Synthesis, Characterization, and Biological Studies of Organotin(IV) Derivatives with o- or p-hydroxybenzoic Acids

Organotin(IV) complexes with o- or p-hydroxybenzoic acids (o-H2BZA or p-H2BZA) of formulae [R2Sn(HL)2] (where H2L = o-H2BZA and R = Me- (1), n-Bu- (2)); [R3Sn(HL)] (where H2L = o-H2BZA and R = n-Bu- (3), Ph- (4) or H2L = p-H2BZA and R = n-Bu- (5), Ph- (6)) were synthesized by reacting a methanolic solution of di- and triorganotin(IV) compounds with an aqueous solution of the ligand (o-H2BZA or p-H2BZA) containing equimolar amounts of potassium hydroxide. The complexes were characterized by elemental analysis, FT-IR, Far-IR, TGA-DTA, FT-Raman, Mössbauer spectroscopy, 1H, 119Sn-NMR, UV/Vis spectroscopy, and Mass spectroscopy. The X-ray crystal structures of complexes 1 and 2 have also been determined. Finally, the influence of these complexes 1–6 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically studied and the results showed that triorganotin(IV) complex 6 has the lowest IC50 value. Also complexes 1–6 were studied for their in vitro cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, and the results showed that the complexes have high activity against these cell lines with triphenyltin((IV) complex 4 to be the most active one

Study of the biological interactions of different food components

Flavonoids are a group of chemical molecules found in plants, characterized by the presence of several phenolic units. Flavonoids posses strong antioxidant and anticancer properties. These molecules can act as scavengers of reactive oxygen species (ROS) and as inhibitors of various active enzymes. Thus, the aim of this study was to examine the in vitro cytotoxic properties of flavanols (catechin epicatechin, EGCG)-a group of flavonoids- and their activity as in vivo inhibitors of oxidative stress caused by ozone administration on healthy Wistar rats. Methodology: For the in vitro studies, Trypan Blue exclusion assay and MTT assay were used for cell viability and cell proliferation, respectively, of LMS, MCF-7 and MRC-5 cells. Flow cytometry was used for the determination of apoptosis/necrosis on LMS cells. For the in vivo studies, female Wistar rats aged 3-6 months were used. Oxidative stress was induced by intra-peritoneal administration of 6.1μg/kg body weight of ozone. Flavanols mixture (20mg/kg body weight) was also administrated intra-peritoneally before and after ozone-induced oxidative stress. The Blue CrO5 assay was used for estimation of Total Antioxidant Capacity (TAC) and Liquid Chromatography-Mass Spectra (LC-MS) for the determination of malonaldehyde levels in urine. SOD and GPx enzyme activity were determined by commercial available kits. Hematological indices, indicators of nutrition and metabolism, levels of TNF-a, plasma levels of zinc and copper were also measured. Results: In vitro incubation of various flanavols with tumor cell lines presented an inhibition of cell proliferation. These molecules acted through apoptosis on cancer cells lines. Among the flavanols tested EGCG exerted the highest cytotoxic activity while epicatechin and catechin showed similar but weaker activity. According to the in vivo findings the ozone doses used in this study and the chosen route of administration caused a significant increase in oxidative stress in adult Wistar rats, as shown by significantly increased levels of MDA in urine and a significant decrease in plasma TAC. The results show that flavanols may act as modulators of TAC and maintain the activity of endogenous antioxidant defense enzymes. Conclusion: Flavanols are chemical molecules that have strong biological activity with strong health benefits. Their role and their use as therapeutic agents to treat or prevent diseases or pathogenic situations is promising but requires further researchΤα φλαβονοειδή είναι μια ομάδα χημικών μορίων που απαντάται στα φυτά και χαρακτηρίζεται από την παρουσία πολλών φαινολικών μονάδων. Τα φλαβονοειδή παρουσιάζουν ισχυρές αντιοξειδωτικές και αντικαρκινικές ιδιότητες. Τα μόρια ενεργούν ως δεσμευτές των ενεργών ριζών οξυγόνου και ως αναστολείς διαφόρων ενεργών ενζύμων. Σκοπός της μελέτης ήταν να εξετάσει τις in vitro αντικαρκινικές ιδιότητες των φλαβανολών (κατεχίνη επικατεχίνη, EGCG) και τη δραστηριότητά τους ως in vivo αναστολείς του οξειδωτικού στρες που προκαλείται από τη χορήγηση όζοντος. Μεθοδολογία: Για τις in vitro μελέτες η μέθοδος Trypan Blue και ΜΤΤ χρησιμοποιήθηκαν για το προσδιορισμό της κυτταρικής βιωσιμότητας και των πολλαπλασιασμό των LMS, MCF-7 και MRC-5 κυττάρων. Η κυτταρομετρία ροής χρησιμοποιήθηκε για τον προσδιορισμό της απόπτωσης/νέκρωσης στα κύτταρα LMS. Για τις in vivo μελέτες, χρησιμοποιήθηκαν θηλυκοί επίμυες Wistar, ηλικίας 3-6 μηνών. Το οξειδωτικό στρες προκλήθηκε από ενδοπεριτοναϊκή χορήγηση όζοντος (6.1μg/kg σωματικού βάρους) ενώ το μίγμα των φλαβανολών (20mg/kg σωματικού βάρους) χορηγήθηκε επίσης ενδοπεριτοναϊκά. Για την εκτίμηση της συνολικής του αντιοξειδωτικής ικανότητας χρησιμοποιήθηκε η μέθοδος Κυανού του CrO5 και η Υγρή Χρωματογραφία-Φασφατογράφου Μάζας (LC-MS) για τον προσδιορισμό των επιπέδων της μαλονικής διαλδεϋδης στα ούρα. Η δραστηριότητα των ενζύμων υπεροξειδάση της γλουταθειόνης (SOD) και υπεροξειδάσης της γλουταθειόνης (GPx) μετρήθηκε με εμπορικά διαθέσιμα kits. Μετρήθηκαν επίσης αιματολογικοί δείκτες, δείκτες διατροφής και μεταβολισμού, τα επίπεδα του παράγοντα νέκρωσης TNF-α και τα επίπεδα ψευδαργύρου και του χαλκού στο πλάσμα του αίματος. Αποτελέσματα: Η επώαση των διάφορων φλαβανοών με καρκινικές σειρές κυττάρων ανέστειλε τον κυτταρικό πολλαπλασιασμό. Τα μόρια αυτά οδήγησαν τα καρκινικά κύτταρα σε αποπτωτικό θάνατο. Από τι φλαβανόλες η EGCG εμφάνισε τη μεγαλύτερη κυτταροτοξική δράση ενώ η επικατεχίνη και κατεχίνη έδειξαν παρόμοια, αλλά ασθενέστερη δράση. Σύμφωνα με τα in vivo αποτελέσματα οι δόσεις όζοντος που χρησιμοποιήθηκαν την παρούσα μελέτη και η επιλεγμένη οδός χορήγησης προκάλεσαν σημαντική αύξηση του οξειδωτικού στρες στους ενήλικες επίμυες, όπως φαίνεται από την αύξηση των επιπέδων MDA στα ούρα και τη σημαντική μείωση της TAC στο πλάσμα. Τα αποτελέσματα της παρούσας έρευνας αποδεικνύουν ότι οι φλαβανόλες μπορούν να λειτουργήσουν σαν διαμορφωτές της TAC και να διατηρήσουν την δραστηριότητα των ενδογενών αντιοξειδωτικών αμυντικών ενζύμων. Συμπέρασμα: Οι φλαβανόλες είναι χημικά μόρια που παρουσιάζουν έντονη βιολογική δραστηριότητα με ισχυρά οφέλη υγείας. Ο ρόλος τους και η χρήση τους ως θεραπευτικοί παράγοντες για την αντιμετώπιση ή πρόληψη ασθενειών ή παθογενετικών καταστάσεων είναι ελπιδοφόρος ωστόσο απαιτείται περαιτέρω ερευνητική δράση και θεμελίωση των αποτελεσμάτω

Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells

14-18Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 × 10-3Μ completely inhibited platelet aggregation (p2 levels (p<0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p<0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 ± 34, 450 ± 34 and 62 ± 2.4% (p<0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol

Vanadium(V) complexes with siderophore vitamin e-hydroxylamino-triazine ligands

Novel vitamin E chelate siderophore derivatives and their VV and FeIII complexes have been synthesised and the chemical and biological properties have been evaluated. In particular, the α-and δ-tocopherol derivatives with bis-methyldroxylamino triazine (α-tocTHMA) and (δ-tocDPA) as well their VV complexes, [V2VO3(α-tocTHMA)2] and [V2IVO3(δ-tocTHMA)2], have been synthesised and characterised by infrared (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and ultra violet-visible (UV-Vis) spectroscopies. The dimeric vanadium complexes in solution are in equilibrium with their respefrctive monomers, H2O + [V2VO2(μ-O)]4+ = 2 [VVO(OH)]2+. The two amphiphilic vanadium complexes exhibit enhanced hydrolytic stability. EPR shows that the complexes in lipophilic matrix are mild radical initiators. Evaluation of their biological activity shows that the compounds do not exhibit any significant cytotoxicity to cells

Vanadium(V) complexes with siderophore vitamin e-hydroxylamino-triazine ligands

Novel vitamin E chelate siderophore derivatives and their VV and FeIII complexes have been synthesised and the chemical and biological properties have been evaluated. In particular, the α-and δ-tocopherol derivatives with bis-methyldroxylamino triazine (α-tocTHMA) and (δ-tocDPA) as well their VV complexes, [V2VO3(α-tocTHMA)2] and [V2IVO3(δ-tocTHMA)2], have been synthesised and characterised by infrared (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and ultra violet-visible (UV-Vis) spectroscopies. The dimeric vanadium complexes in solution are in equilibrium with their respefrctive monomers, H2O + [V2VO2(μ-O)]4+ = 2 [VVO(OH)]2+. The two amphiphilic vanadium complexes exhibit enhanced hydrolytic stability. EPR shows that the complexes in lipophilic matrix are mild radical initiators. Evaluation of their biological activity shows that the compounds do not exhibit any significant cytotoxicity to cells

Carpal Tunnel Syndrome Automated Diagnosis: A Motor vs. Sensory Nerve Conduction-Based Approach

The objective of this study was to evaluate the effectiveness of machine learning classification techniques applied to nerve conduction studies (NCS) of motor and sensory signals for the automatic diagnosis of carpal tunnel syndrome (CTS). Two methodologies were tested. In the first methodology, motor signals recorded from the patients’ median nerve were transformed into time-frequency spectrograms using the short-time Fourier transform (STFT). These spectrograms were then used as input to a deep two-dimensional convolutional neural network (CONV2D) for classification into two categories: patients and controls. In the second methodology, sensory signals from the patients’ median and ulnar nerves were subjected to multilevel wavelet decomposition (MWD), and statistical and non-statistical features were extracted from the decomposed signals. These features were utilized to train and test classifiers. The classification target was set to three categories: normal subjects (controls), patients with mild CTS, and patients with moderate to severe CTS based on conventional electrodiagnosis results. The results of the classification analysis demonstrated that both methodologies surpassed previous attempts at automatic CTS diagnosis. The classification models utilizing the motor signals transformed into time-frequency spectrograms exhibited excellent performance, with average accuracy of 94%. Similarly, the classifiers based on the sensory signals and the extracted features from multilevel wavelet decomposition showed significant accuracy in distinguishing between controls, patients with mild CTS, and patients with moderate to severe CTS, with accuracy of 97.1%. The findings highlight the efficacy of incorporating machine learning algorithms into the diagnostic processes of NCS, providing a valuable tool for clinicians in the diagnosis and management of neuropathies such as CTS

Healing effects of quercetin on full thickness epidermal thermal injury in Wistar rats

There are many difficulties in treatment and management of a thermal injury, especially after topical application of the therapeutic agents. Quercetin is a well known agent, which exhibit antioxidant, anti-inflammatory and angiogenic functions. This study was carried out to investigate the effect of quercetin on thermal injury healing in a rat model. Ninety female Wistar rats were used. Animals were inflicted with a reproducible full-thickness burn and randomized into three groups to receive no treatment (control group, CG), local application of a quercetin solution (quercetin group, QG) as well as application of the glyceryl trioctanoate, the solvent used to prepare the solutions (solvent group, SG). The size and healing progress of each wound was recorded and evaluated by means of clinical evaluation, planimetry and histological examination on days 0, 3, 6, 12, 21, and 31. Even though a significantly accelerated wound healing and faster re-epithelialization was recorded in QG compared to other groups, quercetin application failed to lead to a rapid healing of full-thickness burns. The use of quercetin could to be an alternative treatment of burn wounds but further research is needed to evaluate the effective doses for speeding up healing time