RESUMO
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that progresses from hepatic steatosis to non-alcoholic steatohepatitis, cirrhosis, and liver cancer, posing a huge burden on human health. Existing research has confirmed that forkhead box O1 (FOXO1), as a member of the FOXO transcription factor family, is upregulated in MAFLD. Its activity is closely related to nuclear-cytoplasmic shuttling and various post-translational modifications including phosphorylation, acetylation, and methylation. FOXO1 mediates the progression of MAFLD by regulating glucose metabolism, lipid metabolism, insulin resistance, oxidative stress, hepatic fibrosis, hepatocyte autophagy, apoptosis, and immune inflammation. This article elaborates on the regulatory role of FOXO1 in MAFLD, providing a summary and new insights for the current status of drug research and targeted therapies for MAFLD.
RESUMO
Lateral flow immunoassays (LFIAs) are recognized for their practicality in homecare and point-of-care testing, owing to their simplicity, cost-efficiency, and rapid visual readouts. Despite these advantages, LFIAs typically fall short in sensitivity, particularly in detecting viruses such as SARS-CoV-2, thus limiting their broader application. In response to this challenge, we have innovated an approach to substantially enhance LFIA sensitivity. This involves the integration of a water-soluble dextran-methacrylate polymer wall with a 15% grafting degree positioned between the test and control lines on the LFIA strip. This novel modification significantly improved the sensitivity of the assay, achieving detection limits as low as 50 pg mL-1 and enhancing the sensitivity by 5-20-fold relative to existing LFIA kits available on the market. Furthermore, our developed LFIA kit (WSPW-LFIA) demonstrated exceptional specificity for SARS-CoV-2. Coupled with a straightforward fabrication process and robust stability, the WSPW-LFIA represents a promising advancement for real-time in vitro diagnosis across a spectrum of diseases.
Assuntos
COVID-19 , Polímeros , SARS-CoV-2 , SARS-CoV-2/imunologia , Humanos , COVID-19/diagnóstico , Imunoensaio/métodos , Polímeros/química , Técnicas Biossensoriais , Antígenos Virais/análise , Água , Sensibilidade e Especificidade , Limite de Detecção , Teste Sorológico para COVID-19/métodos , DextranosRESUMO
The objective is to preliminary evaluated postoperative leukocyte counts as a surrogate for the surgical stress response in NSCLC patients who underwent RATS or VATS for further prospective analyses with proper assessment of surgical stress response and tissue trauma. We retrospectively analyzed patients with stageI-IIIA NSCLC who underwent RATS or VATS at a hospital between 8 May 2020 and 31 December 2021. Analysis of leukocytes (including neutrophils and lymphocytes) and albumin on postoperative days (PODs) 1 and 3 in patients with NSCLC treated with RATS or VATS after propensity score matching (PSM). In total, 1824 patients (565 RATS and 1259 VATS) were investigated. The two MIS groups differed significantly with regard to operative time (p < 0.001), chronic lung disease (p < 0.001), the type of pulmonary resection (p < 0.001), the excision site of lobectomy (p = 0.004), and histology of the tumor (p = 0.028). After PSM, leukocyte and neutrophil levels in the RATS group were lower than those in the VATS group on PODs 1 and 3, with those on POD 3 (p < 0.001) being particularly notable. While lymphocyte levels in the RATS group were significantly lower than those in the VATS group only at POD 1 (p = 0.016). There was no difference in albumin levels between the RATS and VATS groups on PODs 1 and 3. The surgical stress response and tissue trauma was less severe in NSCLC patients who underwent RATS than in those who underwent VATS, especially reflected in the neutrophils of leukocytes.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Cirurgia Torácica Vídeoassistida , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Contagem de Leucócitos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Albuminas , Neoplasias Pulmonares/cirurgiaRESUMO
Cholangiocarcinoma (CCA) is a malignancy with an extremely poor prognosis, and much remains unknown about its pathogenesis and treatment modalities. Circular RNA (circRNA) has been proven to play regulatory roles in various tumorigenesis, yet its potential function and mechanism in cholangiocarcinoma require further investigation. This study is the first to identify the aberrant expression and functional role of a novel circRNA, circ_0007534, derived from the DDX42 gene, in cholangiocarcinoma. Compared to the normal control group, the expression of circ_0007534 was significantly elevated in the tissues and cells with CCA and that high expression correlated with lymph node invasion and poor prognosis. Functional experiments indicated that downregulating circ_0007534 markedly inhibited the proliferation, migration, invasion, stemness, and anti-anoikis ability of CCA cells, as well as the tumor growth and liver and lung metastasis in nude mice. Mechanistic studies revealed that DDX42, as the parent gene of circ_0007534, can mutually regulate each other's expression. Predominantly located in the cytoplasm, circ_0007534 can form a complex with the RNA-binding protein DDX3X, which enhances the stability of DDX42 mRNA, thereby upregulating the expression of DDX42. This creates a positive feedback loop among the three, collectively promoting the progression of cholangiocarcinoma. In conclusion, this study sheds light on the pivotal role and molecular mechanism of circ_0007534 in the development of CCA, offering potential new targets for early diagnosis and treatment.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Anoikis , Camundongos Nus , Retroalimentação , Linhagem Celular Tumoral , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
This study thoroughly investigated the role of the long non-coding RNA LOXL1-AS1 in the pathogenesis of cholangiocarcinoma (CCA). Through bioinformatics analysis and tissue samples validation, the study found that LOXL1-AS1 was significantly elevated in CCA, with its high expression closely tied to clinical pathological features and prognosis. In vitro and in vivo experiments revealed that LOXL1-AS1 was crucial in regulating CCA cell apoptosis, proliferation, migration, and invasion. Further investigations using FISH, subcellular localization experiments, RNA pull down, and RIP uncovered that LOXL1-AS1 primarily resided in the cytoplasm and influenced CCA progression by modulating the JAK2/STAT3 signaling pathway. Notably, LOXL1-AS1 might regulate the activity of JAK2 through modulating its ubiquitination and degradation. YY1 had also been found to act as an upstream transcription factor of LOXL1-AS1 to impact CCA cell malignancy. These findings shed light on the pivotal role of LOXL1-AS1 in CCA and offered potential directions for novel therapeutic strategies, providing a fresh perspective on tumor pathogenesis.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , RNA Longo não Codificante , Fator de Transcrição STAT3 , Humanos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de SinaisRESUMO
Addressing the challenges of chemodynamic therapies (CDTs) relying on Fenton reactions in malignant tumors is an active research area. Here, we report a method to develop pH-responsive hybrid nanoparticles for enhanced chemodynamic tumor treatment. Reactive CaO2 nanoparticles (core) are isolated by biocompatible ZIF-8 doped with Fe2+ (shell), and then encapsulated by macrophage membranes (symbolized as CaO2@Fe-ZIF-8@macrophage membrane or CFZM), thus endowed with high stability under normal physiological conditions. Our design features active tumor-homing by the macrophage-membrane coating, tumor microenvironment (TME)-responsive cargo release, and self-supplied hydrogen peroxide for promotion of the Fenton reaction. We demonstrate the improved delivery/tumor cell uptake of CFZM, the efficient production of toxic ËOH with self-supplied H2O2 in CFZM, and high-efficacy tumor ablation on BALB/c mice bearing CT26 tumor cells. This offers a translational strategy to develop active tumor-targeting and TME-responsive nanotherapeutics with enhanced CDT against malignant tumors.
Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Peróxido de Hidrogênio , Citoplasma , Macrófagos , Camundongos Endogâmicos BALB C , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
Antimicrobial-resistant bacterial infections threaten to become the number one cause of death by the year 2050. Since the speed at which antimicrobial-resistance develops is exceeding the pace at which new antimicrobials come to the market, this threat cannot be countered by making more, new and stronger antimicrobials. Promising new antimicrobials should not only kill antimicrobial-resistant bacteria, but also prevent development of new bacterial resistance mechanisms in strains still susceptible. Here, PAMAM-dendrimers are clustered using glutaraldehyde to form megamers that are core-loaded with ciprofloxacin and functionalized with HA-SNO. Megamers are enzymatically disintegrated in an acidic pH, as in infectious biofilms, yielding release of ciprofloxacin and NO-generation by HA-SNO. NO-generation does not contribute to the killing of planktonic Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, but in a biofilm-mode of growth short-lived NO-assisted killing of both ciprofloxacin-susceptible and ciprofloxacin-resistant bacterial strains by the ciprofloxacin released. Repeated sub-culturing of ciprofloxacin-susceptible bacteria in presence of ciprofloxacin-loaded and HA-SNO functionalized PAMAM-megamers does not result in ciprofloxacin-resistant variants as does repeated culturing in presence of ciprofloxacin. Healing of wounds infected by a ciprofloxacin-resistant S. aureus variant treated with ciprofloxacin-loaded, HA-SNO functionalized megamers proceed faster through NO-assisted ciprofloxacin killing of infecting bacteria and stimulation of angiogenesis.
Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Camundongos , Animais , Ciprofloxacina/farmacologia , Antibacterianos/farmacologia , Ácido Hialurônico/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Resistência Microbiana a Medicamentos , Anti-Infecciosos/farmacologia , Biofilmes , Concentração de Íons de Hidrogênio , Pseudomonas aeruginosaRESUMO
Children with low immunity and weak resistance are at high risk for influenza, and infection with the influenza virus can be life-threatening in severe cases. This article reported on the investigation and management of a clustered of influenza A cases in a pediatric ward. The clustered influenza A cases were caused by a community-infected influenza A chaperone who was the source of infection, and was most likely spread in close proximity through droplets or aerosols in the same hospital ward. This person caused the influenza A hospital-acquired infections in 2 children (aged 11 months and 12 months, respectively) in the hospital. After taking timely case management and ward management, the prognosis of the three infected patients was good and there was no outbreak of influenza-like illness in the pediatric ward. It is recommended that during the peak of the influenza season, air disinfection should be strengthened and windows should be opened for ventilation in medical institutions, while patients and accompanying staff should be strengthened to wear masks and other publicity, and influenza vaccination should be encouraged, so as to reduce cross-transmission and prevent outbreaks of hospital-acquired infections.
Assuntos
Infecção Hospitalar , Influenza Humana , Viroses , Humanos , Infecção Hospitalar/prevenção & controle , Surtos de Doenças/prevenção & controle , Hospitais , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , LactenteRESUMO
Treatment of acute bacterial meningitis is difficult due to the impermeability of the blood-brain barrier, greatly limiting the antibiotic concentrations that can be achieved in the brain. Escherichia coli grown in presence of iron-oxide magnetic nanoparticles secrete large amounts of magnetic outer-membrane vesicles (OMVs) in order to remove excess Fe from their cytoplasm. OMVs are fully biomimetic nanocarriers, but can be inflammatory. Here, non-inflammatory magnetic OMVs were prepared from an E. coli strain in which the synthesis of inflammatory lipid A acyltransferase was inhibited using CRISPR/Cas9 mediated gene knockout. OMVs were loaded with ceftriaxone (CRO) and meso-tetra-(4-carboxyphenyl)porphine (TCPP) and magnetically driven across the blood-brain barrier for sonodynamic treatment of bacterial meningitis. ROS-generation upon ultrasound application of CRO- and TCPP-loaded OMVs yielded similar ROS-generation as by TCPP in solution. In vitro, ROS-generation by CRO- and TCPP-loaded OMVs upon ultrasound application operated synergistically with CRO to kill a hard-to-kill, CRO-tolerant E. coli strain. In a mouse model of CRO-tolerant E. coli meningitis, CRO- and TCPP-loaded OMVs improved survival rates and clinical behavioral scores of infected mice after magnetic targeting and ultrasound application. Recurrence did not occur for at least two weeks after arresting treatment.
Assuntos
Antibacterianos , Meningites Bacterianas , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Espécies Reativas de Oxigênio , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Meningites Bacterianas/tratamento farmacológico , Proteínas da Membrana Bacteriana ExternaRESUMO
Hepatocellular carcinoma (HCC) is a highly malignant tumor that carries a significant risk of morbidity and mortality. This type of cancer is prevalent in Asia due to the widespread presence of risk factors. Unfortunately, HCC often goes undetected until it has reached an advanced stage, making early detection and treatment critical for better outcomes. Alpha-fetoprotein (AFP) is commonly used in clinical practice for diagnosing HCC, but its sensitivity and specificity are limited. While surgery and liver transplantation are the main radical treatments, drug therapy and local interventions are better options for patients with advanced HCC. Accurately assessing treatment efficacy and adjusting plans in a timely manner can significantly improve the prognosis of HCC. Non-coding RNA gene transcription products cannot participate in protein production, but they can regulate gene expression and protein function through the regulation of transcription and translation processes. These non-coding RNAs have been found to be associated with tumor development in various types of tumors. Noncoding RNA released by tumor or blood cells can circulate in the blood and serve as a biomarker for diagnosis, prognosis, and efficacy assessment. This article explores the unique role of circulating noncoding RNA in HCC from various perspectives.
RESUMO
Bacterially induced sepsis requires rapid bacterial detection and identification. Hours count for critically ill septic patients, while current culture-based detection requires at least 10 h up to several days. Here, we apply a microfluidic device equipped with a bacterially activated, macrophage-membrane-coating on nanowired-Si adsorbent surfaces for rapid, bacterial detection and Gram-identification in bacterially contaminated blood. Perfusion of suspensions of Gram-negative or Gram-positive bacteria through a microfluidic device equipped with membrane-coated adsorbent surfaces detected low (<10 CFU/mL) bacterial levels. Subsequent, in situ fluorescence-staining yielded Gram-identification for guiding antibiotic selection. In mixed Escherichia coli and Staphylococcus aureus suspensions, Gram-negative and Gram-positive bacteria were detected in the same ratios as those fixed in suspension. Results were validated with a 100% correct score by blinded evaluation (two observers) of 15 human blood samples, spiked with widely different bacterial strains or combinations of strains, demonstrating the potential of the platform for rapid (1.5 h in total) diagnosis of bacterial sepsis.
Assuntos
Bactérias , Sepse , Humanos , Suspensões , Dispositivos Lab-On-A-Chip , Escherichia coli , Macrófagos , Sepse/diagnósticoRESUMO
Biliary tract cancer (BTC) is a devastating malignancy that is notoriously difficult to diagnose and is associated with high mortality. Circular RNA (circRNA) is a class of endogenous non-coding RNA which has been regarded as the key regulator of tumor initiation and progression, including BTC. Circular RNA nuclear receptor interacting protein 1 (circ_NRIP1), as a circular RNA, is abnormally expressed in many human tumors and exhibits diverse functions in cancer progression. However, its biological significance in BTC has not been thoroughly investigated. In this research, we elucidated that circ_NRIP1 was notably overexpressed in both BTC tissues and cells. We further established a correlation between circ_NRIP1 expression and clinicopathological features in BTC patients, highlighting its clinical relevance. Through functional assays, we observed that knockdown of circ_NRIP1 significantly inhibited tumor cell proliferation, invasion, stemness maintenance, and epithelial-mesenchymal transition, indicating its active involvement in promoting BTC progression. Additionally, it attenuated growth of xenograft and metastasis models. Mechanically, we revealed that circ_NRIP1 served as the competing endogenous RNA to sequester miR-515-5p through complementary base pairing mechanism, thereby upregulated AKT2 expression and indirectly activated PI3K/AKT/mTOR signaling pathway. Generally, targeting the circ_NRIP1/miR-515-5p/AKT2 axis and aberrant activation of the PI3K/AKT/mTOR pathway may hold promising therapeutic strategies for BTC. Our research contributes to a better understanding of the underlying biological basis of BTC and paves the way for the development of innovative treatment approaches.
Assuntos
Neoplasias do Sistema Biliar , MicroRNAs , Humanos , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transição Epitelial-Mesenquimal/genética , Proteína 1 de Interação com Receptor Nuclear/genética , Proteína 1 de Interação com Receptor Nuclear/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células/genética , Neoplasias do Sistema Biliar/genética , Movimento CelularRESUMO
This study provides a novel method of preparing lotus seed starch nanocrystals (LS-SNCs) using acid hydrolysis combined with ultrasonic-assisted acid hydrolysis (U-LS-SNCs) and evaluates the structural characteristics of starch nanocrystals using scanning electron microscopy; analysis of particle size, molecular weight, and X-ray diffraction patterns; and FT-IR spectroscopy. The results showed that the preparation time of U-LS-SNCs could be reduced to 2 days less than that for LS-SNCs. The smallest particle size and molecular weight were obtained after a 30 min treatment with 200 W of ultrasonic power and 5 days of acid hydrolysis. The particle size was 147 nm, the weight-average molecular weight was 3.42 × 104 Da, and the number-average molecular weight was 1.59 × 104 Da. When the applied ultrasonic power was 150 W for 30 min and acid hydrolysis was applied for 3 days, the highest relative crystallinity of the starch nanocrystals was 52.8%. The modified nanocrystals can be more widely used in various applications such as food-packaging materials, fillers, pharmaceuticals, etc.
RESUMO
INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is one of the most common glomerulonephritic diseases in the world. Several lines of evidence have suggested that dyslipidemia is related to the disease progression and prognosis of IgAN. However, the study is scarce on the clinicopathological characteristics and outcomes of IgAN with dyslipidemia. METHODS: This study retrospectively analyzed 234 patients with biopsy-proven idiopathic IgAN at the Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and June 2021. The participants were divided into dyslipidemia (n = 119) and non-dyslipidemia (n = 115), and the dyslipidemia group was also divided into the following 4 groups: hypertriglyceridemia group, hypercholesterolemia group, mixed hyperlipidemia group, and low high-density lipoprotein cholesterol group. The estimated glomerular filtration rate (eGFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The prevalence of dyslipidemia in IgAN patients in our center was 50.9% (119/234). The patients with dyslipidemia presented with higher systolic blood pressure (BP), diastolic BP, serum creatinine, uric acid, hemoglobin, proteinuria, and eGFR (p < 0.05). Proportions of males, hypertension, and chronic kidney disease stage 2â¼5 were also higher in the dyslipidemia group (p < 0.05). Similarly, the pathological characteristics performed were worse in the dyslipidemia group. Most dyslipidemia patients had a higher percentage of mesangial hypercellularity (M1) and tubular atrophy/interstitial fibrosis (T1â¼2) in the Oxford Classification's scoring system (p < 0.05). Multivariate logistic regression analysis revealed that male gender (odds ratio [OR] = 2.397, 95% confidence interval [CI]: 1.051-5.469, p = 0.038) and proteinuria (OR = 1.000, 95% CI: 1.000-1.001, p = 0.035) were possible risk factors for dyslipidemia. A total of 13 patients (13.8%) in the dyslipidemia group had an endpoint event, of which 6 patients (6.4%) had a ≥50% decrease in eGFR from baseline and 7 patients (7.4%) reached the end-stage renal disease stage. Kaplan-Meier survival curve analysis showed that patients in the dyslipidemia group had a worse outcome than those in the non-dyslipidemia group (log-rank test, p = 0.048). CONCLUSIONS: IgAN patients with dyslipidemia presented more severe clinicopathological characteristics. Male gender and proteinuria are significantly associated with the occurrence of dyslipidemia in IgAN patients. Patients in the dyslipidemia group had a worse prognosis than those in the non-dyslipidemia group, which may be essential for the disease management of IgAN and help identify the high-risk patients.
Assuntos
Dislipidemias , Glomerulonefrite por IGA , Falência Renal Crônica , Humanos , Masculino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Estudos Retrospectivos , China/epidemiologia , Prognóstico , Progressão da Doença , Taxa de Filtração Glomerular , Falência Renal Crônica/complicações , Proteinúria/complicações , Dislipidemias/complicaçõesRESUMO
The phenotypic changes of circulating tumor cells (CTCs) during the epithelial-mesenchymal transition (EMT) have been a hot topic in tumor biology and cancer therapeutic development. Here, an integrated platform of single-cell fluorescent enzymatic assays with superwetting droplet-array microchips (SDAM) for ultrasensitive functional screening of epithelial-mesenchymal sub-phenotypes of CTCs is reported. The SDAM can generate high-density, volume well-defined droplet (0.66 nL per droplet) arrays isolating single tumor cells via a discontinuous dewetting effect. It enables sensitive detection of MMP9 enzyme activities secreted by single tumor cells, correlating to their epithelial-mesenchymal sub-phenotypes. In the pilot clinical double-blind tests, the authors have demonstrated that SDAM assays allow for rapid identification and functional screening of CTCs with different epithelial-mesenchymal properties. The consistency with the clinical outcomes validates the usefulness of single-cell secreted MMP9 as a biomarker for selective CTC screening and tumor metastasis monitoring. Convenient addressing and recovery of individual CTCs from SDAM have been demonstrated for gene mutation sequencing, immunostaining, and transcriptome analysis, revealing new understandings of the signaling pathways between MMP9 secretion and the EMT regulation of CTCs. The SDAM approach combined with sequencing technologies promises to explore the dynamic EMT plasticity of tumors at the single-cell level.
Assuntos
Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes , Humanos , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Metaloproteinase 9 da Matriz/genética , Células Neoplásicas Circulantes/metabolismo , Método Duplo-CegoRESUMO
Eradication of infectious biofilms is becoming increasingly difficult due to the growing number of antibiotic-resistant strains. This necessitates development of nonantibiotic-based, antimicrobial approaches. To this end, we designed a heterocatalytic metal-organic framework composed of zirconium 1,4-dicarboxybenzene (UiO-66) with immobilized Pt nanoparticles (Pt-NP/UiO-66). Pt-NP/UiO-66 enhanced singlet-oxygen generation compared with Pt nanoparticles or UiO-66, particularly in an acidic environment. Singlet-oxygen generation degraded phosphodiester bonds present in eDNA gluing biofilms together and therewith dispersed biofilms. Remaining biofilms possessed a more open structure. Concurrently, Pt-NP/UiO-66 stimulated macrophages to adapt a more M1-like, "fighting" phenotype, moving faster toward their target bacteria and showing increased bacterial killing. As a combined effect of biofilm dispersal and macrophage polarization, a subcutaneous Staphylococcus aureus biofilm in mice was more readily eradicated by Pt-NP/UiO-66 than by Pt nanoparticles or UiO-66. Therewith, heterocatalytic Pt-NP/UiO-66 metal-organic frameworks constitute a nonantibiotic-based strategy to weaken protective matrices and disperse infectious biofilms, while strengthening macrophages in bacterial killing.
Assuntos
Doenças Transmissíveis , Estruturas Metalorgânicas , Camundongos , Animais , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/química , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , Oxigênio/farmacologiaRESUMO
Circular RNAs (circRNAs), a novel type of covalently closed non-coding RNAs, are widely expressed in eukaryotes and viruses. Accumulating evidence has shown that circRNAs play key roles in the pathophysiological changes process of human diseases and can affect cancer development and progression through regulating target genes expression, linear RNA transcription and protein generation. Recent studies had found that circRNA-UBAP2 (ubiquitin binding associated protein 2) was aberrantly expressed in various human tumors and could affect tumor cells proliferation, migration, invasion, cell cycle, anti-apoptosis, radioresistance, chemoresistance and other malignant biological behavioral progress. Mechanistic studies further revealed that circUBAP2 could affect the occurrence and development of human tumors through multiple different molecular regulatory pathways in vivo and in vitro. In addition, the abnormal expression of circUBAP2 was significantly correlated with the clinicopathological characteristics of malignant tumors and had potential value as biomarkers for the diagnosis and prognosis evaluation of cancer patients, which deserved further study. This review had summarized and discussed the oncogenic roles and clinical performances of circUBAP2 in various human malignancies with a focus on biological functions and molecular mechanisms, which could help to elevate the understanding to the roles of circRNAs and continue subsequent studies on circUBAP2.
Assuntos
Neoplasias , RNA Circular , Humanos , Neoplasias/genética , Prognóstico , RNA/genética , RNA Circular/genética , Ubiquitinas , Proteínas de Transporte/metabolismoRESUMO
The post-translational modification of proteins enables cells to respond promptly to dynamic stimuli by controlling protein functions. In higher plants, SPINDLY (SPY) and SECRET AGENT (SEC) are two prominent O-glycosylation enzymes that have both unique and overlapping roles; however, the effects of their O-glycosylation on fruit ripening and the underlying mechanisms remain largely unknown. Here we report that SlSPY affects tomato fruit ripening. Using slspy mutants and two SlSPY-OE lines, we provide biological evidence for the positive role of SlSPY in fruit ripening. We demonstrate that SlSPY regulates fruit ripening by changing the ethylene response in tomato. To further investigate the underlying mechanism, we identify a central regulator of ethylene signalling ETHYLENE INSENSITIVE 2 (EIN2) as a SlSPY interacting protein. SlSPY promotes the stability and nuclear accumulation of SlEIN2. Mass spectrometry analysis further identified that SlEIN2 has two potential sites Ser771 and Thr821 of O-glycans modifications. Further study shows that SlEIN2 is essential for SlSPY in regulating fruit ripening in tomatoes. Collectively, our findings reveal a novel regulatory function of SlSPY in fruit and provide novel insights into the role of the SlSPY-SlEIN2 module in tomato fruit ripening.
Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
The interactions between starch and protein, the essential components of lotus seed, strongly influence the quality of lotus seed processing by-products. This study investigated the effects of lotus seed starch-protein (LS-LP) interactions on the structural, thermal and gelatinization properties of LS-LP mixtures, using LS/LP ratios of 6:1, 6:2, 6:3, 6:4, 6:5, or 1:1, after heat treatment (95 °C, 30 min). Fourier transform infrared peaks at 1540 cm-1 and 3000-3600 cm-1 revealed the major interactions (electrostatic and hydrogen bonding) between LS and LP. The UV-visible absorption intensities (200-240 nm) of LS-LP mixtures increased with increased protein content. X-ray diffraction and electron microscopy revealed that LS-LP consists of crystalline starch granules encapsulated by protein aggregates. Increasing the addition of protein to the mixtures restricted the swelling of the starch granules, based on their solubility, swelling properties and thermal properties. Viscometric analysis indicated that the formation of LS-LP mixtures improved structural and storage stability. These findings provide a practicable way to control the thermal and gelatinization properties of lotus seed starch-protein mixtures, by changing the proportions of the two components, and provide a theoretical basis for developing novel and functional lotus-seed-based foods.