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1.
Microb Pathog ; : 106950, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303958

RESUMO

A worldwide hazard to human health is posed by the growth of toxic bacteria that have contaminated fresh, processed, cereal, and seed products in storage facilities. As the number of multidrug-resistant pathogenic microorganisms rises, we must find safe, and effective antimicrobials. The use of green synthesis nanoparticles to combat microbial pathogens has gained a rising interest. The current study showed Aspergillus fumigatus was applied as a promising biomass for the green synthesis of biogenic silver nanoparticles (Ag NPs). The UV-visible spectra of biosynthesized Ag NPs appeared characteristic surface plasmon absorption at 475 nm, round-shaped with sizes ranging from 17.11 to 75.54 nm and an average size of 50.37 ± 2.3 nm. In vitro tests were conducted to evaluate the antibacterial, antioxidant, and anticancer effects of various treatment procedures for Ag NP applications. The synthesized Ag NPs was revealed biological activity against Aspergillus flauvas, A. niger, Bacillus cereus, Candida albicans, Esherichia coli, Pseudomonas aerugonosa, and Staphylococcus aureus under optimum conditions. The test bacteria were sensitive to low Ag NPs concentrations. (5, 10, 11, 8, 7, 10, and 7 mg/mL) was observed for the mentioned-before tested microorganisms, respectively. The bacterial pathogens described above experienced their biofilm formation effectively suppressed by Ag NPs at sub-inhibitory doses. Ag NPs were tested using scanning electron microscopy (SEM) to verify their antibacterial efficacy towards S. aureus and P. aeruginosa. These findings clearly show how harmful Ag NPs are to pathogenic bacteria. The Ag NPs showed antitumor activity with IC50 at 5 µg/mL against human HepG-2 and MCF-7 cellular carcinoma cells, while 50 mg/mL was required to induce 70% of normal Vero cell mortality. These findings imply that green synthetic Ag NPs can be used on cancer cell lines in vitro for anticancer effect beside their potential as a lethal factor against some pathogenic microbes.

2.
J Neurol Surg B Skull Base ; 85(5): 509-516, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39228889

RESUMO

Objective This aim of this study was to address the outcome of endoscopic reconstruction of the sellar floor by extended inferior turbinate flap. Patients and Methods This is a retrospective study of 34 patients with a recurrent pituitary tumor. They were treated between March 2018 and December 2021 by endoscopic extended endonasal approach with the reconstruction of the sellar floor by an extended posterior pedicle inferior turbinate flap. The clinical and radiological follow-up was performed immediately postoperation and regularly every 3 months up to 1 year, and the available data from the last follow-up visit were included in the analysis. Results The patients' age ranged between 40 and 65 years, with a slight female predominance (55.9%). Headache was the main presentation (47.1%), and functional tumors were found in 50.0% patients. Visual disturbances were field defects among 61.8% and papilledema among 52.9% patients. Preoperative endoscopy revealed postseptectomy as the significant finding (73.5%), followed by postseptectomy and adhesion (14.7%) and finally postseptectomy and hypertrophied inferior turbinate (11.8%). Total tumor resection was achieved in 76.5%, visual improvement was recorded in 52.9%, and no complications were reported in 82.4% patients. Cerebrospinal fluid (CSF) leak was not reported in any of the studied patients. Finally, total resection was significantly associated with younger age, non-functioning tumor and improvement of headache. Conclusion The extended inferior turbinate flap is an effective and safe approach for sellar floor reconstruction in endoscopic endonasal surgery for recurrent pituitary tumors. The extension overcomes the relatively small inferior flap and its limited arc of rotation.

3.
Sci Rep ; 14(1): 18052, 2024 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103395

RESUMO

The novelty of this study lies in demonstrating a new approach to control wilt diseases using Jania ethyl acetate extract. In the current investigation, the potential impacts of Jania sp. ethyl acetate extract (JE) on Tomato Fusarium oxysporum wilt (FOW) have been studied. The in vitro antifungal potential of JE against F. oxysporum (FO) was examined. GC-MS investigation of the JE revealed that, the compounds possessing fungicidal action were Phenol,2-methoxy-4-(2-propenyl)-,acetate, Eugenol, Caryophyllene oxide, Isoespintanol, Cadinene, Caryophylla-4(12),8(13)-dien-5à-ol and Copaen. Jania sp. ethyl acetate extract exhibited strong antifungal potential against FO, achieving a 20 mmzone of inhibition. In the experiment, two different methods were applied: soil irrigation (SI) and foliar application (FS) of JE. The results showed that both treatments reduced disease index present DIP by 20.83% and 33.33% respectively. The findings indicated that during FOW, proline, phenolics, and the antioxidant enzymes activity increased, while growth and photosynthetic pigments decreased. The morphological features, photosynthetic pigments, total phenol content, and antioxidant enzyme activity of infected plants improved when JE was applied through soil or foliar methods. It is interesting to note that the application of JE had a substantially less negative effect on the isozymes peroxidase and polyphenol oxidase in tomato plants, compared to FOW. These reactions differed depending on whether JE was applied foliarly or via the soil. Finally, the use of Jania sp. could be utilized commercially as an ecologically acceptable method to protect tomato plants against FOW.


Assuntos
Fusarium , Doenças das Plantas , Solanum lycopersicum , Solanum lycopersicum/microbiologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/efeitos dos fármacos , Fusarium/patogenicidade , Fusarium/efeitos dos fármacos , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Doenças das Plantas/prevenção & controle , Alga Marinha , Imunidade Vegetal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Rodófitas , Antifúngicos/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-39147447

RESUMO

Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells. We used a well-known animal model of high-fat diet-induced obesity in this investigation, and testicular dysfunction was determined by sperm DNA damage, spermatocyte chromosomal abnormalities, and spermiogram analysis. Following a 12-week high-fat diet challenge, mice were randomly assigned to dulaglutide (0.6 mg/kg/day) or saline treatments for five weeks. Testes and sperm cells were collected 24 h after the last dulaglutide injection. Untreated obese mice had a lower testes/body weight ratio, more sperm DNA damage, diakinesis-metaphase I chromosomal abnormalities, a lower sperm count/motility, more cell morphological defects, and an altered testicular redox balance. In obese mice, dulaglutide injection efficiently restored all disturbed parameters to their control levels. Dulaglutide injection into healthy mice exhibited no significant harmful effects at the applied regimen. As a result, we infer that dulaglutide therapy might bring obese men additional benefits by recovering testicular dysfunction induced by obesity.


Assuntos
Dieta Hiperlipídica , Modelos Animais de Doenças , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Obesidade , Proteínas Recombinantes de Fusão , Testículo , Animais , Masculino , Fragmentos Fc das Imunoglobulinas/farmacologia , Obesidade/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Camundongos , Proteínas Recombinantes de Fusão/farmacologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Dano ao DNA/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Aberrações Cromossômicas/efeitos dos fármacos , Doenças Testiculares/tratamento farmacológico
5.
J Biochem Mol Toxicol ; 38(7): e23764, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38963172

RESUMO

Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.


Assuntos
Dano ao DNA , Metilação de DNA , Reparo do DNA , Dieta Hiperlipídica , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Oxirredução , Proteínas Recombinantes de Fusão , Animais , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Metilação de DNA/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/farmacologia , Dano ao DNA/efeitos dos fármacos , Camundongos , Reparo do DNA/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Masculino , Oxirredução/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , Estresse Oxidativo/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos C57BL
6.
Artigo em Inglês | MEDLINE | ID: mdl-39032854

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is marked by impaired social interactions, and increased repetitive behaviors. There is evidence of genetic changes in ASD, and several of these altered genes are linked to the process of DNA repair. Therefore, individuals with ASD must have improved DNA repair efficiency to mitigate risks associated with ASD. Despite numerous milestones in ASD research, the disease remains incurable, with a high occurrence rate and substantial financial burdens. This motivates scientists to search for new drugs to manage the disease. Disruption of glucagon-like peptide-1 (GLP-1) signaling, a regulator in neuronal development and maintains homeostasis, has been associated with the pathogenesis and progression of several neurological disorders, such as ASD. Our study aimed to assess the impact of semaglutide, a new GLP-1 analog antidiabetic medication, on behavioral phenotypes and DNA repair efficiency in the BTBR autistic mouse model. Furthermore, we elucidated the underlying mechanism(s) responsible for the ameliorative effects of semaglutide against behavioral problems and DNA repair deficiency in BTBR mice. The current results demonstrate that repeated treatment with semaglutide efficiently decreased autism-like behaviors in BTBR mice without affecting motor performance. Semaglutide also mitigated spontaneous DNA damage and enhanced DNA repair efficiency in the BTBR mice as determined by comet assay. Moreover, administering semaglutide recovered oxidant-antioxidant balance in BTBR mice. Semaglutide restored the disrupted DNA damage/repair pathways in the BTBR mice by reducing Gadd45a expression and increasing Ogg1 and Xrcc1 expression at both the mRNA and protein levels. This suggests that semaglutide holds great potential as a novel therapeutic candidate for treating ASD traits.


Assuntos
Reparo do DNA , Peptídeos Semelhantes ao Glucagon , Animais , Masculino , Peptídeos Semelhantes ao Glucagon/farmacologia , Reparo do DNA/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Comportamento Animal/efeitos dos fármacos
7.
Mol Biol Rep ; 51(1): 824, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023688

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a global life-threatening problem and therapeutic interventions are still encountered. IQGAP genes are involved in HCC oncogenesis. The modulatory effect of statins on the expression of IQGAP genes is still unclear. This study aims to study the effect of free SV and chitosan (CS) decorated simvastatin (SV) loaded solid lipid nanoparticles (C-SV-SLNs) on HCC mortality. METHODS AND RESULTS: Plain, SV-SLN, and C-SV- SLN were prepared and characterized in terms of particle size (PS), zeta potential (ZP), and polydispersity index (PDI). The biosafety of different SLN was investigated using fresh erythrocytes, moreover, cytotoxicity was investigated using HepG2 cell lines. The effect of SLNs on IQGAPs gene expression as well as JNK, HDAC6, and HDAC8 activity was investigated using PCR and MOE-docking. The current results displayed that SV-SLNs have nanosized, negative ZP and are homogenous, CS decoration shifts the ZP of SLN into cationic ZP. Furthermore, all SLNs exhibited desirable biosafety in terms of no deleterious effect on erythrocyte integrity. SV solution and SV-SLN significantly increase the mortality of HepG2 compared to undertreated cells, however, the effect of SV-SLN is more pronounced compared to free SV. Remarkably, C-SV-SLN elicits high HepG2 cell mortality compared to free SV and SV-SLN. The treatment of HepG2 cells with SV solution, SV-SLN, or C-SV-SLN significantly upregulates the IQGAP2 gene with repression of IQGAP1 and IQGAP3 genes. MOE-docking studies revealed both SV and tenivastatin exhibit interactions with the active sites of JNK, HDAC6, and HDAC8. Moreover, tenivastatin exhibited greater interactions with magnesium and zinc compared to SV. CONCLUSIONS: This research provides novel insights into the therapeutic potential of SV, SV-SLN and C-SV-SLNs in HCC treatment, modulating critical signaling cascades involving IQGAPs, JNK, and HDAC. The development of C-SV-SLNs presents a promising strategy for effective HCC therapy.


Assuntos
Carcinoma Hepatocelular , Quitosana , Histona Desacetilases , Neoplasias Hepáticas , Nanopartículas , Proteínas Ativadoras de ras GTPase , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Células Hep G2 , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Quitosana/farmacologia , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo , Nanopartículas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tamanho da Partícula , Lipossomos , Proteínas Repressoras
8.
ACS Omega ; 9(23): 24916-24924, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38882142

RESUMO

A novel photoprobe, Tb-acetylacetone (Tb-ACAC) doped within a modified epoxy cellulose polymer immobilized with CA-125 monoclonal antibody, offers an accurate and highly selective method for early ovarian cancer (OC) diagnosis by detecting cancer antigen 125 (CA-125) in serum samples. This approach leverages quenching of the Tb-ACAC luminescence upon binding to CA-125. Characterization of the photoprobe film through UV-vis and fluorescence measurements confirmed the presence of Tb-ACAC within the polymer matrix. In aqueous solution (pH 6.8, λex = 365 nm), the characteristic emission band of Tb-ACAC at λem = 546.2 nm exhibited significant quenching upon CA-125 binding. This quenching effect enabled the sensitive and specific detection of CA-125 in diverse serum samples from OC patients, demonstrating the applicability, simplicity, and effectiveness of this novel approach.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38821673

RESUMO

Diabetes mellitus is a complex metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors that increase the risk of cancer development. However, it is unclear whether the increased cancer risk is due to poor glycemic control or the use of some antidiabetic medications. Therefore, we investigated the genetic and epigenetic changes in somatic cells in a mouse model of diabetes and studied whether multiple exposures to the antidiabetic medication dapagliflozin influence these changes. We also elucidated the mechanism(s) of these ameliorations. The micronucleus test and modified comet assay were used to investigate bone marrow DNA damage and methylation changes. These assays revealed that dapagliflozin is non-genotoxic in the tested regimen, and oxidative DNA damage and hypermethylation were significantly higher in diabetic mice. Spectrophotometry also evaluated oxidative DNA damage and global DNA methylation, revealing similar significant alterations induced by diabetes. Conversely, the dapagliflozin-treated diabetic animals significantly reduced these changes. The expression of some genes involved in DNA repair and DNA methylation was disrupted considerably in the somatic cells of diabetic animals. In contrast, dapagliflozin treatment significantly restored these disruptions and enhanced DNA repair. The simultaneous effects of decreased oxidative DNA damage and hypermethylation levels suggest that dapagliflozin can be used as a safe antidiabetic drug to reduce DNA damage and hypermethylation in diabetes, demonstrating its usefulness in patients with diabetes to control hyperglycemia and decrease the development of its subsequent complications.


Assuntos
Compostos Benzidrílicos , Dano ao DNA , Metilação de DNA , Diabetes Mellitus Experimental , Glucosídeos , Estresse Oxidativo , Animais , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Metilação de DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Hipoglicemiantes/farmacologia , Testes para Micronúcleos , Reparo do DNA/efeitos dos fármacos , Ensaio Cometa
10.
Chemosphere ; 355: 141668, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490614

RESUMO

Oily wastewater from the oil industry and oil spill accidents has become a serious environmental problem and has attracted worldwide attention. The present study reports on the successful preparation of a novel magnetic Ni-Al oxide/Zn0.4Co0.6F2O4 mesoporous aerogel (MNA) as a highly selective adsorbent for oil removal from water. Oleic acid (OA) and Triton X-100 (TX) were used as hydrophobic agents for MNA surface modification. It was found that the attached amount of OA on the mesoporous MNA aerogel is 3.5 times larger than that of TX, giving an advantage to MNA-OA in oil separation. The MNA-OA displayed superhydrophobicity (contact angle ∼150°) and superparamagnetism properties that allowed the adsorbent to be used selectively for oil removal. The MNA-OA was found to have a high oil removal efficiency of ∼97% with an adsorption capacity of ∼2 g/g. Furthermore, the produced magnetic adsorbent has high stability due to the strong chemical binding of OA, which is demonstrated by its good reusability performance. Throughout five separate runs, the MNA-OA was shown to be a very efficient and reusable adsorbent for oily wastewater.


Assuntos
Óxidos , Águas Residuárias , Água , Octoxinol , Nanopartículas Magnéticas de Óxido de Ferro , Zinco
11.
Obes Surg ; 34(1): 183-191, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37989926

RESUMO

PURPOSE: Studies are still ongoing to determine whether Helicobacter pylori (HP) may affect the results of laparoscopic sleeve gastrectomy (LSG). The main research objectives were HP prevalence in patients with severe obesity and the effects of HP status on outcomes. PATIENTS AND METHODS: This multicenter retrospective study included patients with severe obesity who had LSG. The patients were grouped into three groups based on the HP status of preoperative endoscopic biopsies and postoperative specimen results: group I (negative HP), group II (eradicated HP), and group III (positive HP). The primary outcome was the overall postoperative morbidities. RESULTS: One thousand six hundred fifteen patients who underwent LSG for severe obesity were included in this study. Seven hundred fifty (46.4%) patients had negative HP, and 637 (39.4%) patients had eradicated HP, whereas 228 (14.1%) patients had positive HP. The antral and gastric body wall thickness was significantly noticed with positive HP. The groups had no significant differences regarding postoperative complication frequency, severity, and hospital mortality. The rates of gastric leakage in the three groups do not differ significantly. BMI > 50, gastropexy, gastric thickness, and antral resection were found to be independent risk factors for the occurrence of postoperative complications after LSG. There was no statistical significance as regards postoperative %TWL and %EWL among the three groups. CONCLUSION: The early results of LSG do not appear to be impacted by HP's status. The early postoperative course is unaffected by HP eradication anymore. Therefore, routine preoperative HP testing may not be as necessary, and management can be finished after LSG.


Assuntos
Helicobacter pylori , Laparoscopia , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Laparoscopia/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Obesidade/cirurgia , Prevalência , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
12.
Biomater Sci ; 12(3): 725-737, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38099834

RESUMO

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surfaces by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.


Assuntos
Melanoma , Nanopartículas , Piperazinas , Piridinas , Camundongos , Humanos , Animais , Melanoma/tratamento farmacológico , Simulação de Acoplamento Molecular , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Tensoativos , Portadores de Fármacos/química , Quinase 4 Dependente de Ciclina
13.
bioRxiv ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38045274

RESUMO

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn , and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surface by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37973297

RESUMO

Diabetes-related complications are becoming increasingly common as the global prevalence of diabetes increases. Diabetes is also linked to a high risk of developing cancer. This raises the question of whether cancer vulnerability is caused by diabetes itself or the use of antidiabetic drugs. Chromosomal instability, a source of genetic modification involving either an altered chromosomal number or structure, is a hallmark of cancer. Saxagliptin has been approved by the FDA for diabetes treatment. However, the detailed in vivo effects of prolonged saxagliptin treatment on chromosomal instability have not yet been reported. In this study, streptozotocin was used to induce diabetes in mice, and both diabetic and non-diabetic mice received saxagliptin for five weeks. Fluorescence in situ hybridization was conducted in combination with a bone marrow micronucleus test for measuring chromosomal instability. Our results indicated that saxagliptin is neither mutagenic nor cytotoxic, under the given treatment regimen. Diabetic mice had a much higher incidence of micronuclei formation, and a centromeric DNA probe was present inside the majority of the induced micronuclei, indicating that most of these were caused by chromosome nondisjunction. Conversely, diabetic mice treated with saxagliptin exhibited a significant decrease in micronuclei induction, which were centromeric-positive and centromeric-negative. Diabetes also causes significant biochemical changes indicative of oxidative stress, such as increased lipid peroxidation and decreased reduced/oxidized glutathione ratio, which was reversed by saxagliptin administration. Overall, saxagliptin, the non-mutagenic antidiabetic drug, maintains chromosomal integrity in diabetes and reduces micronuclei formation by restoring redox imbalance, further indicating its usefulness in diabetic patients.


Assuntos
Diabetes Mellitus Experimental , Inibidores da Dipeptidil Peptidase IV , Neoplasias , Animais , Camundongos , Aneugênicos , Instabilidade Cromossômica , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/dietoterapia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Hipoglicemiantes/farmacologia , Hibridização in Situ Fluorescente , Mutagênicos , Neoplasias/complicações
15.
Surg Endosc ; 37(12): 9318-9325, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37891370

RESUMO

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become an increasingly popular bariatric procedure. LSG still conveys some risks, including early staple line complications such as bleeding and leaks. It has been proposed that staple line complications can be reduced by staple line reinforcement (SLR). This study aimed to compare the short-term efficacy and safety of the SLR during LSG by oversewing versus no SLR in an Egyptian cohort over a period of 11 years. PATIENTS AND METHODS: This is a retrospective study that analyzed data from patients undergoing LSG by the same surgeon over a period of 11 years. The patients' early postoperative complications were compared according to performing SLR. RESULTS: The SLR group showed significantly longer surgery time (p = 0.021) and a lower rate of postoperative bleeding (p = 0.027). All leakage cases occurred in the non-SLR group (0.7% vs. 0.0%) without statistical significance (p = 0.212). The two mortality cases occurred in the non-SLR group. The LOS was comparable in the two groups (p = 0.289). CONCLUSION: This study confirms the short-term benefits of SLR by oversewing during LSG in terms of a lower incidence of 30-day morbidity, particularly bleeding, and lower rates of reoperation, with a clinically questionable longer operation time.


Assuntos
Laparoscopia , Obesidade Mórbida , Humanos , Estudos Retrospectivos , Laparoscopia/métodos , Egito , Grampeamento Cirúrgico/métodos , Obesidade Mórbida/cirurgia , Gastrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
18.
Obes Surg ; 33(10): 3237-3245, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37624489

RESUMO

PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent unappealing laparoscopic sleeve gastrectomy (LSG) sequel. The study's purpose was to determine the prevalence, risk factors of PONV, and management of PONV after LSG. PATIENTS AND METHODS: This multicenter retrospective study included patients with morbid obesity who had LSG between January 2022 and April 2023. The age range for LSG was 16 to 65 years, and the eligibility requirements included morbid obesity according to international guidelines. RESULTS: PONV was experienced by 74.6% of patients who underwent LSG at 6 h postoperative. Multivariate analysis revealed that female gender, smokers, preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were found to be independent protective variables against the development of PONV. Combined intravenous ondansetron and metoclopramide improved 92.6% of patients who developed PONV. Dexamethasone and antihistamines drugs are given for 42 cases with persistent PONV after using intravenous ondansetron and metoclopramide. Pain management postoperatively by opioid-free analgesia managed PONV. Helicobacter pylori status has no role in the development of PONV after LSG. CONCLUSION: Female gender, smoking, presence of preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were observed to be independent protective factors against the occurrence of PONV. Combined intravenous ondansetron and metoclopramide improved PONV. Dexamethasone and antihistamines drugs are given for persistent PONV.


Assuntos
Refluxo Gastroesofágico , Laparoscopia , Obesidade Mórbida , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Náusea e Vômito Pós-Operatórios/epidemiologia , Estudos Retrospectivos , Metoclopramida , Ondansetron/uso terapêutico , Prevalência , Obesidade Mórbida/cirurgia , Fatores de Risco , Dor , Analgésicos Opioides/uso terapêutico , Gastrectomia/efeitos adversos , Dexametasona , Laparoscopia/efeitos adversos
19.
RSC Adv ; 13(31): 21318-21326, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37465571

RESUMO

A low-cost, accurate, and highly selective method was used for the assessment of the human chorionic gonadotropin ß-hCG in the serum of breast and prostate cancer patients. This method is based on enhancing the intensity of luminescence displayed by the optical sensor N/S-doped carbon dots (CQDs) upon adding different concentrations of ß-hCG. The luminescent optical sensor was synthesized and characterized through absorption and emission and is tailored to present blue luminescence at λem = 345 nm and λex = 288 nm at pH 7.8 in DMSO. The enhancement of the luminescence intensity of the N/S-doped CQDs, especially, the characteristic band at λem = 345 nm, is typically used for determining ß-hCG in different serum samples. The dynamic range is 1.35-22.95 mU mL-1, and the limit of detection (LOD) and quantitation limit of detection (LOQ) are 0.235 and 0.670 mU mL-1, respectively. This method was practical, simple, and relatively free from interference effect. It was successfully applied to measure PCT in the samples of human serum, and from this method, we can assess some biomarkers of cancer-related diseases in human body.

20.
Toxics ; 11(7)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37505601

RESUMO

The pathophysiology of autism is influenced by a combination of environmental and genetic factors. Furthermore, individuals with autism appear to be at a higher risk of developing cancer. However, this is not fully understood. Aflatoxin B1 (AFB1) is a potent food pollutant carcinogen. The effects of AFB1 on genomic instability in autism have not yet been investigated. Hence, we have aimed to investigate whether repeated exposure to AFB1 causes alterations in genomic stability, a hallmark of cancer and apoptosis in the BTBR autism mouse model. The data revealed increased micronuclei generation, oxidative DNA strand breaks, and apoptosis in BTBR animals exposed to AFB1 when compared to unexposed animals. Lipid peroxidation in BTBR mice increased with a reduction in glutathione following AFB1 exposure, demonstrating an exacerbated redox imbalance. Furthermore, the expressions of some of DNA damage/repair- and apoptosis-related genes were also significantly dysregulated. Increases in the redox disturbance and dysregulation in the DNA damage/repair pathway are thus important determinants of susceptibility to AFB1-exacerbated genomic instability and apoptosis in BTBR mice. This investigation shows that AFB1-related genomic instability can accelerate the risk of cancer development. Moreover, approaches that ameliorate the redox balance and DNA damage/repair dysregulation may mitigate AFB1-caused genomic instability.

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