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1.
EMBO J ; 39(10): e103111, 2020 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-32187724

RESUMEN

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Beclina-1/metabolismo , Quinasa de Punto de Control 2/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Autofagia , Línea Celular , Modelos Animales de Enfermedad , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Ratones , Estrés Oxidativo , Fosforilación
2.
Anal Chem ; 96(23): 9424-9429, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38825761

RESUMEN

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.


Asunto(s)
Candida auris , Técnicas de Amplificación de Ácido Nucleico , Recombinasas , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Recombinasas/metabolismo , Candida auris/genética , Candidiasis/diagnóstico , Candidiasis/microbiología , Límite de Detección , ADN de Hongos/genética , ADN de Hongos/análisis
3.
Biochem Biophys Res Commun ; 695: 149463, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38176172

RESUMEN

Cisplatin-induced acute kidney injury (AKI) restricts the use of cisplatin as a first-line chemotherapeutic agent. Our previous study showed that prophylactic vitamin C supplementation may act as an epigenetic modulator in alleviating cisplatin-induced AKI in mice. However, the targets of vitamin C and the mechanisms underlying the epigenetics changes remain largely unknown. Herein, whole-genome bisulfite sequencing and bulk RNA sequencing were performed on the kidney tissues of mice treated with cisplatin with prophylactic vitamin C supplementation (treatment mice) or phosphate-buffered saline (control mice) at 24 h after cisplatin treatment. Ascorbyl phosphate magnesium (APM), an oxidation-resistant vitamin C derivative, was found that led to global hypomethylation in the kidney tissue and regulated different functional genes in the promoter region and gene body region. Integrated evidence suggested that APM enhanced renal ion transport and metabolism, and reduced apoptosis and inflammation in the kidney tissues. Strikingly, Mapk15, Slc22a6, Cxcl5, and Cd44 were the potential targets of APM that conferred protection against cisplatin-induced AKI. Moreover, APM was found to be difficult to rescue cell proliferation and apoptosis caused by cisplatin in the Slc22a6 knockdown cell line. These results elucidate the mechanism by which vitamin C as an epigenetic regulator to protects against cisplatin-induced AKI and provides a new perspective and evidence support for controlling the disease process through regulating DNA methylation.


Asunto(s)
Lesión Renal Aguda , Antineoplásicos , Ratones , Animales , Cisplatino/efectos adversos , Antineoplásicos/farmacología , Desmetilación del ADN , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/prevención & control , Riñón/metabolismo , Apoptosis , Magnesio/metabolismo , Vitaminas/farmacología , Suplementos Dietéticos , Ácido Ascórbico/metabolismo , Fosfatos/metabolismo , Ratones Endogámicos C57BL
4.
Appl Environ Microbiol ; 90(7): e0055724, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38953658

RESUMEN

Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.


Asunto(s)
Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Antibacterianos/farmacología , Temperatura , Alcoholes/metabolismo , Alcoholes/farmacología
5.
J Biochem Mol Toxicol ; 38(1): e23516, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37728154

RESUMEN

Oxidized low-density lipoprotein (ox-LDL) mediated inflammatory damage, which possibly induces atherosclerosis (AS); however, the role of miRNA in this process has rarely been reported. In this paper, we study the ox-LDL-related endothelial cell damage and changes of macrophages. The bioinformatics method was used to analyze the expression changes of miRNA in AS patients, luciferase assay was used to study the interaction of protein and miRNA, and co-IP and ubiquitination experiments were used to analyze protein interaction. Flow cytometry was used to detect the polarization of macrophages. Database analysis showed that the expression of miR-21-5p was upregulated in AS patients. Luciferase assay showed that miR-21-5p can bind to SKP2 and subsequently influence ubiquitination of EP300. Overexpression of EP300 strengthens the HMGB1-induced acetylation and subsequently mediates the dissociation of HMGB1 from SIRT1, and thus HMGB1 could be secreted outside the cell. The HMGB1 released from endothelial cells can promote macrophage M1 polarization. This study shows that ox-LDL activates the SKP2/EP300 pathway through promoting upregulation of miR-21-5p, thereby acetylating and secreting HMGB1 outside the endothelium, subsequently enhancing macrophage polarization to further stabilize the inflammation situation.


Asunto(s)
Proteína HMGB1 , MicroARNs , Humanos , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Células Endoteliales/metabolismo , MicroARNs/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Luciferasas/metabolismo , Apoptosis , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Proliferación Celular , Proteína p300 Asociada a E1A/metabolismo
6.
Appl Microbiol Biotechnol ; 108(1): 45, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38175238

RESUMEN

Veillonella spp. are Gram-negative opportunistic pathogens present in the respiratory, digestive, and reproductive tracts of mammals. An abnormal increase in Veillonella relative abundance in the body is closely associated with periodontitis, inflammatory bowel disease, urinary tract infections, and many other diseases. We designed a pair of primers and a probe based on the 16S rRNA gene sequences of Veillonella and conducted real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR) to quantify the abundance of Veillonella in fecal samples. These two methods were tested for specificity and sensitivity using simulated clinical samples. The sensitivity of qPCR was 100 copies/µL, allowing for the accurate detection of a wide range of Veillonella concentrations from 103 to 108 CFU/mL. The sensitivity of ddPCR was 11.3 copies/µL, only allowing for the accurate detection of Veillonella concentrations from 101 to 104 CFU/mL because of the limited number of droplets generated by ddPCR. ddPCR is therefore more suitable for the detection of low-abundance Veillonella samples. To characterize the validity of the assay system, clinical samples from children with inflammatory bowel disease were collected and analyzed, and the results were verified using isolation methods. We conclude that molecular assays targeting the 16S rRNA gene provides an important tool for the rapid diagnosis of chronic and infectious diseases caused by Veillonella and also supports the isolation and identification of Veillonella for research purposes. KEY POINTS: • With suitable primer sets, the qPCR has a wider detection range than ddPCR. • ddPCR is suitable for the detection of low-abundance samples. • Methods successfully guided the isolation of Veillonella in clinical sample.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Veillonella , Niño , Humanos , Bioensayo , Enfermedades Inflamatorias del Intestino/diagnóstico , Mamíferos , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN Ribosómico 16S/genética
7.
J Med Virol ; 95(7): e28898, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37409619

RESUMEN

Ovarian cancers, especially high-grade serous ovarian cancer (HGSOC), are one of the most lethal age-independent gynecologic malignancies. Although pathogenic microorganisms have been demonstrated to participate in the pathogenesis of multiple types of tumors, their potential roles in the development of ovarian cancer remain unclear. To gain an insight into the microbiome-associated pathogenesis of ovarian cancer and identify potential diagnostic biomarkers, we applied different techniques to analyse the microbiome and serum metabolome of different resources. We found that the vaginal microbiota in ovarian cancer mouse models was under dysbiosis, with altered metabolite configurations that may result from amino acid or lysophospholipid metabolic processes. Local therapeutic intervention with a broad spectrum of antibiotics was effective in reversing microbiota dysbiosis and suppressing carcinogenic progression. As the ovary is situated deeply in the pelvis, it is difficult to directly monitor the ovarian microbial community. Our findings provide alternative options for utilizing the vaginal bacteria as noninvasive biomarkers, such as Burkholderia (area under the curve = 0.8843, 95% confidence interval: 0.743-1.000), which supplement the current invasive diagnostic methods for monitoring ovarian cancer progression and contribute to the development of advanced microbe-based diagnosis and adjuvant therapies.


Asunto(s)
Microbiota , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Disbiosis/metabolismo , Disbiosis/microbiología , Neoplasias Ováricas/diagnóstico , Vagina , Biomarcadores
8.
J Biomed Sci ; 30(1): 75, 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37653407

RESUMEN

BACKGROUND: Klebsiella aerogenes can cause ventilator-associated pneumonia by forming biofilms, and it is frequently associated with multidrug resistance. Phages are good antibiotic alternatives with unique advantages. There has been a lack of phage therapeutic explorations, kinetic studies, and interaction mechanism research targeting K. aerogenes. METHODS: Plaque assay, transmission electron microscopy and whole-genome sequencing were used to determine the biology, morphology, and genomic characteristics of the phage. A mouse pneumonia model was constructed by intratracheal/endobronchial delivery of K. aerogenes to assess the therapeutic effect of phage in vivo. Bioinformatics analysis and a prokaryotic protein expression system were used to predict and identify a novel capsule depolymerase. Confocal laser scanning microscopy, Galleria mellonella larvae infection models and other experiments were performed to clarify the function of the capsule depolymerase. RESULTS: A novel lytic phage (pK4-26) was isolated from hospital sewage. It was typical of the Podoviridae family and exhibited serotype specificity, high lytic activity, and high environmental adaptability. The whole genome is 40,234 bp in length and contains 49 coding domain sequences. Genomic data show that the phage does not carry antibiotic resistance, virulence, or lysogenic genes. The phage effectively lysed K. aerogenes in vivo, reducing mortality and alleviating pneumonia without promoting obvious side effects. A novel phage-derived depolymerase was predicted and proven to be able to digest the capsule, remove biofilms, reduce bacterial virulence, and sensitize the bacteria to serum killing. CONCLUSIONS: The phage pK4-26 is a good antibiotic alternative and can effectively relieve pneumonia caused by multidrug-resistant K. aerogenes. It carries a depolymerase that removes biofilms, reduces virulence, and improves intrinsic immune sensitivity.


Asunto(s)
Bacteriófagos , Enterobacter aerogenes , Neumonía , Animales , Ratones , Bacteriófagos/genética , Cinética , Antibacterianos , Modelos Animales de Enfermedad
9.
Int J Gynecol Cancer ; 33(6): 882-889, 2023 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-37001894

RESUMEN

OBJECTIVE: This retrospective study aimed to evaluate the survival outcomes in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIICp cervical cancer patients receiving different adjuvant treatment modalities after radical hysterectomy. METHODS: From January 2008 to December 2012, patients diagnosed with cervical cancer who underwent radical hysterectomy plus retroperitoneal lymphadenectomy with pathologically confirmed positive lymph nodes, and received either radiotherapy, concurrent chemoradiation, or sequential chemoradiation, were included in this study. Survival analysis was performed according to different adjuvant treatment modalities and after adjustment using propensity score matching. RESULTS: A total of 192 stage IIICp cervical cancer patients were eligible. In multivariate analysis, only sequential chemoradiation versus radiotherapy was associated with both overall survival (HR 0.44, 95% CI 0.21 to 0.94, p=0.035) and disease-free survival (HR 0.26, 95% CI 0.11 to 0.57, p<0.001). The 5-year overall survival for radiotherapy, concurrent chemoradiation, and sequential chemoradiation was 71.6%, 81.7%, and 81.5%, respectively. No significant difference in overall survival was noted between the three groups (radiotherapy vs concurrent chemoradiation, p=0.15; radiotherapy vs sequential chemoradiation, p=0.09; concurrent chemoradiation vs sequential chemoradiation, p=0.95). However, sequential chemoradiation significantly increased disease-free survival compared with radiotherapy alone (79.2% vs 63.1%, p=0.028). After propensity score matching in the baseline characteristics, both overall survival (88.0% vs 71.6%, p=0.028) and disease-free survival (88.0% vs 63.1%, p=0.021) were improved in the sequential chemoradiation group compared with radiotherapy alone; no significant differences were noted between sequential chemoradiation and concurrent chemoradiation (overall survival 88.0% vs 83.8%, p=0.50; disease-free survival 88.0% vs 75.8%, p=0.28). CONCLUSION: In this cohort of FIGO 2018 IIICp cervical cancer patients, post-operative sequential chemoradiation was associated with higher survival compared with radiotherapy alone after propensity matching. Future prospective studies are required to further elucidate the optimal modality in node-positive cervical cancer.


Asunto(s)
Obstetricia , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Estadificación de Neoplasias , Escisión del Ganglio Linfático , Histerectomía
10.
Lancet Oncol ; 22(4): 439-449, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33705695

RESUMEN

BACKGROUND: The benefits of secondary cytoreduction for platinum-sensitive relapsed ovarian cancer are still widely debated. We aimed to assess the efficacy of secondary cytoreduction plus chemotherapy versus chemotherapy alone in this patient population. METHODS: This multicentre, open-label, randomised, controlled, phase 3 trial (SOC-1), was done in four primarily academic centres in China (two in Shanghai, one in Hangzhou, and one in Guangzhou). Eligible patients were women aged 18 years and older with platinum-sensitive relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months after the end of first-line platinum-based chemotherapy and were predicted to have potentially resectable disease according to the international model (iMODEL) score and PET-CT imaging. iMODEL score was calculated using six variables: International Federation of Gynecology and Obstetrics stage, residual disease after primary surgery, platinum-free interval, Eastern Cooperative Oncology Group performance status, serum level of cancer antigen 125 at recurrence, and presence of ascites at recurrence. An iMODEL score of 4·7 or lower predicted a potentially complete resection. As per a protocol amendment, patients with an iMODEL score of more than 4·7 could only be included if the serum level of cancer antigen 125 was more than 105 U/mL, but the principal investigators assessed the disease to be resectable by PET-CT. Eligible participants were randomly assigned (1:1) via a permuted block design (block size of six) and stratified by study centre, iMODEL score, residual disease at primary surgery, and enrolment in the Shanghai Gynecologic Oncology Group SUNNY trial, to undergo secondary cytoreductive surgery followed by intravenous chemotherapy (six 3-weekly cycles of intravenous paclitaxel [175 mg/m2] or docetaxel [75 mg/m2] combined with intravenous carboplatin [area under the curve of 5 mg/mL per min]; surgery group) or intravenous chemotherapy alone (no surgery group). Primary endpoints were progression-free survival and overall survival, analysed in all participants randomly assigned to treatment, regardless of treatment received (intention-to-treat [ITT] population). Here, we report the final analysis of progression-free survival and the prespecified interim analysis of overall survival. Safety was assessed in all participants who received their assigned treatment and had available adverse event data. This study is registered with ClinicalTrials.gov, NCT01611766, and is ongoing but closed to accrual. FINDINGS: Between July 19, 2012, and June 3, 2019, 357 patients were recruited and randomly assigned to the surgery group (182) or the no surgery group (175; ITT population). Median follow-up was 36·0 months (IQR 18·1-58·3). In the no surgery group, 11 (6%) of 175 participants had secondary cytoreduction during second-line therapy while 48 (37%) of 130 participants who had disease progression crossed-over and had surgery at a subsequent recurrence. Median progression-free survival was 17·4 months (95% CI 15·0-19·8) in the surgery group and 11·9 months (10·0-13·8) in the no surgery group (hazard ratio [HR] 0·58; 95% CI 0·45-0·74; p<0·0001). At the interim overall survival analysis, median overall survival was 58·1 months (95% CI not estimable to not estimable) in the surgery group and 53·9 months (42·2-65·5) in the no surgery group (HR 0·82, 95% CI 0·57-1·19). In the safety population, nine (5%) of 172 patients in the surgery group had grade 3-4 surgical morbidity at 30 days, and no patients in either group had died at 60 days after receiving assigned treatment. The most common grade 3-4 adverse events during chemotherapy were neutropenia (29 [17%] of 166 patients in the surgery group vs 19 [12%] of 156 patients in the no surgery group), leucopenia (14 [8%] vs eight [5%]), and anaemia (ten [6%] vs nine [6%]). Four serious adverse events occurred, all in the surgery group. No treatment-related deaths occurred in either group. INTERPRETATION: Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer, and patients should be counselled about the option of secondary cytoreduction in specialised centres. Long-term survival outcomes will be assessed using mature data on overall survival. FUNDING: Zhongshan Development Program. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Adulto , Anciano , Bevacizumab/administración & dosificación , Carboplatino/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Supervivencia sin Progresión
11.
J Gene Med ; 23(2): e3286, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33037712

RESUMEN

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women and is also the leading cause of cancer death for which the treatment and methods of diagnosis remain unsatisfied. Long non-coding RNA (lncRNA) plays an important role in the occurrence and development of tumors, including breast cancer. We aimed to seek new and efficient treatment targets by analyzing the lncRNA expression profiles of breast cancer. METHODS: A competitive endogenous RNA microarray was used to investigate the profiles of differentially expressed lncRNAs. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) validated the top differentially expressed lncRNAs in 107 pairs of breast cancer tissues and adjacent normal tissues. cis- and trans-regulation mRNAs of lncRNAs were used to perform enrichment analysis. Cell function assays were used to explore the functions of ST8SIA6-AS1. RESULTS: Seven lncRNAs, comprising ST8SIA6-AS1, lnc-HIST1H2BJ-5:1, lnc-PRICKLE2-3:2, RP1-86C11.7, RP11-15F12.1, ZNF670-ZNF695 and lnc-STRN3-12:1, were shown to be significantly up-regulated in breast cancer. lncRNA ST8SIA6-AS1 was associated with TNM staging and Ki-67 index. The cell function assays showed that ST8SIA6-AS1 can promote the proliferation, migration and invasion of breast cancer cells. The functions of ST8SIA6-AS1 were explored and the competing endogenous RNA mode showed that miR-4252 was a potential candidate. Its target genes were further predicted. The lncRNA-protein mode showed three potential candidate RNA binding proteins: NONO, QKI and RBMX. CONCLUSIONS: lncRNA ST8SIA6-AS1 can promote the proliferation, migration and invasion of breast cancer cells. By hypothesizing two different functional modes of ST8SIA6-AS1, we found lncRNA ST8SIA6-AS1 may contribute to breast cancer progression through miR-4252 or interacting with RNA binding proteins: NONO, QKI and RBMX.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Biomarcadores de Tumor , Línea Celular , Movimiento Celular , Proliferación Celular , Proteínas de Unión al ADN/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Humanos , Análisis por Micromatrices/métodos , Estadificación de Neoplasias , Proteínas de Unión al ARN/metabolismo
12.
Biochem Biophys Res Commun ; 557: 135-142, 2021 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-33865221

RESUMEN

Gastric cancer (GC) is the most common cancer worldwide. Although advances in the treatments, the oncogenic mechanisms are still largely unknown. RNF168 (ring-finger nuclear factor 168) is an important regulator of DNA double-strand break (DSB) repair, and its defects have been involved in the pathogenesis of a number of human diseases including cancer. However, its effects on GC are still unclear. In the study, we demonstrated that RNF168 expression was remarkably down-regulated in human GC tissues, and its low expression showed worse overall survival rate in GC patients. Importantly, we here reported that RNF168 directly interacted with Ras homolog gene family member C (RHOC) and induced its ubiquitination to promote RHOC degradation. RHOC exhibited higher expression in human GC tissues, and its knockdown significantly restrained cell proliferation, migration and invasion in GC cell lines. Moreover, RHOC knockdown led to a significant reduction in GC tumor growth in a xenograft mouse model. Additionally, histone deacetylase 1 (HDAC1) was found to be markedly decreased in GC cells with RHOC knockdown. Intriguingly, RHOC suppression-ameliorated proliferative and migratory ability in GC cells were significantly diminished by HDAC1 over-expression. Our in vivo studies finally confirmed that RHOC inhibition dramatically reduced the lung metastasis in nude mice. Collectively, all our results demonstrated that RNF168 directly interacted with RHOC to induce its degradation via promoting its ubiquitination, contributing to the inhibition of cell proliferation and metastasis in GC through decreasing HDAC1. Thus, targeting RNF168/RHOC/HDAC1 axis might be promising to develop effective therapies for GC treatment.


Asunto(s)
Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Histona Desacetilasa 1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Gástricas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Proteína rhoC de Unión a GTP/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Histona Desacetilasa 1/genética , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína rhoC de Unión a GTP/genética
13.
Eur J Clin Microbiol Infect Dis ; 40(8): 1705-1711, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33733396

RESUMEN

Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen in community-acquired pneumonia. The community-acquired respiratory distress syndrome (CARDS) toxin is the only known virulence factor of M. pneumoniae. It is worth exploring whether this toxin can be used as a candidate antigen for the serodiagnosis of M. pneumoniae. In this study, the full-length, N-terminal, and C-terminal regions of the CARDS toxin were expressed and purified, and serological reactions were evaluated using ELISA. A total of 184 serum samples were collected and tested using a commercialized test kit. Eighty-seven samples were positive, and 97 samples were negative for infection. The purified recombinant proteins were used as antigens to test the serum via indirect ELISA. The sensitivity of the CARDS toxin, the N-terminal region, and the C-terminal region were 90.8%, 90.8%, and 92.0%, respectively. The specificity of the CARDS toxin, the N-terminal region, and the C-terminal region were 85.6%, 73.2%, and 93.8%, respectively. All three CARDS toxin proteins exhibited good reactivity, of which the C-terminal region had a good discrimination ability in human sera. This may have a potential diagnostic value for M. pneumoniae infections.


Asunto(s)
Proteínas Bacterianas/sangre , Toxinas Bacterianas/sangre , Mycoplasma pneumoniae/aislamiento & purificación , Neumonía por Mycoplasma/microbiología , Ensayo de Inmunoadsorción Enzimática/métodos , Regulación Bacteriana de la Expresión Génica , Humanos , Mycoplasma pneumoniae/metabolismo , Sensibilidad y Especificidad , Pruebas Serológicas
14.
Cell Biol Int ; 45(11): 2304-2315, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34369049

RESUMEN

Previous studies have shown that circ_0040414 is highly expressed in the blood of patients with heart failure (HF), which suggests that circ_0040414 is associated with heart failure (HF). However, the functional involvement of circ_0040414 in HF and its potential mechanism remains unclear. Consistent with previous studies, our study showed that the expression of circ_0040414 in the peripheral blood of patients with chronic heart failure (CHF) was significantly higher than that of healthy control, which indicated that circ_0040414 could be used as a diagnostic biomarker in patients with CHF. In cardiomyocytes, circ_0040414 increased the level of proapoptotic proteins Bax, cleaved-caspase 3 and reduced the expression of antiapoptotic protein Bcl-2. It also promoted inflammatory factors IL-6, TNF-α, and IL-ß, but inhibited cell proliferation. In terms of mechanism, circ_0040414 upregulated the expression of phosphatase and tensin homolog (PTEN) through sponging miR-186-5p to inhibit AKT signaling activity. Our study uncovered a novel role and the mechanism of circ_0040414 in controlling CHF, enriched the molecular regulatory network in CHF, and may provide a possible strategy for the treatment of CHF.


Asunto(s)
Insuficiencia Cardíaca/genética , ARN Circular/genética , Adulto , Anciano , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Enfermedad Crónica , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Inflamación/genética , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Miocitos Cardíacos/metabolismo , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Circular/metabolismo , Transducción de Señal
15.
BMC Pediatr ; 21(1): 218, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33947371

RESUMEN

BACKGROUND: Niemann-Pick C disease is a rare autosomal recessive lysosomal lipid storage disorder. Some primary immunodeficiency diseases patients developed regional disease or disseminated disease after vaccinating BCG. It is unclear whether NPC gene deficiency is associated with Mycobacteria infection. CASE PRESENTATION: We report and discuss a case of a child who presented at the age of 6 months with NPC1 and BCG-itis. The patient was treated with Miglustat and the symptom of lymphadenopathy was improved. CONCLUSIONS: We reasonably speculate that NPC1 is a susceptibility gene of Mtb infection and mainly affects innate immunity. Once diagnosed, the infant should not be vaccinated with BCG and early treated.


Asunto(s)
Vacuna BCG , Enfermedad de Niemann-Pick Tipo C , Vacuna BCG/efectos adversos , Niño , Familia , Humanos , Lactante , Enfermedad de Niemann-Pick Tipo C/diagnóstico , Enfermedad de Niemann-Pick Tipo C/genética
16.
Sensors (Basel) ; 21(7)2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33916389

RESUMEN

The credibility of sensor data is essential for security monitoring. High-credibility data are the precondition for utilizing data and data analysis, but the existing data credibility evaluation methods rarely consider the spatio-temporal relationship between data sources, which usually leads to low accuracy and low flexibility. In order to solve this problem, a new credibility evaluation method is proposed in this article, which includes two factors: the spatio-temporal relationship between data sources and the temporal correlation between time series data. First, the spatio-temporal relationship was used to obtain the credibility of data sources. Then, the combined credibility of data was calculated based on the autoregressive integrated moving average (ARIMA) model and back propagation (BP) neural network. Finally, the comprehensive data reliability for evaluating data quality can be acquired based on the credibility of data sources and combined data credibility. The experimental results show the effectiveness of the proposed method.

17.
J Cell Physiol ; 235(11): 7945-7959, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31943203

RESUMEN

Breast cancer (BC) is a globally common cancer with the highest and increasing morbidity and mortality among females. Novel biomarkers are warranted to be discovered for the early detection, treatment, and prognosis of BC. In this study, we investigated the profiles of differentially expressed (DE) circular RNAs (circRNAs) by competing endogenous RNAs (ceRNA) microarray to construct a genome-wide circRNA profile. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis of the host genes (HGs) of circRNAs. A total of 4,370 DE circRNAs were detected and GO and KEGG analysis showed that they were significantly associated with cell cycle, DNA replication, BC, and familial BC. We validated the differential circRNAs and relevant HGs through quantitative real-time polymerase chain reaction and constructed a putative circRNA-microRNA-messenger RNA regulatory network. Eight circRNAs, including hsa_circ_0069094, hsa_circ_0062558, hsa_circ_0074026, hsa_circ_0079876, hsa_circ_0017536, hsa_circ_0023302, hsa_circ_0017650, and hsa_circ_0017545, were validated significantly DE in BC tissue and associated with TNM staging, lymph node infiltration, and Ki67. Hsa_circ_0069094, hsa_circ_0079876, hsa_circ_0017650, and hsa_circ_0017526 were upregulated in plasma. This study revealed the general expression characteristics of specific DE circRNAs in BC and hsa_circ_0069094, hsa_circ_0079876, hsa_circ_0017650, and hsa_circ_0017526 might be promising candidate targets.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Detección Precoz del Cáncer , ARN Circular/genética , Neoplasias de la Mama/patología , Biología Computacional , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Análisis por Micromatrices
18.
Anal Chem ; 92(14): 9699-9705, 2020 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-32441935

RESUMEN

A novel coronavirus (SARS-CoV-2) was recently identified in patients with acute respiratory disease and spread quickly worldwide. A specific and rapid diagnostic method is important for early identification. The reverse-transcription recombinase-aided amplification (RT-RAA) assay is a rapid detection method for several pathogens. Assays were performed within 5-15 min as a one-step single tube reaction at 39 °C. In this study, we established two RT-RAA assays for the S and orf1ab gene of SARS-CoV-2 using clinical specimens for validation. The analytical sensitivity of the RT-RAA assay was 10 copies for the S and one copy for the orf1ab gene per reaction. Cross-reactions were not observed with any of the other respiratory pathogens. A 100% agreement between the RT-RAA and real-time PCR assays was accomplished after testing 120 respiratory specimens. These results demonstrate that the proposed RT-RAA assay will be beneficial as it is a faster, more sensitive, and more specific tool for the detection of SARS-CoV-2.


Asunto(s)
Betacoronavirus/química , Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos , Neumonía Viral/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Bacterias/química , Bacterias/genética , COVID-19 , Reacciones Cruzadas , Sondas de ADN , Genes Virales , Humanos , Pandemias , Plásmidos , Poliproteínas , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , SARS-CoV-2 , Sensibilidad y Especificidad , Proteínas Virales/genética , Virus/química , Virus/genética
19.
BMC Infect Dis ; 20(1): 79, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31992210

RESUMEN

BACKGROUND: Mycoplasma pneumoniae is one of the most common causative pathogens of community-acquired pneumonia (CAP), accounting for as many as 30-50% of CAP during peak years. An early and rapid diagnostic method is key for guiding clinicians in their choice of antibiotics. METHODS: The recombinase-aided amplification (RAA) assay is a recently developed, rapid detection method that has been used for the detection of several pathogens. The assays were performed in a one-step single tube reaction at 39° Celsius within 15-30 min. In this study, we established an RAA assay for M. pneumoniae using clinical specimens for validation and commercial real-time PCR as the reference method. RESULTS: The analytical sensitivity of the RAA assay was 2.23 copies per reaction, and no cross-reactions with any of the other 15 related respiratory bacterial pathogens were observed. Compared with the commercial real-time PCR assay used when testing 311 respiratory specimens, the RAA assay obtained 100% sensitivity and 100% specificity with a kappa value of 1. CONCLUSIONS: These results demonstrate that the proposed RAA assay will be of benefit as a faster, sensitive, and specific alternative tool for the detection of M. pneumoniae.


Asunto(s)
Mycoplasma pneumoniae/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Neumonía por Mycoplasma/microbiología , Recombinasas/genética , Adolescente , Niño , Preescolar , Infecciones Comunitarias Adquiridas/microbiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
20.
World J Surg Oncol ; 18(1): 133, 2020 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-32552905

RESUMEN

BACKGROUND: Sentinel lymph node (SLN) biopsy is an attractive technique that is widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. METHODS: Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered successful. Patients' clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. RESULTS: Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in the obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion, and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed a significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P < 0.001) and lymph node metastasis (40.9% versus 3.8%, P < 0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also have a high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected. CONCLUSIONS: In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection. The risk of having undetected metastasis is high when SLN is positive; therefore, further lymphadenectomy may be necessary for these patients.


Asunto(s)
Escisión del Ganglio Linfático/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Ganglio Linfático Centinela/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Neoplasias del Cuello Uterino/patología
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