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1.
Artigo em Inglês | MEDLINE | ID: mdl-34750905

RESUMO

AIM: To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality. METHODS: In a prospective cohort study, critically ill children (1 month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated. RESULTS: Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR) = 2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR = 1.525, 95% CI: 1.142, 2.037) and haematological (OR = 1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR = 1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality. CONCLUSIONS: Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade.

2.
Front Mol Biosci ; 8: 719056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778370

RESUMO

Most ovarian cancers, despite improvement in management of cancer, are still diagnosed at an advanced stage. Early detection plays an essential role in reducing ovarian cancer mortality and, therefore, is critically needed. Liquid biopsies-based approaches hold significant promise for cancer detection. The present study investigates a panel of epigenetic biomarkers for the detection of epithelial ovarian cancer. A qPCR assay has been developed based on the assessment of DNA methylation markers in circulating cell-free DNA as a minimally invasive tool. Herein, the promoter methylation of seven ovarian cancer-specific genes (RASSF1A, DAPK1, SOX1, HOXA9, HIC1, SPARC, and SFRP1) was analyzed quantitatively in 120 tissue samples by MethyLight assay. The best-performing genes were further evaluated for their methylation status in 70 matched serum cell-free DNA of cancerous and non-cancerous samples. Additionally, DNA methylation patterns of these best-performing genes were validated by clonal bisulfite sequencing. The ROC (Receiver-operator characteristic) curves were constructed to evaluate the diagnostic performances of both individual and combined gene panels. The seven candidate genes displayed a methylation frequency of 61.0-88.0% in tissue samples. The promoter methylation frequencies for all the seven candidate genes were significantly higher in cancer samples than in normal matched controls. In tissue samples, the multiplex MethyLight assay for HOXA9, HIC1, and SOX1 were the best performing gene panels in terms of sensitivity and specificity. The three best-performing genes exhibited individual frequencies of 53.0-71.0% in serum CFDNA, and the multiplex assay for these genes were identified to discriminate serum from cancer patients and healthy individuals (area under the curve: HOXA9+HIC1 = 0.95, HIC1+SOX1 = 0.93 and HOXA9+SOX1 = 0.85). The results of MethyLight showed high concordance with clonal bisulfite sequencing results. Individual genes and combined panel exhibited better discriminatory efficiencies to identify ovarian cancer at various stages of disease when analyzed in tissue and serum cell-free DNA. We report a qPCR-based non-invasive epigenetic biomarker assay with high sensitivity and specificity for OC screening. Our findings also reveal the potential utility of methylation-based detection of circulating cell-free tumor DNA in the clinical management of ovarian cancer.

3.
JGH Open ; 5(10): 1190-1196, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34622007

RESUMO

Background and Aim: Human Leukocyte Antigen DQ (HLA-DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case-control study, we used next-generation sequencing to determine HLA-DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Methods: HLA-DQA1 and ~DQB1 loci were amplified, using long-range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA-international ImMunoGeneTics (IMGT) database. Results: HLA-DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64-12.47) and HLA-DQB1*02:01 (OR 8.59, 95% CI 5.75-12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA-DQA1*05:01 ~ HLA-DQB1*02:01 (OR 8.56, 95% CI 5.67-13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA-DQA1*05:01 ~ HLA-DQB1*02:01 (OR 2.34, 95% CI 1.61-3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA-DQA1*05:01 ~ HLA-DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. Conclusion: HLA-DQA1*05:01 ~ HLA-DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg.

4.
Dig Dis Sci ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499270

RESUMO

BACKGROUND: While celiac disease (CeD) is considered to affect primarily the small intestine, pathological changes in other parts of the gastrointestinal tract (GIT) are also known to occur. IgA anti-tissue transglutaminase-2 antibody (anti-TG2 Ab) deposits at the site of involvement is one of the methods to establish CeD-related tissue pathology. AIMS: To explore the utility of IgA anti-TG2 Ab deposits in pan-gastrointestinal mucosal biopsies as evidence of CeD-related pathologies. METHODS: Forty-two treatment-naive patients with CeD and 45 patients with irritable bowel syndrome were included as cases and controls, respectively. Mucosal biopsies were collected from the esophagus, stomach, duodenum, and rectosigmoid regions at baseline from cases and controls, and additionally after 6-months of gluten-free diet in cases. All biopsies were evaluated for histological changes and subjected to dual-color immunohistochemical staining for identifying IgA anti-TG2 Ab deposits. RESULTS: Significantly higher number of patients with CeD had lymphocytic esophagitis (9.7% vs. 0%, P = 0.05), lymphocytic gastritis (35% vs. 8.8%, P < 0.01) and lymphocytic colitis (17.4% vs. 0%, P < 0.05) than that in controls. IgA anti-TG2 Ab deposits were observed in significantly more numbers in esophagus (30.9% vs. 6%, P < 0.001), stomach (62.2% vs. 9.3%, P < 0.01), duodenum (88.5% vs. 0%, P < 0.001) and rectum (17.4% vs. 0%, P < 0.05) than that in controls. There was a decline, but not statistically significant, in severity of lymphocytosis and intensity of IgA anti-TG2 Ab deposits in follow-up biopsies. CONCLUSION: Significantly higher number of patients with CeD had evidence of lymphocytic infiltration and IgA anti-TG2 deposits along GIT suggesting that CeD affects other parts of GIT.

5.
Int J Cancer ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569064

RESUMO

Oral cavity squamous cell carcinoma (OSCC) affects more than 30 000 individuals in the United States annually, with smoking and alcohol consumption being the main risk factors. Management of early-stage tumors usually includes surgical resection followed by postoperative radiotherapy in certain cases. The cervical lymph nodes (LNs) are the most common site for local metastasis, and elective neck dissection is usually performed if the primary tumor thickness is greater than 3.5 mm. However, postoperative histological examination often reveals that many patients with early-stage disease are negative for neck nodal metastasis, posing a pressing need for improved risk stratification to either avoid overtreatment or prevent the disease progression. To this end, we aimed to identify a primary tumor gene signature that can accurately predict cervical LN metastasis in patients with early-stage OSCC. Using gene expression profiles from 189 samples, we trained K-top scoring pairs models and identified six gene pairs that can distinguish primary tumors with nodal metastasis from those without metastasis. The signature was further validated on an independent cohort of 35 patients using real-time polymerase chain reaction (PCR) in which it achieved an area under the receiver operating characteristic (ROC) curve and accuracy of 90% and 91%, respectively. These results indicate that such signature holds promise as a quick and cost effective method for detecting patients at high risk of developing cervical LN metastasis, and may be potentially used to guide the neck treatment regimen in early-stage OSCC.

6.
3 Biotech ; 11(6): 304, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34194897

RESUMO

This research article attempts a bibliometric analysis of global research on biofertilizers carried out from 2000 to 2019. The main purpose of this analysis is in technology foresight; to understand where the research interest lies within the domain of biofertilizer and also to identify the major research networks. The analysis is based on 344 research articles identified using the ISI Web of Science tool, which is processed further using VOSviewer. The results demonstrated that there is an increase in the number of articles, particularly from countries like Brazil, India China, the USA, and Iran. The research focus has been on the assessment of nitrogen fixation capacity of biofertilizers, and the yield improvement due to biofertilizers, and the economics of biofertilizer application. Our findings can act as a useful reference for the researchers, and provide insights for directing future research on biofertilizers.

7.
Indian J Gastroenterol ; 40(4): 402-409, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34244963

RESUMO

BACKGROUND: While the small intestine is the main site of disease, many other organs are affected by celiac disease (CeD). Dental enamel defects (DED) are common in patients with CeD, and these are one of the indicators of CeD, even when no other symptom of CeD is present. Data on dental and oral cavity manifestations in Asian patients with CeD are scanty. The purpose of the current study was to evaluate dental and oral manifestations in Asian patients with CeD. METHODS: We recruited 118 patients with biopsy-confirmed CeD (36 treatment naïve and 82 on follow-up for at least 1 year on gluten-free diet [GFD]) and 40 controls. Diagnosis was made as per the standard criteria. Oral and dental manifestations were evaluated by a dental surgeon. The DED were evaluated according to Aine's criteria. RESULTS: Overall higher number of patients with CeD (66.9%), both treatment naïve (69.4%) and those on GFD (65.8%) had DED in comparison to controls (20%) (odds ratio, 8.1, 95% confidence interval [CI] 3.4-19.2; p<0.001). Specific/bilaterally symmetrical DED were significantly higher in patients with CeD than controls. Recurrent aphthous ulcers were also significantly higher in patients with CeD. Approximately 80.6% and 63.4% treatment-naïve patients and those on GFD, respectively reported dry mouth sensation, which was significantly higher than the controls. CONCLUSION: Almost two-third of patients with CeD had DED. Physicians and dietitians caring for patients with CeD should be trained in identification of DED and other oral manifestations of CeD.

8.
J Clin Pathol ; 74(12): 766-773, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33789921

RESUMO

AIMS: Despite clinical evidence of liver involvement in patients with coeliac disease (CeD), there is a lack of a method to prove this association. METHODS: Of 146 treatment-naive patients with CeD, 26 had liver dysfunction. Liver biopsies and corresponding small intestinal biopsies were obtained from these 26 patients. Multicolour immunohistochemical and immunofluorescence confocal microscopic studies were performed on paraffin-embedded tissue to detect the IgA/anti-TG2 deposits. Follow-up liver biopsies were taken after a gluten-free diet. RESULTS: Twenty-six out of the 146 patients (17.8%) with suspected coeliac-associated liver disease on histological examination revealed irregular sinusoidal dilatation in 15 (57.6%), steatohepatitis in 4 (15.3%), non-specific chronic hepatitis in 3 (11.5%), autoimmune hepatitis in 2 (7.6%) biopsies, including cirrhosis in one of them, irregular perisinusoidal fibrosis and changes of non-cirrhotic portal fibrosis in one biopsy each (3.8%). IgA/anti-tTG deposits were observed in 22 (84.6%) liver biopsies by dual immunohistochemistry technique, and in 24 (92.3%) by confocal immunofluorescence technique and in all corresponding duodenal biopsies (100%). Overall, IgA/anti-tTG deposits showed 100% sensitivity, 77% specificity and 85% positive predictive value for establishing an association of extraintestinal pathology and CeD using archived tissues. Follow-up liver biopsies could be obtained in five patients; four of them showed not only resolution of the histological lesions but disappearance of IgA/anti-tTG co-localisation. CONCLUSIONS: Data of the present study adds to the body of evidence that liver lesions in patients with CeD are disease related and may have been caused by a similar pathogenic mechanism that causes intestinal changes.


Assuntos
Autoanticorpos/análise , Doença Celíaca/imunologia , Proteínas de Ligação ao GTP/imunologia , Imuno-Histoquímica , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Fígado/imunologia , Transglutaminases/imunologia , Adolescente , Adulto , Biópsia , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Feminino , Imunofluorescência , Humanos , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Fígado/patologia , Masculino , Microscopia Confocal , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Eur J Clin Nutr ; 75(8): 1245-1253, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33462461

RESUMO

OBJECTIVE: Gluten-free (GF) diet is the only reliable treatment for patients with celiac disease (CeD), but data on the extent of gluten contamination in GF food available in India is scanty. We evaluated gluten content in labeled, imported, and non-labeled GF food products currently available in the Indian market. METHODS: Overall, 794 processed and commercially available packaged GF products (labeled GF (n = 360), imported GF (n = 80), and non-labeled/naturally GF (n = 354)) were collected from supermarkets of National Capital Region of India. Those unavailable in stores were purchased from e-commerce sites or directly from the manufacturers. Gluten level in them was determined by Ridascreen Gliadin sandwich R5 enzyme-linked immunosorbent assay (R-Biopharm AG, Germany). As per Codex Alimentarius and Food Safety and Standard Authority of India, "gluten free" labeled products must not contain > 20 mg/kg of gluten. RESULTS: Overall, 10.1% of 794 GF products including 38 (10.8%) of 360 labeled and 42 (11.8%) of 354 non-labeled/naturally GF food products had gluten content > 20 mg/kg (range: 24.43-355 and 23.2-463.8 mg/kg, respectively). None of the imported GF products had gluten more than the recommended limits. Contaminated products most commonly belonged to cereal and their products (flours, coarse grains, pasta/macaroni, snack foods) pulse flours, spices, and bakery items. CONCLUSIONS: A substantial proportion (10.1%) of GF food products (both labeled and non-labeled) available in India have gluten content greater than the prescribed limits of <20 mg/kg. Physicians, dietitians, support group, and patients with CeD should be made aware of this fact and regulatory bodies should ensure quality assurance.


Assuntos
Doença Celíaca , Glutens , Dieta Livre de Glúten , Farinha , Rotulagem de Alimentos , Humanos
10.
ISA Trans ; 109: 380-388, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33041012

RESUMO

This paper presents an interesting application of two different generalized integrators connected in a cascade configuration. A Second-Order Generalized Integrator (SOGI) and a Reduced-Order Generalized Integrator (ROGI) controller have been considered to cascade. The designed controller is applied to filter distortions in the grid voltage to generate a synchronizing signal as well as estimate the fundamental component of load current. Thus, their combination can achieve synchronization as well as find application in the improvement of the power quality of the distribution grid. In addition, the performance of SOGI-ROGI with the frequency locked loop (FLL) under frequency variations has been improved. Extensive simulation and hardware results are presented to illustrate the actions of designed controller under normal and distorted grid conditions. Results under highly distorted grid and non-linear loading conditions are presented vis-à-vis simple generalized integrators considered independently.

11.
Intest Res ; 19(1): 106-114, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32312034

RESUMO

BACKGROUND/AIMS: Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease. METHODS: Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan. RESULTS: In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively. CONCLUSIONS: Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.

13.
Indian J Gastroenterol ; 39(6): 608-613, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33098064

RESUMO

Alanine aminotransferase (ALT) is a cytosolic enzyme specific to hepatocytes, and its elevated level in the peripheral blood denotes liver cell injury. Detection of persistently elevated ALT levels during routine health check-up in asymptomatic or symptomatic individuals provides a window of opportunity to explore the causes of liver cell damage and for the timely institution of appropriate treatment. This was a retrospective study using a subset of the data from a previous community-based prospective study done for the estimation of the prevalence of celiac disease (CD) in India,  during which estimation of ALT levels in the blood samples of participants was also carried out. Of the 11,053 individuals (4399 [39.8%] males; mean age 37.9 ± 13.3 years) screened, 6209 consented to provide blood samples for testing for CD. Of these, assessment of serum ALT levels was done in 6083 (2235 [36.7%] males) patients. ALT was elevated above the upper limit of normal (ULN) (> 40 IU/L) in 1246 (20.5%) of the participants and > 1.5 times (> 60 IU/L) in 329 (5.4%) participants. The ALT levels were elevated more frequently in men as compared to women (29.4% vs. 15.3%, p < 0.001). There was a significant positive correlation (Pearson correlation coefficient [r] = 0.25, p < 0.0001) between ALT levels and body mass index (BMI). With increasing age, there was a significant decrease in the proportion of subjects with ALT ≥ 1.5× ULN (p < 0.001). Our results suggest that a high proportion (20.5%) of individuals otherwise considered healthy have values of ALT level in the serum above the "normal" range/cut-off suggesting likely ongoing underlying liver damage. There is a need for measures to evaluate and, if found, treat the underlying cause for the same.


Assuntos
Alanina Transaminase/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Saúde Pública/estatística & dados numéricos , Adulto , Fatores Etários , Biomarcadores/sangue , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores Sexuais , Adulto Jovem
14.
Sci Rep ; 10(1): 14722, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895425

RESUMO

Objectives of the current work were to investigate the role of photoperiod and melatonin in the alteration of immune responses in a reptilian species. Animals were kept on a regimen of short or long days. Blood was obtained and leucocytes were isolated to study various innate immune responses. Lymphocytes were separated from blood by density gradient centrifugation and were used to study proliferation. Respiratory burst activity was measured through nitrobluetetrazolium reduction assay while nitric oxide production by leucocytes was assayed by nitrite assay. Lymphocytes were isolated and used to study proliferation with and without B and T cell mitogens. Photoperiodic manipulation acted differentially on leucocyte counts. Nitrite release was increased while superoxide production was decreased in cultures obtained from the snakes kept on the short day regimen. Significant enhancement of mitogen induced lymphocyte proliferation was observed in cultures from the animals kept in either long or short days compared to cultures from the animals kept in natural ambient day length. Use of in vitro melatonin showed that lymphocytes from the animals, kept in long days, were more reactive. Photoperiod induces changes in immune status which may permit adaptive functional responses in order to maintain seasonal energetic budgets of the animals. Physiological responses (like elevated immune status) are energetically expensive, therefore, animals have evolved a strategy to reduce immune functions at times when energy is invested in reproductive activities. Natrix piscator breeds from September to December and elevated pineal hormone in winter suppresses reproduction while immunity is stimulated.


Assuntos
Ritmo Circadiano/imunologia , Colubridae/imunologia , Imunidade Celular/imunologia , Imunidade Inata/imunologia , Animais , Cruzamento/métodos , Proliferação de Células/fisiologia , Água Doce , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Masculino , Melatonina/imunologia , Fotoperíodo , Reprodução/imunologia , Estações do Ano
16.
NMR Biomed ; 33(8): e4305, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32394522

RESUMO

Celiac disease (CeD) is an autoimmune enteropathy caused by gluten intake in genetically predisposed individuals. We investigated the metabolism of CeD by metabolic profiling of intestinal mucosa, blood plasma and urine using NMR spectroscopy and multivariate analysis. The metabolic profile of the small intestinal mucosa was compared between patients with CeD (n = 64) and disease controls (DCs, n = 30). The blood plasma and urinary metabolomes of CeD patients were compared with healthy controls (HCs, n = 39). Twelve metabolites (proline (Pro), arginine (Arg), glycine (Gly), histidine (His), glutamate (Glu), aspartate, tryptophan (Trp), fumarate, formate, succinate (Succ), glycerophosphocholine (GPC) and allantoin (Alln)) of intestinal mucosa differentiated CeD from controls. The metabolome of blood plasma with 18 metabolites (Pro, Arg, Gly, alanine, Glu, glutamine, glucose (Glc), lactate (Lac), acetate (Ace), acetoacetate (AcAc), ß-hydroxybutyrate (ß-OHB), pyruvate (Pyr), Succ, citrate (Cit), choline (Cho), creatine (Cr), phosphocreatine (PCr) and creatinine) and 9 metabolites of urine (Pro, Trp, ß-OHB, Pyr, Succ, N-methylnicotinamide (NMN), aminohippurate (AHA), indoxyl sulfate (IS) and Alln) distinguished CeD from HCs. Our data demonstrated changes in nine metabolic pathways. The altered metabolites were associated with increased oxidative stress (Alln), impaired healing and repair mechanisms (Pro, Arg), compromised anti-inflammatory and cytoprotective processes (Gly, His, NMN), altered energy metabolism (Glc, Lac, ß-OHB, Ace, AcAc, Pyr, Succ, Cit, Cho, Cr and PCr), impaired membrane metabolism (GPC and Cho) and intestinal dysbiosis (AHA and IS). An orthogonal partial least square discriminant analysis model provided clear differentiation between patients with CeD and controls in all three specimens. A classification model built by combining the distinguishing metabolites of blood plasma and urine samples gave an AUC of 0.99 with 97.7% sensitivity, 93.3% specificity and a predictive accuracy of 95.1%, which was higher than for the models built separately using small intestinal mucosa, blood plasma and urine. In conclusion, a panel of metabolic biomarkers in intestinal biopsies, plasma and urine samples has potential to differentiate CeD from controls and may complement traditional tests to improve the diagnosis of CeD.


Assuntos
Doença Celíaca/metabolismo , Mucosa Intestinal/metabolismo , Espectroscopia de Ressonância Magnética , Metaboloma , Adolescente , Adulto , Aminoácidos/análise , Aminoácidos/sangue , Aminoácidos/urina , Biópsia , Doença Celíaca/sangue , Doença Celíaca/urina , Dispepsia/metabolismo , Feminino , Refluxo Gastroesofágico/metabolismo , Humanos , Mucosa Intestinal/química , Intestino Delgado/química , Intestino Delgado/metabolismo , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Sensibilidade e Especificidade
17.
Sci Rep ; 10(1): 6163, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249798

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

18.
Int J Cancer ; 147(6): 1740-1752, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32191343

RESUMO

Accumulated evidence revealed that aberrant CpG island hypermethylation plays an important role in carcinogenesis which can serve as a promising target for molecular detection in body fluids. Despite a myriad of attempts to diagnose ovarian cancer (OC) at an early stage, this clinical aim remains a major challenge. To date, no single biomarker is able to accurately detect early OC in either tissue or body fluid. Aberrant DNA methylation patterns in circulating DNA provide highly specific cancer signals. In our study, we establish a novel panel of methylation-specific genes for the development of a TaqMan based qPCR assay to quantify methylation levels. We analyzed promoter methylation of homeobox A9 (HOXA9) and hypermethylated in cancer 1 (HIC1) quantitatively in 120 tissue samples and in 70 matched serum cell-free DNA (CFDNA) of cancerous and noncancerous samples by MethyLight assay. HOXA9 and HIC1 methylation occurred in 82.3 and 80.0% of OC tissue samples in singleplex assay, thereby confirming that methylation was highly cancer-specific. When either or both gene promoter showed methylation, the sensitivity was 88.2% with a specificity of 88.6% in tissue samples. The combined sensitivity for this novel marker panel in serum CFDNA was 88.9% (area under the curve [AUC] = 0.95). In contrast, no hypermethylation was observed in serum from matched cancer-free control women. Our results confirm the elevated performance of novel epigenetic marker panel (HOXA9 and HIC1) when analyzed in tissue and matched serum samples. Our findings reveal the potential of this biomarker panel as a suitable diagnostic serum biomarker for early screening of OC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/diagnóstico , Detecção Precoce de Câncer/métodos , Proteínas de Homeodomínio/genética , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Ovarianas/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/cirurgia , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Ilhas de CpG/genética , Metilação de DNA , Detecção Precoce de Câncer/instrumentação , Epigênese Genética , Epigenômica/instrumentação , Epigenômica/métodos , Estudos de Viabilidade , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/sangue , Humanos , Fatores de Transcrição Kruppel-Like/sangue , Biópsia Líquida/métodos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Ovário/patologia , Ovário/cirurgia , Valor Preditivo dos Testes , Período Pré-Operatório , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , Adulto Jovem
19.
J Gastroenterol Hepatol ; 35(3): 438-445, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31498492

RESUMO

BACKGROUND AND AIM: Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non-invasive biomarker(s) that can predict the presence of villous abnormalities. METHODS: Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I-FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut-off values were derived, and the results were further validated in a prospective validation cohort. RESULTS: While level of plasma citrulline was significantly lower, the levels of plasma I-FABP and serum Reg1α were significantly higher in patients with CeD (n = 131) in comparison with healthy (n = 216) and disease controls (n = 133), and their levels reversed after a gluten-free diet (GFD). In the model of predicted enteropathy (n = 70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I-FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was  ≤ 30 µM/L and I-FABP levels were ≥ 1100 pg/mL, respectively. The results were validated in a prospective validation cohort (n = 104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade > 2 at calculated cut-off values of citrulline and I-FABP. CONCLUSIONS: Plasma citrulline  ≤ 30 µM/L is the most consistent, highly reproducible non-invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD.


Assuntos
Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Citrulina/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Mucosa Intestinal/anormalidades , Litostatina/sangue , Adulto , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Valor Preditivo dos Testes , Adulto Jovem
20.
Plant J ; 101(1): 87-100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483536

RESUMO

Auxin signaling mediated by various auxin/indole-3-acetic acid (Aux/IAAs) and AUXIN RESPONSE FACTORs (ARFs) regulate lateral root (LR) development by controlling the expression of downstream genes. LATERAL ROOT PRIMORDIUM1 (LRP1), a member of the SHORT INTERNODES/STYLISH (SHI/STY) family, was identified as an auxin-inducible gene. The precise developmental role and molecular regulation of LRP1 in root development remain to be understood. Here we show that LRP1 is expressed in all stages of LR development, besides the primary root. The expression of LRP1 is regulated by histone deacetylation in an auxin-dependent manner. Our genetic interaction studies showed that LRP1 acts downstream of auxin responsive Aux/IAAs-ARFs modules during LR development. We showed that auxin-mediated induction of LRP1 is lost in emerging LRs of slr-1 and arf7arf19 mutants roots. NPA treatment studies showed that LRP1 acts after LR founder cell specification and asymmetric division during LR development. Overexpression of LRP1 (LRP1 OE) showed an increased number of LR primordia (LRP) at stages I, IV and V, resulting in reduced emerged LR density, which suggests that it is involved in LRP development. Interestingly, LRP1-induced expression of YUC4, which is involved in auxin biosynthesis, contributes to the increased accumulation of endogenous auxin in LRP1 OE roots. LRP1 interacts with SHI, STY1, SRS3, SRS6 and SRS7 proteins of the SHI/STY family, indicating their possible redundant role during root development. Our results suggested that auxin and histone deacetylation affect LRP1 expression and it acts downstream of LR forming auxin response modules to negatively regulate LRP development by modulating auxin homeostasis in Arabidopsis thaliana.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Epigênese Genética/genética , Epigênese Genética/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Mutação/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
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