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1.
Heliyon ; 10(9): e30762, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38765132

RESUMEN

In survival and stochastic lifespan modeling, numerous families of distributions are sometimes considered unnatural, unjustifiable theoretically, and occasionally superfluous. Here, a novel parsimonious survival model is developed using the Bilal distribution (BD) and the Kavya-Manoharan (KM) parsimonious transformation family. In addition to other analytical properties, the forms of probability density function (PDF) and behavior of the distributions' hazard rates are analyzed. The insights are theoretical as well as practical. Theoretically, we offer explicit equations for the single and product moments of order statistics from Kavya-Manoharan Bilal Distribution. Practically, maximum likelihood (ML) technique, which is based on simple random sampling (SRS) and ranked set sampling (RSS) sample schemes, is employed to estimate the parameters. Numerical simulations are used as the primary methodology to compare the various sampling techniques.

2.
Clin Exp Hepatol ; 10(1): 30-38, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38765909

RESUMEN

Aim of the study: Jaundice in newborns is a sign of skin and sclera pigmentation. Hyperbilirubinemia and these phenomena do, however, have a relationship. According to many clinical studies, elevated blood bilirubin and low vitamin E (VE) levels in newborns are associated. The aim of the study was to investigate the association of oxidative stress of neonatal hyperbilirubinemia in patients who underwent phototherapy with additional vitamin E supplementation (25 mg/kg/day over the course of three days) and patients without additional vitamin E. Material and methods: A set of 100 neonatal indirect hyperbilirubinemia patients was enrolled at neonatal intensive care units (NICUs) of the pediatric departments at Al Azhar University Hospitals during the period from February 2021 to October 2022 after obtaining signed written informed consent of all neonates' parents with an explanation of the aim of study. Results: Significant differences were found between the studied groups regarding serum bilirubin on the third day of admission (p = 0.039). Patients who were treated with vitamin E had lower serum bilirubin on the third day of admission (8.25 ±3.41) than the control group (11.66 ±3.22). Also, among the VE group, serum bilirubin was significantly decreased on the third day of admission (8.25 ±3.41) compared to zero days of admission (14.10 ±4.39) (p = 0.041). Conclusions: Vitamin E supplementation has an important role in treatment of indirect hyperbilirubinemia in neonates. Early administration of vitamin E in preterm neonates resulted in a significant decrease of serum bilirubin and increased total antioxidant capacity. Vitamin E supplementation in full term decreased the duration of phototherapy.

3.
Sci Rep ; 14(1): 6955, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521823

RESUMEN

A neutrosophic statistic is a random variable and it has a neutrosophic probability distribution. So, in this paper, we introduce the new neutrosophic Birnbaum-Saunders distribution. Some statistical properties are derived, using Mathematica 13.1.1 and R-Studio Software. Two different estimation methods for parameters estimation are introduced for new distribution: maximum likelihood estimation method and Bayesian estimation method. A Monte-Carlo simulation study is used to investigate the behavior of parameters estimates of new distribution, compare the performance of different estimates, and compare between our distribution and the classical version of Birnbaum-Saunders. Finally, study the validity of our new distribution in real life.

4.
J Pharm Pharmacol ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38538077

RESUMEN

OBJECTIVES: Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury. METHODS: Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR. KEY FINDINGS: SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL. CONCLUSIONS: SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway.

5.
Bioorg Chem ; 144: 107158, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38301427

RESUMEN

A new series of pyranopyrazole-based derivatives were designed and synthesized. The synthesized compounds were assessed for their cytotoxic efficacy against A549 human lung carcinoma and MCF-7 human breast carcinoma cell lines. Three compounds (1b, 4b, and 7b) exhibited 1.3- to 2.3-fold more antiproliferative activity than that of doxorubicin against the A549 cell line. In comparison to doxorubicin, compounds 1d and 3b were 4.1- and 1.04-fold, respectively more powerful against MCF-7 cancer cells. All the synthesized compounds were found to be more selective toward A549 cancer cells than the normal human fibroblast BJ cells. Of interest, compounds 1b and 7b exhibited promising cytotoxicity and SIs of 27.72 and 25.30, respectively, towards A549 cancer cells, higher than that of doxorubicin (SI 4.81). The most potent compounds 1b, 1d, 3b, 4b, and 7b were then subjected to in vitro Topo II inhibition assay. They showed IC50 values in the range of 2.07 to 8.86 µM. Of particular interest, compound 7b (IC50 = 2.07 µM), exhibited higher Topo II inhibitory activity than that of doxorubicin (IC50 = 2.56 µM). The significant Topo II inhibition of compound 7b was explained by molecular docking simulations into the Topo II active site. Compound 7b halted the cell cycle in the S phase in A549 cancer cells. It induced total apoptosis and necrosis of 20.73- and 4-fold, respectively, greater than the control. This evidence was supported by a 3.59-fold increase in the level of apoptotic caspase-9 and a remarkable elevation of the Bax/BCL-2 ratio. The physiochemical parameters of compound 7b were aligned with Lipinski's rule of five.


Asunto(s)
Antineoplásicos , Inhibidores de Topoisomerasa II , Humanos , Estructura Molecular , Relación Estructura-Actividad , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Antineoplásicos/química , Doxorrubicina/farmacología , Apoptosis , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales
7.
PLoS One ; 19(2): e0297822, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38319952

RESUMEN

Studies on students' perceptions and expectations during physical education (PE) online learning remain scarce. Centered on self-determination theory, the present cross-sectional study aims to identify gender differences and predictors affecting motivation, psychological needs satisfaction (PNS), and academic achievement during PE online learning. Data were collected from Saudi students' (N = 308, 161 females and 147 males) responses to the PE autonomy, relatedness, competence, and motivation questionnaires. Welch's t-test for unequal sample sizes, multiple linear regression, and binary logistic regression were used to compare means and to predict the relationships between the independent and dependent variables. The results showed higher autonomy and competence perceptions in female than in male students, but no differences were observed in relatedness. Female students presented higher intrinsic motivations, lower amotivation perceptions than males. However, no gender differences were recorded in extrinsic motivation. Students with less experience in online learning and weak grade point averages (GPAs) are more susceptible to having a high level of amotivation. Gender, GPA, and prior experience with online learning are the common predictors for all PNS and amotivation, while GPA and prior experience with online learning are the determinants of intrinsic motivation. GPA is affected by prior experience with online learning, autonomy, competence, intrinsic motivation, and amotivation. Therefore, teachers are encouraged to adapt their didactic-pedagogical behaviors during PE online learning according to students' motivation and autonomy perceptions. Structuring teaching activities with more individualized support for autonomy, competence, intrinsic motivation, and students' online skills/competencies ensures better learning efficiency and academic achievements.


Asunto(s)
Éxito Académico , Educación a Distancia , Humanos , Masculino , Femenino , Motivación , Educación y Entrenamiento Físico , Factores Sexuales , Estudios Transversales , Arabia Saudita , Estudiantes/psicología , Satisfacción Personal , Autonomía Personal
8.
Sci Rep ; 14(1): 2924, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316847

RESUMEN

This study proposes a novel approach that combines machine learning models to predict soil compaction using the soil cone index values. The methodology incorporates support vector regression (SVR) to gather input data on key soil parameters, and the output data from SVR are used as inputs for additional machine learning techniques such as Gradient Boosting, Decision Tree, Artificial Neural Networks, and Adaptive Neuro-Fuzzy Inference System. Evaluation of Artificial Intelligent techniques shows that the XGBoost model outperforms others, exhibiting high accuracy and reliability with low mean square error and high correlation coefficient. The effectiveness of the XGBoost model has implications for soil management, agricultural productivity, and land suitability evaluations, particularly for renewable energy projects. By integrating advanced AI techniques, stakeholders can make informed decisions about land use planning, sustainable farming practices, and the feasibility of renewable energy installations. Overall, this research contributes to soil science by demonstrating the potential of AI techniques, specifically the XGBoost model, in accurately predicting soil compaction and supporting optimal soil management practices.

9.
Chem Biodivers ; 21(3): e202301617, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38193652

RESUMEN

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC50 =3.3, 4.2 and 6.8 µg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.


Asunto(s)
Actinobacteria , Adenocarcinoma , Antozoos , Antineoplásicos , Neoplasias del Colon , Streptomyces , Animales , Humanos , Actinobacteria/química , Océano Índico , Actinomyces , Agar/metabolismo , Células CACO-2 , Simulación del Acoplamiento Molecular , Antineoplásicos/farmacología , Antineoplásicos/metabolismo
10.
Microbiology (Reading) ; 169(11)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37990974

RESUMEN

Antibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure. Furthermore, there is a growing array of evidence that persistence is a 'stepping-stone' for the development of genetic antimicrobial resistance. Urinary tract infections (UTIs) are a major contributor to antibiotic consumption worldwide, and are known to be both persistent (i.e. affecting the host for a prolonged period) and recurring. Currently, in clinical settings, routine laboratory screening of pathogenic isolates does not determine the presence or the frequency of persister cells. Furthermore, the majority of research undertaken on antibiotic persistence has been done on lab-adapted bacterial strains. In the study presented here, we characterized antibiotic persisters in a panel of clinical uropathogenic Escherichia coli isolates collected from hospitals in the UK and Australia. We found that a urine-pH mimicking environment not only induces higher levels of antibiotic persistence to meropenem and colistin than standard laboratory growth conditions, but also results in rapid development of transient colistin resistance, regardless of the genetic resistance profile of the isolate. Furthermore, we provide evidence for the presence of multiple virulence factors involved in stress resistance and biofilm formation in the genomes of these isolates, whose activities have been previously shown to contribute to the formation of persister cells.


Asunto(s)
Infecciones por Escherichia coli , Infecciones Urinarias , Escherichia coli Uropatógena , Humanos , Colistina/farmacología , Meropenem/farmacología , Meropenem/uso terapéutico , Escherichia coli Uropatógena/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Bacterias/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología
11.
Comput Math Methods Med ; 2023: 8952946, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37953930

RESUMEN

This paper is interested in the Bayesian and non-Bayesian estimation of the stress-strength model and the mean remaining strength when there is fuzziness for stress and strength random variables having Lindley's distribution with different parameters. A fuzzy is defined as a function of the difference between stress and strength variables. In the context of Bayesian estimation, two approximate algorithms are used importance sampling algorithm and the Monte Carlo Markov chain algorithm. For non-Bayesian estimation, maximum likelihood estimation and maximum product of spacing method are used. The Monte Carlo simulation study is performed to compare between different estimators for our proposed models using statistical criteria. Finally, to show the ability of our proposed models in real life, real medical application is introduced.


Asunto(s)
Algoritmos , Neoplasias , Humanos , Teorema de Bayes , Simulación por Computador , Cadenas de Markov
12.
Arch Pharm (Weinheim) ; 356(12): e2300250, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37792247

RESUMEN

This study comprises the design and synthesis of novel nicotinic acid-based cytotoxic agents with selective inhibitory efficacy against the vascular endothelial growth factor receptor-2 (VEGFR-2). Screening of novel compounds for cytotoxicity was assessed against 60 human cancer cell lines. The two most active compounds, 5b and 5c, and the reference drugs sorafenib and doxorubicin were investigated against HCT-15, PC-3, and CF-295 cancer cell lines. Compound 5c exhibited the highest cytotoxic potential compared to doxorubicin against the HCT-15 and PC-3 tumor cell lines. Moreover, it exhibited higher cytotoxic potential and selectivity toward the HCT-15 cell panel compared with sorafenib. Compound 5c demonstrated promising VEGFR-2 inhibition (concentration needed to inhibit cell viability by 50%, IC50 = 0.068 µM) and superior VEGFR-2 selectivity over the epidermal growth factor receptor and platelet-derived growth factor receptor-ß enzymes. It also reduced the total and phosphorylated VEGFR-2 and induced apoptosis, as evidenced by a 4.3-fold rise in caspase-3 levels. The antioxidant potential of the new compounds was determined via measuring the superoxide dismutase (SOD) levels, among which compound 5c exhibited an SOD level almost comparable to ascorbic acid. These results suggested that compound 5c exhibited dual cytotoxic and antioxidant activities. Docking of 5c into the VEGFR-2 pocket showed a similar binding mode to sorafenib. Moreover, the ADME (absorption, distribution, metabolism, and excretion) profile of 5c outlined drug-likeness. Finally, The density functional theory calculations displayed an increased binding affinity of 5c to the target enzyme.


Asunto(s)
Antineoplásicos , Neoplasias , Niacina , Humanos , Sorafenib/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Estructura Molecular , Relación Estructura-Actividad , Niacina/farmacología , Antioxidantes/farmacología , Factor A de Crecimiento Endotelial Vascular/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos/química , Doxorrubicina/farmacología , Superóxido Dismutasa/metabolismo , Simulación del Acoplamiento Molecular , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Diseño de Fármacos
13.
Sci Rep ; 13(1): 16254, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37758788

RESUMEN

There is a lack of epidemiological data on fascioliasis in Egypt regarding disease characteristics and treatment outcomes across different governorates. We aimed to identify the demographic, epidemiologic, clinical, laboratory, and radiological characteristics and treatment outcomes of patients diagnosed with fascioliasis in Egypt. Data on human fascioliasis were collected retrospectively from patients' medical records in the period between January 2018 and January 2020. The study included 261 patients. More than 40% of enrolled patients were in the age group of 21-40 years old. Geographically, 247 (94.6%) were from Assiut Governorate with 69.3% were from rural areas. The most frequent symptoms were right upper quadrant pain (96.9%), and fever (80.1%). Eosinophilia was found in 250 cases (95.8%). Hepatic focal lesions were detected in 131 (50.2%); out of them 64/131 (48.9%) had a single lesion. All patients received a single dose of 10 mg/kg of triclabendazole, 79.7% responded well to a single dose, while in 20.3% a second ± a third dose of treatment was requested. After therapy, there was a reduction in leucocytes, Fasciola antibodies titer, eosinophilic count, bilirubin, and liver enzymes with an increase in hemoglobin level. According to our findings, a high index of suspicion should be raised in cases with fever, right upper abdominal pain, and peripheral eosinophilia, and further imaging workup is mandated to detect hepatic focal lesions. Prompt treatment by triclabendazole can serve as a standard-of-care regimen even for suspected cases.


Asunto(s)
Eosinofilia , Fasciola hepatica , Fascioliasis , Animales , Humanos , Adulto Joven , Adulto , Fascioliasis/diagnóstico por imagen , Fascioliasis/tratamiento farmacológico , Triclabendazol/uso terapéutico , Estudios Retrospectivos , Egipto/epidemiología , Dolor Abdominal
14.
Drug Dev Res ; 84(8): 1595-1623, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37751330

RESUMEN

Selective cyclooxygenase (COX)-2 inhibitors have several advantages over nonselective COX inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]), including the absence of adverse effects (renal and hepatic disorders) associated with the long-term use of standard NSAIDs, as well as an improved gastrointestinal profile. The pyridazine nucleus is regarded as a promising scaffold for the development of powerful COX-2 inhibitors, particularly when selectively functionalized. This article summarizes some methods for the synthesis of pyridazine derivatives. Furthermore, it covers all of the pyridazine derivatives that have appeared as selective COX-2 inhibitors, making it useful as a reference for the rational design of novel selective COX-2 inhibitors.


Asunto(s)
Antiinflamatorios no Esteroideos , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Ciclooxigenasa 2 , Antiinflamatorios no Esteroideos/efectos adversos , Tracto Gastrointestinal , Riñón
15.
Toxicon ; 233: 107252, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37597789

RESUMEN

Aflatoxin B1 (AFB1) is common carcinogen causing acute and chronic hepatocyte injuries. This study aimed to determine the bioactive components of Teucrium polium methanolic extract (TPE) and to evaluate their protective role against AFB1-induced oxidative damage, cytotoxicity, and genotoxicity in rats. Six groups of male albino rats were treated orally for 4 weeks including the control group, the ِAFB1-treated group (80 µg/kg b.w.), the groups treated with low (LD) or high (HD) dose TPE (50 or 100 mg/kg b.w.), and the groups treated with AFB1 plus TEP (LD) or TPE (HD). Blood and serum samples were collected for different assays. The GC-MS identified 34 compounds, the major compounds were pinene, germacrene D, α-cadinol, α-thujene, epi-bicyclosesquiphellandrene, and limonene. Animals that received AFB1 showed significant changes in all indicators of oxidative stress, biochemistry, cytokines, MNPCEs, comet tail formation in bone marrow, mRNA expression of inflammatory-related genes, Nrf2, and iNOS beside histological changes in the liver. TPE at the two doses tested showed insignificant changes in all tested parameters. The extract could normalize most of these parameters and the hepatic structure in AFB1-treated animals in a dose-dependent fashion. therefore, we concluded that TPE supplementation is effective for protection against AFB1 in endemic areas.


Asunto(s)
Aflatoxina B1 , Teucrium , Masculino , Animales , Ratas , Aflatoxina B1/toxicidad , Estrés Oxidativo , Bioensayo , Carcinógenos
16.
Sci Rep ; 13(1): 6179, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-37061568

RESUMEN

Recurrence and progression rates vary widely among different histological subtypes of bladder cancer (BC). Normal-appearing mucosa in non-muscle invasive bladder cancer and muscle-invasive bladder cancer in cystoscopy and histopathology is a factor in staging and treatment. Telocytes (TCs) are spindle-shaped cells that connect with other cell types allowing communication though cytoskeletal signaling. They are involved in tissue regeneration and pathogenesis of diseases and cancer. In this study, 12 normal-appearing tissues from urinary bladder with BC, both invasive and non-invasive were evaluated in patients who had either trans-urethral resection of bladder tumor or cystectomy. In each case, cystoscopy, intraoperative inspection, and histopathology all confirmed the absence of cancerous elements. Five patients with neurogenic bladder were used as a control group. Immunohistochemistry revealed that c-Kit + cells were intensively distributed in bladder layers from BC samples, while they were seldom detected in the control group. Ultrastructural examination of reprocessed tissue showed an intense distribution of TCs and telopodes in the submucosa and between smooth muscle cells in BC. Telopodes were numerous, arborizing, and intercommunicating. Whereas TCs and telopodes were scarce in the neurogenic bladder. Also, cancerous tissue had the highest expression level of ezrin protein, and this level gradually decreased as we moved away from the tumor. Our finding of TCs number in normal-appearing tissues in conjunction with ezrin expression may compete invasiveness and possibly a trail to reduce recurrence rates.


Asunto(s)
Carcinoma de Células Transicionales , Telocitos , Neoplasias de la Vejiga Urinaria , Vejiga Urinaria Neurogénica , Humanos , Vejiga Urinaria/patología , Vejiga Urinaria Neurogénica/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Telocitos/metabolismo , Invasividad Neoplásica/patología
17.
Heliyon ; 9(4): e15288, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37101621

RESUMEN

Background: Hepatocellular carcinoma (HCC) is an aggressive human cancer with a poor prognosis. Long non-coding RNAs (lncRNA) have multiple functions: epigenomic regulation, gene transcription, protein-coding gene translation, and genome defense. The involvement of lncRNAs in therapy offers a vast step in cancer treatment. Objective: In the current study, a novel therapeutic regimen using polymer nanoparticle-mediated delivery of lncRNA was designed to control the progression of hepatocarcinogenesis. Methods: One hundred mice were divided into 5 groups. The first group served as a normal-control group and was injected with saline, whereas the pathological-control group (the second group) was injected with N-Nitrosodiethylamine (DEN) weekly for 16 weeks. Group 3, Group 4, and Group 5 were injected intrahepatically with polymer nanoparticles (NPs) alone, lncRNA MEG3 alone, and conjugated NPs, respectively, once/week for four weeks starting on the 12th week after DEN injection. After 16 weeks, animals were euthanized, and liver specimens and blood samples were collected for pathological, molecular, and biochemical assessment. Results: Compared to the pathological-control group, nanoconjugates lncRNA MEG3 demonstrated a significant improvement in histopathology and tumour-associated biomarkers. Furthermore, the expression of the SENP1 and PCNA was downregulated. Conclusion: MEG3 conjugated nanoparticles can be considered a novel therapeutic regimen for HCC.

18.
Egypt J Immunol ; 30(2): 83-98, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37031410

RESUMEN

Diabetic retinopathy (DR) is a typical microvascular complication of diabetes mellitus (DM) and it remains one of the leading causes of vision loss worldwide. Studies postulated that a distinct metabolic signature of DR exists and can be resolved from that of diabetes alone. Serum Semaphorin3A (Sema3A) levels have also been found to be correlated with the phenotypes of diabetic retinopathy. We aimed to analyze and identify serum metabolites and serum Sema3A levels that could be useful biomarkers of DR progression. This cross-sectional study included 45 type 2 diabetes (T2D) patients. Diabetic patients were divided into three groups based on the status of their complications: non-DR (NDR, n=15), non-proliferative DR (NPDR, n=15), and proliferative DR (PDR, n=15) groups. Serum metabolomic profiles of these patients were determined by using high-performance liquid chromatography-mass spectrometry (HPLC-MS), and serum Sema3A levels measured by ELISA. Metabolomics analysis revealed a set of metabolites that were altered in the serum of PDR patients as compared with NPDR and NDR groups. Among these metabolites total asymmetric dimethylarginine (ADMA) and Kynurenine were potential predictors of PDR patients. Significantly higher serum levels of Sema3A in PDR patients as compared with NPDR and NDR groups (p < 0.001), their serum levels were positively correlated with the central macular thickness (r= 0.952, p < 0.001) and negatively correlated with the superficial macular density (r=-0.952, p < 0.001). In conclusion, the metabolite signatures identified in this study and serum Sema3A levels could be proposed as biomarkers for DR development and progression in T2D patients. However, Sema3A was superior to metabolomics in the prediction of the severity of DR.


Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Retinopatía Diabética/complicaciones , Retinopatía Diabética/metabolismo , Semaforina-3A , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Biomarcadores
19.
Indian J Surg Oncol ; 14(1): 243-248, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36891412

RESUMEN

This study aims to assess survival rates in early breast cancer patients treated by conservative breast therapy (CBT), including radiotherapy, compared with those treated by modified radical mastectomy (MRM) alone. The South Egypt Cancer Institute and the Assiut University Oncology Department patients' records, from January 2010 to December 2017, were searched for T1-2N0-1M0 breast cancer patients treated by CBT or MRM. Patients who did not receive chemotherapy were excluded to reduce the treatment variation. The 5-year locoregional disease-free survival (LRDFS) was 97.3% for the CBT patients was and 98.0% for the MRM patients (P = .675). The 5-year distant disease-free survival (DDFS) was 93.6% for CBS and 85.7% for MRM (P = 0.033). The DFS was 91.9% for the BCT patients and 85.3% for the MRM patients (P = 0.045). The 5-year OS was 98.2% for the CBT patients and 94.3% for the MRM patients, (P = 0.02). By Cox regression analysis, the CBT resulted in significantly better OS, (P = 0.018) and the HR = 0.350, 95% CI 0.146-0.837. The adjusted OS, estimated by the propensity score-based weights, remained superior in CBT than in MRM patients (P < 0.001). CBT resulted in better DDFS, DFS, and OS than MRM. Future randomized trials are needed to confirm these findings and determine the cause.

20.
Chem Biol Interact ; 373: 110399, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36774993

RESUMEN

BACKGROUND: Early diagnosis and treatment of endometrial hyperplasia (EH) remains mandatory for endometrial cancer (EC) prevention. OBJECTIVE: To study the possible protective effect of eicosapentaenoic acid (EPA) in EH - induced by estradiol valerate (EV) in rats. METHODS/MATERIALS: Adult female Wistar rats were given EV with or without EPA for 10 days. The uterine changes were evaluated by both physical (weight index) and histopathological methods. The markers of oxidative stress (Uterine malondialdehyde (MDA) and serum total antioxidant capacity (TAC) as well as serum estradiol and progesterone levels, and apoptosis (uterine caspase-3) were determined. Immunohistochemical estimations of nuclear factor kappa B (NF-κB) and vascular endothelial growth factor (VEGF) in addition to hypoxia-inducible factor 1 alpha (HIF-1α) immunoblotting were measured in uterine tissue. KEY FINDINGS: EV showed significant increase in uterine weight index that is accompanied with histopatholigical evidences of EH. Such changes were associated with significant alterations in oxidative stress markers, modulation of estradiol and progesterone serum levels, an increase in HIF-1α, NF-κB and VEGF immuno-expressions and a significant decrease in caspase-3. EPA, in either dose, showed significant amelioration in uterine weight index as well as in histopathological changes. Such effect was accompanied with significant improvement in the measured hormonal levels, oxidative stress, apoptosis, and inflammatory parameters. CONCLUSIONS: EPA in the used doses provided biochemical and histopathological improvement in EV-induced EH via modulation of NF-κB/HIF-1α/VEGF signaling pathway.


Asunto(s)
Hiperplasia Endometrial , FN-kappa B , Humanos , Ratas , Femenino , Animales , FN-kappa B/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Caspasa 3/metabolismo , Ácido Eicosapentaenoico , Progesterona , Ratas Wistar , Transducción de Señal , Estradiol , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
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