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1.
Pathol Res Pract ; 255: 155215, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38412656

RESUMO

Extreme response of the immune system develops cytokine storm which might be crucial in the pathology of COVID-19. The research aims to evaluate the serum level of IL-6, TNF-α, and IP-10 in severe, mild, and pre-vaccinated one-dose COVID-19 patients and investigate their clinical value and effect in the disease development among different groups of patients. A total of 72 samples were collected 18 as healthy control and 54 from confirmed COVID-19 patients including 18 mild, 18 severe, and 18 pre-vaccinated (one dose). It was confirmed that the severe group of COVID-19 patients had the highest circulating IL-6, TNF- α, and IP-10. IL-6 level in mild and pre-vaccinated (one dose) was significantly lower than in severe. In conclusion, IL-6, TNF-α, and IP-10 are associated with the pathogenicity of COVID-19, furthermore, vaccination could help to control severity of the disease.


Assuntos
COVID-19 , Citocinas , Humanos , Fator de Necrose Tumoral alfa , Quimiocina CXCL10 , Interleucina-6
2.
Saudi J Biol Sci ; 30(11): 103821, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38020556

RESUMO

SARS-CoV-2, which initiated the worldwide COVID-19 epidemic in 2019, has rapidly emerged and spread, resulting in significant public health challenges worldwide. The COVID-19 severity signs and their association with specific genes have been investigated to better comprehend this phenomenon. In this study, several genes were investigated to see whether they correspond with COVID-19 sickness severity. This research aims to determine and evaluate certain gene expression levels associated with the immune system, as these genes were reported to play important roles in immune control during the COVID-19 outbreak. We analyzed two immunity-linked genes: CD27 and SAMHD1 in COVID-19 patients' samples using RT-PCR, compared them to the samples from recovered, immunized, and healthy individuals. These data were examined to determine the potential relationships between clinical patterns, illness severity, and progression, and SARS-CoV-2 infection immunology. We observed that CD27 gene expression was higher in COVID-19 vaccinated and control groups, but lower in active and recovered COVID-19 patients. On the other hand, SAMHD1 gene expression was elevated in infected and recovered COVID-19 groups. According to our study, the proteins CD27 and SAMHD1 are essential for controlling the immunological response to COVID-19. Changes in their expression levels could increase the susceptibility of patients to severe complications associated with the disease. Therefore, the gene expression level of these proteins could serve as viable prognostic markers for COVID-19.

3.
Oncol Lett ; 26(5): 477, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37809047

RESUMO

Breast cancer (BC) is one of the most widespread types of cancer affecting females, and therefore, early diagnosis is critical. BC is a complex heterogeneous disease affected by several key pathways. Among these, WNT proteins and their frizzled receptors (FZD) have been demonstrated to be crucial in regulating a number of cellular and molecular events in BC tumorigenesis. The role of the WNT receptor, FZD8, in BC has received minimal attention; for that reason, the present study examined the prognostic value of its protein expression pattern in a BC cohort. FZD8 cytoplasmic expression pattern analysis revealed that ~38% of the primary samples presented with a high expression profile, whereas ~63% of the samples had a low expression profile. Overall, ~46% of the malignant tissues in the lymph node-positive samples exhibited an increased FZD8 cytoplasmic expression, whereas 54% exhibited low expression levels. An increased expression of FZD8 was associated with several clinicopathological characteristics of the patients, including a low survival rate, tumor vascular invasion, tumor size and grade, and molecular subtypes. Affymetrix microarray triple-negative BC datasets were analyzed and compared with healthy breast tissues in order to predict the potential interfering microRNAs (miRNAs) in the WNT/FZD8 signaling pathway. A total of 29 miRNAs with the potential to interact with the WNT/FZD8 signaling pathway were identified, eight of which exhibited a significant prediction score. The target genes for each predicted miRNA were identified. On the whole, the findings of the present study suggest that FZD8 is a potential prognostic marker for BC, shedding some light onto the silencing mechanisms involved in the complex BC signaling.

4.
Front Genet ; 14: 1221815, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37799140

RESUMO

The claudin multigene family is associated with various aberrant physiological and cellular signaling pathways. However, the association of claudins with survival prognosis, signaling pathways, and diagnostic efficacy in colon cancer remains poorly understood. Methods: Through the effective utilization of various bioinformatics methods, including differential gene expression analysis, gene set enrichment analysis protein-protein interaction (PPI) network analysis, survival analysis, single sample gene set enrichment analysis (ssGSEA), mutational variance analysis, and identifying receiver operating characteristic curve of claudins in The Cancer Genome Atlas colon adenocarcinoma (COAD). Results: We found that: CLDN2, CLDN1, CLDN14, CLDN16, CLDN18, CLDN9, CLDN12, and CLDN6 are elevated in COAD. In contrast, the CLDN8, CLDN23, CLDN5, CLDN11, CLDN7, and CLDN15 are downregulated in COAD. By analyzing the public datasets GSE15781 and GSE50760 from NCBI-GEO (https://www.ncbi.nlm.nih.gov/geo/), we have confirmed that CLDN1, CLDN2, and CLDN14 are significantly upregulated and CLDN8 and CLDN23 are significantly downregulated in normal colon, colon adenocarcinoma tumor, and liver metastasis of colon adenocarcinoma tissues from human samples. Various claudins are mutated and found to be associated with diagnostic efficacy in COAD. Conclusion: The claudin gene family is associated with prognosis, immune regulation, signaling pathway regulations, and diagnosis of COAD. These findings may provide new molecular insight into claudins in the treatment of colon cancer.

5.
Front Mol Biosci ; 10: 1172403, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37214337

RESUMO

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity. Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-ß1 (TGFß1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done. Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFß1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin's therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin's higher binding affinity than taurine. Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.

6.
Saudi J Biol Sci ; 30(4): 103596, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36879671

RESUMO

Background: Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking. Method: The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study. Results: The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2) were identified along with the eight gene modules that were significantly related to the protein-protein interaction (PPI). The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort. Conclusions: The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis.

7.
J Clin Med ; 12(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36675642

RESUMO

BACKGROUND: By the end of 2019, the COVID-19 pandemic spread all around the world with a wide spectrum of clinical presentations ranging from mild to moderate to severe or critical cases. T cell subtype dysregulation is mostly involved in the immunopathogenic mechanism. The present study aimed to highlight the role of monitoring T cell subtypes and their activation (expression of CD38) in COVID-19 patients compared to healthy subjects and their role in predicting severity and patients' outcomes. MATERIALS: The study involved 70 adult COVID-19 confirmed cases stratified into three groups: a mild/asymptomatic group, a clinically moderate group, and a clinically severe/critical group. Flow cytometry analysis was used for the assessment of CD3+ cells for total T cell count, CD4+ cells for helper T cells (Th), CD8+ cells for cytotoxic T cells (Tc), CD4+CD25+ cells for regulatory T cells (T reg), and CD38 expression in CD4+ T cells and CD8+ T cells for T cell activation. RESULTS: A statistically significant difference was found between COVID-19 cases and healthy controls as regards low counts of all the targeted T cell subtypes, with the lowest counts detected among patients of the severe/critical group. Furthermore, CD38 overexpression was observed in both CD4+ and CD8+ T cells. CONCLUSION: Decreased T cell count, specifically CD8+ T cell (Tc), with T cell overactivation which was indicated by CD38 overexpression on CD4+ and CD8+ T cells had a substantial prognostic role in predicting severity and mortality among COVID-19 patients. These findings can provide a preliminary tool for clinicians to identify high-risk patients requiring vigilant monitoring, customized supportive therapy, or ICU admission. Studies on larger patient groups are needed.

8.
Molecules ; 27(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889390

RESUMO

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod_09) with a relatively stable structure (with a minimum free energy of -32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Aptâmeros de Nucleotídeos/química , Humanos , Neoplasias/diagnóstico , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento , Técnica de Seleção de Aptâmeros/métodos
9.
Dokl Biochem Biophys ; 504(1): 128-136, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35759141

RESUMO

The study aimed to determine the interaction of using LS and CA in combination on liver, kidney, and heart functions in rats and to evaluate the role of antioxidant effects of LS against CA-induced hepato-renal toxicity. This study was conducted on 36 male rats divided into four groups (n = 9). The groups were; the control, LS-treated (10 g/100 g of food), CA-treated (5 g/100 g of food), and combined LS plus CA-treated groups for 6 weeks. Kidney, liver and heart functions as well as oxidant/antioxidant profile were biochemically assessed in the serum using ELISA. The impact of LS and CA on kidney and liver was histopathologically assessed. Rats fed on diet supplemented with LS for 6 weeks showed no significant change in serum levels of the biochemical markers of liver, kidney and heart functions, while supplementation with CA significant increased (p < 0.001) the serum levels of these markers compared to the control group. Combined administration of LS and CA significantly reduced the serum levels of these parameters compared to CA-treated group. Oxidative markers significantly increased while the antioxidants one decreased in CA-treated group compared to the control. Combined LS and CA significantly improve the oxidant/antioxidant profile as well as histopathological impact compared to CA-treated group.


Assuntos
Antioxidantes , Lepidium sativum , Animais , Antioxidantes/farmacologia , Biomarcadores , Ácido Cítrico , Rim , Fígado , Masculino , Oxidantes/farmacologia , Ratos
10.
Front Mol Biosci ; 9: 783735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237656

RESUMO

Wnt signalling receptors, Frizzleds (FZDs), play a pivotal role in many cellular events during embryonic development and cancer. Female breast cancer (BC) is currently the worldwide leading incident cancer type that cause 1 in 6 cancer-related death. FZD receptors expression in cancer was shown to be associated with tumour development and patient outcomes including recurrence and survival. FZD6 received little attention for its role in BC and hence we analysed its expression pattern in a Saudi BC cohort to assess its prognostic potential and unravel the impacted signalling pathway. Paraffin blocks from approximately 405 randomly selected BC patients aged between 25 and 70 years old were processed for tissue microarray using an automated tissue arrayer and then subjected to FZD6 immunohistochemistry staining using the Ventana platform. Besides, Ingenuity Pathway Analysis (IPA) knowledgebase was used to decipher the upstream and downstream regulators of FZD6 in BC. TargetScan and miRabel target-prediction databases were used to identify the potential microRNA to regulate FZD6 expression in BC. Results showed that 60% of the BC samples had a low expression pattern while 40% showed a higher expression level. FZD6 expression analysis showed a significant correlation with tumour invasion (p < 0.05), and borderline significance with tumour grade (p = 0.07). FZD6 expression showed a highly significant association with the BC patients' survival outcomes. This was mainly due to the overall patients' cohort where tumours with FZD6 elevated expression showed higher recurrence rates (DFS, p < 0.0001, log-rank) and shorter survival times (DSS, p < 0.02, log-rank). Interestingly, the FZD6 prognostic value was more potent in younger BC patients as compared to those with late onset of the disease. TargetScan microRNA target-prediction analysis and validated by miRabel showed that FZD6 is a potential target for a considerable number of microRNAs expressed in BC. The current study demonstrates a potential prognostic role of FZD6 expression in young BC female patients and provides a better understanding of the involved molecular silencing machinery of the Wnt/FZD6 signalling. Our results should provide a better understanding of FZD6 role in BC by adding more knowledge that should help in BC prevention and theranostics.

11.
Int J Mol Sci ; 22(23)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34884678

RESUMO

Ovarian cancer (OC) is the deadliest among all gynecological cancers. Epidemiological studies showed that obesity might influence many cancers including OC. One of the key factors that may link obesity and OC is leptin (LEP), known as an adipokine with pleiotropic effects on body homeostasis. This study aims to investigate the expression pattern of LEP, assess the methylation profiles of LEP and their associations with clinicopathological features including survival outcomes of OC patients. The protein expression of LEP was evaluated in 208 samples using both tissue microarray and immunohistochemistry techniques. The methylation profiles of LEP were measured in 63 formalin-fixed, paraffin-embedded tumor tissues by quantitative polymerase chain reaction using a MethyLight assay. Our results showed a significant association of LEP protein overexpression with several clinicopathological variables, mainly tumor subtype, LVI, age of menarche, tumor size and stage (p < 0.04). Kaplan-Meier analysis (using low expression versus high expression as a discriminator) indicated that LEP protein overexpression is a powerful positive prognosticator of both OC recurrence (DFS) and disease-specific survival (DSS) in our OC cohort (log-rank p = 0.01 and p = 0.002, respectively). This implies that patients with high LEP expression profiles live longer with less recurrence rates. Methylation analysis results demonstrated a clear association between no/low LEP protein expression pattern (38%) and LEP promoter CpG island hypermethylation (43%). Results of this study suggest that LEP is a powerful prognosticator of OC recurrence and DSS. LEP expression in OC seems to be regulated by its promoter hypermethylation through gene partial/total silencing. Further multi-institutional studies using larger cohorts are required to demystify the intricate molecular functions of this leptin-driven effects in OC pathophysiology and to accurately assess its theranostic potential and validate its prognostic/predictive power in OC onset, progression towards more effective and personalized management of OC patients.


Assuntos
Leptina/metabolismo , Neoplasias Ovarianas/metabolismo , Metilação de DNA , Feminino , Humanos , Leptina/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Medicina de Precisão , Prognóstico , Regiões Promotoras Genéticas , Arábia Saudita/epidemiologia
12.
Mol Clin Oncol ; 15(3): 181, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34277000

RESUMO

Among all gynecological cancers, ovarian cancer (OC) is one of the deadliest types of cancer worldwide. Epigenetic silencing of some genes has been reported to be associated with OC. In this context, Klotho (KL) gene methylation is a promising biomarker for OC. The present study aimed to investigate the methylation profiles of KL and assess its prognostic value. A total of 63 formalin-fixed paraffin-embedded tissue samples from patients with primary OC were collected and analyzed in the present study. The methylation profiles of KL were assessed by performing DNA bisulfate treatment followed by DNA promoter methylation analysis using the MethyLight assay. The results revealed KL promoter hypermethylation in 62% of the OC cohort. Additionally, significant associations were observed between KL methylation profiles and tumor subtype (P<0.0001) and tumor site (P=0.039). Furthermore, Kaplan-Meier analysis revealed that a worse disease-specific survival was significantly associated with hypermethylated KL (P=0.03, log-rank; hazard ration, 0.58; 95% confidence interval (CI), 0.26-0.90). Cox regression multivariate analysis indicated that KL promoter methylation was an independent OC prognostic indicator (P=0.029). The current study suggested that KL may be a novel biomarker to predict prognosis in patients with OC, since patients with higher KL promoter methylation were more likely to have a poor prognosis and would therefore require frequent follow-up and integrative personalized therapeutic approaches.

13.
Saudi J Biol Sci ; 28(6): 3249-3253, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34121862

RESUMO

Apolipoprotein B100 (ApoB100) is a glycoprotein and a member of the adipokine family. It plays a central role in lipoprotein metabolism. Many research studies have revealed a strong relation between ApoB100 and metabolic syndrome (MetS) and insulin resistance. In our research, we examined the relationship between ApoB100 rs693 gene polymorphism, body mass index (BMI) and the probability of MetS in young female students studying at King Abdulaziz University (KAU) in Saudi Arabia. The study group comprised 141 females whose ages ranged from 18 to 25 years. Anthropometric measurements and biochemical parameters were measured alongside a genetic analysis of ApoB100 rs693. The BMI, glucose concentration and total cholesterol level were found to be significantly associated with the ApoB100 rs693 gene. The differences noted between control and MetS groups regarding glucose concentrations were statistically significant (P = 0.001). A growing number of young females are being diagnosed with MetS in KAU because of unhealthy eating habits, in combination with the absence of physical exercise, causing increased body weight and the potential progression of chronic diseases. Our study showed that the allele associated with hypertensive individuals at ApoB100 rs693 and MetS may have a direct genetic influence. Further research on expanded sample sizes, however, is required in order to draw rigid conclusions.

14.
Front Pharmacol ; 12: 663417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040528

RESUMO

Background: Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory, and antidepressant activities of pumpkin were previously reported. Objectives: This study aimed to evaluate the efficacy of the combined topical and oral application of pumpkin fruit (Cucurbita pepo L.) extract (PE) in relieving CD associated with chronic stress-induced depression and compare it to the topical pumpkin extract alone and to the standard treatment. Materials and Methods: Forty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression and then exposed to (1-fluoro-2, 4-dinitrofluorobenzene, DNFB) for 2 weeks for induction of CD. Those rats were assigned into 4 groups (n = 10 each); untreated, betamethasone-treated, PE-treated and pumpkin extract cream, and oral-treated groups. Treatments were continued for 2 weeks. All groups were compared to the negative control group (n = 10). Depression was behaviorally and biochemically confirmed. Serum and mRNA levels of pro-inflammatory cytokines, such as TNF-α, IL-6, COX-2, and iNOS, were assessed. Oxidant/antioxidant profile was assessed in the serum and skin. Histopathological and immunohistochemical assessments of affected skin samples were performed. Results: Pumpkin extract, used in this study, included a large amount of oleic acid (about 56%). The combined topical and oral administration of PE significantly reduced inflammatory and oxidative changes induced by CD and depression compared to the CD standard treatment and to the topical PE alone. PE significantly alleviated CD signs and the histopathological score (p < 0.001) mostly through the downregulation of pro-inflammatory cytokines and the upregulation of antioxidants. Conclusion: Pumpkin extract, applied topically and orally, could be an alternative and/or complementary approach for treating contact dermatitis associated with depression. Further studies on volunteer patients of contact dermatitis are recommended.

15.
Diabetes Metab Syndr ; 13(4): 2399-2402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405650

RESUMO

OBJECTIVE: To examine the association between increased body mass index (BMI) values and the risk of metabolic syndrome (MetS) in young female science students. METHODOLOGY: The study population was 174 female students aged 18-25 years attending King Abdulaziz University (KAU) in the Kingdom of Saudi Arabia (KSA). Anthropometric measurements obtained included weight, height, waist, and hips circumferences. Blood pressure was also measured, and blood samples were collected for measurements of total cholesterol, triglyceride (TG), high-density lipoprotein (HDL), fasting blood glucose (FBG), and other biochemical parameters. RESULTS: Around 17.7% of the students were at risk of developing MetS, with three or more risk factors detected, and 45% of the students had one or two risk factors. Increased BMI values were associated with an elevated risk of developing MetS, as 41.4% of the overweight students and 44.8% of the obese students had three or more risk factors. CONCLUSION: The prevalence of MetS is increasing in Young female university in the KSA as a result of an unhealthy lifestyle, including a lack of physical activity, leading to increased weight and the possible development of chronic diseases.


Assuntos
Exercício Físico , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Estudantes/estatística & dados numéricos , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Seguimentos , Humanos , Síndrome Metabólica/etiologia , Prevalência , Prognóstico , Fatores de Risco , Arábia Saudita/epidemiologia , Universidades , Circunferência da Cintura , Adulto Jovem
16.
Int J Biol Macromol ; 135: 1246-1251, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31181276

RESUMO

Nano-biopolymers could be employed for the delivery of active compounds to increase their stability, bioavailability, efficacy and sustainability. The bioactive chitosan polymer (Cts) was extracted from grown fungus, Cunninghamella elegans, and used for loading ceftriaxone (CFT) and forming the nano-conjugates using tripolyphosphate (TPP) - ionic crosslinking method. The characterization of synthesized CFT/chitosan nanoparticles (NCT) revealed that they chemically crosslinked and had particles' size mean of 56 nm. The CFT loading capacity onto NCT was 54.37%, while its entrapment efficiency was apparently high (79.43%); the maximum released of CFT was 78% from NCT composite after 90 h from dialysis. The CFT/NCT antibacterial activity was confirmed against 3 strains of Staphylococcus aureus (methicillin resistants), using disc diffusion and scanning images of electron microscope, which elucidate that CFT/NCT nano-composite had a vigorous action toward bacterial cells; most cells were ruptured and exploded after 6 h of exposure and entirely lysed after 9 h. The formulation of CFT/NCT nano-composite is exceedingly recommended for enhancing drug biocidal activity, especially against resistant bacterial strains.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Ceftriaxona/química , Quitosana/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanocompostos/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Análise Espectral
17.
Bioorg Chem ; 88: 102937, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31048120

RESUMO

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.


Assuntos
Antineoplásicos/farmacologia , Butilaminas/farmacologia , Espermidina/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Butilaminas/síntese química , Butilaminas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cricetinae , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Estrutura Molecular , Espermidina/síntese química , Espermidina/química , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacos
18.
Oncol Lett ; 3(1): 176-180, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22740876

RESUMO

In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49-14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19-0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene.

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