Carbon Nanofiber-Sodium Alginate Composite Aerogels Loaded with Vitamin D: The Cytotoxic and Apoptotic Effects on Colon Cancer Cells.

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. A substantial body of literature supports the crucial role of vitamin D (VD) in the etiology, progression, prognosis, and treatment of cancer. Recent clinical studies have found an inverse correlation between CRC incidence and serum VD levels. However, the low water solubility of VD and its anticarcinogenic activity at supraphysiological plasma levels, which causes hypercalcemia, required carrier systems. Carbon-based nanomaterials are excellent eco-friendly candidates, with exceptional chemical resistance, efficient mechanical properties, and negligible weight. Furthermore, composite aerogels manufactured from these nanomaterials have gained interest due to their extensive surface areas and porous structures, which make them suitable for delivering drugs. Our research aimed to study the development of composite aerogels loaded with VD by utilizing carbon nanofibers (CNFs) in an aerogel matrix provided to colon cancer cells. For this purpose, Aero1 as a drug delivery system was first prepared and characterized using XRD, FTIR, and SEM methods. Biochemical methods were employed to evaluate the antiproliferative, apoptotic, and anti-migratory effects on colon cancer cells. FTIR and XRD measurements confirmed the production of aerogels. SEM analysis revealed that aerogels have a non-uniform surface. The findings showed that aerogels can effectively deliver VD to the colon cancer cells, while also inhibiting cancer cell proliferation and migration. This research suggests that the Aero1 drug delivery system could be a valuable tool in the fight against colon cancer and other health issues.

The Effects of Apocynin on Monosodium Glutamate Induced Liver Damage of Rats.

Monosodium glutamate (MSG) is found in refined foods. Apocynin (APO) is a selective NADPH oxidase (NOX) inhibitor. The aim of this experimental study was to investigate possible effects of MSG and the curative effects of APO in rats. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (Normal control, APO, MSG and MSG + APO, n:7 for each group). The MSG and MSG + APO groups received 120 mg/kg MSG solution orally for 28 consecutive days. The APO and MSG + APO groups received 25 mg/kg APO solution orally for 5 days until the end of the experiment. At the end of the experiment, all rats were sacrificed and liver tissue and blood samples were taken for histological, ultrastructural, and biochemical analyses. In the MSG group, vacuolization and loss in glycogen content in the hepatocytes, leukocyte infiltration and fibrosis in the liver parenchyme and portal triads, were observed. Terminal deoxynucleotidyl transferase dUTP (TUNEL)-positivity and NADPH oxidase (NOX)-2-positivity were higher in the MSG group compared with the other experimental groups. The concentrations of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin, malondialdehyde (MDA), and myeloperoxidase (MPO) were higher, whereas albumin, glutathione (GSH), and superoxide (SOD) levels were lower in the MSG group. All these data has been reversed in MSG + APO group. The histological and biochemical criteria indicated the prominent ameliorating effect of APO on MSG -induced liver injury.

Apocynin Ameliorates Monosodium Glutamate Induced Testis Damage by Impaired Blood-Testis Barrier and Oxidative Stress Parameters.

BACKGROUND: the aim of this study was to investigate the effects of apocynin (APO) on hormone levels, the blood-testis barrier, and oxidative biomarkers in monosodium glutamate (MSG) induced testicular degeneration. METHODS: Sprague Dawley male rats (150-200 g; n = 32) were randomly distributed into four groups: control, APO, MSG, and MSG + APO. MSG and MSG + APO groups were administered MSG (120 mg/kg) for 28 days. Moreover, the APO and MSG + APO groups received APO (25 mg/kg) during the last five days of the experiment. All administrations were via oral gavage. Finally, biochemical analyses were performed based on the determination of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), as well as light and transmission electron microscopic examinations, assessment of sperm parameters, ZO-1, occludin, NOX-2, and TUNEL immunohistochemistry were evaluated. RESULTS: MSG increased both the oxidative stress level and apoptosis, decreased cell proliferation, and caused degeneration in testis morphology including in the blood-testis barrier. Administration of apocynin reversed all the deteriorated morphological and biochemical parameters in the MSG + APO group. CONCLUSIONS: apocynin is considered to prevent testicular degeneration by maintaining the integrity of the blood-testis barrier with balanced hormone and oxidant/antioxidant levels.

Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity.

Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 µM, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 µM. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.

Exercise improves testicular morphology and oxidative stress parameters in rats with testicular damage induced by a high-fat diet.

Obesity and male infertility are problems that affect population. Exercise is a nonpharmacological way to reduce the negative health effects of obesity. The purpose of this study was to examine the effects of exercise on hormone levels, blood-testis barrier, and inflammatory and oxidative biomarkers in rats that became obese due to a high-fat diet (HFD). Male rats received a standard diet (STD group) or a HFD (HFD group) for 18 weeks. During the final 6 weeks of the experiment, swimming exercises (1 h/5 days/week) were given to half of these animals (STD + EXC and HFD + EXC groups). Finally, blood and testicular tissues were analysed by biochemical and histological methods. Body weight, leptin, malondialdehyde, interleukin-6, TNF-alpha and myeloperoxidase levels, apoptotic cells and DNA fragmentation were increased, and testis weight, insulin, FSH, LH, testosterone, glutathione and superoxide dysmutase levels, proliferative cells, ZO-1, occludin, and gap junction protein Cx43 immunoreactivity were decreased in the HFD group. All these hormonal, morphological, oxidative and inflammatory biomarkers were enhanced in the HFD + EXC group. It is thought that exercise protected testicular cytotoxicity by regulating hormonal and oxidant/antioxidant balances and testicular function, inhibiting inflammation and apoptosis, as well as preserving blood-testis barrier.

Investigation of 3D-printed chitosan-xanthan gum patches.

In this study, using a new polymer combination of Chitosan(CH)/Xanthan Gum(XG) has been exhibited for wound dressing implementation by the 3D-Printing method, which was fabricated due to its biocompatible, biodegradable, improved mechanical strength, low degradation rate, and hydrophilic nature to develop cell-mimicking, cell adhesion, proliferation, and differentiation. Different concentrations of XG were added to the CH solution as 0.25, 0.50, 0.75, 1, and 2 wt% respectively in the formic acid/distilled water (1.5:8.5) solution and rheologically characterized to evaluate their printability. The results demonstrated that high mechanical strength, hydrophilic properties, and slow degradation rate were observed with the presence and increment of XG concentration within the 3D-Printed patches. Moreover, in vitro cell culture research was conducted by seeding NIH 3T3 fibroblast cells on the patches, proving the cell proliferation rate, viability, and adhesion. Finally, 1% XG and 4% CH containing 3D-Printed patches were great potential for wound dressing applications.

Apocynin reduces cytotoxic effects of monosodium glutamate in the brain: A spectroscopic, oxidative load, and machine learning study.

Herein, we examined the modulatory effects ofApocynum (APO) on Monosodium Glutamate (MSG)-induced oxidative damage on the brain tissue of rats after long-term consumption of blood serum components by biochemical assays, Fourier transform infrared spectroscopy(FTIR), and machine learning methods. Sprague-Dawley male rats were randomly divided into the Control, Control + APO, MSG, and MSG + APO groups (n = 8 per group). All administrations were made by oral gavage saline, MSG, or APO and they were repeated for 28 days of the experiments. Brain tissue and blood serum samples were collected and analyzed for measurement levels ofmalondialdehyde (MDA),glutathione (GSH),myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and Spectroscopic analysis. After 29 days, the results were evaluated using machine learning (ML). The levels of MDA and MPO showed changes in the MSG and MSG + APO groups, respectively. Changes in the proteins and lipids were observed in the FTIR spectra of the MSG groups. Additionally, APO in these animals improved the FTIR spectra to be similar to those in the Control group. The accuracy of the FTIR results calculated by ML was 100%. The findings of this study demonstrate that Apocynin treatment protectsagainst MSG-induced oxidative damage by inhibitingreactive oxygen speciesand upregulatingantioxidant capacity, indicating its potential in alleviatingthe toxic effects of MSG.

Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study.

PURPOSE: The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. METHOD: Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 µL of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. RESULTS: The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. CONCLUSION: The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.

Morphological evaluation of the effects of exercise on high-fat-diet-induced liver damage in rats.

BACKGROUND/AIMS: This study was aimed to investigate the protective effects of swimming exercise on nonalcoholic fatty liver disease (NAFLD) associated with high fat diet-induced obesity, using microscopical and biochemical parameters. MATERIALS AND METHODS: Sprague Dawley male rats were fed either standard chow (STD group; 6% fat) or high-fat diet (HFD group; 45% fat) for 18 weeks. Animals were divided into four groups, STD, STD + EXC, HFD, HFD + EXC. Exercise groups were submitted to swimming training 5 days of week and 1h of per day, during the last 6 weeks of the experiment. At the end of the experiment, liver samples were evaluated for morphologically and ultrastructurally. Moreover, malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in liver samples. RESULTS: Normal morphology of liver parancyma with hepatocytes and sinusoids was observed in the STD and STD+EXC groups. Steatosis, lipid accumulation, ballooned hepatocytes, decrease of glycogen deposits and fibrosis in periportal area were observed in HFD group. Liver MDA level was increased and GSH level was decreased in HFD group. Exercise treatment ameliorated these morphological and oxidative changes in HFD induced liver damage. CONCLUSION: Based on morphological and biochemical analysis, we could conclude that swimming training ameliorated obesity-induced liver damage by regulating lipid accumulation and oxidative damage.

Evaluation of biochemical parameters in Rubus tereticaulis treated rats and its implications in wound healing.

We evaluated the effects of Rubus tereticaulis in healing process by determining the total carbonyl content, collagen synthesis, and total protein level on rat wounded tissues. Wounds were performed in the back of 54 Wistar rats, using a biopsy punch instrument with 0.6 mm in diameter. Rats were randomly divided into three groups: (i) un-treatment wounds group served as "controls", (ii) Madecassol® used as "positive control" group, and (iii) the application of topical cream of R. tereticaulis served as "treatment" group of wound healing. The animals were killed at the end of experiment under anesthesia with ketamine, and tissue samples were collected for the evaluation at three times intervals (3rd, 7th, and 14th day). The wounded areas were analyzed for total carbonyl content, collagen, and total protein levels by HPLC, ELISA, and spectrophotometric methods, respectively. Total carbonyl content in the treatment group was significantly lower in comparison with control group on 3rd day (2.839 ± 0.438 vs. 3.216 ± 0.216 nmol carbonyl/mol protein; p < 0.5) and 14th days (4.222 ± 0.128 vs. 4.784 ± 0.077 nmol carbonyl/mol protein; p < 0.05), respectively. New collagen formation on the wound sites after the initial injury was noted in the treated and positive control groups (5.310 ± 0.331 vs. 5.164 ± 0.377 mg collagen/g wet tissue) at the 3rd day than control group (2.180 ± 0.718 mg collagen/g wet tissue, p < 0.01), and in treated and positive control groups at 7th day (9.654 ± 0.201, 9.053 ± 1.062 mg collagen/g wet tissue, p < 0.01); and in treated and positive control groups at 14th day (8.469 ± 0.236, 5.631 ± 0.531 mg collagen/g wet tissue, respectively; p < 0.05) in comparison with the control group. Total protein level of samples did not change significantly between the groups. Thus, application of R. tereticaulis ameliorated the wound healing process in rats as it facilitated collagen formation through healing of the wound. Evaluating total carbonyl content by HPLC could be useful as an advance procedure for quantification of healing.

Synthesis and Anticancer and Antimicrobial Evaluation of Novel Ether-linked Derivatives of Ornidazole.

OBJECTIVES: Some novel 1-(2-methyl-5-nitro-1H-imidazol-1-yl)-3-(substituted phenoxy)propan-2-ol derivatives (3a-g) were designed and synthesized. MATERIALS AND METHODS: Compounds 3a-g were obtained by refluxing ornidazole (1) with the corresponding phenolic compounds (2a-g) in the presence of anhydrous K2CO3 in acetonitrile. RESULTS: Following the structure elucidation, the in vitro antimicrobial activity and cytotoxic effects of compounds 3a-g on K562 leukemia and NIH/3T3 mouse embryonic fibroblast cells were measured. As a part of this study, the compliance of the compounds with the drug-likeness properties was evaluated. The physico-chemical parameters (log P, TPSA, nrotb, number of hydrogen bond donors and acceptors, logS) were calculated using the software OSIRIS. CONCLUSION: All the synthesized compounds except 3a showed significant activity (MIC=4-16 µg mL-1) against the bacterial strain Bacillus subtilis as compared to the standard drug, whereas antileukemic activities were rather limited. Furthermore, all the compounds were nontoxic and the selectivity index outcome indicated that the antileukemic and antimicrobial effects of the compounds were selective with good estimated oral bioavailability and drug-likeness scores.

Effects of dapagliflozin in experimental sepsis model in rats.

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p<0.05). Dapagliflozin also decreased oxidative stress (MDA) in lung tissue and decreased inflammation (MPO) in lung and liver tissue (p<0.05). Caspase 8 and 9 levels in kidney, lung, and liver tissue were increased (p<0.05) in the dapagliflozin group compared with the sepsis group. According to the histopathological results, sepsis was moderately improved in renal tissue and slightly attenuated in lung and liver tissue with the administration of dapagliflozin. CONCLUSION: Dapagliflozin had a preventive effect on sepsis-induced kidney damage, but the protective effect was mild in lung and liver tissue in the present study.

Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats.

We investigated the protective effects of swimming exercise on high-fat diet-induced heart and aorta damage by evaluating oxidative stress and the endothelial nitric oxide (NO) system. Sprague Dawley rats were fed either standard chow (STD, 6% fat) or high-fat diet (HFD; 45% fat) for 18 weeks, with half of the animals trained by daily swimming sessions (EXC; 1 h per day for 5 days/week) for the last 6 weeks of the experimental period and half kept sedentary (SED). Heart and aorta tissues were prepared for routine light and electron microscopy evaluation. Endothelial NOS (eNOS) and inducible NOS (iNOS) distribution in the tissue samples were examined by immunohistochemistry. Biochemical examinations, including blood serum lipid profiles, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and tissue NO levels were measured. Deteriorated heart and aorta morphology, increased MDA levels and iNOS-immunoreactivity (iNOS-ir), as well as decreased GSH, NO, SOD, and eNOS-ir parameters were observed in the HFD + SED group. These morphological and biochemical parameters were ameliorated in the HFD + EXC group. Our study revealed that obesity-induced iNOS activation and increased oxidative stress in cardiac and aorta tissues. Exercise protected the obesity-induced cardiac and aortic tissue damage by modulating oxidant/antioxidant balance via involvement of the NO system.

Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats.

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.

Reference intervals for growth arrest-specific 6 protein in adults.

The objective of this study was to establish reference intervals for growth arrest-specific 6 (GAS6), a vitamin K-dependent protein, in human adult plasma according to the Guideline of Clinical and Laboratory Standards Institute (CLSI) C28-A3. Blood samples were collected from 308 healthy volunteers aged 18-72 (157 female, 151 male). A non-parametric approach was used to calculate the reference interval. The plasma GAS6 reference interval was determined, with 90% confidence interval: the lower limit (2.5 percentile) was 2.5 (1.9-3.1) µg/L and the upper limit (97.5 percentile) = 18.8 (18.0-22.3) µg/L. Harris-Boyd's test did not suggest partitioning by age or gender: medians for males [7.8 (5.8-10.7) µg/L] and females [9.9 (7.1-13.5) µg/L]. Three age-subgroups were tested: 18-29 years (n = 168); 30-44 years (n = 73); 45-72 years (n = 67). The intra- and inter-assay variations were 12.6% (mean, 5.2 ± 0.7 µg/L) and 14.0% (mean, 9.2 ± 1.3 µg/L), respectively. The mean recovery was 104%. This study reports plasma GAS6 reference intervals established first according to the guideline of CLSI C28-A3.

Evaluation of Cardiovascular Risk Factors, Haematological and Biochemical Parameters, and Serum Endocan Levels in Patients with Lichen Planus.

BACKGROUND AND OBJECTIVE: The current study aimed to evaluate cardiovascular risk factors, haematological and biochemical parameters, and serum endocan concentrations in lichen planus (LP) patients. METHODS: This study was conducted with 86 cases, including 43 LP patients and 43 healthy controls. Cardiovascular risk factors, haematological and biochemical parameters, and endocan levels were evaluated. RESULTS: The serum endocan concentrations of LP patients were not significantly different from those of the healthy controls (p > 0.05). There were no significant differences in the serum endocan levels according to classification by cardiovascular risk factors and smoking history (p > 0.05). In the LP group, white blood cell count, platelet distribution width and monocyte count/high-density lipoprotein cholesterol ratios were significantly higher when compared to the healthy controls (p < 0.05). The LP group had a lower mean platelet volume than the healthy controls (p < 0.05). CONCLUSIONS: Serum endocan levels did not change significantly in patients with LP, and there were significant differences in haematological and biochemical parameters.

Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells.

In this study, a series of thiosemicarbazide derivatives 12-14, 1,2,4-triazol-3-thione derivatives 15-17 and compounds bearing 2-(4H-1,2,4-triazole-3-ylthio)acetamide structure 18-32 have been synthesized starting from phenolic compounds such as 2-naphthol, paracetamol and thymol. Structures and purity of the target compounds were confirmed by the use of their chromatographic and spectral data besides microanalysis. All of the synthesized new compounds 12-32 were evaluated for their anti-HIV activity. Among these compounds, three representatives 18, 19 and 25 were selected and evaluated by the National Cancer Institute (NCI) against the full panel of 60 human cancer cell lines derived from nine different cancer types. Antiproliferative effects of the selected compounds were demonstrated in human tumor cell lines K-562, A549 and PC-3. These compounds inhibited cell growth assessed by MTT assay. Compound 18, 19 and 25 exhibited anti-cancer activity with IC50 values of 5.96 µM (PC-3 cells), 7.90 µM (A549/ATCC cells) and 7.71 µM (K-562 cells), respectively. After the cell viability assay, caspase activation and Bcl-2 activity of the selected compounds were measured and the loss of mitochondrial membrane potential (MMP) was detected. Compounds 18, 19 and 25 showed a significant increase in caspase-3 activity in a dose-dependent manner. This was not observed for caspase-8 activity with compound 18 and 25, while compound 19 was significantly elevated only at the dose of 50 µM. In addition, all three compounds significantly decreased the mitochondrial membrane potential and expression of Bcl-2.

Association between the growth arrest-specific 6 (Gas6) gene polymorphism c.834 + 7G>A and preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a hypertensive disease of pregnancy complicating 2-8% of all pregnancies. The exact pathophysiology still remains unknown. Growth arrest-specific 6 (Gas6) is a member of the vitamin K-dependent protein family and it has been suggested as a novel atherothrombotic risk factor with anti-angiogenic and pro-atherogenic properties. The goal of the our study was to investigate the relationships between the c.834 + 7G > A polymorphism of GAS6, plasma Gas6 levels and PE. METHODS: A total of 150 women, including 82 preeclamptic pregnant women and 68 normotensive pregnant (NP) women, were recruited in the current study. Blood samples were taken from all participants. Plasma Gas6 levels measured by an enzyme-linked immunosorbent assay. GAS6 polymorphism was determined using a PCR-RFLP method. RESULTS: The plasma Gas6 levels of preeclamptic patients were significantly lower than those of NP women (8.65 ± 3.70 ng/ml and 10.89 ± 4.23 ng/ml respectively, p < 0.001). The GG genotype was the most prevalent, and the risk of PE was 3.5-fold higher in pregnant women with GG genotype compared to woman with AA genotype (p < 0.01). The A allele was less frequent in preeclamptic patients than in control subjects (OR = 2.118, 95% CI = 1.330-3.371, p < 0.001). CONCLUSIONS: Our results suggest that GAS6 c.834 + 7G > A polymorphism may have a pivotal role in the pathogenesis of PE suggesting that the A allele has a protective role for PE.

Synthesis of Diflunisal Thiazolidinones as Anticancer Agents.

A series of diflunisal 4-thiazolidinones were synthesized. Some selected compounds were determined at one dose towards the full panel of 60 human cancer cell lines by National Cancer Institute. 2',4'-Difluoro-4-hydroxy-N-[4-oxo-2-(thiophen-2-yl)-1,3-thiazolidin-3-yl]biphenyl- 3-carboxamide (4a) demonstrated the most marked effect on K-562 cancer cell line with 58.59 % growth inhibition at 10 µM. Compound 4a was evaluated in vitro using the MTT colorimetric method against human leukemia cell line K-562 and mouse embryonic fibroblasts cell line NIH- 3T3 at different doses for cell viability and growth inhibition. Compound 4a exhibited anticancer activity with IC50 value of 5.2 µM against K-562 cells and did not display cytotoxicity towards NIH-3T3 cells compared with diflunisal. In addition, this compound could be an interesting prototype as an antiproliferative agent.