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1.
Sci Rep ; 14(1): 14382, 2024 06 22.
Article in English | MEDLINE | ID: mdl-38909063

ABSTRACT

Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole's biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.


Subject(s)
Antifungal Agents , Fluconazole , Microbial Sensitivity Tests , Monoterpenes , Nanostructures , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/administration & dosage , Fluconazole/pharmacology , Fluconazole/chemistry , Monoterpenes/pharmacology , Monoterpenes/chemistry , Nanostructures/chemistry , Lipids/chemistry , Drug Synergism , Drug Carriers/chemistry , Particle Size , Candida/drug effects
2.
Sci Rep ; 14(1): 6884, 2024 03 22.
Article in English | MEDLINE | ID: mdl-38519561

ABSTRACT

Mosquito-borne diseases represent a growing health challenge over time. Numerous potential phytochemicals are target-specific, biodegradable, and eco-friendly. The larvicidal activity of essential oils, a jasmine blend consisting of Jasmine oil and Azores jasmine (AJ) (Jasminum sambac and Jasminum azoricum) and peppermint (PP) Mentha arvensis and their nanoformulations against 2nd and 4th instar larvae of Culex pipiens, was evaluated after subjecting to different concentrations (62.5, 125, 250, 500, 1000, and 2000 ppm). Two forms of phase-different nanodelivery systems of layered double hydroxide LDH and oil/water nanoemulsions were formulated. The synthesized nanoemulsions showed particle sizes of 199 and 333 nm for AJ-NE and PP-NE, with a polydispersity index of 0.249 and 0.198, respectively. Chemical and physiochemical analysis of TEM, SEM, XRD, zeta potential, drug loading capacity, and drug release measurements were done to confirm the synthesis and loading efficiencies of essential oils' active ingredients. At high concentrations of AJ and PP nanoemulsions (2000 ppm), O/W nanoemulsions showed higher larval mortality than both LDH conjugates and crude oils. The mortality rate reached 100% for 2nd and 4th instar larvae. The relative toxicities revealed that PP nanoemulsion (MA-NE) was the most effective larvicide, followed by AJ nanoemulsion (AJ-NE). There was a significant increase in defensive enzymes, phenoloxidase, and α and ß-esterase enzymes in the treated groups. After treatment of L4 with AJ, AJ-NE, PP, and PP-NE, the levels of phenoloxidase were 545.67, 731.00, 700.00, and 799.67 u/mg, respectively, compared with control 669.67 u/mg. The activity levels of α-esterase were 9.71, 10.32, 8.91, and 10.55 mg α-naphthol/min/mg protein, respectively. It could be concluded that the AJ-NE and PP-NE nanoformulations have promising larvicidal activity and could act as safe and effective alternatives to chemical insecticides.


Subject(s)
Culex , Insecticides , Jasminum , Oils, Volatile , Animals , Mentha piperita , Monophenol Monooxygenase , Oils, Volatile/pharmacology , Insecticides/pharmacology , Esterases , Larva
3.
Sci Rep ; 14(1): 6248, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38486053

ABSTRACT

Mosquitoes are one of the deadliest and most hazardous animals on Earth, where they transmit several diseases that kill millions of people annually. There is an ongoing search almost everywhere in the world for more effective and contemporary ways to control mosquitoes other than pesticides. Phytochemicals are affordable, biodegradable biological agents that specialize in eliminating pests that represent a risk to public health. The effectiveness of Acacia nilotica methanol and aqueous leaf extracts against 4th instar larvae was evaluated. The results revealed that the methanol extract of A. nilotica had a noticeable influence on the mortality rate of mosquito larvae, especially at high concentrations. Not only did the mortality rate rise significantly, but the hatching of the mosquito eggs was potentially suppressed.Terpenes, fatty acids, esters, glycosides, pyrrolidine alkane, piperazine, and phenols were the most prevalent components in the methanol extract, while the aqueous extract of A. nilotica exclusively showed the presence of fatty acids. The insecticidal susceptibility tests of both aqueous and alcoholic extract of A. nilotica confirmed that the Acacia plant could serves as a secure and efficient substitute for chemical pesticides because of its promising effect on killing larvae and egg hatching delaying addition to their safety as one of the natural pesticides. Molecular docking study was performed using one of the crucial and life-controlling protein targets, fatty acid binding protein (FABP) and the most active ingredients as testing ligands to describe their binding ability. Most of the structurally related compounds to the co-crystallized ligand, OLA, like hexadecanoic acid furnished high binding affinity to the target protein with very strong and stable intermolecular hydrogen bonding and this is quite similar to OLA itself. Some other structural non-related compounds revealed extraordinarily strong binding abilities like Methoxy phenyl piperazine. Most of the binding reactivities of the majortested structures are due to high structure similarity between the positive control, OLA, and tested compounds. Such structure similarity reinforced with the binding abilities of some detected compounds in the A. nilotica extract could present a reasonable interpretation for its insecticidal activity via deactivating the FABP protein. The FABP4 enzyme inhibition activity was assessed for of both methanolic and aqueous of acacia plant extract and the inhibition results of methanol extract depicted noticeable potency if compared to orlistat, with half-maximal inhibitory concentration (IC50) of 0.681, and 0.535 µg/ml, respectively.


Subject(s)
Acacia , Culex , Insecticides , Animals , Humans , Acacia/chemistry , Molecular Docking Simulation , Methanol , Insecticides/pharmacology , Insecticides/chemistry , Fatty Acids , Piperazines
4.
Molecules ; 29(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38202854

ABSTRACT

(1) Background: A molecular hybridization docking approach was employed to develop and detect a new category of naturally activated compounds against Culex pipiens as acetylcholinesterase inhibitors via designing a one-pot multicomponent nano-delivery system. (2) Methods: A nanostructure lipid carrier (NLC), as a second generation of solid lipid nanoparticles, was used as a carrier to deliver the active components of curcumin (Cur), geraniol (G), and linalool (L) in one nanoformulation after studying their applicability in replacing the co-crystallized ligand imidacloprid. (3) Results: The prepared nanostructure showed spherical-shaped, polydisperse particles ranging in size from 50 nm to 300 nm, as found using a transmission electron microscope. Additionally, dynamic light scattering confirmed an average size of 169 nm and a highly stable dispersed solution, as indicated by the zeta potential (-38 mV). The prepared NLC-Cur-LG displayed competitive, high-malignancy insecticidal activity against fourth instar C. pipiens with an elevated rate of death of 0.649 µg/mL. The treatment, due to the prepared nanostructure, affects oxidative stress enzymes, e.g., hydrogen peroxide (4 ppm), superoxide dismutase (SOD) (0.03 OD/mg), and protein carbonyl (0.08 OD/mg), and there are observable upward and downward fluctuations when using different concentrations of NLC-Cur-LG, suggesting significant problems in its foreseeable insecticidal activity. The acetylcholinesterase activity was assessed by an enzyme inhibition assay, and strengthened inhibition occurred due to the encapsulated NLCs (IC50 = 1.95 µg/mL). An investigation of the gene expression by Western blotting, due to treatment with NLC-Cur-LG, revealed a severe reduction of nearly a quarter of what was seen in the untreated group. As a preliminary safety step, the nanoformulation's toxicity against normal cell lines was tested, and a reassuring result was obtained of IC50 = 158.1 µg/mL for the normal lung fibroblast cell line. (4) Conclusions: the synthesized nanoformulation, NLC-Cur-LG, is a useful insecticide in field conditions.


Subject(s)
Acyclic Monoterpenes , Culex , Curcumin , Insecticides , Nanostructures , Monoterpenes , Acetylcholinesterase , Cholinesterase Inhibitors/pharmacology , Curcumin/pharmacology , Insecticides/pharmacology , Lipids
5.
Molecules ; 28(19)2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37836800

ABSTRACT

(1) Background: Few studies have been carried out to appraise abamectin toxicity toward Locusta migratoria nymphs. (2) Methods: This study aimed to evaluate the cytotoxic effect of abamectin as an insecticide through examining the changes and damage caused by this drug, in both neurosecretory cells and midgut, using L. migratoria nymphs as a model of the cytotoxic effect. Histopathological change in the brain was examined in both normal and abamectin-treated fifth-instar nymphs. Neurosecretory cells (NSCs) were also examined where there were loosely disintegrated cells or vacuolated cytoplasm. (3) Results: The results showed distinct histological changes in the gastrointestinal tract of L. migratoria nymphs treated with abamectin, with significant cellular damage and disorganization, i.e., characteristic symptoms of cell necrosis, a destroyed epithelium, enlarged cells, and reduced nuclei. The observed biochemical changes included an elevation in all measured oxidative stress parameters compared to untreated controls. The malondialdehyde activities (MDAs) of the treated nymphs had a five- to six-fold increase, with a ten-fold increase in superoxide dismutase (SOD), nine-fold increase in glutathione-S-transferase (GST), and four-fold increase in nitric oxide (NO). (4) Conclusions: To further investigate the theoretical method of action, a molecular docking simulation was performed, examining the possibility that abamectin is an inhibitor of the fatty acid-binding protein Lm-FABP (2FLJ) and that it binds with two successive electrostatic hydrogen bonds.


Subject(s)
Insecticides , Locusta migratoria , Animals , Molecular Docking Simulation , Locusta migratoria/metabolism , Insecticides/toxicity , Insecticides/metabolism , Oxidative Stress , Insect Proteins/chemistry
6.
Sci Rep ; 13(1): 12522, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37532732

ABSTRACT

Solid lipid nanoparticles second generation, nanostructure lipid carrier (NLC), is one of the most important biodegradable nanoparticles. Nanostructure Lipid carrier (NLC) was used to encapsulate methylene blue (MB) dye, carvacrol and citronellal and their efficacy as insecticidal against Culex pipiens (Cx. pipiens) were distinguished. The prepared nanoformulation revealed very good physicochemical properties, especially the homogeneity of the particle size. Transmission electron microscope showed spherical shaped nanoparticles within range less than 200 nm. The prepared NLC-MB-MT system showed a very competitive insecticidal activity and high virulence against the mosquito larvae with higher mortality rate of LC50 of 0.141 µl/mL, in addition to high level of Oxidative stress parameters obtained through all the tested enzymes including hydrogen peroxide (4.8 ppm), protein carbonyl amount (0.12 OD/mg protein), ascorbic acid (0.15 mg) and Superoxide dismutase (SOD) showed strong increasing (0.09 OD/mg protein/min) at 6 µg/mL, respectively. Whereas paradoxical results of the oxidative stress enzymes were obtained from different concentration of nanoformulation that introduce a convenient reason for their potential insecticidal effect. The cytotoxic effect of NLC-MB-MT was evaluated using WI38 human lung cell lines, the LC50 was 6.4 mg/mL. The low cytotoxic reactivity towards the tested cell line makes the NLC-MB-MT nanoformulation has its promising insecticidal efficacy. Molecular docking study for each component were done against acetylcholine esterase protein and accepted binding modes achieved by the three compounds.


Subject(s)
Culex , Insecticides , Nanostructures , Animals , Humans , Monoterpenes/pharmacology , Methylene Blue/pharmacology , Molecular Docking Simulation , Insecticides/pharmacology , Insecticides/chemistry , Lipids/pharmacology , Larva
7.
Polymers (Basel) ; 14(18)2022 Sep 11.
Article in English | MEDLINE | ID: mdl-36145944

ABSTRACT

This study aims to investigate the two-way shear strength of concrete slabs with FRP reinforcements. Twenty-one strength models were briefly outlined and compared. In addition, information on a total of 248 concrete slabs with FRP reinforcements were collected from 50 different research studies. Moreover, behavior trends and correlations between their strength and various parameters were identified and discussed. Strength models were compared to each other with respect to the experimentally measured strength, which were conducted by comparing overall performance versus selected basic variables. Areas of future research were identified. Concluding remarks were outlined and discussed, which could help further the development of future design codes. The ACI is the least consistent model because it does not include the effects of size, dowel action, and depth-to-control perimeter ratio. While the EE-b is the most consistent model with respect to the size effect, concrete compressive strength, depth to control perimeter ratio, and the shear span-to-depth ratio. This is because of it using experimentally observed behavior as well as being based on mechanical bases.

8.
Reprod Domest Anim ; 57(11): 1353-1362, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35864721

ABSTRACT

The physiological effects of dietary boron (B) supplementation for farm animals specifically goat on male fertility are still scarce and need deep investigation. Thus, the current study was designed to investigate how adding B to the diet of male goats affected their testicular and thyroid activity. For that purpose, twelve male goats were divided randomly into two groups (six animals each); control group that was fed the basal diet and B group that was fed the basal diet containing 70 mg B/kg diet for 6 months. Serum samples were collected at different intervals, while testicular biopsies were obtained at the end of the experiment. The results showed that 6 months of dietary B supplementation resulted in a significant increment in serum B concentration. The results of repeated measure analysis showed that there were significant GROUP and TIME × GROUP interactions effects on blood testosterone levels (F = 119.408, p = .000 and F = 6.794, p = .013, respectively), demonstrating that compared with control, B supplementation caused a significant rise in serum testosterone levels over time. However, the mean animal body weights and the serum levels of triiodothyronine (T3) and thyroxine (T4) were kept comparable with the control ones at the different time points. The most striking finding is that B supplementation increased significantly the mRNA expression of the CYP17A1 which is essential for steroidogenesis (p < .001). In addition, a histological examination of testicular tissue corroborated our findings and demonstrated that B supplementation had a positive effect. As a result, B might be considered an excellent food supplement that could be safely added to the male goats' diet at the current dose to improve their reproductive capacity.


Subject(s)
Boron , Goats , Animals , Male , Animal Feed/analysis , Boron/pharmacology , Diet/veterinary , Dietary Supplements , Goats/physiology , Testosterone , Thyroid Gland
9.
Molecules ; 27(8)2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35458623

ABSTRACT

(1) Background: Mosquito control with essential oils is a growing demand. This work evaluated the novel larvicidal and adulticidal activity of fennel and green tea oils and their Layered double hydroxides (LDHs) nanohybrid against Culex pipiens (Cx. pipiens) in both laboratory and field conditions and evaluated their effect against non-target organisms; (2) Methods: Two types of nanoclays, MgAl-LDH and NiAl-LDH were synthesized and characterized using PXRD, TEM and SEM, whereas their elemental analysis was accomplished by SEM-EDX; (3) Results: Mg and Ni LDHs were synthesized by the co-precipitation method. The adsorption and desorption of active ingredients were conducted using LC MS/MS, with reference to the SEM-EXD analysis. The desorption process of MgAl-LDH intercalated green tea oil was conducted using ethanol, and reveled significant peaks related to polyphenols and flavonoids like Vanillin, Catechin, Daidzein, Ellagic acid, Naringenin, Myricetin and Syringic acid with concentrations of 0.76, 0.73, 0.67, 0.59, 0.52, 0.44 and 0.42 µg/g, respectively. The larvicidal LC50 values of fennel oil, Mg-LDH-F, and Ni-LDH-F were 843.88, 451.95, 550.12 ppm, respectively, whereas the corresponding values of green tea were 938.93, 530.46, and 769.94 ppm. The larval reduction percentage of fennel oil and Mg-LDH-F reached 90.1 and 96.2%, 24 h PT and their persistence reached five and seven days PT, respectively. The reduction percentage of green tea oil and Mg-LDH-GT reached 88.00 and 92.01%, 24 h PT and their persistence reached five and six days PT, respectively. Against adults, Mg-LDH-GT and Ni-LDH-GT were less effective than green tea oil as their LC95 values were 5.45, 25.90, and 35.39%, respectively. The reduction in adult density PT with fennel oil, Mg-LDH-F, green tea oil, and Mg-LDH-GT reached 83.1, 100, 77.0, and 99.0%, respectively, 24 h PT and were effective for three days. Mg-LDH-GT and Mg-LDH-F increased the predation Cybister tripunctatus (71% and 69%), respectively; (4) Conclusions: For the first time, Mg-LDH-GT and Mg-LDH-F was the best system loaded with relatively good desorption release to its active ingredients and significantly affected Cx. pipiens larvae and adults in both laboratory and field circumstances, and it could be included in mosquito control.


Subject(s)
Culex , Foeniculum , Insecticides , Oils, Volatile , Animals , Insecticides/pharmacology , Larva , Tandem Mass Spectrometry , Tea
10.
Sci Rep ; 12(1): 4406, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35292687

ABSTRACT

Mosquitoes and mosquito-borne diseases represent an increasing global challenge. Plant extract and/or oils could serve as alternatives to synthetic insecticides. The larvicidal effects of 32 oils (1000 ppm) were screened against the early 4th larvae of Culex pipiens and the best oils were evaluated against adults and analyzed by gas chromatography-mass spectrometry (GC mass) and HPLC. All oils had larvicidal activity (60.0-100%, 48 h Post-treatment, and their Lethal time 50 (LT50) values ranged from 9.67 (Thymus vulgaris) to 37.64 h (Sesamum indicum). Oils were classified as a highly effective group (95-100% mortalities), including Allium sativum, Anethum graveolens, Camellia sinensis, Foeniculum vulgare, Nigella sativa, Salvia officinalis, T. vulgaris, and Viola odorata. The moderately effective group (81-92% mortalities) included Boswellia serrata, Cuminum cyminum, Curcuma aromatic, Allium sativum, Melaleuca alternifolia, Piper nigrum, and Simmondsia chinensis. The least effective ones were C. sativus and S. indicum. Viola odorata, Anethum graveolens, T. vulgaris, and N. sativa provide 100% adult mortalities PT with 10, 25, 20, and 25%. The mortality percentages of the adults subjected to 10% of oils (H group) were 48.89%, 88.39%, 63.94%, 51.54%, 92.96%, 44.44%, 72.22%, and 100% for A. sativum, An. graveolens, C. sinensis, F. vulgare, N. sativa, S. officinalis, T. vulgaris, and V. odorata, respectively. Camellia sinensis and F. vulgare were the most potent larvicides whereas V. odorata, T. vulgaris, An. graveolens and N. sativa were the best adulticides and they could be used for integrated mosquito control.


Subject(s)
Culex , Insecticides , Oils, Volatile , Animals , Egypt , Insecticides/chemistry , Insecticides/pharmacology , Larva , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Plant Oils/pharmacology
11.
Molecules ; 27(6)2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35335302

ABSTRACT

(1) Background: The control of mosquitoes with essential oils is a growing demand. (2) Methods: This study evaluated the novel larvicidal and adulticidal activity of fennel and green tea oils and their nanostructured lipid carriers (NLC) against Culex pipiens (C. pipiens) in the laboratory, field conditions and evaluated their effect against non-target organisms. SLN type II nanoformulations were synthesized and characterized using dynamic light scattering (DLS), zeta potential and transmission electron microscope. (3) Results: The synthesized NLCs showed spherical shaped, homogenous, narrow, and monomodal particle size distribution. The mortality percent (MO%) post-treatment (PT) with 2000 ppm for 24 h with fennel oil and NLC fennel (NLC-F) reached 85% (LC50 = 643.81 ppm) and 100% (LC50 = 251.71), whereas MO% for green tea oil and NLC green tea (NLC-GT) were 80% (LC50 = 746.52 ppm) and 100% (LC50 = 278.63 ppm), respectively. Field trial data showed that the larval reduction percent of fennel oil and NLC-F reached 89.8% and 97.4%, 24 h PT and the reduction percent of green tea oil and NLC-GT reached 89% and 93%, 24 h PT with persistence reached 8 and 7 days, for NLC-F and NLC-GT, respectively. The adulticidal effects showed that NLC-F and NLC-GT (100% mortality) were more effective than fennel and green tea oils (90.0% and 83.33%), with 24 h PT, respectively. Moreover, their reduction of adult density after spraying with LC95 X2 for 15 min, with fennel oil, NLC-F, and green tea oil, NLC-GT were 83.6%, 100%, 79.1%, and 100%, respectively, with persistence (>50%) lasting for three days. The predation rate of the mosquitofish, Gambusia affinis, and the bug, Sphaerodema urinator, was not affected in both oil and its NLC, while the predation rate of the beetle, Cybister tripunctatus increased (66% and 68.3%) by green tea oil and NLC-GT, respectively. (4) Conclusions: NLCs nanoformulation encapsulated essential oils was prepared successfully with unique properties of size, morphology, and stability. In vitro larvicidal and adulticidal effects against C. pipiens supported with field evaluations have been performed using essential oils and their nanoformulations. The biological evaluation of nanoformulations manifested potential results toward both larvicidal and adulticidal compared to the essential oils themselves, especially NLC encapsulated fennel oil which had promising larvicidal and adulticidal activity.


Subject(s)
Culex , Foeniculum , Nanostructures , Oils, Volatile , Animals , Tea
12.
Anticancer Agents Med Chem ; 22(14): 2558-2576, 2022.
Article in English | MEDLINE | ID: mdl-35023461

ABSTRACT

BACKGROUND: Cancer is a disease illustrated by a shift in the controlled mechanisms that control both cell proliferation and differentiation. It is regarded as a prime health problem worldwide and a leading cause of human death rate exceeded only by cardiovascular diseases. Many reported works are concerned with discovering new antitumor compounds, encouraging us to synthesize new anticancer agents. OBJECTIVE: In this work, we aimed to synthesize target molecules from 1,3-dicarbonyl compounds through heterocyclization reactions. METHODS: The reaction of either 4-methylaniline (1a) or 1-naphthylamine (1b) with diethyl malonate (2) gave the anilide derivatives 3a and 3b, respectively. The latter underwent a series of heterocyclization reactions to give the pyridine, pyran, and thiazole derivatives confirmed by the required spectral data. RESULTS: The in-vitro antitumor evaluation of the newly synthesized products against three cancer cell lines, MCF-7, NCI-H460, SF-268, and WI 38, which were used as the normal cell lines, was conducted, and the data revealed that compounds 11a, 18b, 18c, and 20d showed high antitumor activity and 20d individualized with potential antitumor activity towards cell lines with lowest cytotoxicity effect. Both EGFR and PIM-1 enzymes inhibition were investigated for the compound 20d, and it was found that the inhibition effect of compound 20d was promising for each enzyme, showing IC50 = 45.67 ng and 553.3 ng for EGFR and PIM-1, respectively. CONCLUSION: Molecular docking results of compound 20d showed strong binding interactions with both the enzymes, where good binding modes were obtained in the case of EGFR, which was closely similar to the binding mode of standard Erlotinib.While 20d showed complete superimposition binding interactions with VRV-cocrystallized ligand of PIM-1 that may expound the in-vitro antitumor activity.


Subject(s)
Antineoplastic Agents , Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation , Drug Screening Assays, Antitumor , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins c-pim-1/metabolism , Structure-Activity Relationship
13.
SICOT J ; 6: 21, 2020.
Article in English | MEDLINE | ID: mdl-32579105

ABSTRACT

INTRODUCTION: Unstable trochanteric fractures are challenging with a high rate of implant failure and re-operation. Cephalomedullary nails proved to be a rational management choice for these injuries, yet other management options have not been well assessed. The aim of this study was to compare the use of DHS with trochanteric stabilizing plate (TSP) and proximal femoral locked plate (PFLP) in unstable pertrochanteric fractures. METHODS: This randomized controlled trial (RCT) included 40 patients (22 males, 18 females) with unstable pertrochanteric fractures (AO/OTA 31A2.2/A2.3). The patients were randomized into group 1 managed by DHS with TSP while group 2 was managed by PFLP. All patients were followed up for 1 year. Patients were assessed radiographically and clinically using Harris hip score (HHS) at 3, 6 and 12 months. Operative time, estimated blood loss and time to union were also compared. RESULTS: The difference of intra-operative variables, including operative time and intra-operative blood loss, between both groups was statistically insignificant. Time to bony union was faster in the first group with a statistically significant P value (p = 0.04). Functional outcome per HHS was significantly better in group 1 (p < 0.01) and implant failure in group 1 occurred statistically lesser (p < 0.01). DISCUSSION: DHS with TSP appears to be a good option of management for unstable pertrochanteric fractures. In contrast, the use of PFLP in unstable pertrochanteric fractures in the elderly does not appear to be a good alternative.

14.
Bioorg Chem ; 84: 456-467, 2019 03.
Article in English | MEDLINE | ID: mdl-30576909

ABSTRACT

A series of novel 2-imino-4-thiazolidinone derivatives 4a,b was synthesized through reaction of unsymmetrical thioureas 3a,b with chloroacetic acid. Condensation of 4a,b with aromatic aldehydes 5a-eyielded the corresponding 5-arylidene derivatives 6a-j. In addition, the reaction of 4a,b with 4-arylazo-3-hydroxybenzaldehydes 8a-c furnished the respective mono-arylazo-4-thiazolidinones10a-f. All the newly synthesized compounds were confirmed by their elemental analysis and spectral data. The antifungal activity of the newly synthesized compounds was assessed and the compounds 6d, 6e, 6i, 6j, 9a,b and 10a-frevealedhigher antifungal activity towards Alternaria solani than to the standard Ridomil gold plus. Moreover, the DNA toxicity of 4-thiazolidinone derivatives 6d, 9a, 10b, 10c and 10f on the nucleic acid of Alternaria solani (KT354939) was performed and the results showed qualitatively more than 70% cleavage. Also, compounds 6i, 6j, 9b, 10c and 10f were docked inside the active site of 1ZOYenzyme and suitable binding with the active site of amino acids, were displayed according to their bond lengths, angles and conformational energy.


Subject(s)
Antifungal Agents/chemical synthesis , Drug Design , Thiazolidinediones/chemistry , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Aspergillus/drug effects , Binding Sites , DNA/chemistry , DNA/metabolism , Microbial Sensitivity Tests , Molecular Docking Simulation , Nucleic Acid Conformation , Structure-Activity Relationship , Thiazolidinediones/metabolism , Thiazolidinediones/pharmacology
15.
Singapore medical journal ; : 216-219, 2013.
Article in English | WPRIM (Western Pacific) | ID: wpr-359129

ABSTRACT

<p><b>INTRODUCTION</b>Laparoscopic simple closure (LSC) coupled with Helicobacter pylori eradication is a well-recognised treatment for perforated duodenal ulcers. This study aimed to evaluate its safety and efficacy.</p><p><b>METHODS</b>This was a retrospective cohort study conducted on patients who underwent LSC of perforated duodenal ulcers from January 2002 to December 2009. Patients were stratified according to the American Society of Anesthesiologist classification and Boey's risk score.</p><p><b>RESULTS</b>Of the 213 patients, 22 (10.3%) were excluded as they required conversion to open surgery. 191 (89.7%) patients who underwent successful laparoscopic repair were included in the study. The median age of the patients was 39 (range 19-73) years, and the majority were male (n = 180, 94%). Median duration of pre-hospital symptoms was eight hours and median time from admission to surgery was six hours. Median operative time was 65 minutes and median hospital stay was five days. Ten patients (median age 53.5 years) required intensive care unit admission. Two patients developed leakage from the suture line - one required re-exploration and the other was managed conservatively. Four patients had intra-abdominal abscesses - one required re-exploration, while three were managed by percutaneous radiological drainage. One patient developed pneumonia and one had pulmonary embolism. There were no surgical site infections. All patients were followed up as surgical outpatients (median duration 36 days). None of the patients required definitive surgery. There was one death in the cohort.</p><p><b>CONCLUSION</b>LSC of perforated duodenal ulcers is a reliable, safe and minimally invasive procedure that has low morbidity.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Duodenal Ulcer , Diagnosis , General Surgery , Laparoscopy , Methods , Peptic Ulcer Perforation , General Surgery , Postoperative Complications , Retrospective Studies , Time Factors , Treatment Outcome
16.
Prehosp Disaster Med ; 19(3): 201-7, 2004.
Article in English | MEDLINE | ID: mdl-15571195

ABSTRACT

Numerous examples exist of the benefits of the timely access to information in emergencies and disasters. Information technology (IT) is playing an increasingly important role in information-sharing during emergencies and disasters. The effective use of IT in out-of-hospital (OOH) disaster response is accompanied by numerous challenges at the human, applications, communication, and security levels. Most reports of IT applications to emergencies or disasters to date, concern applications that are hospital-based or occur during non-response phases of events (i.e., mitigation, planning and preparedness, or recovery phases). Few reports address the application of IT to OOH disaster response. Wireless peer networks that involve ad hoc wireless routing networks and peer-to-peer application architectures offer a promising solution to the many challenges of information-sharing in OOH disaster response. These networks offer several services that are likely to improve information-sharing in OOH emergency response, including needs and capacity assessment databases, victim tracking, event logging, information retrieval, and overall incident management system support.


Subject(s)
Computer Communication Networks , Disaster Planning , Emergency Medical Services/organization & administration , Information Dissemination , Information Systems , Telecommunications , Humans
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