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Soft-bodied aquatic organisms have exhibited remarkable capabilities in navigating and moving within liquid environments serving as a profound inspiration for the development of bionic robots with intricate movements. Traditional rigid components are being replaced by stimulus-responsive soft materials such as hydrogels and shape memory polymers, leading to the creation of dynamically responsive soft robots. In this study, the development of a bionic robot inspired by the shape of an octopus and the adsorptive properties of its tentacles, specifically tailored for targeted stimulation and pH sensing in the cervix, are presented. This approach involves the design of a soft, water-based Janus adhesive hydrogel patch that adheres to specific parts of the cervix and responds to pH changes through external stimuli. The hydrogel patch incorporates inverse opal microstructures mimicking the legs of an octopus, to facilitate efficient and stable locomotion, unidirectional transport of biofluids, and pH-responsive behavior. This miniature bionic robot showcases controlled adhesion and precise unidirectional fluid transport highlighting its potential for targeted stimulus response and pH sensing in the uterine cervical tract. This breakthrough opens new avenues for medical applications within the expanding field of soft-bodied robotics.
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The standout characteristic of the orchid perianth is the transformation of the upper median petal into a distinctively formed lip, which gives orchid flowers their typically zygomorphic symmetry and makes them the most popular ornamental plants worldwide. To study orchid flower development, two WUSCHEL-related homeobox (WOX) genes, PaWOX3 and PaWOX3B, were identified in Phalaenopsis. PaWOX3 and PaWOX3B mRNAs accumulate abundantly during early reproductive development and perianths of young buds, significantly decrease in mature flower and absent in vegetative leaves and roots. PaWOX3 and PaWOX3B virus-induced gene silencing (VIGS) knockdown in Phalaenopsis significantly reduces floral bud numbers, suggesting that PaWOX3/PaWOX3B may be involved in flower initiation. Transgenic Arabidopsis ectopically expressing repressor forms of PaWOX3/PaWOX3B and their Oncidium orthologue, OnPRS, exhibit lateral organ development defects, implicating these genes likely have function in regulating growth and differentiation for lateral organs. Neither PaWOX3, PaWOX3B single nor PaWOX3/PaWOX3B double VIGS Phalaenopsis altered the flower morphology. Interestingly, double silencing of PaWOX3 or PaWOX3B with OAGL6-2, which controlled the identity/formation of lips, altered the symmetry of 'BigLip' produced in OAGL6-2 VIGS. This result indicated that the levels of PaWOX3/PaWOX3B are still sufficient to maintain the symmetry for the OAGL6-2 VIGS 'BigLip'. However, the symmetry of the OAGL6-2 VIGS 'BigLip' can not be maintained once the expression of PaWOX3 or PaWOX3B is further reduced. Thus, in addition to control lip identity, this study further found that OAGL6-2 could cooperate with functionally redundant PaWOX3/PaWOX3B in maintaining the symmetric axis of lip.
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Background: The Jinchan Yishen Tongluo Formula (JCYSTLF) has the effect of delaying senescence in diabetic kidneys. However, the mechanism is not clear. Purpose: Combination methods to investigate the anti-senescence mechanism of JCYSTLF in diabetic kidneys. Methods: The main compounds of JCYSTLF were characterized by LC-MS/MS, and the anti-senescence targets of JCYSTLF were screened via network analysis. Then, we performed in vivo and in vitro experiments to validate the results. Results: The target profiles of compounds were obtained by LC-MS/MS to characterize the primary function of JCYSTLF. Senescence was identified as a key biological functional module of JCYSTLF in the treatment of DN via constructing compounds-target-biological network analysis. Further analysis of senescence-related targets recognized the HIF-1α/autophagy pathway as the core anti-senescence mechanism of JCYSTLF in diabetic kidneys. Animal experiments showed, in comparison with valsartan, JCYSTLF showed an improvement in urinary albumin and renal pathological damage. JCYSTLF enhanced the ability of diabetic kidneys to clear senescence-related proteins via regulating autophagy confirmed by autophagy inhibitor CQ. However, HIF-1α inhibitor 2-ME weakened the role of JCYSLTF in regulating autophagy in diabetic kidneys. Meanwhile, over-expressed HIF-1α in HK-2 cells decreased the levels of SA-ß-gal, p21 and p53 induced by AGEs. Upregulated HIF-1α could reverse the blocking of autophagy induced by AGEs in HK-2 cells evaluated by ptfLC3. Conclusion: We provided in vitro and in vivo evidence for the anti-senescence role of JCYSTLF in regulating the HIF-1α/autophagy pathway.
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In vivo surgical interventions require effective management of biofluids, including controlling bleeding and removing excess biofluids such as bile, wound exudate, and blood. To address these issues, recent advances have emerged, such as self-sealing needles, drug-eluting stents, and shear-thinning hydrogels. However, complications associated with intestinal mucosal injury and secondary damage still persist. Therefore, a multifunctional stent is urgently required that can effectively remove excessive biofluid. Surface wettability of biliary stents is crucial in biofluid management, and conventional coatings can cause adhesion to wound tissue. To overcome this issue, we developed an interpenetrating Janus wettability stent coating, enabling unidirectional draining of excessive biofluid from its hydrophobic side to hydrophilic side, thereby preventing biofluid from wetting the wound. Furthermore, we demonstrate a directional biofluid movement using a self-pumping dressing in an infected tissue model, providing a new approach for in situ biofluid collection and disease diagnosis by detecting metal ion changes. Overall, our integrated system presents an opportunity to design wound dressings with effective biofluid management and metal ion detection capabilities.
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Biónica , Stents Liberadores de Fármacos , Stents , MetalesRESUMEN
BACKGROUND: Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation. OBJECTIVE: We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP. METHODS: Nasal tissues were obtained from 113 patients with CRSwNP and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp-derived MAIT cells were analyzed by RNA sequencing to study their effects on neutrophils. RESULTS: Endotypes of CRSwNP were classified as paucigranulocytic (n = 21), eosinophilic (n = 29), neutrophilic (n = 39), and mixed granulocytic (n = 24). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ+ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A+ MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared with controls. RNA sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp-derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of MAIT and MAIT17 cells were positively correlated with local proinflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyp-derived MAIT cells promoted neutrophil migration, survival, and activation. CONCLUSIONS: MAIT cells from neutrophilic CRSwNP demonstrate type 17 functional properties and promote neutrophil infiltration in nasal mucosa.
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Células T Invariantes Asociadas a Mucosa , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Inflamación/complicaciones , Citocinas , Enfermedad CrónicaRESUMEN
BACKGROUND: Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation. METHOD: PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity. RESULTS: The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03-1.54, p = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19-2.22, p = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19-2.47, p = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, p = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65-1.17, p = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (r= -0.49; 95% CI= -0.75, -0.24; p < 0.001) and inflammatory markers (r = 0.43; 95% CI= 0.03, 0.84; p = 0.036) in non-dialysis patients. CONCLUSIONS: Increased circulating TMAO concentrations increase the risk of all-cause mortality in non-dialysis and non-black dialysis CKD patients. Moreover, elevated TMAO levels raise the cardiovascular mortality risk in non-black dialysis patients.Key messagesNon-dialysis and non-black dialysis CKD patients with higher circulating TMAO concentrations are associated with an increased risk of all-cause mortality.Non-black dialysis patients with higher concentrations of TMAO are associated with an increased risk of cardiovascular mortality.Circulating TMAO concentrations have a strong negative correlation with GFR and a positive correlation with inflammation biomarkers in non-dialysis CKD patients.
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Enfermedades Cardiovasculares , Microbioma Gastrointestinal , Insuficiencia Renal Crónica , Humanos , Enfermedades Cardiovasculares/etiología , Microbioma Gastrointestinal/fisiología , Inflamación/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapiaRESUMEN
We previously found that the RING-type E3 ligase DEFECTIVE IN ANTHER DEHISCENCE1- (DAD1-) Activating Factor (DAF) controls anther dehiscence by activating the jasmonate biosynthetic pathway in Arabidopsis. Here, we show that in Arabidopsis, the DAF ancestor was duplicated into three genes (DAF, Ovule Activating Factor (OAF), DAFL2), which evolved divergent partial functions from their ancestor through subfunctionalization. In this case, DAF-DAD1-JA signaling regulates anther dehiscence, whereas OAF controls ovule development by negatively regulating cinnamyl alcohol dehydrogenase 9 (CAD9) activity and being negatively regulated by miR847 itself in Arabidopsis. Downregulation of OAF or upregulation of CAD9 and miR847 caused similar abortion of ovule formation due to precocious ovule lignification in transgenic Arabidopsis. Interestingly, only one DAF-like gene, PaOAF, exists in the monocot orchids, which has likely evolved through nonfunctionalization and maintains a conserved function as Arabidopsis OAF in regulating ovule development since defective ovules were observed in the virus-induced gene silencing (VIGS) PaOAF Phalaenopsis orchids. The absence of the DAF ortholog and its function in orchids is likely due to the evolution of stamens to a unique pollinium structure that lacks the feature of anther dehiscence. These findings expand the current knowledge underlying the multifunctional evolution and diverse functionalization of duplicate gene pairs within/among plants.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Óvulo Vegetal/genética , Óvulo Vegetal/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Regulación hacia ArribaRESUMEN
A total of 179 normal full-term pregnant women and their newborns were randomly selected. Umbilical venous blood was extracted after the delivery, and the serum level of 25(OH)D3 was measured. Forty 2 days, 3 months, 6 months, and one year after the birth to be asked about the occurrence and development of infant eczema. Thirteen cases were lost to follow-up. The median concentration of 25(OH)D3 in the cord blood was 25.40 ng/mL. Thirty eight cases (22.9%) were vitamin D deficient (<20 ng/mL), 77 cases (46.4%) were vitamin D insufficient (20-30 ng/mL), and 51 cases (30.7%) were vitamin D sufficient (≥30 ng/mL). The incidence of eczema in the umbilical cord blood vitamin D sufficient group was lower than that in the deficient and insufficient groups (p < .05). Sufficient umbilical cord blood vitamin D levels are associated with a lower incidence of eczema in infants up to one year of age. IMPACT STATEMENTWhat is already known on this subject? A number of studies have suggested that vitamin D levels in early life are related to the occurrence of allergic diseases, but the conclusions are not uniform.What do the results of this study add? The rate of sufficient umbilical cord blood vitamin D was low in the Songjiang area of Shanghai. Sufficient umbilical cord blood vitamin D levels (≥30 ng/mL) are associated with a lower incidence of eczema in infants up to 1 year of age.What are the implications of these findings for clinical practice and/or further research? At present, the dose of vitamin D for pregnant women at home and abroad is not consistent, so the specific dose of vitamin D for pregnant women to maintain the foetus needs further discussion. It is expected that a reasonable recommended dose can be developed to reduce the risk of allergic diseases in future generations from a primary prevention perspective.
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Dermatitis Atópica , Eccema , Deficiencia de Vitamina D , Lactante , Recién Nacido , Femenino , Humanos , Embarazo , Vitamina D , Sangre Fetal , China , Vitaminas , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Calcifediol , Eccema/epidemiología , Eccema/etiologíaRESUMEN
FOREVER YOUNG FLOWER (FYF) has been reported to play an important role in regulating flower senescence/abscission. Here, we functionally analyzed five Arabidopsis FYF-like genes, two in the FYF subgroup (FYL1/AGL71 and FYL2/AGL72) and three in the SOC1 subgroup (SOC1/AGL20, AGL19, and AGL14/XAL2), and showed their involvement in the regulation of flower senescence and/or abscission. We demonstrated that in FYF subgroup, FYF has both functions in suppressing flower senescence and abscission, FYL1 only suppresses flower abscission and FYL2 has been converted as an activator to promote flower senescence. In SOC1 subgroup, AGL19/AGL14/SOC1 have only one function in suppressing flower senescence. We also found that FYF-like proteins can form heterotetrameric complexes with different combinations of A/E functional proteins (such as AGL6 and SEP1) and AGL15/18-like proteins to perform their functions. These findings greatly expand the current knowledge behind the multifunctional evolution of FYF-like genes and uncover their regulatory network in plants.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Senescencia de la PlantaRESUMEN
Cognitive aging is a major risk factor for neurodegenerative diseases and has a great impact on the living quality of older individuals. However, the precise mechanisms underlying cognitive aging remain elusive. Accumulating evidence has demonstrated that interleukin 17A (IL-17A) is responsible for cognitive decline in the process of various neurological diseases. Thus, we conducted this study aiming to investigate the role of IL-17A in cognitive aging. In the present study, 31 aging (65-85 years) and 25 young (18-35 years) patients scheduled for elective removal of internal fixation surgery with spinal anesthesia were included for measurements of preoperative cognitive function, serum and cerebrospinal fluid (CSF) levels of IL-17A. For animal study, RNAseq and Kyoto Encyclopedia of Genes and Genomes pathways were used to identify differentially expressed genes between young and aging mice. For the treatment groups, young (2-3 months) and aging (16-18 months) mice received intraperitoneally with IL-17A and anti-IL-17A antibody, respectively. Twenty-four hours later, neurocognitive behavioral tests were conducted. Our results suggested that differentially expressed genes between young and aging mice were mainly enriched in IL-17 pathways. Serum and CSF levels of IL-17A increased significantly in aging patients and were negatively correlated with mini-mental state examination scores. Both young mice receiving IL-17A and aging mice showed impaired memory, increased blood-brain barrier permeability, overactivated microglia and increased inflammatory mediators in the hippocampus. Additionally, aging mice showed a significantly decreased θ power in the task-related neural oscillations. Notably, intraperitoneal injection of anti-IL-17A antibody alleviated increased blood-brain barrier permeability, microglial activation, neuroinflammation, θ oscillation disruption and cognitive decline of aging mice. In conclusion, our study demonstrated that IL-17A may be an initiating factor of cognitive aging.
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Envejecimiento Cognitivo , Interleucina-17 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Hipocampo/metabolismo , Humanos , Interleucina-17/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Adulto JovenRESUMEN
Diabetic nephropathy (DN), a severe microvascular complication of diabetes, is one of the leading causes of end-stage renal disease. Huayu Tongluo Recipe (HTR) has been widely used in the clinical treatment of DN in China, and its efficacy is reliable. This study aimed to explore the renoprotective effect of HTR and the underlying mechanism. Male Sprague-Dawley rats were fed with high sugar and fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. Rats in each group were respectively given drinking water, HTR, and irbesartan by gavage for 16 weeks. 24-hour urine samples were collected every 4 weeks to detect the content of total protein and 8-OHdG. Blood samples were taken to detect biochemical indicators and inflammatory markers at the end of 16th week. Renal tissue was collected to investigate pathological changes and to detect oxidative stress and inflammatory markers. AMPK/Nrf2 signaling pathway and fibrosis-related proteins were detected by immunohistochemistry, immunofluorescence, real-time PCR, and western blot. 24h urine total protein (24h UTP), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), and triglyceride (TG) were decreased in the rats treated with HTR, while there was no noticeable change of blood glucose. HTR administration decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in kidneys, complying with reduced 8-OHdG in the urine. The levels of TNF-α, IL-1ß, and MCP1 and the expression of nuclear NFκB were also lower after HTR treatment. Furthermore, HTR alleviated pathological renal injury and reduced the accumulation of extracellular matrix (ECM). Besides, HTR enhanced the AMPK/Nrf2 signaling and increased the expression of HO-1 while it inhibited the Nox4/TGF-ß1 signaling in the kidneys of STZ-induced diabetic rats. HTR can inhibit renal oxidative stress and inflammation to reduce ECM accumulation and protect the kidney through activating the AMPK/Nrf2 signaling pathway in DN.
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As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.
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OBJECTIVE: Studies have demonstrated that tetrandrine reverses multidrug resistance (MDR) in animal models or cell lines derived from multiple cancer types. We examined the potential MDR reversal activity of tetrandrine in a multidrug-resistant variant of a human laryngeal cancer Hep-2 cell line and explored potential mechanisms involved. METHODS: We developed the multidrug-resistant variant cell line (Hep-2/v) by exposing Hep-2 cells to stepwise increasing concentrations of vincristine (VCR). After Hep-2 or Hep-2/v cells were treated with tetrandrine (2.52 µg/mL), MDR was measured by MTT assay, rhodamine 123 retention was measured by flow cytometry, and mRNA and protein expression of multidrug resistance 1 (MDR1), regulator of G-protein signaling 10 (RGS10), high-temperature requirement protein A1 (HTRA1), and nuclear protein 1 (NUPR1) were detected by real-time reverse transcription-PCR and western blotting, respectively. RESULTS: Tetrandrine significantly lowered the half-maximal inhibitory concentration (IC50) of VCR in Hep-2/v cells, resulting in a 2.22-fold reversal of MDR. Treatment with tetrandrine increased rhodamine 123 retention, downregulated the mRNA and protein expression of MDR1 and RGS10, and upregulated expression of HTRA1 in Hep-2/v cells. CONCLUSION: We showed that tetrandrine exerts anti-MDR activity in Hep-2/v cells, possibly by inhibiting MDR1 overexpression-mediated drug efflux and by altering expression of HTRA1 and RGS10.
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Neoplasias Laríngeas , Proteínas RGS , Bencilisoquinolinas , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Serina Peptidasa A1 que Requiere Temperaturas Altas , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/genéticaRESUMEN
Using Landsat 5/TM and Landsat 8/OLI images in 2000 and 2017, based on remote sensing ecological index (RSEI) model, combined with meteorological observation data and socio-economic data in Nanjing from 2000 to 2017, we analyzed and evaluated the ecological environment changes and the characteristic ecological areas in Nanjing. The results showed that the average RSEI of Nanjing decreased from 0.626 to 0.618 during 2000-2017. The RSEI values could be divided into five grades: bad, poor, fair, good and excellent. The proportion of area above good grade decreased from 61.0% to 57.1%, while that below poor grade increased slightly. Compared with 2000, the proportion of areas with improved ecological environment quality was 34.5%, 34.7% area had deteriorated, and 30.8% area remained unchanged in 2017. Among them, the ecological quality of main urban area had significantly improved, and the area with improved ecological quality exceeded that of deterioration. The ecological quality of new urban area and suburbs had deteriorated. The area with poor ecological environment exceeded the area of improvement. Among the three ecological protection areas, the ecological quality of Zijin Mountain was significantly better than that of Laoshan Mountain and Jiangxinzhou. The urbanization rate was negatively correlated with RSEI, with a correlation coefficient of -0.91. The urbanization process would have negative impacts on the ecological environment in general. However, strict protection and management measures could maintain the good ecological environment even improve it.
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Ecosistema , Urbanización , China , Monitoreo del Ambiente , Tecnología de Sensores RemotosRESUMEN
The inflammatory response is one of the most important factors in the occurrence and development of acute lung injury (ALI). Hypoxiainducible factor1α (HIF1α) and the NODlike receptor 3 (NLRP3) inflammasome have been demonstrated to serve an important role in the pathogenesis of ALI. The objective of the present study was to investigate whether HIF1α could regulate activation of the NLRP3 inflammasome and its potential function and specific mechanism in bleomycin (BLM)induced ALI. Activation of the NLRP3 inflammasome and secretion of IL1ß were detected following silencing of HIF1α or NFκB, respectively, in BLMtreated A549 and RLE6TN cells. The results demonstrated that the NLRP3 inflammasome could be activated after BLM treatment. HIF1α and NFκB expression significantly increased in the BLM group. The levels of NFκB and NLRP3 inflammasomeassociated proteins, including NLRP3, apoptosisassociated specklike protein containing CARD and caspase1, markedly decreased after treating A549 and RLE6TN cells with HIF1α small interfering RNA. Activation of the NLRP3 inflammasome was also inhibited after silencing NFκB. Furthermore, the levels of IL1ß markedly decreased in the cellular culture supernatants following inhibition of HIF1α and NFκB. Therefore, the present study indicated that HIF1α could modulate the activation of the NLRP3 inflammasome and the secretion of IL1ß through NFκB signaling in BLMinduced ALI. The current results improve understanding of the mechanism of ALI and may provide new ideas for identifying therapeutic targets of ALI.
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Lesión Pulmonar Aguda/metabolismo , Bleomicina/efectos adversos , Regulación de la Expresión Génica/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células A549 , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Animales , Bleomicina/farmacología , Humanos , Interleucina-1beta/biosíntesis , FN-kappa B/metabolismo , RatasRESUMEN
PURPOSE: Probe-based confocal laser endomicroscopy (pCLE) enables in vivo, in situ tissue characterisation without changes in the surgical setting and simplifies the oncological surgical workflow. The potential of this technique in identifying residual cancer tissue and improving resection rates of brain tumours has been recently verified in pilot studies. The interpretation of endomicroscopic information is challenging, particularly for surgeons who do not themselves routinely review histopathology. Also, the diagnosis can be examiner-dependent, leading to considerable inter-observer variability. Therefore, automatic tissue characterisation with pCLE would support the surgeon in establishing diagnosis as well as guide robot-assisted intervention procedures. METHODS: The aim of this work is to propose a deep learning-based framework for brain tissue characterisation for context aware diagnosis support in neurosurgical oncology. An efficient representation of the context information of pCLE data is presented by exploring state-of-the-art CNN models with different tuning configurations. A novel video classification framework based on the combination of convolutional layers with long-range temporal recursion has been proposed to estimate the probability of each tumour class. The video classification accuracy is compared for different network architectures and data representation and video segmentation methods. RESULTS: We demonstrate the application of the proposed deep learning framework to classify Glioblastoma and Meningioma brain tumours based on endomicroscopic data. Results show significant improvement of our proposed image classification framework over state-of-the-art feature-based methods. The use of video data further improves the classification performance, achieving accuracy equal to 99.49%. CONCLUSIONS: This work demonstrates that deep learning can provide an efficient representation of pCLE data and accurately classify Glioblastoma and Meningioma tumours. The performance evaluation analysis shows the potential clinical value of the technique.
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Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Endoscopía , Microscopía Confocal , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Variaciones Dependientes del ObservadorRESUMEN
OBJECTIVE: To investigate the clinical indicators for early identification of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children. METHODS: The clinical data of 142 children with Mycoplasma pneumoniae pneumonia (MPP) between January 2014 and June 2015 were retrospectively studied. Among the 142 children, there were 32 cases of RMPP and 110 cases of non-refractory MPP. The clinical data were compared between the RMPP and non-refractory MPP groups. RESULTS: The percentage of school-age children in the RMPP group was higher than in the non-refractory MPP group (P<0.05). The mean onset age in the RMPP group was older than the non-refractory MPP group (P<0.05). Steroid was used in 93.8% of RMPP children compared with 7.3% of non-refractory MPP children (P<0.001). Consolidation of lung on chest X-Ray was shown in 87.5% of RMPP children compared with 42.7% of non-refractory MPP children (P<0.001). The incidence of pleural effusion in the RMPP group was higher than in the non-refractory MPP group (P<0.001). The RMPP group had higher percentages of individuals with CRP>40 mg/L and ESR>30 mm/h+LDH>300 IU/L than the non-refractory MPP group (P<0.05). CONCLUSIONS: RMPP is common in school-age children. Consolidation of lung on chest X-Ray, pleural effusion and increased levels of CRP and ESR+LDH may be helpful to early identification of RMPP in children.
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Neumonía por Mycoplasma/diagnóstico , Proteína C-Reactiva/análisis , Calcitonina/sangre , Niño , Preescolar , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Neumonía por Mycoplasma/sangre , Precursores de Proteínas/sangre , Estudios RetrospectivosRESUMEN
Activation of the renin-angiotensin system (angiotensin-converting enzyme [ACE]/angiotensin II [Ang II] and angiotensin-converting enzyme 2 [ACE2]/Ang-1-7) has been implicated in the pathophysiology of inflammatory response and acute lung injury (ALI). Previous studies have shown that the ACE inhibitor captopril (Cap) may be a potent therapeutic drug for ALI. However, the mechanisms of its protective effects on ALI are still largely unknown. In this study, we evaluated the effects of Cap on preventing lipopolysaccharide (LPS)-induced lung injury and further investigated the underlying mechanisms of these protective effects. Rats were intraperitoneally pretreated with Cap (50 mg/kg) 30 min prior to an intravenous administration of LPS (7.5 mg/kg). Furthermore, following a 30-min pretreatment with Cap (10 mol/mL) or combined with the ACE2 inhibitor MLN4760 (10 mol/mL), rat pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS (1 mg/mL). Captopril pretreatment significantly attenuated LPS-induced pathophysiological changes in the lung, inhibited secretion of tumor necrosis factor α and interleukin 6, reduced the ratio of Ang II to Ang-1-7, and reversed the increased ratio of ACE to ACE2, which was remarkably decreased from 7.07 (LPS only) to 1.71 (LPS + Cap). The protective effects of Cap on ALI were also confirmed by in vitro studies, in which Cap suppressed LPS-induced secretion of proinflammatory cytokines and modulated the expression levels of ACE and ACE2. After Cap pretreatment, the ratio of ACE to ACE2 expression was remarkably decreased from 5.18 (LPS alone) to 1.52 (LPS + Cap). Furthermore, Cap given before LPS administration led to inhibition of p38 mitogen-activated protein kinase (MAPK), ERK (extracellular signal-regulated kinase) 1/2, and JNK (c-Jun N-terminal kinase) phosphorylation in PMVECs, whereas MLN4760 abolished the protective effects of Cap on LPS-induced secretion of proinflammatory cytokines and abolished Cap-induced blockade of p38MAPK, ERK1/2, and JNK phosphorylation. Our findings reveal that Cap exerts protective effects on LPS-induced lung injury and the cytotoxicity of PMVECs, and these effects may, at least in part, regulate the balance of ACE and ACE2 expression and inhibit the activation of MAPKs.