There is shortage of extensive clinicopathologic studies of cellular senescence because the most reliable senescence biomarker, the detection of Senescence-Associated-beta-galactosidase activity (SA-β-gal), is inapplicable in archival material and requires snap-frozen tissues. We validated the histochemical Sudan-Black-B (SBB) specific stain of lipofuscin, an aggregate of oxidized proteins, lipids and metals, known to accumulate in aged tissues, as an additional reliable approach to detect senescent cells independently of sample preparation. We analyzed cellular systems in which senescence was triggered by replicative exhaustion or stressful stimuli, conditional knock-in mice producing precancerous lesions exhibiting senescence, and human preneoplastic lesions known to contain senescent cells. In the above settings we demonstrated co-localization of lipofuscin and SA-β-gal in senescent cells in vitro and in vivo (cryo-preserved tissue), strongly supporting the candidacy of lipofuscin for a biomarker of cellular senescence. Furthermore, cryo-preserved tissues positive for SA-β-gal were formalin-fixed, paraffin-embedded, and stained with SBB. The corresponding SA-β-gal positive tissue areas stained specifically for lipofuscin by SBB, whereas tissues negative for SA-β-gal were lipofuscin negative, validating the sensitivity and specificity of the SBB staining to visualize senescent cells in archival material. The latter unique property of SBB could be exploited in research on widely available retrospective tissue material.
Lasko et al., 1991;Latif et al., 1992;Cunningham et al., 1993;Adamson et al., 1994). A number of oncogenic and tumoursuppressor gene functions have been demonstrated in squamous cell carcinoma of the head and neck (SCCHN) (Field et al., 1989(Field et al., , 1991Field, 1992) To date only two global analyses of the whole genome have been undertaken with the view to determine the fractional allele loss (FAL) of specific tumours and thus provide information concerning the 'genetic burden' of the disease during its progression as measured by clinicopathological parameters and survival data. This type of analysis has been undertaken in colorectal (Vogelstein et al., 1989) and bladder cancers (Knowles et al., 1994), and provides an indication of interacting genetic mechanisms in the development of these diseases. In addition, the results of such detailed allelotypes may aid the interpretation of carcinogenesis and the development of molecular progression models for specific tumours.We have undertaken a very comprehensive allelotype of SCCHN using 145 microsatellite markers in order to identify common regions of allelic imbalance and to analyse the interactions of these regions by calculating the fractional allele loss (FAL) in these tumours. Materias and methods Specimens
Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation of the epigenetic machinery. In the context of human malignant melanoma, a number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells. On such basis, ITCs could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies.
The coronavirus disease-2019 (coVid-19) pandemic, caused by the new coronavirus SarS-coV-2, has spread around the globe with unprecedented consequences for the health of millions of people. While the pandemic is still in progress, with new incidents being reported every day, the resilience of the global society is constantly being challenged. under these circumstances, the future seems uncertain. SarS-coV-2 coronavirus has spread panic among civilians and insecurity at all socio-political and economic levels, dramatically disrupting everyday life, global economy, international travel and trade. The disease has also been linked to the onset of depression in many individuals due to the extreme restriction measures that have been taken for the prevention of the rapid spreading of coVid-19. First, the socioeconomic , political and psychological implications of the coVid-19 pandemic were explored. Substantial evidence is provided for the consequences of the pandemic on all aspects of everyday life, while at the same time we unravel the role and the pursuits of national regimes during this unforeseen situation. The second goal of this review is related to the scientific aspect of the pandemic. Hence, we explain why SarS-coV-2 is not a so-called 'invisible enemy', and also attempt to give insight regarding the origin of the virus, in an effort to reject the conspiracy theories that have arisen during the pandemic. Finally, rational strategies were investigated for successful vaccine development. We are optimistic that this review will complement the knowledge of specialized scientists and inform non-specialized readers on basic scientific questions, and also on the social and economic implications of the coVid-19 pandemic. Contents 1. introduction 2. death and the solitude of the dead 3. Many questions arise from the words 'cost-profit' 4. The 'invisible enemy' from a scientific perspective 5. is SarS-coV-2 indeed invisible? 6. The right strategy for vaccine development 7. Treatments and vaccines 8. The 'competitive nature' of man and reality 9. The extreme rivalries among the powerful of the world may have an economic basis 10. There is irrefutable evidence that SarS-coV-2 is not only contagious but also highly related to social class 11. The conspiracy theories as an antidote to the scientific truth 12. Thoughts regarding international research on the viral origins 13. The lack of prevention strategies against the SarS-coV-2 pandemic 14. critical remarks 15. conclusions and thoughts for a better relationship between man and the environment
Fertilization is the fusion of the male and female gamete. The process involves the fusion of an oocyte with a sperm, creating a single diploid cell, the zygote, from which a new individual organism will develop. The elucidation of the molecular mechanisms of fertilization has fascinated researchers for many years. In this review, we focus on this intriguing process at the molecular level. Several molecules have been identified to play a key role in each step of this intriguing process (the sperm attraction from the oocyte, the sperm maturation, the sperm and oocyte fusion and the two gamete pronuclei fusion leading to the zygote). Understanding the molecular mechanisms of the cell-cell interactions will provide a better understanding of the causes of fertility issues due to fertilization defects.
Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin (DOX) and curcumin (CUR) was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug's aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumour efficacy of the drug loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted SCID mice and visualized with μCT imaging. Histological and TUNEL assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.
Since the outbreak of the coronavirus 2019 (COVID-19) pandemic, there has been widespread concern that social isolation, financial stress, depression, limited or variable access to health care services and other pandemic-related stressors may contribute to an increase in suicidal behaviors. In patients who have recovered from COVID-19, an increased risk of developing suicidal behaviors may be noted, while post-COVID syndrome comprises another potential risk factor contributing to increased suicidal behaviors. Despite the initial alarming predictions for an increase in suicide rates due to the COVID-19 pandemic, the majority of published studies to date suggest that experienced difficulties and distress do not inevitably translate into an increased number of suicide-related deaths, at least not in the short-term. Nevertheless, the long-term mental health effects of the COVID-19 pandemic have yet to be unfolded and are likely to remain for a long period of time. Suicide prevention and measures aiming at promoting well-being and mitigating the effects of COVID-19 on mental health, particularly among vulnerable groups, should thus be a priority for healthcare professionals and policymakers amidst the evolving COVID-19 pandemic. Contents 1. Introduction 2. Suicidal behaviors in the context of the COVID-19 pandemic 3. Conclusion
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