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1.
Mol Genet Genomics ; 299(1): 56, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787424

RESUMEN

Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.


Asunto(s)
Beclina-1 , Neoplasias de la Mama , Clasificación del Tumor , ARN Mensajero , Humanos , Femenino , Beclina-1/genética , Beclina-1/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Persona de Mediana Edad , Adulto , ARN Mensajero/genética , ARN Mensajero/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Supervivencia sin Enfermedad , Biomarcadores de Tumor/genética , Anciano , Egipto
2.
Cell Biochem Funct ; 41(6): 642-657, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37342005

RESUMEN

The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,ß-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.


Asunto(s)
Mimusops , Extractos Vegetales , Ratas , Masculino , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Mimusops/química , Hígado , Peso Corporal , Hojas de la Planta
3.
Cellulose (Lond) ; 30(6): 3505-3522, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36994234

RESUMEN

In this work, new chitosan derivative nanofibers that exhibit antibacterial properties were successfully fabricated. The two CS Schiff base derivatives (CS-APC and CS-2APC) were prepared by incorporating 4-amino antipyrine moiety in two different ratios, followed by a reductive amination to obtain the corresponding derivatives CS-APCR and CS-2APCR. Spectral analyses were used to confirm the chemical structure. The molecular docking evaluation of CS-APC, CS-APCR, and CS was conducted on DNA topoisomerase IV, thymidylate kinase and SARS-CoV-2 main protease (3CLpro) active sites. CS-APCR showed a well-fitting into the three enzyme active sites with docking score values of - 32.76, - 35.43 and - 30.12 kcal/mol, respectively. The nanocomposites of CS derivatives were obtained by electrospinning the blends of CS-2APC and CS-2APCR with polyvinyl pyrrolidone (PVP) at 20 kV. The morphology of the nanofibers was investigated by scanning electron microscopy (SEM). It was found that fiber diameters were significantly decreased when CS-2APC and CS-2APCR were incorporated into pure PVP to reach 206-296 nm and 146-170 nm, respectively, compared to 224-332 nm for pure PVP. The derivatives of CS and their nanofibers with PVP were found to have antibacterial activities against two strains of Staphylococcus aureus and Escherichia coli. Data revealed that CS-2APC nanofibers showed antibacterial activity to the two strains of E. coli less than CS-2APCR nanofibers.

4.
BMC Oral Health ; 23(1): 967, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053146

RESUMEN

BACKGROUND: In-vitro data from a clinically well-known lithium disilicate ceramic reference was used to assess the expected performance of resin-based materials in implant dentistry. The purpose of the study was to compare the bond strength and marginal adaptation of nano-ceramic hybrid composite crowns cemented to stock cement-retained abutments to lithium disilicate crowns. METHODS: Twenty abutment analogs were embedded into auto-polymerizing acrylic resin blocks. The blocks were divided into 2 groups according to the restorative crown material. The 2 groups were divided as follows: Resin nano-ceramic group and lithium disilicate group. Abutment analogs in both groups were scanned using a laboratory scanner, and the restorations were designed, manufactured, and cemented with resin cement over the corresponding group. All samples were tested for marginal adaptation and bond strength after storage for 24 hours at 37 °C in 100% humidity. Data were collected, tabulated, and statistically analysed using the appropriate tests. Normality was checked using Shapiro Wilk test and Q-Q plots. Data were normally distributed. Variables were presented using mean, 95% Confidence Interval (CI) and standard deviation in addition to median and Inter Quartile Range (IQR). Differences between groups regarding debonding forces was assessed using independent t test. Two Way ANOVA was performed to assess the effect of material and bonding on marginal gap. All tests were two tailed and p value was set at < 0.05. RESULTS: Marginal gap and debonding force values were significantly different according to the type of material used (P < .05). Resin nano-ceramic crowns presented lower marginal gap values before (20.80 ± 8.87 µm) and after (52.11 ± 22.92 µm) bonding than lithium disilicate crowns. The debonding force value for resin nano-ceramic crowns (284.30 ± 26.44 N) was significantly higher than that for lithium disilicate crowns (253.30 ± 33.26 N). Adhesive failure mode was detected in all the specimens in both groups. CONCLUSIONS: The type of material used for implant-supported cement-retained crowns had a statistically significant effect on marginal adaptation and bond strength. Resin nano-ceramic implant-supported cement-retained crowns had better marginal adaptation and higher bond strength than those manufactured using lithium disilicate.


Asunto(s)
Coronas , Cementos Dentales , Humanos , Cementos de Ionómero Vítreo , Materiales Dentales , Cerámica , Cementos de Resina , Diseño Asistido por Computadora , Ensayo de Materiales
5.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-35055029

RESUMEN

Electrically conductive materials that are fabricated based on natural polymers have seen significant interest in numerous applications, especially when advanced properties such as self-healing are introduced. In this article review, the hydrogels that are based on natural polymers containing electrically conductive medium were covered, while both irreversible and reversible cross-links are presented. Among the conductive media, a special focus was put on conductive polymers, such as polyaniline, polypyrrole, polyacetylene, and polythiophenes, which can be potentially synthesized from renewable resources. Preparation methods of the conductive irreversible hydrogels that are based on these conductive polymers were reported observing their electrical conductivity values by Siemens per centimeter (S/cm). Additionally, the self-healing systems that were already applied or applicable in electrically conductive hydrogels that are based on natural polymers were presented and classified based on non-covalent or covalent cross-links. The real-time healing, mechanical stability, and electrically conductive values were highlighted.


Asunto(s)
Materiales Biocompatibles/química , Biopolímeros/química , Conductividad Eléctrica , Hidrogeles/química , Animales , Fenómenos Químicos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Polimerizacion , Ingeniería de Tejidos
6.
Wound Repair Regen ; 29(3): 425-431, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33476473

RESUMEN

Keloids result from uncontrolled inflammation and fibrosis during wound healing. Vitamin D can regulate skin proliferation and inflammation. Fibroblasts are vitamin D-responsive target cells and are source of koebnerisin (an antimicrobial peptide released during inflammation and wound healing). This study aimed to assess the levels and correlations between the serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin (S100A15) in patients with keloids. Nineteen patients with keloids and 20 matched controls were recruited. From each keloid patient, a serum sample and two biopsies were taken from the keloid (lesional) (Tissue A) and from normal skin (non-lesional) (Tissue B). From controls, a serum sample and a tissue biopsy from normal skin were taken. Serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin were measured in retrieved samples using ELISA. Results revealed a significantly lower serum 25-Hydroxyvitamin D, tissue vitamin D receptors, as well as, serum and tissue koebnerisin in keloid patients compared to controls. Tissue 25-Hydroxyvitamin D was significantly lower in keloidal skin biopsy (Tissue A) compared to non-lesional normal skin biopsy (Tissue B). Tissue koebnerisin showed a significant positive correlation with tissue vitamin D receptors, and a significant negative correlation with tissue 25-Hydroxyvitamin D. There was a significant negative correlation between serum 25-Hydroxyvitamin D and duration of keloid. Accordingly, low serum and tissue 25-Hydroxyvitamin D and deficient tissue vitamin D receptors contribute to the pathogenesis of keloids. This can be partly mediated by dysregulation of the antimicrobial peptide; koebnerisin. Artificial antimicrobial peptides and koebnerisin-modifying drugs, for example, vitamin D and TNF-α inhibitors can have a role in keloid prevention and treatment.


Asunto(s)
Queloide , Deficiencia de Vitamina D , Péptidos Antimicrobianos , Estudios de Casos y Controles , Fibroblastos/patología , Humanos , Queloide/patología , Proteína A7 de Unión a Calcio de la Familia S100 , Cicatrización de Heridas
7.
Am J Dermatopathol ; 43(9): 653-655, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-33577178

RESUMEN

ABSTRACT: Crystalglobulinemia (CG) is a rare disorder characterized by crystallization of monoclonal immunoglobulins in the microcirculation leading to multiorgan vascular thrombosis and ischemic injury. The main cause of CG is multiple myeloma. We report a case of a 52-year-old man who presented with widespread necrotizing plaques and ulcerations. A skin biopsy revealed eosinophilic rectangular-shaped crystals occluding the lumina of blood vessels with no associated features of vasculitis. The crystals were Periodic acid-Schiff stain positive. The findings were diagnostic of CG. Extensive work up lead to the discovery of multiple myeloma. Awareness of CG is important because it may be the first presenting manifestation of an underlying serious hematological malignancy.


Asunto(s)
Inmunoglobulinas/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Úlcera Cutánea/patología , Vasos Sanguíneos , Cristalización , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Úlcera Cutánea/etiología
8.
Arch Biochem Biophys ; 679: 108205, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31758927

RESUMEN

This study suggested that methylseleninic acid (MSA) could respond to the inflammatory signaling associated with ionizing radiation-induced testicular damage. Mature male rats were divided into four groups: negative control, whole body γ-irradiated (IRR) (5 Gy), MSA (0.5 mg/kg, daily for nine consecutive days), and MSA+ IRR groups. MSA increased serum testosterone level and testicular glutathione peroxidase (GPx) as well as decreased the percentage of sperm abnormalities. Radiation prompted inflammatory signaling in the testes through increasing phospho-janus kinase1 (p-JAK1), phospho-signal transducers and activators of transcription 3 (p-STAT3) protein expressions. This induced increment in the inflammatory markers including nuclear factor- kappa B (NF-κB) and interleukin-1beta (IL-1ß) levels. Also, radiation induced elevation of nitric oxide (NO) and malondialdhyde (MDA) levels with consequent reduction in testicular reduced glutathione level (GSH) and superoxide dismutase (SOD) activity. MSA significantly counteracted the radiation effect on testicular nuclear factor erythroid-2-related factor-2 (Nrf2) and suppressor of cytokine signaling (Socs3) protein expressions. In summary, this investigation proposed that MSA preserved spermatogenesis through increasing testosterone levels and GPx activity. Additionally, it diminished testicular inflammation by increasing of Nrf2 and Socs3 levels leading to reducing of p-JAK1, p-STAT3 and NF-κB levels. Histopathological examination results of testicular tissues showed a coincidence with the biochemical analysis.


Asunto(s)
Quinasas Janus/metabolismo , Compuestos de Organoselenio/farmacología , Protectores contra Radiación/farmacología , Factores de Transcripción STAT/metabolismo , Testículo/efectos de los fármacos , Testículo/efectos de la radiación , Animales , Antioxidantes/metabolismo , Glutatión/metabolismo , Interleucina-1beta/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Ratas , Ratas Sprague-Dawley , Cabeza del Espermatozoide/efectos de los fármacos , Cabeza del Espermatozoide/patología , Cabeza del Espermatozoide/efectos de la radiación , Superóxido Dismutasa/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Testículo/citología , Testículo/metabolismo
9.
Pediatr Res ; 87(1): 74-80, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31216566

RESUMEN

OBJECTIVE: We assessed oxidant-antioxidant status and evaluated the role of lipid peroxidation, oxidative DNA damage, and protein oxidation in the development and severity of neonatal respiratory distress syndrome (RDS). METHODS: Forty preterm neonates with RDS were compared with another 40 preterm neonates without RDS enrolled as controls. Total antioxidant capacity (TAC), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), 8-hydroxy-2-deoxyguanosine (8-OHdG), and trace elements (copper and zinc) were measured in cord blood (day 0) for all neonates and repeated on day 3 for the RDS group. RESULTS: Day 0 serum levels of MDA, AOPPs, and 8-OHdG were significantly higher in neonates with RDS than controls with a further increase on day 3. Days 0 and 3 levels of TAC, copper, and zinc were significantly lower in the RDS group compared with controls. Elevated serum levels of 8-OHdG and AOPPs were associated with severe RDS, invasive mechanical ventilation, and high mortality rate. 8-OHdG and AOPPs were positively correlated with MDA, oxygenation index, duration of ventilation, and duration of hospitalization. CONCLUSIONS: Increased lipid, protein, and DNA oxidation is accompanied by alterations in the antioxidant defense status, which may play a role in the pathogenesis and severity of RDS.


Asunto(s)
8-Hidroxi-2'-Desoxicoguanosina/sangre , Productos Avanzados de Oxidación de Proteínas/sangre , Daño del ADN , Peroxidación de Lípido , Estrés Oxidativo , Carbonilación Proteica , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Biomarcadores/sangre , Peso al Nacer , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Masculino , Malondialdehído/sangre , Estudios Prospectivos , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Índice de Severidad de la Enfermedad , Factores de Tiempo
10.
Dermatol Ther ; 33(6): e13998, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32648977

RESUMEN

Vitiligo is an autoimmune disease characterized by patches of depigmentation. Zinc is an antiapoptotic molecule that exhibits antioxidant properties. The study aimed to investigate the serum levels of zinc in vitiligo patients compared to healthy controls and to whether exists a correlation between disease severity and serum levels of zinc. Fifty patients with vitilgo (group A) and 50 age and sex matched healthy controls (group B) were recruited and serum zinc level was measured using atomic absorption spectrophotometry and results were compared and correlated to each other and to disease severity and extension. The mean serum zinc levels in group A was 50.93 ± 11.02 in comparison to a mean of 77.09 ± 12.16 in group B (P = .049, T = -1.993). Vitiligo area severity index (VASI) scores in the vitiligo group ranged from 0.5 to 27 with a mean ± SD of (9.19 ± 4.47). A high statistically significant negative correlation was demonstrated between serum zinc levels and the extension of vitiligo (P value = .0001 and R value = - 0.835). A significant association exists between vitiligo and serum zinc levels. Serum zinc levels correlated negatively with vitiligo disease severity and extension. Zinc supplementation and use can be of potential importance in setting vitiligo treatment protocols.


Asunto(s)
Vitíligo , Antioxidantes , Humanos , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Vitíligo/diagnóstico , Zinc
11.
Dermatol Surg ; 46(9): e38-e44, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31851017

RESUMEN

BACKGROUND: Fractional CO2 laser has been shown effective in improving pigmentation, pruritus, and tightness of hypertrophic burn scars. However, there is no consensus on the optimal treatment parameters. OBJECTIVE: To compare effectiveness of different densities of fractional CO2 laser in the treatment of mature hypertrophic burn scars. MATERIALS AND METHODS: The study included 25 patients, each with 3 or more mature hypertrophic burn scars. Scars were randomly assigned to treatment with low-, medium-, and high-density fractional CO2 laser. Each scar received 3 sessions of laser at 1-month interval. The degree of improvement was assessed clinically using Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) scores, and histologically through evaluation of collagen (Masson's Trichrome stain) before and 1 month after end of therapy. RESULTS: High-density parameters showed significant higher improvement in VSS and POSAS assessment scores (p-value < .001). Pliability and relief are the most improved parameters. Histopathological evaluation revealed a significant drop in the mean area percent of collagen in the 3 used parameters, with highest improvement with high-density laser treatment (p-value < .001). CONCLUSION: High-density fractional CO2 laser treatment provides more improvement in burn scars both clinically and histopathologically.


Asunto(s)
Quemaduras/complicaciones , Cicatriz Hipertrófica/terapia , Terapia por Láser/métodos , Láseres de Gas/uso terapéutico , Adolescente , Adulto , Cicatriz Hipertrófica/etiología , Cicatriz Hipertrófica/patología , Femenino , Humanos , Terapia por Láser/instrumentación , Masculino , Piel/patología , Piel/efectos de la radiación , Resultado del Tratamiento , Cicatrización de Heridas/efectos de la radiación , Adulto Joven
12.
Neurosurg Focus ; 47(1): E20, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31261125

RESUMEN

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.


Asunto(s)
Modelos Animales de Enfermedad , Aneurisma Intracraneal/patología , Modelos Biológicos , Aneurisma Roto/cirugía , Animales , Perros , Embolización Terapéutica , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Ratones , Conejos , Ratas , Porcinos
13.
Pediatr Nephrol ; 30(10): 1835-42, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25980471

RESUMEN

BACKGROUND: Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. The aim of our study was to evaluate and compare renal functional and structural integrity in 50 infants with IDA and 50 healthy controls and to assess the relation between IDA and oxidative stress and response to iron therapy. METHODS: This was a prospective study in which peripheral blood samples were collected from all study subjects and the following laboratory investigations performed: serum iron profile, urinary microalbumin, urinary leucine aminopeptidase (LAP), fractional excretion of sodium (FeNa), serum total antioxidant capacity (TAC), serum malondialdehyde (MDA), serum and urinary trace elements (iron, copper, zinc, calcium and magnesium). All patients received oral iron therapy and were followed-up for 3 months. RESULTS: The levels of baseline urinary markers were higher among the patients with IDA than among the controls (p < 0.05). Patients had a lower pre-therapy TAC and lower serum zinc and magnesium levels than controls as well as higher MDA and serum copper levels (p < 0.05). MDA level was positively correlated to microalbumin and LAP level (p < 0.05). Urinary LAP concentration was positively correlated to urinary trace element concentrations (p < 0.05). A significant decrease in microalbumin, LAP, FeNa, and urinary trace elements was observed post-iron therapy while hemoglobin and ferritin levels were increased (p < 0.05). CONCLUSION: Among the study subjects, IDA had an adverse influence on renal functional and structural integrity which could be reversed with iron therapy. Oxidative stress played an important role in the pathogenesis of renal injury in IDA.


Asunto(s)
Anemia Ferropénica/fisiopatología , Tasa de Filtración Glomerular/fisiología , Compuestos de Hierro/uso terapéutico , Hierro/sangre , Riñón/fisiopatología , Estrés Oxidativo , Insuficiencia Renal/prevención & control , Administración Oral , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/metabolismo , Biomarcadores/sangre , Biomarcadores/orina , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Compuestos de Hierro/administración & dosificación , Masculino , Estudios Prospectivos , Especies Reactivas de Oxígeno/metabolismo , Insuficiencia Renal/etiología , Insuficiencia Renal/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
16.
Radiol Case Rep ; 19(9): 3975-3978, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39050641

RESUMEN

Supernumerary kidney is a highly uncommon congenital anomaly characterized by the presence of at least 1 or more extra kidneys in variable positions and morphology. Due to the scarcity in the medical literature, not much is known about this condition. The additional kidney typically has its own collecting system, vascular supply, and distinct encapsulated parenchyma. In this case, we present a 38-year-old male with a right supernumerary kidney who was initially investigated for a renal artery aneurysm. In the case of our patient, the discovery of a supernumerary kidney influenced the course of management and prevented unnecessary intervention and procedure. This emphasizes the importance of thorough imaging and diagnostic techniques in patients to accurately identify and characterize such anomalies.

17.
BMC Complement Med Ther ; 24(1): 65, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291462

RESUMEN

BACKGROUND: Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study. METHODS: Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC-MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented. RESULTS: Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site. CONCLUSION: The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination.


Asunto(s)
Diabetes Mellitus Tipo 2 , Própolis , Humanos , Acarbosa/farmacología , Acarbosa/química , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Quempferoles , Própolis/farmacología , Simulación del Acoplamiento Molecular , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Egipto , Calidad de Vida , alfa-Glucosidasas/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , alfa-Amilasas/metabolismo
18.
Sci Adv ; 10(16): eadm8815, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38630817

RESUMEN

Organisms surveil and respond to their environment using behaviors entrained by metabolic cues that reflect food availability. Mitochondria act as metabolic hubs and at the center of mitochondrial energy production is the protonmotive force (PMF), an electrochemical gradient generated by metabolite consumption. The PMF serves as a central integrator of mitochondrial status, but its role in governing metabolic signaling is poorly understood. We used optogenetics to dissipate the PMF in Caenorhabditis elegans tissues to test its role in food-related behaviors. Our data demonstrate that PMF reduction in the intestine is sufficient to initiate locomotor responses to acute food deprivation. This behavioral adaptation requires the cellular energy regulator AMP-activated protein kinase (AMPK) in neurons, not in the intestine, and relies on mitochondrial dynamics and axonal trafficking. Our results highlight a role for intestinal PMF as an internal metabolic cue, and we identify a bottom-up signaling axis through which changes in the PMF trigger AMPK activity in neurons to promote foraging behavior.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Mitocondrias/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Transducción de Señal
19.
Sci Rep ; 14(1): 13621, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871725

RESUMEN

In the current study, we evaluated the in vitro antibacterial efficacy of the roots' extracts of Jasminum officinale, Rosa damascene and Paeonia officinalis against MRSA (methicillin-resistant Staphylococcus aureus) by well diffusion technique. The root extract of P. officinalis exerted a potent anti-MRSA with MIC 0.4673 µg/ml, while both J. officinale and R. damascene exhibited very weak activity. Therefore, chemical profiling of the crude extract P. officinalis roots assisted by LC-HR-ESI-MS was performed and led to the dereplication of twenty metabolites of different classes, in which terpenes are the most abundant compounds. On a molecular level, network pharmacology was used to determine the targets of active metabolites to bacterial infections, particularly MRSA. Online databases PubChem, UniProt, STRING, and Swiss Target Prediction were used. In addition to using CYTOSCAPE software to display and analyze the findings, ShinyGO and FunRich tools were used to identify the gene enrichment analysis to the set of recognized genes. The results detected the identified metabolites were annotated by 254 targets. ALB, ACHE, TYMS, PRKCD, PLG, MMP9, MMP2, ERN1, EDNRA, BRD4 were found to be associated with MRSA infection. The top KEGG pathway was the vascular smooth muscle contraction pathway according to enrichment FDR. The present study suggested a possible implication of P. officinalis roots as a potent candidate having a powerful antibacterial activity against MRSA.


Asunto(s)
Jasminum , Metabolómica , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Paeonia , Extractos Vegetales , Rosa , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Rosa/química , Metabolómica/métodos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Paeonia/química , Jasminum/química , Farmacología en Red , Antibacterianos/farmacología , Raíces de Plantas/química
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 123063, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37390719

RESUMEN

The target of the current study is to create a novel hybrid nanocomposite (Cs@Pyc.SOF) by combining the anti-hepatitis C virus (HCV) drug sofosbuvir with the nano antioxidant pycnogenol (Pyc) and nano biomolecules like chitosan nanoparticles (Cs NPs). The characterization procedure works to verify the creation of nanocomposite (NCP) using several different techniques. UV-Vis spectroscopy is used to measure SOF loading efficiency. The various concentrations of the SOF drug were used to determine the binding constant rate Kb, which was found to be 7.35 ± 0.95 min-1 with an 83% loading efficiency. At pH 7.4, the release rate was 80.6% after two hours and 92% after 48 h, whereas at pH 6.8, it was 29% after two hours and 94% after 48 h. After 2 and 48 h, the release rate in water was 38% and 77%, respectively. . The SRB technique for fast screening is used for the cytotoxicity test, where the investigated composites show a safety status and high viability against the examined cell line. The cytotoxicity assay of the SOF hybrid materials has been identified with cell lines like mouse normal liver cells (BNL). So, Cs@Pyc.SOF was recommended as a substitute medication for the therapy of HCV, but the results need clinical studies.


Asunto(s)
Quitosano , Hepatitis C , Animales , Ratones , Sofosbuvir , Antivirales/uso terapéutico , Hepacivirus , Preparaciones Farmacéuticas , Quimioterapia Combinada , Hepatitis C/tratamiento farmacológico , Análisis Espectral , Ribavirina
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