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1.
Science ; 383(6679): 205-211, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38207021

RESUMO

Antibodies are produced at high rates to provide immunoprotection, which puts pressure on the B cell translational machinery. Here, we identified a pattern of codon usage conserved across antibody genes. One feature thereof is the hyperutilization of codons that lack genome-encoded Watson-Crick transfer RNAs (tRNAs), instead relying on the posttranscriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Antibody-secreting cells had increased I34 levels and were more reliant on I34 for protein production than naïve B cells. Furthermore, antibody I34-dependent codon usage may influence B cell passage through regulatory checkpoints. Our work elucidates the interface between the tRNA pool and protein production in the immune system and has implications for the design and selection of antibodies for vaccines and therapeutics.


Assuntos
Anticorpos , Formação de Anticorpos , Linfócitos B , Uso do Códon , Cadeias Pesadas de Imunoglobulinas , Inosina , RNA de Transferência , Formação de Anticorpos/genética , Códon/genética , Inosina/genética , Inosina/metabolismo , RNA de Transferência/genética , Anticorpos/genética , Humanos , Linfócitos B/imunologia , Cadeias Pesadas de Imunoglobulinas/genética
2.
Biosens Bioelectron ; 197: 113732, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741959

RESUMO

CRISPR diagnostics (CRISPR-Dx) offer a wide range of enhancements compared to traditional nanobiosensors by taking advantage of the excellent trans-cleavage activity of the CRISPR/Cas systems. However, the single-stranded DNA/RNA reporters of the current CRISPR-Dx suffer from poor stability and limited sensitivity, which make their application in complex biological environments difficult. In comparison, nanomaterials, especially metal nanoparticles, exhibits robust stability and desirable optical and electrocatalytical properties, which make them ideal as reporter molecules. Therefore, biosensing research is moving towards the use of the trans-cleavage activity of CRISPR/Cas effectors on metal nanoparticles and apply the new phenomenon to develop novel nanobiosensors to target various targets such as viral infections, genetic mutations and tumor biomarkers, by using different sensing methods, including, but not limited to fluorescence, luminescence resonance, colorimetric and electrochemical signal readout. In this review, we explore some of the most recent advances in the field of CRISPR-powered nanotechnological biosensors. Demonstrating high accuracy, sensitivity, selectivity and versatility, nanobiosensors along with CRISPR/Cas technology offer tremendous potential for next-generation diagnostics of multiple targets, especially at the point of care and without any target amplification.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Sistemas CRISPR-Cas/genética , DNA/genética , DNA de Cadeia Simples
3.
Asian Pac J Cancer Prev ; 21(4): 1135-1142, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32334482

RESUMO

BACKGROUND: HER2 is the target of the therapeutic agents which are used to treat HER2-positive breast cancer. Reports have shown that the HER2 oncogene expression and its association with clinicopathological factors remain unclear in breast cancer (BC) patients.  This study aimed to determine the correlation between HER2 expression and clinicalpathological characteristics of breast cancer in Vietnamese women. METHODS: Between June 2016 and August 2018, paraffin-embedded specimens from 237 patients with primary invasive breast carcinoma in Hue University Hospital and Hue Center Hospital, Hue city, Vietnam were examined for pathological features. The gene expression of HER2, ER, PR and Ki-67 were determined by immunohistochemistry (IHC). The gene amplification of Her2 was assessed by using Dual color in situ hybridization (DISH). RESULTS: The most frequent histological type was invasive carcinoma of no special type (NST) with 77.35%, the highest percentage of patients with Grade II was detected (59.36%), tumor size > 2 cm accounted for 71.31% of cases, Lymph node metastases were available in 57.86% cases. Most patients were diagnosed at stage II (59.18%). The majority of patients were classified as moderate Nottingham prognostic index (54.9%). Estrogen receptor and Progesterone receptor were positive in 53.16% and 50.63%, respectively. 76.37% of cases were in high expression group of Ki-67 (≥14%). HER2 IHC 2+, 3+ were accounted for 28.69% and HER2 gene amplification was detected in 31% cases. HER2 gene amplification and/or overexpression was significantly associated with cell proliferation index Ki67. Furthermore, HER2 gene expression tended to be more frequently found in tumors with large tumor size, high grade, high stage and high Nottingham prognostic index and confirmed their prognostic independent role. CONCLUSIONS: Our data indicated that HER2 gene expression was significantly correlated with cell proliferation index Ki67, but not significantly associated with another clinicopathological factors in breast cancer of Vietnamese women.
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Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Amplificação de Genes , Receptor ErbB-2/metabolismo , Adulto , Biomarcadores Tumorais/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Estudos Transversais , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Receptor ErbB-2/genética , Vietnã/epidemiologia
4.
Semin Cutan Med Surg ; 34(1): 42-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25922957

RESUMO

Radiation injury to the skin is a major source of dysfunction, disfigurement, and complications for thousands of patients undergoing adjunctive treatment for internal cancers. Despite the great potential for affecting quality of life, radiation injury has received little attention from dermatologists and is primarily being managed by radiation oncologists. During our volunteer work in Vietnam, we encountered numerous children with significant scarring and depigmentation of skin from the outdated use of radioactive phosphorus P32 in the treatment of hemangiomas. This dangerous practice has left thousands of children with significant fibrosis and disfigurement. Currently, there is no treatment for radiation dermatitis. Here, we report a case series using the combination of laser treatment, including pulsed-dye laser, fractional CO2 laser, and epidermal grafting to improve the appearance and function of the radiation scars in these young patients. We hope that by improving the appearance and function of these scars, we can improve the quality of life for these young patients and potentially open up a new avenue of treatment for cancer patients affected with chronic radiation dermatitis, potentially improving their range of motion, cosmesis, and reducing their risk of secondary skin malignancies.

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