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1.
Cureus ; 16(5): e60601, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38894779

RESUMO

Aims Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. This study assesses the level of knowledge about COPD among undergraduate students that makes it different from other respiratory illnesses. Methods A cross-sectional study was conducted among undergraduate students at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS). The Bristol Chronic obstructive pulmonary disease Knowledge Questionnaire (BCKQ) was used to evaluate the knowledge about COPD, epidemiology, symptoms, exercise, smoking, and breathlessness domains. The questionnaire was distributed among the different male colleges. Results There were 304 respondents from five colleges. The overall BCKQ mean score was 15.16±4.52 (maximum 30). The mean score was highest for the Colleges of Pharmacy (18.89±2.17) and Medicine (18.00±3.84), and the College of Science and Health Professions had the lowest score (11.56±5.58). The highest overall means for the different domains (max=5) were for smoking (2.19±1.2), and epidemiology (2.83±1.27), while symptoms of COPD (2.23±1.06) and breathlessness (1.96±1.13) were the lowest among the domains. Conclusions There was a low level of understanding among undergraduate students in general, but the Colleges of Medicine and Pharmacy had better knowledge. On the other hand, the College of Science and Health Professions had a lower score. This indicates some areas for improvement in the education program. Appropriate development in the education program is recommended, such as increasing the awareness of symptoms of COPD and other aspects of the disease.

2.
Cureus ; 16(4): e59374, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38817488

RESUMO

Primary immunodeficiency (PID) Disorders include a variable group of diseases that are classified according to the functional defects encountered. Chronic granulomatous disease (CGD) is inherited as an X-linked recessive disorder in many cases, and it is the clinical model of disorders of phagocytosis. Skin and solid organs abscesses are the most common presenting symptoms; we will report the case of a four-day-old boy admitted to our hospital for a neck mass with purulent discharges associated with umbilical stump and circumcision site infection; the diagnosis of CGD was later confirmed by the Dihydrorhodamine (DHR) test that turned out to be positive.

3.
J Med Virol ; 96(3): e29527, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511514

RESUMO

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Vacina BNT162 , SARS-CoV-2 , Soroterapia para COVID-19 , Anticorpos Neutralizantes , Citotoxicidade Celular Dependente de Anticorpos , Anticorpos Antivirais , Vacinação
4.
Cureus ; 15(10): e47856, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021845

RESUMO

INTRODUCTION: Deep vein thrombosis (DVT) is a medical disorder that arises when a coagulation of blood forms in a deep vein, entirely or partially blocking veins, and commonly affects the lower limb. The occurrence is fairly common worldwide and it is said to increase with age, with males being at a higher risk than females. OBJECTIVE: This study aims to determine the prevalence and risk factors of DVT among adult surgical patients in Aseer Central Hospital in the Aseer Region of Saudi Arabia. METHODS: This is a cross-sectional study involving 602 adult surgical patients hospitalized in the Aseer Central Hospital. Self-administered questionnaires were used to collect data from the respondents, and the data collected were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States). Statistical tests of association were used among the categorical variables. Association between variables was considered significant when p-value was less than 0.05. Binary logistic regression was performed to eliminate the effect of confounders in determining the risk factors for developing DVT among the respondents. RESULTS: The questionnaire response rate was 100%, with the mean age of the respondents being 44.2 ± 19.7 years. The prevalence of DVT was 7% (n=42). Obesity with adjusted OR (aOR) 17.9 (95%CI =5.39-59.18), hypertension with aOR 0.3 (95%CI =0.08-1.03), ischemic heart disease with aOR4.5 (95%CI =1.18-16.83), and orthopedics aOR 0.1 (95%CI=0.013-.240) were found to be independent risk factors for developing DVT among the respondents (p-value <=0.05). Other variables like diabetes, contraception, and pregnancy were not statistically associated with the development of DVT (p-value> 0.05) in these respondents. CONCLUSION: The findings of this study indicated a significantly low prevalence in comparison to Saudi Arabian research. Key risk factors included obesity (18x higher risk), ischemic heart disease, and hypertension. Surgery location, orthopedic cast, and Doppler ultrasound also influenced risk, while age and sex weren't significant predictors.

5.
Environ Sci Pollut Res Int ; 30(27): 71322-71339, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37160857

RESUMO

Nitrite has been linked to a variety of health issues, as well as cancer and oxygen deficiency when its allowable limit is exceeded. Nitrite monitoring and detection are required due to the negative effects on public health. Metal-organic frameworks (MOFs)-based nanomaterials/composites have recently been shown to have the potential for various biological and medical applications like sensing, imaging, and drug delivery. As a result, this research creates an efficient electrochemical sensor by incorporating MOFs into polyaniline (PANI)/carbon nanotube (CNT) cast on the GCE. In situ oxidative polymerization was used to construct an aluminum succinate MOF (Al-Succin)-incorporated CNT/PANI nanocomposite (PANI/CNT@Al-Succin) and well characterized by various characterization techniques, namely, field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric-differential thermal analysis (TGA-DTA), cyclic voltammetry (CV), and four probes to measure DC electrical conductivity. Cyclic voltammetry and linear sweep voltammetry techniques were employed to detect nitrite on the surface of PANI/CNT@Al-Succin-modified glassy carbon electrode (GCE). PANI/CNT@Al-Succin-modified GCE demonstrated good current response and electrocatalytic property towards nitrite compared to bare GCE. The newly synthesized electrode exhibited a high electrocatalytic activity towards nitrite oxidation and showed a linear response ranging from 5.7 to 74.1 µM for CV and 8.55-92.62 µM for LSV. The obtained LOD values for CV (1.16 µM) and LSV (0.08 µM) were significantly below the WHO-defined acceptable nitrite limit in drinking water. Results of recovery studies for real samples of apple juice, orange juice, and bottled water were 98.92%, 99.38%, and 99.90%, respectively. These values show practical usability of PANI/CNT@Al-Succin in real samples.


Assuntos
Água Potável , Estruturas Metalorgânicas , Nanocompostos , Nanotubos de Carbono , Nanotubos de Carbono/química , Nitritos/análise , Alumínio/análise , Ácido Succínico , Espectroscopia de Infravermelho com Transformada de Fourier , Técnicas Eletroquímicas/métodos , Nanocompostos/química , Água Potável/análise , Succinatos/análise
6.
OMICS ; 27(4): 171-179, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37043379

RESUMO

Signal transducer and activator of transcription 6 (STAT6) is a multifunctional protein that plays critical functions in cell proliferation, apoptosis, differentiation, and angiogenesis. Mutations in STAT6 may contribute to the development of certain complex diseases such as cancer. This study examined single amino acid substitutions in STAT6 to pinpoint deleterious variants and their related structural and functional impairments. Data on STAT6 mutations were obtained from the Ensembl database and analyzed to evaluate the selected mutations for their pathogenicity and destabilizing or harmful effects. Specifically, we analyzed aggregation propensity, nonpacking density, and accessible surface area on the chosen mutations. The results suggest that seven out of eight mutations are less soluble, which might lead to aggregation, disrupt ordered helices, and alter strand propensity. Four mutations lay in the conserved regions of the protein, as revealed by the Consurf analysis. We found that three mutations, E318G, L365F, and R562H, change hydrophobic contacts and lead to frustration of STAT6, which can alter its stability, contributing to disease progression in cancer. In conclusion, these findings inform how single amino acid changes can destabilize STAT6. This has implications for cancer progression which warrants further experimental research.


Assuntos
Neoplasias , Humanos , Substituição de Aminoácidos , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Neoplasias/genética , Proliferação de Células
7.
Front Mol Biosci ; 10: 1158058, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968276

RESUMO

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a pronounced fibrotic tumor microenvironment, which impairs treatment response. Type I and V collagens are responsible for the densely packed fibrils in the tumor fibrosis environment. While the role of the major type I collagen in cancer is well described, less is known about the minor type V collagen. Quantifying collagen propeptides in serum has been shown to have prognostic and predictive value. In this study, we evaluated the clinical utility of measuring the propeptide of type V collagen (PRO-C5) in serum from a discovery cohort and a validation cohort of patients with PDAC as well as in non-pancreatic solid tumor types to explore the relevance of the PRO-C5 biomarker in cancer. Methods: Serum PRO-C5 was measured in three cohorts: a discovery cohort (19 healthy controls, 12 patients with chronic pancreatitis and 33 patients with PDAC (stage I-IV)), a validation cohort (800 patients with PDAC (stage I-IV)), and a non-pancreatic solid tumor type cohort of 33 healthy controls and 200 patients with 10 different non-pancreatic solid tumor types. The levels of serum PRO-C5 in patients with cancer were compared to levels in healthy controls. The association between PRO-C5 levels and overall survival (OS) was evaluated in patients with PDAC after adjusting for established prognostic factors. Results: PRO-C5 was significantly increased in serum from patients with PDAC compared to healthy controls (p < 0.001). High PRO-C5 levels were significantly associated with short OS in both the discovery- and the validation cohort, especially in early stages of PDAC (validation cohort stage II, HR = 2.0, 95%CI1.2-3.4). The association was independent of other prognostic parameters including stage, performance status and CA19-9. Furthermore, serum levels of PRO-C5 were significantly increased in serum from patients with other non-pancreatic solid tumor types compared to healthy controls. Conclusion: High levels of serum PRO-C5 is prognostic for short OS in patients with PDAC and may provide clinical value in many other tumor types beyond PDAC. This underlines the importance of type V collagen in tumor fibrosis. PRO-C5 could have the potential to be used in several aspects within drug discovery, patient stratification and drug efficacy.

8.
J Biomol Struct Dyn ; 41(22): 13415-13424, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36752377

RESUMO

Tyrosine-protein kinase CSK otherwise known as C-terminal Src kinase (CSK), is involved in multiple pathways and processes, including regulating cell growth, differentiation, migration, and immune responses. Altered expression of CSK has been associated with various complexities, including cancer, CD45 deficiency, Osteopetrosis and lupus erythematosus. Important auxiliary roles of CSK in cancer progression make it a crucial target in developing novel anticancer therapy. Thus, CSK inhibitors are of concern as potent immuno-oncology agents. In this perspective, phytochemicals can be a significant source for unraveling novel CSK inhibitors. In this study, we carried out a systematic structure-based virtual screening of bioactive phytoconstituents against CSK to identify its potential inhibitors. After a multi-step screening process, two hits (Shinpterocarpin and Justicidin B) were selected based on their druglike properties and binding affinity towards CSK. The selected hits were further analyzed for their stability and interaction via all-atom molecular dynamics (MD) simulations. The selected hits indicated their potential as selective binding partners of CSK, which can further be used for therapeutic development against CSK-associated malignancies.Communicated by Ramaswamy H. Sarma.


Assuntos
Neoplasias , Quinases da Família src , Humanos , Proteína Tirosina Quinase CSK/metabolismo , Quinases da Família src/metabolismo , Simulação de Dinâmica Molecular
9.
PLoS One ; 18(2): e0278079, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36749795

RESUMO

BACKGROUND: HIV and Syphilis are common STIs, which have become a concern and burden on healthcare systems, as many infections go untreated and lead to potentially serious complications. HIV is usually diagnosed with Western blot, PCR, and p24 antigen testing. Whereas, Syphilis is mainly diagnosed through clinical findings and serologic testing. The Medical Commission Department (MC) under MOPH is responsible for screening all newcomers to Qatar, aiming to keep the country free from serious infectious diseases. OBJECTIVE: We aimed to evaluate the diagnostic efficiency of the protocols used in the MC for screening HIV and Syphilis infections. METHODS: We conducted a retrospective study of samples analyzed by 4th Generation ARCHITECT® HIV Ag/Ab Combo and Rapid Plasma Reagin (RPR) between January to December 2019. ARCHITECT® HIV Ag/Ab Combo positive samples were confirmed by INNO-LIA™ HIVI/II and RT-PCR. RPR-reactive samples were confirmed by ARCHITECT® Syphilis Treponema pallidium Antibody (Syphilis TPA) assay. RESULTS: For HIV, data were collected from 585,587 individuals, of which 595 (0.1%) were positive by the ARCHITECT® HIV Ag/Ab Combo (Analyzer A). When all initially positive sera were re-tested on newly collected blood samples using different ARCHITECT® HIV Ag/Ab Combo analyzer (analyzer B), 99.8% (594/595) of samples were also positive, suggesting high reproducibility. The positive predictive value (PPV) between ARCHITECT® HIV Ag/Ab Combo and the INNO-LIA™ HIVI/II confirmatory assay was 31.8%. The PPV between ARCHITECT® HIV Ag/Ab Combo and HIV-PCR assay was 26.8%. Retrospective data for Syphilis were collected from a total of 97,298 individuals who visited the MC, of which 198 (0.20%) were initially positive by RPR. The PPV between RPR and Syphilis TPA confirmatory assay was 36.6%. CONCLUSION: Despite the high rate of false positivity using ARCHITECT® HIV Ag/Ab Combo and RPR screening assays, both assays have proven to be highly effective as screening testing methods.


Assuntos
Infecções por HIV , HIV-1 , Sífilis , Humanos , Infecções por HIV/diagnóstico , Anticorpos Anti-HIV , Estudos Retrospectivos , Sífilis/diagnóstico , Catar , Reprodutibilidade dos Testes , Programas de Rastreamento , Treponema , Sensibilidade e Especificidade , Imunoensaio/métodos , HIV-2
10.
Front Immunol ; 14: 1061255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817441

RESUMO

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.


Assuntos
COVID-19 , Imunoterapia Adotiva , Humanos , Vacina BNT162 , Linfócitos T CD4-Positivos , Projetos Piloto , Linfócitos T/imunologia , Memória Imunológica
11.
Curr Med Chem ; 30(23): 2592-2594, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36579388
12.
Cells ; 11(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36497023

RESUMO

Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p < 0.01 to p < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p < 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90−10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24−10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/diagnóstico , Colágeno , Colágenos Fibrilares , Fibrose , Microambiente Tumoral , Neoplasias Pancreáticas
13.
J Infect Public Health ; 15(11): 1193-1211, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36240530

RESUMO

Acute gastroenteritis is the cause of considerable mortality and morbidity worldwide, particularly among children under five years in underdeveloped countries. Most acute gastroenteritis (AGE) cases are attributed to viral etiologies, including rotavirus, norovirus, adenovirus, astrovirus, and sapovirus. This paper aimed to determine the prevalence rate of different viral etiologies of AGE in the Middle East and North Africa (MENA) region. Moreover, this paper explored rotavirus phylogenetic relatedness, compared VP7 and VP4 antigenic regions of rotavirus with vaccine strains, and explored the availability of vaccines in the MENA region. The literature search identified 160 studies from 18 countries from 1980 to 2019. The overall prevalence of rotavirus, norovirus, adenovirus, astrovirus, and sapovirus were 29.8 %, 13.9 %, 6.3 %, 3.5 %, and 3.2 % of tested samples, respectively. The most common rotavirus genotype combinations in the MENA region were G1P[8], G9P[9], and G2P[4], whereas GII.4 was the predominant norovirus genotype all of which were reported in almost all the studies with genotyping data. The comparison of VP7 and VP4 between circulating rotavirus in the MENA region and vaccine strains has revealed discrete divergent regions, including the neutralizing epitopes. Rotavirus vaccine was introduced to most of the countries of the MENA region; however, only a few studies have assessed the effectiveness of vaccine introduction. This paper provides a comprehensive update on the prevalence of the different viral agents of AGE in the MENA region.


Assuntos
Gastroenterite , Norovirus , Vacinas contra Rotavirus , Rotavirus , Criança , Humanos , Lactente , Pré-Escolar , Epidemiologia Molecular , Filogenia , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Rotavirus/genética , Genótipo , Norovirus/genética , África do Norte/epidemiologia , Oriente Médio/epidemiologia , Variação Genética , Fezes
14.
Infect Genet Evol ; 105: 105367, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36115643

RESUMO

Acute gastroenteritis (AGE) is associated with significant global morbidity and mortality, especially among children under five years of age. Viruses are well established as etiologic agents of gastroenteritis since they are the most common pathogens that contribute to the disease burden in developing countries. Despite the advances in molecular diagnosis, a substantial proportion of AGE etiology remain unresolved. We implemented a viral metagenomics pipeline to determine the potential viral etiology associated with AGE among children under the age of five years in Qatar with undiagnosed etiology. Following enriching for the viral genome, ∼1.3 billion sequences were generated from 89 stool specimens using the Illumina HiSeq platform, of which 7% were mapped to viral genomes. Human viruses were detected in 34 specimens (38.2%); 14 were adenovirus, nine coxsackievirus A16, five rotavirus (G9P[8] and G4P[8]), four norovirus (GII), one influenza A virus (H3), and one respiratory syncytial virus A (RSVA). In conclusion, the viral metagenomics approach is useful for determining AGE's etiology when routine molecular diagnostic assays fail.


Assuntos
Gastroenterite , Rotavirus , Vírus , Humanos , Criança , Lactente , Pré-Escolar , Catar/epidemiologia , Fezes , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Rotavirus/genética , Vírus/genética
15.
Biomolecules ; 12(9)2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36139154

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a hard-to-treat cancer due to the collagen-rich (fibrotic) and immune-suppressed microenvironment. A major driver of this phenomenon is transforming growth factor beta (TGF-ß). TGF-ß is produced in an inactive complex with a latency-associated protein (LAP) that can be cleaved by plasma kallikrein (PLK), hereby releasing active TGF-ß. The aim of this study was to evaluate LAP cleaved by PLK as a non-invasive biomarker for PDAC and tumor fibrosis. An ELISA was developed for the quantification of PLK-cleaved LAP-TGF-ß in the serum of 34 patients with PDAC (stage 1−4) and 20 healthy individuals. Biomarker levels were correlated with overall survival (OS) and compared to serum type III collagen (PRO-C3) and type VI collagen (PRO-C6) pro-peptides. PLK-cleaved LAP-TGF-ß was higher in patients with PDAC compared to healthy individuals (p < 0.0001). High levels (>median) of PLK-cleaved LAP-TGF-ß were associated with poor OS in patients with PDAC independent of age and stage (HR 2.57, 95% CI: 1.22−5.44, p = 0.0135). High levels of PLK-cleaved LAP-TGF-ß were associated with high PRO-C3 and PRO-C6, indicating a relationship between the PLK-cleaved LAP-TGF-ß fragment, TGF-ß activity, and tumor fibrosis. If these preliminary results are validated, circulating PLK-cleaved LAP-TGF-ß may be a biomarker for future clinical trials.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Biomarcadores/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Colágeno Tipo III , Colágeno Tipo VI , Complemento C3 , Fibrose , Humanos , Neoplasias Pancreáticas/metabolismo , Calicreína Plasmática , Prognóstico , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Neoplasias Pancreáticas
16.
Int J Mol Sci ; 23(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35456962

RESUMO

In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO-C20, using a monoclonal antibody raised against the C-terminus. PRO-C20 and PRO-C1, an ELISA targeting the N-terminal pro-peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO-C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO-C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p < 0.01−p < 0.0001). PRO-C1 was only elevated in patients with ovarian cancer. PRO-C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p < 0.0001). High PRO-C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52−11.9, p-value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO-C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/patologia , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Feminino , Humanos , Masculino , Colágenos não Fibrilares/metabolismo , Neoplasias Pancreáticas/patologia , Microambiente Tumoral , Neoplasias Pancreáticas
17.
Int J Biol Macromol ; 206: 363-370, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35240212

RESUMO

Styrene butadiene rubber (SBR), is a synthetic polymer and the most abundantly used in the tire industry, which have good collaborative properties with additives and fillers. In present work, we aim to synthesize SBR composite having the properties of graphene oxide filler and made it to be biodegradable. In composite preparation, we fabricated styrene-butadiene rubber/graphene oxide/lignin composites by adding biodegradable biomolecule of lignin fillers at varying 1-3 wt% quantities amount. Those prepared SBR composites were characterized using advanced analysis techniques, and also their biodegradability was. From microscopy examination results, the morphology of pure SBR composite had been improved after the addition of graphene oxide, while the 1 wt% lignin filled SBR sample revealed well-integrated morphology with crest-and-trough-like feature, showcasing the lignin fibrils could strengthen the molecular interaction between graphene oxide nano sheet and SBR rubber. For 2 wt% lignin filled SBR sample, it exhibited large protuberants due to the aggregation effect of lignin fibrils. However, bulky and bundle structure of protuberant was more significantly formed in 3 wt% lignin filled SBR, as a result of poor interface between lignin and SBR rubber. The porosity had also been improved for 1 wt% lignin filled SBR sample, imparting it with great surface area to act as tire in automobile application. The physico-chemical analysis also detected the trace of graphene oxide and lignin functional groups in the SBR composite. In addition, the thermal analysis revealed those lignin-filled composites had stable heat tolerance behavior, which suitably used in extreme weather condition. Moreover, the 1 wt% lignin filled SBR sample exhibited good characteristics in both mechanical and biodegradable properties. Thus, the composite of 1 wt% lignin filled SBR could be regarded as a promising candidate for green tire application in the future.


Assuntos
Lignina , Borracha , Automóveis , Butadienos , Elastômeros , Grafite , Lignina/química , Óxidos/química , Borracha/química , Estireno , Estirenos
18.
Gels ; 8(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35323274

RESUMO

Styrene-butadiene rubber (SBR) is a synthetic polymer primarily used in the tire industry, due to its good collaborative properties with additives and fillers. In the present work, we aim to synthesize an SBR composite reinforced with graphene oxide filler to be made biodegradable. In composite preparation, we fabricated styrene-butadiene rubber/graphene oxide/collagen (SBR/GO/COL) composites by adding a biodegradable biomolecule of elastin collagen fillers at 1.5 wt% and 2.5 wt%. Those prepared SBR/GO/COL composites, along with pure SBR and SBR/GO as control samples, were characterized using advanced analysis techniques, and their biodegradability was also evaluated. From microscopy examination results, the morphology of pure SBR had been improved after the addition of GO for SBR/GO composite by revealing a compact structure with a smoother surface. As for the SBR/GO/1.5COL sample, the 1.5 wt% COL filler was found to be effectively embedded in the SBR/GO matrix. However, the 2.5 wt% COL amount led to the formation of an aggregated structure in the SBR/GO/2.5COL sample due to the unreacted interface between COL filler and SBR/GO. The porosity had also been improved for SBR/GO/1.5COL sample, imparting it with a surface area suitable for tires in the automobile industry. From elemental analysis, the presence of nitrogen was detected for the collagen-filled SBR composite, proving the successful incorporation of collagen fibrils. The physicochemical analysis also detected a trace of graphene oxide and collagen functional groups in the SBR composite. In addition, the thermal analysis revealed those collagen-filled composites had stable heat tolerance behavior, which is suitably used in extreme weather conditions. Moreover, the SBR/GO/1.5COL sample exhibited good characteristics in both mechanical and biodegradable properties. Thus, the product of SBR/GO/1.5COL could be regarded as a promising composite for green tires in the auto industry in the future.

19.
J Coll Physicians Surg Pak ; 32(2): 259-261, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35108806

RESUMO

Peritoneal carcinomatosis (PC) is a common presentation of several gastrointestinal and gynecological malignancies. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is a treatment regimen recently introduced in Pakistan for PC. The goal of cytoreductive surgery is complete removal of macroscopic disease. HIPEC is administered following surgery, with the aim of eliminating disease at a microscopic level. In this study, 11 patients, who underwent CRS+HIPEC at the Shifa International Hospital, Islamabad, Pakistan, were selected. Disease severity was classified using PCI score. There were 54.5% women and 45.5% men with mean age of 48.5 ± 12.5 years. The mean PCI score was 20.3 ± 3.4. The mean time from diagnosis was 12.7 ± 11.6 months. A complete tumor resection (CC-0) was achieved in 10 (90.9%) patients, while the rest were CC-1. The duration of HIPEC circulation was 90 minutes in every patient. Postoperative morbidity was observed in 2 (18.2%) patients. No 30-day perioperative mortality was seen. It was concluded that with effective patient selection, surgical skills and center experience, CRS+HIPEC can have low perioperative morbidity and mortality, and complete cytoreduction leads to prolonged overall survival. Key Words: Peritoneal carcinomatosis, Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy.


Assuntos
Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Adulto , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia
20.
Chem Asian J ; 17(3): e202101117, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34904384

RESUMO

Here, nanocomposites of thallium oxide doped multi-walled carbon nanotube (Tl2 O MWCNT NCs) were prepared by utilizing a wet-chemical method (WCM) in an alkaline phase at low temperature. Different optical procedures (FTIR: Fourier Transform Infra-Red Spectroscopy, XRD: Powder X-ray diffraction, FESEM: Field-Emission Scanning Electron Microscopy, XEDS: X-ray Electron Dispersive Spectroscopy, TEM: Tunneling Electron Microscopy, and XPS: X-ray photoelectron spectroscopy) were used to fully characterize (optical, structural, crystalline, morphological, and elemental etc.) of the prepared Tl2 O MWCNT NCs. Modification of the thin-layer with NCs onto glassy carbon electrode (GCE) is prepared and applied for the selective and sensitive enzyme-free detection of L-cysteine by an electrochemical approach. Using a reliable current-voltage approach, analytical sensing indexes such as sensitivity, LDR, LOD, LOQ, durability, and interference were assessed by fabricated sensor probe (GCE/Tl2 O MWCNT NCs/CPM) in selective detection of L-cysteine at room temperature, whereas nafion was used as conducting polymer matrix (CPM) during the fabrication of GCE with NCs. L-cysteine calibration plot was found to be linear over an extensive range of concentration. The calibration curve was used to calculate the sensing parameters such as sensitivity (316.46 pAµM-1 cm-2 ), LOD down to (∼18.90±1.89 pM), and LOQ (63.0 pM) of the prepared sensor. The use of a simple WCM to validate the Tl2 O.MWCNT NCs is a good approach for developing a NCs-based sensor for enzyme-free biomolecule identification and detection in the biomedical and health care fields in a broad scale. This proposed sensor (GCE/Tl2 O MWCNT NCs/CPM) is used to detect selective L-cysteine in real biological samples such as human, mouse, and rabbit serum and found acceptable and satisfactory results.


Assuntos
Nanocompostos , Nanotubos de Carbono , Animais , Cisteína , Técnicas Eletroquímicas , Eletrodos , Camundongos , Óxidos , Coelhos , Tálio
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