Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
J Appl Genet ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358594

RESUMEN

Head and neck squamous cell carcinoma (HNSC) is a diverse group of tumors arising from oral cavity, oropharynx, larynx, and hypopharynx squamous epithelium, posing significant morbidity. Aquaporins (AQPs) are membrane proteins forming water channels, some associated with carcinomas. Chromobox (CBX) family is known to modulate physiological and oncological processes. In our study, we analyzed AQPs and CBXs having significant expression followed by their prognostic and mutational assessment. Next, we performed enrichment and tumor infiltration analysis followed by HPA validation. Lastly, we established a 3-node miRNA-TF-mRNA regulatory network and performed protein-protein docking of the highest-degree subnetwork motif between TF and mRNA. Significant upregulation of CBX3/2 and downregulation of AQP3/5/7 correlated with poor overall survival (OS) in HNSC patients. The most significant pathway, GO-BP, GO-MF, and GO-CC terms associated with AQP3 and CBX3 were passive transport by aquaporins, response to vitamin, glycerol channel activity, and condensed chromosome, centromeric region. AQP3 negatively correlated with [Formula: see text] T cells, positively with [Formula: see text] T cells and B cells, and negatively with tumor purity, whereas CBX3 positively correlated with [Formula: see text] T cells, negatively with [Formula: see text] T cells and B cells, and positively with tumor purity. Three-node miRNA-TF-mRNA regulatory network revealed a highest-degree subnetwork motif comprising one TF (SMAD3), one miRNA (miR-423-5p), and one mRNA (AQP3). Protein-protein interaction studies suggested a direct interaction between AQP3 and Smad3 proteins. We concluded that AQP3 and CBX3 hold potential as treatment strategies and individual prognostic biomarkers, while further protein-protein interaction studies of AQP3 could offer insights into its interactions with Smad3 proteins.

2.
Emerg Microbes Infect ; 12(2): 2278899, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37929689

RESUMEN

Exchange of antimicrobial resistance genes via mobile genetic elements occur in the gut which can be transferred from mother to neonate during birth. This study is the first to analyse transmissible colistin resistance gene, mcr, in pregnant mothers and neonates. Samples were collected from pregnant mothers (rectal) and septicaemic neonates (rectal and blood) and analysed for the presence of mcr, its transmissibility, genome diversity, and exchange of mcr between isolates within an individual and across different individuals (not necessarily mother-baby pairs). mcr-1.1 was detected in rectal samples of pregnant mothers (n = 10, 0.9%), but not in neonates. All mcr-positive mothers gave birth to healthy neonates from whom rectal specimen were not collected. Hence, the transmission of mcr between these mother-neonate pairs could not be studied. mcr-1.1 was noted only in Escherichia coli (phylogroup A & B1), and carried few resistance and virulence genes. Isolates belonged to diverse sequence types (n = 11) with two novel STs (ST12452, ST12455). mcr-1.1 was borne on conjugative IncHI2 bracketed between ISApl1 on Tn6630, and the plasmids exhibited similarities in sequences across the study isolates. Phylogenetic comparison showed that study isolates were related to mcr-positive isolates of animal origin from Southeast Asian countries. Spread of mcr-1.1 within this study occurred either via similar mcr-positive clones or similar mcr-bearing plasmids in mothers. Though this study could not build evidence for mother-baby transmission but the presence of such genes in the maternal specimen may enhance the chances of transmission to neonates.


Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Animales , Recién Nacido , Femenino , Humanos , Embarazo , Antibacterianos/farmacología , Proteínas de Escherichia coli/genética , Filogenia , Madres , Colistina , Plásmidos/genética , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana
3.
J Appl Genet ; 64(4): 737-748, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37653284

RESUMEN

Lung cancer is one of the most commonly occurring malignant cancers with the highest rate of mortality globally. Difference between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) and their treatment strategies according to genetic markers may be helpful in reducing the cancer progression and increasing the overall survival (OS) in patients. LUSC is known for comparatively less typical onco-drivers, target therapy resistance, marked genomic complexity, and a reasonably higher mutation rate. The mRNA-seq data and clinical information of LUAD and LUSC cohorts from UCSC Xena comprising 437 and 379 patient samples were extracted. Differential expression and weighted network analyses revealed 47 and 18 hub differentially expressed genes (DEGs) corresponding to LUAD and LUSC cohorts. These hub DEGs were further subjected to protein-protein interaction network (PPIN) and OS analyses. Lower mRNA expression levels of both RPS15A and RPS7 worsened the OS of LUSC patients. Additionally, both these prognostic biomarkers were validated via external sources such as UALCAN, cBioPortal, TIMER, and HPA. RPS7 had higher mutation frequency compared to RPS15A and showed significant negative correlations with infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, and macrophages. Our findings provided novel insights into biomarker discovery and the critical role of ribosomal biogenesis especially smaller ribosomal subunit in pathogenesis of LUSC.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Pronóstico , Multiómica , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/genética , Pulmón/patología , ARN Mensajero/metabolismo
4.
Funct Integr Genomics ; 23(3): 223, 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37410302

RESUMEN

The anillin actin-binding protein (ANLN) is immensely overexpressed in cancers, including lung cancer (LC). Phytocompounds have gained interest due to their broader potential and reduced unwanted effects. Screening numerous compounds presents a challenge, but in silico molecular docking is pragmatic. The present study aims to identify the role of ANLN in lung adenocarcinoma (LUAD), along with identification and interaction analysis of anticancer and ANLN inhibitory phytocompounds followed by molecular dynamics (MD) simulation. Using a systematic approach, we found that ANLN is significantly overexpressed in LUAD and mutated with a frequency of 3.73%. It is linked with advanced stages, clinicopathological parameters, worsening of relapse-free survival (RFS), and overall survival (OS), pinpointing its oncogenic and prognostic potential. High-throughput screening and molecular docking of phytocompounds revealed that kaempferol (flavonoid aglycone) interacts strongly with the active site of ANLN protein via hydrogen bonds, Vander Waals interactions, and acts as a potent inhibitor. Furthermore, we discovered that ANLN expression was found to be significantly higher (p) in LC cells compared to normal cells. This is a propitious and first study to demonstrate ANLN and kaempferol interactions, which might eventually lead to removal of rout from cell cycle regulation posed by ANLN overexpression and allow it to resume normal processes of proliferation. Overall, this approach suggested a plausible biomarker role of ANLN and the combination of molecular docking subsequently led to the identification of contemporary phytocompounds, bearing symbolic anticancer effects. The findings would be advantageous for pharmaceutics but require validation using in vitro and in vivo methods. HIGHLIGHTS: • ANLN is significantly overexpressed in LUAD. • ANLN is implicated in the infiltration of TAMs and altering plasticity of TME. • Kaempferol (potential ANLN inhibitor) shows important interactions with ANLN which could remove the alterations in cell cycle regulation, imposed by ANLN overexpression eventually leading to normal process of cell proliferation.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Proteínas de Microfilamentos/metabolismo , Quempferoles , Pronóstico , Simulación del Acoplamiento Molecular , Multiómica , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo
6.
OMICS ; 27(5): 227-236, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37155625

RESUMEN

Breast cancer (BC) is the second-most common type and among the leading causes of worldwide cancer-related deaths. There is marked person-to-person variability in susceptibility to, and phenotypic expression and prognosis of BC, a predicament that calls for personalized medicine and individually tailored therapeutics. In this study, we report new observations on prognostic hub genes and key pathways involved in BC. We used the data set GSE109169, comprising 25 pairs of BC and adjacent normal tissues. Using a high-throughput transcriptomic approach, we selected data on 293 differentially expressed genes to establish a weighted gene coexpression network. We identified three age-linked modules where the light-gray module strongly correlated with BC. Based on the gene significance and module membership features, peptidase inhibitor 15 (PI15) and KRT5 were identified as our hub genes from the light-gray module. These genes were further verified at transcriptional and translational levels across 25 pairs of BC and adjacent normal tissues. Their promoter methylation profiles were assessed based on various clinical parameters. In addition, these hub genes were used for Kaplan-Meier survival analysis, and their correlation with tumor-infiltrating immune cells was investigated. We found that PI15 and KRT5 may be potential biomarkers and potential drug targets. These findings call for future research in a larger sample size, which could inform diagnosis and clinical management of BC, thus paving the way toward personalized medicine.


Asunto(s)
Neoplasias de la Mama , Transcriptoma , Humanos , Femenino , Transcriptoma/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Pronóstico , Medicina de Precisión , Perfilación de la Expresión Génica
7.
ACS Omega ; 8(13): 12098-12123, 2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37033843

RESUMEN

Here, we have investigated some physicochemical parameters to understand the molecular interactions by means of density (ρ) measurement, measurement of viscosity (η), refractive index(n D) measurement, and conductance and surface tension measurements between two significant aqueous ionic liquid solutions: benzyl trimethyl ammonium chloride (BTMAC) and benzyl triethyl ammonium chloride (BTEAC) in an aqueous l-methionine (amino acid) solution. The apparent molar volume (Φv), coefficient of viscosity (B), and molar refraction (R M) have been used to analyze the molecular interaction behavior associated in the solution at various concentrations and various temperatures. With the help of some important equations such as the Masson equation, the Jones-Doles equation, and the Lorentz-Lorenz equation, very significant parameters, namely, limiting apparent molar volumes (Φv 0 ), coefficient of viscosity (B), and limiting molar refraction (R M 0), respectively, are obtained. These parameters along with specific conductance (κ) and surface tension (σ) are very much helpful to reveal the solute-solvent interactions by varying the concentration of solute molecules and temperature in the solution. Analyses of Δµ1 0#, Δµ2 0#, TΔS 2 0#, ΔH 2 0#, and thermodynamic data provide us valuable information about the interactions. We note that l-Met in 0.005 molality BTEAC ionic liquid at 308.15 K shows maximum solute-solvent interaction, while l-Met in 0.001 molality BTMAC aqueous solution of ionic liquid at 298.15 K shows the minimum one. Spectroscopic techniques such as Fourier transform infrared (FTIR), 1H-NMR, and UV-vis also provide supportive information about the interactions between the ionic liquid and l-methionine in aqueous medium. Furthermore, adsorption energy, reduced density gradient (RDG), and molecular electrostatic potential (MESP) maps obtained by the application of density functional theory (DFT) have been used to determine the type of interactions, which are concordant with the experimental observations.

8.
J Microsc Ultrastruct ; 10(1): 1-6, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35433263

RESUMEN

Background: The pathogenesis of oral submucous fibrosis (OSF) still remains conflicting and has been linked to alterations in epithelial thickness, fibrosis, and vascularity. Although changes in these individual parameters have been extensively studied in relation to epithelial dysplasia their combined relation with dysplasia has not been studied much. Any such relation, if present, may further help in understanding this disease process. Therefore, the aim of this study was to assess the relationship between epithelial thickness, fibrosis, and vascularity with dysplasia in OSF. Materials and Methods: The study consisted of 30 OSF patients. Incisional biopsy was taken from the most fibrosed area of the buccal mucosa. Hematoxylin-Eosin-stained slides were assessed for epithelial thickness, fibrosis, and vascularity using image analysis software. The slides were also assessed for epithelial dysplasia. Relationship of epithelial atrophy, fibrosis, and vascularity with dysplasia was assessed using one-way ANOVA. Pearson's correlation coefficient was used for evaluating the relationship between epithelial thickness, fibrosis, and vascularity. Results: Epithelial dysplasia was found in all patients. Eleven patients had mild (36. 67%), thirteen had moderate (43.33%), and six had severe (20%) dysplasia. None of the parameters were found to have a significant relationship with dysplasia. However, moderate and positive correlation was found between epithelial thickness and fibrosis. This relation was statistically significant. Conclusion: Positive correlation between epithelial thickness and fibrosis in present study therefore contradicts the hypothesis of fibrosis induced epithelial atrophy. As dysplasia is influenced by multiple factors therefore habits and burning sensation needs to be incorporated in future studies assessing dysplasia in OSF.

9.
Biology (Basel) ; 10(8)2021 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-34439992

RESUMEN

Head and neck squamous cell carcinoma (HNSC) is one of the most common malignant tumors worldwide with a high rate of morbidity and mortality, with 90% of predilections occurring for oral squamous cell carcinoma (OSCC). Cancers of the mouth account for 40% of head and neck cancers, including squamous cell carcinomas of the tongue, floor of the mouth, buccal mucosa, lips, hard and soft palate, and gingival. OSCC is the most devastating and commonly occurring oral malignancy, with a mortality rate of 500,000 deaths per year. This has imposed a strong necessity to discover driver genes responsible for its progression and malignancy. In the present study we filtered oral squamous cell carcinoma tissue samples from TCGA-HNSC cohort, which we followed by constructing a weighted PPI network based on the survival of patients and the expression profiles of samples collected from them. We found a total of 46 modules, with 18 modules having more than five edges. The KM and ME analyses revealed a single module (with 12 genes) as significant in the training and test datasets. The genes from this significant module were subjected to pathway enrichment analysis for identification of significant pathways and involved genes. Finally, the overlapping genes between gene sets ranked on the basis of weighted PPI module centralities (i.e., degree and eigenvector), significant pathway genes, and DEGs from a microarray OSCC dataset were considered as OSCC-specific hub genes. These hub genes were clinically validated using the IHC images available from the Human Protein Atlas (HPA) database.

10.
J Oral Maxillofac Pathol ; 25(Suppl 1): S37-S41, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34083968

RESUMEN

Mucoceles are common cystic lesions in the oral cavity. It may occur in different locations in the oral mucosa due to trauma or obstruction of minor salivary gland ducts with the lower lip as the predominant site. However, mucoceles located on the ventral surface of the tongue originating from the anterior lingual salivary glands are extremely rare and often overlooked during screening procedures because of their asymptomatic nature. Here, we report an interesting case of mucocele on the anterior ventral surface of the tongue in an 11-year-old female based on the clinical and histopathological diagnosis. Moreover, mucoceles should be considered as one of the differential diagnoses while evaluating a growth involving the ventral surface of the tongue in young female children.

11.
Vaccine ; 39(30): 4108-4116, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34120764

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500 µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also elicited Th-1 response as evidenced by elevated IFN-γ levels.


Asunto(s)
COVID-19 , Vacunas de ADN , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Formación de Anticuerpos , Vacunas contra la COVID-19 , China , Escherichia coli , Cobayas , Humanos , Ratones , Modelos Animales , Conejos , Ratas , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/genética
12.
J Family Med Prim Care ; 10(3): 1327-1331, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34041173

RESUMEN

BACKGROUND: Anemia is the commonest nutritional deficiency disorder in the world, particularly in developing countries. Though anemia is easily treatable and largely preventable disease if timely detected, it still continues to be significantly prevalent among pregnant women. AIM: The aim of this study was to measure the extent of anemia in pregnancy and to assess the association of risk factors with anemia. STUDY DESIGN: Hospital-based cross-sectional descriptive study. MATERIALS AND METHODS: A total of 200 women were selected among pregnant women attending antenatal clinic. Sampling was done by selecting every fifth woman visiting antenatal clinic within the duration of two months on alternate days. Data were collected using a predesigned, pretested semi-structured schedule. Hemoglobin concentrations were also recorded for each patient. Data were analyzed using Chi-square test and 'T' test of significance. A value of P < 0.05 was considered significant. RESULTS: We found overall prevalence of anemia to be 90% among pregnant women. Most of the anemic patients (60.5%) belong to moderate severity according to the World Health Organization classification. Three factors namely socioeconomic status, gravida and time of 1st antenatal visit were significantly associated with prevalence of anemia in pregnancy (P < 0.05). CONCLUSION: In this study, a high prevalence of anemia was found in pregnant women. Low socioeconomic status, multigravida and delayed visit to antenatal clinic were significantly associated with anemia in pregnancy. So, awareness and education programs should be generated to make people come to know about anemia, its complications during pregnancy and ways to prevent it.

13.
J Oral Maxillofac Pathol ; 25(3): 478-484, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35281146

RESUMEN

Background: It has been reported that oral squamous cell carcinoma (OSCC) is associated with the presence of potentially malignant disorders (PMDs) in 15%-48% of cases. Among PMDs, oral leukoplakia (OL) is the most common, with 16%-62% of cases associated with OSCC. Hence, in the present study, we have analyzed demographic data and re-evaluated immunohistochemical (IHC) data of OL cases and aimed to correlate the clinical, histopathological and IHC aspects of OL. Materials and Methods: The data of histopathologically diagnosed cases of OL were retrieved from the archives. These data were further evaluated for age, gender, duration, site, size, side, habits, clinical staging and histopathological grading. IHC re-evaluation of OL tissues was done using epithelial cadherin (E-cadherin), n = 20; human MutL homolog 1 (hMLH1), n = 30; CD1a (n = 30); vimentin (n = 30); Ki-67 (n = 30); heat shock protein-70 (HSP-70), n = 30; p16INK4, n = 20; and mucin-1 (MUC1), n = 30. All the results and observations were subjected to descriptive statistical analysis. Results: The male: female ratio was 7.5:1; right side and buccal mucosa were more commonly affected. The duration of the lesion ranged from 1 to 30 years. One hundred and twelve patients were habituated to tobacco chewing, while 171 patients came with a combined habit of smoke and smokeless tobacco usage. Clinically, most of the lesions were of stage 2 while histopathologically they were of mild dysplasia. There was a decrease in the immunoexpression of E-cadherin, hMLH1 and CD1a, while there was an increase in the immunoexpression of vimentin, Ki-67, HSP-70, MUC1 and p16INK4. Conclusion: The study of different biomarkers such as cytoplasmic, membranous and nuclear in OL will help in better understanding and application of a reliable marker for diagnostic and prognostic purpose.

14.
J Oral Maxillofac Pathol ; 24(1): 113-116, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32508458

RESUMEN

BACKGROUND: Regardless of the form of treatment, long-term follow-up of the patient is an absolute necessity. This study aimed to follow surgically treated patients visiting our department of oral pathology over 5 years (January 2011-December 2015) to monitor recurrence of the condition, patient compliance and reasons for noncompliance. MATERIALS AND METHODS: We conducted half-yearly recall for patients visiting our department from January 2011 to December 2015. Patients were recalled through the use of letters, telephonic reminders and e-mails. RESULTS: The study included 171 recalled patients of whom, 42 (24.56%) reported for follow-up, while the remaining 129 (75.43%) did not report for follow-up. Of the 42 reporting patients, 26 (61.90%) reported once, 10 (23.81%) twice and 6 (14.28%) three times. Recurrence of the condition was reported in two cases. The reasons for noncompliance included: financial constraints (22.48%), casual attitude (37.20%), reported to nearby hospitals (5.42%) and lack of time (11.62%). Some patients could not be sent reminder letters due to incomplete address (7.75%), the wrong pin code (6.97%), change of address (4.65%), locked house (3.10%) and death of the patient (0.77%). CONCLUSION: This study highlights patient recall appointment noncompliance, ascribing various reasons to the patient's attrition rate for recall appointments. Probable solutions for increasing the compliance for recall need to be addressed, and further research should be conducted to evaluate these solutions.

15.
Head Neck Pathol ; 14(3): 733-741, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31873936

RESUMEN

Giant cell tumour (GCT) is locally aggressive benign neoplasm of long bones whereas giant cell granulomas; central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG); are tumour-like conditions of the oral cavity. This study aimed to evaluate and compare the immunohistochemical expression of p63 in GCT, CGCG, PGCG and determine whether p63 can be used as a diagnostic, prognostic and differential biomarker between these entities. Histopathologically diagnosed 10 cases of GCT, 20 cases of CGCG and 20 cases of PGCG were subjected to p63 immunohistochemical staining. The percentage of p63-positive cells was semi-quantitatively assessed on the whole section. Intergroup comparison was done using Kruskal-Wallis test and one-way ANOVA. The value p < 0.05 was considered to be statistically significant and value p < 0.01 was considered to be statistically highly significant. p63 immunoexpression was seen in 100% (10/10) cases of GCT whereas CGCG and PGCG revealed the complete absence of p63 immunopositivity. These results showed a highly significant difference in p63 expression between GCT, CGCG and PGCG (p < 0.01). No difference was noted between CGCG and PGCG. GCT is a distinct entity when compared with CGCG and PGCG. Even aggressive CGCG also did not show p63 immunopositivity, so it is not a prognostic marker. Also, p63 cannot differentiate between CGCG and PGCG.


Asunto(s)
Biomarcadores de Tumor/análisis , Tumor Óseo de Células Gigantes/patología , Granuloma de Células Gigantes/patología , Enfermedades Maxilomandibulares/patología , Proteínas de la Membrana/biosíntesis , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven
16.
Heliyon ; 4(1): e00519, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29560435

RESUMEN

BACKGROUND: Assessing immune response after rotavirus vaccination consists in measuring serum or plasma IgA and IgG antibodies, but these assays provide very little information about the mucosal immune response. Thus the development of assays for detection of mucosal immune response following rotavirus vaccination is essential. We evaluate to assess circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immune responses to rotavirus vaccine. METHODS: 372 subjects, aged 6 weeks, were enrolled in the study. All the subjects were assigned to receive two doses of Rotarix® vaccine. Using a micro-modified whole blood-based ELISPOT assay, circulating rotavirus type-specific IgA- and IgG-ASCs, including gut homing ß7+ ASCs, were enumerated on week 6 before the first dose of Rotarix vaccination at 7 weeks of age and week 18 after the second vaccination at 17 weeks of age. Plasma samples collected before vaccination, and after two doses of Rotarix® vaccination were tested for plasma rotavirus IgA titers. RESULTS: Two doses of Rotarix® provided to induce sero-protective titer of ≥ 20 Units in 35% of subjects. Total blood IgA- ASC responses were detected in 26.4% of subjects who were non-responder before vaccination. Among responders, 47% of the subjects also have sero-protective plasma IgA titers. DISCUSSION: Our results suggest that virus-specific blood gut homing ASCs were detected and provide insight into mucosal immune response after rotavirus vaccination. Further studies are needed to evaluate the duration of such immune responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the rotavirus immunization program.

17.
Heliyon ; 3(1): e00223, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28194449

RESUMEN

BACKGROUND: The final endgame strategy of global polio eradication initiative includes switching from trivalent oral poliovirus vaccines (tOPV) to bivalent oral polio vaccine (bOPV), and introduction of inactivated poliovirus vaccine (IPV). This study compares IPV with tOPV week 39 boost in Indian infants. METHODS: Starting 28 March 2012, we enrolled 372 Indian infant-mother pairs from Kolkata, India in an open-label, block-randomized, controlled trial comparing a 39 week tOPV to an IPV boost among infants immunized with three doses of tOPV. The primary outcome was mucosal immunity to poliovirus as measured by fecal polio virus shedding after OPV challenge. The secondary outcome was humoral response as defined by >1:8 titers for neutralizing antibodies at week 40. Seroconversion was measured by change in level of antibody titers from week 18 to week 40. The analyses were performed by both intention-to-treat (ITT) and per-protocol (PP) comparing the occurrences of outcomes between the arms of the study. FINDINGS: Both the study arms provided equivalent mucosal immunity at 52 weeks with a total shedding prevalence of 28%. Vaccination with IPV resulted in significantly higher seroconversion rates for Polio type 2 (p = 0.03) and Polio type 3 (p < 0.01). CONCLUSIONS: This study indicates that an IPV boost at week 39 is equivalent to tOPV in intestinal immunity, and provides higher seroconversion compared to tOPV. The major limitation of the study was the additional OPV doses receive by infants during pulse polio immunization resulted in additional mucosal boosting, diminishing the impact of IPV or tOPV boost at week 39. However, IPV for OPV boost should prove to be a step forward in the global polio eradication initiative to reduce the problem of circulating vaccine-derived poliovirus (cVDPV).

18.
Clin Vaccine Immunol ; 23(7): 610-7, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27193041

RESUMEN

Developing countries are burdened with Shigella diarrhea. Understanding mucosal immune responses associated with natural Shigella infection is important to identify potential correlates of protection and, as such, to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies against highly conserved invasive plasmid antigens (IpaC, IpaD20, and IpaD120) and two recently identified surface protein antigens, pan-Shigella surface protein antigen 1 (PSSP1) and PSSP2, common to all virulent Shigella strains. We examined blood and stool specimens from 37 diarrheal patients admitted to the Infectious Diseases & Beliaghata General Hospital, Kolkata, India. The etiological agent of diarrhea was investigated in stool specimens by microbiological methods and real-time PCR. Gut-homing (α4ß7 (+)) antibody-secreting cells (ASCs) were isolated from patient blood by means of combined magnetic cell sorting and two-color enzyme-linked immunosorbent spot (ELISPOT) assay. Overall, 57% (21 of 37) and 65% (24 of 37) of the patients were positive for Shigella infection by microbiological and real-time PCR assays, respectively. The frequency of α4ß7 (+) IgG ASC responders against Ipas was higher than that observed against PSSP1 or PSSP2, regardless of the Shigella serotype isolated from these patients. Thus, α4ß7 (+) ASC responses to Ipas may be considered an indirect marker of Shigella infection. The apparent weakness of ASC responses to PSSP1 is consistent with the lack of cross-protection induced by natural Shigella infection. The finding that ASC responses to IpaD develop in patients with recent-onset shigellosis indicates that such responses may not be protective or may wane too rapidly and/or be of insufficient magnitude.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Diarrea/patología , Disentería Bacilar/patología , Proteínas de la Membrana/inmunología , Células Plasmáticas/inmunología , Shigella/inmunología , Adolescente , Adulto , Anciano , Células Productoras de Anticuerpos/inmunología , Femenino , Hospitalización , Humanos , Inmunofenotipificación , India , Integrinas/análisis , Masculino , Persona de Mediana Edad , Células Plasmáticas/química , Adulto Joven
19.
J Clin Diagn Res ; 10(2): DC22-5, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27042464

RESUMEN

INTRODUCTION: In the present era we are left behind with limited options for the treatment of serious infections caused by multidrug resistant S.aureus, most remarkably nosocomially acquired Methicillin resistant S.aureus (MRSA). The problem increases more when these strains easily become multidrug resistant (MDR) due to biofilm formation. Those staphylococcal species that are vancomycin and linezolid resistant are also resistant to other antistaphylococcal agents which call for an urgent intervention to develop newer antimicrobial agents. AIM: The present study was undertaken with the aim to evaluate the antibiofilm effect of EDTA against the biofilm forming MRSA isolates, isolated from different clinical infections. MATERIALS AND METHODS: The biofilms formed on polystyrene microtitre plates by the MRSA strains were treated by different concentrations of EDTA to find out its anti-biofilm activity. Further simultaneously the antibiotic susceptibility pattern was noted down to check whether the MRSA strains become MSSA (Methicillin sensitive S.aureus). RESULTS: Our data demonstrates that EDTA at 4mM concentration inhibits biofilm of MRSA and at 20 mM have an ability to reduce and dissociate the biofilm membrane, allowing the antibiotics to enter and convert MRSA strains into MSSA. CONCLUSION: These findings suggest that commercially available EDTA could be used in future to control MRSA and its biofilm- related infections.

20.
Iran J Pathol ; 10(1): 17-22, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26516321

RESUMEN

BACKGROUND & OBJECTIVES: Tubular adenomas are rare benign epithelial tumours of breast affecting predominantly females of child bearing age group. Till now, very small number of cases have been reported in the literature. Present study was carried out to evaluate the clinico-pathological features of tubular adenoma cases diagnosed during three years study period along with discussion of possible differential diagnoses. METHODS: Overall, 346 female breast biopsies were diagnosed as benign lesions in three years (2010-2012), of which 10 cases of tubular adenomas were identified. Available clinical, radiological and cytological data of these cases were analysed retrospectively in detail. RESULT: Tubular adenomas were identified from 16 to 48 years of age with a predilection to younger age group (60% within 30 years). Most of the tubular adenomas were small and circumscribed mimicking fibroadenoma in almost all the cases. Diagnosis of tubular adenoma in each case was possible only after histological examination. Pre-operative diagnosis of tubular adenoma was not established by cytological and radiological evaluation in any case. CONCLUSION: Tubular adenomas are clinically indistinguishable from other benign breast neoplasms and it should be considered as potential differential diagnosis during histopathological evaluation of breast biopsies.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...