In contrast to the livestock industry, sperm cryopreservation has not yet been successfully established in the poultry industry. This is because poultry sperm cells have a unique shape and membrane fluidity, differing from those of livestock sperm. The objective of this review is to discuss the cellular and molecular characteristics of rooster spermatozoa as a cause for their generally low freezability. Furthermore, here, we discuss novel developments in the field of semen extenders, cryoprotectants, and freezing processes, all with the purpose of increasing the potential of rooster sperm cryopreservation. Currently, it is very important to improve cryopreservation of rooster sperm on a global scale for the protection of gene resources due to the incidence of epidemics such as avian influenza.
- MeSH
- drůbež MeSH
- kryoprezervace veterinární MeSH
- kryoprotektivní látky MeSH
- kur domácí MeSH
- motilita spermií MeSH
- sperma * MeSH
- spermie MeSH
- uchování spermatu * veterinární MeSH
- zmrazování MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Triple negative breast cancer (TNBC) is a particularly aggressive and difficult-to-treat subtype of breast cancer that requires the development of novel therapeutic strategies. To pave the way for such developments it is essential to characterize new molecular players in TNBC. MicroRNAs (miRNAs) constitute interesting candidates in this regard as they are frequently deregulated in cancer and contribute to numerous aspects of carcinogenesis. METHODS AND RESULTS: Here, we discovered that miR-4649-5p, a miRNA yet uncharacterized in breast cancer, is associated with better overall survival of TNBC patients. Ectopic upregulation of the otherwise very low endogenous expression levels of miR-4646-5p significantly decreased the growth, proliferation, and migration of TNBC cells. By performing whole transcriptome analysis and physical interaction assays, we were able to identify the phosphatidylinositol phosphate kinase PIP5K1C as a direct target of miR-4649-5p. Downregulation or pharmacologic inhibition of PIP5K1C phenocopied the growth-reducing effects of miR-4649-5p. PIP5K1C is known to play an important role in migration and cell adhesion, and we could furthermore confirm its impact on downstream PI3K/AKT signaling. Combinations of miR-4649-5p upregulation and PIP5K1C or AKT inhibition, using the pharmacologic inhibitors UNC3230 and capivasertib, respectively, showed additive growth-reducing effects in TNBC cells. CONCLUSION: In summary, miR-4649-5p exerts broad tumor-suppressive effects in TNBC and shows potential for combined therapeutic approaches targeting the PIP5K1C/PI3K/AKT signaling axis.
- MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- pohyb buněk genetika MeSH
- proliferace buněk genetika MeSH
- protoonkogenní proteiny c-akt genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- triple-negativní karcinom prsu * farmakoterapie genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The classical hypothesis proposes that the lack of recombination on sex chromosomes arises due to selection for linkage between a sex-determining locus and sexually antagonistic loci, primarily facilitated by inversions. However, cessation of recombination on sex chromosomes could be attributed also to neutral processes, connected with other chromosome rearrangements or can reflect sex-specific recombination patterns existing already before sex chromosome differentiation. Three Coleonyx gecko species share a complex X1X1X2X2/X1X2Y system of sex chromosomes evolved via a fusion of the Y chromosome with an autosome. We analyzed synaptonemal complexes and sequenced flow-sorted sex chromosomes to investigate the effect of chromosomal rearrangement on recombination and differentiation of these sex chromosomes. The gecko sex chromosomes evolved from syntenic regions that were also co-opted also for sex chromosomes in other reptiles. We showed that in male geckos, recombination is less prevalent in the proximal regions of chromosomes and is even further drastically reduced around the centromere of the neo-Y chromosome. We highlight that pre-existing recombination patterns and Robertsonian fusions can be responsible for the cessation of recombination on sex chromosomes and that such processes can be largely neutral.
Ropeginterferon alfa-2b, nejnovější přípravek ze skupiny pegylovaných forem interferonu, prokázal jako jediný z dostupných léčivých přípravků schopnost dosáhnout nejen hematologické, ale i molekulární odpovědi u vysokého procenta pacientů s pravou polycytemií. V randomizovaných multicentrických studiích PROUD-PV a CONTINUATION-PV byla prokázána dlouhodobá superiorita tohoto přípravku v účinnosti, ale i bezpečnosti ve srovnání s hydroxyureou. Na základě těchto předností byla terapie ropeginterferonem alfa-2b zařazena do první linie terapie pacientů s pravou polycytemií nízkého rizika i podle nejnovějších doporučení European Leukemia Net z roku 2021.
Ropeginterferon alfa-2b, the newest form of pegylated interferon, evinced as the only one with potential to achieve hematological and molecular response in substantial proportion of patients with polycythaemia vera. Multicentric randomized studies PROUD-PV and CONTINUATION-PV have shown its long-term superiority in the efficacy and safety when comparing with hydroxyurea. Based on these benefits the newest 2021 European Leukemia Net guidelines recommend ropeginterferon alfa-2b as first line therapy of patients with low-risk polycythemia vera.
- Klíčová slova
- studie PROUD‐PV, studie CONTINUATION‐PV, Ropeg-IFN,
- MeSH
- agregace buněk genetika účinky léků MeSH
- hematologické testy MeSH
- interferon alfa-2 škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- mutace MeSH
- myeloproliferativní poruchy MeSH
- polycythaemia vera * diagnóza komplikace terapie MeSH
- polyethylenglykoly terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
Most cancer-related deaths among patients with solid tumors are caused by metastases. Migrastatic strategies represent a unique therapeutic approach to prevent all forms of cancer cell migration and invasion. Because the migration machinery has been shown to promote metastatic dissemination, successful migrastatic therapy may reduce the need for high-dose cytotoxic therapies that are currently used to prevent the risk of metastatic dissemination. In this review we focus on anti-invasive and antimetastatic strategies that hold promise for the treatment of solid tumors. The best targets for migrastatic therapy would be those that are required by all forms of motility, such as ATP availability, mitochondrial metabolism, and cytoskeletal dynamics and cell contractility.
- MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- pohyb buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer's disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer's disease and in the neuronal migration process using the APP/PS1 Alzheimer's mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer's disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer's based on senolytic compounds or pro-neurogenic factors.
Hepatocellular carcinoma (HCC) is a global healthcare challenge, which affects more than 815,000 new cases every year. Activated hepatic stellate cells (aHSCs) remain the principal cells that drive HCC onset and growth. aHSCs suppress the anti-tumor immune response through interaction with different immune cells. They also increase the deposition of the extracellular matrix proteins, challenging the reversion of fibrosis and increasing HCC growth and metastasis. Therapy for HCC was reported to activate HSCs, which could explain the low efficacy of current treatments. Conversely, recent studies aimed at the deactivation of HSCs show that they have been able to inhibit HCC growth. In this review article, we discuss the role of aHSCs in HCC pathophysiology and therapy. Finally, we provide suggestions for the experimental implementation of HSCs in HCC therapies.
Adjuvant therapy and radiotherapy improves the survival of patients with metastatic and locally advanced gastric cancer (GC). However, the resistance to radiotherapy limits its clinical usage. Rhotekin 2 (RTKN2) functions as an oncogene and confers resistance to ultraviolet B-radiation and apoptosis- inducing agents. Here, the role of RTKN2 in radiosensitivity of GC cell lines was investigated. RTKN2 was found to be elevated in GC tissues and cells. A series of functional assays revealed that overexpression of RTKN2 induced GC cell proliferation, promoted GC cell migration and invasion, while inhibiting GC cell apoptosis. However, silence of RTKN2 promoted GC cell apoptosis, while repressing GC cell proliferation, invasion and migration. GC cells were exposed to irradiation, and data from cell survival and apoptotic assays showed that knock-down of RTKN2 enhanced radiosensitivity of GC through up-regulation of apoptosis and down-regulation of proliferation in irradiation-exposed GC cells. Moreover, the protein expression of β-catenin and c-Myc in GC cells was enhanced by RTKN2 over-expression, but reduced by RTKN2 silence. Interference of RTKN2 down-regulated nuclear β-catenin expression, while up-regulating cytoplasmic β-catenin in GC. In conclusion, RTKN2 contributed to cell growth and radioresistance in GC through activation of Wnt/β-catenin signalling.
- MeSH
- beta-katenin metabolismus MeSH
- intracelulární signální peptidy a proteiny metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory žaludku * genetika patologie radioterapie MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- regulace genové exprese u nádorů MeSH
- signální dráha Wnt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Non-small cell lung cancer (NSCLC) results in high mortality and has gained increasing attention. C-Phycocyanin (C-PC) has been identified as a potential therapeutic inhibitor for NSCLC, but its underlying mechanism remains obscure. The gene expression of the long noncoding RNA neighbour of BRCAI RNA 2 (NBR2) in NSCLC cells was evaluated by quantitative reverse transcription-PCR. The cell capacity for proliferation and migration was examined by EdU and wound-healing assays. Furthermore, the viability and apoptosis of cells was measured with CCK-8 and annexin V/PI, respectively. Next, the protein level of activation of adenosine monophosphate- activated protein kinase and the rapamycin kinase (mTOR) signalling pathway-associated molecules was evaluated by western blotting. H292 cells were pre-treated with C-PC or transfected with plasmids encoding NBR2 or the shNBR2 plasmid, to over-express or knock down NBR2 expression, respectively. NBR2 expression was robustly down-regulated in NSCLC cell lines compared with a normal cell line (BEAS-2B). NBR2 over-expression inhibited migration and promoted apoptosis of H292 cells. Treatment of H292 cells with C-PC enhanced NBR2 levels in a dose- and time-dependent manner. Downregulation of NBR2 in H292 cells inhibited the activity of C-PC on cell proliferation, viability and clone formation. Further mechanistic investigation showed that the down-regulation of NBR2 abolished the modulatory effects of C-PC on the AMPK/mTOR signalling pathway. In conclusion, C-PC inhibits H292 cell growth by enhancing the NBR2/AMPK signalling pathway.
- MeSH
- adenosinmonofosfát farmakologie terapeutické užití MeSH
- annexin A5 farmakologie terapeutické užití MeSH
- apoptóza MeSH
- fykokyanin metabolismus farmakologie terapeutické užití MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory plic * farmakoterapie genetika metabolismus MeSH
- nemalobuněčný karcinom plic * farmakoterapie genetika metabolismus MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- proteinkinasy aktivované AMP genetika metabolismus farmakologie MeSH
- RNA dlouhá nekódující * genetika MeSH
- sinkalid metabolismus farmakologie terapeutické užití MeSH
- sirolimus farmakologie terapeutické užití MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of the collective cell migration phenomenon and the involvement of various cell types during this process is needed. Here, an in vitro platform based on inverted-pyramidal microwells to follow and quantify the collective migration of hundreds of tumor cell clusters at once is developed. These results indicate that mesenchymal stromal cells (MSCs) or cancer-associated fibroblasts (CAFs) in the heterotypic tumor cell clusters may facilitate metastatic dissemination by transporting low-motile cancer cells in a Rac-dependent manner and that extracellular vesicles secreted by mesenchymal cells only play a minor role in this process. Furthermore, in vivo studies show that cancer cell spheroids containing MSCs or CAFs have faster spreading rates. These findings highlight the active role of co-traveling stromal cells in the collective migration of tumor cell clusters and may help in developing better-targeted therapies.
- MeSH
- buňky stromatu MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- nádorové buněčné linie MeSH
- nádory * patologie MeSH
- pohyb buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
