiPSCs) on a microwell chip that facilitates the uniform aggregation and chemical induction of hiPSC-derived pancreatic progenitors. Using time-resolved single-cell transcriptional profiling and immunofluorescence imaging of the forming PDLOs, we identified differentiation routes from pancreatic progenitors through ductal intermediates to two types of mature duct-like cells and a few non-ductal cell types.

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We here present a method that combines genetic code expansion with CRISPR/Cas9 genome engineering to label endogenously expressed proteins with high spatiotemporal resolution. The method exploits the use of an orthogonal tRNA/tRNA synthetase pair in conjugation with noncanonical amino acids to create stop codon read through events. To demonstrate the functionality of the method, we pulse labeled endogenous β-actin and tumor protein p53 with a minimally invasive HA tag at their C-termini.

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  • Second harmonic generation (SHG) microscopy is an advanced imaging technique that allows researchers to study proteins like myosin and collagen without external labels in living or extracted tissues.
  • The development of polarization resolved SHG microscopy enhances this technique by providing additional details about different molecular states.
  • This study introduces two methods using linear polarized light to capture myosin's molecular dynamics within mammalian muscle cells at a high speed of 1 millisecond, paving the way for new discoveries in molecular behavior in real-time conditions.
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Nuclear Ca(2+) is important for the regulation of several nuclear processes such as gene expression. Localized Ca(2+) signals (LCSs) in skeletal muscle fibers of mice have been mainly studied as Ca(2+) release events from the sarcoplasmic reticulum. Their location with regard to cell nuclei has not been investigated.

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Ca(2+) regulates several important intracellular processes. We combined second harmonic generation (SHG) and two photon excited fluorescence microscopy (2PFM) to simultaneously record the SHG signal of the myosin filaments and localized elementary Ca(2+) release signals (LCSs). We found LCSs associated with Y-shaped structures of the myosin filament pattern (YMs), so called verniers, in intact mouse skeletal muscle fibers under hypertonic treatment.

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Insulin stimulates glucose uptake in adult skeletal muscle by promoting the translocation of GLUT4 glucose transporters to the transverse tubule (T-tubule) membranes, which have particularly high cholesterol levels. We investigated whether T-tubule cholesterol content affects insulin-induced glucose transport. Feeding mice a high-fat diet (HFD) for 8 wk increased by 30% the T-tubule cholesterol content of triad-enriched vesicular fractions from muscle tissue compared with triads from control mice.

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Gastric necrosis is a rare condition because of the rich blood supply and the extensive submucosal vascular network of the stomach. "Gas-bloat" syndrome is a well known Nissen fundoplication postoperative complication. It may cause severe gastric dilatation, but very rarely an ischemic compromise of the organ.

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Extracellular nucleotides such as adenosine triphosphate (ATP) play a role in biliary epithelial cell function. Since nucleotide receptors are potential targets for various diseases related to epithelial cell dysfunction and cancer, the purpose of this study was to investigate the expression and to functionally characterize the nucleotide receptor subtypes in biliary epithelial cancer cells (Mz-Cha-1). Extracellular ATP dose-dependently resulted in an intracellular Ca(2+) increase (mean effective concentration (EC(50)) 40 μM).

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