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1.
Asian Pac J Cancer Prev ; 25(6): 2023-2032, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38918664

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients. MATERIAL & METHODS: We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival. RESULTS: Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival. CONCLUSIONS: Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Gene Amplification , Receptor, ErbB-2 , Humans , Male , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/mortality , Female , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Middle Aged , Egypt/epidemiology , Prognosis , Survival Rate , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Aged , Adult , Follow-Up Studies , In Situ Hybridization, Fluorescence , Lymphatic Metastasis , Neoplasm Staging , Immunohistochemistry
2.
J Biochem ; 175(1): 69-83, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37787553

ABSTRACT

Glutathione transferase Pi (GSTP1) expression is increased in many cancer types and is associated with multidrug resistance and apoptosis inhibition. Inhibitors of GSTP1-1 have the potential to overcome drug resistance and improve chemotherapy efficacy as adjuvant agents. This study investigated the effects of catechin and gossypol on human glutathione transferase Pi (GSTP1-1) activity and their cytotoxic effects on breast cancer cells (MCF-7) individually and in combination with tamoxifen (TAM). Gossypol effectively inhibited the enzyme with an IC50 value of 40 µM, compared to 200 µM for catechin. Gossypol showed stronger inhibition of GSTP1-1 activity (Ki = 63.3 ± 17.5 µM) compared to catechin (Ki = 220 ± 44 µM). Molecular docking analysis revealed their binding conformations to GSTP1-1, with gossypol binding at the subunit interface in an un-competitive manner and catechin showing mixed non-competitive inhibition. Gossypol had severe cytotoxic effects on both MCF-7 cells and normal BJ1 cells, while catechin had a weak cytotoxic effect on MCF-7 cells only. Combination therapy with TAM resulted in cytotoxicity of 27.3% and 35.2% when combined with catechin and gossypol, respectively. Gossypol showed higher toxicity to MCF-7 cells, but its strong effects on normal cells raised concerns about selectivity and potential side effects.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Catechin , Gossypol , Humans , Female , Glutathione Transferase/metabolism , MCF-7 Cells , Molecular Docking Simulation , Gossypol/pharmacology , Catechin/pharmacology , Antineoplastic Agents/pharmacology
3.
Life Sci ; 327: 121806, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37257579

ABSTRACT

AIMS: Roflumilast, a well-known phosphodiesterase-4 (PDE-4) inhibitor, possess an anti-inflammatory activity with approved indications in chronic obstructive pulmonary disease. This study aimed to evaluate the neuroprotective role of roflumilast in ovariectomy (OVX)-induced depressive-like behavior in female rats and to shed light on a potential autophagy enhancing effect. MAIN METHODS: Rats were randomly divided into four groups: sham, OVX, OVX + roflumilast (1 mg/kg, p.o), and OVX + roflumilast + chloroquine (CQ) (50 mg/kg, i.p). Drugs were administered for 4 weeks starting 2 weeks after OVX. KEY FINDINGS: Roflumilast improved the depressive-like behaviors observed in OVX rats as evidenced by decreasing both forced swimming and open field immobility times while, increasing % sucrose preference and number of open field crossed squares. Histopathological analysis provides further evidence of roflumilast's beneficial effects, demonstrating that roflumilast ameliorated the neuronal damage caused by OVX. Roflumilast antidepressant potential was mediated via restoring hippocampal cAMP and BDNF levels as well as down-regulating PDE4 expression. Moreover, roflumilast revealed anti-inflammatory and anti-apoptotic effects via hindering TNF-α level and diminishing Bax/Bcl2 ratio. Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression. The autophagy inhibitor CQ was used to demonstrate the suggested pathway. SIGNIFICANCE: The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities. Roflumilast could offer a more secure alternative to hormone replacement therapy for postmenopausal depression treatment.


Subject(s)
AMP-Activated Protein Kinases , Depression , Ovariectomy , Phosphodiesterase 4 Inhibitors , Animals , Female , Rats , AMP-Activated Protein Kinases/metabolism , Autophagy , Autophagy-Related Protein-1 Homolog/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Ovariectomy/adverse effects , Phosphodiesterase 4 Inhibitors/pharmacology , TOR Serine-Threonine Kinases
4.
Environ Sci Pollut Res Int ; 30(18): 53548-53565, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36859644

ABSTRACT

Herein, eco-friendly mesoporous magnetic activated carbon-based agro-waste nanosorbents incorporating antimicrobial silver nanoparticles (Mag@AC1-Ag and Mag@AC1-Ag) have been prepared. Various techniques (XRD, SEM/EDX, TEM, FTIR, and BET analysis) were employed to characterize the prepared nanosorbents before being utilized as novel nanosorbents to remove Pb+2 and Cd+2 ions. Mag@AC1-Ag and Mag@AC1-Ag exhibited rapid and excellent uptake of Pb+2 and Cd+2. The pseudo-second-order kinetics and the Langmuir isotherm are more suitable for the explanation of the experimental results. The thermodynamic parameters showed that the Pb+2 and Cd+2 sorption by the nanosorbents was a spontaneous and endothermic reaction. The prepared nanosorbents can be effectively regenerated using HCl and recycled up to the fifth cycle. These nanosorbents' potential uses for eliminating Pb+2 and Cd+2 from real water samples were evaluated. Moreover, the results revealed that both Mag@AC1-Ag and Mag@AC2-Ag exhibited high antimicrobial activity against fecal coliform (gram-negative) and Bacillus subtilis (gram-positive).


Subject(s)
Metal Nanoparticles , Water Pollutants, Chemical , Wastewater , Cadmium/analysis , Charcoal , Lead/analysis , Silver/analysis , Adsorption , Magnetic Phenomena , Kinetics , Water Pollutants, Chemical/analysis , Hydrogen-Ion Concentration
5.
Prev Nutr Food Sci ; 27(3): 282-298, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-36313063

ABSTRACT

The function of antioxidant polyphenols has been demonstrated for their ability to protect against a variety of diseases. However, some antioxidants have been shown to be pro-oxidant. Some of the important antioxidant enzymes are glutathione transferases (GST), which are involved in maintaining redox homeostasis. GST class Pi (GSTP1-1) hyper-activation is a feature that is found in cancer. This work aims to demonstrate the relationship between the phytochemicals of 18 plants and their ability to act as antioxidant/pro-oxidant agents, as well as their effects on the activity of GSTP1-1 and their cellular toxicity. Tamarindus indica, Cinnamomum verum, and Alpinia galanga extracts had high phytochemical contents, moderate heavy metal levels, and antioxidant/pro-oxidant activities. Among the main plant components identified using high-performance liquid chromatography, only chlorogenic acid, catechin, and quercetin can function as antioxidants and pro-oxidants. Hibiscus sabdariffa, C. verum, A. galanga, T. indica, Gossypium arboreum, and Punica granatum were among the plant extracts examined that inhibited the activity of the purified recombinant GSTP1-1, with the inhibition constant values ranging from 0.48 to 1.67 mg of gallic acid equivalent/g. The level of cytotoxicity was also studied to determine the effects of these extracts on human Caucasian breast cancer. The findings revealed that plants with high phenol content had an antioxidant/pro-oxidant capacity as well as inhibition of the activity of GST. However, the cytotoxic effect was not associated with all of the extracts, which indicates that polyphenols interact with other components that may influence their observed behavior.

6.
Ann Hematol ; 100(7): 1701-1709, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33982136

ABSTRACT

Immune thrombocytopenia (ITP) is a disorder in which autoantibodies are responsible for destruction and decreased production of platelets. In the meantime, thrombocytopenia is frequent in patients with myelodysplastic syndromes (MDS) and immune clearance of megakaryocytes could be a reason. The aim of the present study is to evaluate and compare IgG binding to megakaryocytes in bone marrow of ITP and MDS patients to determine megakaryocytes targeting by autoantibodies in vivo as a mechanism of platelet underproduction in these disorders. The study was carried out on 20 ITP (group I) patients, 20 thrombocytopenic patients with (MDS) (group II), and 20 non-ITP patients as a control (group III) who were admitted to Minia University Hospital. Serial histological sections from bone marrow biopsies were stained for IgG. All patients in group I and 50% of group II patients showed bleeding tendency and the difference was significant (p < 0.001). No patient experienced fatigue in group I while 35% of patients in group II complained of easy fatigability, and the difference was significant (p < 0.008). High IgG antibody binding was found in ITP and MDS compared to the control group but no significant difference between ITP and MDS patients (14/20 (70%) vs. 13/20 (65%)) (p value = 0.736). Antibody binding to megakaryocytes in a proportion of MDS patients suggests that immune-mediated mechanism underlies platelet underproduction in those patients.


Subject(s)
Immunoglobulin G/metabolism , Megakaryocytes/metabolism , Thrombocytopenia/immunology , Adult , Anemia, Aplastic/complications , Anemia, Megaloblastic/complications , Autoantibodies/immunology , Autoantibodies/metabolism , Bone Marrow/immunology , Bone Marrow/pathology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/immunology , Male , Megakaryocytes/immunology , Middle Aged , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/pathology , Thrombocytopenia/etiology , Thrombocytopenia/pathology , Young Adult
7.
Toxicol Mech Methods ; 31(6): 437-449, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33775218

ABSTRACT

This study investigates the hepatoprotective effect of bone marrow mononuclear cells (BM-MNCs) transplantation, N-acetylcysteine (NAC) and α-lipoic acid (ALA). Rats were administrated carbon tetrachloride (CCl4) (1 mg/kg, i.p.) twice/week for 8 weeks for the induction of hepatotoxicity. 7 groups of rats were used as follows: Normal control, CCl4, CCl4 co-administered with BM-MNCs (1 × 106 in 0.1 ml PBS, i.v.), or NAC (300 mg/kg, p.o) or ALA (100 mg/kg, p.o) single or combination. Liver function was tested by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin as well as interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (Gpx), superoxide dismutase (SOD) and catalase (CAT) activities in liver homogenates. Besides that, estimation of DNA damage was performed. In addition to Micronucleus test and histopathological investigation. CCl4 treated rats showed elevation in ALT, AST, TNF-α, IL-6 and MDA accompanied by reduction in ALB, IL-10, SOD, CAT, GPx and TAC and increased the number of DNA breaks in liver tissue, showed many micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow. NAC, ALA, BM-MNCs and their combination caused a reduction of ALT, AST, while, increase albumin, CAT, TAC, GPx, SOD as compared to CCl4 treated groups. Also decrease in MDA, IL-6 and TNF-α concurrently with an increase in IL-10. Moreover, BM-MNCs, NAC, ALA, and their combination decreased DNA tail %, and the count of MnPCEs. BM-MNCs combination with NAC or ALA exerted significant antioxidant, anti-inflammatory and anti-cytogenetical aberrations effect compared to each of them alone.HighlightsCCl4 elevated ALT, AST, TNF-α, IL-6 and MDACCl4 reduced ALB, IL-10, SOD, CAT, GPx and TACCCl4 increased the number of DNA breaks in liverNAC, ALA and BM-MNCs reduced ALT, AST, while, increase albumin, CAT, TAC, GPx, SODNAC, ALA and BM-MNCs decreased in MDA, IL-6 and TNF-α and increased IL-10 [Figure: see text].


Subject(s)
Chemical and Drug Induced Liver Injury , Acetylcysteine/metabolism , Animals , Antioxidants/metabolism , Bone Marrow , Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Liver/metabolism , Oxidative Stress , Rats , Thioctic Acid/metabolism
8.
Animals (Basel) ; 10(10)2020 Oct 05.
Article in English | MEDLINE | ID: mdl-33027914

ABSTRACT

The potential effects of cacao bean meal, Theobroma cacao L., (CBM) on the growth, health status, blood biochemical parameters, antioxidant, immune status, physiological parameters, female reproductive performance, and gonadal histological features of fantail goldfish (Carassius auratus, L.) were evaluated using a complete randomized block design with sex as a block. The trial lasted for 60 days. A total of 54 healthy fantail goldfish (36 broodstock females and 18 broodstock males) were randomly allocated into three treatments with supplementation of three levels of cocoa powder 0, 5, and 10 g kg-1 diet, CBM0, CBM5, and CBM10, respectively, with the sex ratio being four females:two males per replicate. The body weight gain and feed conversion ratio of males were increased in the CBM10 treatment (p < 0.05). The CBM10 diet improved relative feed costs (p < 0.05). Females fed on the CBM10 diet had an increase in the serum level of total protein (p = 0.001). Females fed on a diet supplemented with CBM5 showed a decrease in the serum level of triglyceride compared to females fed on CBM0 and CBM10 diets (p = 0.03). CBM10 diet increased the serum superoxide dismutase (SOD) activity of fish compared to CBM0 and CBM5 diets (p = 0.004). Serum levels of testosterone and estradiol were significantly increased in males fed on the CBM10 diet. The female reproductive performance was improved by CBM supplementation (p < 0.05). Ovarian histology exhibited increased granulation and follicle numbers after dietary CBM supplementation compared to the control treatment. Therefore, cacao bean meal can be used as a feed supplement in the diets of fantail goldfish for improving the growth, health status, and female reproductive performance, economic efficiency, and gonadal histological structure.

9.
J Phys Chem Lett ; 10(10): 2487-2492, 2019 May 16.
Article in English | MEDLINE | ID: mdl-31039610

ABSTRACT

The interaction of water with the most prominent surfaces of Fe3O4, (001) and (111), is directly compared using a combination of temperature-programmed desorption, temperature-programmed low energy electron diffraction (TP LEED), and scanning probe microscopies. Adsorption on the (√2 × âˆš2)R45°-reconstructed surface of Fe3O4(001) is strongly influenced by the surface reconstruction, which remains intact at all coverages. Close to the completion of the first monolayer, however, the ad-layer adopts a longer-range (2 × 2) superstructure. This finding is discussed in the context of a similar (2 × 2) superstructure recently observed on the (111) facet, which exists over a significantly larger range of temperatures and coverages. In both cases, the long-range order is evidence that water-water interactions exert a significant influence on the structure already prior to the nucleation of the second layer. We conclude that the stability differences stem from the smaller unit cell on the (111) surface, and the ability of water to more easily form stable hexagonal ice-like structures on the hexagonal substrate.

10.
World J Nucl Med ; 18(4): 378-388, 2019.
Article in English | MEDLINE | ID: mdl-31933554

ABSTRACT

The aim of our study was to evaluate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in prediction of response to neoadjuvant chemotherapy (NAC) in pediatric osteosarcoma (OS) patients compared to percentage of tumor necrosis after surgical excision of the tumor. Forty-six pediatric OS patients treated with neoadjuvant chemotherapy and surgery were underwent PET/CT and MRI before, after 3 cycles, and after the completion of neoadjuvant chemotherapy. Imaging parameters include maximum standardized uptake value (SUVmax1, 2, and 3), tumor liver ratio (TLR 1, 2, and 3), and MRI tumor volume (MRTV 1, 2, and 3) at initial assessment before starting NAC, after finishing three cycles and after finishing 6 cycles before tumor excision, respectively. Cutoff values of the PET/CT and MRI parameters were determined using receiver operating characteristic (ROC) curve analysis and percentage of tumor necrosis of postsurgical specimen. Fourteen patients were good responders (30.4%), with more than 90% tumor necrosis, while 31 patients were poor responders (67.4%). The results of one patient were missed. We noticed that higher sensitivity for detecting poor responders was detected by SUVmax3/1, TLR3/1, and MRTV2/1 ratio cutoff values, while higher specificity was detected by TRL2 and SUVmax3 cutoff values. ROC curve analysis of MRTV2/1 and MRTV3/1 ratio was fair in predicting poor responders. PET/CT parameters are capable of predicting histological response to NAC in OS patients with overall sensitivity and specificity higher than MRI parameters.

11.
Hematol Oncol Stem Cell Ther ; 12(1): 26-31, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30336122

ABSTRACT

OBJECTIVE/BACKGROUND: Chronic lymphocytic leukemia is one of the commonest leukemias affecting adults. CD39 inhibits T-cell and Natural killer (NK) cell responses by hydrolyzing adenosine triphosphate and adenosine diphosphate, suppressing the immune system. We investigated expression of CD39 on CD4+ T Lymphocytes in chronic lymphocytic leukemia (CLL) patients and its relationship with deletion 6q, its association with disease stage and survival. METHODS: Thirty CLL patients and 20 matched controls were included in the study. Bone marrow studies with immunophenotyping, CD39, CD38, and ZAP-70, and detection of del 6q by FISH were performed. RESULTS: CD39+ CD4+ T helper cells in CLL patients were significantly expressed compared with the controls (p < .001). Levels of CD39+ CD4+ T cells were significantly expressed in high risk CLL patients. Del 6q was detected in 63.3% of patients and it correlated with CD39, CD38, and ZAP-70, and advanced stage disease. There was a significant relation between response to treatment and CD39 expression and del 6q, also there was a significant difference in overall survival (OS) between patients with and without Del 6q. CONCLUSION: CD39 expression on CD4+ Tcells and del 6q act as prognostic markers in CLL. Blocking or inhibition of CD39 may be a target for new immune therapy for CLL.


Subject(s)
Apyrase , CD4-Positive T-Lymphocytes/metabolism , Chromosome Deletion , Chromosomes, Human, Pair 6/genetics , Gene Expression Regulation, Neoplastic , Leukemia, Lymphocytic, Chronic, B-Cell , Neoplasm Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Apyrase/biosynthesis , Apyrase/genetics , CD4-Positive T-Lymphocytes/pathology , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Neoplasm Proteins/genetics , Prospective Studies
12.
Vet World ; 11(7): 1006-1014, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30147273

ABSTRACT

AIM: This study aimed to create rapid characterization and genotyping of Pasteurella multocida (PM) protocol using modern molecular biology techniques. MATERIALS AND METHODS: Thirty bacterial isolates were characterized by capsular and somatic identification using conventional procedure followed by multiplex polymerase chain reaction (PCR), restriction endonucleases analysis (REA), and finally confirmed by sequence analysis. Two local vaccine strains and two field isolates were identified as PM Type A and B. RESULTS: A total of 30 isolates were found positive for PM either morphologically and biochemically; however, multiplex PCR technique identified only 22 isolates as Pasteurella species using universal primers while 8 isolates were found negative for PM. 12 of 22 isolates (54%) were characterized at the same reaction into PM Type A, five isolates (23%) were Type B and the rest five isolates (23%) of tested isolates were negative for Types A, B, and D. Hemorrhagic septicemia Type B: 2 or B: 5 could be identified somatically within PM capsular serogroup B using PCR technique. Somatic characterization of PM was done using REA that could identify all PM Type A into A:1 and all PM Type B into B: 2. These protocols were verified for its accuracy and reliability by sequence analysis of two vaccine strains of PM Type A and B that were characterized previously by biochemical and serological methods as well as two selected isolates from the 22 positive isolates representing PM Type A and B. CONCLUSION: PCR and REA could confirm the identity of PM and provide a rapid and reliable characterization in comparison with biochemical analysis and conventional serotyping that may take up to 2 weeks. Hence, they can reduce the time needed for polyvalent vaccine production and when the reference antisera are unavailable. Moreover, the identity of Omp-H for vaccine and field strains may provide better data to control Pasteurellosis in Egypt.

13.
Phys Chem Chem Phys ; 20(23): 15764-15774, 2018 Jun 13.
Article in English | MEDLINE | ID: mdl-29868669

ABSTRACT

We monitored adsorption of water on a well-defined Fe3O4(111) film surface at different temperatures as a function of coverage using infrared reflection-absorption spectroscopy, temperature programmed desorption, and single crystal adsorption calorimetry. Additionally, density functional theory was employed using a Fe3O4(111)-(2 × 2) slab model to generate 15 energy minimum structures for various coverages. Corresponding vibrational properties of the adsorbed water species were also computed. The results show that water molecules readily dissociate on regular surface Fetet1-O ion pairs to form "monomers", i.e., terminal Fe-OH and surface OH groups. Further water molecules adsorb on the hydroxyl covered surface non-dissociatively and form "dimers" and larger oligomers, which ultimately assemble into an ordered (2 × 2) hydrogen-bonded network structure with increasing coverage prior to the formation of a solid water film.

14.
Angew Chem Int Ed Engl ; 57(5): 1409-1413, 2018 01 26.
Article in English | MEDLINE | ID: mdl-29205761

ABSTRACT

The initial stages of water adsorption on magnetite Fe3 O4 (111) surface and the atomic structure of the water/oxide interface remain controversial. Herein, we provide experimental results obtained by infrared reflection-absorption spectroscopy (IRAS) and temperature-programmed desorption (TPD), corroborated by density functional theory (DFT) calculations showing that water readily dissociates on Fetet sites to form two hydroxo species. These act as an anchor for water molecules to form a dimer complex which self-assembles into an ordered (2×2) structure. Water ad-layer ordering is rationalized in terms of a cooperative effect induced by a hydrogen-bonding network.

15.
Future Med Chem ; 10(2): 157-181, 2018 01.
Article in English | MEDLINE | ID: mdl-29235906

ABSTRACT

AIM: Synthesis of novel glutathione S-transferases (GSTs) inhibitors constitutes a promising strategy in cancer treatment. Results & methodology: A new set of benzimidazoles clubbed with various heterocycles as GST inhibitors and anticancer agents were synthesized. The biological results proved the potential of the new compounds as GST inhibitors, specifically compounds 7 and 14 which produced more potency than ethacrynic acid by three- and tenfold, respectively. Most compounds exhibited promising cytotoxic activity against breast and colon cancer cell lines. Molecular modeling studies revealed that compounds 7 and 14 showed good binding with the amino acids of the GST protein. CONCLUSION: Both compounds 7 and 14 fulfilled the Lipinski's rule of five suggesting them as new promising GST inhibitors and anticancer agents.


Subject(s)
Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Enzyme Inhibitors/pharmacology , Glutathione Transferase/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Humans , Models, Molecular , Molecular Structure
16.
Ticks Tick Borne Dis ; 5(5): 528-36, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24953796

ABSTRACT

Rhipicephalus (Boophilus) annulatus is a bloodsucking ectoparasite that causes severe production losses in the cattle industry. This study aims to evaluate the in vitro effects of tannic acid, hematin (GST inhibitors) and different plant extracts (rich in tannic acid) on the activity of the recombinant glutathione S-transferase enzyme of the Egyptian cattle tick R. annulatus (rRaGST), in order to confirm their ability to inhibit the parasitic essential detoxification enzyme glutathione S-transferase. Extraction with 70% ethanol of Hibiscus cannabinus (kenaf flowers), Punica granatum (red and white pomegranate peel), Musa acuminata (banana peel) (Musaceae), Medicago sativa (alfalfa seeds), Tamarindus indicus (seed) and Cuminum cyminum (cumin seed) were used to assess: (i) inhibitory capacities of rRaGST and (ii) their phenolic and flavonoid contents. Ethanol extraction of red pomegranate peel contained the highest content of phenolic compounds (29.95mg gallic acid/g dry tissue) compared to the other studied plant extracts. The highest inhibition activities of rRaGST were obtained with kenaf and red pomegranate peel (P. granatum) extracts with IC50 values of 0.123 and 0.136mg dry tissue/ml, respectively. Tannic acid was the more effective inhibitor of rRaGST with an IC50 value equal to 4.57µM compared to delphinidine-HCl (IC50=14.9±3.1µM). Gossypol had a weak inhibitory effect (IC50=43.7µM), and caffeic acid had almost no effect on tick GST activity. The IC50 values qualify ethacrynic acid as a potent inhibitor of rRaGST activity (IC50=0.034µM). Cibacron blue and hematin showed a considerable inhibition effect on rRaGST activity, and their IC50 values were 0.13µM and 7.5µM, respectively. The activity of rRaGST was highest for CDNB (30.2µmol/min/mg protein). The enzyme had also a peroxidatic activity (the specific activity equals 26.5µmol/min/mg protein). Both tannic acid and hematin inhibited rRaGST activity non-competitively with respect to GSH and competitively with respect to CDNB. While red pomegranate extracts inhibited rRaGST activity competitively with respect to GSH, uncompetitive inhibition was observed with respect to CDNB.


Subject(s)
Glutathione Transferase/antagonists & inhibitors , Phenols/pharmacology , Plant Extracts/pharmacology , Recombinant Proteins/metabolism , Rhipicephalus/enzymology , Animals , Gene Expression Regulation, Enzymologic/drug effects , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Kinetics , Phenols/chemistry , Plant Extracts/chemistry , Substrate Specificity
17.
Sci Technol Adv Mater ; 9(1): 015007, 2008 Jan.
Article in English | MEDLINE | ID: mdl-27877944

ABSTRACT

We investigated the doping of thin polyaniline (PANI) films, prepared by the chemical oxidation of aniline, with different acids. The initial step in the investigation is the preparation of PANI films from aqueous hydrochloric acid solution. This is followed by dedoping with ammonia to obtain a PANI base, which is subsequently doped with strong acids (e.g. hydrochloric, sulfuric, phosphoric and trichloroacetic acids) and with a weak acid (acetic acid). The dopant weight fraction ( w ), which is connected with the gain of mass during the doping of PANI, was determined in situ using a quartz crystal microbalance (QCM). The behavior of PANI upon doping with different anions derived from strong acids indicates that both proton and the anion uptake into the polymer chains occur sharply, rapidly, completely, and reversibly. However the uptake in the case in acetic acid is characterized by slow diffusion. The doping was studied at different concentrations of acetic acid. A second cycle of dedoping-redoping was also performed. The kinetics of the doping reaction is dominated by Fickian diffusion kinetics. The diffusion coefficients (D) of the dopant ions into the PANI chains were determined using the QCM and by UV-Vis absorption spectroscopy in the range of (0.076-1.64)× 10-15 cm2 s-1. It was found that D in the second cycle of doping is larger than that evaluated from the first cycle of doping for high concentrations of acetic acid. D for the diffusion and for the dopant ion expulsion from the PANI chains was also determined during the redoping process. It was found that D for acetic acid ions in the doping process is larger than that calculated for the dedoping process.

18.
Invest Ophthalmol Vis Sci ; 47(6): 2515-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16723464

ABSTRACT

PURPOSE: To use an experimental animal model to study the effect on intraocular pressure (IOP) of methylcellulose 2% application in trabeculectomy, followed by histologic assessment. METHODS: Trabeculectomy was performed on albino rabbits' eyes. The study comprised two groups, each group consisting of five rabbits. The right eyes were subjected to trabeculectomy, and the left eyes served as the control. In both groups 1 and 2, trabeculectomy was performed in the right eyes, but in group 2, trabeculectomy was followed by injection of methylcellulose 2% into the anterior chamber. The methylcellulose was allowed to pass through the trabeculectomy site into the subconjunctival space, and an extra amount was injected by the same cannula under the conjunctiva in the area of the trabeculectomy from the edge of the periotomy. Measurement of IOP was performed with a Shiotz tonometer once weekly for 4 weeks. Specimens were obtained from the operative site, and semithin sections were prepared, stained with toluidine blue, and examined by light microscopy (LM). RESULTS: A significant difference in the decrease of IOP (P<0.0001) was observed between the two groups after 4 weeks of surgery. During the 4 weeks after trabeculectomy, the mean IOP was 18.2+/-0.45 mm Hg without methylcellulose injection and 18.3+/-0.77 mm Hg in the control eyes, and 9.8+/-0.84 mm Hg with methylcellulose injection, 18.25+/-0.7 mm Hg in the control eyes. The histopathological findings in group 1 (without methylcellulose injection) showed the subscleral spaces to be less fenestrated, with deposition of dense collagen bundles intermingled with the fibrocytes, some of which were active with prominent mitosis. In contrast, in group 2 (injected with methylcellulose), the subscleral space appeared fenestrated with irregularly and widely spaced segmented collagen bundles. CONCLUSIONS: Methylcellulose may have antihealing properties that serve to decrease IOP in trabeculectomy. Although more work is needed in humans, because human tissue may be different in its response to the same procedure, the use of methylcellulose could be very promising.


Subject(s)
Conjunctiva/drug effects , Methylcellulose/pharmacology , Sclera/drug effects , Trabeculectomy , Wound Healing/drug effects , Animals , Anterior Chamber/drug effects , Conjunctiva/pathology , Injections , Intraocular Pressure/drug effects , Methylcellulose/administration & dosage , Models, Animal , Rabbits , Sclera/pathology
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