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1.
PLoS One ; 19(9): e0307616, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39283907

RESUMEN

This study investigates the impact of cooling methods on the electrical efficiency of photovoltaic panels (PVs). The efficiency of four cooling techniques is experimentally analyzed. The most effective approach is identified as water-spray cooling on the front surface of PVs, which increases efficiency by 3.9% compared to the case without cooling. The results show that water-spray cooling raises the PV's temperature to 41°C, while improving its average daytime efficiency to 22%. Air-cooling, water-cooling in the tubes behind the PV, and aluminum oxide-water nanofluid cooling in the tubes behind the PV improve efficiency by 1.1%, 1.9%, and 2.7%, respectively. The findings highlight the potential of water-spray cooling as a cost-effective and efficient method to enhance PV efficiency and contribute to the global effort towards renewable energy.


Asunto(s)
Energía Solar , Suministros de Energía Eléctrica , Frío , Electricidad , Agua/química , Óxido de Aluminio/química
2.
Infect Drug Resist ; 17: 3879-3890, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257442

RESUMEN

Background: The COVID-19 pandemic's first wave and subsequent lockdowns disrupted global healthcare systems, significantly impacting essential services including tuberculosis (TB) care. Non-adherence to anti-TB drugs is a critical concern, leading to treatment failure, drug resistance, and increased morbidity and mortality. This study assessed the rate and determinants of non-adherence to TB treatment among patients at TB centers during the first wave of the pandemic. Material and Methods: A cross-sectional study was conducted from June 15 to July 30, 2020, involving 255 TB patients at three centers in Mogadishu. Data were gathered using the Morisky Medication Adherence Scale-8 (MMAS-8) through structured interviews and analyzed using descriptive statistics and binary logistic regression. Results: The study found a 34.5% non-adherence rate during the pandemic. Key reasons for non-adherence included forgetting to take medication (33%), feeling well (29%), experiencing side effects (18%), and fear of contracting COVID-19 (16%). Significant factors associated with non-adherence were age groups 25-34 years (OR = 2.96, p = 0.024) and 35-44 years (OR = 4.55, p = 0.005), unemployment (OR = 2.57, p = 0.037), smoking (OR = 3.49, p = 0.029), tobacco use (OR = 4.15, p = 0.034), proximity to a health facility (OR = 0.44, p = 0.033), perception of healthcare providers as very friendly (OR = 0.24, p = 0.031) or friendly (OR = 0.45, p = 0.023), being in the continuous treatment phase (OR = 3.2, p < 0.001), and experiencing adverse treatment effects (OR = 2.42, p = 0.003). Conclusion: Non-adherence to anti-tuberculosis treatment was notably high in Mogadishu during the first wave of the pandemic, necessitating targeted interventions to improve adherence.

4.
AAPS PharmSciTech ; 25(5): 131, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849687

RESUMEN

Lipid-based vectors are becoming promising alternatives to traditional therapies over the last 2 decades specially for managing life-threatening diseases like cancer. Cationic lipids are the most prevalent non-viral vectors utilized in gene delivery. The increasing number of clinical trials about lipoplex-based gene therapy demonstrates their potential as well-established technology that can provide robust gene transfection. In this regard, this review will summarize this important point. These vectors however have a modest transfection efficiency. This limitation can be partly addressed by using functional lipids that provide a plethora of options for investigating nucleic acid-lipid interactions as well as in vitro and in vivo nucleic acid delivery for biomedical applications. Despite their lower gene transfer efficiency, lipid-based vectors such as lipoplexes have several advantages over viral ones: they are less toxic and immunogenic, can be targeted, and are simple to produce on a large scale. Researchers are actively investigating the parameters that are essential for an effective lipoplex delivery method. These include factors that influence the structure, stability, internalization, and transfection of the lipoplex. Thorough understanding of the design principles will enable synthesis of customized lipoplex formulations for life-saving therapy.


Asunto(s)
Técnicas de Transferencia de Gen , Terapia Genética , Lípidos , Liposomas , Humanos , Lípidos/química , Terapia Genética/métodos , Liposomas/química , Animales , Transfección/métodos , Vectores Genéticos/química , Ácidos Nucleicos/química , Ácidos Nucleicos/administración & dosificación
5.
Sci Rep ; 14(1): 13068, 2024 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844495

RESUMEN

Diabetic nephropathy represents one of the main long-term complications in T2DM patients. Cigarette smoking represents one of modifiable renal risk factors to kidney damage due to lead (Pb) exposure in these patients. Our goal is to investigate serum copeptin and Kidney injury molecule-1 (KIM-1) and urinary lead (UPb) in type 2 diabetes mellitus (T2DM) patients even smokers and non-smokers groups and compared to corresponding health controls and assess its associations with Angiotensin-Converting enzyme Insertion/Deletion polymorphism [ACE (I/D)] polymorphism in diabetic nephropathy progression in those patients. In present study, 106 T2DM patients and 102 healthy control individuals were enrolled. Serum glucose, copeptin, KIM-1, total cholesterol (TChol), triglycerides (TG), estimated glomerular filtration rate (eGFR) and UPb levels and ACE (I/D) polymorphisms were assessed in both groups. Results mentioned to significant variations in all parameters compared to in T2DM group compared to control group. Serum copeptin and UPb demonstrated significant difference in diabetic smokers (DS) and diabetic non-smokers (DNS) groups while KIM-1 exhibited significant change between DNS and healthy control non-smokers (CNS) groups. Positive relation was recorded between serum glucose and KIM-1 while negative one was found between serum copeptin and TChol. D allele was associated with significant variation in most parameters in T2DM, especially insertion/deletion (ID) polymorphism. ROC curve analysis (AUC) for serum copeptin was 0.8, p < 0.044 and for Kim-1 was 0.54, p = 0.13 while for uPb was 0.71, p < 0.033. Serum copeptin and UPb might be a prognostic biomarker for renal function decline in smoker T2DM patients while KIM-1 was potent marker in non-smoker T2DM with association with D allele of ACE I/D gene polymorphism.


Asunto(s)
Diabetes Mellitus Tipo 2 , Glicopéptidos , Receptor Celular 1 del Virus de la Hepatitis A , Peptidil-Dipeptidasa A , Polimorfismo Genético , Humanos , Masculino , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/sangre , Femenino , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Glicopéptidos/sangre , Persona de Mediana Edad , Receptor Celular 1 del Virus de la Hepatitis A/genética , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/etiología , Mutación INDEL , Fumadores , Estudios de Casos y Controles , Adulto , Predisposición Genética a la Enfermedad , Tasa de Filtración Glomerular , Biomarcadores/sangre , Curva ROC
6.
Vasc Health Risk Manag ; 20: 21-26, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38222901

RESUMEN

Background: Intracerebral hemorrhage (ICH) is a serious condition characterized by bleeding within the brain tissue. Although the use of sildenafil, a vasodilator agent for erectile dysfunction, has been associated with rare cases of ICH, the combination of sildenafil usage and smoking as risk factors for ICH has not yet been reported. This case report describes the occurrence of ICH in a patient with a history of both sildenafil usage and heavy smoking. Case Presentation: A 53-year-old male, with a history of smoking and regular sildenafil use, was brought to the emergency department due to loss of consciousness with right-side weakness, he initially experienced with nausea, vomiting and dizziness after taking sildenafil 100mg tablet once. The Glasgow Coma Score (GCS) was 10 with side hemiparesis. Non-contrast CT revealed left thalamic acute hemorrhage with ventricular extension. Furthermore, a head CT angiography ruled out any vascular anomalies after that the patient was admitted to the intensive care unit (ICU) for conservative management. After three days on clinical and neurological improvement, the patient was transferred to the inpatient ward for further management, monitoring and physiotherapy. On day 6, the patient was discharged and planned for flow up. Conclusion: This rare case highlights the need for further research and awareness regarding the potential risks associated with the combination of sildenafil and heavy smoking. Healthcare professionals should carefully evaluate the individual risk factors of patients, educate them about potential complications, and consider alternative treatments if necessary. Additionally, patients should be encouraged to quit smoking and adopt a healthy lifestyle to minimize the risk of cerebrovascular events.


Asunto(s)
Fumar Cigarrillos , Disfunción Eréctil , Masculino , Humanos , Persona de Mediana Edad , Citrato de Sildenafil/efectos adversos , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/diagnóstico por imagen , Factores de Riesgo
7.
Vasc Health Risk Manag ; 19: 779-787, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025520

RESUMEN

Background: Natural killer (NK) cells are important components of adaptive and innate immune responses. NK cell subsets have different functions and may play a role in vascular disorders. This study aimed to evaluate the proportions of NK cells and their subsets to determine whether they can be used as markers of venous thrombosis and to identify whether there was a link between NK cell proportion and citrullinated histone (H3) levels. Patients and Methods: This study included 100 participants divided into Group I (n=50, patients with deep venous thrombosis (DVT)) and Group II (n=50, age- and sex-matched healthy controls). Group I was further categorized into Group Ia (n=25, patients with acute DVT) and Group Ib (n=25, patients with chronic DVT). The proportions of NK cells and their subsets were evaluated by flow cytometry using CD3/CD16/CD56. The levels of citrullinated histones (H3) were estimated using enzyme-linked immunosorbent assay (ELISA). Results: Compared to the control group, DVT patients had a significantly lower proportion of (CD56 dim/CD16+) NK cells, a significantly higher proportion of (CD56-/CD16+) NK cells and a high level of citrullinated histone (H3). Conclusion: NK cell subsets and citrullinated histone (H3) could be used as markers for DVT and as targets for therapeutic drugs to inhibit the formation or progression of thrombosis.


Asunto(s)
Histonas , Células Asesinas Naturales , Humanos , Antígeno CD56/metabolismo , Células Asesinas Naturales/metabolismo , Citometría de Flujo
8.
Diabetes Metab Syndr Obes ; 16: 2617-2625, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37663202

RESUMEN

Background: One of the major issues affecting global health is Diabetes mellitus (DM), not only in terms of the disease itself but also its complications. Macrovascular complications are both common and serious, affecting many patients. This study aimed to assess fasting C-peptide levels and correlate them with the severity of the peripheral arterial disease complicating type 2 DM (T2DM). Patients and Methods: This study included 200 participants who were categorized into two groups: Group I (n=100, patients with T2DM complicated by femoropopliteal arterial atherosclerosis) and Group II (n=100, healthy age- and sex-matched individuals serving as controls). Fasting C-peptide levels were estimated using an immunochemiluminometric assay. Results: Fasting C-peptide levels were significantly higher in Group I than in the control group. Fasting C-peptide levels were positively correlated with the severity of atherosclerosis. In addition, the receiver operating characteristic (ROC) curve analysis revealed that fasting C-peptide levels served as a specific and sensitive marker for detecting the severity of this disease. Conclusion: Fasting C-peptide levels can be used as a sensitive and specific indicator of the severity of femoropopliteal arteriosclerosis that complicates T2DM.

9.
Int J Pharm ; 646: 123385, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37678473

RESUMEN

The evolution of a safe and effective therapeutic system to conquer SAR-CoV-2 infection deemed to be a crucial worldwide demand. Curcumin (CUR) is a phytomedicinal polyphenolic drug that exhibited a well-reported anti-SAR-CoV-2. However, the therapeutic activity of CUR is hindered by its poor intestinal permeability and diminished aqueous solubility. Therefore, this study strived to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) bilosomes (TPGS-Bs) adopting 23 full factorial designs to improve solubility and intestinal permeability of CUR, hence boosting its anti-SARS-CoV-2 activity. Eight experimental runs were attained considering three independent variables: soybean phosphatidylcholine amount (mg) (SPC amount), bile salt amount (mg) (BS amount), and TPGS amount (mg). The optimum formula (F4) exhibited EE % (88.5 ± 2.4 %), PS (181.5 ± 21.6 nm), and ZP (-34.5 ± 3.7 mV) with desirability value = 0.739 was picked as an optimum formula. Furthermore, the optimum formula (F4) was extra coated with chitosan (CS) to improve permeability and anti-SAR-CoV-2 activity. Caco-2 cell uptake after 2 hr revealed the superiority of CS-F4 and F4 by 6 and 5 folds relative to CUR dispersion, respectively. Furthermore, CS-F4 exhibited a significantly higher anti-SARS-CoV-2 activity with IC50 (0.24 µg/ml) by 8.3 times than F4 (1.99 µg/ml). Besides, the mechanistic study demonstrated that the two formulae imparted antiviral activity by inhibiting the spike protein by virucidal potentialities. In addition, the conducted molecular docking and MD simulations towards the SARS-CoV-2 Mpro enzyme confirmed the interaction of CUR with key residues of the virus enzymes. Based on the preceded, CS-F4 could be assumed to be used to effectively eradicate SARS-CoV-2 infection.

10.
ERJ Open Res ; 9(5)2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37753277

RESUMEN

In healthy asymptomatic smokers with normal FEV1/FVC, abnormal CT lung volumes that reflect small airway dysfunction and emphysema could be used as a biomarker to identify susceptible smokers at increased risk of progressing to COPD https://bit.ly/3XZDj1s.

11.
Biol Open ; 12(8)2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37581305

RESUMEN

This review highlights the largely understudied behavior of gliding locomotion, which is exhibited by a diverse range of animals spanning vertebrates and invertebrates, in air and in water. The insights in the literature gained from January 2022 to December 2022 continue to challenge the previously held notion of gliding as a relatively simple form of locomotion. Using advances in field/lab data collection and computation, the highlighted studies cover gliding in animals including seabirds, flying lizards, flying snakes, geckos, dragonflies, damselflies, and dolphins. Altogether, these studies present gliding as a sophisticated behavior resulting from the interdependent aspects of morphology, sensing, environment, and likely selective pressures. This review uses these insights as inspiration to encourage researchers to revisit gliding locomotion, both in the animal's natural habitat and in the laboratory, and to investigate questions spanning gliding biomechanics, ecology, sensing, and the evolution of animal flight.


Asunto(s)
Lagartos , Odonata , Animales , Alas de Animales/anatomía & histología , Locomoción , Vuelo Animal , Fenómenos Biomecánicos
12.
Int J Pharm ; 643: 123259, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37479100

RESUMEN

The incidences of antimicrobial resistance in particular, Methicillin-Resistant Staphylococcus aureus (MRSA) have increased during the last two decades. However, conventional dosage forms are unable to evade the barrier effect of the stratum corneum to permit deep penetration of the skin to resolve deep skin infections. There is, therefore, an urgent need for an advanced drug delivery system. Thus the study reported herein was aimed to fabricate a novasome-loaded luteolin (LUT) to improve its topical delivery and to enhance its antibacterial activity. The system was investigated for the impact of the type of surfactant, stearic acid concentration (g %), cholesterol amount (mg) and Brij 52 amount (mg) on the percent entrapment efficiency, particle size, poly-dispersity index and zeta potential. Statistical optimization of these factors was conducted using the Design-Expert® software. The optimum formulation was further in-vitro characterized by release study, differential scanning calorimetry, transmission electron microscope, x-ray diffraction and antibacterial activity. Formulation F2 composed of Span 60, 0.4 g % of stearic acid, 100 mg cholesterol and 30 mg Brij 52 was selected as the optimum formula based on the highest desirability value (0.634). F2 demonstrated enhanced antimicrobial activity with lower minimum inhibitory concentrations against a panel of MRSA clinical isolates when compared to LUT dispersion. Furthermore, the F2 formula exhibited higher anti-virulence activity by effectively inhibiting biofilm formation and suppressing α-hemolysin activity in MRSA isolates. It also demonstrated improved biosafety based on cytotoxicity assessment on human skin fibroblasts (HSF). Finally, when assessed in an in vivo skin infection mouse model, the F2 formula and commercially available fusidic acid preparation significantly reduced the microbial load of infected skin lesions compared to both the negative control and LUT dispersion-treated groups. Based on the aforementioned results, the validity of novasomes as a nano-carrier to boost in vitro and in vivo anti-MRSA activity of LUT could be affirmed.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Animales , Ratones , Ácidos Grasos no Esterificados , Luteolina/farmacología , Luteolina/uso terapéutico , Cetomacrogol/farmacología , Cetomacrogol/uso terapéutico , Antibacterianos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
13.
Antibiotics (Basel) ; 12(7)2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37508191

RESUMEN

Antibiotic-resistant bacteria represent a serious public health threat. For that reason, the development of new and effective antibiotics to control pathogens has become necessary. The current study aims to search for new microorganisms expressing antibiotic production capacity. Fifteen sites covering a wide range of harsh environmental conditions in Egypt were investigated. Two hundred and eighty bacterial isolates were obtained and then tested against pathogenic bacteria using the agar disk diffusion technique. Fifty-two (18.6% of the total) of the isolates exhibited antagonistic properties, which affected one or more of the tested pathogens. The isolate 113 was identified as Bacillus licheniformis and isolate 10 was identified as Brevibacillus borstelensis using the 16S rRNA technique. The B. licheniformis strain was stronger in antibiotic production against S. typhi, M. luteus, and P. ariginosa, whereas the strain Br. borstelensis was more efficient against B. cereus, E. coli, and Klebs. sp. The sensitivity of the strains to commercial antibiotics showed that B. licheniformis was highly sensitive to seven commercial antibiotics, whereas Br. borstelensis was sensitive to nine antibiotics. The two strains were subjected to ethyl methanesulfonate (EMS) mutagenesis to obtain mutants with a higher antibiotic production. The total bacterial count was measured after treatment with EMS mutagen and showed a significant gradual increase in the antimicrobial activity, which was achieved via shaking in the presence of EMS for 60 min. High antimicrobial activities were noted with 17 and 14 mutants from the B. licheniformis and Br. borstelensis strains, respectively. The mutant B. licheniformis (M15/Amo) was more active than the parent strain against S. aureus (212.5%), while the mutant Br. borstelensis (B7/Neo) was more effective against S. typhi (83.3%). The present study demonstrates the possibility of obtaining potent antibiotic-producing bacteria in hot spring waters and further improving the indigenous bacterial capacity to produce antibiotics by using EMS mutagenesis.

14.
J Diabetes Investig ; 14(10): 1192-1201, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37394883

RESUMEN

AIMS/INTRODUCTION: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. MATERIALS AND METHODS: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay. RESULTS: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. CONCLUSIONS: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Enfermedad Arterial Periférica , Humanos , Pie Diabético/etiología , Monocitos/patología , Colecalciferol , Enfermedad Arterial Periférica/complicaciones , Lipoproteínas HDL
15.
J Enzyme Inhib Med Chem ; 38(1): 2202357, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37092260

RESUMEN

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a-g) were assessed in Vero E6 cells via MTT assay to calculate the CC50 and inhibitory concentration 50 (IC50) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with an IC50 value of 0.73 µg/mL. Moreover, F3e was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure-activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity.HighlightsEmulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g).The most potent 3e-loaded EMLs (F3e) showed an IC50 value of 0.73 µg/mL against SARS-CoV-2.F3e exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition.Molecular docking, molecular dynamics (MD) simulations, and MM-GBSA calculations were performed.Structure-activity relationship (SAR) study was discussed to study the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide on the anti-SARS-CoV-2 activity.


Asunto(s)
COVID-19 , Nanopartículas , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Antivirales/farmacología , Simulación de Dinámica Molecular , Inhibidores de Proteasas
16.
Int J Pharm ; 640: 122980, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37116601

RESUMEN

Nowadays, conventional anticancer therapy suffers many pitfalls, including drastic side effects and limited therapeutic efficacy resulting from diminished oral bioavailability. So, in an attempt to enhance their poor solubility and oral bioavailability along with the cytotoxic activity, the developed lead compounds (C1 and C2) were loaded in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified vesicles adopting thin film hydration technique. The formulations of the aforementioned candidates (F1 and F2, respectively) were elected as the optimum formula with desirability values of 0.701 and 0.618, respectively. Furthermore, an outstanding enhancement in the drug's cytotoxic activity against different cancer cell lines (MCF-7, HepG-2, MDA-MB-321, A375, and MGC-803) after being included in the nano-TPGS-modified optimum formula was noticed relative to the unformulated compounds. The formula F1 showed the best cytotoxic activities against HepG-2 with an IC50 = 3 µM. Furthermore, regarding MCF-7, F1 was shown to be the most potent and protective among all the tested formulations with an IC50 = 6 µM. Besides, F1 exerted the best caspase 3/7 activity stimulation (around a 5-folds increase) compared to control in the MCF-7 cell line. Notably, it was disclosedthat both C1 and C2 induced cell cycle arrest at the resting S growth phase. Moreover, C1 and C2 decreased tubulin concentrations by approximately 2-folds and 6-folds, respectively. Meanwhile, the conducted molecular docking studies ensure the eligible binding affinities of the assessed compounds. Besides, MD simulations were performed for 1000 ns to confirm the docking results and study the exact behavior of the target candidates (C1 and C2) toward the CBS.


Asunto(s)
Antineoplásicos , alfa-Tocoferol , Humanos , alfa-Tocoferol/química , Disponibilidad Biológica , Colchicina , Proyectos de Investigación , Ácidos y Sales Biliares , Simulación del Acoplamiento Molecular , Vitamina E/química , Polietilenglicoles/química , Antineoplásicos/farmacología , Succinatos
17.
Pharmaceutics ; 15(2)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36839928

RESUMEN

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 23 factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 ± 2.86%), an appropriate size of 370.10 ± 10.31 nm, PDI; 0.398 ± 0.001, and ZP; -5.40 ± 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 ± 6.77 nm) and a shift from negative to positive zeta potential (+21.63 ± 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (Papp) being 2.05 × 10-4 cm/min and 2.91 × 10-4 cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 × 10-5 cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.

18.
Drug Deliv ; 30(1): 2162157, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36587813

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels the evolution of safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility and massive degradation in GIT and liver which in turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain PEGylated edge activator along with the traditional components as (Span 60, cholesterol and bile salts) were proposed to boost both permeability and bioavailability of RSV. The investigation of the prominent effect of the diverse variables on the characteristics of the vesicles and picking of the optimum formula were conducted via construction of 23 factorial experiment. The appraisal of the formulae was conducted on the basis of entrapment efficiency percent (EE%), particle size (PS) and zeta potential (ZP). In addition, the spherical shaped optimal formula (F5) exhibited EE% of 86.1 ± 2.9%, PS of 228.9 ± 8.5 nm, and ZP of -39.8 ± 1.3 mV. The sorted optimum formula (F5) exhibited superior dissolution behaviors, and boosted Caco-2 cells cellular uptake by a round 4.7 folds relative to RSV dispersion. In addition, F5 demonstrated a complete in vitro suppression of SARS-CoV-2 at a concentration 0.48 µg/ml with 6.6 times enhancement in antiviral activity relative to RSV dispersion. The accomplished molecular modeling heavily provided proof for the possible interactions of resveratrol with the key residues of the SARS-CoV2 Mpro enzyme. Finally, F5 could be proposed as a promising oral panel of RSV for curation from SARS-CoV-2 infection.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Células CACO-2 , Resveratrol/farmacología , Antivirales/farmacología , ARN Viral , Polietilenglicoles , Permeabilidad , Tamaño de la Partícula
19.
Asian J Surg ; 46(1): 483-491, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35750611

RESUMEN

BACKGROUND: We described our local experiences with a single-layer wrapping technique for the vascular anastomoses in patients with Adamantiadis-Behçet's aortic/aortoiliac aneurysms using InterGard Silver-impregnated Dacron® patch prosthesis. METHODS: Between January 2013 to December 2019, we retrospectively reviewed 20 patients presented with Adamantiadis-Behçet's aortic/aortoiliac aneurysms. All patients presented with Adamantiadis-Behçet's aortic/aortoiliac aneurysms. Two groups were analyzed, Group I, considered as a control group (n = 20). While group II (n = 20), of which prosthetic wrapping was performed. Follow up took place for a maximum of 24 months. RESULTS: during a six-year retrospective study period, 20 patients were recruited. They included 15 males and five females (ratio 3:1). The median age was 30.5 ± 4.2 years. Anastomotic pseudoaneurysms were reported in group I (control, [non-wrapping group]). While group II doesn't (wrapping group). Paired samples t test revealed a significant difference between those underwent wrapping and those with non-wrapping (p = .019 and .038). False aneurysms were reported in 80% of the non-wrapping group as estimated by the Kaplan-Meier curves. While Log-rank test results revealed a significant difference between both the studied groups (p < .008). Primary graft patency was 90% at 24 months as reported by the Kaplan-Meier survival method. CONCLUSIONS: adjunctive wrapping for vascular anastomoses using Intergard Silver-impregnated Dacron® patch in patients with Adamantiadis-Behçet's aortic/aortoiliac aneurysms is an applicable, simple, and reliable technique. It was associated with low morbidity and mortality rates. Moreover, we discussed a relatively old technique aiming to explore its success and safety in treating arterial aneurysms in Adamantiadis-Behçet's disease patients.


Asunto(s)
Aneurisma Falso , Aneurisma de la Aorta Abdominal , Aneurisma de la Aorta , Síndrome de Behçet , Masculino , Femenino , Humanos , Adulto , Síndrome de Behçet/cirugía , Síndrome de Behçet/complicaciones , Estudios Retrospectivos , Tereftalatos Polietilenos , Plata , Aneurisma de la Aorta/complicaciones , Aneurisma Falso/complicaciones
20.
Int J Pharm ; 628: 122274, 2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36228884

RESUMEN

The utilization of the proper and safe analgesics was considered a major concern in pain alleviation especially that associated with surgical procedures. Novel analgesics as Tapentadol hydrochloride (TAP) was involved efficiently instead of the common opioids to overcome the subsequent severe and common adverse effects associated with opioids utilization. Unfortunately, the extensive first pass metabolism limits the oral bioavailability of TAP and predisposes to a diminished duration of action, hence larger frequent doses of TAP will be required. Therefore, the target of this study was to lodge TAP into PEGylated transferosomes to boost its transdermal delivery. The PEGylation contemplated to boost both TAP permeability and bioavailability besides offering extra resilience to the vesicles. The impact of diverse variables on the characteristics of the vesicles and distinguishing the optimal formula were implemented adopting 23 factorial experiment via Design Expert® software. The resulted eight formulae were fabricated by thin film hydration technique, additionally they were evaluated based on the findings of entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and the optimal one was involved in further assessments. The optimal formula (F8) exhibited spherical vesicles with EE% of 77.9 ± 3.4 %, PS of 150.5 ± 5.33 nm, PDI of 0.47 ± 0.05, ZP of -40.7 ± 4.6 mV and it also revealed greater deformability index (30.9 ± 6.1 g) relative to traditional transferosomes (12.15 ± 2.49 g). In addition, confocal laser scanning microscopy examination affirmed the superior penetration of Rhodamine B (RhB) dye thorough the rat's skin from F8 relative to the dye solution. The safety of F8 was confirmed by histopathological study. Moreover, dermato-kinetic study disclosed that TAP exhibited higher retention within the rat's skin form F8 relative to TAP dispersion. Furthermore, the in vivo pharmacodynamics activities conducted on male rats confirmed the superiority of F8 over the drug dispersion in alleviation the induced pain by IP injection of acetic acid and by formation of paw incisions. Collectively, the credibility of F8 as panel for transdermal delivery of TAP with boosted bioavailability and analgesic activity could be ensured on the basis of the obtained findings.


Asunto(s)
Analgésicos Opioides , Liposomas , Masculino , Ratas , Animales , Disponibilidad Biológica , Tapentadol , Sistemas de Liberación de Medicamentos/métodos , Ratas Wistar , Administración Cutánea , Tamaño de la Partícula , Analgésicos , Polietilenglicoles , Dolor Postoperatorio , Empleo
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