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Naturally occurring peroxides received great interest and attention from scientific research groups worldwide due to their structural diversity, versatile biological activities, and pharmaceutical properties. In the present review, we describe the historical discovery of natural peroxides from plants systematically and update the researchers with recently explored ones justifying their structural caterogrization and biological/pharmaceutical properties intensively. Till the end of 2023, 192 peroxy natural products from plants were documented herein for the first time implying most categories of natural scaffolds (e. g. terpenes, polyketides, phenolics and alkaloids). Numerically, the reported plants' peroxides have been classified into seventy-four hydro-peroxides, hundred seven endo-peroxides and eleven acyl-peroxides. Endo-peroxides (cyclic alkyl peroxides) are an important group due to their high variety of structural frameworks, and we have further divided them into "four-, five-, six and seven"-membered rings. Biosynthetically, a shedding light on the intricate mechanisms behind the formation of plant-derived peroxides are addressed as well.
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Owing to its high interest as prolific source of diverse bioactive compounds referred in our previous research work, we have scaled-up the fermentation of the marine Aspergillus terreus LGO13 on a liquid culture medium to isolate and identify the very minor/further promising bioactive secondary metabolites and to study their antibacterial, cytotoxic, and antiviral properties. Twenty-three known bioactive metabolites, including the recently discovered microbial natural product N-benzoyl-tryptophan (1), were obtained herein. Their structures were determined using HR-ESI-MS 1D/2D NMR spectroscopy and data from the literature. The biological properties of the microbial extract and the resulting compounds were examined using a set of microorganisms, cervix carcinoma KB-3-1, nonsmall cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulations were used to investigate the potential targets of the separated metabolites as anti-SARS-CoV-2 drugs. According to the current study, a viral protein that may be the target of anticovid drugs is a papain-like protease (PLpro), and chaetominine (2) appears to be a viable choice against this protein. We evaluated the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2 based on MD data. Chaetominine (2) and azaspirofuran A (9) displayed intermediate selectivity indices (SI = 6.6 and 3.2, respectively), while fumitremorgin C (6) displayed a high selectivity index (SI = 19.77). These findings show that fumitremorgin C has promising antiviral action against SARS-CoV-2.
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BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen responsible for complicated UTIs and exhibits high antibiotic resistance, leading to increased mortality rates, especially in cases of multidrug-resistant strains. This study aimed to investigate the antibiotic susceptibility patterns and genomic characterization of XDR strains identified in end-stage liver disease patients who underwent liver transplants. METHODS: In this study, a number of 30 individuals who underwent liver transplants were registered. Ninety urine and 60 wound site swab samples were collected and processed for culturing, identification, and antimicrobial sensitivity. Extensively drug-resistant strain EMARA01 was confirmed through Sanger sequencing and was then processed for whole genome sequencing to characterize the genomic pattern. Sequencing data were processed for de novo assembly using various tools and databases, including genome annotation, serotype identification, virulence factor genes, and antimicrobial resistance gene. Pangenome analysis of randomly selected 147 reference strains and EMAR01 sequenced strain was performed using the Bacterial Pan Genome Analysis (BPGA) software. RESULTS: Of these total examined samples, nosocomial infection due to P. aeruginosa was detected in twelve patients' samples. AST analysis showed that P. aeruginosa strains exhibit resistance to tobramycin, erythromycin, and gentamicin, followed by piperacillin and ofloxacin, and no strains exhibit resistance to meropenem and imipenem. The CARD database identified 59 AMR genes similar to the EMAR01 strain genome and mostly belong to the family involved in the resistance-nodulation-cell division (RND) antibiotic efflux pump. Five genes; nalC, nalD, MexR, MexA, and MexB, exhibit resistance to 14 classes of antibiotics, while two AMR; CpxR, and OprM, exhibit resistance to 15 classes of drugs. Pangenome analysis revealed that the pan-genome remained open, suggesting the potential for acquiring accessory and unique genes. Notably, the genes predominantly involved in amino acid transport metabolism were identified using the KEGG database. CONCLUSIONS: This study provides valuable insights into the antimicrobial resistance profile, genetic features, and genomic evolution of P. aeruginosa strains causing UTIs in liver transplant patients. The findings emphasize the significance of comprehending AMR mechanisms and genetic diversity in P. aeruginosa for developing effective treatment strategies and infection control measures.
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Antibacterianos , Farmacorresistência Bacteriana Múltipla , Transplante de Fígado , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Infecções Urinárias , Sequenciamento Completo do Genoma , Humanos , Farmacorresistência Bacteriana Múltipla/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Transplante de Fígado/efeitos adversos , Egito , Infecções Urinárias/microbiologia , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Masculino , Feminino , Genoma Bacteriano/genética , Adulto , Infecção Hospitalar/microbiologia , Pessoa de Meia-Idade , Fatores de Virulência/genéticaRESUMO
Soft corals, particularly Sarcophyton sp. are rich in metabolites with variety of biological activities. In this study, a pyran-based 9-exo-methylene-10-hydroxy-sarcotrocheliol (1) and 2-dehydro-4-peroxy-sarcophine (2), two new cembranoide diterpenes, were isolated together with 9-hydroxy-10,11-dehydro-sarcotrocheliol, sarcotrocheliol, sarcotrocheliol acetate, sarcophine, (+)-7α,8ß-dihydroxydeepoxysarcophine, (±)-sarcophytonine B, and peridinin from the organic extract of Sarcophyton glaucum collected at the coasts of Hurghada, Egypt. The structures of the new diterpenes 1-2 were identified based on cumulative analyses of HRESIMS and NMR (1D/2D NMR) spectra. The relative configurations of both compounds were verified by NOESY spectra and comparison with our recently reported analogues. The compounds showed no antimicrobial activity against a set of diverse tested microorganisms.
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Antozoários , Diterpenos , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , Antozoários/química , Animais , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Egito , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificaçãoRESUMO
Silver nanoparticles (Ag-NPs) have a unique mode of action as antibacterial agents in addition to their anticancer and antioxidant properties. In this study, microbial nanotechnology is employed to synthesize Ag-NPs using the cell filtrate of Streptomyces enissocaesilis BS1. The synthesized Ag-NPs are confirmed by ultraviolet-visible (UV-Vis), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Also, the effects of different factors on Ag-NPs synthesis were evaluated to set the optimum synthesis conditions. Also, the antibacterial, antibiofilm, and anticancer activity of Ag-NPs was assessed. The X-ray diffraction (XRD) analysis confirmed the crystalline nature of the sample and validated that the crystal structure under consideration is a face-centered cubic (FCC) pattern. The TEM examination displayed the spherical particles of the Ag-NPs and their average size, which is 32.2 nm. Fourier transform infrared spectroscopy (FTIR) revealed significant changes in functionality after silver nanoparticle dispersion, which could be attributed to the potency of the cell filtrate of Streptomyces enissocaesilis BS1 to act as both a reducing agent and a capping agent. The bioactivity tests showed that our synthesized Ag-NPs exhibited remarkable antibacterial activity against different pathogenic strains. Also, when the preformed biofilms of Pseudomonas aeruginosa ATCC 9027, Salmonella typhi ATCC 12023, Escherichia coli ATCC 8739, and Staphylococcus aureus ATCC 6598 were exposed to Ag NPs 50 mg/ml for 24 hours, the biofilm biomass was reduced by 10.7, 34.6, 34.75, and 39.08%, respectively. Furthermore, the Ag-NPs showed in vitro cancer-specific sensitivity against human breast cancer MCF-7 cell lines and colon cancer cell line Caco-2, and the IC50 was 0.160 mg/mL and 0.156 mg/mL, respectively. The results of this study prove the ease and efficiency of the synthesis of Ag-NPs using actinomycetes and demonstrate the significant potential of these Ag-NPs as anticancer and antibacterial agents.
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Nanopartículas Metálicas , Prata , Streptomyces , Humanos , Prata/química , Nanopartículas Metálicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Células CACO-2 , Antibacterianos/farmacologia , Escherichia coli , Extratos Vegetais/farmacologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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BACKGROUND: Hydatid cyst disease (HCD) is common in certain locations. Surgery is associated with postoperative biliary fistula (POBF) and recurrence. The primary aim of this study was to identify whether occult cysto-biliary communication (CBC) can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase (ALP) levels in predicting POBF and recurrent HCD. AIM: To identify whether occult CBC can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD. METHODS: From September 2010 to September 2016, a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty. Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence. RESULTS: There was a highly statistically significant association (P ≤ 0.001) between cystic fluid biochemical indices and the development of biliary complications (of 16 patients with POBF, 15 patients had high cyst fluid bilirubin and ALP levels), where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications. There was a highly statistically significant association (P ≤ 0.001) between biliary complications, biochemical indices, and the occurrence of recurrent HCD (of 30 patients with recurrent HCD, 15 patients had high cyst fluid bilirubin and ALP; all 16 patients who had POBF later developed recurrent HCD), where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts, respectively. CONCLUSION: Occult CBC can predict recurrent HCD. Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.
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The widespread use of computed tomography (CT) has increased the incidence of small renal cell masses. We aimed to evaluate the usefulness of the angular interface sign (ice cream cone sign) to differentiate a broad spectrum of small renal masses using CT. The prospective study included CT images of patients with exophytic renal masses ≤ 4 cm in maximal dimension. The presence or absence of an angular interface of the renal parenchyma with the deep part of the renal mass was assessed. Correlation with the final pathological diagnosis was performed. The study included 116 patients with renal parenchymal masses of a mean (± SD) diameter of 28 (± 8.8) mm and a mean age of 47.7 (±12.8) years. The final diagnosis showed 101 neoplastic masses [66 renal cell carcinomas (RCC), 29 angiomyolipomas (AML), 3 lymphomas, and 3 oncocytomas] and 15 non-neoplastic masses [11 small abscesses, 2 complicated renal cysts, and 2 granulomas]. Angular interface sign was statistically comparable in neoplastic versus non-neoplastic lesions (37.6% versus 13.3%, respectively, P = 0.065). There was a statistically higher incidence of the sign when comparing benign versus malignant neoplastic masses (56.25 vs. 29%, respectively, P = 0.009). Also, comparing the sign in AML versus RCC was statistically significant (52% of AML versus 29% of RCC, P = 0.032). The angular interface sign seems beneficial in predicting the nature of small renal masses. The sign suggests benign rather than malignant small renal masses.
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A new series of nitric oxide-releasing estra-1,3,5,16-tetraene analogs (NO-∆-16-CIEAs) was designed and synthesized as dual inhibitors for EGFR and MRP2 based on our previous findings on estra-1,3,5-triene analog NO-CIEA 17 against both HepG2 and HepG2-R cell lines. Among the target compounds, 14a (R-isomer) and 14b (S-isomer) displayed potent anti-proliferative activity against both HepG2 and HepG2-R cell lines in comparison to the reference drug erlotinib. Remarkably, compound 14a resulted in a prominent reduction in EGFR phosphorylation at a concentration of 1.20 µM with slight activity on the phosphorylation of MEK1/2 and ERK1/2. It also inhibits MRP2 expression in a dose-dependent manner with 24% inhibition and arrested the cells in the S phase of the cell cycle. Interestingly, compound 14a (estratetraene core) exhibited a twofold increase in anti-proliferative activity against both HepG2 and HepG2-R in comparison with the lead estratriene analog, demonstrating the significance of the designed ∆-16 unsaturation. The results shed a light on compound 14a and support further investigations to combat multidrug resistance in chemotherapy of hepatocellular carcinoma patients.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Doadores de Óxido Nítrico/farmacologia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Óxido Nítrico/metabolismo , Receptores ErbB , Proliferação de Células , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
In this study, bacterial cellulose (BC) impregnated with green synthesized silver nanoparticles (AgNPs) is evaluated as an antimicrobial membrane for wound-healing treatment. Green synthesized silver nanoparticles using Moringa oleifera leaf extract were characterized using UVâvisible spectroscopy, FTIR, X-ray diffraction, and transmission electron microscopy. The results confirmed that the resulted particles were Ag2O and metallic Ag in nanoscale with an average size ranged from 24 to 40 nm. The green synthesized nanoparticles incorporated within both bacterial cellulose and filter paper discs showed excellent antibacterial activities against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027. There was no significant difference noticed between bacterial cellulose and filter paper holding capacity to nanoparticles and there was lack of interaction between bacterial cellulose and impregnated nanoparticles as elaborated by Fourier transform infrared spectral analyses. Scanning electron microscopy investigation showed major distortions effects of green synthesized silver nanoparticles on bacterial cell morphology.
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Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Pseudomonas aeruginosa , Nanopartículas Metálicas/química , Staphylococcus aureus , Prata/farmacologia , Celulose , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Difração de Raios XRESUMO
Four bioactive metabolites; ergosterol (1), peroxy ergosterol (2), α-cyclopiazonic acid (3) and kojic acid (4), were isolated from the fungal sp. Trichoderma viride MM21. Their structures were assigned by cumulative analysis of NMR and mass spectra, and comparison with literature. The antimicrobial activity of the fungus supernatant, mycelial cake, cumulative crude extract and compounds 1-4 was broadly studied against 11 diverse pathogens, revealing auspicious activity results. Based on the molecular docking, ergosterol (1) and peroxy ergosterol (2) were picked up to be computationally tested against topoisomerase IV of Staphylococcus aureus. The nominated enzyme is a possible target for the antibacterial activity of triterpenoidal/steroidal compounds. Compounds 1, 2 showed a deep inserting inside the enzyme groove recording a good binding affinity of -8.1 and -8.4 kcal/mol, respectively. Noteworthy that the antibacterial activity of ergosterol was higher (14-17 mm) than peroxy ergosterol (11-14 mm), although ergosterol formed only one hydrogen bond with the target, while peroxy ergosterol formed three hydrogen bonds. Such higher antibacterial activity of ergosterol may be attributed to its interference with other proteins included in this inhibition. The cytotoxic activity was tested against brine shrimp, revealing 100% mortality for the supernatant, crude extract and whole isolated compounds. Such strong cytotoxicity is attributed most likely to the abundant productivity/concentration of α-cyclopiazonic acid and kojic acid.
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Antibacterianos , Hypocreales , Simulação de Acoplamento Molecular , Antibacterianos/química , Ergosterol/farmacologia , Estrutura MolecularRESUMO
The fungal endophyte Aspergillus sp. strain FVL2, isolated from the traditional medicinal fennel plant, Foeniculum vulgare, was investigated for secondary metabolites. Fermentation on rice medium followed by chromatographic separation delivered three new natural products, 7-demethyl-neosulochrin (1), fumigaclavine I (3) and N-benzoyl-tryptophan (6) together with further 14 known metabolites, 1-O-methyl-sulochrin-4'-sulfate, questin, laccaic acid, isorhodoptilometrin, fumigaclavine A, fumigaclavine C, fumitremorgin C, fumigaquinazoline C, tryptoquivaline J, trypacidin, 3'-O-demethyl-sulochrin, 1-O-methyl-sulochrin, protocatechuic acid, and vermelone. The chemical structures of the new metabolites were determined by NMR spectroscopy and ESI HR mass spectrometry. For fumigaclavine I, we observed the partial deuterium transfer from the solvent to the enol form with a remarkable high stereo selectivity. The discovery of the new seco-anthraquinone 7-demethyl-neosulochrin (1) revealed a second type of ring cleavage by a questin oxygenase. The discovery of diverse secondary metabolites broadens the chemical space of Aspergillus.
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Foeniculum , Endófitos/química , Aspergillus/química , Benzoatos/metabolismoRESUMO
Fatty acids derived from oils and fats of different plant and animal resources are considered one of the most valuable renewable precursors of the synthetic chemical and pharmaceutical industries. On the other hand, heterocyclic compounds are well known nowadays by their constitution of many commercialized drugs due to their unique biological activities. Combination between fatty acids and heterocyclic compounds has made important advances in the construction of valuable biologically relevant molecules in pharmaceutical industry. This review casts light on the synthetic pathways for construction of the fatty acid-heterocycle hybrid up to date in a simple classification and arranged manner.
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Ácidos Graxos , Compostos Heterocíclicos , Animais , Ácidos Graxos/química , Óleos , Gorduras , PlantasRESUMO
Background: Surgical resection with clear surgical cut margins is the mainstay of managing malignant breast neoplasms. Multiple techniques have been suggested to enhance resection status during breast-conserving surgery (BCS), including intraoperative ultrasonography (IOUS). Herein, we conducted the current investigation to reveal the benefit of IOUS on the achievement of R0 resection. Patients and Methods. This retrospective investigation included 140 patients who underwent BCS. They were divided into two groups: the IOUS group (40 cases) and the control group (100 cases). Our primary objective was to determine the free resection margin status (R0). Results: Both study groups expressed statistically comparable demographic and clinical data. Additionally, histopathological examination revealed no significant difference between the two groups regarding the tumor type, stage, or grade. Nonetheless, the R0 resection margin was more frequently encountered in association with IOUS application (97.5% compared to 79% in the control group), and that difference was statistically significant (p=0.007). Conclusion: The application of IOUS has a significant beneficial impact on the outcomes of BCS. It is associated with a marked decline in positive resection margins, and its application should be encouraged in the breast oncological practice.
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Neoplasias da Mama , Mastectomia Segmentar , Humanos , Feminino , Mastectomia Segmentar/métodos , Margens de Excisão , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , UltrassonografiaRESUMO
Background: Obesity is a chronic condition that affects millions globally; consequently, bariatric surgery is the key to this serious issue. Bariatric procedures are rapidly expanding in number and methods to address the recognized problems. So, it would make a sense for surgeons and patients if there is a more physiological bypass surgery technique in Morbid obesity. This study aims to evaluate the outcome proposed technique. Patients and methods: The present study is a retrospective analysis on 256 participants subjected to the proposed bypass procedure from December 1999 to January 2017, the participants were followed up for an interval of 3years. Results: The findings of the present study revealed a significant Excess Weight Loss (EWL). In addition, patients experienced decreased calcium, iron, vitamin B12, Hemoglobin, zinc, and Prothrombin Concentration. However, three to six months after surgery, they experienced a significant improvement until they reached normal levels without any supplement by the end of 12,18 months, with a three-year follow-up. Conclusion: This proposed Bypass Operation aims to adequate digestions as well as selective absorption without inducing any vital deficit. Most of study's population showed no elements inadequacies, although few percentages emerged during the interval of maximal weight reduction, and it were transient and minimal. No minerals or vitamins were needed.
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AIM: The aim of the present study is to evaluate the effect of Ag-Au NPs formulation as surface pretreatment by assessing the microshear bond strength, ultra-morphological, and elemental characteristics of gold-silver nanoparticle-treated dentin to resin composite with different adhesive modes. MATERIALS AND METHODS: A total of 60 extracted sound human permanent molars were selected to test the microshear bond strength of composite resin to dentin (40 teeth) and 20 molars were used to assess the ultramorphological and elemental characteristics of silver-gold nanoparticles using environmental scanning electron microscope (ESEM) with energy-dispersive X-ray (EDX) analyzer. The specimens were randomly divided into two main groups according to measured tests either microshear bond strength or elemental analysis. For the bond-strength testing group, 40 teeth were equally distributed into two main groups (20 each) according to dentin-surface pretreatment with or without the use of silver-gold nanoparticles. Then, each group was further divided into two subgroups (10 specimens for each) according to adhesive mode. For ultramorphological and elemental analysis, 20 teeth were equally divided into similar previously mentioned groups according to treatment modalities (5 teeth per group). The multimode bonding agent used in this study was single-bond universal, 3M. The data were collected and statistically analyzed. The significance level was set at p ≤0.05. RESULTS: The results showed that different etching modes had no statistically significant effect. Also, pretreatment had no statistically significant effect. The interaction between the two variables also had no statistically significant effect. Majority of samples in all groups had mixed failure mode. Ultramorphological examination of the tested samples treated with silver-gold nanoparticles revealed proper dispersion of nanoparticles in dentin. CONCLUSIONS: The new formulation of silver-gold nanoparticles did not interfere with the bond strength and sealing ability of resin composite restoration in different adhesion modes. CLINICAL SIGNIFICANCE: The cavity disinfection with silver-gold nanoparticles did not affect the marginal integrity of resin composite restoration. Further studies should be done to evaluate the impact of application of silver-gold nanoparticles in long duration with other adhesive systems in the clinical scenario.
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Nanopartículas Metálicas , Prata , Humanos , Ouro , Cimentos Dentários , Resinas Compostas , DentinaRESUMO
Novel thiazole derivatives possessing phenyl sulfonyl moiety were designed and synthesized as B-RAFV600E kinase inhibitors based on the clinically-approved anticancer drug, dabrafenib. All target compounds showed significant inhibition of B-RAFV600E kinase enzyme at nanomolar levels. Compounds 7b and 13a revealed excellent B-RAFV600E inhibitory activity, superior to that of dabrafenib with IC50 values of 36.3 ± 1.9, 23.1 ± 1.2, and 47.2 ± 2.5 nM, respectively. Moreover, the title compounds were much more selective toward B-RAFV600E kinase than B-RAF wild type. In addition, the most potent compounds were further evaluated for their anticancer activity against B-RAFV600E-mutated and wild type melanoma cells. A positive correlation between the cytotoxic activity and selectivity for B-RAF V600E over B-RAF wild type was clearly observed for compounds 7b, 11c, 13a, and 17. All the screened compounds potently inhibited the growth of WM266.4 melanoma cells with IC50 values in the range from 1.24 to 17.1 µM relative to dabrafenib (IC50 = 16.5 ± 0.91 µM). Compounds 7b, 11a and 11c, 13a, and 17 were much more potent than dabrafenib against B-RAFV600E-mutated WM266.4 melanoma cells. Furthermore, compound 7b suppressed the phosphorylation of downstream ERK1/2 from WM266.4 cells. Also, the docking study revealed the proper orientation and well-fitting of the title compounds into the ATP binding site of B-RAFV600E kinase.
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Introduction: Sickle cell disease is characterized by the production of abnormal hemoglobin, which affects hemoglobin molecule stability during hypoxia and leads to the formation of sickle cells, resulting in increased hematic viscosity, hemolysis, and microvascular blockage. Vasoocclusion is assumed to be the primary cause of vision-threatening retinopathy in sickle cell disease. The aim of this study was to improve the early detection of sickle cell retinopathy (SCR) in children with sickle cell disease (SCD) and investigate the link between systemic and ocular symptoms. Methods: This cross-sectional study comprised children with SCD. The patient files provided a detailed medical history. The laboratory tests included a blood count, reticulocyte count, and Hb electrophoresis. The slit lamp, fundus, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were all part of the ophthalmological examination. Results: The study comprised 15 children with sickle cell disease who met the inclusion and exclusion criteria, with a mean age of 11.15 ± 1.29 years. Nine of the children were males (60%) and six were females (40%). 8 (53.3%) of the children had Hb SS, three (20%) had Hb SC, three (20%) had Hb SB+, and one (6.7%) had Hb SB0. Four children (26.7%) had poor visual acuity. A fundus examination revealed significant abnormal findings in 12 of the 7 children's eyes (40 percent). Macular thinning was detected by OCT in 10 eyes of 7 children (33.3%). Flow voids at the deep retinal capillary plexus were detected by OCTA in 10 eyes of 7 children (33.3%). Longer disease duration, higher reticulocytic percent, more painful crises, and noncompliance with hydroxyurea medication were all linked to the existence of eye abnormalities on fundus examination and OCT. Conclusion: OCTA can show early retinal damage in sickle cell patients with macular changes. Sickle cell retinopathy is usually associated with more severe disease.
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Anemia Falciforme , Doenças Retinianas , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Criança , Estudos Transversais , Feminino , Angiofluoresceinografia/efeitos adversos , Angiofluoresceinografia/métodos , Humanos , Masculino , Doenças Retinianas/complicações , Doenças Retinianas/etiologia , Tomografia de Coerência Óptica/efeitos adversos , Tomografia de Coerência Óptica/métodosRESUMO
The objective of this study was to define the frequency of the bovine aortic arch in patients with coarctation using the tomographic studies. This is a descriptive retrospective study involving analysis of reports of computed tomographic angiography done at the Prince Sultan Cardiac center for 700 children with congenital heart diseases over a span of about 10 years from April 1, 2008, to August 1, 2018. Cases with coarctation of aorta were chosen to determine the frequency of the bovine aortic arch using the tomographic studies. From a total of 700 cases which underwent computed tomographic angiography, 117 (16.71%) were diagnosed with coarctation and 19 (2.71%) had bovine arch. Among the 117 patients with coarctation, the total number of patients with bovine arch was 7 patients representing 5.98%, while in patients without coarctation we found a total number of bovine arches of 12 out of 583 patients representing 2.06%. Patients having coarctation with normal branching pattern were at a slight increased incidence of atrial septal defect, ventricular septal defect and anomalous pulmonary venous return than patients having coarctation with bovine arch. In the face of increased incidence of bovine aortic arch in patients with coarctation, we recommend multislice computed tomographic angiography as a noninvasive and potentially safe and accurate method to precisely delineate the branching pattern of the arch of aorta in patients with coarctation before the interventional procedures and surgeries.
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Coartação Aórtica , Aorta , Aorta Torácica/cirurgia , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/epidemiologia , Criança , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Diseases and epidemics in the current days need new types of antibiotics in order to be able to eliminate them. The goal of this research is to use metagenomics to identify isolated utilitarian gene (s) as antimicrobial specialists. Collection of diverse locations from sea sediment samples from Alexandria and extraction of total DNA, restriction enzyme fragmentation, cloning into pUC19 vector, and expression of the isolated gene(s) in E. coli DH5α were all part of the process. Characterization of Antimicrobial agent was done for the best clone for antimicrobial agent's production to detect efficiency, optimum pH, thermal stability, pH stability, effect of different compounds on antimicrobial activity, and residual activity of product after preservation in room temperature. Amino acid sequence of RSMM C3 gene (1250 bp) was 72% identity with Herbaspirillum sp. The ideal temperature level of the RSMM C3 antimicrobial agent production was 36 °C. The antimicrobial agent RSMM C3's stability was stable at -20 °Celsius for up to two months without thawing. The antibacterial agent RSMM C3 was stable at 4 °C for 14 days without loss in activity. The ideal pH level of the RSMM C3 antimicrobial agent was 6. Remain activity was gradually decreased at pH 5, 6, 6.5 and 7 (86.1, 96.9, 97.2 and 94.9%, respectively). On the other hand, residual activity was (92 and 84%) at (pH 7.5 and 8) for 8 days. The tested antimicrobial RSMM C3 was stable against 1 mM of different compounds (DMSO, Glycerol, NaCl, CaCl2, MgCl2, ZnCl2, FeSO4, MnSO4 and CuSO4). The research provides for the Metagenomics technique that has the ability for the production of novel antimicrobial agents produced by clone RSMM C3 which has a wide spectrum activity towards different microorganisms comparing to other antibiotics as Ampicillin and Tetracycline.