RESUMO
In this paper, a photoelectrochemical (PEC)-surface-enhanced Raman scattering (SERS) dual-mode biosensor is constructed coupled with a dual-recognition binding-induced DNA walker with a carbon nitride nanosheet (C3N4)/MXene-gold nanoparticles (C/M-Au NPs) accelerator, which is reliable and capable for sensitive and accurate detection of Staphylococcus aureus (S. aureus). Initially, a photoactive heterostructure is formed by combining C3N4 and MXene via a simple electrostatic self-assembly as they possess well-matched band-edge energy levels. Subsequently, in situ growth of gold nanoparticles on the formed surface results in better PEC performance and SERS activity, because of the synergistic effects of surface plasmon resonance and Schottky barrier. Furthermore, a three-dimensional, bipedal, and dual-recognition binding-induced DNA walker is introduced with the formation of Pb2+-dependent DNAzyme. In the presence of S. aureus, a significant quantity of intermediate DNA (I-DNA) is generated, which can open the hairpin structure of Methylene Blue-tagged hairpin DNA (H-MB) on the electrode surface, thereby enabling the switch of signals for the quantitative determination of S. aureus. The constructed PEC-SERS dual-mode biosensor that can be mutually verified under one reaction effectively addresses the problem of the low detection accuracy of traditional sensors. Experimental results revealed that the effective combination of PEC and SERS is achieved for amplification detection of S. aureus with a detection range of 5-108 CFU/mL (PEC) and 10-108 CFU/mL (SERS), and a detection of limit of 0.70 CFU/mL (PEC) and 1.35 CFU/mL (SERS), respectively. Therefore, this study offers a novel and effective dual-mode sensing strategy, which has important implications for bioanalysis and health monitoring.
Assuntos
Nanopartículas Metálicas , Infecções Estafilocócicas , Humanos , Ouro , Staphylococcus aureus , DNARESUMO
BACKGROUND: Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. METHODS: By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. RESULTS: Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CONCLUSIONS: CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transativadores/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Camundongos , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Análise de Sobrevida , Transativadores/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR-34b-5p in ALI was determined by transfection of a miR-34b-5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT-PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR-34b-5p levels were closely associated with PGRN expression in the lung homogenates. The gain- and loss-of-function analysis, dual-luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR-34b-5p. Intravenous injection of miR-34b-5p antagomir in vivo significantly inhibited miR-34b-5p up-regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR-34b-5p knockdown attenuates lung inflammation and apoptosis in an LPS-induced ALI mouse model by targeting PGRN. This study shows that miR-34b-5p and PGRN may be potential targets for ALI treatments.
Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Apoptose/genética , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , Pneumonia/genética , Progranulinas/genética , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/patologia , Transdução de Sinais/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Detecção Precoce de Câncer , Carcinoma de Pequenas Células do Pulmão/sangue , Idoso , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Feminino , Humanos , Queratina-19/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Proteínas Recombinantes/sangue , Serpinas/sangue , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
Introduction: The present study presents the development and validation of a clinical prediction model using random survival forest (RSF) and stepwise Cox regression, aiming to predict the probability of pelvic inflammatory disease (PID) progressing to sepsis. Methods: A retrospective cohort study was conducted, gathering clinical data of patients diagnosed with PID between 2008 and 2019 from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients who met the Sepsis 3.0 diagnostic criteria were selected, with sepsis as the outcome. Univariate Cox regression and stepwise Cox regression were used to screen variables for constructing a nomogram. Moreover, an RSF model was created using machine learning algorithms. To verify the model's performance, a calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were utilized. Furthermore, the capabilities of the two models for estimating the incidence of sepsis in PID patients within 3 and 7 days were compared. Results: A total of 1064 PID patients were included, of whom 54 had progressed to sepsis. The established nomogram highlighted dialysis, reduced platelet (PLT) counts, history of pneumonia, medication of glucocorticoids, and increased leukocyte counts as significant predictive factors. The areas under the curve (AUCs) of the nomogram for prediction of PID progression to sepsis at 3-day and 7-day (3-/7-day) in the training set and the validation set were 0.886/0.863 and 0.824/0.726, respectively, and the C-index of the model was 0.8905. The RSF displayed excellent performance, with AUCs of 0.939/0.919 and 0.712/0.571 for 3-/7-day risk prediction in the training set and validation set, respectively. Conclusion: The nomogram accurately predicted the incidence of sepsis in PID patients, and relevant risk factors were identified. While the RSF model outperformed the Cox regression models in predicting sepsis incidence, its performance exhibited some instability. On the other hand, the Cox regression-based nomogram displayed stable performance and improved interpretability, thereby supporting clinical decision-making in PID treatment.
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Mucin1 (MUC1) is an extensively glycosylated transmembrane protein that is widely distributed and overexpressed on the surface of cancer cells, playing an important role in tumor occurrence and metastasis. Therefore, highly sensitive detection of MUC1 is of great significance for early diagnosis, treatment monitoring, and prognosis of cancer. Here, an ultra-sensitive photoelectrochemical (PEC) sensing platform was developed based on an aptamer amplification strategy for highly selective and sensitive detection of MUC1 overexpressed in serum and on cancer cell surfaces. The sensing platform utilized copper phthalocyanine to fabricate porous organic polymers (CuPc POPs), and was effectively integrated with g-C3N4/MXene to form a ternary heterojunction material (g-C3N4/MXene/CuPc POPs). This material effectively improved electron transfer capability, significantly enhanced light utilization, and greatly enhanced photoelectric conversion efficiency, resulting in a dramatic increase in photocurrent response. MUC1 aptamer 1 was immobilized on a chitosan-modified photoelectrode for the selective capture of MUC1 or MCF-7 cancer cells. When the target substance was present, MUC1 aptamer 2 labeled with methylene blue (MB) was specifically adsorbed on the electrode surface, leading to enhanced photocurrent. The concentration of MUC1 directly correlated with the number of MB molecules attracted to the electrode surface, establishing a linear relationship between photocurrent intensity and MUC1 concentration. The PEC biosensor exhibited excellent sensitivity for MUC1 detection with a wide detection range from 1 × 10-7 to 10 ng/mL and a detection limit of 8.1 ag/mL. The detection range for MCF-7 cells was from 2 × 101 to 2 × 106 cells/mL, with the capability for detecting single MCF-7 cells. The aptamer amplification strategy significantly enhanced PEC performance, and open up a promising platform to establish high selectivity, stability, and ultrasensitive analytical techniques.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Eletroquímicas , Mucina-1 , Polímeros , Mucina-1/análise , Humanos , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Células MCF-7 , Porosidade , Polímeros/química , Limite de Detecção , Técnicas Biossensoriais/métodos , Indóis/química , Processos Fotoquímicos , Compostos Organometálicos/químicaRESUMO
The basic mechanism of heterosis has not been systematically and completely characterized. In previous studies, we obtained three economically important fishes that exhibit rapid growth, WR (WCC â × RCC â), WR-II (WR â × WCC â), and WR-III (WR-II â × 4nAU â), through distant hybridization. However, the mechanism underlying this rapid growth remains unclear. In this study, we found that WR, WR-II, and WR-III showed muscle hypertrophy and higher muscle protein and fat contents compared with their parent species (RCC and WCC). Candidate genes responsible for this rapid growth were then obtained through an analysis of 12 muscle transcriptomes. Notably, the mRNA level of mstnb (myostatin b), which is a negative regulator of myogenesis, was significantly reduced in WR, WR-II, and WR-III compared with the parent species. To verify the function of mstnb, a mstnb-deficient mutant RCC line was generated using the CRISPR-Cas9 technique. The average body weight of mstnb-deficient RCC at 12 months of age was significantly increased by 29.57% compared with that in wild-type siblings. Moreover, the area and number of muscle fibers were significantly increased in mstnb-deficient RCC, indicating hypertrophy and hyperplasia. Furthermore, the muscle protein and fat contents were significantly increased in mstnb-deficient RCC. The molecular regulatory mechanism of mstnb was then revealed by transcription profiling, which showed that genes related to myogenesis (myod, myog, and myf5), protein synthesis (PI3K-AKT-mTOR), and lipogenesis (pparγ and fabp3) were highly activated in hybrid fishes and mstnb-deficient RCC. This study revealed that low expression or deficiency of mstnb regulates somatic growth by promoting myogenesis, protein synthesis, and lipogenesis in hybrid fishes and mstnb-deficient RCC, which provides evidence for the molecular mechanism of heterosis via distant hybridization.
Assuntos
Hibridização Genética , Desenvolvimento Muscular , Miostatina , Animais , Miostatina/genética , Miostatina/metabolismo , Desenvolvimento Muscular/genética , Vigor Híbrido/genética , Masculino , Peixes/genética , Peixes/crescimento & desenvolvimento , Peixes/metabolismo , Feminino , Transcriptoma , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismoRESUMO
Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex â ¡ (MHCâ ¡), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.
Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo W-135 , Animais , Camundongos , Sorogrupo , Toxoide Tetânico , Polissacarídeos Bacterianos , Vacinas Conjugadas , Anticorpos Antibacterianos , Imunidade Celular , Imunoglobulina G , Infecções Meningocócicas/prevenção & controleRESUMO
OBJECTIVE: To evaluate the application value of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in early diagnosis of lung cancer. METHODS: Retrospective analyses were conducted for 347 cases of pulmonary space-occupying lesions at Zhongshan Hospital from June 2010 to October 2012. The diagnostic validity of PET/CT and fluorodeoxyglucose maximum standardized uptake value (SUVmax) of lesions were compared respectively. Among different morphological characteristics, pathologic types and levels of tumor markers. The diagnostic value of PET/CT was also evaluated along with serum tumor markers for lung cancer. RESULTS: SUVmax was positively correlated with lesion size (r = 0.484, P < 0.05) and negatively with tumor differentiation degree (r = -0.232, P < 0.01). It was significantly higher in tumor marker positive group than the negative group (10.6 ± 5.5 vs 7.6 ± 5.4, P < 0.05). The diagnostic specificity, sensitivity and accuracy of PET/CT were 50.0%, 96.6% and 89.3% in lung cancer. And the greater the lesion, the higher the diagnostic accuracy (P < 0.05). PET/CT plus serum tumor markers could boost the diagnostic specificity of lung cancer by 30% (P < 0.01). CONCLUSIONS: (18)F-FDG PET/CT has high diagnostic values for early stage pulmonary nodules. It can also suggest the differentiation degree of lung cancer. Combined use of serum tumor markers and (18)F-FDG PET/CT increases the early diagnostic specificity of lung cancer.
Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/sangue , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: There have been many significant advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC). However, the mechanism underlying the progression of NSCLC is still not clear. Plant homodomain finger-like domain-containing protein 5A (PHF5A) plays an important role in processes of chromatin remodeling, morphological development of tissues and organs and maintenance of stem cell pluripotency. This study aims to investigate the role of PHF5A in the proliferation and migration of NSCLC. METHODS: A549 and PC-9 PHF5A overexpression cell lines were constructed. PHF5A expression was decreased in H292 and H1299 cells by using siRNA. Flow cytometry was used to detect the cell cycle. MTT assay and clone formation assay were used to examine the proliferative ability of NSCLC, while migration assay and wound healing assay were performed to evaluate the ability of migration. Western blot analysis was used to measure the expressions of PI3K, p-AKT and the associated downstream factors. RESULTS: Up-regulation of PHF5A in A549 and PC-9 cells increased the proliferation rate, while down-regulation of PHF5A in H292 and H1299 cells inhibited the proliferation rate at 24 h, 48 h and 72 h (P<0.05). The metastatic ability was elevated in the PHF5A-overexpresion groups, while reduced in the PHF5A-down-regulation group (P<0.05). In addition, reduced expression of PHF5A induced cell cycle arrest at G1/S phase (P<0.05). Furthermore, decreased expression of PHF5A reduced the expression levels of PI3K, phosphorylation of AKT, c-Myc (P<0.05) and elevated the expression of p21 (P<0.05). CONCLUSIONS: These results demonstrated that PHF5A may play an important role in progression of NSCLC by regulating the PI3K/AKT signaling pathway.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Transativadores/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Background: The correlation between potential risk factors such as obesity (leg fat percentage (left), arm fat percentage (left), waist circumference, body fat percentage, trunk fat percentage), smoking behaviors (past tobacco smoking, smoking initiation, smoking/smokers in household, current tobacco smoking) and reproductive traits (age first had sexual intercourse (AFS), age at menarche (AAM), and age at first birth (AFB)) have been linked to the occurrence of spontaneous abortion (SA). However, the causal associations between these factors and SA remain unclear. Methods: We conducted univariable and multivariable Mendelian randomization (MR) analyses to evaluate the associations of obesity, smoking behavior and reproductive traits with SA. To select appropriate genetic instruments, we considered those that had reached the genome-wide significance level (P < 5 × 10-8) in their corresponding genome-wide association studies (GWAS) involving a large number of individuals (ranging from 29,346 to 1,232,091). SA was obtained from the FinnGen consortium, which provided summary-level data for 15,073 SA cases and 135,962 non-cases. Results: Assessed individually using MR, the odds ratios (ORs) of SA were 0.728 (P = 4.3608×10-8), 1.063 (P = 0.0321), 0.926 (P = 9.4205×10-4), 1.141 (P = 7.9882×10-3), 5.154 (P = 0.0420), 1.220 (P = 0.0350), 1.228 (P = 0.0117), 0.795 (P = 0.0056), 1.126 (P = 0.0318), for one standard deviation (SD) increase in AFS, AAM, AFB, smoking initiation, smoking/smokers in household, arm fat percentage (left), leg fat percentage (left), waist circumference and body fat percentage, 0.925 (P = 0.4158) and 1.075 (P = 0.1479) for one SD increase in past tobacco smoking, trunk fat percentage for one SD increase in SA. In multivariable MR (MVMR), only AFS (OR = 0.802; P = 0.0250), smoking initiation (OR = 1.472, P = 0.0258), waist circumference (OR = 0.813, P = 0.0220) and leg fat percentage (left) (OR = 4.446, P = 0.043) retained a robust effect. Conclusion: Smoking behaviors, reproductive traits and obesity-related anthropometric indicators are potential causal factors for SA. Higher leg fat percentage; smoking initiation; and lower waist circumference and AFS may increase the risk of SA. Understanding the causal relationship for SA may provide more information for SA intervention and prevention strategies.
Assuntos
Aborto Espontâneo , Análise da Randomização Mendeliana , Gravidez , Feminino , Humanos , Estudo de Associação Genômica Ampla , Aborto Espontâneo/etiologia , Aborto Espontâneo/genética , Índice de Massa Corporal , Fumar/epidemiologia , Fumar/efeitos adversos , Obesidade/epidemiologia , Obesidade/genéticaRESUMO
Pertussis is a severe human respiratory tract infectious disease caused by Bordetella pertussis that primarily affects infants and young children. However, the acellular pertussis vaccine currently administered can induce antibody and Th2 immune responses but fails to prevent the nasal colonization and transmission of B. pertussis, causing a resurgence of pertussis, so improved pertussis vaccines are urgently needed. In this study, we created a two-component pertussis vaccine candidate containing a conjugate prepared from oligosaccharides and pertussis toxin. After demonstrating the ability of the vaccine to induce a mixed Th1/Th2/Th17 profile in a mouse model, the strong in vitro bactericidal activity and IgG response of the vaccine were further demonstrated. In addition, the vaccine candidate further induced efficient prophylactic effects against B. pertussis in a mouse aerosol infection model. In summary, the vaccine candidate in this paper induces antibodies with bactericidal activity to provide high protection, shorten the duration of bacterial existence, and further reduce disease outbreaks. Therefore, the vaccine has the potential to be the next generation of pertussis vaccines.
Assuntos
Bordetella pertussis , Coqueluche , Criança , Animais , Camundongos , Humanos , Pré-Escolar , Toxina Pertussis , Vacina contra CoquelucheRESUMO
Food-borne pathogens are one of the leading causes of food poisoning, which vigorously affect food safety and human health. Therefore, the development of early and rapid detection methods for food pollution evaluation is the key to food safety and quality control. Herein, a simple and inexpensive photoelectrochemical (PEC) sensor is developed for highly selective and ultrasensitive detection of Staphylococcus aureus (S. aureus). The technique is based on "signal-off" that employs Cu-C3N4-TiO2 heterostructures as photoactive materials and monolayer Cu-C3N4 nanozyme as a signal amplifier. In the presence of S. aureus, the aptamer-modified Cu-C3N4 (Cu-C3N4@Apt, a signal amplifier) and S. aureus were specifically anchored on the surface of the ligand-modified photoelectrode. The Cu-C3N4@Apt nanozyme acted as a peroxidase to catalyze the oxidation of 4-chloro-1-naphthol (4-CN) to produce insoluble precipitate on the electrode surface and resulted in a significant decrease in photocurrent. Based on the signal-amplification by the Cu-C3N4@Apt nanozyme, the constructed PEC sensor demonstrated a wide linear range between 10-108 CFU/mL for the S. aureus detection with the detection limit (LOD) as low as 3.40 CFU/mL. Furthermore, the PEC sensor was capable of determining S. aureus in spiked orange juice and milk, with the recovery of 91%-113%, indicating the reliability of the sensor for S. aureus detection in real samples. This investigation provides a feasible strategy for the design of highly selective and ultrasensitive PEC sensors to determine analytes in complex systems.
Assuntos
Técnicas Biossensoriais , Staphylococcus aureus , Técnicas Biossensoriais/métodos , Dimaprit/análogos & derivados , Técnicas Eletroquímicas/métodos , Humanos , Ligantes , Limite de Detecção , Peroxidases , Reprodutibilidade dos Testes , TitânioRESUMO
Distant hybridization can combine whole genomes from parent species and result in changes in the phenotypes and genotypes in hybrids. The characteristics of many hybrid fishes with even number of chromosomes have been reported, but the hybrids with odd number chromosomes are rarely reported. Blunt snout bream (Megalobrama amblycephala, BSB, 2n = 48) and rare gudgeon (Gobiocypris rarus, RG, 2n = 50) belong to two different subfamilies and have quite different biological characteristics. In this study, we obtain the hybrids (BR) derived from the inter-subfamily hybridization of female BSB and male RG. We investigate the fertilization rate, hatching rate, morphological traits, chromosomal numbers, DNA content, growth rates, and 5S rDNA in the BR. The results show that the BR is an allodiploid fish with 49 chromosomes, and all the measurable traits are significantly different (p < 0.05) among BR, BSB, and BR. Interestingly, the upper part of the BR body color is similar to BSB (gray), the lower part of the BR body color is similar to RG (light yellow), and the BR inherits a unique light yellow wide longitudinal band from the RG. Furthermore, the BR has a fast growth rate compared with RG. The 5S rDNA of the BR inherits the specific bands of its parental 5S rDNA respectively and has some mutations, which show obvious recombination, heredity, and variability in BR. This study will be of great significance in fish genetic breeding.
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OBJECTIVE: to highlight the clinical manifestation, histologic characteristics, diagnostic and therapeutic method of tracheal lobular capillary hemangioma (LCH). METHODS: the clinical, auxiliary examinational and pathological data of two patients with tracheal LCH were presented, and relevant literatures were reviewed. RESULTS: LCH is a polypoid form of capillary hemangioma which usually occurs on skin or muscosal surface of oral and nasal, rarely be seen in trachea. The most common presenting symptom of tracheal LCH is recurrent haemoptysis, CT scan can help to make diagnosis. Transbronchoscopic interventional therapy is the most effective treatment for tracheal LCH. Histologic examination can help to make the extreme diagnosis. CONCLUSIONS: tracheal LCH is a scarce benign lesion of tracheal. There isn't any typical clinical manifestation and auxiliary examination. Histologic examination can make a definite diagnosis, and bronchoscopes plays the most effective part in diagnosis and therapy.
Assuntos
Granuloma Piogênico , Neoplasias da Traqueia , Adolescente , Broncoscopia , Feminino , Granuloma Piogênico/diagnóstico , Granuloma Piogênico/terapia , Hemoptise , Humanos , Masculino , Neoplasias da Traqueia/diagnóstico , Neoplasias da Traqueia/terapiaRESUMO
BACKGROUND: Previous studies have provided conflicting evidence about the increased overall survival (OS) in lung cancer patients with diabetes mellitus (DM) compared with those without DM. This study assessed progression-free survival (PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients. METHODS: Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai. The data included patient sex, age, body mass index (BMI), smoking status, history of DM, level of blood glucose, pathological type, clinical stage of cancer, chemotherapy regimen, and history of anti-DM drugs. The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS. For comparison of PFS/OS in lung cancer with or without DM, patients were divided into three groups: lung cancer with DM, lung cancer without DM but with elevated level of blood glucose, lung cancer without DM or elevated level of blood glucose. RESULTS: In total, the data from 200 lung cancer patients (138 males/62 females, aged 29.0 to 78.0 years, mean 60.0â±â8.6 years) were collected. For the comparison of PFS/OS in lung cancer patients with or without DM, patients were divided into three groups: lung cancer with DM (nâ=â31); lung cancer without DM but with elevated levels of blood glucose (nâ=â40); and lung cancer without both DM and elevated levels of blood glucose (nâ=â128), whereas 1 patient dropped out of the study. All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months. Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM (log-rank, Pâ<â0.05, Pâ<â0.01); the median PFS in lung cancer with DM was 12.0 months (95% confidence interval [CI], 4.0-16.0) vs. 6.0 months in those without DM (95% CI, 5.8-6.3); and the median OS in lung cancer patients with DM was 37.0 months (95% CI, 29.0-46.6) vs. 12.0 months in those without DM (95% CI, 10.9-13.1). For the other two groups of patients without DM, there was a trend toward a shorter PFS and OS in patients with elevated blood glucose compared with those without elevated blood glucose. Cox regression showed that PFS in lung cancer patients was favorably associated with the usage of anti-DM drugs, BMI, clinical stage of cancer, and chemotherapy regimen (all Pâ<â0.05) but was inversely associated with the level of blood glucose (Pâ<â0.05). CONCLUSIONS: Lung cancer patients with DM have prolonged PFS and OS compared with those without DM, and the level of blood glucose was inversely associated with PFS. The current results indicate that PFS may be a meaningful intermediate endpoint for OS and that the levels of blood glucose hopefully represent a prognostic factor in lung cancer patients.
Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Glicemia/metabolismo , China , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Lung cancer is the most common and lethal cancer worldwide, especially in developing countries. Nonsmall cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer. In aprevious study, the protein expression of ubiquitin conjugating enzyme E2 C (UBE2C/UbcH10) in NSCLC tissues and cells was found to be significantly higher than that in adjacent tissues and normal lung epithelial cells. Further study revealed that the aberrant expression of UbcH10 in NSCLC tumors or cancer cells was caused by inactivation of the posttranscriptional regulation mechanism, and thus microRNAs (miRNAs) may play an important. In the present study, it was demonstrated that the expression of microRNA, hsamiR6613p, was downregulated and UbcH10 was upregulated in 12 pairs of NSCLC tumors and three NSCLC cell lines. A reporter gene assay revealed that overexpression of hsamiR6613p effectively reduced the activity of luciferase expressed by a vector bearing the 3' untranslated region of UbcH10 mRNA. Ectopic hsamiR6613p overexpression mediated by lentiviral infection decreased the expression of UbcH10. Infection of LvmiR6613p inhibited cell growth and invasion in A549 and SKMES1 cells. Mechanistically, hsamiR6613p induced cell cycle G2 arrest through regulation of spindle assembly checkpoint (SAC) function. On the basis of the proposed mechanisms, the objective of the study was to inhibit the proliferation of A549 and SKMES1 by expressing hsamiR6613p in vivo and in vitro. Collectively, our results indicated that downregulation of hsamiR6613p was involved in NSCLC and restoration of hsamiR6613p impaired the growth of NSCLC cell lines A549 and SKMES1, suggesting that hsamiR6613p may be a potential target molecule for the therapy of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Células A549 , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Interferência de RNA , Enzimas de Conjugação de Ubiquitina/metabolismo , Regulação para CimaRESUMO
Osteopontin (OPN) is known to be overexpressed in numerous carcinomas. Although abundant OPN has been reported to be correlated with poor survival in non-small cell lung cancer (NSCLC) but their clinical and prognostic significance in SCLC remains unknown. In this study, RNA-sequencing was used to obtain gene expression data in SCLC tissue samples and OPN expression levels were then investigated using qPCR, immunohistochemical and Western blot. We found OPN was one of the most upregulated genes. Besides, the correlation of OPN with tumor clinicopathological characteristics was evaluated and we found OPN was associated with advanced tumor stages. In addition, Kaplan-Meier survival analysis and Cox analyses revealed OPN expression was an independent predictor for overall survival (OS) (P= 0.013) and progression-free survival (PFS) (P=0.008). A high level of OPN was correlated with pT classification and pN classification (P<0.05). Moreover, In vitro experiments, by test the biological function of OPN via colony formation, wound healing, Transwell assays, and western blotting, we found that overexpression of OPN induced cell proliferation, migration, and invasion; down-regulation of OPN inhibited these. Overexpression of OPN stimulates epithelial-mesenchymal transition (EMT) whereas OPN silencing prevents the EMT. IN CONCLUSION: OPN appears to contribute to the malignant mechanism of SCLC and is a promising and significant prognostic predictor in patients with SCLC. Specific silence of OPN could be a future direction to develop a novel therapeutic strategy for SCLC patients.
RESUMO
Blocking PcrV, an essential component of the Type III secretion system (TTSS), has demonstrated efficacy against Pseudomonas aeruginosa infections. However, most of the results came from laboratory strains. Whether it is applicable to clinically isolated multi-drug resistant (MDR) strains is unknown. In this study we investigated the expression level of TTSS in clinically isolated MDR P. aeruginosa strains and the effects of anti-PcrV antibody on MDR isolate induced acute lung injury (ALI). The expression level of TTSS was quantified in 53 isolates including 25 MDR strains and 28 susceptible strains. We investigated the effect of anti-PcrV antibody through a murine model induced by instillation of a MDR strain into the left lung through trachea. Our results showed that the expression level of TTSS in MDR strains is comparable to susceptible strains. Anti-PcrV ensured the survival of challenged mice, reduced the bacteria numbers and attenuated lung inflammation and injury. This study proved that anti-PcrV may be a potentially effective strategy against MDR P. aeruginosa induced ALI.