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In this study, we prepared photo-crosslinked modified HAP (hydroxy apatite)/polyvinyl alcohol (PVA) composite nanofiber scaffold for cell growth applications. HAP was synthesized and then modified with 4-vinylbenzene boronic acid (VBBA) to obtain 4-VBBA-HAP. By means of the simultaneous UV electrospinning technique 4-VBBA-HAP/PVA composite was obtained. The structure and morphology of electrospun membranes were investigated by scanning electron microscopy) and Fourier transform infrared spectroscopy technique. Nanofibers were treated with collagen solution via the spraying method. For the cell culture applications ECV304 and SAOS cells were seeded on the chosen electrospun fibrous scaffolds. [ABSTRACT FROM PUBLISHER]

The plant chemistry and cytotoxic activity of Colchicum baytopiorum CD Brickell (Liliaceae/Colchicaceae), an endemic species growing in Turkey, has been studied for the first time. Nine known alkaloids were isolated and their structures were identified by spectral methods (UV, IR, 1H-NMR, and ESI/MS), and the presence of three alkaloids, which could not be isolated from the plant, was also detected by LC/MS/MS spectrometry. Phenolic acids were elaborated using LC/MS and 11 phenolic acids were identified. The presence of two flavonoids appeared to be valuable for chemotaxonomic purposes. Guided by the brine shrimp lethality test (BSLT), methanol extracts were tested for cytotoxic activity by colorimetric MTT test on K562 and HL60 cells. Except the seed extract, all methanol extracts showed more cytotoxic activity on HL60 cells (IC50: 6.5– < 0.1 μg/mL) than on K562 cells (IC50: > 500–44 μg/mL). [ABSTRACT FROM AUTHOR]

In this study, new 2-indolinone-indole hybrid compounds (4a-s) carrying a benzoyl moiety were synthesized and their cytotoxic effects were examined against pancreatic (MIA-PaCa-2) and colon (HT-29 and HCT-116) cancer cells by MTT assays. Most of the tested compounds exhibited a better inhibitory activity and safety profile than the reference standard sunitinib malate against MIA-PaCa-2 and HCT-116 cancer cells. Compound 4e displayed the greatest cytotoxic effect on HCT-116 cell with an IC 50 value of 0.16 µM and a remarkable selectivity profile (SI > 625). Compound 4g exhibited a selective activity against HCT-116 cancer cell (IC 50  = 0.34 µM), with no activity against the other cells at the highest concentrations tested. Compound 4b demonstrated a potent inhibitory activity against MIA-PaCa-2 cell (IC 50  = 0.54 µM). General tyrosine kinase inhibitor (TKI) activities and apoptotic effects were examined for compounds 4b, 4e and 4g. The tested compounds were observed to significantly reduce general TK activities in HCT-116 cell and induce apoptosis in HCT-116 and MIA-PaCa-2 cells. Lead compound 4e, the most effective general TKI, was determined to have a specific SRC kinase inhibitor effect in HCT-116 cell and the molecular modelling studies were performed to understand the potential binding mode at the ATP-binding domain of SRC kinase., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Dr. Nilgun Karali reports financial support was provided by Istanbul University Scientific Research Projects Unit. Prof. Dr. Nilgun Karali and Assoc. Prof. Dr. Gokce Cihan Ustundag has patent licensed to TR 2020 050104. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

This study explores the therapeutic potential of albumin-bound Zn(II)-thiosemicarbazone compounds (Alb-ZnTcA, Alb-ZnTcB) against breast cancer cells. Previous research indicates that these compounds hinder cancer cell proliferation by blocking DNA synthesis, promoting oxidative stress to induce apoptosis, and disrupting the cell cycle to inhibit cellular division. This study focuses on the loading and characterization of these potentially chemically unstable compounds on bovine serum albumin-based nanocarriers. Accordingly, unlike previous studies using albumin nanoparticles, in this study, ultraviolet light was used to precisely bind the therapeutic agent to albumin during the integration of thiosemicarbazones, achieving controlled nanoparticle size to control nanoparticle size. The mean diameter of Alb-ZnTcA nanoparticles was 32 nm, while Alb-ZnTcB exhibited an average diameter of 43 nm. Notably, Alb-ZnTcA displayed the highest cytotoxicity toward breast cancer cells, suggesting an optimal size for cellular uptake. Additionally, albumin-bound compounds showed enhanced cytotoxicity at lower concentrations, potentially minimizing adverse side effects. Apoptosis analysis indicated that both Alb-ZnTcA and Alb-ZnTcB induce cell death predominantly through apoptosis, effectively preventing the uncontrolled proliferation of cancer cells. These findings demonstrate the potential of Zn(II)-thiosemicarbazone compounds loaded on albumin-based nanocarriers for breast cancer treatment. The increased potency of Alb-ZnTcA and Alb-ZnTcB compared to free compounds, along with their ability to activate apoptotic signaling pathways in MCF-7 breast cancer cells, highlights a promising approach for future cancer therapies. This study suggests that albumin-bound Zn(II)-thiosemicarbazone compounds could offer a targeted and effective strategy in breast cancer treatment, leveraging the advantages of nanocarrier-based delivery systems., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Three novel mixed-ligand Ni(ıı) complexes were synthesized from a 3,5-dihalogenosalicylaldehyde- S -methyl isothiosemicarbazone ligand (3,5-dichloro for Complex I, 3,5-dibromo for Complex II, and 3,5-diiodo for Complex III) and diethanolamine. The synthesized compounds were characterized by elemental analysis, FT-IR, UV-Vis and 1 H-NMR spectroscopy. Solid-state structures of Complex I and Complex II were determined by the single-crystal X-ray diffraction technique. Both the complexes were found to have a distorted square planar geometry, with coordination of azomethine nitrogen, phenolate oxygen, terminal amine of the thiosemicarbazone ligand and amine nitrogen of diethanolamine. The cytotoxic effects of the ligands and the complexes were evaluated against two different types of cancer cells (THP-1 human leukaemia monocytic cell line and MDA-MB-231 aggressive breast cancer cell line) and healthy cells (HUVEC human umbilical vein endothelial cell line) by using the MTT method. The findings demonstrated that the chloro-derivatives exhibited better efficacy compared to cisplatin in targeting the monocytic leukemia cell line while displaying reduced toxicity towards healthy cells.

The interaction of a multi-component system consisting of benzene-1,4-diyldimethanimine-bridged dimeric zinc-phthalocyanine groups (4OMPCZ) with calf thymus DNA (ct-DNA) was investigated using UV-Vis absorption, fluorescence emission spectroscopy methods, and viscosity measurements. The binding constant, K b , which is an important parameter to gain information about the binding mode, was found as 9.7 × 10 7 M -1 from the UV-Vis absorption studies. Another important spectrophotometric tool is competitive displacement assays with Ethidium bromide and Hoechst 33342. Through this experiment, a higher K SV value was obtained with Hoechst for the phthalocyanine derivative, 4OMPCZ, and the ct-DNA complex than with ethidium bromide. Additionally, molecular docking studies were conducted to calculate the theoretical binding constant and visualize the interactions of 4OMPCZ with a model DNA. According to docking results, although the interactions are mainly located in the major groove of the DNA helix, due to the wrapping, these interactions can also be extended to the minor groove of the DNA. Spectrophotometric, molecular docking, and viscosity studies revealed that the interaction of 4OMPCZ with DNA is likely to be via the major and minor grooves. The in vitro cytotoxic activity of 4OMPCZ was evaluated by MTT assay on human colon cancer cells (HT29) after 72 h of treatment. 4OMPCZ indicated significant cytotoxic activity when stimulated with UV light compared to the standard chemotherapy drugs, fluorouracil (5-FU), and cisplatin on HT29 colon cancer cells. The IC 50 value of 4OMPCZ displayed considerably lower concentrations compared to the standard drugs, 5-FU, and cisplatin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: 1,25(OH)2D3(Calcitriol), which is a broad regulatory molecule, plays a role in changing the efficacy of chemotherapeutic drugs. Cisplatin is one of a current standard chemotherapy regimen for bladder cancer. Increasing the effectiveness of the treatment and reducing the side effects to chemotherapeutics are of great importance in bladder cancer. We aimed to investigate the effect of the combination of cisplatin and calcitriol in order to create a possible advantage in treatment of bladder cancer., Methods: T24, ECV-304 and HUVEC cell lines were treated with calcitriol and cisplatin individually and in combination. Dose determination and combination treatments of calcitriol and cisplatin were evaluated using the MTT assay for cytotoxicity analysis on the cells. Annexin V-PI staining method was used for apoptosis determination by flow cytometry. Also the P-gp expression levels were determined by flow cytometry., Results: The combination treatment increased the anti-proliferative efficacy compared to the efficacy in cisplatin alone in T24 cells and reduced the cytotoxicity in the HUVEC healthy cells compared to cisplatin alone. Combination treatment achieved significantly higher apoptosis rate in T24 cells compared with the rates in treatment of cisplatin alone. However apoptosis decreased in HUVEC cell line. P-gp ratios were increased in HUVEC and decreased in T24 cells with combination treatment compared to the numbers in the control cells. The rate of apoptosis and P-gp levels showed no significant change in ECV-304 cells., Conclusion: Our study revealed that the combination of calcitriol and cisplatin allows the use of cisplatin at lower doses in T24 bladder cancer cell line., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Two types of MgAl layered double hydroxide nanoparticles, MgAl LDH, at Mg:Al ratio of 2:1 and 3:1were prepared and used as inorganic fillers to improve the mechanical properties of poly(lactic acid)/poly(ethylene oxide) (PLA/PEO) electrospun composite fibers. Their detailed structural characterization was performed using X-ray diffraction (XRD) and transmission electron spectroscopy (TEM) techniques. Spectroscopic, thermal, mechanical, and morphological properties of the electrospun composite fibers, and cell proliferation on their surface, were examined. XRD and TEM analyses showed that the LDH nanoparticles were 50 nm in size and the Mg:Al ratio did not affect the average spacing between crystal layers. Fourier transform infrared (FTIR) and thermal analyses (TA) revealed the compatibility of the filler and the polymer matrix. The nanoparticles considerably improved the mechanical properties of the electrospun mats. The tensile strength and elongation at break values of the composite samples increased from 0.22 MPA to 0.40 MPa and 12.2 % to 45.66 %, respectively, resulting from the interaction between LDH and the polymer matrix. Scanning electron microscopy (SEM) and MTT analyses demonstrated that the electrospun composite fibers supported the SaOS-2 cells attachment and proliferation on the fiber surfaces, along with their suitable cytocompatibility., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Carboplatin (CP), a platinum analog, is one of the most widely used chemotherapeutic agents in the treatment of colorectal cancer. Although platinum-based drugs are quite effective in anticancer treatments, their use in a wide spectrum and effective treatment possibilities are limited due to their systemic side effects and drug resistance development. In recent years, studies have focused on increasing the therapeutic efficacy of platinum-based drugs with drug delivery systems. Gelatin, a protein, obtained by the hydrolysis of collagen, is a biocompatible and biodegradable material that can be used in nano drug delivery systems. In this study, CP-loaded gelatin-based NPs (CP-NPs) were exposed to IR light in different temperatures at 30, 35, 40, 45, and 50 °C and characterized by FESEM-EDX, FTIR, UV-Vis, DLS. Accordingly, we synthesized gelatin-based CP-NPs of different sizes between 10-290 nm by exposure to IR. We found that CP-NPs-50, 16 nm nano-sized, obtained at 50 °C had the most cytotoxicity and was 2.2 times more effective than the free drug in HCT 116 colon cancer cells. Moreover, we showed that the cytotoxicity of CP-NPs-50 in normal HUVEC cells was lower. Additionally, we demonstrated that CP-NPs enhanced apoptotic activity while not developing MDR1-related resistance in colon cancer cells. In this study, for the first time drug loaded gelatin-based nanoparticles were synthesized in different sizes with a newly self-assembly method by exposing them to infrared light at different temperatures and their anticancer effects were evaluated subsequently., (© 2022. The Author(s).)

Aim: The present study aims to identify the anticancer effect of novel 1H-indole-2,3-dione 3- thiosemicarbazone derivatives. These compounds could be promising anticancer agents in leukemia treatment., Background: Conventional chemotherapeutic agents accumulate in both normal and tumor cells due to nonspecificity. For effective cancer treatment, new drugs need to be developed to make chemotherapeutics selective for cancer cells. The ultimate goal of cancer treatment is to reduce systemic toxicity and improve the quality of life., Methods: In this study, the anticancer effects of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives (A-L) were investigated in chronic myelogenous leukemia K562, Burkitt's lymphoma P3HR1, acute promyelocytic leukemia HL60 cells, and vincristine-resistant sublines of K562 and P3HR1 cells. Additionally, the compounds were tested on lymphoid-derived cells from ALL patients. In order to investigate the particular mechanism of death caused by the cytotoxic effects of the compounds, immunohistochemical caspase 3 staining was performed in P3HR1 cells, and the resulting apoptotic activities were demonstrated., Results: All tested compounds have been found to have cytotoxic effects against lymphoma cells at submicromolar concentrations (IC 50 = 0.89-1.80 μM). Most compounds show significant selectivity for the P3HR1 and P3HR1 Vin resistance. The most effective and selective compound is 4-bromophenyl substituted compound I (IC 50 =0.96 and 0.89 μM). Cyclohexyl and benzyl substituted compounds D and E have also been found to have cytotoxic effects against K562 cell lines (IC 50 =2.38 μM), while the allyl substituted compound C is effective on all cell lines (IC 50 =1.13-2.21 μM). 4-Fluorophenyl substituted F compound has been observed to be effective on all cells (IC 50 =1.00-2.41 μM) except K562 cell. Compound C is the only compound that shows inhibition of HL-60 cells (IC 50 = 1.13 μM). Additionally, all compounds exhibited cytotoxic effects on lymphoidderived cells at 1μM concentration. These results are in accordance with the results obtained in lymphoma cells., Conclusion: All compounds tested have submicromolar concentrations of cytotoxic effects on cells. These compounds hold potential for use in future treatments of leukemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The attempts to explore and optimize the efficiency of diabetic wound healing's promotors are still in progress. Incorporation of cerium oxide nanoparticles (nCeO 2 ) in appropriate nanofibers (NFs) can prolong and maximize their promoting effect for the healing of diabetic wounds, through their sustained releases, as well as the nanofibers role in mimicking of the extra cellular matrix (ECM). The as-prepared nCeO 2 were analyzed by using UV-Vis spectroscopy, XRD, SEM-EDX, TEM and FTIR, where TEM and SEM images of both aqueous suspension and powder showed spherical/ovoid-shaped particles. Biodegradable trilayer NFs with cytobiocompatibility were developed to sandwich nCeO 2 in PVA NFs as a middle layer where PLA NFs were electrospun as outer bilayer. The nCeO 2 -loaded trilayer NFs were characterized by SEM, XRD, FTIR and DSC. A two-stage release behavior was observed when the nanoceria was released from the trilayer-based nanofibers; an initial burst release took place, and then it was followed by a sustained release pattern. The mouse embryo fibroblasts, i.e., 3T3 cells, were seeded over the nCeO 2 -loaded NFs mats to investigate their cyto-biocompatibility. The presence and sustained release of nCeO 2 efficiently enhance the adhesion, growth and proliferation of the fibroblasts' populations. Moreover, the incorporation of nCeO 2 with a higher amount into the designed trilayer NFs demonstrated a significant improvement in morphological, mechanical, thermal and cyto-biocompatibility properties than lower doses. Overall, the obtained results suggest that designated trilayer nanofibrous membranes would offer a specific approach for the treatment of diabetic wounds through an effective controlled release of nCeO 2 .

Diabetic wounds have a slow healing process and easy to be infected. In addition to current drug treatments, supportive approaches are needed for diabetic wound treatment. In this study, we aimed to load Aloe Vera (AV) and Hypericum perforatum oil (HPO) with PCL/Ge (Poly (ɛ-caprolactone)/Gelatine) polymeric biodegradable by electrospinning method into nanofiber dressings on an experimental diabetic wound model to compare the diabetic wound healing effect. Changes in the amount and chemical structure of phospholipids, proteins, and lipids were investigated in the blood and serum samples of the animals using Fourier transform infrared (FTIR) analysis. To evaluate biological events associated with the wound repair process in inflammatory phase we used oxidant and antioxidant status to determine the healing status of wounds such as Total antioxidant status (TAS), Total oxidant level (TOS) and tumor necrosis factor alpha (TNF-α) levels. TOS level increased in DM groups and decreased in the AV and HPO group. Oxidative stress index decreased and TNF-α level increased in the HPO group. FTIR spectra showed changes in the phospholipids, proteins, and carbon chain of lipids in the whole blood as well as serum of DM rats. FTIR spectra combined with Principal component analysis (PCA) showed, that treated DM rats by AV and HPO caused return chemical structure of blood and serum to this observed in control group. Higher similarity with control group for HPO rats was observed. HPO is better than AV in the alternative for healing on diabetic wound. Thus, we have demonstrated that IR spectroscopy and multivariate data analysis and biochemical assays are consistent and correlative with each other., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Harmful illicit drug use, such as opioid use disorder (OUD), causes multiple diseases that result in physiological, pathological, and structural changes in serum biochemical parameters based on the period of use. Fourier-transform infrared (FTIR) spectrometry is a noninvasive optical technique that can provide accurate evidence about the biochemical compounds of analytical samples. This technique is based on the detection of functional groups and the spectral analysis of the region of the selected bands, which provides a reliable and accurate tool for evaluating changes in the biochemical parameters of OUD patients. In the present study, the Attenuated Total Reflection (ATR)-FTIR technique and clinical laboratory biochemical results were used to investigate the phospholipid-protein balance in the blood serum of participants with OUD by comparing their data to that of healthy controls. To compare the biochemical laboratory results with serum vibrational spectroscopy, we used infrared (IR) spectroscopy to distinguish the serum of the OUD patients, who had an average duration of use of 7.31 ± 3.8 years (ranging from 6 to 15 years). We aimed to compare the clinical reports with findings from IR spectroscopy coupled with chemometrics analysis, principal component analysis (PCA), and linear discriminant analysis (LDA). The serum samples of the OUD male patients (n = 20) and healthy male individuals (n = 14) were evaluated using FTIR spectroscopy (range of 4000 cm -1 - 400 cm -1 ). We focused on the areas where the results showed significant band differences and significant chemometric differences at the fingerprint region (1800 cm -1 - 900 cm -1 ), Amide I (1700 cm -1 -1600 cm -1 ), C-H stretching band (3000 cm -1 -2800 cm -1 ), triglyceride (Tg) levels and cholesterol esters (1800 cm -1 -1700 cm -1 ), and total protein region (1700 cm -1 -1350 cm -1 ). The intensity of these band areas was significantly different (p < 0.01) between OUD patients and healthy controls. Moreover, different bands on the serum spectrum of the OUD patients were explored. The results successfully specified the distinctions between OUD and the healthy controls (HCs). We compared the results with biochemical markers, such as albumin (Alb), Tg, and total cholesterol (Tc) levels of the patients, as well as the data of the healthy subjects obtained from the hospital. Additionally, we found that the Tg, Tc, and Alb levels decreased as the duration of heroin use increased based on the biochemical markers of the OUD patients. The laboratory biochemical reports and the vibrational spectroscopic analysis were correlated. The confidence of specificity, sensitivity, and accuracy was 100%, 92.85%, and 97.06% in the second derivative, respectively. Thus, we demonstrated that IR spectroscopy, multivariate data analysis, and clinical reports are consistent and correlated. Furthermore, FTIR is a simple and readily available diagnostic test that can successfully differentiate the serum samples of OUD patients from those of healthy subjects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one-pot synthesis method. The structures were characterized by elemental analysis, IR, 1 H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single-crystal X-ray diffraction. The findings showed that the metal atom adopts a slightly distorted square-pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O─H···O and C─H···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake-flask method, another pharmacokinetic parameter. The findings showed that the IC 50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies., (© 2020 Wiley Periodicals, Inc.)

Purpose: The effects of four different self-adhesive resin cement materials on cell viability and apoptosis after direct and indirect exposure were evaluated using different cell culture techniques., Materials and Methods: Self-adhesive cements were applied to NIH/3T3 mouse fibroblasts by the extract test method, cell culture inserts, and dentin barrier test method. After exposure periods of 24 h and 72 h, the cytotoxicity of these self-adhesive materials was evaluated using the MTT assay (viability) and the Annexin-V-FITC/PI staining (apoptosis)., Results: The lowest cell viability was found in cells exposed to BeautiCem SA for 24 h in the extract test method. Cell viability was reduced to 70.6% compared to negative controls. After the 72 h exposure period, viability rate of cell cultures exposed to BeautiCem SA decreased more than 2- fold (29.5%) while cells exposed to RelyX U200 showed the highest viability rate of 71.4%. In the dentin barrier test method, BeautiCem SA induced the highest number of cells in apoptosis after a 24 h exposure (4.1%). Panavia SA Cement Plus was the material that caused the lowest number of cells in apoptosis (1.5%)., Conclusion: The used self-adhesive cements have showed different cytotoxic effects based on the evaluation method. As exposure time increased, the materials showed more cytotoxic and apoptotic effects. BeautiCem SA caused significantly more severe cytotoxic and apoptotic effects than other cements tested. Moreover, cements other than BeautiCem SA have caused necrotic cell death rather than apoptotic cell death., (© 2020 The Korean Academy of Prosthodontics.)

Background: The effect of Aloctin, a lectin purified from Aloe vera leaves, and aloe emodin an anthraquinone glycoside purified from the leaves of the same plant, on several cancer cell lines was investigated., Methods: Aloctin was isolated from A. vera leaf skin by ammonium sulphate precipitation and CNBr-Sepharose 4B-ovalbumin affinity chromatography. Specific new ligands for Aloctin were detected as fetuin and avidin by hemagglutination inhibition tests. The cytotoxic effect of Aloctin and aloe emodin on various human cancer cell lines was tested using MTT assay. Imatinib was tested as standard positive control. The mechanism underlying was tested by the Annexin V-FITC/PI test, with flow cytometry., Results: The most sensitive cells to Aloctin and aloe emodin treatment, were identified as AGS human gastric adenocarcinoma cells. The effect was concentration dependent. It was shown that this effect does not occur by apoptosis or necrosis. In Aloctin-imatinib combinations studies, Aloctin significantly increased the cytotoxic effect of imatinib in a dose-dependent manner. It is expected that the results of this study will reveal important findings for the future use of A. vera lectin as well as aloe emodin in cancer research and contribution to lectin biochemistry., .

Eighteen of the iron(III) and nickel(II) complexes with tetradentate thiosemicarbazidato ligands were synthesized and described, by analytical and spectroscopic methods. Two complexes as an example to the iron and nickel centered ones were crystallographically analyzed to confirm the molecular structures. Cytotoxic effects of the complexes on K562 chronic myeloid leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. For comparison, human umbilical vein endothelial cells (HUVECs) was used as a noncancerous cell line. While four of the iron(III) complexes exhibited the antileukemic effect with 50% inhibition of cell growth (IC 50 ) values in the 3.4 to 6.9 μg/mL range on K562 cell line, the nickel(II) complexes showed no significant effect on both cell lines. The complexes Fe4, Fe5, and Fe6, bearing 4-methoxy substituent exhibited relatively high antiproliferative activity on both cell lines. Complex Fe3 with 3-methoxy and S-allyl groups exhibited a selectivity between K562 and HUVEC cells by IC 50 values of 6.9 and >10 μg/mL, respectively. Lipophilicity, a key parameter for bioavailability and oral administration, was found in the range of -0.3 and +1.3 that desired for drug active ingredients. The results were discussed in the context of a structure-activity relationship., (© 2019 Wiley Periodicals, Inc.)

Background: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects., Aims: To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations., Study Design: Cell culture study., Methods: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5‑diphenyl‑tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 μM and of imatinib from 5 to 50 μM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software., Results: In our study, the IC 50 values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 μM, 100 μM, and >200 μM, respectively. Luteolin (100 μM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p<0.05). Among the flavonoids studied, the combination of luteolin and imatinib was the most effective and is therefore recommended for its cytotoxic activity in the K562 cell line. After 72 h of incubation at their respective IC 50 concentrations, all flavonoids were associated with an apoptosis rate of approximately 50%. P-glycoprotein activity was increased in all groups. Combination treatment may provide better outcomes in terms of cytotoxicity and thus reduce the dosages of imatinib used., Conclusion: The combination of some flavonoids and imatinib mesylate may increase the cytotoxic effect; However, the antagonistic effect should be considered in combined use on k562 cells.

Haematopoietic stem cells can self-renew and produce progenitor cells, which have a high proliferation capacity. Chemotherapeutic drugs are toxic to normal cells as well as cancer cells, and glucocorticoids (GCs), which are essential drugs for many chemotherapeutic protocols, efficiently induce apoptosis not only in malignant cells but also in normal haematopoietic cells. Studies have shown that haematopoietic cytokines can prevent the apoptosis induced by chemotherapy and decrease the toxic effects of these drugs. However, the apoptosis induction mechanism of GCs in CD34 + haematopoietic cells and the anti-apoptotic effects of cytokines have not been well elucidated. In this study, we investigated the apoptotic effects of GCs on CD34 + , a haematopoietic stem/progenitor cell (HSPC) population, and demonstrated the protective effects of haematopoietic cytokines. We used a cytokine cocktail containing early-acting cytokines, namely, interleukin-3 (IL-3), thrombopoietin, stem cell factor and flt3/flk2 ligand, and dexamethasone and prednisolone were used as GCs. Apoptotic mechanisms were assessed by immunohistochemical staining and quantified using H-scoring. Dexamethasone and prednisolone induced apoptosis in CD34 + HSPCs. GC treatment caused a significant increase in apoptotic Fas, caspase-3, cytochrome c and Bax, but a significant decrease in anti-apoptotic Bcl-2. Furthermore, as expected, cytokines caused a significant decrease in all apoptotic markers and a significant increase in Bcl-2. Thus, our findings suggest that CD34 + HSPCs are an extremely sensitive target for GCs and that cytokines protect these cells from GC-induced apoptosis.

In this study, one of the most promising methods of tailoring a composite scaffold material in nano sized diameters, electrospinning method were used to produce Polycaprolactone (PCL)/Graphene Oxide (GO)/Iron(II, III) Oxide (Fe 3 O 4 ) nanocomposite fibers as biocompatible scaffolds for biomedical applications. Products were analyzed by scanning electron microscopy (SEM) for morphological analysis of the electrospun nanocomposites and Fourier Transform Infrared Spectroscopy (FTIR) was used to determine functional groups of the PCL, GO, and Fe 3 O 4 materials in the electrospun nanocomposites. For physical properties, viscosity, density, permittivity, dielectric loss and liquid and solid state alternating current conductivity, measurements were done for each nanocomposite fibers. Effects of concentration percentage of GO on permittivity, dielectric loss and AC conductivity have been analyzed by using measured and calculated data. Trend lines have been drawn for permittivity, dielectric loss and conductivity via concentration percentage of GO. The relation between ac conductivity and frequency have been studied for each concentration percentage of GO and interpretations have been done by using the obtained results., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, zwitterionic phosphorylcholine grafted electrospun chitosan fiber was accomplished in three steps: (1) Azide groups on the chitosan were regioselectively replaced with hydroxyl side group and then the product was electrospun. (2) Chitosan based macroinitiator was prepared using an azide-alkyne click reaction from azide-functionalized electrospun chitosan fiber. (3) Poly(2-methacryloyloxyethyl phosphorylcholine) (MPC) was grafted onto the electrospun chitosan fiber by atom transfer radical polymerization (ATRP) in order to enhance cellular viability and proliferation of 3T3, ECV and Saos. The structure of surface modified chitosan was characterized by Fourier transform infrared spectrometer (FT-IR) and 1 H nuclear magnetic resonance ( 1 H NMR). The surface morphology of the nanofibers was investigated by scanning electron microscope (SEM). In-vitro cellular attachment and spreading experiments of 3T3, ECV304 and Saos were performed on electrospun chitosan fibers in the presence and the absence of MPC grafting. Poly(MPC) grafted electrospun fiber showed an excellent performance due to phosphorylcholine groups mimicking the natural phospholipid., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aim: to evaluate changes in visual acuity and compliance after CAM therapy in patients that initially failed to respond to occlusion or were non-compliant., Material and Methods: Twenty nine patients aged 4-10 years that failed to improve under occlusion therapy were included in this prospective study. Patients were divided into two groups according to the age (16 patients of 4-7 years of age and 13 patients of 8-10 years of age) and two other groups according to the type of amblyopia (15 anisometropic and 14 strabismic cases). CAM stimulation was prescribed to all patients for six days. Occlusion therapy was then recommenced. Best corrected visual acuity was measured before the CAM course, immediately after, at 3- and 6-month follow-ups, and on the last visit., Results: Visual acuities in all study groups increased significantly immediately after the CAM therapy with further improvement during the follow-up period., Conclusion: CAM therapy for amblyopia is helpful in improving visual acuity as well as patients' compliance to subsequent occlusion therapy.

Background: Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel., Methods: Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT)., Results: 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p<0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p<0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively)., Conclusion: This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: We aimed to evaluate the influence of current antifibrotic agents as well as the possible results obtained by combining these agents. This study included α-tocopherol, a strong antifibrotic and an efficient neuromediator of pathways used by other agents., Materials and Methods: Mitochondrial Bcl-2, Bax, cytochrome c and cytoplasmic caspase-3 expression, as well as toxic effect patterns, mitosis and cellular reactions due to α-tocopherol alone or combined with paclitaxel, mitomycin C and 5-flurouracil (5-FU), was studied in series obtained from human endothelial and primary Tenon's fibroblast cell cultures., Results: The strongest apoptotic effect in both cell groups belonged to paclitaxel, followed by mitomycin C, and despite the overall suppressive effect of the α-tocopherol combination, mitomycin C increased its efficiency on the endothelial cells. The apoptosis/necrosis ratio was highest in α-tocopherol and lowest in paclitaxel, with α-tocopherol generally decreasing necrosis. Bax was observed at a high level with mitomycin C. Cytotoxicity was the highest with paclitaxel, and the caspase-3 reaction was markedly higher with mitomycin C in both cell types. In the α-tocopherol and 5-FU slides, mitosis and a layered formation were observed. The addition of α-tocopherol reduced the cytotoxicity of all antifibrotic agents in both cell series by decreasing the cell numbers, leading to necrosis., Conclusions: Alone or in combination, the use of α-tocopherol and 5-FU is safer than other agents. By suppressing the cytotoxic effects of other antifibrotic agents, α-tocopherol is a promising drug for improving the effects of antifibrotics in many aspects of medicine. In addition, it has the potential to play a role beyond its antioxidant and antifibrotic activity in ocular surgery.

Nickel is a strong immunological sensitizer and may result in contact hypersensitivity. Case reports of allergic reactions to intraoral nickel have occasionally been reported in the published work and these allergic reactions are generally of a delayed type (type IV). Here, we present a case of a nickel allergic patient displaying frequent laryngeal edema attacks which required treatment with epinephrine injections followed by parenteral corticosteroid doses. Her complaints ceased after the removal of the dental bridge and the foods containing nickel. In summary, we propose that in the case of recurrent laryngeal edema attacks without any explainable cause, an allergic reaction due to nickel exposure should be taken into consideration., (© 2013 Japanese Dermatological Association.)

The physiological mechanisms of decreased NK activity of β-Thalassemia major (BTM) patients are unknown. To assess in vitro effects of mononuclear cells and their cytokine secretion on NK activity, we compared activator receptor levels and cytotoxic activity of purified NK cells and NK cells in mononuclear cells (MNC) pools. We collected cell supernatant from unincubated and incubated MNC with K562 cells and measured their secreted cytokines levels. CD16 was lower on the surface of NK cells in MNC pools from BTM patients compared to healthy volunteers. This inhibition does not appear when NK cells were purified. NKp30 levels in NK cells decreased both as purified cells and as part of a pool of MNC in BTM patients. After incubation of MNC pools with K562 target cells, we found that supernatant levels of IL10, TGFβ1 and IL15 cytokines were also significantly higher in BTM patients compared to healthy volunteers., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The S-methyl-thiosemicarbazones of the 2-hydroxy-R-benzaldehyde (R = H, 3-OH 3-OCH(3) or 4-OCH(3)) reacted with the corresponding aldehydes in the presence of FeCl(3) and NiCl(2). New ONNO chelates of iron(III) and nickel(II) with hydroxy- or methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and (1)H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N(1)-4-methoxysalicylidene-N(4)-4-methoxysalicylidene-S-methyl-thiosemicarbazidato-iron(III) complex showed selective anti-leukemic effects in K562 cells while has no effect in ECV304 cells in the 0.53 microg/ml (IC(50)) concentrations. Also, some methoxy-substituted nickel(II) chelates exhibit high cytotoxic activity against both of these cell lines in low concentrations. Cytotoxicity data were evaluated depending on cell lines origin and position of the substituents on aromatic rings.

In this study a new branched methacrylated poly(propylene glycol-co-lactic acid) (PPG-PLA-IEM) and methacrylated cellulose acetate butyrate resin (CAB-IEM) were synthesized. Hydrogels with various amounts of PPG-PLA-IEM and CAB-IEM (25, 50 and 75 wt% IEM modified) were prepared by photopolymerization. Collagen tethered PEG-monoacrylate (PEGMA-collagen) was prepared and introduced as a bioactive moiety to modify the hydrogel in order to enhance cell affinity. In vitro attachment and growth of 3T3 mouse fibroblasts and human umbilical vein endothelial cells (HUVEC) on the hydrogels with and without collagen were also investigated. It was observed that, the collagen improves the cell adhesion onto the hydrogel surface. With the increasing amount of collagen, cell viability increased by 28% for ECV304 (P < 0.05) and 30% for 3T3 (P < 0.05).

An experimental approach to increasing the effectiveness of leukemia treatment with S-phase-specific cytotoxics is to increase the cycling of leukemia cells with growth factors. However, growth factors may have a different relationship with non-cell-cycle-specific agents. The authors examined the effects of granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interferon-alpha (INF-alpha) on the cytotoxic effects of the alkylating agent busulfan on the erythro-myeloid cell line K562. G-CSF and GM-CSF increased the proliferation and colony-forming ability of K562 cells and protected the cells from busulfan effects. INF-alpha decreased the colony-forming ability and proliferation of the K562 cells and demonstrated a possibly additive effect with busulfan. In the cell line K562, the growth factors G-CSF and GM-CSF protected the cells from the non-cell-cycle-specific alkylating agent busulfan, whereas IFN-alpha demonstrated an additive cytotoxic effect.

Reactions of 2-hydroxy-3-methoxy, 2-hydroxy-4-methoxy-benzaldehyde with 3- and 4-methoxy-substituted salicylaldehyde S-methyl-thiosemicarbazones in the presence of FeCl(3) and NiCl(2) resulted in the corresponding methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazone chelates. Characterisation of the compounds in the [Fe(L)Cl] and [Ni(L)] general formula was accomplished by means of elemental analysis, conductivity and magnetic measurements, (1)H NMR, UV-vis, IR and mass spectroscopy. Cytotoxicity and proliferation experiments using K562 chronic myeloid leukemia cell line and ECV 304 human endothelial cell line imply that the iron(III) chelates may have anti-leukemic effects with 3.5 microg/dl LD(50) dose.

In this study, the in vitro effects of vitamin C and selenium on natural killer (NK) cell activity of ss-thalassemia major patients was investigated. At first, significant decreased NK activity was found at E:T ratios of 1:1, 5:1, and 10:1 in whole thalassemia patients. Low-dose selenium treatment enhanced NK activity in patients but there was no change in the control group. High-dose selenium decreased NK activity significantly in splenectomized patients. Different doses vitamin C enhanced NK activity significantly in both splenectomized and unsplenectomized patients. According to these results, selenium dosage should be arranged carefully in thalassemia patients, whereas vitamin C can be used confidently.