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1.
Braz. j. biol ; 84: e252555, 2024. tab, ilus
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1364519

RESUMEN

The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.


O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.


Asunto(s)
Conejos , Tetracloruro de Carbono , Aceite de Palma , Biomarcadores/sangre , Hígado
2.
Braz. j. biol ; 84: e249472, 2024. tab, ilus
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1364512

RESUMEN

Leaf rust, caused by Puccinia triticina, is the most common rust disease of wheat. The fungus is an obligate parasite capable of producing infectious urediniospores. To study the genetic structure of the leaf rust population 20 RAPD primers were evaluated on 15 isolates samples collected in Pakistan. A total of 105 RAPD fragments were amplified with an average of 7 fragments per primer. The number of amplified fragments varied from 1 to 12. GL Decamer L-07 and GL Decamer L-01 amplified the highest number of bands (twelve) and primer GL Decamer A-03 amplified the lowest number of bands i.e one. Results showed that almost all investigated isolates were genetically different that confirms high genetic diversity within the leaf rust population. Rust spores can follow the migration pattern in short and long distances to neighbor areas. Results indicated that the greatest variability was revealed by 74.9% of genetic differentiation within leaf rust populations. These results suggested that each population was not completely identical and high gene flow has occurred among the leaf rust population of different areas. The highest differentiation and genetic distance among the Pakistani leaf rust populations were detected between the leaf rust population in NARC isolate (NARC-4) and AARI-11and the highest similarity was observed between NARC isolates (NARC-4) and (NARC-5). The present study showed the leaf rust population in Pakistan is highly dynamic and variable.


A ferrugem da folha, causada por Puccinia triticina, é a ferrugem mais comum do trigo. O fungo é um parasita obrigatório, capaz de produzir urediniósporos infecciosos. Para estudar a estrutura genética da população de ferrugem da folha, 20 primers RAPD foram avaliados em 15 amostras de isolados coletadas no Paquistão. Um total de 105 fragmentos RAPD foram amplificados com uma média de 7 fragmentos por primer. O número de fragmentos amplificados variou de 1 a 12. GL Decamer L-07 e GL Decamer L-01 amplificaram o maior número de bandas (doze), e o primer GL Decamer A-03 amplificou o menor número de bandas, ou seja, um. Os resultados mostraram que quase todos os isolados investigados eram geneticamente diferentes, o que confirma a alta diversidade genética na população de ferrugem da folha. Os esporos de ferrugem podem seguir o padrão de migração em distâncias curtas e longas para áreas vizinhas. Os resultados indicaram que a maior variabilidade foi revelada por 74,9% da diferenciação genética nas populações de ferrugem. Esses resultados sugeriram que cada população não era completamente idêntica e um alto fluxo gênico ocorreu entre a população de ferrugem da folha de diferentes áreas. A maior diferenciação e distância genética entre as populações de ferrugem da folha do Paquistão foram detectadas entre a população de ferrugem da folha no isolado NARC (NARC-4) e AARI-11 e a maior similaridade foi observada entre os isolados NARC (NARC-4) e (NARC-5). O presente estudo mostrou que a população de ferrugem da folha no Paquistão é altamente dinâmica e variável.


Asunto(s)
Triticum/parasitología , Biomarcadores , Plagas Agrícolas , Hongos/genética , Puccinia/genética
3.
Adv Kidney Dis Health ; 30(1): 47-52, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36723282

RESUMEN

Omics applications in nephrology may have relevance in the future to improve clinical care of kidney disease patients. In a short term, patients will benefit from specific measurement and computational analyses around biomarkers identified at various omics-levels. In mid term and long term, these approaches will need to be integrated into a holistic representation of the kidney and all its influencing factors for individualized patient care. Research demonstrates robust data to justify the application of omics for better understanding, risk stratification, and individualized treatment of kidney disease patients. Despite these advances in the research setting, there is still a lack of evidence showing the combination of omics technologies with artificial intelligence and its application in clinical diagnostics and care of patients with kidney disease.


Asunto(s)
Enfermedades Renales , Nefrología , Humanos , Inteligencia Artificial , Aprendizaje Automático , Biomarcadores , Enfermedades Renales/diagnóstico
4.
PLoS One ; 18(2): e0269436, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36724153

RESUMEN

Cystatin C, a cysteine protease inhibitor, is used as a biomarker of renal function. It offers several advantages compared to creatinine, and formulas for the estimation of the glomerular filtration rate based on cystatin C have been developed. Recently, several proteoforms of cystatin C have been discovered, including an intact protein with a hydroxylated proline at the N-terminus, and N-terminal truncated forms. There is little knowledge about the biological significance of these proteoforms. METHODS: Cross-sectional study of patients with different stages of chronic renal disease (pre-dialysis n = 53; hemodialysis n = 51, renal transplant n = 53). Measurement of cystatin C proteoforms by MALDI-TOF MS, assessment of medicine prescription using the first two levels of the Anatomical Therapeutic chemical system from patients' records. RESULTS: Patients receiving hemodialysis had the highest cystatin C concentrations, followed by pre-dialysis patients and patients with a renal transplant. In all groups, the most common proteoforms were native cystatin C and CysC 3Pro-OH while the truncated forms made up 28%. The distribution of the different proteoforms was largely independent of renal function and total cystatin C. However, the use of corticosteroids (ATC-L02) and immunosuppressants (ATC-H04) considerably impacted the distribution of proteoforms. CONCLUSION: The different proteoforms of cystatin C increased proportionally with total cystatin C in patients with chronic kidney disease. Prescription of corticosteroids and immunosuppressants had a significant effect on the distribution of proteoforms. The biological significance of these proteoforms remains to be determined.


Asunto(s)
Trasplante de Riñón , Insuficiencia Renal Crónica , Humanos , Cistatina C , Estudios Transversales , Insuficiencia Renal Crónica/terapia , Tasa de Filtración Glomerular , Biomarcadores , Inmunosupresores , Creatinina/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-36724195

RESUMEN

BACKGROUND AND OBJECTIVES: Primary progressive multiple sclerosis (PPMS) displays a highly variable disease progression with a characteristic accumulation of disability, what makes difficult its diagnosis and efficient treatment. The identification of microRNAs (miRNAs)-based signature for the early detection in biological fluids could reveal promising biomarkers to provide new insights into defining MS clinical subtypes and potential therapeutic strategies. The objective of this cross-sectional study was to describe PPMS miRNA profiles in CSF and serum samples compared with other neurologic disease individuals (OND) and relapsing-remitting MS (RRMS). METHODS: First, a screening stage analyzing multiple miRNAs in few samples using OpenArray plates was performed. Second, individual quantitative polymerase chain reactions (qPCRs) were used to validate specific miRNAs in a greater number of samples. RESULTS: A specific profile of dysregulated circulating miRNAs (let-7b-5p and miR-143-3p) was found downregulated in PPMS CSF samples compared with OND. In addition, in serum samples, miR-20a-5p and miR-320b were dysregulated in PPMS against RRMS and OND, miR-26a-5p and miR-485-3p were downregulated in PPMS vs RRMS, and miR-142-5p was upregulated in RRMS compared with OND. DISCUSSION: We described a 2-miRNA signature in CSF of PPMS individuals and several dysregulated miRNAs in serum from patients with MS, which could be considered valuable candidates to be further studied to unravel their actual role in MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that specific miRNA profiles accurately distinguish PPMS from RRMS and other neurologic disorders.


Asunto(s)
MicroARNs , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Crónica Progresiva/genética , Estudios Transversales , Biomarcadores , Recurrencia
6.
World J Surg Oncol ; 21(1): 27, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36721236

RESUMEN

BACKGROUND: Recent evidence suggests that the box H/ACA small nucleolar RNA (snoRNA)-ended long noncoding RNA (lncRNA), SLERT, plays a critical role in gene regulation. However, its role in cancer remains undetermined. Herein, we explored its implication in human endometrial cancer (EC). METHODS: EC plasma and tissue samples were collected for the detection of SLERT expression using qRT-PCR method. The functional investigation was tested by CCK-8 and transwell assays. Luciferase reporter, RNA pull-down, and immunoprecipitation (RIP) assays were used to determine the regulatory network involved in SLERT. The in vivo effect of SLERT was tested by caudal vein lung metastasis model. RESULTS: Stable knockdown of SLERT significantly inhibited EC cell (KLE and AN3CA) migration and invasion, while it did not affect cell viability. SLERT induced epithelial-mesenchymal transition (EMT) via elevating N-cadherin and Vimentin and downregulating E-cadherin. Further investigation showed that SLERT directly binds to METTL3, increasing the m6A levels of BDNF mRNA; then, the m6A sites were read by IGF2BP1, enhancing BDNF mRNA stability, followed by the activation of BDNF/TRKB signaling, an inducer of EMT. The animal model showed that overexpression of SLERT increased EC cell lung metastasis, and this effect was effectively blocked by BDNF silencing or treatment with TRKB inhibitor k252a. Clinically, EC patients have high levels of SLERT both in tissue or plasma, which might be used as a biomarker of diagnosis and prognosis. CONCLUSION: Our findings, for the first time, uncover the metastasis-promoting effect of SLERT in EC via in vitro and in vivo evidence, providing a potential therapeutic target for metastatic EC treatment.


Asunto(s)
Neoplasias Endometriales , Neoplasias Pulmonares , ARN Largo no Codificante , Animales , Femenino , Humanos , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo/genética , Cadherinas , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Pulmonares/secundario , Metiltransferasas
7.
J Neuroinflammation ; 20(1): 20, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36721258

RESUMEN

Chronic microglia activation post-stroke is associated with worse neurological and cognitive outcomes. However, measurement of microglia activation in vivo is currently limited. Plasma derived extracellular vesicles (EVs) are cell-specific indicators that may allow for non-invasive measurement of microglia phenotype. The aim of this study was to identify activation-state specific microglia EVs (MEVs) in vitro followed by validation in an experimental stroke model. Following pro-inflammatory activation, MEVs contain the microglia protein TMEM119 alongside increased expression of the Toll-like receptor 4 co-receptor CD14. Immunoprecipitation followed by fluorescent nanoparticle tracking analysis (ONI Nanoimager) was used to confirm the isolation of TMEM119+/CD14+ EVs from rat plasma. Electron microscopy confirmed that TMEM119 and CD14 localize to the MEV membrane. To model ischemia, plasma was collected from 3-month wildtype Fischer344 rats prior to, 7 and 28 days after endothelin-1 or saline injection into the dorsal right striatum. Fluorescently labelled MEVs were directly measured in the plasma using nanoflow cytometry (Apogee A60 Microplus). We report a significant increase in circulating TMEM119+/CD14+ EVs 28-days post-stroke in comparison to baseline levels and saline-injected rats, which correlated weakly with stroke volume. TMEM119+/MHC-II+ EVs were also increased post-stroke in comparison to baseline and saline-injected animals. This study is the first to describe an EV biomarker of activated microglia detected directly in plasma following stroke and represents a future tool for the measurement of microglia activity in vivo.


Asunto(s)
Vesículas Extracelulares , Microglía , Accidente Cerebrovascular , Animales , Ratas , Biomarcadores , Cuerpo Estriado , Fenotipo
8.
J Transl Med ; 21(1): 67, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36726153

RESUMEN

BACKGROUND: Frailty, defined as physical performance impairment, is a common condition in older adults and can anticipate the development of sarcopenia, a geriatric syndrome characterized by loss of muscle strength and mass. microRNAs (miRNAs) are short molecules of RNA endowed with the ability to modulate gene expression; miRNAs are present in serum and are considered potential biomarkers for several diseases. Serum concentration of miR-451a, miR-93-5p, miR-155-5p, miR-421-3p, miR-425-5p, miR-495-3p and miR-744-5p was recently shown to be altered in sarcopenic patients. METHODS: We verified if a particular miRNAs pattern could be detected in frailty as well by analyzing these molecules in 50 frail and 136 robust subjects. Additionally, a subgroup of these subjects (15 frail and 30 robust) underwent a 12-week program based on a multicomponent exercise protocol (VIVIFRAIL) consisting of resistance training, gait retraining, and balance training. After the program, serum miRNAs concentration was measured again, to verify whether the physical activity had an effect on their concentration. Moreover, clinical characteristics and indicators of physical performance of all subjects were compared before and after intervention to verify the effect of the VIVIFRAIL program. RESULTS: At the end of the multicomponent exercise program, Short Physical Performance Battery (SPPB) score as well right and left handgrip (p < 0.05) were significantly increased in frail subjects; right and left handgrip significantly were increased also in robust subjects (p < 0.05). Interestingly, the variation of SPPB was significantly higher in frail compared to robust subjects (p < 0.0001). Moreover, at the end of the program, in frail compared to robust subjects: miR-451a serum concentration was significantly increased (frail: 6.59 × 104; 1.12 × 104-2.5 × 105 c/ng; robust: 2.31 × 104; 1.94 × 103-2.01 × 105 c/ng) (p < 0.05); and 2) miR-93-5p and miR-495-3p serum concentration was reduced, whereas that of miR-155-5p was significantly increased (p < 0.05 in both cases). Serum concentration of miR-93-5p and miR-495-3p was decreased, and that of miR-155-5p was increased at the end of the program in robust subjects alone, statistical significance being reached for miR-93-5p alone (p = 0.02). CONCLUSION: These results suggest that serum miR-451a should be investigated as a potential biomarker for frailty and show that the VIVIFRAIL multicomponent program modulates circulatory miRNAs expression, at least in older adults.


Asunto(s)
Fragilidad , MicroARNs , Sarcopenia , Humanos , Anciano , Fragilidad/genética , Anciano Frágil , Fuerza de la Mano , MicroARNs/genética , Biomarcadores , Ejercicio Físico
9.
Tex Heart Inst J ; 50(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36724451

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is common in middle-aged adults and has been associated with various cardiovascular disorders; endothelial dysfunction may play a role in the pathogenesis of these disorders in patients with OSA. Endothelial cell specific molecule-1 (endocan) is a marker of vascular pathology, which is correlated with endothelial dysfunction. This study investigates the relationship between serum endocan levels and OSA severity in patients with hypertension. METHODS: A retrospective review included 48 patients with OSA and hypertension but without conventional cardiovascular risk factors, and 67 patients with OSA who did not have hypertension. The correlation between serum endocan levels and the apnea-hypopnea index (AHI) was investigated in both groups. RESULTS: There was a significant correlation between the serum endocan level and the AHI in patients with OSA and hypertension (r = 0.308; P = .033), but there was no such correlation in patients without hypertension (r = 0.193; P = .118). However, when both groups were combined (ie, all patients with OSA), there was a significant correlation between serum endocan levels and the AHI (r = 0.228; P = .014). On multiple logistic regression analysis, endocan levels were independent predictors of OSA severity in patients with OSA and hypertension (P = .029). CONCLUSION: In patients with OSA and hypertension, serum endocan levels are significantly correlated with the AHI. Measurement of endocan may have a place in evaluating patients with OSA and hypertension for adverse cardiovascular events, and they may even help to guide OSA therapy for these patients.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Apnea Obstructiva del Sueño , Adulto , Persona de Mediana Edad , Humanos , Biomarcadores , Polisomnografía/efectos adversos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Enfermedades Cardiovasculares/etiología
10.
JCO Precis Oncol ; 7: e2200351, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36724411

RESUMEN

PURPOSE: Adjuvant imatinib treatment is recommended for patients with localized gastrointestinal stromal tumor (GIST) at high risk of recurrence. Almost half of high-risk patients are cured by surgery alone, indicating a need for improved selection of patients for adjuvant therapy. The aim of this study was to investigate if genomic tumor complexity could be used as a prognostic biomarker. METHODS: The discovery cohort consisted of patients who underwent resection of primary GIST at Oslo University Hospital between 1998 and 2020. Karyotypes were categorized as simple if they had ≤ 5 chromosomal changes and complex if there were > 5 chromosomal aberrations. Validation was performed in an independent patient cohort where chromosomal imbalances were mapped using comparative genomic hybridization. RESULTS: Chromosomal aberrations were detected in 206 tumors, of which 76 had a complex karyotype. The most frequently observed changes were losses at 14q, 22q, 1p, and 15q. The 5-year recurrence-free survival (RFS) in patients classified as very low, low, or intermediate risk was 99%. High-risk patients with a simple tumor karyotype had an estimated 5-year RFS of 94%, and patients with a complex karyotype had an estimated 5-year RFS of 51%. A complex karyotype was associated with poor RFS in patients with and without adjuvant imatinib treatment and in multivariable analysis adjusted for tumor site, size, mitotic count, and rupture. The prognostic impact of genomic complexity was confirmed in the validation cohort. In both cohorts, the 5-year disease-specific survival was > 90% for high-risk patients with genomically simple tumors. CONCLUSION: Genomic tumor complexity is an independent prognostic biomarker in localized, high-risk GIST. Recurrences were infrequent for tumors with simple karyotypes. De-escalation of adjuvant imatinib treatment should be explored in patients with cytogenetically simple GISTs.


Asunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Humanos , Mesilato de Imatinib/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Hibridación Genómica Comparativa , Quimioterapia Adyuvante , Biomarcadores , Genómica , Aberraciones Cromosómicas/inducido químicamente
11.
South Med J ; 116(2): 188-194, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36724534

RESUMEN

OBJECTIVES: Low-income Latinx youth are disproportionately affected by obesity, which results in an increased risk of cardiometabolic abnormalities. Biomarker tracking may be useful for the early identification of obesity comorbidities in young Latinx children. Hence, we aimed to compare cardiometabolic biomarkers between age- and sex-matched pairs of elementary school-aged Latinx children with obesity versus healthy weight. METHODS: This case-control study compared cardiometabolic biomarkers between 13 pairs of age- and sex-matched elementary school-age (median 6.5 years) Latinx children with obesity (body mass index for age ≥ 95th percentile) as compared with their healthy weight (between the 5th and 85th percentiles) counterparts. Anthropometric measures and a fasted venous blood sample were taken for the analysis of lipids, glycemic, inflammatory, endocrine, and hepatic markers. Group differences were tested by the Mann-Whitney U or χ2 test. RESULTS: Cases had higher insulin (P = 0.003), hemoglobin A1c (P = 0.002), triglycerides (P = 0.023), and C-reactive protein (P < 0.001) and lower high-density lipoprotein (P = 0.002). Hepatic markers were similar, with alanine aminotransferase elevated among both groups. CONCLUSIONS: The aforementioned biomarkers may be more sensitive to higher adiposity risk in this young Latinx population; however, elevated hepatic markers may indicate an ethnic/genetic predisposition to abnormal liver function. Research should be replicated in a larger group to confirm these findings.


Asunto(s)
Enfermedades Cardiovasculares , Obesidad , Adolescente , Niño , Humanos , Estudios de Casos y Controles , Factores de Riesgo , Obesidad/epidemiología , Obesidad/complicaciones , Índice de Masa Corporal , Biomarcadores , Enfermedades Cardiovasculares/epidemiología , Hispánicos o Latinos
12.
Adv Cancer Res ; 157: 23-56, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36725111

RESUMEN

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%-90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase early detection of HCC and the proportion of patients that can be offered curative therapies. Recent work in novel mass spec-based methods for glycomic and glycopeptide analysis for discovery and confirmation of markers for early detection of HCC versus cirrhosis is reviewed in this chapter. Results from recent work in these fields by several groups and the progress made in developing markers of early HCC which can outperform the current serum-based markers are described and discussed. Also, recent developments in isoform analysis of glycans and glycopeptides and in various mass spec fragmentation methods will be described and discussed.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Espectrometría de Masas , Biomarcadores , Biomarcadores de Tumor , Glicopéptidos/análisis
13.
Adv Cancer Res ; 157: 57-81, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36725113

RESUMEN

The development of robust cancer biomarkers is the most effective way to improve overall survival, as early detection and treatment leads to significantly better clinical outcomes. Many of the cancer biomarkers that have been identified and are clinically utilized are glycoproteins, oftentimes a specific glycoform. Aberrant glycosylation is a common theme in cancer, with dysregulated glycosylation driving tumor initiation and metastasis, and abnormal glycosylation can be detection both on the tissue surface and in serum. However, most cancer types are heterogeneous in regard to tumor genomics, and this heterogeneity extends to cancer glycomics. This limits the sensitivity of standalone glycan-based biomarkers, which has slowed their implementation clinically. However, if targeted biomarker development can take into account genomic tumor information, the development of complementary biomarkers that target unique cancer subgroups can be accomplished. This idea suggests the need for algorithm-based cancer biomarkers, which can utilize multiple biomarkers along with relevant demographic information. This concept has already been established in the detection of hepatocellular carcinoma with the GALAD score, and an algorithm-based approach would likely be effective in improving biomarker sensitivity for additional cancer types. In order to increase cancer diagnostic biomarker sensitivity, there must be more targeted biomarker development that considers tumor genomic, proteomic, metabolomic, and clinical data while identifying tumor biomarkers.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores de Tumor/genética , Proteómica , Glicoproteínas , Biomarcadores , Glicómica , Polisacáridos
14.
Zhongguo Zhong Yao Za Zhi ; 48(2): 507-516, 2023 Jan.
Artículo en Chino | MEDLINE | ID: mdl-36725240

RESUMEN

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide , Periploca , Ratas , Animales , Cisteína , Citidina Difosfato Colina , Farmacología en Red , Fosforilcolina , Metabolómica , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Glicerofosfolípidos , Metionina , Purinas , Cromatografía Líquida de Alta Presión
15.
Zhongguo Zhong Yao Za Zhi ; 48(2): 492-506, 2023 Jan.
Artículo en Chino | MEDLINE | ID: mdl-36725239

RESUMEN

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.


Asunto(s)
Medicamentos Herbarios Chinos , Glomerulonefritis , Ratas , Animales , Creatinina , Ácido Araquidónico , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/farmacología , Glomerulonefritis/tratamiento farmacológico , Metabolómica , Biomarcadores , Proteínas Sanguíneas , Urea
16.
Artículo en Chino | MEDLINE | ID: mdl-36725293

RESUMEN

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.


Asunto(s)
Encefalopatías , Intoxicación por Monóxido de Carbono , Estimulación Transcraneal de Corriente Directa , Humanos , Intoxicación por Monóxido de Carbono/complicaciones , Estimulación Transcraneal de Corriente Directa/efectos adversos , Pronóstico , Oxígeno , Encefalopatías/etiología , Subunidad beta de la Proteína de Unión al Calcio S100 , Fosfopiruvato Hidratasa , Biomarcadores
17.
Artículo en Chino | MEDLINE | ID: mdl-36725300

RESUMEN

Welding operations are widely present in the manufacturing production process, involving a large number of occupational groups, and are the key occupations where work injuries and occupational diseases occur in China. For different welding processes and welding materials, the content and focus of occupational health monitoring are different. At present, the item of occupational health examination in welding operation is in poor consistency with the on-site exposure of occupational hazard factors, and it is mainly concentrated in the stage of disease development, which can not reflect the early health damage caused by welding dust exposure in time. The emergence of biomarkers of welding dust can make up for this defect. Therefore, it is of great significance to describe the current situation of occupational health monitoring of welding dust and summarize the research progress of related biomarkers for the early prevention of diseases caused by welding dust and the practice of occupational health monitoring.


Asunto(s)
Contaminantes Ocupacionales del Aire , Exposición Profesional , Salud Laboral , Soldadura , Exposición Profesional/análisis , Polvo/análisis , Biomarcadores , Contaminantes Ocupacionales del Aire/efectos adversos , Contaminantes Ocupacionales del Aire/análisis
18.
Se Pu ; 41(2): 131-141, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-36725709

RESUMEN

Alcohol intake is an important risk factor for cardiovascular disease, liver disease, and diabetes. The accurate and objective evaluation of alcohol intake is important for disease prevention and intervention, as well as alcohol intake monitoring. Phosphatidylethanol (PEth) is a potential clinical biomarker of alcohol consumption. Monitoring PEth levels can provide an objective and quantitative basis for alcohol intake studies. Unlike other current alcohol biomarkers, PEth can only be produced in the presence of alcohol. Therefore, PEth is highly specific for alcohol intake and not affected by confounding factors, such as age, gender, hypertension, kidney disease, liver disease, and other comorbidities. Because of its long half-life and high specificity for alcohol intake, PEth may be used as a tool for monitoring drinking behavior in the clinical, transportation, and other fields. Given rapid developments in mass spectrometry technology over the past decade, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the preferred method for PEth detection. However, most current LC-MS/MS methods focus on the determination of one or several PEth homologs, and the number of PEth homologs that can be determined simultaneously is relatively limited. Moreover, the detection capacity of the available methods remains insufficient, and their analytical sensitivity for some PEth homologs must be further improved. In this study, a novel LC-MS/MS method based on an intelligent scheduled time-zone negative multiple reaction monitoring acquisition technology (Scheduled-MRM) was developed. The technology monitors two ion channels in each PEth to ensure reliable results and can quantify 18 PEth homologs in human whole blood simultaneously. Methanol-methyl tert-butyl ether-water was used as the extraction system. An XBridge C18 column (100 mm×2.1 mm, 3.5 µm) was selected for gradient elution with 2.5 mmol/L ammonium acetate isopropanol solution and 2.5 mmol/L ammonium acetate aqueous solution-acetonitrile (50∶50, v/v) as the mobile phases. Negative electronic spray ionization in scheduled-MRM mode was applied for MS/MS detection. The method was validated to have a linear range of 10-2500 ng/mL with correlation coefficients greater than 0.9999. The limits of detection and quantification were 0.7-2.8 and 2.2-9.4 ng/mL, respectively, and the spiked recoveries ranged from 91.0% to 102.2%. The method was confirmed to be simple, rapid, and precise, and subsequently validated for the measurement of 18 PEth homologs in human blood. Scheduled-MRM can assign a suitable scan time to each ion channel and effectively reduce the number of concurrent ion pairs monitored per unit time. This technology overcomes the problem of insufficient dwell time caused by an excessive number of ion channels, thereby avoiding the redundant monitoring of non-retention times. Scheduled-MRM significantly improved the detection sensitivity, data acquisition quality, and signal response of the proposed method. Whole blood samples from 359 volunteers with regular drinking habits were analyzed using this method. The total PEth concentrations ranged from 51.13 ng/mL to 2.89 µg/mL, with a mean of 363.16 ng/mL. PEth 16∶0/18∶1 and 16∶0/18∶2 were the two most abundant homologs, with mean concentrations of 74.21 and 48.75 ng/mL, accounting for approximately 20.43% and 13.42%, respectively, of the total PEth. Spearman correlation analyses showed that the PEth homologs correlated well with each other, γ-glutamyltransferase, a clinically available biological marker of alcohol, and other clinical biochemical parameters related to liver and kidney function. Overall, the method was demonstrated to be sensitive, precise, and accurate; thus, it may be an effective tool for monitoring alcohol intake in the clinical and other fields.


Asunto(s)
Etanol , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Tecnología , Biomarcadores , Cromatografía Líquida de Alta Presión
19.
Radiología (Madr., Ed. impr.) ; 65(1): 3-11, ene.-feb. 2023. ilus, tab
Artículo en Español | IBECS | ID: ibc-215018

RESUMEN

Introducción El objetivo del estudio fue determinar el desempeño diagnóstico de la ecografía pélvica transabdominal, la evaluación del desarrollo mamario por ecografía y la edad ósea en la identificación del inicio de la pubertad, en población pediátrica femenina de la Clínica Las Américas, Medellín, Colombia. Métodos Se incluyeron pacientes femeninas de 11 años o menos, remitidas entre marzo de 2016 y marzo de 2019 por la aparición de signos de inicio de la pubertad. Se usó como estándar de referencia para el diagnóstico de pubertad la medición basal de hormona luteinizante (LH) sérica, con la cual se comparó la ultrasonografía pélvica y mamaria, así como la edad ósea. Se realizaron cálculos de sensibilidad, especificidad, valores predictivos positivo y negativo (VPP y VPN), razones de verosimilitud (LR+y LR-) y análisis por subgrupos de edades. Se analizaron 43 pacientes. La evaluación ecográfica del desarrollo mamario demostró la sensibilidad más alta (94,1%) dentro de todos los parámetros de imagen evaluados, aunque con baja especificidad. No obstante, características como la longitud del cuerpo del útero mayor de 3,0cm y la presencia de eco endometrial fueron altamente específicas para la identificación del inicio de la pubertad, particularmente en pacientes de 8 años o menos. Conclusión La ecografía pélvica, la valoración ecográfica del Tanner mamario y la evaluación de la edad ósea son herramientas útiles para la confirmación por imagen del inicio de la pubertad. Los resultados de este estudio apoyan su utilización en la práctica clínica, en el abordaje de trastornos puberales en niñas. (AU)


Introduction This study aimed to determine the diagnostic performance of transabdominal pelvic ultrasonography and bone age in identifying the onset of puberty in girls at the Clínica Las Américas in Medellín, Colombia. Methods We included girls aged ≤ 11 years referred to our clinic between March 2016 and March 2019 for signs of puberty. We compared the findings on pelvic and breast ultrasonography and bone age versus the baseline measurement of luteinizing hormone (LH) in serum, used as the reference standard for identifying the onset of puberty. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios, analyzing subgroups of patients of different ages. Results We analyzed 43 patients. Ultrasound assessment of breast development had the highest sensitivity (94.1%) of all the imaging parameters evaluated, but its specificity was low. However, characteristics such as the length of the body of the uterus> 3.0cm and the presence of endometrial echoes were highly specific for identifying the onset of puberty, particularly in patients aged ≤ 8 years. Conclusion Pelvic ultrasonography, ultrasonographic assessment of Tanner stage of breast development, and the evaluation of bone age are useful tools for the imaging confirmation of the onset of puberty. The results of this study support the use of these techniques in clinical practice in the workup for pubertal disorders in girls. (AU)


Asunto(s)
Humanos , Femenino , Pubertad/fisiología , Biomarcadores/sangre , Determinación de la Edad por el Esqueleto/métodos , Mano/diagnóstico por imagen , Endometrio/diagnóstico por imagen , Pubertad Precoz/diagnóstico , Estudios Transversales , Sensibilidad y Especificidad , Valor Predictivo de las Pruebas
20.
Med. intensiva (Madr., Ed. impr.) ; 47(2): 84-89, feb. 2023.
Artículo en Inglés | IBECS | ID: ibc-215029

RESUMEN

Objective Survivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. Design Observational and prospective study. Setting Three Spanish Intensive Care Units. Patient Patients with sepsis or septic shock according to Sepsis-3 Consensus criteria. Interventions Serum survivin concentrations were determined at moment of sepsis diagnosis. Main variable of interest Mortality at 30 days. Results A total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946–0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943–0.989; p=0.004). Conclusions There is an association between septic patient mortality and low blood survivin concentrations (AU)


Objetivo Survivina es un miembro de la familia de proteínas inhibidoras de apoptosis. No existen datos sobre la asociación entre la mortalidad de los pacientes sépticos y las concentraciones de survivina en sangre. Por tanto, el objetivo de este estudio fue determinar si existe esa asociación. Diseño Estudio observacional y prospectivo. Ámbito Tres Unidades de Cuidados Intensivos españolas. Pacientes Pacientes con sepsis o shock séptico según criterios del Consenso Sepsis-3. Intervenciones Se determinaron las concentraciones séricas de survivina en el momento del diagnóstico de la sepsis. Variable de interés principal Mortalidad a los 30 días. Resultados Un total de 204 pacientes se incluyeron en el estudio, 75 (36,8%) de los cuales fallecieron en los primeros 30 días. Menor edad (p<0,001), niveles séricos de ácido láctico (p=0,001), tasa de shock séptico (p=0,001) y SOFA (p<0,001), y mayores niveles de survivina en suero (p=0,001) exhibieron los pacientes supervivientes (n=129) en comparación con los fallecidos (n=75). El análisis de regresión logística múltiple mostró una asociación entre las concentraciones séricas de survivina y la mortalidad independientemente del SOFA, ácido láctico, edad, INR, tiempo de tromboplastina parcial activada (aPTT) y tratamiento antimicrobiano empírico adecuado (OR=0,968; IC 95%=0,946-0,990; p=0,005), y también independientemente del APACHE-II, ácido láctico, plaquetas, INR, aPTT y tratamiento antimicrobiano empírico adecuado (OR=0,966; IC 95%=0,943-0,989; p=0,004). Conclusiones Existe una asociación entre la mortalidad de los pacientes sépticos y las concentraciones bajas de survivina en sangre (AU)


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Survivin/sangre , Sepsis/sangre , Sepsis/mortalidad , Estudios Prospectivos , Biomarcadores/sangre , Curva ROC
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