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1.
Physiol Res ; 73(2): 227-237, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38710058

RESUMO

Nephrotoxicity as a cause of acute kidney injury (AKI) induced by cisplatin (CP), limits its usefulness as an anticancer agent. Diminazene, an angiotensin converting enzyme 2 activator, exhibited renoprotective properties on rat models of kidney diseases. This research aims to investigate the salutary effect of diminazene in comparison with lisinopril or valsartan in CP-induced AKI. The first and second groups of rats received oral vehicle (distilled water) for 9 days, and saline injection or intraperitoneal CP (6 mg/kg) on day 6, respectively. Third, fourth, and fifth groups received intraperitoneal injections of CP on day 6 and diminazene (15 mg/kg/day, orally), lisinopril (10 mg/kg/day, orally), or valsartan (30 mg/kg/day, orally), for 9 days, respectively. 24h after the last day of treatment, blood and kidneys were removed under anesthesia for biochemical and histopathological examination. Urine during the last 24 h before sacrificing the rats was also collected. CP significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin, calcium, phosphorus, and uric acid. It also increased urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase/creatinine ratio, and reduced creatinine clearance, as well the plasma concentrations of inflammatory cytokines [plasma tumor necrosis factor-alpha, and interleukin-1beta], and significantly reduced antioxidant indices [catalase, glutathione reductase , and superoxide dismutase]. Histopathologically, CP treatment caused necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. Diminazine, lisinopril, and valsartan ameliorated CP-induced biochemical and histopathological changes to a similar extent. The salutary effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Keywords: Cisplatin, Diminazene, ACE2 activator, Lisinopril, Valsartan, Acute kidney injury.


Assuntos
Injúria Renal Aguda , Cisplatino , Diminazena , Lisinopril , Ratos Wistar , Valsartana , Animais , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/tratamento farmacológico , Lisinopril/farmacologia , Cisplatino/toxicidade , Valsartana/farmacologia , Masculino , Diminazena/análogos & derivados , Diminazena/farmacologia , Diminazena/uso terapêutico , Ratos , Antineoplásicos/toxicidade , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo
2.
Cureus ; 16(3): e55564, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38576638

RESUMO

Aortic dissection (AD) is a rare but often lethal condition if not properly and urgently treated. Most often, patients arrive with acute hemodynamic instability and ripping chest agony. The patient's life depends critically on a correct diagnosis made as soon as possible. We describe a 60-year-old man who arrived at the emergency room with symptoms of a brain stroke, including poor consciousness, left-sided weakness, and speech disturbance associated with hemodynamic instability, and chest pain. Thoracic aortic arch dissection was observed on CT angiography (CTA). In addition, CTA revealed that the dissection extends proximally into the left common carotid artery, left subclavian artery, brachiocephalic trunk, and right common carotid artery and distally to the left common iliac artery, coupled with significant stenosis of the left common iliac artery. Proper management of blood pressure (BP) parameters is life-saving for the patient. Since our hospital did not offer cardiothoracic surgery services, the patient was transferred to a different institution, where he received medical care immediately from an expert team and had surgery.

3.
Transl Oncol ; 45: 101961, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631259

RESUMO

Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944-5p, miR-105-5p, miR-486-5p, miR-506-5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs-CCAT-1, MALAT-1, or H19-markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486-5p, miR-506-5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944-5p and miR-105-5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105-5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105-5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.

5.
Coron Artery Dis ; 35(4): 309-313, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411142

RESUMO

BACKGROUND: The role of coronary artery spasm (CAS) was extended beyond variant angina to ischemic heart disease in general, including effort angina, unstable angina, acute myocardial infarction (MI) and sudden death. It is difficult and cumbersome to examine CAS during coronary angiography. Risk factors for CAS include smoking and genetic polymorphisms. AIM: We aimed to investigate the association of the interleukin-6 (IL-6) polymorphism with catheter-induced CAS in Egyptian patients who undergo coronary angiography. METHODS: This is a case-control study. Two hundred patients with chronic coronary artery disease who underwent elective coronary angiography were included in the study. Patients were divided into two groups: the non-CAS group (100 patients) and the CAS group (100 patients). The subjects were genotyped to the -572 C>G (rs 1800796) polymorphism of the IL-6 gene by PCR-restriction fragment length polymorphism. RESULTS: We found that patients with CAS have more risk factors for atherosclerosis compared to those without CAS. Smoking, the IL-6 GG genotype, and the G allele were independent risk factors for CAS. CONCLUSION: We concluded that the GG genotype and G allele of the IL-6 gene are associated with CAS. Smoking, the GG genotype, and the G allele of the IL-6 gene are independent predictors of catheter-induced CAS.


Assuntos
Angiografia Coronária , Vasoespasmo Coronário , Predisposição Genética para Doença , Interleucina-6 , População do Norte da África , Fumar , Humanos , Egito/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Interleucina-6/genética , Vasoespasmo Coronário/genética , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/epidemiologia , Estudos de Casos e Controles , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Idoso , Cateterismo Cardíaco , Frequência do Gene , Fenótipo , Cateteres Cardíacos , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único , Polimorfismo Genético
6.
Heliyon ; 10(4): e26190, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390109

RESUMO

In this study a frequency scaling law for 3D anatomically representative supravalvular aortic stenosis (SVAS) cases is proposed. The law is uncovered for stethoscopy's preferred auscultation range (70-120 Hz). LES simulations are performed on the CFD solver Fluent, leveraging Simulia's Living Heart Human Model (LHHM), modified to feature hourglass stenoses that range between 30 to 80 percent (mild to severe) in addition to the descending aorta. For physiological hemodynamic boundary conditions the Windkessel model is implemented via a UDF subroutine. The flow-generated acoustic signal is then extracted using the FW-H model and analyzed using FFT. A preferred receiver location that matches clinical practice is confirmed (right intercostal space) and a correlation between the degree of stenosis and a corresponding acoustic frequency is obtained. Five clinical auscultation signals are tested against the scaling law, with the findings interpreted in relation to the NHS classification of stenosis and to the assessments of experienced cardiologists. The scaling law is thus shown to succeed as a potential quantitative decision-support tool for clinicians, enabling them to reliably interpret stethoscopic auscultations for all degrees of stenosis, which is especially useful for moderate degrees of SVAS. Computational investigation of more complex stenotic cases would enhance the clinical relevance of this proposed scaling law, and will be explored in future research.

7.
Parasite Epidemiol Control ; 25: e00340, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38333559

RESUMO

Tick-borne diseases have a major adverse effect on livestock worldwide, causing enormous economic losses in meat and milk production as well threatening animal and public health. In this study, we aimed to detect and characterize piroplasms isolated from cattle and buffalo in southern Egypt, using molecular techniques. Three hundred blood samples were collected from cattle and buffalo in two governorates in southern Egypt. All 300 samples (100%) were confirmed to contain DNA, as they exhibited bands of bovine ß-actin gene at the expected 227 bp for cattle and buffalo. The samples were analyzed by PCR for the presence of piroplasms, specifically Babesia bovis, Babesia bigemina, and Theileria annulata. Samples positive for the piroplasma 18S ribosomal RNA gene were further examined for two additional genes, spherical body protein 4 gene, to provide an enhanced degree of specificity for the identification of B. bovis and B. bigemina, and the major merozoite surface antigen gene for T. annulata. The infection rate for piroplasma spp. was 60/300 (20%). The positivity rates were 10.7% (32/300) for T. annulata, 5.3% (16/300) for B. bovis, and 4% (12/300) for B. bigemina. By host species, 42/150 (28%) cattle and 18/150 (12%) buffalo were positive for piroplasms. None of the isolates sequenced for the B. bovis isolates from buffalo in this study showed 100% identity with any sequence deposited in GenBank for the small subunit ribosomal RNA gene (maximum identity value = 99.74%). Similarly, no T. annulata small subunit ribosomal RNA gene sequence identified in this study exhibited 100% identity with any sequence deposited in GenBank (maximum identity value = 99.89%). The current study provides a partial sequence of the T. annulata merozoite-piroplasm surface antigen gene, as well as the B. bovis and B. bigemina spherical body protein 4 genes, in cattle and buffalo in southern Egypt, and is the first report on these piroplasma genes in cattle and buffalo in southern Egypt.

8.
Emerg Radiol ; 31(2): 141-149, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265604

RESUMO

PURPOSE: This study aims to evaluate the added value of duplex Doppler examination to the routinely graded compression grayscale ultrasound (US) for patients with suspected acute appendicitis (AA) in correlation with surgical management outcomes. METHODS: The study lasted from January 2020 to March 2021. Throughout that period, patients who had suspected appendicitis were included with a visible appendix in the grayscale US. These patients were categorized clinically based on Alvarado's score. They underwent graded compression grayscale US of the appendix and duplex Doppler study. Subsequently, they were assigned for non-contrast multislice computed tomography (MSCT) according to Alvarado's score and underwent either emergency appendicectomy or conservative clinical management afterward. A Student's t-test was used to determine if there were significant differences in the mean values between the groups. The diagnostic performance of spectral Doppler US for the diagnosis of AA was depicted. RESULTS: Eighty-four patients with visualized color flow in the appendicular Doppler US were enrolled, with 60 (71.4%) having AA, and 24 (28.6%) not having appendicitis. Spectral Doppler criterion of PSV greater than 8.6 cm/s demonstrated a high sensitivity of 91.67% and specificity of 77.78% for patients with Alvarado score ranging from 4 to 7, and appendiceal MOD ranging from 6 to 8 mm, while a discriminatory criterion of RI greater than 0.51 had a high sensitivity of 100% and a relatively lower specificity of 66.67%. CONCLUSION: The patients with AA have significantly higher point PSV and point RI values than those without AA and are especially useful in equivocal patients whose MODs and Alvarado scores are in the diagnostically equivocal ranges of 6-8 mm and 4-7, respectively, with the point PSV and RI demonstrating negative predictive value 87.5% and 100%.


Assuntos
Apendicite , Apêndice , Humanos , Apendicite/diagnóstico por imagem , Apendicite/cirurgia , Ultrassonografia Doppler , Apêndice/diagnóstico por imagem , Ultrassonografia/métodos , Valor Preditivo dos Testes , Doença Aguda , Sensibilidade e Especificidade
9.
Br J Oral Maxillofac Surg ; 62(2): 157-163, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38238115

RESUMO

The nationwide extension of the electric scooter (e-scooter) scheme, which began in 2020, aimed to alleviate public transport congestion, to reduce pollution and peak-time road traffic. This retrospective study evaluates the range of e-scooter-related maxillofacial trauma before the recent scheme extension and compares the findings with existing literature on this topic. The Queen Elizabeth Hospital Birmingham, United Kingdom (UK) operates as a Level 1 Regional Major Trauma Centre and serves a population of four million. All patient records between September 2021 to September 2022 were analysed to establish the types of e-scooter-related maxillofacial trauma sustained. A Pearson's chi-squared test was used to assess for significant associations between variables recorded. Falls accounted for the majority of injuries (44.3%), and soft tissue lacerations were the most common maxillofacial injury (38%). Statistically significant results were measured in the following variables: gender and intoxication status (p = 0.007), helmet status and injuries sustained in maxillofacial and non-maxillofacial regions (p = 0.043), mechanism of injury and injuries sustained in both the maxillofacial and non-maxillofacial regions (p = 0.045). E-scooters are an emerging concern within the UK. Further studies across the UK are required to assess the frequency of e-scooter-related injuries. Such data may prove useful in determining the government's decision on e-scooter use on UK roads.


Assuntos
Cabeça , Traumatismos Maxilofaciais , Humanos , Estudos Retrospectivos , Dispositivos de Proteção da Cabeça , Traumatismos Maxilofaciais/epidemiologia , Traumatismos Maxilofaciais/etiologia , Reino Unido/epidemiologia
10.
RSC Adv ; 14(2): 1513-1526, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38174234

RESUMO

The structure-activity relationship of a new tert-butylphenylthiazole series, with a pyrimidine linker, was investigated. We wished to expand knowledge of this novel class of antibiotics by generating 21 new derivatives bearing ≥2 heteroatoms in their side chains. Their activity was examined against isolates of methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. Two compounds with 1,2-diaminocyclohexane as a nitrogenous side chain showed promising activity against the highly infectious MRSA USA300 strain, with a minimum inhibitory concentration (MIC) of 4 µg mL-1. One of these two compounds demonstrated potent activity against C. difficile, with a MIC of 4 µg mL-1. Moderate activities against a C. difficile strain with a MIC of 8 µg mL-1 were noted. Some new compounds possessed antifungal activity against a wild fluconazole-resistant C. albicans strain, with MIC values of 4-16 µg mL-1. ADME and metabolism-simulation studies were performed for the most promising compound and compared with lead compounds. Our results revealed that one compound possessed greater penetration of bacterial membranes and metabolic resistance, which aided a longer duration of action against MRSA.

11.
Int J Psychiatry Med ; : 912174241230886, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38282460

RESUMO

OBJECTIVE: There are contradicting reports regarding the relationship between cannabis use and male sexual functions with almost no data about synthetic cannabinoids (SC) and its effect on male sexual functions. This study investigates psychological concerns related to male sexual functions among cannabis and SC users. The research aims to assess different sexual functions and aspects of sexual psychopathology in cannabis and SCs dependent men compared to controls. METHOD: Thirty male patients with cannabis dependence, thirty male patients with SCs dependence and thirty matched controls from the outpatient clinic of Kasr Al Ainy hospital, Egypt, were assessed using Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID-I), International Index of Erectile Function (IIEF), and Sexuality scale. RESULTS: The means of IIEF questionnaire in the cannabis and SC group were significant lower than the means of the control group (P < .001) except the orgasmic function in cannabis group (P = .052). In the SCs group, sexual depression was higher and preoccupation lower than the cannabis (P < .020; P < .003, respectively) and control groups (P < .001; P < .001, respectively). The duration and dose of intake of cannabis and SCs correlated significant with sexual esteem, sexual preoccupation and all domains of IIEF. CONCLUSION: Cannabis and SC dependence were associated with lower erectile function, sexual desire, intercourse satisfaction and overall satisfaction, and lower orgasmic functions in the SC group than controls. Both groups showed higher sexual depression, lower sexual esteem and sexual preoccupation than controls. SC has a higher negative impact on male sexual functions and psychopathology than cannabis.

13.
Acta Cardiol ; 78(7): 828-837, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37694719

RESUMO

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.


Assuntos
Insuficiência Cardíaca , Pacientes Ambulatoriais , Humanos , Projetos Piloto , Redução de Custos , Insuficiência Cardíaca/terapia , Hospitalização
15.
Comput Biol Chem ; 107: 107958, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37714080

RESUMO

Novel thiazolidine-2,4-dione derivatives, 11a-g, were designed, and synthesized targeting the VEGFR-2 protein. The in vitro studies indicated the abilities of the synthesized derivatives to inhibit VEGFR-2 and prevent the growth of two different cancer cell types, HepG2 and MCF-7. Compound 11 f exhibited the strongest anti-VEGFR-2 activity (IC50 = 0.053 µM). As well, compound 11 f showed impressive anti-proliferative activity against the mentioned cancer cell lines with IC50 values of 0.64 ± 0.01 and 0.53 ± 0.04 µM, respectively. Additionally, compound 11 f arrested the MCF-7 cell cycle at the S phase and increased the overall apoptosis percentage. Furthermore, cell migration assay revealed that compound 11 f has a significant ability to prevent migration and healing potentialities of MCF-7. Moreover, computational studies were used to conduct the molecular investigation of the VEGFR-2-11 f complex. The kinetic and structural features of the complex were examined using molecular dynamics simulations and molecular docking. Besides, Principal component analysis (PCA) was used to explain the dynamics of the VEGFR-2-11 f complex at various spatial scales. The DFT calculations also provided further clarity regarding compound 11 f's structural and electronic features. To evaluate how closely the developed compounds might look like drugs, ADMET and toxicity experiments were computed. To conclude, the presented study demonstrates the potential of compound 11 f as a viable anti-cancer drug, which can serve as a prototype for future structural modifications and further biological investigations.


Assuntos
Antineoplásicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosforilação , Inibidores de Proteínas Quinases , Relação Estrutura-Atividade , Tiazolidinas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
16.
Sci Rep ; 13(1): 15455, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723280

RESUMO

Polystyrene (PS) is a thermoplastic polymer used in food packaging and the manufacture of trays and cups, among other applications. In this work, the preparation of a membrane by electrospinning blended sulphonated expanded PS waste and polybutylenesuccinate (PBS) is described. The fiber quality is controlled by selecting the right polymers' ratios and solvents. Investigation of the structure of the produced membranes by Fourier transform infrared spectroscopy-attenuated total reflectance confirmed the successful sulphonation of expanded PS and the appearance of characteristic (PBS) bands in the prepared blends. Morphology study of the electrospun membranes using a scanning electron microscope revealed that the quality of the fibers is improved significantly by increasing the amount of PBS in the blend solution. Moreover, continuous and more homogenous fibers are produced by increasing the ratio of PBS to 2%. The efficiency of the prepared membranes in dye removal was tested using methylene blue. The effects of different parameters such as, pH, contact time, temperature, and dye concentration have been studied. Also, kinetic and adsorption isotherm models as well as the durability of the prepared membranes were investigated. The membrane prepared from PSS/1% PBS demonstrated the highest dye uptake (846 mol) with good regeneration efficiency. The adsorption process was found to be endothermic and fits the Freundlich isotherm and pseudo-second-order kinetic model. The values of activation energy for the adsorption process are 36.98, 30.70, and 43.40 kJ/mol over PSS, PSS/1% PBS and PSS/2% PBS, respectively.

17.
Sultan Qaboos Univ Med J ; 23(3): 344-350, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37655083

RESUMO

Objectives: This study aimed to explore real-world data on the long-term survival of cancer patients using historical records from the Surveillance, Epidemiology, and End Results (SEER) Programme. Long-term survival is an important endpoint in the management of different malignancies. It is rarely assessed due to the unfeasibility of follow-up for a long duration of time. Besides reporting the five-year relative survival, the 10- and 20-year survival rates for different types of cancers were analysed. Additionally, survival trends as a function of time, age and tumour type were reviewed and reported. Methods: The study used SEER*Stat (Version 8.3.6.1) for data acquisition from the SEER 9 Regs (November 2019) database. Data from patients diagnosed with cancer between 1975 and 2014 were retrieved and included in the analysis. Results: For patients diagnosed with any malignant disease (N = 4,412,024), there was a significant increase in median overall survival over time (P <0.001). The 20-, 10-, and 5-year survival rates were higher in solid tumours compared to haematological malignancies (50.8% versus 38%; 57% versus 47.4%; and 62.2% versus 57.4%, respectively). The highest 20-year relative survival rates were observed in thyroid cancer (95.2%), germ cell and trophoblastic neoplasms (90.3%), melanoma (86.8%), Wilms' tumour (86.2%) and prostate cancer (83.5%). Conclusion: Long-term follow-up data were suggestive of high 20-year relative survival rates for most tumour types. Relative survival showed an improving trend over time, especially in solid tumours.


Assuntos
Neoplasias , Taxa de Sobrevida , Humanos , Neoplasias/mortalidade
18.
Comput Biol Chem ; 106: 107928, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37480629

RESUMO

In this study, new thieno[2,3-d]pyrimidine derivatives that could have potential anticancer activity by inhibiting the VEGFR-2 receptor have been designed, synthesized, and investigated. The thieno[2,3-d]pyrimidine derivatives showed strong in vitro abilities to inhibit VEGFR-2 and to prevent cancer cell growth in two different types of cancer cells, MCF-7 and HepG2. Particularly, compound 22 showed the most potent anti-VEGFR-2 activity with an IC50 value of 0.58 µM. Additionally, compound 22 exhibited good anti-proliferative activity against both MCF-7 and HepG2 cancer cell lines, with IC50 values of 11.32 ± 0.32 and 16.66 ± 1.22 µM, respectively. Further investigations revealed that compound 22 induced cell cycle arrest at the G2/M phase and promoted both early and late apoptosis in the MCF-7 cancer cells. Compound 22 also increased the level of BAX (2.8-fold), and reduced the level of Bcl-2 (2.2-fold), hence increasing the rate of apoptosis. Compound 22 also revealed 2.9-fold and 2.8-fold higher levels of caspase-8 and caspase-9, respectively, in the treated MCF-7 cancer cells compared to the control cell lines. The MD simulations showed that the VEGFR-2-22 complex was structurally and energytically stable over 100 ns, while the MM-GBSA study indicated its stable thermodynamic behavior. The bi-dimensional projection analysis confirmed the proper binding of the VEGFR-2-22 complex, while the DFT studies provided optimized geometry, charge distribution, FMO, ESP, the total density of state, and QTAIM maps of compound 22. Finally, computational ADMET studies were performed to assess the drug development potential of the thieno[2,3-d]pyrimidine derivatives. Overall, this study suggests that compound 22 has the potential as an anticancer lead compound by inhibiting VEGFR-2, which may be a guide for future drug design and development.


Assuntos
Antineoplásicos , Pirimidinas , Pirimidinas/farmacologia , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular , Desenho de Fármacos
19.
J Diabetes Res ; 2023: 7559078, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223639

RESUMO

Diabetes mellitus (DM) is one of the most common diseases worldwide. DM may disrupt hormone regulation. Metabolic hormones, leptin, ghrelin, glucagon, and glucagon-like peptide 1, are produced by the salivary glands and taste cells. These salivary hormones are expressed at different levels in diabetic patients compared to control group and may cause differences in the perception of sweetness. This study is aimed at assessing the concentrations of salivary hormones leptin, ghrelin, glucagon, and GLP-1 and their correlations with sweet taste perception (including thresholds and preferences) in patients with DM. A total of 155 participants were divided into three groups: controlled DM, uncontrolled DM, and control groups. Saliva samples were collected to determine salivary hormone concentrations by ELISA kits. Varying sucrose concentrations (0.015, 0.03, 0.06, 0.12, 0.25, 0.5, and 1 mol/l) were used to assess sweetness thresholds and preferences. Results showed a significant increase in salivary leptin concentrations in the controlled DM and uncontrolled DM compared to the control group. In contrast, salivary ghrelin and GLP-1 concentrations were significantly lower in the uncontrolled DM group than in the control group. In general, HbA1c was positively correlated with salivary leptin concentrations and negatively correlated with salivary ghrelin concentrations. Additionally, in both the controlled and uncontrolled DM groups, salivary leptin was negatively correlated with the perception of sweetness. Salivary glucagon concentrations were negatively correlated with sweet taste preferences in both controlled and uncontrolled DM. In conclusion, the salivary hormones leptin, ghrelin, and GLP-1 are produced either higher or lower in patients with diabetes compared to the control group. In addition, salivary leptin and glucagon are inversely associated with sweet taste preference in diabetic patients.


Assuntos
Diabetes Mellitus , Glucagon , Humanos , Peptídeo 1 Semelhante ao Glucagon , Paladar , Grelina , Percepção Gustatória , Leptina , Fatores de Transcrição
20.
Mol Biol Rep ; 50(7): 5747-5753, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37219667

RESUMO

BACKGROUND: Nitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization. METHODS AND RESULTS: 200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm. CONCLUSION: The eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.


Assuntos
Arteriopatias Oclusivas , Cateterismo Cardíaco , Óxido Nítrico Sintase Tipo III , Artéria Radial , Humanos , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/genética , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Cateterismo Periférico/efeitos adversos , Genótipo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Fatores de Risco
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