Atiprimod triggered apoptotic cell death via acting on PERK/eIF2α/ATF4/CHOP and STAT3/NF-ΚB axis in MDA-MB-231 and MDA-MB-468 breast cancer cells.

PURPOSE: The constitutive activation of STAT3 through receptor tyrosine kinases triggered breast cancer cell growth and invasion-metastasis. Atiprimod impacts anti-proliferative, anti-carcinogenic effects in hepatocellular carcinoma, lymphoma, multiple myeloma via hindering the biological activity of STAT3. Dose-dependent atiprimod evokes first autophagy as a survival mechanism and then apoptosis due to prolonged ER stress in pituitary adenoma cells. The therapeutic efficiency and mechanistic action of atiprimod in breast cancer cells have not been investigated yet. Thus, we aimed to modulate the pivotal role of ER stress in atiprimod-triggered apoptosis in MDA-MB-231 and MDA-MB-468 breast cancer cells. RESULTS: Dose- and time-dependent atiprimod treatment inhibits cell viability and colony formation in MDA-MB-468 and MDA-MB-231 breast cancer cells. A moderate dose of atiprimod (2 µM) inhibited STAT3 phosphorylation at Tyr705 residue and also suppressed the total expression level of p65. In addition, nuclear localization of STAT1, 3, and NF-κB was prevented by atiprimod exposure in MDA-MB-231 and MDA-MB-468 cells. Atiprimod evokes PERK, BiP, ATF-4, CHOP upregulation, and PERK (Thr980), eIF2α (Ser51) phosphorylation's. However, atiprimod suppressed IRE1α-mediated Atg-3, 5, 7, 12 protein expressions and no alteration was observed on Beclin-1, p62 expression levels. PERK/eIF2α/ATF4/CHOP axis pivotal role in atiprimod-mediated G1/S arrest and apoptosis via Bak, Bax, Bim, and PUMA upregulation in MDA-MB-468 cells. Moreover, atiprimod renders MDA-MB-231 more vulnerable to type I programmed cell death by plasmid-mediated increased STAT3 expression. CONCLUSION: Atiprimod induced prolonged ER stress-mediated apoptosis via both activating PERK/eIF2α/ATF4/CHOP axis and suppressing STAT3/NF-κB transcription factors nuclear migration in TBNC cells.

A comprehensive bibliometric overview: antibiotic resistance and Escherichia coli in natural water.

The environment is the most important reservoir for both resistance mechanisms and gene transfer in biological science studies. This study gives a bibliometric overview of studies of "antibiotic resistance" and "Escherichia coli" in the field of "Agricultural and Biological Sciences" from 2015 to 2019 to assess both research trends and scholarly networks in diverse research disciplines. The two keywords of "antibiotic resistance" and "Escherichia coli" were selected to search in the Scopus database. Each review article was categorized into materials, natural waters (i.e., seawater, freshwater) and wastewater, journal name, and quartile in category of the journal, the year of publication, and the country. Bibliometric indicators and visualization maps were utilized to analyse the retrieved data quantitatively and qualitatively. A total of 1376 publications in the field of agricultural and biological sciences over the last 5 years were obtained using the keywords of antibiotic resistance and Escherichia coli. With additional keywords of freshwater and wastewater, 4 and 24 studies were obtained, respectively. Wastewater was found to be the most common working environment for the keywords of antibiotic resistance and Escherichia coli. It is also found that the studies of antibiotic resistance are mainly conducted in wastewater environments, focusing on human and food health. Working under "One Health" consisting of human, animal and agriculture, and environmental health could be the only permanent and effective approach to solving antibiotic resistance-related issues.

An alternative material for an effective treatment technique proposal in the light of bibliometric profile of global scientific research on antibiotic resistance and Escherichia coli.

Antibiotic resistance is considered by the countries to be a global health issue and a huge threat to public health. The reduction of resistant microorganisms from water/wastewater is of importance in environmental sciences since they are resistant in the aquatic environment. In this study, a bibliometric analysis of literature from the field of environmental science in water ecosystems from 2015 to 2019 was carried out using the keywords "Antibiotic Resistance (AR)" and "Escherichia coli". Furthermore, using the keywords of "Fresh Water," "Sea Water," and "Waste Water," 155, 52, and 57 studies were discovered, respectively. It is found that 217 studies of the total 2115 studies investigated on AR are mostly performed in the "Waste Water" by considering human health. Given the studies, an up-to-date solution should be proposed since the release of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) from wastewater treatment plants needs to be mitigated. For this reason, it is obvious that working on micro and macro ecosystems will increase the probability of solutions in antibiotic resistance. A discussion of removal techniques for coliform bacteria, particularly antibiotic resistant Escherichia coli, was presented. One of the unique values of this study is to offer an innovative solution that removing them by metal-organic frameworks (MOFs) are emerging crystalline hybrid materials. MOFs are used for environmental, biological, and food antimicrobial substances efficiently. Therefore, we can give inspiration to the future studies of antimicrobial resistance removal via adsorption using MOFs as adsorbents. Graphical Abstract.