Folia Biologica最新文献

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid with promising anticancer potential. Anaemia is a frequent adverse effect of anticancer treatment caused in part by eryptosis and haemolysis. Thus, it is important to investigate the role of DHA in red blood cell (RBC) death. RBCs were treated with anticancer concentrations (10-100 μM) of DHA under different physiological conditions, and fluorescence-assisted cell sorting was employed to measure eryptotic markers. Cell membrane scrambling was detected by annexin-V-FITC labelling, cytoplasmic Ca2+ by Fluo4/AM, cell size by forward scatter (FSC), and oxidative stress by H2DCFDA. Haemolytic markers were also assayed by photometric methods. DHA caused significant phospholipid scrambling with Ca2+ accumulation, loss of cellular volume, and oxidative stress. These changes were associated with dacrocyte formation, as revealed by electron microscopy. Moreover, DHA exhibited a dual effect on membrane integrity: it was haemolytic under isotonic conditions and anti-haemolytic in hypotonic environments. Importantly, inhibition of Rac1 GTPase activity with NSC23766 significantly reduced DHA-mediated haemolysis, as did co-administration of either sucrose or polyethylene glycol 8,000. Conversely, the presence of 125 mM KCl and urea without extracellular Ca2+ significantly exacerbated DHA toxicity. In conclusion, this is the first report that identifies key biochemical mechanisms underlying the cytotoxic effects of DHA in RBCs, promoting further development and validation of DHA in anticancer therapy.

We aimed to explore the development and cell communication of osteoblasts and osteoclasts with aneuploidy variation in giant cell tumour of bone (GCTB). We predicted the diploid and aneuploid cells in tissue samples using the CopyKAT package. The Monocle2 package was used to analyse differentiation trajectories of aneuploid cells. We used the CellChat package to observe the signalling pathways and ligand-receptor pairs for the two interaction types, "Cell-Cell Contact" and "Secreted Signalling", respectively. A total of 9,117 cells were obtained including eight cell types. Most aneuploid cells were osteoblasts. As the cell differentiation trajectory matured, we found that aneuploid osteoblasts first increased the inflammatory response activity and then enhanced the ability to activate T cells, whereas osteoclasts gradually enhanced the cellular energy metabolism, cell adhesion, cell proliferation and immune response; the activated biological functions were gradually weakened. The analysis by CellChat indicated that CTLA4 or TIGIT might act as important immune checkpoint genes to attenuate the inhibitory effect of aneuploid osteoclasts on NK/T cells, thereby enhancing the activity of NK/T cells. Our study found that both osteoblasts and osteoclasts might be involved in the development of GCTB, which may provide a new direction for the treatment of GCTB.

The study aimed to investigate changes in the eye axial length in juvenile guinea pigs and the expression of scleral specificity protein 1 (Sp1) and collagen type I (Col-I) under different light environments with varying spectral composition. The animals were randomly divided into five groups: natural light (N), LED light with a low colour temperature (L), E light (E), Fulia light (F), and Gulia light (G). Axial lengths were measured every two weeks, and the expression of Sp1 and Col-I in the sclera was assessed by immunohistochemistry, Western blot and RT-qPCR. After 4, 6, 8, 10, and 12 weeks of light exposure, the L and G groups showed considerably longer axial lengths than the N group, with the L group exhibiting significantly longer axial lengths compared with the E and F groups. The protein and mRNA expression levels of Sp1 and Col-I, ranked from highest to lowest, were as follows: N, E, F, G, and L. The expression of Sp1 and Col-I was positively correlated, but both were negatively correlated with the length of the eye axis. The E group demonstrated higher Sp1 and Col-I expression than the other artificial light groups. Artificial light with a continuous, full spectrum lacking peaks and valleys can inhibit the elongation of the eye axis in juvenile guinea pigs and has a protective effect against myopia. There may be a certain relationship between Sp1 and Col-I, and the transforming growth factor-β1-Sp1-Col-I signalling pathway may play a crucial role in myopic scleral extracellular matrix remodelling.

Recent studies have highlighted the significant role of 5-hydroxymethylcytosine (5hmC) in carcinogenesis. However, the specific role of 5hmC in osteosarcoma (OS) remains largely unexplored. The-re-fore, this study aimed to investigate the function of 5hmC and TET3 in OS. In this study, we found a decreased total level of 5hmC in OS tissues. The expression of the TET3 protein was also decreased in OS. Importantly, the decreased levels of TET3 were associated with a decreased disease-free survival (DFS) rate in patients. To investigate the role of TET3 and 5hmC in OS, we manipulated the levels of TET3 in MG-63 cells. Silencing TET3 in these cells resulted in a twofold increase in proliferation. Additio-nally, the level of 5hmC decreased in these cells. Con-versely, over-expression of TET3 in MG-63 cells led to the expected inhibition of proliferation and invasion, accompanied by an increase in 5hmC levels. In conclusion, both 5hmC and TET3 protein levels were decreased in OS. Additionally, the over-expression of TET3 inhibited the proliferation of MG-63 cells, while the suppression of TET3 had the opposite effect. These findings suggest that decreased levels of 5hmC and TET3 may serve as potential markers for OS.

T-cell lymphomas (TCLs) are a rare and heterogeneous subgroup of non-Hodgkin lymphomas (NHLs), forming only 10 % of all NHL cases in Western countries. Resulting from their low incidence and heterogeneity, the current treatment outcome is generally unfavorable, with limited availability of novel therapeutic approaches. Therefore, the recent success of immune checkpoint inhibitors (ICIs) in cancer treatment motivated their clinical investigation in TCLs as well. Multiple studies showed promising results; however, cases of TCL hyperprogression following ICI treatment and secondary T-cell-derived malignancies associated with ICI treatment of other cancer types were also reported. In our review, we first briefly summarize classification of T-cell-derived malignancies, general anti-tumor immune response, immune evasion, and immune checkpoint signaling. Next, we provide an overview of immune checkpoint molecule deregulation in TCLs, summarize available studies of ICIs in TCLs, and review the above-mentioned safety concerns associa-ted with ICI treatment and T-cell-derived malignancies. Despite initial promising results, further studies are necessary to define the most suitable clinical applications and ICI therapeutic combinations with other novel treatment approaches within TCL treatment. ICIs, and their combinations, might hopefully bring the long awaited improvement for the treatment of T-cell-derived malignancies.

Coronary heart disease (CHD) is one of the most commonly seen cardiovascular conditions across the globe. Junctional cadherin 5 associated (JCAD) protein is found in the intercellular junctions of endothelial cells and linked to cardiovascular diseases. Nonetheless, the influence of JCAD on cardiomyocyte injury caused by CHD is unclear. A model of H2O2-induced H9c2 cell injury was constructed, and JCAD mRNA and protein levels were assessed by qRT-PCR and Western blot. The impacts of JCAD on the proliferation or apoptosis of H9c2 cells were explored by CCK-8 assay, Western blot and TUNEL staining. The effect of JCAD on the inflammatory response and vascular endothelial function of H9c2 cells was detected using ELISA kits. The levels of Wnt/β-catenin pathway-related proteins were assessed by Western blot. H2O2 treatment led to a rise in the levels of JCAD in H9c2 cells. Over-expression of JCAD promoted H2O2-induced cellular injury, leading to notably elevated contents of inflammatory factors, along with vascular endothelial dysfunction. In contrast to over-expression of JCAD, silencing of JCAD attenuated H2O2-induced cellular injury and inhibited apoptosis, inflammatory response and vascular endothelial dysfunction. Notably, JCAD could regulate the Wnt/β-catenin pathway, while DKK-1, Wnt/β-catenin pathway antagonist, counteracted the enhancing impact of JCAD over-expression on H2O2-induced H9c2 cell injury, further confirming that JCAD acts by regulating the Wnt/β-catenin pathway. In summary, over-expression of JCAD promoted H2O2-induced H9c2 cell injury by activating the Wnt/β-catenin pathway, while silencing of JCAD attenuated the H2O2-induced cell injury.

The maximal nuclear and cell body diameters of leukaemic agranular myeloblasts ("type 1" without azurophilic granules) were measured in bone marrow smears of patients suffering from acute myeloblastic leukaemia with minimal differentiation (M0 AML), without and with maturation (M1 and M2 AML), refractory anaemia with excess of myeloblasts (RAEB) and chronic phase of the myeloid leukaemia (CML) to provide more information on the cytoplasmic space estimate occupied by the nucleus. The largest size of the cytoplasmic space occupied by the nucleus in agranular myeloblasts was noted in M0 and M1 AML in comparison with M2 AML or RAEB, and especially with CML. Similarly, agranular myeloblasts with nuclear bodies occupying more than 90 per cent of the cell space were most frequent in M0 and M1 AML (> 50 %), less frequent in M2 and RAEB (~ 20 %) but very rare in CML (~ 5 %). According to electron microscopy, the very narrow cytoplasmic shell surrounding the nucleus in such myeloblasts did not possess any space for structural components characteristic of the granulocytic cell lineage. Thus, the basic morphology of these myeloblasts would correspond to morphological features of a less differentiated committed stem cell. It should be noted that such cells may be easily recognized in currently stained bone marrow or peripheral blood smears.

We aimed to detect the levels of T-lympho-cyte subsets and serum tumour markers in patients with non-small cell lung cancer (NSCLC) before chemotherapy, and to investigate the predictive value of their combined detection for the prognosis of NSCLC patients undergoing chemotherapy. The clinical data of 110 NSCLC patients treated with chemotherapy from January 2019 to February 2021 were analysed retrospectively. All patients were followed up for one year and divided into good prognosis group (surviving cases) and poor prognosis group (deceased cases). The predictive value of T-lymphocyte subsets combined with serum tumour markers for prognosis was analysed. The proportions of patients with tumour-node-metastasis stages III-IV, lymph node metastasis and poor differentiation were higher in the poor prognosis group than those in the good prognosis group (P < 0.05). Cox regression analysis revealed that high expression of CD4+ and CEA represented protective factors for poor prognosis of NSCLC patients undergoing chemotherapy [odds ratio (OR) < 1, P < 0.05], while high expression of CA125 was a risk factor (OR > 1, P < 0.05). All the areas under the receiver operating characteristic curves of single indicator detection (CD4+, CEA and CA125 levels) and their combined detection for prediction of the poor prognosis of NSCLC patients undergoing chemotherapy were > 0.70, which was highest in the case of combined detection. T-lymphocyte subsets and serum tumour markers are closely related to the prognosis of NSCLC patients undergoing chemotherapy, and their combined detection is of high predictive value.

Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1β/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1β/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1β/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1β/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.

Folia Biologica celebrates 70 years of continuous publication of research papers. The first volume was published in Prague in 1954 on behalf of the Institute of Molecular Genetics of the Czechoslovak Academy of Sciences (since 1990 the Academy of Sciences of the Czech Republic) under the subtitle "International edition of the journal Czechoslovakian Biology". Born in the dark days of the Cold War, Folia Biologica provided a thin but important link between the politically controlled science behind the Iron Curtain in the former Czechoslovakia and that of the free Western world. Initially, the journal focused on research papers in the fields of experimental medicine, immunology, virology, and experimental zoology. Since 1961 (Volume 7), Folia Biologica has been indexed in the Web of Science database. The first issue of Volume 7 was introduced by a review article by Peter Brian Medawar (1915-1987), winner of the 1960 Nobel Prize in Physiology or Medicine "for the discovery of acquired immunological tolerance", which is reprinted in this anniversary issue [1].In the late 1960s, during the political relaxation that culminated in the Prague Spring, cooperation with free Western science intensified and enabled a lively scientific dialogue between Czechoslovak and foreign biological scientists, namely immunologists, molecular biologists, and virologists, as illustrated by a series of original research articles from Folia Biologica by Georg Davis Snell (1903-1996) and Jean Dausset (1916-2009), who were awarded the Nobel Prize in Physiology and Medicine in 1980 "for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions", which led to the discovery of the major histocompatibility system (MHC) [2-7]. Another powerful example is an article in Folia Biologica by François Jacob (1920-2013), who was awarded the Nobel Prize in 1965 for discoveries that helped elucidate the transcriptional control of enzyme levels [8].Despite the years of political repression during the "normalization" period following the invasion of the Warsaw Pact troops into Czechoslovakia in 1968, the scientists and editors of Folia Biologica from the Academy of Sciences were able to maintain vibrant contacts with the world's leading scientists. In 1981, the journal changed its subtitle to "Journal of Cellular and Molecular Biology". In 1983, Folia Biologica published the article by Renato Dulbecco (1914-2012), who was awarded the Nobel Prize in 1975 for "discoveries concerning the interaction between tumor viruses and the genetic material of the cell"[9].With further orientation towards human molecular medicine, the journal entered the era after the Velvet Revolution in 1989, which represented the desired end of political control over national science. The interest of Czechoslovak and Czech scientists in publishing in Folia Biologica began to decline at the end of the 1990s, when they had at their disposal the full rang