Breast cancer, as a heterogenous malign disease among the top five leading causes of cancer death worldwide, is defined as by far the most common malignancy in women. It contributes to 25% of all cancer-associated deaths after menopause. Breast cancer is categorized based on the expression levels of cell surface and intracellular steroid receptors [estrogen, progesterone receptors, and human epidermal growth factor receptor (HER2)], and the treatment approaches frequently include antiestrogen, aromatase inhibitors, and Herceptin. However, the management and prevention strategies due to adverse side effects stress the patients. The unsuccessful treatments cause to raise the drug levels, leading to excessive toxic effects on healthy cells, and the development of multidrug-resistance (MDR) in the tumor cells against chemotherapeutic agents. MDR initially causes the tumor cells to gain a metastatic character, and subsequently, the patients do not respond adequately to treatment. Endoplasmic reticulum (ER) stress is one of the most important mechanisms supporting MDR development. ER stress-mediated chemotherapeutic resistance is very common in aggressive tumors. The in vitro and in vivo experiments on breast tumors indicate that ER stress-activated protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)- activating transcription factor (ATF4) signal axis plays an important role in the survival of tumors and metastasis. Besides, ER stress-associated oncogenic microRNAs (miRNAs) induce chemoresistance in breast tumors. We aimed to have a look at the development of resistance mechanisms due to ER stress as well as the involvement of ER stress-associated miRNA regulation following the chemotherapeutic regimen in the human breast tumors. We also aimed to draw attention to potential molecular markers and therapeutic targets.
Plants have been used for the prevention and treatment of diseases since the early days of humankind and constitute the natural sources of today's modern medicine. Approximately one-quarter of approved drugs are derived from plants. Plant steroids are a group of biologically active secondary metabolites with a 5𝛼 and 5𝛽 gonane carbon skeleton. There is immense chemical diversity in plant steroids due to the side chains, oxidation status of the carbons in the tetracyclic core, and methyl groups. Plant steroids are classified into several groups based on their biological functions and structures, also on their mechanism of biosynthesis. All subtypes have been investigated for their anti-cancer, immunomodulatory, anti-inflammatory, and anti-viral properties. The novel coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), which carries an RNA genome. An intense effort has been made in terms of effective treatment strategies and vaccine development since it was declared a pandemic. Nucleoside analogs such as favipiravir and remdesivir are used to block RNA-dependent RNA polymerase enzymes. Other strategies including neuraminidase inhibitors, chloroquine, and hydroxychloroquine as immunomodulatory agents, stem cell and cytokine based therapies are being conducted. One part of the therapies against SARS-CoV-2 is focused on the spike (S) protein of the virus that binds to the host receptor, angiotensin-converting enzyme 2 (ACE2). It has been suggested that SARS-CoV-2 S protein has a free fatty acid-binding pocket, and according to molecular simulations, steroids are ligands that bind to this pocket. Therefore, this review summarizes the plant steroid biological actions as well as their anti-viral potential against SARS-CoV-2 infection.
Heavy metals have potentially detrimental impacts on the whole body or on certain organs. They may induce various sorts of severe disorders, including neuro-, nephro-, carcino-, terato-, and immunological. Humans are exposed to them by breathing, eating, and drinking. Especially, the water sources from which drinking water is derived can represent a route of transmission of heavy metals to the humans. Therefore, waterborne heavy metals even at trace level have become a concern all across the world, including Turkey. The objective of this study was to investigate the elemental concentrations of nine major heavy metals (B, Cr, Ni, Cu, As, Cd, Sb, Hg and Pb) in 125 water samples (25 samples of each of plastic-bottled, glass-bottled, natural mineral, tap and well water) from Istanbul, Turkey using ICP-MS method. Sample preparation and analytical procedure were conducted according to the methods of EPA-3005A and EPA-6020A. Descriptive statistics and associations between the elemental levels in the sampling groups were evaluated by one-way ANOVA using SPSS-19 statistical package programme (P-value<0.05). Our study demonstrated that analyses showed a large range in concentration for most of the elements. Overall, 91.2% of all the waters analyzed fell within the Guideline values recommended by the Ministry of Health in Turkey. However, 8.8% of the samples (7 natural mineral water, 2 tap water, 2 bottled-water and 1 well water) for B, and 0.8% of the samples (1 well water) for Ni were above the safe limits. Based on the order of elemental concentrations, plastic-bottled waters had B > Cu > As > Ni > Pb > Cr > Sb > Cd, glass-bottled waters had B > As > Cu > Ni > Cr > Sb > Pb > Cd, natural mineral waters had B > Cu > As > Ni > Cr > Sb > Hg > Pb > Cd, tap waters had B > Cu > As > Ni > Cr > Pb > Sb > Hg > Cd, and well waters had B > Cu > Ni > As > Cr > Pb > Hg > Sb > Cd. Statistically, there was a positive and significant correlation existing between Ni, Cd, Sb and Pb in the waters, which indicated towards their common source of origin. In conclusion, our study indicated that there was low-to-moderate heavy metal contamination in all the drinking- and well- water samples. There is no a severe health risk for the consumers living in Istanbul because Turkey does not have no other population large enough like Istanbul in which to study high exposures of heavy metals through the waters for human consumption and use.
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