Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators. Video Abstract.
The phenomenon of retinal vein pulsation is still not a deeply understood topic in retinal hemodynamics. In this paper, we present a novel hardware solution for recording retinal video sequences and physiological signals using synchronized acquisition, we apply the photoplethysmographic principle for the semi-automatic processing of retinal video sequences and we analyse the timing of the vein collapse within the cardiac cycle using of an electrocardiographic signal (ECG). We measured the left eyes of healthy subjects and determined the phases of vein collapse within the cardiac cycle using a principle of photoplethysmography and a semi-automatic image processing approach. We found that the time to vein collapse (Tvc) is between 60 ms and 220 ms after the R-wave of the ECG signal, which corresponds to 6% to 28% of the cardiac cycle. We found no correlation between Tvc and the duration of the cardiac cycle and only a weak correlation between Tvc and age (0.37, p = 0.20), and Tvc and systolic blood pressure (-0.33, p = 0.25). The Tvc values are comparable to those of previously published papers and can contribute to the studies that analyze vein pulsations.
- Publikační typ
- časopisecké články MeSH
In 2022, we celebrated 200 years since the birth of Johann Gregor Mendel. Although his contributions to science went unrecognized during his lifetime, Mendel not only described the principles of monogenic inheritance but also pioneered the modern way of doing science based on precise experimental data acquisition and evaluation. Novel statistical and algorithmic approaches are now at the center of scientific work, showing that work that is considered marginal in one era can become a mainstream research approach in the next era. The onset of data-driven science caused a shift from hypothesis-testing to hypothesis-generating approaches in science. Mendel is remembered here as a promoter of this approach, and the benefits of big data and statistical approaches are discussed.
- MeSH
- genetika * MeSH
- imaginace * MeSH
- lidé MeSH
- promotorové oblasti (genetika) MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Mitochondria generate energy and building blocks required for cellular growth and function. The notion that mitochondria are not involved in the cancer growth has been challenged in recent years together with the emerging idea of mitochondria as a promising therapeutic target for oncologic diseases. Pentamethinium salts, cyan dyes with positively charged nitrogen on the benzothiazole or indole part of the molecule, were originally designed as mitochondrial probes. In this study, we show that pentamethinium salts have a strong effect on mitochondria, suppressing cancer cell proliferation and migration. This is likely linked to the strong inhibitory effect of the salts on dihydroorotate dehydrogenase (DHODH)-dependent respiration that has a key role in the de novo pyrimidine synthesis pathway. We also show that pentamethinium salts cause oxidative stress, redistribution of mitochondria, and a decrease in mitochondria mass. In conclusion, pentamethinium salts present novel anti-cancer agents worthy of further studies.
- Publikační typ
- tisková chyba MeSH
Multispectral imaging is used in various applications including astronomy, industry and agriculture. In retinal imaging, the single-shot multispectral image stack is typically acquired and analyzed. This multispectral analysis can provide information on various structural or metabolic properties. This paper describes the multispectral improvement of a video-ophthalmoscope, which can acquire retinal video sequences of the optic nerve head and peripapillary area using various spectral light illumination. The description of the multispectral video imaging is provided and several applications are described. These applications include multispectral retinal photoplethysmography, visualization of spontaneous vein pulsation and multispectral RGB image generation.
Head and neck squamous cell carcinomas (HNSCC) belong among severe and highly complex malignant diseases showing a high level of heterogeneity and consequently also a variance in therapeutic response, regardless of clinical stage. Our study implies that the progression of HNSCC may be supported by cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) and the heterogeneity of this disease may lie in the level of cooperation between CAFs and epithelial cancer cells, as communication between CAFs and epithelial cancer cells seems to be a key factor for the sustained growth of the tumour mass. In this study, we investigated how CAFs derived from tumours of different mRNA subtypes influence the proliferation of cancer cells and their metabolic and biomechanical reprogramming. We also investigated the clinicopathological significance of the expression of these metabolism-related genes in tissue samples of HNSCC patients to identify a possible gene signature typical for HNSCC progression. We found that the right kind of cooperation between cancer cells and CAFs is needed for tumour growth and progression, and only specific mRNA subtypes can support the growth of primary cancer cells or metastases. Specifically, during coculture, cancer cell colony supporting effect and effect of CAFs on cell stiffness of cancer cells are driven by the mRNA subtype of the tumour from which the CAFs are derived. The degree of colony-forming support is reflected in cancer cell glycolysis levels and lactate shuttle-related transporters.
- Publikační typ
- časopisecké články MeSH
The main dose-limiting side effect of cisplatin is nephrotoxicity. The utilization of cisplatin is an issue of balancing tumour toxicity versus platinum-induced nephrotoxicity. In this study, we focused on intraorgan distribution of common essential trace elements zinc, copper, and iron in healthy mouse kidneys and distribution of platinum after cisplatin treatment. Renal distribution in 12 nontreated Nu-Nu mice (males) was assessed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Furthermore, 9 Nu-Nu mice were treated with cisplatin. The order of elements concentration in kidneys was as follows: Fe > Zn > Cu. All three metals showed the higher concentrations at the cortex and medulla (28.60, 3.35, and 93.83 μg/g for Zn, Cu, and Fe, respectively) and lower concentration at the pelvis and the urinary tract (20.20, 1.93, and 62.48 μg/g for Zn, Cu, and Fe, respectively). No statistically significant difference between cortex and medulla was observed for these elements. After platinum treatment, the concentration of platinum in kidneys was enhanced more than 60-times, p < 0.001. Platinum significantly showed the highest accumulation in cortex (2.11 μg/g) with a gradient distribution. Platinum was less accumulated in medulla and pelvis than in cortex, and the lowest accumulation occurred in the urinary tract (1.13 μg/g). Image processing has been successfully utilized to colocalize metal distribution using LA-ICP-MS and histological samples images.
- MeSH
- buňky PC-3 MeSH
- cisplatina škodlivé účinky farmakologie toxicita MeSH
- hmotnostní spektrometrie metody MeSH
- ledviny účinky léků metabolismus patologie MeSH
- lidé MeSH
- měď analýza MeSH
- myši nahé MeSH
- myši MeSH
- platina analýza MeSH
- spektrální analýza metody MeSH
- železo analýza MeSH
- zinek analýza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
