Organotin Compound Derived from 3-Hydroxy-2-formylpyridine Semicarbazone: Synthesis, Crystal Structure, and Antiproliferative Activity

The novel diphenyltin(IV) compound [Ph2(HyFoSc)Sn] (2), where H2HyFoSc (1) is 3-hydroxy-2-formylpyridine semicarbazone, was prepared and characterized by vibrational and NMR (1H, 13C) spectroscopy. The structure of [Ph2(HyFoSc)Sn] was confirmed by single-crystal X-ray crystallography. The doubly deprotonated ligand is coordinated to the tin atom through the enolic-oxygen, the azomethine-nitrogen, and phenolic-oxygen, and so acts as an anionic tridentate ligand with the ONO donors. Two carbon atoms complete the fivefold coordination at the tin(IV) center. Intermolecular hydrogen bonding, C–H → π, and π → π interactions combine to stabilize the crystal structure. Compounds 1 and 2 have been evaluated for antiproliferative activity in vitro against the cells of three human tumor cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A549 (nonsmall cell lung carcinoma), and a mouse fibroblast L-929 cancer cell line

Interactions of the dipeptide paralysin β-Ala-Tyr and the aminoacid Glu with phospholipid bilayers

AbstractExisting evidence points out that the biological activity of β-Ala-Tyr may in part related to its interactions with the cell membranes. For comparative reasons the effects of Glu were also examined using identical techniques and conditions. In order to examine their thermal and dynamic effects on membrane bilayers a combination of DSC, Raman and solid state NMR spectroscopy on DPPC/water model membranes were applied and the results were compared. DSC data showed that Glu perturbs to a greater degree the model membrane compared to β-Ala-Tyr. Thus, alteration of the phase transition temperature and half width of the peaks, abolishment of the pretransition and influence on the enthalpy of the phase transition were more pronounced in the Glu loaded bilayers. Raman spectroscopy showed that incorporation of Glu in DPPC/water bilayers increased the order in the bilayers in contrast to the effect of the dipeptide. Several structural and dynamical properties of the DPPC multilamellar bilayers with and without the dipeptide or Glu were compared using high resolution C-13 MAS (Magic Angle Spinning) spectra and spectral simulations of inhomogeneously broadened, stationary P-31 NMR lineshapes measured under CP (Cross-polarization) conditions. These methods revealed that the aminoacid Glu binds in the close realm of the phosphate in the hydrophilic headgroup of DPPC while β-Ala-Tyr is located more deeply inside the hydrophobic zone of the bilayer. The P-31 NMR simulations indicated restricted fast rotary motion of the phospholipids about their long axes in the organized bilayer structure. Finally, by the applied methodologies it is concluded that the two molecules under study exert dissimilar thermal and dynamic effects on lipid bilayers, the Glu improving significantly the packing of the lipids in contrast to the smaller and opposite effect of the dipeptide

Effects of antifibrotic agents on TGF-β1, CTGF and IFN-γ expression in patients with idiopathic pulmonary fibrosis

SummaryIdiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-γ-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-β, CTGF) and immunomodulatory/antimicrobial activity (IFN-γ), in the lungs of patients with IPF.Fourteen (14) patients with an established diagnosis of IPF received either 200μg of IFN-γ-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor β1 (TGF-β1), connective-tissue growth factor (CTGF), and interferon-γ (IFN-γ) genes in lung tissue before and after treatment with IFN-γ-1b or colchicine.Marked mRNA expression of TGF-β1 and CTGF, but complete lack of interferon-γ was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-γ gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-β1 remained almost stable before and after treatment, in the IFN-γ-1b group, while TGF-β1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-γ-1b group (p=0.04). In addition, the IFN-γ-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02).In conclusion, we report the effect of antifibrotic agents (IFN-γ-1b and colchicine) in TGF-β, CTGF, and endogenous IFN-γ gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings

Conformational analysis of AT1 antagonist valsartan using 2DNMR spectroscopy and computational analysis: determination of thermodynamic parameters through dynamic NMR spectroscopy and semi-empirical calculations

AbstractArticles published in this journal are Indexed or Abstracted in Chemical Abstracts, Elsevier's Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE, Compendex, GEOBASE, FLUIDEX, TEXTILE

Microbes and us: microbiology literacy in Greece

Microbes are ubiquitous and provide numerous services to humans and our planet. However, a query arises as to whether these microbial services are valued by the general public especially after unprecedented conditions like the COVID-19 pandemic. In this context a survey was conducted to investigate the concept of microbe in Greece. Thematic analysis of 672 anonymous responses (age range 4–75yo) received for the open-ended prompt “What is the first thing that comes to mind when you hear the word microbe?” revealed five thematic categories: Negative emotions, Fuzzy associations, Biology, Entities and Health. Almost 80% of responses fell under “Biology” and “Health” and the general pattern of answers was the same across all age groups. Microbes took a variety of forms in the minds of respondents, however, the concept of “microbe” seems to be more unshaped at younger ages (4–11yo), as revealed in children's language choices. Overall, the often-negative perception of microorganisms seems to be confirmed in this study. Although this research was limited to participants from Greece, it remains relevant to other countries around the world as well. We discuss the reasons behind this negative perception and offer suggestions for reversing it

There is no significant correlation of adenomyosis with benign, premalignant and malignant gynecological pathologies. Retrospective study on 647 specimens

Objectives: The aim of this study is to identify the prevalence of benign, premalignant and malignant gynecological pathologies in women with adenomyosis who underwent gynecological surgery. Material and methods: The medical records collected between 1985 and 2020 were retrospectively reviewed. The pathology reports were studied from 647 cases where adenomyosis was presented. The estimated prevalence of benign, premalignant and malignant gynecological disorders in the general population was further evaluated. Results: The mean age of women with adenomyosis was 54.1 ± 10.4 years old. Out of 647 patients, in 18.5% of the specimens we detected isolated adenomyosis and in 81.5% of cases a coexistence of one or more gynecological diseases, while in 84 out of 647 patients (13%) there was coexistence of adenomyosis with more than one gynecological condition (benign or malignancy). Among all cases, uterine leiomyomas were observed in 61.3% of patients, followed by endometrial polyps (11.9%), endometriosis (11.6%), endometrial hyperplasia (7.1%), endometrial cancer (3.6%), ovarian (1.4%) and cervical cancer (0.8%) (p < 0.001).Additionally, we found that women with a simultaneous co-existence of adenomyosis, leiomyomas and endometrial polyps or hyperplasia were younger (p < 0.01) in comparison to cases with malignancy. Conclusions: Adenomyosis presents a common benign but often progressing myometrial condition that it is underestimated in clinical practice. Even though some studies suggest a potential association with several gynecological pathologies, we did not confirm a significant difference of adenomyosis prevalence between benign, premalignant and malignant gynecological conditions compared with the general population. Further investigation is required to confirm our results

Comparative study of the AT1 receptor prodrug antagonist candesartan cilexetil with other sartans on the interactions with membrane bilayers

AbstractDrug–membrane interactions of the candesartan cilexetil (TCV-116) have been studied on molecular basis by applying various complementary biophysical techniques namely differential scanning calorimetry (DSC), Raman spectroscopy, small and wide angle X-ray scattering (SAXS and WAXS), solution 1H and 13C nuclear magnetic resonance (NMR) and solid state 13C and 31P (NMR) spectroscopies. In addition, 31P cross polarization (CP) NMR broadline fitting methodology in combination with ab initio computations has been applied. Finally molecular dynamics (MD) was applied to find the low energy conformation and position of candesartan cilexetil in the bilayers. Thus, the experimental results complemented with in silico MD results provided information on the localization, orientation, and dynamic properties of TCV-116 in the lipidic environment. The effects of this prodrug have been compared with other AT1 receptor antagonists hitherto studied. The prodrug TCV-116 as other sartans has been found to be accommodated in the polar/apolar interface of the bilayer. In particular, it anchors in the mesophase region of the lipid bilayers with the tetrazole group oriented toward the polar headgroup spanning from water interface toward the mesophase and upper segment of the hydrophobic region. In spite of their localization identity, their thermal and dynamic effects are distinct pointing out that each sartan has its own fingerprint of action in the membrane bilayer, which is determined by the parameters derived from the above mentioned biophysical techniques

Prevalence of hepatitis B and C markers in high-risk hospitalised patients in Crete: a five-year observational study

BACKGROUND: So far the prevalence of viral hepatitis infection in hospitalized patients has not been extensively studied. Therefore we conducted the present five-year observational study to evaluate the prevalence of HBV and HCV infection in high-risk hospitalized patients of Crete, the largest Greek island, Due to the homogeneous population, epidemiological studies can be accurately done. METHODS: The study was carried out in two out of four District General Hospitals, and in the University Hospital of the island. Markers for HBV and HCV were studied and statistically evaluated according to age, sex and geographical area, in a well-defined hospitalized population. RESULTS: The total prevalence of HBsAg and anti-HCV in the three prefectures during the five-year study is 2.66% and 4.75% respectively. Overall the relative risks were higher in males than females for each hepatitis marker (p < 0.001). Higher prevalence of HBcAb was found in the 41–60 years age group for both sexes (males 36.17%, females 27.38%). Peak HBsAg prevalence was found in the age group of 21–40 and 41–60 years for males (5.4%) and females (3.09%) respectively. Anti-HCV prevalence increases with age reaching the highest prevalence in the age group of 41–60 years for males (7.19%) and in the 61–90 years age group for females (7.16%). For both sexes significant differences between the three locations were identified. For HBsAg a higher prevalence in Heraklion (3.96%) compared to Chania (2.30%, males: p < 0.0001, females: p < 0.05) and Rethymnon (1.45%, males: p < 0.01, females: p < 0.0001) was detected. For HCV a significantly higher prevalence in Heraklion (6.54%) compared to Chania (2.39%, males: p < 0.001, females: p < 0.001) but not in Rethymnon (5.15%, NS). A lower prevalence rate of HBcAb in Heraklion compared to Chania (20.07% versus 23.05%, males: p < 0.001, females: p < 0.001) was found. CONCLUSIONS: These results were possibly overestimated, but nevertheless reflect the situation of the general population within the island as shown by our previous publications in other study groups. Moreover they contribute to the mapping of viral hepatitis prevalence in a geographical area of Southern Europe and may be helpful in planning public health interventional strategies

Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients

Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients