RESUMO
Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications1,2. Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer3-5. High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype. Here we show that hyperglycaemic conditions have an adverse effect on the DNA 5-hydroxymethylome. We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo. Treatment with the anti-diabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels. These findings define a novel 'phospho-switch' that regulates TET2 stability and a regulatory pathway that links glucose and AMPK to TET2 and 5hmC, which connects diabetes to cancer. Our data also unravel an epigenetic pathway by which metformin mediates tumour suppression. Thus, this study presents a new model for how a pernicious environment can directly reprogram the epigenome towards an oncogenic state, offering a potential strategy for cancer prevention and treatment.
Assuntos
Adenilato Quinase/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus/metabolismo , Glucose/metabolismo , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animais , DNA/química , DNA/metabolismo , Metilação de DNA , Diabetes Mellitus/genética , Dioxigenases , Estabilidade Enzimática , Epigênese Genética , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/genética , Fosforilação , Fosfosserina/metabolismo , Especificidade por Substrato , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND AND OBJECTIVE: This study comprehensively evaluates the distribution patterns and antimicrobial resistance profiles of urinary pathogens in Preoperative midstream urine cultures collected from patients with urinary calculi in China over the last two decades. METHODS: A cross-sectional analysis of 41 studies was conducted. A systematic search across various databases, including Wanfang Data, CNKI, SinoMed, Embase, PubMed, and Web of Science, was carried out, covering the time period from 2002 to 2022. Using R 4.2.1 software, a meta-analysis was performed to assess heterogeneity using Cochran's Q test and the I2 statistic. RESULTS: In the analysis of preoperative midstream urine cultures from Chinese patients with urinary calculi, gram-negative bacteria dominated at 69%, with Escherichia coli (43%), Klebsiella pneumoniae (8%), Proteus mirabilis (6%), Pseudomonas aeruginosa (5%), Acinetobacter baumannii (3%), and Enterobacter cloacae (4%) being prominent. Gram-positive organisms included Enterococcus faecalis (9%), Enterococcus faecium (5%), and Staphylococcus aureus (4%). Over time, proportions of Proteus mirabilis, Enterococcus faecalis, and Staphylococcus aureus decreased, while Klebsiella pneumoniae and Pseudomonas aeruginosa increased. Notably, Escherichia coli proportion reduced from 37 to 33% within the last two decades. Antimicrobial resistance analysis indicated declining resistance in E. coli (e.g., co-trimoxazole from 73 to 55%, gentamicin from 64 to 40%), but rising resistance in piperacillin and cefotaxime (34-60%). Enterococcus faecalis exhibited increasing resistance to ampicillin (5-69%), gentamicin (59-94%), and tetracycline (77-89%) over time, while resistance to levofloxacin and ciprofloxacin notably decreased (72-16% and 49-8%, respectively). CONCLUSION: Over the past two decades, the proportion of gram-negative bacteria was declined, while the proportion of gram-positive bacteria increased. Escherichia coli remained the most common pathogen in the urine culture of patients with urinary calculi in China and the resistance of Escherichia coli to commonly used antibiotics increased. Clinicians should select appropriate antibiotics according to the results of urine culture and drug sensitivity test to reduce the occurrence of antibiotic resistance.
Assuntos
Farmacorresistência Bacteriana , Cálculos Urinários , Humanos , China/epidemiologia , Cálculos Urinários/microbiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Estudos Transversais , Período Pré-Operatório , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , População do Leste AsiáticoRESUMO
Casuarina equisetifolia is drought tolerant, salt tolerant, and able to grow in barren environments. It is often used to reduce wind damage, to prevent sand erosion, and to help establish plant communities in tropical and subtropical coastal zones. To determine the basis for its drought tolerance, we conducted transcriptomic and metabolic analyses of young branchlets under a non-drought treatment (D_0h) and 2-, 12-, and 24-h-long drought treatments (D_2h, D_12h, and D_24h). A total of 5033 and 8159 differentially expressed genes (DEGs) were identified in D_2h/D_0h and D_24h/D_0h. These DEGs were involved in plant hormone signal transduction, jasmonic acid (JA) biosynthesis, flavonoid biosynthesis, and phenylpropanoid biosynthesis. A total of 148 and 168 differentially accumulated metabolites (DAMs) were identified in D_12h/D_0h and D_24h/D_0h, which were mainly amino acids, phenolic acids, and flavonoids. In conclusion, C. equisetifolia responds to drought by regulating plant hormone signal transduction and the biosynthesis of JA, flavonoid, and phenylpropanoid. These results increase the understanding of drought tolerance in C. equisetifolia at both transcriptional and metabolic levels and provide new insights into coastal vegetation reconstruction and management.
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Reguladores de Crescimento de Plantas , Transcriptoma , Perfilação da Expressão Gênica/métodos , Metaboloma , Secas , Regulação da Expressão Gênica de PlantasRESUMO
OBJECTIVE: To identify the clinical characteristics of patients who underwent superselective renal arterial embolization (SRAE) after percutaneous nephrolithotomy (PCNL) and to explore the risk factors for failed initial SRAE after PCNL. MATERIALS AND METHODS: Patients who underwent SRAE for severe haemorrhage following PCNL between January 2014 and December 2020 were included in the study. The clinical data of those patients and the parameters and characteristics of the perioperative PCNL and SRAE procedures were collected and analysed. RESULTS: A total of 243 patients were included in this study. A total of 139 patients (57.2%) had a pseudoaneurysm, 25 (10.3%) had an arteriovenous fistula, 50 (20.6%) patients had both a pseudoaneurysm and an arteriovenous fistula, and 29 (11.9%) had an arterial laceration. In 177 patients with single percutaneous access, 125 (70.6%) patients exhibited nontract haemorrhage, and 55 (31.1%) patients exhibited multiple bleeding sites. In 66 patients with multiple percutaneous access, 44 (66.7%) patients exhibited nontract haemorrhage, and 32 (48.5%) patients exhibited multiple bleeding sites. The decrease in Hb before SRAE was 41.4 ± 19.8 g/L. The mean time between PCNL surgery and initial SRAE was 6.4 ± 4.9 days. Serum creatinine was increased after the SRAE procedure. Initial SRAE was successful in 229 (94.2%) patients and failed in 14 (5.8%) patients. Multivariate regression demonstrated that hydronephrosis < 20 mm, total ultrasonographic guidance, solitary kidney, previous ipsilateral renal surgery, PCNL duration > 90 min and multiple bleeding sites were potential risk factors for initial embolization failure. CONCLUSION: Percutaneous access was not the most important reason for post-PCNL severe haemorrhage. SRAE is effective for the treatment of severe haemorrhage following PCNL; however, several factors have an impact on the success of initial SRAE. Additionally, the SRAE procedure may affect renal function.
Assuntos
Falso Aneurisma , Fístula Arteriovenosa , Cálculos Renais , Nefrostomia Percutânea , Humanos , Falso Aneurisma/etiologia , Nefrostomia Percutânea/métodos , Artéria Renal , Rim/fisiologia , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemorragia/terapia , Fatores de Risco , Fístula Arteriovenosa/complicações , Cálculos Renais/cirurgia , Cálculos Renais/complicações , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Although understory addition of nitrogen (UAN) is commonly used to simulate nitrogen deposition in field studies in forest ecosystems, it ignores the effects of atmospheric nitrogen deposition on the canopy. We studied the effects of nitrogen deposition simulated by UAN and by canopy addition of nitrogen (CAN) on leaf structure, chemical properties, Calvin cycle, and photosynthate distribution strategy of representative woody plant species in a subtropical evergreen broadleaved forest in South China. The results showed that maximum photosynthetic rate (Amax) of shrub species Blastus cochinchinensis and Ardisia quinquegona under CAN treatments was significantly higher than that of UAN treatments at the same N addition concentration. The concentrations of intermediates (PGK, DPGA and G3P) in Calvin cycle of B. cochinchinensis and A. quinquegona, and Castanea henryi were significantly increased with CAN treatments, but the opposite was true with UAN treatments. CAN25 significantly increased starch concentrations of shrub species Lasianthus chinensis and B. cochinchinensis, and significantly decreased sucrose concentrations of shrub species A. quinquegona and tree species C. henryi. Correlation analyses showed that nitrogen application amount under different modes helped explain the changes in Amax and Calvin cycle intermediates. In summary, nitrogen deposition may promote the Amax and Calvin cycle of shrub species, and the adaptability of shrub species to nitrogen deposition is higher than that of tree species, which may help to explain the degradation of subtropical evergreen broad-leaved forest.
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Nitrogênio , Árvores , Nitrogênio/análise , Carbono/análise , Ecossistema , Florestas , ChinaRESUMO
The problem of nosocomial infections caused by bacterial growth on material surfaces is an urgent threat to public health. Although numerous materials and methods have been explored to fight against infections, the methods are complicated and the materials are slightly toxic. It is highly desirable to develop an antibacterial strategy that kills bacteria effectively without drug resistance and cytotoxicity. Herein, we present a synergistic antibacterial polylactic acid (PLA) surface with superhydrophobic antibacterial adhesion and photodynamic bactericidal activity. Initially, the surface displayed low-adhesion superhydrophobicity and resisted most bacterial adhesion. Furthermore, completely non-toxic chlorophyll possessed excellent photodynamic bactericidal properties under non-toxic visible light, which was incorporated into micro-/nanoscale PLA surfaces. We achieved efficient antibacterial activity using completely non-toxic materials and a facile non-solvent-induced phase separation process. This non-toxic, simple, good biocompatible, and no drug-resistant strategy has great advantages in combating bacterial infections.
Assuntos
Fotoquimioterapia , Antibacterianos/química , Antibacterianos/toxicidade , Clorofila/farmacologia , Poliésteres/toxicidade , Propriedades de SuperfícieRESUMO
PURPOSE: To explore an appropriate duration of antibiotic therapy before percutaneous nephrolithotomy (PCNL) in patients with positive urine culture. METHODS: From March 2016 to May 2018, consecutive patients with positive urine culture undergoing PCNL were prospectively registered. Initial preoperative antibiotics were given empirically. If needed, antibiotics were upgraded or adjusted to susceptible antibiotic after obtaining antibiotic-sensitivity test. Postoperative systemic inflammatory response syndrome (SIRS) was the primary outcome. RESULTS: Among the 220 participants, the incidence of positive stone culture and SIRS were 85.5% and 36.8%. Escherichia coli (53.6%, 44.5%) and Proteus mirabilis (8.2%, 10.0%) were the top two bacteria in urine and stones. In univariable analysis, patients with postoperative SIRS had a higher rate of stone culture positivity (97.5% VS 78.4%, P < 0.001) and a shorter duration of preoperative antibiotics therapy (3.4 ± 2.7 days versus 4.2 ± 2.8 days, P = 0.037). The landscape of SIRS showed a declining trend as the elongation of preoperative antibiotics (P = 0.039). In a day-by-day comparison, SIRS was less prevalent in patients treated by pre-PCNL antibiotics ≥ 7 days than in those with antibiotics ≤ 6 days (21.7% VS 40.8%, P = 0.017). Multivariable logistic regression confirmed positive stone culture (P = 0.001, OR 11.115) as an independent risk factor and pre-PCNL antibiotics ≥ 7 days (P = 0.048, OR 0.449) as an independent protective factor for SIRS. Preoperative antibiotic ≥ 7 days decreased SIRS from 45.4 to 27.8% and from 9.1 to 0% in patients with a positive and negative stone culture, respectively. CONCLUSION: Exceeding seven days should be appropriate duration of antibiotic therapy before PCNL in patients with positive urine cultures.
Assuntos
Antibioticoprofilaxia , Infecções Bacterianas/prevenção & controle , Cálculos Renais/cirurgia , Cálculos Renais/urina , Nefrolitotomia Percutânea , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Antibioticoprofilaxia/métodos , Infecções Bacterianas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Estudos Prospectivos , Fatores de Tempo , Urina/microbiologiaRESUMO
BACKGROUND: Correct perioperative antibiotic strategies are crucial to prevent postoperative infections during percutaneous nephrolithotomy (PCNL). We aimed to compare the realistic antibiotic strategies applied in China with current urological guidelines. METHODS: Between April and May 2020, urologists from China were invited to finish an online cross-sectional survey. The questionnaire was designed according to the current urological guidelines and literatures. RESULTS: 3393 completed responses were received. 61.1% (2073/3393) respondents had urological experience of more than 10 years. 72.4% urologists chose multiple-dose antibiotics for patients with both negative urine culture (UC-) and negative urine microscopy (UM-) preoperatively. Respondents in central China (OR = 1.518; 95% CI 1.102-2.092; P = 0.011), east China (OR = 1.528; 95% CI 1.179-1.979; P = 0.001) and northeast China (OR = 1.904; 95% CI 1.298-2.792; P = 0.001) were more likely to prescribe multiple-dose antibiotic for UC-UM- patients. Notably, the respondents who finished PCNL exceeded 100 cases per year were in favor of single-dose administration (OR = 0.674; 95% CI 0.519-0.875; P = 0.003). There are only 8.3% urologists chose single-dose antibiotic for UC-UM+ patients, whereas 65.5% administered antibiotics for 1-3 days. Meanwhile, for UC+ patients, 59.0% of the urologists applied antibiotics shorter than 1 week, and only 26.3% of the urologists carried out routine re-examination of UC. Moreover, postoperative antibiotics were frequently prescribed for 3-6 days (1815; 53.5%). Finally, although 88.2% urologists considered stone culture important for management of postoperative antibiotics as the guideline recommended, only 18.5% performed it routinely. CONCLUSIONS: The antibiotic strategies are different between current practice in China and the urological guidelines. The dissimilarities suggested that further studies should be conducted to investigate the reasons of the differences and standardize the application of antibiotics.
Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Urologia , Antibacterianos/uso terapêutico , Estudos Transversais , Humanos , Cálculos Renais/cirurgia , Microscopia , UrináliseRESUMO
PURPOSE: To evaluate the distribution and dynamic trends in constituents of urinary stones in China. MATERIALS AND METHODS: The composition of 23,182 stones were analyzed and then recorded between January 2011 and December 2019. The characteristics in terms of stone patient's gender, age and calendar year were analyzed. RESULTS: Most stones (22,172, 95.64%) had several crystal components, among which 40.25% (8925/22,172) were mixtures with infection components. Calcium oxalate (CaOx) and uric acid (UA) stones were more commonly encountered in men, but calcium phosphate (CaP), magnesium ammonium phosphate (MAP) and carbonate apatite (CA) stones were more prevalent in women (p < 0.05). In males, the proportion of CaOx stones increased up to the age of 40, but subsequently decreased (p < 0.001). Interestingly, females showed an inverse trend regarding CaOx stones (p < 0.001). The proportion of UA stones increased with age (p < 0.001), and CA stones most frequently were recorded at age 20-49. Over the past 9 years, UA, CA, and MAP stones increased over time, whereas there was a tendency for CaOx stones to decrease (p < 0.05). CONCLUSIONS: The scarcity of pure stones and a certain proportion of mixtures with infection stone components (e.g., mixtures of CaOx and CA) suggest that treatment directed against a single stone component is insufficient for effective recurrence prevention. Age and gender were significant determinants of stone composition, and according to the observed chronological trends, it seems that in the future, more UA, CA and MAP stones and fewer CaOx stones may be encountered in the studied population.
Assuntos
Cálculos Urinários/química , Adulto , China/epidemiologia , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Cálculos Urinários/epidemiologia , Adulto JovemRESUMO
PURPOSE: To explore the safety of multiple tract percutaneous nephrolithotomy (PNL) in terms of complication and draw a nomogram to predict the possibility of significant renal function decline (SRFD). MATERIALS AND METHODS: Patients with complex renal calculi appropriate for PNL at our institution between August 2016 and February 2018 were included in the study. The outcome of single and multiple tract PNL was analyzed retrospectively. A nomogram was created to predict the probability of SRFD. RESULTS: 793 (88.4%) patients were treated with single tract PNL (Group 1) and 104 patients (11.6%) treated with multiple tract PNL (Group 2). Group 2 had a significantly greater hemoglobin reduction (16.0 ± 12.5 vs. 11.4 ± 11.8 g/L, p < 0.001), higher rate of postoperative fever (19.2% vs. 11.9%, p = 0.034) and longer duration of the operation (110.6 ± 39.6 vs. 97.8 ± 34.5 min, p < 0.001). A nomogram for predicting the probability of SRFD was constructed based on identified risk factors: patients' age, positive urine culture (UC +), hemoglobin reduction and embolization. The area of receiver operating characteristic (ROC) curve was 70%. Bootstrapping technique utilized to make the calibration plot showed a high reliability of the nomogram. CONCLUSIONS: Multiple tract PNL had a higher risk of hemoglobin reduction and postoperative fever than single tract PNL. Multiple tracts had no effect on SRFD, but old age, UC + , hemoglobin reduction and embolization were risk factors for SRFD. A nomogram with the aim of predicting the probability of SRFD based on these parameters demonstrated good uniformity in internal validation.
Assuntos
Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Cálculos Coraliformes/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
Drought and nitrogen (N) deposition are important components of global climate and environmental change. In this greenhouse study, we investigated the ecophysiological responses of the seedlings of three subtropical forest plant species (Schima superba, Castanopsis fissa, and Michelia macclurei) to short-term experimental drought stress, N addition, and their interaction. The results showed that drought stress reduced the activities of antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)] and total antioxidant capacity (T-AOC), but increased the malondialdehyde (MDA), abscisic acid (ABA), and proline (PRO) contents in plants. The PRO content, T-AOC, and antioxidant enzyme activities were increased, and ABA and MDA contents were decreased by N addition alone. Furthermore, N addition under drought stress increased antioxidant enzymes activities, PRO content, and T-AOC. The treatments, however, did not significantly affect the chlorophyll fluorescence parameters of the species. T-AOC was positively correlated with antioxidant enzyme activities in each species, indicating that antioxidant enzymes were important for plant resistance to oxidative stress. MDA content increased with the increase of ABA content, indicating that ABA may help regulate stomatal movement and drought-induced oxidative injury in plants. T-AOC was positively correlated with PRO content, probably because PRO participated in osmotic regulation of cells and increased osmotic stress resistance. These results indicate that N addition can reduce drought stress of subtropical forest plants and will help researchers predict how evergreen broad-leaved forests will respond to global change in the future.
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Poluentes Atmosféricos/toxicidade , Antioxidantes/metabolismo , Secas , Compostos de Nitrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Árvores/efeitos dos fármacos , China , Monitoramento Ambiental , Fagaceae/efeitos dos fármacos , Fagaceae/metabolismo , Florestas , Osmose/efeitos dos fármacos , Pressão Osmótica/efeitos dos fármacos , Árvores/metabolismo , Clima TropicalAssuntos
Infecções , Cálculos Renais , Urolitíase , Animais , Bactérias , Cálcio , Oxalato de Cálcio , Canais Iônicos , RatosAssuntos
Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Impressão Tridimensional , TecnologiaRESUMO
OBJECTIVE: The connection between triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and stroke risk is controversial. Our goal was to explore this relationship in individuals aged 45 and older enrolled in the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Our analysis encompassed 10,164 participants from the CHARLS cohorts. We applied the Cox proportional-hazards regression model to evaluate the potential correlation between the TG/HDL-C ratio and stroke incidence. Using a cubic spline function and smooth curve fitting within the Cox model allowed us to unearth a possible non-linear pattern in this relationship. We also conducted thorough sensitivity and subgroup analyses to deepen our understanding of the TG/HDL-C ratio's impact on stroke risk. RESULTS: Adjusting for various risk factors, we observed a significant link between the TG/HDL-C ratio and increased stroke risk in individuals aged 45 and above (HR: 1.03, 95% CI 1.00-1.05, P = 0.0426). The relationship appeared non-linear, with an inflection at a TG/HDL-C ratio of 1.85. Ratios below this threshold indicated a heightened stroke risk (HR: 1.28, 95% CI 1.06-1.54, P = 0.0089), while ratios above it did not show a significant risk increase (HR: 1.01, 95% CI 0.98-1.04, P = 0.6738). Sensitivity analysis confirmed the robustness of these findings. Notably, non-smokers exhibited a stronger correlation between the TG/HDL-C ratio and stroke risk compared to past and current smokers. CONCLUSION: Our investigation revealed a significant, yet non-linear, association between the TG/HDL-C ratio and the incidence of stroke among individuals aged 45 and above. Specifically, we found that stroke risk increased in correlation with TG/HDL-C ratio below the threshold of 1.85. These insights may guide healthcare providers in advising and developing more effective strategies for stroke prevention in this demographic.
RESUMO
Theranostic antibacterial wound dressing is highly recommended in practical applications. The conventional methods of integrating diagnostic and therapeutic functions have the disadvantages of complicated preparation, mutual interference, inability to effectively broad spectrum antibacterial property, and easy to induce drug-resistant bacteria. Herein, a pH and light-responsive theranostic antibacterial hydrogel is developed by biopolymers polyvinyl alcohol (PVA) and polyaniline (PANI), and cross-linking with phytic acid (PA), which is widely present in rice bran. The biological polymer-based conductive hydrogel enables timely diagnosis and photothermal sterilization in-situ for wound healing. Because PANI is highly sensitive to pH changes in the bacterial microenvironment, the hydrogel can detect bacterial infections at concentrations as low as 103 CFU/mL. Subsequently, PANI absorbs near-infrared light to achieve on-demand exothermic sterilization (under 808 nm irradiation for 20 min, the killing ratios for Staphylococcus aureus and Escherichia coli reached almost 100 %). In addition, the hydrogel can monitor the intensity of joint movement to avoid wound re-tearing sensitively. In vitro cytotoxicity and hemocompatibility experiments and in vivo full-thickness infected wound model indicate that the hydrogel has good biocompatibility, antibacterial ability, and can accelerate the wound healing effectively. This work will promote the development of wearable electronic devices and precision medicine.
Assuntos
Antibacterianos , Escherichia coli , Hidrogéis , Oryza , Ácido Fítico , Staphylococcus aureus , Cicatrização , Ácido Fítico/química , Ácido Fítico/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Hidrogéis/química , Hidrogéis/farmacologia , Oryza/química , Staphylococcus aureus/efeitos dos fármacos , Animais , Escherichia coli/efeitos dos fármacos , Biopolímeros/química , Biopolímeros/farmacologia , Nanomedicina Teranóstica , Camundongos , Humanos , Álcool de Polivinil/química , Compostos de Anilina/química , Compostos de Anilina/farmacologiaRESUMO
Wounds at joints are difficult to treat and tend to recover more slowly due to the frequent motions. When using traditional hydrogel dressings, they are easy to crack and undergo bacterial infection, difficult to match and monitor the irregular wounds. Integrating multiple functions within a hydrogel dressing to achieve intelligent wound monitoring and healing remains a significant challenge. In this research, a multifunctional hydrogel is developed based on polysaccharide biopolymer, poly(vinyl alcohol), and hydroxylated graphene through dynamic borate ester bonding and supramolecular interaction. The prepared hydrogel not only exhibits rapid self-healing (within 60 s), injectable, conductive and motion monitoring properties, but also realizes in situ bacterial sensing and killing functions. It shows excellent bacterial sensitivity (within 15 min) and killing ability via the changes of electrical signals and photothermal therapy, avoiding the emergence of drug-resistant bacteria. In vivo experiments prove that the hydrogel can promote wound healing effectively. In addition, it displays great electromechanical performance to achieve real-time monitoring and prevent re-tearing of the wound at human joints. The injectable pH-responsive hydrogel with good biocompatibility demonstrates considerable potential as multifunctional bioelectronic dressing for the detection, treatment, management, and healing of infected joint wounds.
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Bandagens , Hidrogéis , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Humanos , Grafite/química , Álcool de Polivinil/química , Nanomedicina Teranóstica/métodos , Condutividade Elétrica , Antibacterianos/química , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacosRESUMO
Randall's plaque (RP) is derived from interstitial mineral deposition and is highly prevalent in renal calcium oxalate (CaOx) stone disease, which is predictive of recurrence. This study shows that histone deacetylase 6 (HDAC6) levels are suppressed in renal tubular epithelial cells in RP samples, in kidney tissues of hyperoxaluria rats, and in hyper-oxalate-treated or mineralized cultured renal tubular epithelial (MDCK) cells in vitro. Mineral deposition in MDCK cells was exacerbated by HDAC6 inhibition but alleviated by HDAC6 overexpression. Surprisingly, the expression of some osteogenic-associated proteins, were not increased along with the increasing of mineral deposition, and result of single-cell RNA sequencing of renal papillae samples revealed that epithelial cells possess lower calcific activity, suggesting that osteogenic-transdifferentiation may not have actually occurred in tubular epithelial cells despite mineral deposition. The initial mineral depositions facilitated by HDAC6 inhibitor were localized in extracellular dome rather than inside the cells, moreover, suppression of HDAC6 significantly increased the calcium content of co-cultured renal interstitial fibroblasts (NRK49F) and enhanced mineral deposition of indirectly co-cultured NRK49F cells, suggesting that HDAC6 may influence trans-MDCK monolayer secretion of mineral. Further experiments revealed that this regulatory role was partially alpha-tubulinLys40 acetylation dependent. Collectively, these results suggest that hyper-oxalate exposure led to HDAC6 suppression in renal tubular epithelial cells, which may contribute to interstitial mineral deposition by promoting alpha-tubulinLys40 acetylation. Therapeutic agents that influence HDAC6 activity may be beneficial in preventing RP and CaOx stone formation.
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Nefropatias , Tubulina (Proteína) , Animais , Ratos , Acetilação , Oxalato de Cálcio , Células Epiteliais/metabolismo , Desacetilase 6 de Histona/metabolismo , Minerais , Tubulina (Proteína)/metabolismoRESUMO
Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. Methods: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database. Employing R software, we conducted bioinformatics analysis to establish an m6A-lncRNA co-expression network. Analyzing the differences between high and low-risk groups, particularly at the immunological level, and subsequently investigating the primary regulatory factors of these lncRNA, validating the findings through experiments, and exploring their specific cellular functions. Results: We identified 50 m6A-related lncRNA with prognostic significance through univariate Cox regression analysis. In parallel, we employed a LASSO-Cox regression model to pinpoint 11 lncRNA and calculate risk scores for bladder cancer patients. Based on the median risk score, patients were categorized into low-risk and high-risk groups. The high-risk cohort exhibited notably lower survival rates than their low-risk counterparts. Further analysis pointed to RBM15 and METTL3 as potential master regulators of these m6A-lncRNA. Experimental findings also shed light on the upregulated expression of METTlL3 and RBM15 in bladder cancer, where they contributed to the malignant progression of tumors. The experimental findings demonstrated a significant upregulation of METTL3 and RBM15 in bladder cancer specimens, implicating their contributory role in the oncogenic progression. Knockdown of METTL3 and RBM15 resulted in a marked attenuation of tumor cell proliferation, invasion, and migration, which was concomitant with a downregulation in the cellular m6A methylation status. Moreover, these results revealed that RBM15 and METTL3 function in a synergistic capacity, positing their involvement in cancer promotion via the upregulation of m6A modifications in long non-coding RNAs. Additionally, this study successfully developed an N-methyl-N-nitrosourea (MNU)-induced rat model of in situ bladder carcinoma, confirming the elevated expression of RBM15 and METTL3, which paralleled the overexpression of m6A-related- lncRNAs observed in bladder cancer cell lines. This congruence underscores the potential utility of these molecular markers in in vivo models that mirror human malignancies. Conclusion: This study not only offers novel molecular targets,but also enriches the research on m6A modification in bladder cancer, thereby facilitating its clinical translation.
RESUMO
Background: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS). Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed. Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients. Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.