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1.
Front Pediatr ; 12: 1409046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774298

RESUMO

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

2.
Environ Res ; 243: 117780, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056613

RESUMO

Groundwater is the second largest water source for daily consumption, only next to surface water resources. Groundwater has been extensively investigated for its pollution level in urban areas. The groundwater quality assessments in industrial areas associated with every urban landscape are still lacking. In order to examine the spatial distribution characteristics, pollution levels, and sources of trace metals in the densely populated Chennai coastal region of Tamilnadu, India, physicochemical parameters and trace element concentrations have been determined in groundwater. 55 groundwater samples from Tamil Nadu's coastal region were collected and analyzed for physicochemical parameters such as pH, (EC), (TDS), and (TH) during the pre-monsoon (June 2015) and post-monsoon (January 2016) seasons. We used trace elements and analyzed them in this study (Mg, Zn, Pb, Ni, Co, Cu, Cr, and Fe). Furthermore, anthropogenic input from industries and power plants exacerbates the pollution of Ni, Mg, Fe, and Mn. Due to evaporites and anthropogenic input, samples with excessive salinity, total hardness, and water quality are considered unsuitable for irrigation or drinking. The results demonstrated that seasonal, geogenic, and anthropogenic influences all have a significant impact on the heterogeneous chemistry of groundwater.


Assuntos
Água Subterrânea , Metais Pesados , Oligoelementos , Poluentes Químicos da Água , Estações do Ano , Monitoramento Ambiental/métodos , Oligoelementos/análise , Índia , Poluentes Químicos da Água/análise , Qualidade da Água , Metais Pesados/análise
3.
J Nanobiotechnology ; 21(1): 375, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833677

RESUMO

Current protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development of implantable memristor devices. It is imperative to discover novel candidate materials for biomemristor with high durability and excellent biosafety for implantable health monitoring. Herein, we initially demonstrate the resistance switching characteristics of a nonvolatile memristor in a configuration of Pt/AlOOH/ITO consisting of biocompatible AlOOH nanosheets sandwiched between a Indium Tin Oxides (ITO) electrode and a platinum (Pt) counter-electrode. The hydrothermally synthesized AlOOH nanosheets have excellent biocompatibility as confirmed through the Cell Counting Kit-8 (CCK-8) tests. Four discrete resistance levels are achieved in this assembled device in responsible to different compliance currents (ICC) for the set process, where the emerging multilevel states show high durability over 103 cycles, outperforming the protein-based biomemristors under similar conditions. The excellent performance of the Pt/AlOOH/ITO memristor is attributed to the significant role of hydrogen proton with pipe effect, as confirmed by both experimental results and density functional theory (DFT) analyses. The present results indicate the nonvolatile memristors with great potential as the next generation implantable multilevel resistive memories for long-term human health monitoring.


Assuntos
Hidróxido de Alumínio , Produtos Biológicos , Humanos , Óxido de Alumínio
4.
Chemosphere ; 338: 139434, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37487978

RESUMO

In order to reduce contamination levels from diverse sources, it is important to understand the factors affecting the natural ecosystems that are impacted by coastal and marine pollution. In this study, we used GIS and remote sensing techniques to investigate and evaluate the distribution of heavy metals (Fe, Mn, Zn, Cr, Pb, Co, and Cu) in surface sediments along Tamil Nadu's East Coast (from Besant Nagar to Sathurangapattinam). The CF and Igeo of metals indicate that sediments contain no evidence of Fe, Mn, or Zn metal pollution in the sediments, with only mild contamination from Co, Cu, and Pb. In contrast, the sediment samples were found to be significantly contaminated with Cr. Heavy metal contamination occurs in the following order, according to our research: Cr > Pb > Cu > Co > Mn > Zn > Fe. Except for sites 8, 10, 11, and 13, where PLI>1 implies that there is no pollution in this area, the PLI values show that most of the locations are contaminated. The ecological risk index (ERI) values for five metals in the study areas are as follows: Cr > Pb > Cu > Mn > Zn. The sediment samples fall into the low-risk and highly polluted to dangerous sediment categories for SPI, according to the Risk index (RI). Based on the Mean Effect Range-Median Quotient (M-ERM-Q), Cu, Pb, Zn, and Cr metals in the research region have a 9-21% probability of being harmful. Statistical approaches show that the majority of heavy metals in sediments are of natural origin. The spatial distribution of heavy metals in surface sediments provides the conceptual framework for practical strategies to protect coastal areas. Many shreds of evidence indicate that anthropogenic inputs from the surrounding land area are primarily responsible for the deposition of these heavy metals in the coastal zone.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Ecossistema , Índia , Chumbo , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Medição de Risco , Monitoramento Ambiental/métodos , Metais Pesados/análise
6.
Nat Commun ; 14(1): 3102, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248221

RESUMO

How climate change in the middle to late Holocene has influenced the early human migrations in Central Asian Steppe remains poorly understood. To address this issue, we reconstructed a multiproxy-based Holocene climate history from the sediments of Kanas Lake and neighboring Tiewaike Lake in the southern Altai Mountains. The results show an exceptionally warm climate during ~6.5-3.6 kyr is indicated by the silicon isotope composition of diatom silica (δ30Sidiatom) and the biogenic silica (BSi) content. During 4.7-4.3 kyr, a peak in δ30Sidiatom reflects enhanced lake thermal stratification and periodic nutrient limitation as indicated by concomitant decreasing BSi content. Our geochemical results indicate a significantly warm and wet climate in the Altai Mountain region during 6.5-3.6 kyr, corresponding to the Altai Holocene Climatic Optimum (AHCO), which is critical for promoting prehistoric human population expansion and intensified cultural exchanges across the Central Asian steppe during the Bronze Age.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36991206

RESUMO

This research is to develop dictated metrics using a multi-proxy approach such as spatial-temporal analysis, statistical evaluation, and hydrogeochemical analysis. We have collected 45 groundwater samples located in the Tamirabarani river basin. To evaluate the aptness of developed metrics for agriculture and domestic needs and eleven years dataset has been analyzed and compared with national and international standards BIS, ICMAR, and WHO Monitoring and all the analysis results revealed that the concentration of calcium (Ca-1679 to 4937 mg/L; and Cl ions 236 to 1126 mg/L) and chloride ions was on the higher side in locations. These higher values may be attributed to the regional point sources as untreated water disposal and off-peak sources as agriculture practices. According to the results of the principal component analysis, the post-monsoon season accounted for an 84.2% variance. The major analyzed cations and anions have been observed in the following order: Na+ > Ca2+ > Mg2+ > K+ and Cl- > HCO3- > SO42- > NO3- respectively. Ca-Mg-HCO3, Mg-Ca-Cl, Na-C1, and infused waters have been discovered in the basin region, indicating that anion and cation dominance is not prevalent. This specifies that groundwater quality in this region is significantly degraded and suffers from extensive salinity due to the urban pollutants mixed with unprotected river sites.

8.
Diabetes ; 72(1): 97-111, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256844

RESUMO

Studies of diabetic glomerular injury have raised the possibility of developing useful early biomarkers and therapeutic approaches for the treatment of type 2 diabetic nephropathy (T2DN). In this study, we found that FGF13 expression is induced in glomerular endothelial cells (GECs) during T2DN progression. Endothelial-specific deletion of Fgf13 potentially alleviates T2DN damage, while Fgf13 overexpression has the opposite effect. Mechanistically, Fgf13 deficiency results in improved mitochondrial homeostasis and endothelial barrier integrity in T2DN. Moreover, FGF13-sensitive alteration of Parkin safeguards mitochondrial homeostasis in endothelium of T2DN through promotion of mitophagy and inhibition of apoptosis. Additionally, it is confirmed that the beneficial effects of Fgf13 deficiency on T2DN are abolished by endothelial-specific double deletion of Fgf13 and Prkn. The effects of Fgf13 deficiency on mitophagy and apoptosis through Parkin-dependent regulation may be distinct and separable events under diabetic conditions. These data show that the bifunctional role of Fgf13 deficiency in promoting mitophagy and inhibiting apoptosis through Parkin can shape mitochondrial homeostasis regulation in GECs and T2DN progression. As a potential therapeutic target for prevention and control of T2DN, a mechanistic understanding of the biofunction of FGF13 may also be relevant to the pathogenesis of other FGF13- and Parkin-associated diseases.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/metabolismo , Células Endoteliais/metabolismo , Endotélio/metabolismo , Endotélio/patologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Homeostase/genética , Diabetes Mellitus/metabolismo
9.
Nanoscale ; 15(1): 294-303, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36484267

RESUMO

Metal-organic frameworks (MOFs) have drawn a lot of interest as prospective starting points for highly effective electromagnetic wave (EMW) absorbers. However, the inevitable shrinkage and probable densification that occur during pyrolysis significantly reduce the microwave-loss capacity. A dual-layer MOF, ZIF-8@ZIF-67, is created and effectively decorated on graphene sheets as a solution to this problem. The shrinkage and densification were then suppressed by the subsequent pulverization effect between the two MOFs. Due to suitable compositions and specialized microstructures, G/Co@C exhibits excellent impedance matching and dissipates EMW by combining magnetic and dielectric loss. The maximum reflection loss of G/Co@C-7/paraffin is -55.0 dB at 5.8 GHz with just 7% filler. Therefore, the preparation of high-efficiency MOF-derived microwave absorbers by the pulverization effect is demonstrated to be an efficient strategy.

11.
Sci Rep ; 12(1): 20599, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36446834

RESUMO

In this paper, a high-absorption and dual-transmission-bands rasorber (HADTR) was proposed. Different from the reported designs, a foam layer and a FR4 layer are added as top layers in HADTR to improve its absorption and oblique incidence performance. The unit cell of resistive layer is concentric metallic rings loaded with chip resistors based on absorption enforced design to ensure its dual-transmission-bands at the same time. The unit cell of band-stop frequency selective surface (BS-FSS) is double metallic square loops loaded with chip inductors on both sides of FR4 substrate, which expands its reflection band (|S11|≥ - 1.0 dB) without destroying its dual-transmission-bands effectively. At normal incidence, for TE and TM polarization, the HADTR has a low-frequency passband up to 1.34 GHz (|S21|≥ - 1.5 dB), a high-frequency passband from 16.04 to 18.00 GHz (|S21|≥ - 1.5 dB) and a wide 90% absorption band from 5.01 to 10.56 GHz; and the reflection coefficient below - 10 dB and - 20 dB is in the range of 4.48-11.70 GHz and 5.48-9.96 GHz, respectively. For TE/TM polarization, the 90% absorption of oblique incidence stability is 40° and 30° respectively. Strong association between measurement and simulation results validates the design method and the HADTR.

12.
J Appl Microbiol ; 133(6): 3708-3718, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36082438

RESUMO

AIMS: To explore how fermented barley extracts could affect obesity-associated inflammatory responses to ameliorate high-fat diet (HFD)-induced obesity, and investigate whether their anti-inflammatory properties were affected by modulating the gut microbiota. METHODS AND RESULTS: Twenty-four male rats were assigned randomly to three groups for 8 weeks. Inflammatory status and gut microbiota in HFD-induced obese rats were measured by enzyme linked immunosorbent assay and 16sRNA sequencing technology. The dietary supplementation of Extract of fermented barley with L. plantarum JDM1 (LFBE) reduced HFD-induced obesity and improved insulin sensitivity. LFBE significantly decreased the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines (tumour necrosis factor-α, interleukin [IL]-6, IL-1ß, monocyte chemotactic protein-1), and increased anti-inflammatory cytokines (IL-10) in serum. In addition, LFBE suppressed the activation of nuclear factor-κB (NF-κB) by inhibiting the inhibitor of NF-κB alpha degradation and phosphorylation of JNK/p38 mitogen-activated protein kinases in adipose tissue. Combined with changes in gut microbiota, these results illustrated that LFBE treatment markedly decreased the proportion of the LPS-producing opportunistic pathogens and increased the proportion of Bifidobacterium. CONCLUSIONS: Administration of LFBE has beneficial effects on ameliorating HFD-induced obesity and insulin resistance, lessening HFD-induced gut microbiota dysbiosis and pro-inflammatory cytokines secretion. SIGNIFICANCE AND IMPACT OF THIS STUDY: The results suggest that fermented barley extracts may be a useful functional compound and beneficial to improve inflammatory status and gut microflora.


Assuntos
Microbioma Gastrointestinal , Hordeum , Resistência à Insulina , Ratos , Masculino , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Hordeum/metabolismo , Lipopolissacarídeos/metabolismo , NF-kappa B/metabolismo , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL
13.
Eur J Pharmacol ; 931: 175193, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35963324

RESUMO

Liver fibrosis is characterized by the abnormal deposition of the extracellular matrix with a severe inflammatory response and/or metabolic disorder. Asiatic acid (AA), a natural compound derived from Centella asiatica, exhibited potent anti-fibrosis effects. This investigation first confirmed the anti-fibrosis effects of AA in TGF-ß-LX-2 cells and CCl4-induced liver fibrosis mice, and then sought to elucidate a novel mechanism of action by integrating network pharmacology and lipidomics. Network pharmacology was used to find potential targets of AA, while lipidomics was used to identify differential metabolites between fibrosis and recovered cohorts. AA could suppress hepatic stellate cell activation in vitro and improve liver fibrosis in vivo. Network pharmacology unveiled the genes involved in pathways in cancer, peroxisome proliferators-activated receptors signaling pathway, and arachidonic acid metabolism pathway. Furthermore, five key genes were found in the both human and mouse databases, indicating that arachidonic acid metabolism was important. Changes in lyso-phosphocholine (22:5), prostaglandin F2α, and other related lipid metabolites also suggested the involvement of arachidonic acid metabolism the anti-fibrotic effect. In summary, our integrated strategies demonstrated that AA targeted multiple targets and impeded the progression of liver fibrosis by ameliorating arachidonic acid metabolism.


Assuntos
Lipidômica , Farmacologia em Rede , Animais , Ácido Araquidônico/metabolismo , Células Estreladas do Fígado , Humanos , Fígado , Cirrose Hepática/patologia , Camundongos , Triterpenos Pentacíclicos , Transdução de Sinais
14.
Sci Total Environ ; 833: 155153, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35413343

RESUMO

Fire plays an important role in carbon emissions and climate changes in the Earth system and global/regional fires in the past have been detected. However, palaeofire history and their potential drivers are poorly understood in Central Asia. We in this study synthesized existing sedimentary charcoal records to reconstruct Holocene fire history in Central Asia and then assessed the relative importance of two potential controls (climatic and anthropogenic factors) on its trends. The results are: (1) Fire activity had insignificantly increased since ~7.9 cal. yr BP in Central Asia, although there was an obvious difference when fire history at different elevations is considered; (2) Periods of high fire activity occurred in the early-middle Holocene following by a decreasing trend in the late Holocene at high elevation, which might be attributed to a cooling temperature and the cooling-caused low biomass burning in the Holocene interval; (3) Episodes of high fire activity were common in the late Holocene and were primarily driven by the wetting-induced increased biomass burning, reinforced by the intensified human activities in middle-low elevation. Our findings could not only provide new unique insight about the long-time-scale fire-human-climate-vegetation interactions and also provide reasonable guidance for fire management given current climate change in Central Asia.


Assuntos
Ecossistema , Incêndios , Ásia , Biomassa , Mudança Climática , Humanos
15.
Chemosphere ; 287(Pt 1): 131974, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34455126

RESUMO

This study provides a feasible scheme for the treatment of municipal sewage through simultaneous partial nitritation, anammox, and denitrification (SNAD) process, which was realized in a single-stage biofilter reactor (BFR). First, the BFR was started up to enrich the anaerobic ammonium-oxidizing bacteria (AnAOB) in the upper part of the reactor through the operation mode of the top influent and bottom effluent. Then, the BFR was inoculated with activated sludge and aerated continuously at the bottom to realize the coupling of SNAD, which was accompanied by a two-point influent from the bottom and top effluent. Results indicated that the high removal efficiency of NH4+-N (93.40%), total nitrogen (TN, 89.95%), and soluble chemical oxygen demand (SCOD, 92.68%) were achieved with an air-water ratio of 4.29 and hydraulic retention time (HRT) of 6 h. During the SNAD steady phase for the treatment of simulated municipal sewage with a soluble chemical organic demand to nitrogen (C/N) ratio of 2.31, low concentrations of NH4+-N (4.13 mg/L), TN (6.44 mg/L), and SCOD (11.29 mg/L) were attained in the effluent. High-throughput sequencing analysis indicated that the relative abundance of Nitrosomonas, Candidatus Brocadia, and Denitratisoma were 0.77%, 0.43%, and 4.07% in the biofilm at the 0-12.5 cm zone, respectively, suggesting successful implementation of the SNAD process.


Assuntos
Compostos de Amônio , Esgotos , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Águas Residuárias
16.
Mar Pollut Bull ; 174: 113232, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34952403

RESUMO

In coastal aquifers, seawater intrusion is a significant groundwater issue. The research paper contributes to the understanding of the consequences of seawater intrusion in the Chennai coastal aquifer from Foreshore Estate to Thirunilai along the coastline. 110 groundwater samples were collected and analyzed for physicochemical parameters such as pH, (EC), (TDS), (TH), major anions (Cl-, NO3-, HCO32-, and SO42-), and cations (Ca2+, Mg2+, Na+, and K+) during the pre-monsoon (June 2014) and post-monsoon (January 2015) seasons. Stable isotopic analyses of 18O were performed on 24 groundwater samples collected from various locations throughout the research region based on EC, TDS, Na, and Cl- concentrations for both seasons. The stable isotopic composition of 18O and Deuterium in groundwater samples was determined for the study region. According to the Correlation matrix and Factor analysis, the main contributors to groundwater salinity as a result of seawater intrusion into the coastal aquifer are EC, TDS, Na+, and Cl-. GMWL exhibits a similar pattern, and the samples have been classified into various molar ratio diagrams to identify seawater intrusions for better evaluation. The result revealed that seasonal, geogenic, and anthropogenic factors always make a significant contribution to the heterogeneous chemistry of groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Efeitos Antropogênicos , Monitoramento Ambiental , Índia , Água do Mar , Poluentes Químicos da Água/análise
17.
Front Physiol ; 12: 660263, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483951

RESUMO

Background/Aims: Diabetic foot ulcers (DFUs) present a major challenge in clinical practice, and hyperglycemia-induced angiogenesis disturbance and endothelial dysfunction likely exacerbate DFUs. The long-acting glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) is a potential activator of AMP-activated protein kinase (AMPK) that appears to enhance endothelial function and have substantial pro-angiogenesis and antioxidant stress effects. Therefore, in this study, we aimed to investigate whether the protective role of Lira in diabetic wound healing acts against the mechanisms underlying hyperglycemia-induced endothelial dysfunction and angiogenesis disturbance. Methods: Accordingly, db/db mice were assessed after receiving subcutaneous Lira injections. We also cultured human umbilical vein endothelial cells (HUVECs) in either normal or high glucose (5.5 or 33 mM glucose, respectively) medium with or without Lira for 72 h. Results: An obvious inhibition of hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance was observed; follow by a promotion of diabetic wound healing under Lira treatment combined with restored hyperglycemia-impaired AMPK signaling pathway activity. AMPKα1/2 siRNA and Compound C (Cpd C), an inhibitor of AMPK, abolished both Lira-mediated endothelial protection and pro-angiogenesis action, as well as the diabetic wound healing promoted by Lira. Furthermore, hypoxia inducible factor-1α (Hif-1α; transcription factors of AMPK substrates) knockdown in HUVECs and db/db mice demonstrated that Lira activated AMPK to prevent hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance, with a subsequent promotion of diabetic wound healing that was Hif-1α-heme oxygenase-1 (HO-1) axis-dependent. Taken together, these findings reveal that the promotion of diabetic wound healing by Lira occurs via its AMPK-dependent endothelial protection and pro-angiogenic effects, which are regulated by the Hif-1α-HO-1 axis.

18.
Bioresour Technol ; 337: 125496, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34320773

RESUMO

The high-rate nitrogen removal in a continuous biofilter anammox reactor (CBAR) was investigated to treat low-concentration nitrogen wastewater. Shortening hydraulic retention time (HRT) gradually could restart CBAR and accumulate anammox bacteria effectively in the reactor, where the carmine anammox granular sludge and biofilm were coexisted well. It spent 21 days to restart CBAR completely after it had been idle for 116 days. Meanwhile, the total nitrogen removal rate remained stable at 86.42% accompanied with a total biomass concentration of 26.02 g-SS/L in 0 ~ 20 cm zone under nitrogen loading rate of 4.25 ± 0.10 kg-N/(m3·day), HRT of 20 min and 25 ℃. In addition, the specific anammox activity of biomass exceeded 0.28 g-N/(g-VSS·day) in 0 ~ 20 cm zone, which was related with a high relative abundance of Candidatus Brocadia (>30%) in the same zone. Thus, it is a feasible approach to adopt CBAR to treat low-concentration nitrogen wastewater efficiently.


Assuntos
Compostos de Amônio , Águas Residuárias , Anaerobiose , Reatores Biológicos , Desnitrificação , Nitrogênio/análise , Oxirredução , Esgotos , Temperatura
19.
Biomaterials ; 275: 120904, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119888

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a significant liver disease without approved therapy, lacking human NAFLD models to aid drug development. Existing models are either under-performing or too complex to allow robust drug screening. Here we have developed a 100-well drug testing platform with improved HepaRG organoids formed with uniform size distribution, and differentiated in situ in a perfusion microfluidic device, SteatoChip, to recapitulate major NAFLD features. Compared with the pre-differentiated spheroids, the in situ differentiated HepaRG organoids with perfusion experience well-controlled chemical and mechanical microenvironment, and 3D cellular niche, to exhibit enhanced hepatic differentiation (albumin+ cells ratio: 66.2% in situ perfusion vs 46.1% pre-differentiation), enriched and uniform hepatocyte distribution in organoids, higher level of hepatocyte functions (5.2 folds in albumin secretion and 7.6 folds in urea synthesis), enhanced cell polarity and bile canaliculi structures. When induced with free fatty acid (FFA), cells exhibit significantly higher level of lipid accumulation (6.6 folds for in situ perfusion vs 4.4 folds for pre-differentiation), altered glucose regulation and reduced Akt phosphorylation in the organoids. SteatoChip detects reduction of steatosis when cells are incubated with three different anti-steatosis compounds, 78.5% by metformin hydrochloride, 71.3% by pioglitazone hydrochloride and 66.6% by obeticholic acid, versus the control FFA-free media (38% reduction). The precision microenvironment control in SteatoChip enables improved formation, differentiation, and function of HepaRG organoids to serve as a scalable and sensitive drug testing platform, to potentially accelerate the NAFLD drug development.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Organoides , Diferenciação Celular , Hepatócitos , Humanos , Fígado , Perfusão
20.
ANZ J Surg ; 91(7-8): 1485-1490, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33908173

RESUMO

BACKGROUND: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception. METHODS: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses. RESULTS: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis. CONCLUSION: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis.


Assuntos
Hemostáticos , Intussuscepção , Criança , Enema , Humanos , Lactente , Intussuscepção/diagnóstico , Intussuscepção/cirurgia , Necrose , Estudos Retrospectivos
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