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1.
J Cardiothorac Surg ; 19(1): 432, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987788

RESUMO

BACKGROUND: Arterial tortuosity syndrome is a rare Autosomal recessive disease that leads to a loss of function of the connective tissues of the body, this happens due to a mutation in the solute carrier family 2 member 10 (SLC2A10) gene. ATS is more likely to occur in Large and medium-sized arteries including the aorta and pulmonary arteries. This syndrome causes the arteries to be elongated and tortuous, This tortuosity disturbs the blood circulation resulting in stenosis and lack of blood flow to organs and this chronic turbulent flow increases the risk of aneurysm development, dissection and ischemic events. CASE PRESENTATION: A 2 years old Arabian female child was diagnosed with ATS affecting the pulmonary arteries as a newborn, underwent a pulmonary arterial surgical reconstruction at the age of 2 years old due to the development of pulmonary artery stenosis with left pulmonary artery having a peak gradient of 73 mmHg with a peak velocity of 4.3 m/s and the right pulmonary artery having a peak gradient of 46 mmHg with a peak velocity of 3.4 m/s causing right ventricular hypertension. After surgical repair the left pulmonary artery has a peak pressure gradient of 20 mmHg, with the right pulmonary artery having a peak pressure gradient of 20 mmHg. CONCLUSION: ATS is a rare genetic condition that affects the great arteries especially the pulmonary arteries causing stenotic and tortuous vessels that may be central branches or distal peripheral branches that leads to severe right ventricular dysfunction and hypertension. We believe that surgical treatment provides the optimum outcomes when compared to transcather approaches especially when the peripheral arteries are involved. Some challenges and hiccups might occur, especially lung reperfusion injury that needs to be diagnosed and treated accordingly.


Assuntos
Artéria Pulmonar , Dermatopatias Genéticas , Malformações Vasculares , Humanos , Artéria Pulmonar/cirurgia , Artéria Pulmonar/anormalidades , Feminino , Malformações Vasculares/cirurgia , Malformações Vasculares/complicações , Pré-Escolar , Dermatopatias Genéticas/cirurgia , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/genética , Procedimentos Cirúrgicos Vasculares/métodos , Estenose de Artéria Pulmonar/cirurgia , Instabilidade Articular/cirurgia , Instabilidade Articular/genética , Procedimentos de Cirurgia Plástica/métodos , Artérias/anormalidades
2.
BMC Chem ; 18(1): 132, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014447

RESUMO

The search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.

3.
Int J Biol Macromol ; 273(Pt 2): 133083, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866289

RESUMO

In recent decades, there has been a concerning and consistent rise in the incidence of cancer, posing a significant threat to human health and overall quality of life. The transferrin receptor (TfR) is one of the most crucial protein biomarkers observed to be overexpressed in various cancers. This study reports on the development of a novel voltammetric immunosensor for TfR detection. The electrochemical platform was made up of a glassy carbon electrode (GCE) functionalized with gold nanoparticles (AuNPs), on which anti-TfR was immobilized. The surface characteristics and electrochemical behaviors of the modified electrodes were comprehensively investigated through scanning electron microscopy, XPS, Raman spectroscopy FT-IR, electrochemical cyclic voltammetry and impedance spectroscopy. The developed immunosensor exhibited robust analytical performance with TfR fortified buffer solution, showing a linear range (LR) response from 0.01 to 3000 µg/mL, with a limit of detection (LOD) of 0.01 µg/mL and reproducibility (RSD <4 %). The fabricated sensor demonstrated high reproducibility and selectivity when subjected to testing with various types of interfering proteins. The immunosensor designed for TfR detection demonstrated several advantageous features, such as being cost-effective and requiring a small volume of test sample making it highly suitable for point-of-care applications.


Assuntos
Técnicas Biossensoriais , Carbono , Eletrodos , Ouro , Nanopartículas Metálicas , Receptores da Transferrina , Ouro/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Carbono/química , Humanos , Imunoensaio/métodos , Limite de Detecção , Técnicas Eletroquímicas/métodos , Reprodutibilidade dos Testes
4.
Orthop Surg ; 16(8): 2011-2018, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38858814

RESUMO

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is the most prevalent spinal deformity affecting healthy children. Although AIS typically lacks symptomatic manifestations, its resultant deformities can affect patients' quality of life (QoL). Evaluating QoL and stress levels is crucial in determining the optimal brace type for AIS patients; however, research comparing the effectiveness of different brace types in this regard is lacking. Therefore, this study aimed to evaluate the impact of Boston versus Chêneau braces on QoL and stress levels in AIS patients. METHODS: This cross-sectional study was conducted at a medical institution in Riyadh, Saudi Arabia, involving 52 eligible patients selected through stratified random sampling based on type of brace as the main stratum. The inclusion criteria were idiopathic scoliosis, age ≥ 10 years, bracing for at least 3 months, and no history of cancer. QoL was evaluated according to the revised Scoliosis Research Society 22-item questionnaire (SRS-22r) and stress levels according to the eight-item Bad Sobernheim stress questionnaire (BSSQ-Brace). Independent-sample t-tests were used to compare brace-related QoL and stress level according to participants' sex and brace type. RESULTS: Overall, 32 participants were treated with Boston braces (seven men and 25 women), with a median (IQR) age of 11.00 years (10.00-13.00), and 20 participants were treated with Chêneau braces (three men, 17 women), with a median (IQR) age of 12.50 years (10.00-14.25). The total SRS-22 score was not significantly different between the brace groups (p = 0.158). However, patients in the Boston brace group reported significantly higher satisfaction levels (median = 4.00, IQR = 3.50-4.50) than did those in the Chêneau brace group (median = 3.25, IQR = 2.38-4.13, p = 0.013, moderate effect size = 0.345, 95% CI = 0.060 to 0.590). Furthermore, the BSSQ-brace total score was significantly higher in the Boston brace group (median = 9.00, IQR = 8.00-12.00) than in the Chêneau brace group (median = 7.50, IQR = 4.75-10.00, p = 0.007, moderate effect size = 0.376, 95% CI = 0.130 to 0.590), indicating higher stress levels in the Chêneau brace group. CONCLUSION: The QoL in AIS patients undergoing brace treatment was comparable across groups. Nonetheless, patients who used Chêneau braces experienced higher stress levels and lower treatment satisfaction rates than did those who used Boston braces. These findings can inform clinical decisions regarding prescription of bracing types and highlight the need for further in-depth research.


Assuntos
Braquetes , Qualidade de Vida , Escoliose , Humanos , Escoliose/terapia , Escoliose/psicologia , Estudos Transversais , Adolescente , Feminino , Masculino , Arábia Saudita , Criança , Inquéritos e Questionários , Estresse Psicológico
5.
Animal Model Exp Med ; 7(3): 195-207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38808561

RESUMO

Glaucoma, an irreversible optic neuropathy, primarily affects retinal ganglion cells (RGC) and causes vision loss and blindness. The damage to RGCs in glaucoma occurs by various mechanisms, including elevated intraocular pressure, oxidative stress, inflammation, and other neurodegenerative processes. As the disease progresses, the loss of RGCs leads to vision loss. Therefore, protecting RGCs from damage and promoting their survival are important goals in managing glaucoma. In this regard, resveratrol (RES), a polyphenolic phytoalexin, exerts antioxidant effects and slows down the evolution and progression of glaucoma. The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina. Additionally, RES plays protective roles in RGCs by promoting cell growth, reducing apoptosis, and decreasing oxidative stress in H2O2-exposed RGCs. RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways. RES could alleviate retinal function impairment by suppressing the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway. Therefore, RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.


Assuntos
Glaucoma , Fármacos Neuroprotetores , Resveratrol , Células Ganglionares da Retina , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Células Ganglionares da Retina/efeitos dos fármacos , Glaucoma/tratamento farmacológico , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos
6.
Int J Biol Macromol ; 265(Pt 1): 130616, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447842

RESUMO

The use of single-walled carbon nanotubes (SWCNTs) in biomedical applications is limited due to their inability to disperse in aqueous solutions. In this study, dispersed -COOH functionalized CNTs with N-succinylated chitosan (CS), greatly increasing the water solubility of CNTs and forming a uniformly dispersed nanocomposite solution of CNTs@CS. Coupling reagent EDC/NHS was used as a linker with the -COOH groups present on the N-succinylated chitosan which significantly improved the affinity of the CNTs for biomolecules. Myoglobin (Mb) is a promising biomarker for the precise assessment of cardiovascular risk, type 2 diabetes, metabolic syndrome, hypertension and several types of cancer. A high level of Mb can be used to diagnose the mentioned pathogenic diseases. The CNTs@CS-FET demonstrates superior sensing performance for Mb antigen fortified in buffer, with a wide linear range of 1 to 4000 ng/mL. The detection limit of the developed Mb immunosensor was estimated to be 4.2 ng/mL. The novel CNTs@CS-FET immunosensor demonstrates remarkable capability in detecting Mb without being affected by interferences from nonspecific antigens. Mb spiked serum showed a recovery rate of 100.262 to 118.55 % indicating great promise for Mb detection in clinical samples. The experimental results confirmed that the CNTs@CS-FET immunosensor had excellent selectivity, reproducibility and storage stability.


Assuntos
Técnicas Biossensoriais , Quitosana , Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Nanocompostos , Nanotubos de Carbono , Humanos , Mioglobina , Técnicas Biossensoriais/métodos , Reprodutibilidade dos Testes , Imunoensaio , Biomarcadores , Técnicas Eletroquímicas/métodos
7.
Clin Case Rep ; 12(3): e8664, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38487644

RESUMO

Mycotic pseudoaneurysms can be a serious and life threatening complication of left sided infective endocarditis. They most commonly affect the major axial vessels. Profunda femoris artery (PFA) aneurysms are rare and present in only 0.5% of all peripheral aneurysms, regardless of the underlying etiology. We present a case of a patient who underwent mitral valve repair for severe mitral regurgitation secondary to culture negative IE which was complicated by multiple mycotic pseudoaneurysm. The PFA pseudoaneurysm which was affected and was complicated with a large hematoma compressing the femoral nerve. This was managed by a staged hybrid approach. Endovascular stenting was performed first to seal the pseudoaneurysm and facilitate open surgical repair using a reversed interposition saphenous vein graft. To the best of our knowledge, this is the first reported case of a PFA mycotic aneurysm (MA) being managed by a hybrid approach using endo-vascular and open surgical repair. MAs and pseudoaneurysms are complex and life threatening conditions requiring meticulous planning for optimal management. Endovascular stenting can be considered as an alternative to surgical management in certain cases or as a bridge to definitive open surgical repair depending on anatomical location and associated complications.

8.
Bioelectrochemistry ; 157: 108671, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38401223

RESUMO

Herein, we fabricated an ultrasensitive electrochemical immunosensor for the quantitative detection of corticosteroid-binding globulin (CBG). CBG is a protein that regulates glucocorticoid levels and is an important biomarker for inflammation. A decrease in CBG levels is a key biomarker for inflammatory diseases, such as septic shock. To enhance the electrochemical performance and provide a large surface area for anti-CBG immobilization, we functionalized the glassy carbon electrode surface with AuNPs. Electrochemical characterization methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the construction of the fabricated immunosensor. The electrochemical signal demonstrated a remarkable sensitivity to the CBG antigen, with a detection range from 0.01 to 100 µg/mL and a limit of detection of 0.012 µg/mL, making it suitable for both clinical and research applications. This label-free immunosensor offers significant advantages, including high sensitivity, low detection limits and excellent selectivity, making it a promising tool for detecting CBG in complex biological samples. Its potential applications include early disease diagnosis, treatment monitoring and studying CBG-related physiological processes.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Carbono/química , Ouro/química , Transcortina , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Imunoensaio , Técnicas Eletroquímicas/métodos , Eletrodos , Biomarcadores , Limite de Detecção
9.
Saudi Med J ; 45(2): 139-146, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309729

RESUMO

OBJECTIVES: To investigate the long-term outcomes of differentiated thyroid cancer (DTC) and the predictive factors for excellent and incomplete responses to therapy on long-term follow-up of patients. METHODS: A retrospective chart review and analysis was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Demographic, histological, and therapeutic data were collected from patients older than 13 years at the time of diagnosis, with a minimum follow-up of 18 months. Outcomes were divided into excellent, indeterminate, biochemically incomplete, and structurally incomplete responses. Odds ratios (ORs) for predictors of incomplete response at the last visit were determined. We first tested associations univariately with incomplete responses, and then variables with significant associations were included in a multivariable logistic model. RESULTS: Among 230 patients with DTC, 61.7% had excellent responses to therapy on long-term follow-up, and 24.3% had incomplete biochemical and structural responses. The median follow-up was 4.6 years. Factors significantly associated with incomplete response to therapy in the multivariate analysis (p<0.05) were age >55 years (OR=5) and lymph node (OR=3.4) and distant metastases (OR=29). Older age did not affect the outcome in low-risk patients with DTC but was significantly associated with incomplete responses in those with intermediate risk (p=0.04) and high risk (p=0.003). CONCLUSION: We strongly advocate incorporating age into recurrence risk assessment for patients with DTC.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Seguimentos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia , Medição de Risco , Prognóstico
10.
BMC Endocr Disord ; 24(1): 10, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38229053

RESUMO

BACKGROUNDS: Although the significance of diet in preventing or managing diabetes complications is highlighted in current literature, there is insufficient evidence regarding the correlation between nutrient patterns and these complications. The objective of this case-control study is to investigate this relationship by analyzing the dietary intake of nutrients in participants with and without type 2 diabetes (T2D). METHODS: A case-control study was conducted at the Tabriz Center of Metabolism and Endocrinology to investigate the relationship between nutrient patterns and type 2 diabetes (T2D). The study enrolled 225 newly diagnosed cases of T2D and 225 controls. The dietary intake of nutrients was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Principal component analysis using Varimax rotation was used to obtain nutrient patterns. Logistic regression analysis was performed to estimate the risk of T2D. RESULTS: The participants' mean (SD) age and BMI were 39.8 (8.8) years and 27.8 (3.6) kg/m2, respectively. The results identified three major nutrient patterns. The first nutrient pattern was characterized by high consumption of sucrose, animal protein, vitamin E, vitamin B1, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin D, Riboflavin, Vitamin B5, copper, and Magnesium. The third nutrient pattern was characterized by fiber, plant protein, vitamin A, riboflavin, vitamin C, calcium, and potassium. Individuals in the highest tertile of nutrient pattern 3 (NP3) had a lower risk of T2D compared to those in the lowest tertile after adjusting for confounders. The odds ratio was 0.52 with a 95% confidence interval of 0.30-0.89 and a P_trend of 0.039. CONCLUSION: This study found that conforming to a nutrient pattern consisting of plant protein, vitamin C, vitamin A, vitamin B2, potassium, and calcium is linked to a lower likelihood of developing T2D.The initial results suggest that following a nutrient pattern that includes these nutrients may reduce the risk of T2D. However, further research is required to confirm the relationship between nutrient patterns and T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Vitamina A , Cálcio , Estudos de Casos e Controles , Nutrientes , Dieta , Vitaminas , Riboflavina , Ácido Ascórbico , Potássio , Proteínas de Plantas
11.
Fundam Clin Pharmacol ; 38(2): 225-237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37753585

RESUMO

BACKGROUND: Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases. OBJECTIVE: The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms. METHODS: The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles. RESULTS: Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage-dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1-EAAT2. CONCLUSION: In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Criança , Humanos , Riluzol/farmacologia , Riluzol/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/farmacologia , Memantina/uso terapêutico
12.
Int J Biol Macromol ; 256(Pt 1): 128312, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000589

RESUMO

In this study, we developed a label-free and ultrasensitive electrochemical biosensor for the detection of transferrin (Tf), an important serum biomarker of atransferrinemia. The biosensor was fabricated by using glassy carbon electrode (GCE) and modified with gold nanoparticles (AuNPs) via electroless deposition. The electrochemical characteristics of the GCE-AuNPs biosensors were characterized using cyclic voltammetry and electrochemical impedance spectroscopy analysis. Differential pulse voltammetry was used for quantitative evaluation of the Tf-antigen by recording the increase in the anodic peak current of GCE-AuNPs biosensor. The GCE-AuNPs biosensor demonstrates superior sensing performance for Tf-antigen fortified in buffer, with a wide linear range of 0.1 to 5000 µg/mL and a limit of detection of 0.18 µg/mL. The studied GCE-AuNPs biosensor showed excellent sensitivity, selectivity, long-term storage stability and simple sensing steps without pretreatment of clinical samples. This GCE-AuNPs biosensor indicates great potential for developing a Tf detection platform, which would be helpful in the early diagnosis of atransferrinemia. The developed GCE-AuNPs biosensor holds great potential in biomedical research related to point of care for the early diagnosis and monitoring of diseases associated with aberrant serum transferrin levels. These findings suggest that the GCE-AuNPs biosensor has great potential for detecting other serum biomarkers.


Assuntos
Técnicas Biossensoriais , Erros Inatos do Metabolismo dos Metais , Nanopartículas Metálicas , Carbono/química , Ouro/química , Nanopartículas Metálicas/química , Transferrina , Técnicas Biossensoriais/métodos , Eletrodos , Técnicas Eletroquímicas/métodos , Limite de Detecção
13.
Nat Prod Res ; 38(5): 848-855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36987594

RESUMO

Cleome viscosa L., a member of the family Cleomaceae, is a potential medicinal plant, known for several bioactive properties such as: anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, wound healing, etc. Our study aimed to isolate a bioactive compound and assess its antibacterial activity. The crystal compound imperatorin was isolated and reported for the first time from the aerial parts of C. viscosa. The isolation was made using silica gel (100-200 mesh) column chromatography. The structure of imperatorin was investigated through single-crystal XRD, unit cell molecules, FTIR, and ESI-MS spectral analysis. The results validated imperatorin's triclinic crystal structure and P2i/c distance group. The electronic structure was also calculated (4.28/6.21 D) along with the frontier molecular orbital, dipole moment, atomic charges, and electrostatic map of particles in gaseous stage and active site. Imperatorin showed highest activity at 40 µg/mL concentration against Gram + ve bacteria: Staphylococcus aureus (3 ± 0.2 mm), Bacillus subtilis (3 ± 0.6 mm), and Gram -ve bacteria: Klebsiella pneumoniae (3 ± 0.2 mm), Escherichia coli (5 ± 0.2 mm). The study highlights that the compound can be isolated in larger quantities as the plant is easily available across the tropics.


Assuntos
Cleome , Furocumarinas , Extratos Vegetais , Extratos Vegetais/química , Cleome/química , Antibacterianos/química , Componentes Aéreos da Planta , Testes de Sensibilidade Microbiana
14.
Front Genet ; 14: 1280051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090147

RESUMO

Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development. Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model. Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195. Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.

15.
Cell Commun Signal ; 21(1): 351, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38098017

RESUMO

Oropharyngeal cancer, a subset of head and neck cancer, is increasingly recognized as a unique clinical entity primarily influenced by high-risk human papillomavirus (HPV) infections, particularly HPV-16. This review delves into the viral life cycle of HPV-16 and its interactions with host cells, with a specific focus on the crucial roles played by the viral oncoproteins E6 and E7. These oncoproteins drive cellular proliferation by targeting critical tumor suppressor proteins like p53 and Rb, resulting in uncontrolled cell growth and genomic instability. Furthermore, the significance of epigenetic modifications induced by HPV-16 and their implications is important for cancer progression. This comprehensive review provides valuable insights into the intricate molecular landscape of HPV-induced oropharyngeal cancer, shedding light on the development of targeted therapies and preventive strategies for this emerging global health concern. Video Abstract.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Neoplasias Orofaríngeas/patologia , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia
16.
Dent J (Basel) ; 11(12)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38132408

RESUMO

Intracanal medicaments with maximal antimicrobial efficacy and minimal damage to resident stem cells are essential for successful regenerative endodontic procedures. 2-Hydroxyisocaproic acid (HICA) could have the attributes of a potential intracanal medicament. This study evaluates its cytotoxicity, genotoxicity, and effects on the odontogenic and osteogenic differentiation of the stem cells of the apical papilla (SCAP). Cytotoxicity and cell viability assays were performed on cells treated for 24, 48, and 72 h with varying concentrations of HICA and compared to the standard intracanal medicament, calcium hydroxide. The genotoxicity was assessed via immunofluorescence for two markers of DNA double-strand breaks: phosphorylated γH2AX and 53BP1. The SCAP differentiation was evaluated based on the alkaline phosphatase activity, Alizarin Red staining, and expression of odontogenic and osteogenic genes (DSPP1, BSP1, OCN, RUNX2) in the presence of selected HICA concentrations. HICA was not cytotoxic at concentrations up to 10 mg/mL, regardless of the exposure time, although it was cytostatic at all tested concentrations. HICA was not genotoxic at concentrations below 5 mg/mL. No difference in cytotoxicity or genotoxicity was found between HICA and calcium hydroxide at 1 mg/mL. HICA retained about 70% of the osteogenic differentiation potential at 1 mg/mL. Within the limitations of this in vitro study, we show that HICA at 1 mg/mL could be a potential intracanal medicament for REPs.

17.
Medicine (Baltimore) ; 102(45): e35347, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37960765

RESUMO

Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has long been found to be dysregulated in human lung adenocarcinomas (LUADs). Nevertheless, the function, mutational profile, epigenetic regulation, co-expression profile, and clinicopathological significance of the GPC3 gene in LUAD progression are not well understood. In this study, we analyzed cancer microarray datasets from publicly available databases using bioinformatics tools to elucidate the above parameters. We observed significant downregulation of GPC3 in LUAD tissues compared to their normal counterparts, and this downregulation was associated with shorter overall survival (OS) and relapse-free survival (RFS). Nevertheless, no significant differences in the methylation pattern of GPC3 were observed between LUAD and normal tissues, although lower promoter methylation was observed in male patients. GPC3 expression was also found to correlate significantly with infiltration of B cells, CD8+, CD4+, macrophages, neutrophils, and dendritic cells in LUAD. In addition, a total of 11 missense mutations were identified in LUAD patients, and ~1.4% to 2.2% of LUAD patients had copy number amplifications in GPC3. Seventeen genes, mainly involved in dopamine receptor-mediated signaling pathways, were frequently co-expressed with GPC3. We also found 11 TFs and 7 miRNAs interacting with GPC3 and contributing to disease progression. Finally, we identified 3 potential inhibitors of GPC3 in human LUAD, namely heparitin, gemcitabine and arbutin. In conclusion, GPC3 may play an important role in the development of LUAD and could serve as a promising biomarker in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Masculino , Glipicanas/genética , Glipicanas/metabolismo , Relevância Clínica , Epigênese Genética , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/patologia , Prognóstico
18.
Food Sci Nutr ; 11(11): 6845-6853, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37970415

RESUMO

The aim of this study was to identify phenolic compounds in walnut leaves from northern Iraq and evaluate their ability to act as antibacterial and antioxidant agents. Phenolic compounds were determined by reversed-phase HPLC. Antibacterial activity was tested against various bacteria. Antioxidant properties were evaluated by various assays, including reducing power and DPPH radical scavenging activity. The HPLC profiles of walnut leaf fractions revealed quercetin, hydroquinone, 4-hydroxybenzoic acid, and caffeic acid in three fractions. The inhibitory activity of DPPH was determined as 47.66, 32.41, and 51.90 µg/mL for fractions I, II, and III, respectively. For ferric reducing power activity, fraction II > fraction III > fraction I and the FRAP activity was observed as 64.43, 73.19, and 68.18 µg/mL for fractions I, II, and III, respectively. All extracted fractions had antibacterial properties against all bacterial strains tested. Observations showed that fraction I was able to produce similar zones of inhibition as streptomycin in most cases. These results suggest that the fractions of this plant extract are plausible natural antioxidants that could be used as prime candidates for the synthesis of antioxidant drugs that can be used for the treatment of many oxidative stress-related diseases.

19.
J Infect Dev Ctries ; 17(10): 1430-1435, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37956373

RESUMO

INTRODUCTION: Urinary tract infections (UTIs) are common in children. UTIs can lead to serious and permanent damage to the urinary tract if treatment is delayed or insufficient, particularly in repeated infections. Knowledge of antibiotic resistance trends aids in the selection of appropriate empiric antibiotics. There is limited data regarding this in Saudi Arabia. This study aimed to investigate uropathogens and their antibiotic resistance patterns in the pediatric community in a tertiary care center. METHODOLOGY: The study population included children aged 0 to 14 years old who had culture-proven UTIs evaluated in the Department of Pediatrics, King Abdulaziz University Hospital in Jeddah, Saudi Arabia from February 2019 to September 2021. RESULTS: Out of 510 UTI episodes, Escherichia coli (54.5%) was the predominant causative pathogen. Of the total episodes, 137 (26.8%) were caused by extended spectrum beta-lactamase (ESBL) producers. In general, the highest resistance was observed against ampicillin (73.2%), cefazolin (54.6%), co-trimoxazole (46%), and cefuroxime (40.6%), whereas amikacin (0.4%), imipenem (0.8%), and meropenem (0.8%) showed the lowest rates of resistance. CONCLUSIONS: Antibiotic resistance is a major concern worldwide due to misuse of antibiotics and subsequent rise of multidrug resistant organisms. Our findings highlight the rise in antibiotic resistance, particularly in E. coli strains. Furthermore, ESBL-producing bacteria were responsible for approximately one-third of UTIs. Our study emphasizes the importance of local antibiograms for pediatric community-acquired infections, as it guides clinicians in every center in the choice of appropriate empiric antibiotic treatment.


Assuntos
Infecções Comunitárias Adquiridas , Infecções Urinárias , Sistema Urinário , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Escherichia coli , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Centros de Atenção Terciária , Arábia Saudita/epidemiologia , beta-Lactamases , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana
20.
Cureus ; 15(9): e44619, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37799250

RESUMO

This case report highlights the unique presentation of dissociative amnesia masking an underlying brief psychotic disorder, triggered by a very intense psycho-social stressor. Learning points from this report center around the importance of considering psychotic as well as affective disorders alongside a presentation of dissociative amnesia, and not only the expected anxious, post-traumatic or personality-oriented states. Our patient, a 37-year-old gentleman, was brought to our emergency department via police referral. He had gaps in his autobiographical memory that, upon receiving a regular dose of benzodiazepines, unraveled bizarre, uncooperative, and agitated behavior as well as marked fluctuations in his daily mental state examinations. Biological management through antipsychotic monotherapy, psychological management through insight-oriented therapy as well as psychological support, and social management revolving around the alleviation of surrounding stressors enabled his safe recovery.

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