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1.
Chemosphere ; 287(Pt 1): 132019, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34450372

RESUMO

The coexistence of antibiotics and heavy metals may result in complex ecotoxicological effects on living organisms. In this work, the combined toxic effects of norfloxacin (NOR) and copper (Cu) on Caenorhabditis elegans (C. elegans) were investigated due to the highly possible co-pollution tendency. The results indicated that locomotion behaviors (frequency of head thrash and body bend) of C. elegans were more sensitive as the exposure time of NOR or Cu prolonged. Meanwhile, the physiological indexes (locomotion behaviors, body length) of C. elegans were more sensitive to the combined pollution that with lower Cu dosage (0.0125 µM), in prolonged exposure experiments. In addition, the toxic effects of NOR-Cu on physiological indexes of C. elegans seemed to be alleviated during prolonged exposure when Cu was 1.25 µM. Similarly, the ROS production and apoptosis level almost unchanged with the addition of NOR compared with Cu (1.25 µM) exposure groups, but both significantly higher than the control groups. Furthermore, compared with Cu (0.0125 µM and 1.25 µM) exposure experiments, the addition of NOR had resulted in the genetic expression decrease of hsp-16.1, hsp-16.2, hsp-16.48, and the oxidative stress in C. elegans seems to be alleviated. However, the significantly decreased of ape-1 and sod-3 expression indicated the disruption of ROS defense mechanism. The irregular change in ace-1 and ace-2 gene expressions in NOR-Cu (0.0125 µM) would result in the locomotion behaviors disorders of C. elegans, and this also explains why C. elegans are more sensitive to the combination of NOR and lower concentration of Cu.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Cobre/toxicidade , Norfloxacino/toxicidade , Estresse Oxidativo
2.
Artif Intell Med ; 121: 102181, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763803

RESUMO

Automatic detection of arrhythmia through an electrocardiogram (ECG) is of great significance for the prevention and treatment of cardiovascular diseases. In Convolutional neural network, the ECG signal is converted into multiple feature channels with equal weights through the convolution operation. Multiple feature channels can provide richer and more comprehensive information, but also contain redundant information, which will affect the diagnosis of arrhythmia, so feature channels that contain arrhythmia information should be paid attention to and given larger weight. In this paper, we introduced the Squeeze-and-Excitation (SE) block for the first time for the automatic detection of multiple types of arrhythmias with ECG. Our algorithm combines the residual convolutional module and the SE block to extract features from the original ECG signal. The SE block adaptively enhances the discriminative features and suppresses noise by explicitly modeling the interdependence between the channels, which can adaptively integrate information from different feature channels of ECG. The one-dimensional convolution operation over the time dimension is used to extract temporal information and the shortcut connection of the Se-Residual convolutional module in the proposed model makes the network easier to optimize. Thanks to the powerful feature extraction capabilities of the network, which can effectively extract discriminative arrhythmia features in multiple feature channels, so that no extra data preprocessing including denoising in other methods are need for our framework. It thus improves the working efficiency and keeps the collected biological information without loss. Experiments conducted with the 12-lead ECG dataset of the China Physiological Signal Challenge (CPSC) 2018 and the dataset of PhysioNet/Computing in Cardiology (CinC) Challenge 2017. The experiment results show that our model gains great performance and has great potential in clinical.


Assuntos
Arritmias Cardíacas , Eletrocardiografia , Algoritmos , Arritmias Cardíacas/diagnóstico , Progressão da Doença , Humanos , Redes Neurais de Computação
3.
Can J Gastroenterol Hepatol ; 2021: 5545181, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805027

RESUMO

Objective: To identify markers that predict the progression to hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: We recruited 125 patients with chronic hepatitis B (CHB) between September 2013 and March 2017. During hospitalization, 25 patients progressed to LF and were classified as the LF group, while the remaining 100 patients were classified as the non-LF (NLF) group. We compared the kinetic changes in clinical and immune indicators including age, total bilirubin level, prothrombin time, model for end-stage liver disease score, interleukin (IL)-6, IL-8, and IL-10 cytokine levels, and number of T helper 17 and regulatory T cells between groups to determine their association with progression to HBV-ACLF. The prognostic value of clinical and immune indicators was determined using the area under the receiver operating characteristic curve (AUC) value. Results: Cox regression analysis suggested that the plasma IL-6 level could predict CHB progression to HBV-ACLF (relative risk = 1.082, 95% confidence interval: 1.006-1.164; P=0.034). The AUC value, sensitivity, and specificity of baseline IL-6 level for predicting HBV-ACLF were 82.63%, 83.3%, and 82.9%, respectively (P=0.001). Conclusion: A high plasma IL-6 level in CHB patients could be an early biomarker for HBV-ACLF.

4.
Anim Cells Syst (Seoul) ; 25(5): 296-311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745436

RESUMO

The aim of this study was to compare the functional characteristics of mesenchymal stromal cells (MSCs) from a sheep model of traumatic temporomandibular joint (TMJ) fibrous and bony ankylosis. A sheep model of bilateral TMJ trauma-induced fibrous ankylosis on one side and bony ankylosis on the contralateral side was used. MSCs from fibrous ankylosed callus (FA-MSCs) or bony ankylosed callus (BA-MSCs) at weeks 1, 2, 4, and 8 after surgery were isolated and cultured. MSCs derived from the bone marrow of the mandibular condyle (BM-MSCs) were used as controls. The MSCs from the different sources were characterized morphologically, phenotypically, and functionally. Adherence and trilineage differentiation potential were presented in the ovine MSCs. These cell populations highly positively expressed MSC-associated specific markers, namely CD29, CD44, and CD166, but lacked CD31 and CD45 expressions. The BA-MSCs had higher clonogenic and proliferative potentials than the FA-MSCs. The BA-MSCs also showed higher osteogenic and chondrogenic potentials, but lower adipogenic capacity than the FA-MSCs. In addition, the BA-MSCs demonstrated higher chondrogenic, but lower osteogenic capacity than the BM-MSCs. Our study suggests that inhibition of the osteogenic and chondrogenic differentiations of MSCs might be a promising strategy for preventing bony ankylosis in the future.

5.
J Hazard Mater ; : 127850, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34836684

RESUMO

The porous organic polymers have been considered as effective materials for gas storage and adsorption. Herein, we synthesized highly crystalline nitrogen-rich covalent triazine frameworks (CTFs) by polycondensation for preparing the novel hyper-cross-linked conjugated polymers (HCCPs) with tunable specific surface area and pore volume through coupling Friedel-Crafts reaction, in which 1,4-Bis(chloromethyl)benzene and 4,4-Bis(chloromethyl)biphenyl as the expansion molecules were pillared between the layers of CTF-HUST. This technology not only increased the specific surface area and total pore volume of CTF-HUST by 2.56 and 4.68 times, but also greatly enhanced the utilization of adsorption sites of CTF-HUST. The HCCP2-1.25 exhibited the highest surface area (1349.29 m2g-1) among these HCCPs and demonstrated excellent adsorption performance for ethyl acetate (1605.14 mg/g), ethanol (1371.49 mg/g), 1,2-Dichloroethane (1971.68 mg/g), benzene (1151.77 mg/g) and toluene (1024.28 mg/g) due to the multiple C-H…O, C-H…Cl, O-H…N and C-H…π interactions between volatile organic compounds (VOCs) and HCCPs framework. Moreover, CO2 and H2 storage capacities of the HCCP2-1.25 were 8.02 wt% and 1.54 wt%, 1.66 and 1.67 times higher than CTF-HUST, respectively. This study developed a simple and effective molecular expansion strategy to synthesize a series of novel high-surface-area porous polymers for potential applications in the environmental field.

6.
Neoplasia ; 23(12): 1192-1203, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34731788

RESUMO

We have previously reported an important role of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase, in the support of critical oncogenic pathways required for oncogenesis and the malignant phenotype of pancreatic cancer. The studies in this report reveal a novel mechanism by which the p53 tumor suppressor inhibits the protein-stability of PR55α via FBXL20, a p53-target gene that serves as a substrate recognition component of the SCF (Skp1_Cullin1_F-box) E3 ubiquitin ligase complex that promotes proteasomal degradation of its targeted proteins. Our studies show that inactivation of p53 by siRNA-knockdown, gene-deletion, HPV-E6-mediated degradation, or expression of the loss-of-function mutant p53R175H results in increased PR55α protein stability, which is accompanied by reduced protein expression of FBXL20 and decreased ubiquitination of PR55α. Subsequent studies demonstrate that knockdown of FBXL20 by siRNA mimics p53 deficiency, reducing PR55α ubiquitination and increasing PR55α protein stability. Functional tests indicate that ectopic p53R175H or PR55α expression results in an increase of c-Myc protein stability with concomitant dephosphorylation of c-Myc-T58, which is a PR55α substrate, whose phosphorylation otherwise promotes c-Myc degradation. A significant increase in anchorage-independent proliferation is also observed in normal human pancreatic cells expressing p53R175H or, to a greater extent, overexpressing PR55α. Consistent with the common loss of p53 function in pancreatic cancer, FBXL20 mRNA expression is significantly lower in pancreatic cancer tissues compared to pancreatic normal tissues and low FBXL20 levels correlate with poor patient survival. Collectively, these studies delineate a novel mechanism by which the p53/FBXL20 axis negatively regulates PR55α protein stability.

7.
Org Biomol Chem ; 19(44): 9637-9640, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34714900

RESUMO

Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9ßH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.

8.
Eur J Protistol ; 81: 125840, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34717075

RESUMO

Though representing a major component of eukaryotic biodiversity, many microbial eukaryotes remain poorly studied, including the focus of the present work, testate amoebae of the order Arcellinida (Amoebozoa) and non-model lineages of ciliates (Alveolata). In particular, knowledge of genome structures and changes in genome content over the often-complex life cycles of these lineages remains enigmatic. However, the limited available knowledge suggests that microbial eukaryotes have the potential to challenge our textbook views on eukaryotic genomes and genome evolution. In this study, we developed protocols for DAPI (4',6-diamidino-2-phenylindole) staining of Arcellinida nuclei and adapted protocols for ciliates. In addition, image analysis software was used to estimate the DNA content in the nuclei of Arcellinida and ciliates, and the measurements of target organisms were compared to those  of well-known model organisms.The results demonstrate that the methods we have developed for nuclear staining in these lineages are effective and can be applied to other microbial eukaryotic groups by adjusting certain stages in the protocols.


Assuntos
Cilióforos , Lobosea , Cilióforos/genética , DNA , Indóis , Filogenia , Coloração e Rotulagem
9.
Front Neurosci ; 15: 758427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690689

RESUMO

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees' truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE's implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE's suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question. Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart. Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 µA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve's center were, on average, half those of leads located near the periphery (54.92 µA vs. 110.71 µA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads' thresholds decreased or remained stable over the 3-week span. The remaining two leads' thresholds increased by 70-74%, possibly due to scarring or device failure. Significance: This work represents an important first step in establishing the MSE's viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.

10.
Zhongguo Zhen Jiu ; 41(10): 1063-8, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628735

RESUMO

OBJECTIVE: To observe the moxibustion sensation and the clinical therapeutic effect of heat-sensitive moxibustion of two different suspension moxibustion methods and imitation moxibustion apparatus on mild to moderate knee osteoarthritis (KOA), and compare the therapeutic effect of different moxibustion methods. METHODS: A total of 90 patients with mild to moderate KOA were randomized into a hand-held group (30 cases, 1 case dropped off), an imitation moxibustion apparatus group (30 cases) and a moxibustion shelf group (30 cases, 1 case dropped off). Ashi point, Dubi (ST 35), Neixiyan (EX-LE 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Liangqiu (ST 34) and Xuehai (SP 10) were selected as the frequent acupoint areas to explore and determine the heat-sensitive acupoints, after that, hand-held suspension moxibustion, suspension moxibustion with imitation moxibustion apparatus and suspension moxibustion with moxibustion shelf were adopted in the 3 groups respectively. The treatment was given once every 2 days, and totally 10-time treatment was required in the 3 groups. The moxibustion sensation (composition of moxibustion sensation, number of moxibustion sensation types in individuals and moxibustion sensation intensity) after each treatment, the visual analogue scale (VAS) score, the Lysholms knee function score and the depth of effusion and thickness of synovial hyperplasia of affected knee joint before and after treatment were observed, and the clinical therapeutic efficacy was compared in the 3 groups. RESULTS: The compositions of moxibustion sensation and numbers of moxibustion sensation types in individuals in the hand-held group and the moxibustion shelf group were richer, the moxibustion sensation intensity was higher than that in the imitation moxibustion apparatus group (P<0.01, P<0.05). After treatment, the VAS scores were decreased, the Lysholms knee function scores were increased compared before treatment in the 3 groups (P<0.01); the VAS score in the hand-held group was lower than the imitation moxibustion apparatus group (P<0.05), the Lysholms knee function scores in the hand-held group and the moxibustion shelf group were higher than the imitation moxibustion apparatus group (P<0.05). After treatment, the depth of effusion and thickness of synovial hyperplasia of affected knee joint were decreased compared before treatment in the 3 groups (P<0.01), and those in the hand-held group and the moxibustion shelf group were lower than the imitation moxibustion apparatus group (P<0.05). The cured and markedly effective rate in the hand-held group was 79.3% (23/29), which was better than 36.7% (11/30) in the imitation moxibuation apparatus group and 58.6% (17/29) in the moxibustion shelf group (P<0.01, P<0.05). CONCLUSION: Heat-sensitive moxibustion can effectively treat knee osteoarthritis, while the different suspension moxibustion methods have an influence on clinical therapeutic effect, hand-held suspension moxibustion has the best efficacy.


Assuntos
Moxibustão , Osteoartrite do Joelho , Temperatura Alta , Humanos , Comportamento Imitativo , Osteoartrite do Joelho/terapia , Sensação , Resultado do Tratamento
11.
Sensors (Basel) ; 21(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34640896

RESUMO

This study was the first to compare the differences in trunk/shoulder kinematics and impact vibration of the upper extremity during backhand strokes in wheelchair tennis players and the able-bodied players relative to standing and sitting positions, adopting an electromagnetic system along with wearable tri-axial accelerometers upon target body segments. A total of 15 wheelchair tennis players and 15 able-bodied tennis players enrolled. Compared to players in standing positions, wheelchair players demonstrated significant larger forward trunk rotation in the pre-preparation, acceleration, and deceleration phase. Significant higher trunk angular velocity/acceleration and shoulder flexion/internal rotation angular velocity/acceleration were also found. When able-bodied players changed from standing to sitting positions, significant changes were observed in the degree of forward rotation of the trunk and shoulder external rotation. These indicated that when the functions of the lower limbs and trunk are lacking or cannot be used effectively, "biomechanical solutions" such as considerable reinforcing movements need to be made before the hitting movement. The differences between wheelchair tennis players and able-bodied players in sitting positions could represent the progress made as the wheelchair players evolve from novices to experts. Knowledge about how sport biomechanics change regarding specific disabilities can facilitate safe and inclusive participation in disability sports such as wheelchair tennis.


Assuntos
Tênis , Cadeiras de Rodas , Fenômenos Biomecânicos , Humanos , Ombro , Extremidade Superior , Vibração
12.
Diabetes ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675006

RESUMO

The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in a hepatic p38α- and FGF21-dependent manner. Mechanistically, through increasing the FGF21 production from liver, hepatic p38 activation increases the influx of fatty acids from adipose tissue to liver, leading to hepatic ectopic lipid accumulation and insulin resistance. Although hepatic p38 activation exhibits favorable effects in peripheral tissues, it impairs the hepatic FGF21 action by facilitating the ubiquitination and degradation of FGF21 receptor cofactor ß-Klotho. Consistently, we show that p38 phosphorylation and FGF21 expffression are increased, ß-Klotho protein levels are decreased in the fatty liver of either mice or patients. In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38α, FGF21, and ß-Klotho in the pathogenesis of nonalcoholic fatty liver disease.

13.
PLoS Genet ; 17(10): e1009792, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34662332

RESUMO

The transformer (tra) gene is essential for female development in many insect species, including the Australian sheep blow fly, Lucilia cuprina. Sex-specific tra RNA splicing is controlled by Sex lethal (Sxl) in Drosophila melanogaster but is auto-regulated in L. cuprina. Sxl also represses X chromosome dosage compensation in female D. melanogaster. We have developed conditional Lctra RNAi knockdown strains using the tet-off system. Four strains did not produce females on diet without tetracycline and could potentially be used for genetic control of L. cuprina. In one strain, which showed both maternal and zygotic tTA expression, most XX transformed males died at the pupal stage. RNAseq and qRT-PCR analyses of mid-stage pupae showed increased expression of X-linked genes in XX individuals. These results suggest that Lctra promotes somatic sexual differentiation and inhibits X chromosome dosage compensation in female L. cuprina. However, XX flies homozygous for a loss-of-function Lctra knockin mutation were fully transformed and showed high pupal eclosion. Two of five X-linked genes examined showed a significant increase in mRNA levels in XX males. The stronger phenotype in the RNAi knockdown strain could indicate that maternal Lctra expression may be essential for initiation of dosage compensation suppression in female embryos.


Assuntos
Compensação de Dosagem (Genética)/genética , Drosophila melanogaster/genética , Genes de Insetos/genética , Animais , Animais Geneticamente Modificados , Austrália , Calliphoridae/genética , Dípteros/genética , Proteínas de Drosophila/genética , Feminino , Genes Ligados ao Cromossomo X/genética , Masculino , Pupa/genética , Interferência de RNA/fisiologia , Splicing de RNA/genética , Proteínas de Ligação a RNA/genética , Ovinos , Fatores de Transcrição/genética , Cromossomo X/genética
14.
Toxicology ; 464: 153014, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34718029

RESUMO

Geniposide has been widely found to ameliorate many metabolic diseases. The recruitment and activation of brown/beige adipocytes are effective and promising methods for counteracting obesity and related diseases. However, the effect of geniposide on thermogenesis of adipocytes and its underlying mechanism have not yet been investigated. Here, we demonstrate that geniposide (25 mg/kg) reduces body temperature and cold tolerance of mice via suppressing thermogenic genes in interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT). Consistently, geniposide (20 mg/mL) suppresses thermogenic capacity of adipocytes (brown adipocytes and 3T3L1 preadipocyte cells) in vitro. Mechanistically, geniposide reduces the level of protein kinase A (PKA) catalytic subunit and further suppresses transcription activity and protein stability of uncoupling protein 1 (UCP1), leading to reduction of thermogenic capacity in adipocytes. Moreover, pharmacological PKA activation reverses geniposide-induced UCP1 inhibition, which indicated that geniposide suppresses thermogenesis of adipocytes via regulating PKA signaling. Together, our findings suggest that geniposide is an inhibitor of fat thermogenesis, establishing a novel function characteristic of geniposide.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34472200

RESUMO

We designed a study to compare the newly developed 5-mg flunarizine hydrochloride capsules (test) to that of its marketed counterpart (5-mg; reference) among healthy adult Chinese volunteers. We performed an open-label, single-center study that consisted of 2 randomized, crossover trials, including a fasting trial and a fed trial. In each part of the study, the subjects were randomly assigned to either receive the test or reference products (5-mg flunarizine) in a 1:1 ratio. Subjects then received the alternative products, following a 14-day washout period. Concentrations of plasma flunarizine were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were evaluated using the WinNonlin software. The analysis of variance and Food and Drug Administration bioequivalence statistical criterion of 90% confidence interval for 80% to 125% range (set at P ≤ .05) of geometric means ratios of test: reference product for peak plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, and AUC from time 0 to infinity were determined. Tolerability was evaluated during the entire study period. Overall, 23 volunteers completed the fasting study, while 40 volunteers completed the fed study. The test formulation was found to be bioequivalent to the marketed formulation, as the 90% confidence interval for the ratio of geometric means of peak plasma concentration (fasting: 87.61%-101.67%; fed: 87.38%-104.06%), AUC from time 0 to time t (fasting: 89.44%-99.92%; fed: 92.65%-98.28%), and AUC from time 0 to infinity (fasting: 95.02%-104.33%; fed: 90.41%-96.96%) were within equivalence limits (80-125%) under both the fasting and fed conditions. When flunarizine was given alongside high-fat meals, time to maximum concentration was delayed ≈3.5 hours compared to fasting conditions. Meantime, high-fat meals increased its exposure by nearly 50%. Furthermore, there were no serious adverse events found among the subjects. This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and postprandial conditions.

16.
Mar Drugs ; 19(9)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564147

RESUMO

Dysregulation of cholesterol homeostasis is a major risk factor of atherosclerosis, which can lead to serious health problems, including heart attack and stroke. Liver X receptor (LXR) α and ß are transcription factors belonging to the nuclear receptor superfamily, which play important roles in cholesterol homeostasis. Selectively activating LXRß provides a promising strategy for the treatment of atherosclerosis. Here, we employed atherosclerotic apoE-knockout mice to evaluate the effects of saringosterol, a phytosterol with potent and selective action for LXRß, which we identified previously in edible marine seaweed Sargassum fusiforme. We found that saringosterol treatment reduced the atherosclerotic plaque burden without having undesirable adverse hepatic effects in apoE-deficient mice fed an atherogenic diet. Meanwhile, reduced serum levels of cholesterol, accompanied by altered expression of LXR-regulated genes involved in cholesterol absorption, transport, efflux, excretion, and elimination, were observed in apoE-knockout mice after saringosterol treatment. Together, our study not only establishes saringosterol as an effective cholesterol-lowering and anti-atherogenic phytosterol but also provides insights into the underlying mechanism.

17.
Environ Technol ; : 1-11, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34582318

RESUMO

In this paper, the acidified multi-walled carbon nanotubes (MWCNTs) film was coated on the quartz crystal microbalance (QCM) to prepare a high-performance sensor for the real-time detection of organic acid gases. The material characteristics of the thin films were analysed by field emission scanning electro microscopy (FESEM), Raman spectra and X-ray photoelectron spectroscopy (XPS). The organic acid vapours' sensing results indicated that acidized-MWCNTs thin film exhibited good frequency response, repeatability, reversibility and stability. There is a clear linear relationship between the frequency offset and the organic acid vapours with concentration below 5.0 ppm, and the detection limit of 0.77 and 0.73 ppm for formic and acetic acid vapours, respectively. The sensor shows the highest response to formic acid vapour than acetic acid vapour which may be ascribed to molecular polarity. Furthermore, a sensing mechanism model was introduced to understand the adsorption reaction between organic acid molecules and acidized-MWCNTs. This paper proves that acidized-MWCNTs is a potential and suitable material for organic acid vapour detection when combined with a QCM sensor.

18.
Med Sci Monit ; 27: e932545, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34400603

RESUMO

BACKGROUND The type of traumatic temporomandibular joint (TMJ) ankylosis depends on the degree of severity of TMJ trauma. Here, we performed comprehensive differential molecular profiling between TMJ fibrous and bony ankylosis. MATERIAL AND METHODS Six sheep were used and a bilateral different degree of TMJ trauma was performed to induce fibrous ankylosis in one side and bony ankylosis in the other side. The ankylosed calluses were harvested at days 14 and 28 postoperatively and analyzed by Affymetrix OviGene-1_0-ST microarrays. DAVID was used to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Ten DEGs, including 7 hub genes from PPI analysis, were confirmed by real-time PCR. RESULTS We found 90 and 323 DEGs at least 2-fold at days 14 and 28, respectively. At day 14, bony ankylosis showed upregulated DEGs, such as TLR8, SYK, NFKBIA, PTPRC, CD86, ITGAM, and ITGAL, indicating a stronger immune and inflammatory response and cell adhesion, while genes associated with anti-adhesion (PRG4) and inhibition of osteoblast differentiation (SFRP1) had higher expression in fibrous ankylosis. At day 28, bony ankylosis showed increased biological process related to new bone formation, while fibrous ankylosis was characterized by a prolonged immune and inflammatory reaction. CONCLUSIONS This study provides a differential gene expression profile between TMJ fibrous and bony ankylosis. Further study of these key genes may provide new ideas for future treatment of TMJ bony ankylosis.

19.
IEEE Trans Cybern ; PP2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464283

RESUMO

This article investigates the optimal control strategy problem for nonzero-sum games of the immune system based on adaptive dynamic programming (ADP). First, the main objective is approximating a Nash equilibrium between the tumor cells and the immune cell population, which is governed through chemotherapy drugs and immunoagents guided by the mathematical growth model of the tumor cells. Second, a novel intelligent nonzero-sum games-based ADP is put forward to solve the optimization control problem by reducing the growth rate of tumor cells and minimizing chemotherapy drugs and immunotherapy drugs. Meanwhile, the convergence analysis and iterative ADP algorithm are specified to prove feasibility. Finally, simulation examples are listed to account for availability and effectiveness of the research methodology.

20.
Acta Oncol ; 60(9): 1122-1129, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34402368

RESUMO

BACKGROUND: The incidence of primary cardiac lymphoma (PCL) is increasing, but the optimal management approach remains unclear. We assessed the clinical characteristics of a single-centre cohort with the goal of determining the optimal management approach. The treatment outcomes and prognostic factors are reported. MATERIAL AND METHODS: All PCL patients were diagnosed via biopsy guided by whole-body imaging (positron emission tomography/computed tomography [PET/CT] and/or contrast-enhanced CT]. Curative therapy involved either surgery or prephase steroids followed by definitive immunochemotherapy, depending on the histological type. The primary outcomes were overall survival (OS) and progression-free survival (PFS); the secondary outcome was the treatment response. RESULTS: Twenty-two PCL patients (14 males, 8 females; age: 59.5 ± 14.7 years [mean ± S.D.]) were histologically confirmed to have diffuse large B-cell lymphoma (DLBCL; n = 17 [77.3%]), fibrin-associated DLBCL (FA-DLBCL) (n = 4 [18.2%]) and Burkitt lymphoma (n = 1 [4.5%]). Seven patients underwent cardiotomy (three for biopsy, four with curative intent). The median and longest follow-up periods were 16.3 and 180.0 months, respectively. The 16 patients who received curative therapy (complete response [CR], n = 15 [93.8%]; partial response [PR], n = 1 [6.2%]) showed better survival than those who did not (5-year OS: 83.0 ± 11.3% vs. 0%; hazard ratio [HR]: 0.025[95% confidence interval, CI: 0.003-0.187], p < 0.001); 5-year PFS: 78.7 ± 11.0% vs. 0%, HR= 0.010[0.001-0.093], p < 0.001). The left ventricular ejection fractions (LVEF) before and after definitive treatment was 63.6 ± 2.4% and 64.6 ± 4.5%, respectively (p = 0.275, power = 0.318). Extrapericardial lesions were associated with poorer survival (5-year OS: 40.0 ± 29.7% vs. 100%, p = 0.027; 5-year PFS:40.0 ± 21.9% vs. 100%, p = 0.010). CONCLUSIONS: Whole-body imaging is essential for diagnosis and prognosis. Curative therapy provided reasonable outcomes and survival; extrapericardial lesions were associated with a poorer treatment response.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
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