Synthesis, structure, and in vitro antitumor activity of some glycoside derivatives of ferrocenyl-chalcones and ferrocenyl-pyrazolines

Some new glycosides of 3-ferrocenyl-1-(4'-hydroxyphenyl)-prop-2-en-1-one were prepared and transformed into the corresponding pyrazoline and pyrazole derivatives. Using methyl-hydrazine, formation of regioisomers was observed. DDQ was found to be a mild and efficient reagent for the pyrazoline-pyrazole dehydroaromatization process. The structure of the new compounds was proved by IR and NMR spectroscopy. The in vitro antitumor activity of the substances was investigated against human leukemia (HL-60) cells by the MTT method. Among these new compounds some chalcone derivatives (3 a, 3 b, 5 a, and 5 b) showed attractive in vitro antitumor effects on human leukemia cells. These molecules contained ferrocenyl moieties and a p-hydroxy-phenolic ring or a size-independent apolar substitution of that.     

Deactivation of Streptococcus mutans Biofilms on a Tooth Surface Using He Dielectric Barrier Discharge at Atmospheric Pressure

This paper presents a study of the effect of the low temperature atmospheric helium dielectric barrier discharge(DBD) on the Streptococcus mutans biofilms formed on tooth surface. Pig jaws were also treated by plasma to detect if there is any harmful effect on the gingiva.The plasma was characterized by using optical emission spectroscopy.Experimental data indicated that the discharge is very effective in deactivating Streptococcus mutans biofilms.It can destroy them with an average decimal reduction time(D-time) of 19 s and about 98%of thein were killed after a treatment time of 30 s.According to the survival curve kinetic an overall 32 s treatment time would be necessary to perform a complete sterilization.The experimental results presented in this study indicated that the helium dielectric barrier discharge,in plan-parallel electrode configuration,could be a very effective tool for deactivation of oral bacteria and might be a promising technique in various dental clinical applications.     

Exposure to 50 Hz magnetic field in apartment buildings with built-in transformer stations in Hungary

Exposure to 50 Hz magnetic field (MF) was evaluated in 31 multi-level apartment buildings with built-in step-down transformer stations. In each building, three apartments were selected: one apartment located immediately above the transformer room (index apartment), one located on the same floor and one on a higher floor. The mean value of measured MFs was 0.98 microT in apartments above transformers, 0.13 microT on the same floor, and 0.1 microT in on higher floors. The mean measured MF value was higher than 0.2 microT in 30 (97%) index apartments, 4 (14%) on the same floor as the index apartments and 4 (13%) on higher floors. The corresponding numbers were 25 (81%), 0 and 0, respectively, when 0.4 microT was used as cut-point. It is concluded that apartments in building with built-in transformers can be reliably classified into high and low-exposure categories based on their location in relation to transformers.     

Web of Science with the Conference Proceedings Citation Indexes: the case of computer science

Google Scholar and Scopus are recent rivals to Web of Science. In this paper we examined these three citation databases through the citations of the book “Introduction to informetrics” by Leo Egghe and Ronald Rousseau. Scopus citations are comparable to Web of Science citations when limiting the citation period to 1996 and onwards (the citation coverage of Scopus)—each database covered about 90% of the citations located by the other. Google Scholar missed about 30% of the citations covered by Scopus and Web of Science (90 citations), but another 108 citations located by Google Scholar were not covered either by Scopus or by Web of Science. Google Scholar performed considerably better than reported in previous studies, however Google Scholar is not very “user-friendly” as a bibliometric data collection tool at this point in time. Such “microscopic” analysis of the citing documents retrieved by each of the citation databases allows us a deeper understanding of the similarities and the differences between the databases.     

PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA

Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer (PCa). Since bombesin analogue aminobenzoic-acid (AMBA) binds to GRPR with high affinity, scandium-44 conjugated AMBA is a promising radiotracer in the PET diagnostics of GRPR positive tumors. Herein, the GRPR specificity of the newly synthetized [⁴⁴Sc]Sc-NODAGA-AMBA was investigated in vitro and in vivo applying PCa PC-3 xenograft. After the in-vitro assessment of receptor binding, PC-3 tumor-bearing mice were injected with [⁴⁴Sc]Sc/[⁶⁸Ga]Ga-NODAGA-AMBA (in blocking studies with bombesin) and in-vivo PET examinations were performed to determine the radiotracer uptake in standardized uptake values (SUV). ⁴⁴Sc/⁶⁸Ga-labelled NODAGA-AMBA was produced with high molar activity (approx. 20 GBq/µmoL) and excellent radiochemical purity. The in-vitro accumulation of [⁴⁴Sc]Sc-NODAGA-AMBA in PC-3 cells was approximately 25-fold higher than that of the control HaCaT cells. Relatively higher uptake was found in vitro, ex vivo, and in vivo in the same tumor with the ⁴⁴Sc-labelled probe compared to [⁶⁸Ga]Ga-NODAGA-AMBA. The GRPR specificity of [⁴⁴Sc]Sc-NODAGA-AMBA was confirmed by significantly (p ≤ 0.01) decreased %ID and SUV values in PC-3 tumors after bombesin pretreatment. The outstanding binding properties of the novel [⁴⁴Sc]Sc-NODAGA-AMBA to GRPR outlines its potential to be a valuable radiotracer in the imaging of GRPR-positive PCa.     

Metabolic Adaptation as Potential Target in Papillary Renal Cell Carcinomas Based on Their In Situ Metabolic Characteristics

Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as “normal” control. We observed higher protein expressions of the “alternative bioenergetic pathway” elements, in correlation with the possible higher glutamine and acetate consumption in PRCC cells instead of higher glycolytic and mTOR activity in CCRCCs. Increased expression of certain metabolic pathway markers correlates with the detected differences in metabolite ratios, as well. The lower lactate/pyruvate, lactate/malate, and higher pyruvate/citrate intracellular metabolite ratios in PRCC compared to CCRCC cell lines suggest that ACHN (PRCC) have lower Warburg glycolytic capacity, less pronounced pyruvate to lactate producing activity and shifted OXPHOS phenotype. However, both studied renal carcinoma cell lines showed higher mTOR activity than tubular epithelial cells cultured in vitro, the metabolite ratio, the enzyme expression profiles, and the higher mitochondrial content also suggest increased importance of mitochondrial functions, including mitochondrial OXPHOS in PRCCs. Additionally, PRCC cells showed significant mTOR inhibitor sensitivity and the used metabolic inhibitors increased the effect of rapamycin in combined treatments. Our study revealed in situ metabolic differences in mTOR and metabolic protein expression patterns of human PRCC and CCRCC tissues as well as in cell lines. These underline the importance in the development of specific new treatment strategies, new mTOR inhibitors, and other anti-metabolic drug combinations in PRCC therapy.     

Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15–45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.     

HaloTag-Targeted Sirtuin-Rearranging Ligand (SirReal) for the Development of Proteolysis-Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2)**

We have discovered the sirtuin-rearranging ligands (SirReals) as a novel class of highly potent and selective inhibitors of the NAD⁺-dependent lysine deacetylase sirtuin 2 (Sirt2). In previous studies, conjugation of a SirReal with a ligand for the E3 ubiquitin ligase cereblon to form a so-called proteolysis-targeting chimera (PROTAC) enabled small-molecule-induced degradation of Sirt2. Herein, we report the structure-based development of a chloroalkylated SirReal that induces the degradation of Sirt2 mediated by Halo-tagged E3 ubiquitin ligases. Using this orthogonal approach for Sirt2 degradation, we show that other E3 ligases than cereblon, such as the E3 ubiquitin ligase parkin, can also be harnessed for small-molecule-induced Sirt2 degradation, thereby emphasizing the great potential of parkin to be used as an E3 ligase for new PROTACs approaches. Thus, our study provides new insights into targeted protein degradation in general and Sirt2 degradation in particular.     

Eugene Garfield on the Web in 2001

This paper reports on the results of an extensive search for information on Eugene Garfield on the World Wide Web. The searches took place in August 2001, using the search terms: “Eugene Garfield”, “Garfield Eugene”, “Gene Garfield”, “E. Garfield” and “Garfield E”. The five major search engines at that time were queried. 9711 different URLs were identified, out of which 4120 were related to Eugene Garfield, the information scientist. About 25% of these pages were characterized using the method of content analysis. The pages were classified into multiple facets: theme, substantiality, page type, publisher, creator, language, domain and site. The findings show that the most frequently mentioned themes (not surprisingly) were the use and theory of citation analysis, the Citation Indexes as products, the Impact Factor and the use of JCR data. Over 50% of the pages were scientific in nature and more than a third of the pages formally cited Garfield’s work. The findings based on the 2001 dataset were not published before.