RESUMEN
Organic fluorophores with dual-state emission (DSE) are rare or difficult to observe because most of them display either aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ). Amazing works have been accomplished, yet most of the DSE compounds were excited by UV light which limits their wide application in bioimaging. In this work, we achieved a visible-light excited DSE fluorophore and realized its imaging in SKOV-3 cells and zebrafish. The naphtho[2',3':4,5]imidazo[1,2-a]pyridine (NIP) core ensures its emission in dilute solution. Meanwhile, the twisted phenyl ring blocks fluorescence quenching induced by the π-π stacking and leads to the emission of the solid. The fluorescence intensity is steady even after 6 h of continuous intense sunlight. More importantly, photostability of NIP in cells is much better than commercial dye (mitochondrial green).
RESUMEN
BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.
Asunto(s)
Autofagia , Proteínas de Unión al GTP , Lesión Pulmonar , Neumonía , Síndrome de Dificultad Respiratoria , Animales , Ratones , Autofagia/efectos de los fármacos , Inflamación/metabolismo , Lipopolisacáridos , Pulmón/metabolismo , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/metabolismo , Neumonía/metabolismo , Enfisema Pulmonar , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/metabolismo , Proteínas de Unión al GTP/antagonistas & inhibidores , Proteínas de Unión al GTP/metabolismoRESUMEN
Microalgae play a significant impact in the biogeochemical cycle of Mn(II) in the aquatic ecosystem. Meanwhile, the inflow of biochar into the water bodies is bound to impact the aquatic organisms. However, the influence of biochar on the manganese transformation in algae-rich water has not drawn much attention. Thus, we studied the effects of rice straw biochar on manganese enrichment and oxidation by a common type of algae in freshwater (Scenedesmus quadricauda). The results showed that Mn(II) was absorbed intracellularly and adsorbed extracellularly by active algal cells. A significant portion of enriched Mn(II) was oxidized to amorphous precipitates MnO2, MnOOH, and Mn2O3. Moreover, the extracellular bound Mn(II) content in the coexistent system of algae and biochar increased compared with the pure Scenedesmus quadricauda system. Nevertheless, the intracellular Mn content was continually lowered as the biochar dose rose from an initial 0.2 to 2.0 g·L-1, suggesting that Mn assimilation of the cell was suppressed. It was calculated that the total enrichment ability of Scenedesmus quadricauda in the algae-biochar coexistent system was 0.31- 15.32 mg Mn/g biomass, more than that in the pure algae system. More importantly, with biochar in the algae system, the amount of generated MnOx increased, and more Mn(II) was oxidized into highly-charged Mn(IV). This was probably because the biochar could relieve the stress of massive Mn(II) on algae and support the MnOx precipitates. In brief, moderate biochar promoted the Mn(II) accumulation by algal cells and its oxidation activity. This study offers deeper insight into the bioconversion of Mn(II) by algae and the potential impact of biochar application to the aquatic system.
Asunto(s)
Carbón Orgánico , Microalgas , Scenedesmus , Ecosistema , Manganeso/metabolismo , Compuestos de Manganeso , Óxidos , Agua/metabolismoRESUMEN
BACKGROUND: Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood. METHODS: To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions. RESULTS: In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation. CONCLUSIONS: These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.
Asunto(s)
Trastornos Relacionados con Anfetaminas , Estimulantes del Sistema Nervioso Central , Disfunción Cognitiva , Metanfetamina , Proteómica , Humanos , Trastornos Relacionados con Anfetaminas/metabolismo , Masculino , Metanfetamina/efectos adversos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/etiología , Adulto , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/farmacología , Femenino , Adulto JovenRESUMEN
OBJECTIVE: To investigate the association between low-dose aspirin use for primary prevention and self-reported kidney stones prevalence in the 40-79 years old population. METHODS: We conducted a cross-sectional study based on the United States population data from the National Health and Nutrition Examination Survey 2011-2018. Baseline demographical and clinical data were collected. The univariate and multivariate regression was performed to identify confounding factors and assess the relationship between aspirin use for primary prevention and the prevalence of self-reported kidney stones. A propensity-score matching was used to identify patients with similar baseline characteristics to adjust for the bias caused by confounding factors. RESULTS: A total of 10,256 low-dose aspirin-use participants were included in this study. 10.4% of participants reported a history of kidney stones, and 18.5% reported a continuous use of low-dose prophylactic aspirin. Multivariate logistic regression analysis showed that low-dose preventive aspirin use had significantly increased the odds of self-reported kidney stones (OR = 1.245; 95% CI: 1.063-1.459; p = 0.007). In subgroup analysis, this finding was primarily limited to males (OR = 1.311), non-hypertensive participants (OR = 1.443), diabetic participants (OR = 1.380), and older (60 ≤ Age < 80) (OR = 1.349). The propensity-score matched analyses supported this result after adjusting for the bias caused by potential confounders (OR = 1.216; 95% CI: 1.011-1.462; p = 0.038). CONCLUSION: In this study, there exists a significant relationship between low-dose aspirin for primary prevention and self-reported kidney stones, primarily among males, no hypertensive participants, diabetics, or older adults. Further studies are needed to elucidate the mechanisms underlying these findings in the future.
Asunto(s)
Diabetes Mellitus , Hipertensión , Cálculos Renales , Masculino , Humanos , Estados Unidos/epidemiología , Anciano , Adulto , Persona de Mediana Edad , Estudios Transversales , Autoinforme , Encuestas Nutricionales , Aspirina/uso terapéutico , Cálculos Renales/epidemiología , Cálculos Renales/prevención & control , Cálculos Renales/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Hipertensión/tratamiento farmacológico , Prevención PrimariaRESUMEN
Chunk decomposition, which requires the mental representation transformation in accordance with behavioral goals, is of vital importance to problem solving and creative thinking. Previous studies have identified that the frontal, parietal, and occipital cortex in the cognitive control network selectively activated in response to chunk tightness, however, functional localization strategy may overlook the interaction brain regions. Based on the notion of a global brain network, we proposed that multiple specialized regions have to be interconnected to maintain goal representation during the course of chunk decomposition. Therefore, the present study applied a beta-series correlation method to investigate interregional functional connectivity in the event-related design of chunk decomposition tasks using Chinese characters, which would highlight critical nodes irrespective to chunk tightness. The results reveal a network of functional hubs with highly within or between module connections, including the orbitofrontal cortex, superior/inferior parietal lobule, hippocampus, and thalamus. We speculate that the thalamus integrates information across modular as an integrative hub while the orbitofrontal cortex tracks the mental states of chunk decomposition on a moment-to-moment basis. The superior and inferior parietal lobule collaborate to manipulate the mental representation of chunk decomposition and the hippocampus associates the relationship between elements in the question and solution phase. Furthermore, the tightness of chunks is not only associated with different processors in visual systems but also leads to increased intermodular connections in right superior frontal gyrus and left precentral gyrus. To summary up, the present study first reveals the task-modulated brain network of chunk decomposition in addition to the tightness-related nodes in the frontal and occipital cortex.
Asunto(s)
Cognición/fisiología , Conectoma/métodos , Imagen por Resonancia Magnética/métodos , Reconocimiento Visual de Modelos/fisiología , Solución de Problemas/fisiología , Adolescente , Adulto , China , Creatividad , Femenino , Voluntarios Sanos , Humanos , Procesamiento de Imagen Asistido por Computador , MasculinoRESUMEN
BACKGROUND: Randall's plaques (RP) are identified as anchored sites for kidney calcium oxalate stones, but the mechanism remains unclear. Given the importance of osteogenic-like cells in RP formation and OCT4 in reprogramming differentiated cells to osteoblasts, the current study explored the potential role of OCT4 in RP formation. METHODS: OCT4 and biomineralization were evaluated in RP, and immunofluorescence co-staining was performed to identify these cells with alteration of OCT4 and osteogenic markers. Based on the analysis of tissue, we further investigated the mechanism of OCT4 in regulating osteogenic-like differentiation of primary human renal interstitial fibroblasts (hRIFs) in vitro and vivo. RESULTS: We identified the upregulated OCT4 in RP, with a positive correlation to osteogenic markers. Interestingly, fibroblast marker Vimentin was partially co-localized with upregulated OCT4 and osteogenic markers in RP. Further investigations revealed that OCT4 significantly enhanced the osteogenic-like phenotype of hRIFs in vitro and in vivo. Mechanically, OCT4 directly bound to BMP2 promoter and facilitated its CpG island demethylation to transcriptionally promote BMP2 expression. Furthermore, combination of RIP and RNA profiling uncovered that lncRNA OLMALINC physically interacted with OCT4 to promote its stabilization via disrupting the ubiquitination. Additionally, OLMALINC was upregulated in fibroblasts in RP visualized by FISH, and a positive correlation was revealed between OLMALINC and OCT4 in RP. CONCLUSIONS: The upregulation of OCT4 in hRIFs was a pathological feature of RP formation, and OLMALINC/OCT4/BMP2 axis facilitated hRIFs to acquire osteogenic-like phenotype under osteogenic conditions, through which the pathway might participate in RP formation. Our findings opened up a new avenue to better understand RP formation in which osteogenic-like process was partially triggered by lncRNAs and pluripotency maintenance related genes.
Asunto(s)
Proteína Morfogenética Ósea 2 , Cálculos Renales , Factor 3 de Transcripción de Unión a Octámeros , ARN Largo no Codificante , Humanos , Proteína Morfogenética Ósea 2/genética , Oxalato de Calcio/metabolismo , Fibroblastos/metabolismo , Riñón/metabolismo , Cálculos Renales/metabolismo , Médula Renal/patología , Fenotipo , ARN Largo no Codificante/genética , Factor 3 de Transcripción de Unión a Octámeros/genéticaRESUMEN
SHJHhr mice line is rhino-like mice with a nonsense Hairless (Hr) mutant, which shows the characteristic of shedding hair and wrinkled skin with increasing age. Through histological analysis and aging indexes detection, SHJHhr mice show an increased thickness skin with degraded hair follicle and dermal cysts and disorganized collagen fibres, as well as decreased level of Hyp. Meanwhile, the aging markers p16 and p21 are significantly higher in SHJHhr mouse skin than ICR mouse skin at same age. Moreover, the data of MDA and SOD show a higher oxidative stress in SHJHhr mouse skin, and the levels of Nrf2 and its targets are significantly downregulated, which suggests SHJHhr mice have a faster aging skin and its reason maybe poor antioxidative protection. Overall, this study shows SHJHhr mice with an accelerated aging skin, which suggests the role of Hr gene in skin aging.
Asunto(s)
Envejecimiento de la Piel , Animales , Colágeno , Ratones , Ratones Pelados , Ratones Endogámicos ICR , Factor 2 Relacionado con NF-E2/genética , Envejecimiento de la Piel/genética , Superóxido DismutasaRESUMEN
The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.
Asunto(s)
COVID-19 , Parvovirinae , Animales , Humanos , Ratones , SARS-CoV-2/genética , COVID-19/prevención & control , Pandemias , Vacunas Sintéticas/genética , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
PURPOSE: To assess the value of procalcitonin (PCT) as an early biomarker for predicting urosepsis caused by Gram-negative (GN) bacteria, Gram-positive (GP) bacteria and fungi following mini-percutaneous nephrolithotomy (mPCNL) and flexible ureteroscopy (FURS). METHODS: A total number of 356 patients with positive preoperative UC (urine cultures) who underwent mPCNL and FURS between June 2017 and January 2021 were retrospectively analyzed. Univariable analysis and multivariable logistic regression analysis were conducted to compare the predictors for urosepsis caused by different organisms. Furthermore, the nomogram was established as a predicted model for urosepsis. RESULTS: Among 356 positive UC, 265 (74.4%) were positive for GN bacteria, 77 (21.4%) for GP bacteria and 14 (3.9%) for fungal pathogens. Escherichia coli (48.9%) were the predominant pathogens and Enterococcus (54/77) were the most common GP bacteria. Multivariate logistic regression analysis showed that positive nitrite (OR 3.31, 95% CI 1.20-9.14; P = 0.021), operative time > 90 min (OR 3.10, 95% CI 1.10-8.75, P = 0.033) and postoperative PCT > 0.1 ng/mL (OR 56.18, 95% CI 15.20-207.64, P < 0.001) were associated with postoperative urosepsis originated in GN infections, while urosepsis caused by GP bacteria and fungi was not associated with PCT > 0.1 ng/mL (P = 0.198), only stone burden > 800 mm2 (OR 3.69, 95% CI 1.01-13.53, P = 0.049) was an independent risk factor. CONCLUSIONS: For patients with positive preoperative UC, postoperative PCT > 0.1 ng/mL was an independent risk factor of post-PCNL and post-FURS urosepsis caused by GN bacteria rather than GP bacteria and fungi.
Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Humanos , Cálculos Renales/cirugía , Nefrolitotomía Percutánea/efectos adversos , Polipéptido alfa Relacionado con Calcitonina , Estudios Retrospectivos , Ureteroscopios , Ureteroscopía/efectos adversosRESUMEN
Huntington's disease is an autosomal-dominant neurodegenerative disease caused by CAG expansion in exon 1 of the huntingtin (HTT) gene. Since mutant huntingtin (mHTT) protein is the root cause of Huntington's disease, oligonucleotide-based therapeutic approaches using small interfering RNAs (siRNAs) and antisense oligonucleotides designed to specifically silence mHTT may be novel therapeutic strategies for Huntington's disease. Unfortunately, the lack of an effective in vivo delivery system remains a major obstacle to realizing the full potential of oligonucleotide therapeutics, especially regarding the delivery of oligonucleotides to the cortex and striatum, the most severely affected brain regions in Huntington's disease. In this study, we present a synthetic biology strategy that integrates the naturally existing exosome-circulating system with artificial genetic circuits for self-assembly and delivery of mHTT-silencing siRNA to the cortex and striatum. We designed a cytomegalovirus promoter-directed genetic circuit encoding both a neuron-targeting rabies virus glycoprotein tag and an mHTT siRNA. After being taken up by mouse livers after intravenous injection, this circuit was able to reprogramme hepatocytes to transcribe and self-assemble mHTT siRNA into rabies virus glycoprotein-tagged exosomes. The mHTT siRNA was further delivered through the exosome-circulating system and guided by a rabies virus glycoprotein tag to the cortex and striatum. Consequently, in three mouse models of Huntington's disease treated with this circuit, the levels of mHTT protein and toxic aggregates were successfully reduced in the cortex and striatum, therefore ameliorating behavioural deficits and striatal and cortical neuropathologies. Overall, our findings establish a convenient, effective and safe strategy for self-assembly of siRNAs in vivo that may provide a significant therapeutic benefit for Huntington's disease.
Asunto(s)
Ingeniería Genética/métodos , Terapia Genética/métodos , Proteína Huntingtina , Enfermedad de Huntington , ARN Interferente Pequeño , Animales , Exosomas/metabolismo , Hígado/metabolismo , Ratones , ARN Interferente Pequeño/farmacología , TransfecciónRESUMEN
Numerous studies have analyzed the state of brain activation about anxiety disorders under emotional stimuli. However, there is no meta-analysis to assess the commonality and specificity activation concerning different subtypes of anxiety. Here, we used ALE to assess this. 29 studies revealed increased bilateral amygdala, anterior cingulate gyrus, parahippocampal gyrus activation in anxiety disorders during emotional stimuli. Moreover, we observed decreased activations in the posterior cingulate, lingual gyrus, and precuneus. In sub-analysis, although different anxiety showed dissimilar activations, the principal activations were observed in limbic lobe, which might indicate the limbic circuit was the main neural reflection of anxiety symptoms.
Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Emociones , Mapeo Encefálico , Trastornos de Ansiedad/diagnóstico por imagenRESUMEN
Iron-oxidizing bacteria played an important role in the treatment of Sb-containing wastewater. In this study, effect of different iron sources on Sb(III) removal ability by isolated iron-oxidizing bacteria (named as IOB-L) was conducted systemically in batch experiment. Moreover, ferrous lactate and zero-valent iron were chosen as iron sources for IOB-L. The results showed that after inoculation of 2% volume of IOB-L, Sb(III) concentration in water decreased from initial 18 mg/L to 4.1 mg/L at optimal pH of 7.0. There was no reaction between Sb(III) and ferrous lactate, whereas corrosion product of iron can adsorb a certain amount of Sb. When active IOB-L cultivated in ferrous lactate, a better removal rate of Sb(III) can be reached with a longer stagnate phase for bacteria. However, Sb(III) removal ability of IOB-L using zero-valent iron as iron source was lower. SEM-EDS, FTIR, and XPS analysis further indicated that ferrous lactate was oxidized by IOB-L and precipitated as biogenic iron oxides which had strong adsorption ability towards Sb(III), whereas zero-valent iron was not a good iron source.
Asunto(s)
Hierro , Agua , Adsorción , Corrosión , Oxidación-ReducciónRESUMEN
In this study, we describe a new rat model of vertebral inflammation-induced caudal intervertebral disc degeneration (VI-IVDD), in which IVD structure was not damaged and controllable segment and speed degeneration was achieved. VI-IVDD model was obtained by placing lipopolysaccharide (LPS) in the caudal vertebral bodies of rats. Rat experimental groups were set as follows: normal control group, group with a hole drilled in the middle of vertebral body and not filled with LPS (Blank group), group with a hole drilled in the middle of vertebral body and filled with LPS (Mid group), and group with hole drilled in the vertebral body in proximity of IVD and filled with LPS (NIVD group). Radiological results of VI-IVDD rats showed a significant reduction in the intervertebral space height and decrease in MRI T2 signal intensity. Histological stainings also revealed that the more the nucleus pulposus and endplate degenerated, the more the annulus fibrosus structure appeared disorganized. Immunohistochemistry analysis demonstrated that the expression of Aggrecan and collagen-II decreased, whereas that of MMP-3 increased in Mid and NIVD groups. Abundant local production of pro-inflammatory cytokines was detected together with increased infiltration of M1 macrophages in Mid and NIVD groups. Apoptosis ratio remarkably enhanced in Mid and NIVD groups. Interestingly, we found a strong activation of the cyclic GMP-AMP synthase /stimulator of interferon gene signalling pathway, which is strictly related to inflammatory and degenerative diseases. In this study, we generated a new, reliable and reproducible IVDD rat model, in which controllable segment and speed degeneration was achieved.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Degeneración del Disco Intervertebral/etiología , Degeneración del Disco Intervertebral/metabolismo , Proteínas de la Membrana/metabolismo , Nucleotidiltransferasas/metabolismo , Transducción de Señal , Espondilitis/complicaciones , Agrecanos/metabolismo , Animales , Apoptosis , Biomarcadores , Biopsia , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Inmunohistoquímica , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/patología , Macrófagos/inmunología , Macrófagos/metabolismo , Imagen por Resonancia Magnética , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Radiografía , Ratas , Espondilitis/etiologíaRESUMEN
BACKGROUND AND AIM: Jointly analyzing structural and functional brain networks enables a better understanding of pathological underpinnings of irritable bowel syndrome (IBS). Multiplex network analysis provides a novel framework to study complex networks consisting of different types of connectivity patterns in multimodal data. METHODS: In the present work, we integrated functional and structural networks to a multiplex network. Then, the multiplex metrics and the inner-layer/inter-layer hub nodes were investigated through 34 patients with IBS and 33 healthy controls. RESULTS: Significantly differential multiplex degree in both left and right parts of calcarine was found, and meanwhile, IBS patients lost inner-layer hub properties in these regions. In addition, the left fusiform was no longer practicing as an inner-layer hub node, while the right median cingulate acted as a new inner-layer hub node in the IBS patients. Besides, the right calcarine, which lost its inner-layer hub identity, became a new inter-layer hub node, and the multiplex degree of the left hippocampus, which lost its inter-layer hub identity in IBS patients, was significantly positively correlated with the IBS Symptom Severity Score scores. CONCLUSIONS: Inner-layer hub nodes of multiplex networks were preferentially vulnerable, and some inner-layer hub nodes would convert into inter-layer hub nodes in IBS patients. Besides, the inter-layer hub nodes might be influenced by IBS severity and therefore converted to general nodes.
Asunto(s)
Encéfalo , Síndrome del Colon Irritable , Encéfalo/fisiopatología , Humanos , Síndrome del Colon Irritable/fisiopatología , Red Nerviosa/fisiopatología , Corteza Visual Primaria/fisiopatologíaRESUMEN
BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson's disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1ß (IL-1ß) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.
Asunto(s)
Microbioma Gastrointestinal/fisiología , Inmunidad/fisiología , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/inmunología , Microglía/inmunología , Enfermedades Neurodegenerativas/inmunología , Porphyromonas gingivalis/inmunología , Administración Oral , Animales , Infecciones por Bacteroidaceae/genética , Infecciones por Bacteroidaceae/inmunología , Células Cultivadas , Neuronas Dopaminérgicas/inmunología , Neuronas Dopaminérgicas/microbiología , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Ratones , Ratones Transgénicos , Microglía/microbiología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/microbiología , Permeabilidad , Sustancia Negra/inmunología , Sustancia Negra/microbiologíaRESUMEN
OBJECTIVE: DNA Methylation of the tumour suppressor gene leading to gene silencing plays an important role in thyroid tumour development. The purpose was to determine the DNA methylation status of phosphatase and tensin homolog (PTEN) and death-associated protein kinase (DAPK) in patients with thyroid nodules and to explore whether they can be used as molecular diagnostic tools to differentiate benign and malignant thyroid nodules. DESIGN, PATIENTS AND MEASUREMENTS: Thyroid tissue and blood samples were obtained from normal healthy individuals (controls) and patients suffering from clinically diagnosed thyroid nodular disease [papillary thyroid carcinoma (PTC), adenoma and nodular goitre]. DNA methylation level, mRNA expression and protein expression of PTEN and DAPK in the thyroid tissues and peripheral blood were detected using methylation-specific PCR, semi-quantitative reverse transcription PCR and Western blot, respectively. Diagnostic sensitivity, specific and accuracy of detection were evaluated between blood and thyroid tissue. RESULTS: There was a significant increase in the level of DNA methylation of PTEN and DAPK in PTC (P < .05) compared with controls and other types of thyroid nodules. Levels of the mRNA of both PTEN and DAPK were lower in PTC in both peripheral blood and tissue samples compared with controls, while there was concomitant decrease of both PTEN and DAPK protein expression in PTC tissues (P < .05). There was no significant difference in diagnostic specificity, sensitivity and accuracy between blood sample and thyroid tissues. CONCLUSIONS: Hypermethylated status of both PTEN and DAPK in peripheral blood and tissue samples can be useful biomarkers for clinical diagnosis and, distinguishing of benign and malignant thyroid nodules.
Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Metilación de ADN/genética , Proteínas Quinasas Asociadas a Muerte Celular , Humanos , Fosfohidrolasa PTEN/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/genéticaRESUMEN
PURPOSE: To identify early predictive factors for urosepsis secondary to mini-percutaneous nephrolithotomy (MPCNL) in patients with negative preoperative urine culture (UC). METHODS: A total of 786 patients with baseline negative UC who underwent MPCNL between January 2017 and June 2019 were retrospectively analyzed. Urosepsis was defined according to the Sepsis-3 definition. Subsequently, perioperative potential risk factors were compared between non-urosepsis and urosepsis groups. RESULTS: Despite negative UC in all patients, the rate of positive stone culture (SC) was 16.0%; the rate of pelvic urine culture (PUC) was 7.5%; 23 cases (2.9%) developed urosepsis after MPCNL. Univariate analysis showed that urosepsis was associated with the female gender, BMI, stone burden, diabetes mellitus and preoperative urine test. Multivariate logistic regression analysis suggested that urine test with positive nitrite and white blood cells and leukocyte esterase (N+WBC+LE+) (OR 17.51, 95% CI 6.75-45.38, P < 0.001) and operative time > 120 min (OR 3.53, 95% CI 1.41-8.85, P = 0.007) were independent risk factors for urosepsis. Additionally, receiver operating characteristic curve analysis of N+WBC+LE+ showed that the area under the curve was 0.785 for predicting the occurrence of urosepsis. Further analysis showed that N+WBC+LE+ provided an efficient prediction of SC+/PUC+ (SC+ or PUC+) with 61.7% sensitivity and 97.3% specificity. CONCLUSIONS: In spite of the baseline negative preoperative UC, 2.9% of patients developed urosepsis after MPCNL. N+WBC+LE + was determined to be an early and efficient prediction of intraoperative bacterial status and urosepsis following MPCNL. Nevertheless, further studies are needed to confirm the results.
Asunto(s)
Cálculos Renales/cirugía , Nefrolitotomía Percutánea/efectos adversos , Complicaciones Posoperatorias/etiología , Sepsis/etiología , Infecciones Urinarias/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefrolitotomía Percutánea/métodos , Complicaciones Posoperatorias/diagnóstico , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Estudios Retrospectivos , Sepsis/diagnóstico , Sepsis/orina , Urinálisis , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orinaRESUMEN
BACKGROUND: Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Studies on MCI progression are important for Alzheimer's disease (AD) prevention. 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) has been proven to be a powerful tool for measuring cerebral glucose metabolism. In this study, we proposed a classification framework for MCI prediction with both baseline and multiple follow-up FDG-PET scans as well as cognitive scores of 33 progressive MCI (pMCI) patients and 46 stable MCI (sMCI) patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHOD: First, PET images were normalized using the Yakushev normalization procedure and registered to the Brainnetome Atlas (BNA). The average metabolic intensities of brain regions were defined as static features. Dynamic features were the intensity variation between baseline and the other three time points and change ratios with the intensity obtained at baseline considered as reference. Mini-mental State Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive section (ADAS-cog) scores of each time point were collected as cognitive features. And F-score was applied for feature selection. Finally, support vector machine (SVM) with radial basis function (RBF) kernel was used for the three above features. RESULTS: Dynamic features showed the best classification performance in accuracy of 88.61% than static features (accuracy of 78.48%). And the combination of cognitive features and dynamic features improved the classification performance in specificity of 95.65% and Area Under Curve (AUC) of 0.9308. CONCLUSION: Our results reported that dynamic features are more representative in longitudinal research for MCI prediction work. And dynamic features and cognitive scores complementarily enhance the classification performance in specificity and AUC. These findings may predict the disease course and clinical changes in individuals with mild cognitive impairment.
Asunto(s)
Disfunción Cognitiva , Pruebas de Estado Mental y Demencia , Tomografía de Emisión de Positrones , Algoritmos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/fisiopatología , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Humanos , Estudios Longitudinales , Pronóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Denis and Ferguson et al.'s three-column spinal theory has been widely accepted and applied. However, this three-column theory was proposed based solely on observation and experience without thorough documented data and analysis. The aim of this study was to analyze and improve Denis and Ferguson et al.'s three-column spinal theory to propose a novel three-column concept in epidemiology, morphology and biomechanics. METHODS: A retrospective analysis of the computed tomography imaging data of patients with a diagnosis of T11-L5 vertebral fractures was conducted between February 2010 and December 2018. Three-dimensional (3D) distribution maps of fracture lines of all subjects were obtained based on 3D mapping techniques. In addition, a 25-year-old health male volunteer was recruited for the vertebral finite element force analysis. RESULTS: The present study enrolled 459 patients (age: 48 ± 11.42 years), containing a total of 521 fractured vertebrae. The fracture lines peaked in the upper and the outer third sections of the vertebra, starting from the anterior part of the vertebral pedicles in 3-D maps. Regarding flexion and extension of the spine, the last third of the vertebral body in front of the spinal canal was one main stress center in the finite element analysis. The stress on the vertebral body was greater in front of the pedicles in the lateral bending. CONCLUSION: The study reveals that the posterior one-third of the vertebral body in front of the spinal canal and the posterior one-third of the vertebral body in front of the pedicle are very different in terms of fracture characteristics and risks to spinal canal (3D maps and stress distributing graphs), therefore, they should be classified as different columns. We provide strong evidence that Su's three-column theory complies with the characteristics of vertebral physiological structure, vertebral fracture, and vertebral biomechanics.