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1.
Am J Med Sci ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619145

RESUMO

OBJECTIVE: Acute respiratory distress syndrome (ARDS) associated with high mortality is the common complication in acute pancreatitis (AP). The aim of this study was to formulate and validate an individualized predictive nomogram for in-hospital incidence of ARDS in Patients with AP. METHOD: From January 2017 to December 2018, 779 individuals with AP were involved in this study. They were randomly distributed into primary cohort (n=560) and validation cohort (n=219). Based on the primary cohort, risk factors were identified by logistic regression model and a nomogram was performed. The nomogram was validated in the primary and validation cohort by the bootstrap validation method. The calibration curve was applied to evaluate the consistency between the nomogram and the ideal observation. RESULTS: There were 728 patients in the non-ARDS group and 51 in the ARDS group, with an incidence of about 6.55%. Five independent factors including white blood cell counts (WBC), prothrombin time (PT), albumin (ALB), serum creatinine (SCR) and triglyceride (TG) were associated with in-hospital incidence of ARDS in Patients with AP. A nomogram was constructed based on the five independent factors with primary cohort of AUC=0.821 and validation cohort of AUC=0.823. Calibration curve analysis indicated that the predicted probability was in accordance with the observed probability in both primary and validation cohorts. CONCLUSIONS: The study developed an intuitive nomogram with easily available laboratory parameters for the prediction of in-hospital incidence of ARDS in patients with AP. The incidence of ARDS for an individual patient can be fast and conveniently evaluated by our nomogram.

2.
Clin Invest Med ; 44(3): E19-24, 2021 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-34600459

RESUMO

PURPOSE: Incidence of contrast induced nephropathy (CIN) and related risk factors in patients with liver cancer and chronic kidney disease after trans-catheter arterial chemoembolization (TACE) is higher. The purpose of this study was to investigate the feasibility and safety of TACE therapy in such patients. METHODS: A retrospective analysis was performed on 103 patients with liver cancer and chronic kidney disease who underwent TACE treatments. TACE was performed according to Seldinger's technique of arterial embolization with minor modifications. Based on CIN diagnostic criteria, patients were divided into non-CIN (n=89) and CIN (n=14) groups. Multiple clinical parameters were assessed for the two groups after TACE. Serum creatinine levels were measured 48-72 h after TACE. RESULTS: Tumor size (>5 cm), TACE frequency, contrast agent dosage, solitary kidney, volume of iodized oil used in the TACE (ml) and urea levels were significantly higher in CIN group in comparison with the non-CIN group, while serum albumin and haemoglobin levels were significantly lower. Multivariate logistic regression analysis confirmed that the volume of iodized oil and TACE frequency were significantly positively correlated, and serum albumin level was negatively correlated in the CIN group. CONCLUSION: Volume of iodized oil, TACE frequency and low serum albumin levels were found to be independent risk factors for CIN after TACE. Thus, it is safe and feasible for hepatocellular carcinoma patients with chronic kidney disease to receive TACE treatment, but adverse events management after TACE needs to be addressed.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34648441

RESUMO

Acoustic Bessel beams are commonly used as ideal sources to study the characteristics for acoustic-vortex (AV) beams, exhibiting prosperous perspectives in contactless object manipulations and acoustic communications. However, accurate Bessel beams are difficult to construct using two-dimensional arrays in practical applications. By integrating active phase control and passive phase modulation to a ring-array of sectorial planar transducers, quasi-Bessel acoustic-vortex (QB-AV) beams of arbitrary order are built by the line-focus of AV fields in the current study. Based on the Snell's refraction law, a circular saw-tooth lens of phase modulation is designed to converge incident waves toward the beam axis at a same deflection angle. QB-AV beams constructed by the main lobes of the sectorial sources are demonstrated by theoretical derivations, numerical simulations and quality evaluations, while those created by the side lobes are neglected to avoid the pressure fluctuations in the near field. Experimental measurements for AV beams of different orders coincide basically with the simulations, demonstrating that line-focused QB-AV beams can be generated along the beam axis across the pressure peak. With the increase of the topological charge, the peak-pressure of the beam decreases accordingly with a reduced effective axial range. The favorable results prove that, as a special kind of diffraction sources, the adjustable QB-AV beams may enable more important biomedical applications where Bessel beams are necessary, especially for the line-focused manipulation of biological and drug particles.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34491105

RESUMO

Background: Volatile organic compounds (VOCs) have been detected in feminine hygiene products (FHPs), especially in tampons and sanitary pads. However, little is known about whether menstrual products can contribute to VOC exposure in women. Our objectives were to: (1) examine the variations of urinary VOC concentrations during menstrual cycles; (2) evaluate the relationships between the use of menstrual products and urinary VOC concentrations; and (3) link urinary VOC concentrations to those measured in menstrual products. Methods: We measured urinary concentrations of 98 target VOCs in 25 reproductive-aged women with 100 repeated measures collected between October 2018 and February 2019. First-morning-void urine samples were collected four times for each woman during one menstrual cycle. Urinary VOC concentrations were measured using gas chromatography-mass spectroscopy. Results: Of 98 target VOCs measured in the urine samples, 36 VOCs were detected. We did not see statistically significant variations in VOC concentrations across the menstrual cycle. After multivariable adjustment, tampon users had significantly higher concentrations of 2-butanone (ß = 1.58 log ng/g, 95% confidence interval [CI]: 0.16-3.00, p = 0.03) and methyl isobutyl ketone (ß = 0.63 log ng/g, 95% CI: 0.03-1.22, p = 0.04), compared with pad users. Higher n-nonane, benzene, and toluene estimated from menstrual products were associated with higher urinary concentrations in women. Conclusion: The use of FHPs during menses might be a potential source of VOCs. A larger cohort study is warranted to confirm our results and evaluate clinical implications.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 558-562, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494526

RESUMO

Objective To investigate the application value of indocyanine green(ICG)in the localization of small pulmonary nodules in video-assisted thoracoscopic surgery(VATS). Methods We retrospectively analyzed the clinical data of 45 patients with small nodules(diameter<1 cm)who received preoperative localization with ICG and underwent VATS wedge resection from October 2020 to February 2021.The data for analysis included patients age,nodule diameter,distance from the parietal pleura,nodule density,success rate of localization,time of localization,incidence of complications,and pathological findings. Results The success rate of localization was 100%.The average nodule size was 6.3 mm,and the nodules were(10±11)mm from the parietal pleura.After localization of 59 nodules,13(22.0%)cases were found to have mild pneumothorax,and 4(6.7%)cases were found to have mild hemorrhage.The success rate of operation was 100%,and 43(72.9%)cases were confirmed adenocarcinoma by postoperative pathology. Conclusion ICG has a high success rate and good safety in the localization of small pulmonary nodules in VATS.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X
7.
J Nat Prod ; 84(9): 2568-2574, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34496568

RESUMO

Twelve guaianolide-type sesquiterpene oligomers with diverse structures were isolated from the whole plants of Ainsliaea fragrans, including a novel trimer (1) and two new dimers (2, 3). The chemical structures of the new compounds were elucidated through spectroscopic data interpretation and computational calculations. Ainsfragolide (1) is an unusual guaianolide sesquiterpene trimer generated with a novel C-C linkage at C2'-C15″, which may be biosynthesized prospectively through a further Michael addition. Cytotoxicity results showed that ainsfragolide (1) was the most potent compound against five cancer cell lines with IC50 values in the range of 0.4-8.3 µM.

8.
Aging Cell ; : e13485, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592792

RESUMO

Atherosclerosis is a serious age-related disease, which has a tremendous impact on health care globally. Macrophage inflammation is crucial for the initiation and progression of atherosclerosis, and microRNAs (miRNAs) recently have emerged as potent modulators of inflammation, while the underlying mechanisms of its involvement in homocysteine (Hcy)-mediated macrophage inflammation of atherosclerosis remain largely unknown. Here, we demonstrated that elevated Hcy inhibits the expression of miR-195-3p, which in turn enhances IL-31 expression and thereby causes the secretion of macrophages pro-inflammatory factors IL-1ß, IL-6 and TNF-α and accelerate atherosclerosis. Furthermore, we identified that Hcy can induce DNA hypermethylation and H3K9 deacetylation of miR-195-3p promoter due to the increased the binding of DNMT3a and HDAC11 at its promoter. More importantly, Sp1 interacts with DNMT3a suppressed the binding of HDAC11 at miR-195-3p promoter and promoted its transcription. In summary, our results revealed a novel mechanism that transcriptional and epigenetic regulation of miR-195-3p inhibits macrophage inflammation through targeting IL-31, which provides a candidate diagnostic marker and novel therapeutic target in cardiovascular diseases induced by Hcy.

9.
PLoS One ; 16(9): e0256966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34478467

RESUMO

Delay of gratification-a form of self-control-is the ability to forsake immediately available rewards in order to obtain larger-valued outcomes in future, which develops throughout the pre-school years. The majority of previous research in this area has been conducted with Western populations, therefore knowledge of Eastern children's performance is scarcer. Here, utilising on a recently published dataset of British children (n = 61), we further tested delay of gratification in 3 to 5-year-old Chinese children (n = 75) using Bramlett et al.'s (2012) delay choice paradigm. The paradigm was previously used in non-human primates and it featured a mechanized rotating tray that sequentially moves rewards within reach. Additionally, we administered 3 inhibitory control tasks and 1 standardised delay choice task to Chinese pre-schoolers (British children were not tested). We aimed to investigate the influence of culture, reward type and reward visibility on pre-schoolers' ability to delay gratification. We found significant age-related improvements in delay of gratification ability in both countries and children performed better when presented with rewards varying in quality than quantity. Consistent with previous cross-cultural literature, Chinese children showed better overall performance than their British peers when reward visibility was manipulated (though reward visibility itself had no significant effect on performance). There were significant correlations in Chinese children's performance in Bramlett et al.'s (2012) delay choice paradigm and performance in some (though not all tested) inhibitory control tasks. We discuss these results in relation to task demands and the broader social orientation of self-control. We concluded that the intuitive comparative assessment of self-control task taps into children's delay of gratification ability. Our results emphasize the importance of testing for socio-cultural influences on children's cognitive development.

10.
Sensors (Basel) ; 21(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34450801

RESUMO

Recent achievements in the field of computer vision, reinforcement learning, and locomotion control have largely extended legged robots' maneuverability in complex natural environments. However, little research focuses on sensing and analyzing the physical properties of the ground, which is crucial to robots' locomotion during their interaction with highly irregular profiles, deformable terrains, and slippery surfaces. A biomimetic, flexible, multimodal sole sensor (FMSS) designed for legged robots to identify the ontological status and ground information, such as reaction force mapping, contact situation, terrain, and texture information, to achieve agile maneuvers was innovatively presented in this paper. The FMSS is flexible and large-loaded (20 Pa-800 kPa), designed by integrating a triboelectric sensing coat, embedded piezoelectric sensor, and piezoresistive sensor array. To evaluate the effectiveness and adaptability in different environments, the multimodal sensor was mounted on one of the quadruped robot's feet and one of the human feet then traversed through different environments in real-world tests. The experiment's results demonstrated that the FMSS could recognize terrain, texture, hardness, and contact conditions during locomotion effectively and retrain its sensitivity (0.66 kPa-1), robustness, and compliance. The presented work indicates the FMSS's potential to extend the feasibility and dexterity of tactile perception for state estimation and complex scenario detection.


Assuntos
Robótica , Percepção do Tato , Biomimética , Humanos , Locomoção
11.
Atherosclerosis ; 333: 32-38, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34419824

RESUMO

BACKGROUND AND AIMS: Symptomatic peripheral artery disease (PAD) is a risk factor for abdominal aortic aneurysm (AAA). However, data on the association of asymptomatic PAD with AAA are limited. We explored the association of symptomatic and asymptomatic PAD with AAA. METHODS: We primarily assessed a prospective association of symptomatic (based on clinical history) and asymptomatic (ankle-brachial index ≤0.9) PAD at baseline (1987-89 [ages 45-64 years]) with incident AAA in a biracial community-based cohort, the Atherosclerosis Risk in Communities Study. We secondarily investigated a cross-sectional association of PAD with ultrasound-based AAA (diameter≥3.0 cm) (2011-13 [ages 67-91 years]). RESULTS: Of 14,148 participants (55.1% female, 25.5% black, 0.9% with symptomatic PAD) in our prospective analysis (median follow-up 22.5 years), 530 (3.7%) developed incident AAA. Symptomatic PAD had a higher hazard ratio (HR) of incident AAA [4.91 (95%CI 2.88-8.37)], as did asymptomatic PAD with ABI≤0.9 [2.33 (1.55-3.51)], compared to the reference ABI>1.1-1.2 in demographically-adjusted models. Crude 15-year cumulative incidence of AAA in these three groups were 12.3%, 3.9%, and 1.5%, respectively. The associations remained significant after accounting for other potential confounders [corresponding HR 2.96 (95%CI 1.73-5.07) and 1.52 (95%CI 1.00-2.30), respectively]. The cross-sectional analysis demonstrated similar patterns with ultrasound-based AAA [odds ratio 2.46 (95%CI 1.26-4.81) for symptomatic PAD and 3.98 (1.96-8.08) for asymptomatic PAD in a demographically-adjusted model]. CONCLUSIONS: Our prospective and cross-sectional data show elevated risk of AAA in both symptomatic and asymptomatic PAD. Our data support the current recommendation of AAA screening in symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well.

13.
Med Sci Monit ; 27: e931286, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333509

RESUMO

BACKGROUND Length of stay (LOS) in the emergency department (ED) should be measured and evaluated comprehensively as an important indicator of hospital emergency service. In this study, we aimed to analyze clinical characteristics of critically ill patients admitted to the ED and identify the factors associated with LOS. MATERIAL AND METHODS All patients with level 1 and level 2 of the Emergency Severity Index who were admitted to the ED from January 2018 to December 2019 were included in this retrospective study. The patients were divided into 2 groups: LOS ≥4 h and LOS <4 h. Variables were comprehensively analyzed and compared between the 2 groups. RESULTS A total of 19 616 patients, including 7269 patients in the LOS ≥4 h group and 12 347 patients in the LOS <4 group, were included. Advanced age, admission in winter and during the night shift, and diseases excluding nervous system diseases, cardiovascular diseases, and trauma were associated with higher risk of LOS. Nervous system diseases, cardiovascular diseases, trauma, and procedures including tracheal intubation, surgery, percutaneous coronary intervention, and thrombolysis were associated with lower risk of LOS. CONCLUSIONS Prolonged LOS in the ED was associated with increased age and admission in winter and during the night shift, while shortened LOS was associated with nervous system diseases, cardiovascular diseases, and trauma, as well as with procedures including tracheal intubation, surgery, percutaneous coronary intervention, and thrombolysis. Our findings can serve as a guide for ED physicians to individually evaluate patient condition and allocate medical resources more effectively.

14.
Nat Prod Res ; 35(16): 2748-2752, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34414845

RESUMO

A new diterpenoid named jatrophacine (1), with an unusual 4,5-seco- rhamnofolane skeleton, was isolated from the roots of Jatropha curcas, together with eleven known diterpenoids. The structure of the new compound was elucidated through a detailed analysis of its 1 D- and 2 D-NMR spectra. The X-ray structure of jatrophol (2) is also presented. Anti-inflammatory activity with LPS-induced RAW 264.7 macrophages revealed that compound 1 strongly inhibited the production of nitric oxide (IC50 = 0.53 µM).


Assuntos
Anti-Inflamatórios , Diterpenos , Jatropha , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Jatropha/química , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Células RAW 264.7
15.
J Mech Behav Biomed Mater ; 123: 104780, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34416536

RESUMO

Zirconia is recognized as a promising dental implant material because of its good biocompatibility, sufficient mechanical strength, minimal ion release and aesthetic effects similar to natural teeth. However, the limitations of inert surface of zirconia affect the long-term efficacy of zirconia implants. To enhance the osseointegration of zirconia implants, titania (TiO2) coating is prepared on the zirconia surface by immersion in a mixed zirconium oxychloride (ZrOCl2) and TiO2 suspension in a water bath. The surface and longitudinal section morphology are observed by scanning electron microscopy (SEM). The chemical composition is evaluated through energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). The roughness and hydrophilicity of zirconia surface are also examined. A three-point bending test is conducted on the samples to explore the effect of this surface treatment on the mechanical strength of zirconia. Vickers hardness measurements are performed to evaluate the gradient change of the longitudinal section of the zirconia substrate. The MC3T3-E1 cells are seeded on zirconia discs, and a LIVE/DEAD double-staining test is conducted to detect the cytotoxicity of the TiO2 coating. The cell morphology is studied through fluorescence microscope. The degrees of cell proliferation, mineralization and alkaline phosphatase (ALP) activity are calculated and compared. Detection of the mRNA expression of osteogenic differentiation-related markers is performed by RT-PCR. A TiO2 coating is generated on the zirconia surface and significantly improves the surface roughness and hydrophilicity while not adversely affecting the mechanical strength of zirconia. The hardness of the zirconia substrate shows a gradient change. The TiO2 coating can promote proliferation, spreading and osteogenic differentiation of MC3T3-E1 cells. These findings suggest that modifying the surface of zirconia with a TiO2 coating may have a favourable osteogenic effect.


Assuntos
Osteogênese , Zircônio , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Titânio
16.
Scientometrics ; : 1-19, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34248230

RESUMO

An abundance of publications on medical professionalism have been published in recent years. Our study aimed to analyze the external characteristics of publications on professionalism using bibliometrics, to describe its current developments and trends, and to explore professionalism research hotspots using co-word analysis. We retrieved literature on professionalism published from 2010 to 2019 from the Web of Science database. Histcite and CiteSpace were used to analyze external characteristics of publications, including publication trends and distributions of publications by country/region, institution, author, and journal. Co-word analysis was conducted to analyze research hotspots, using the Bibliographic Item Co-Occurrence Matrix Builder and Graphical Clustering Toolkit. We constructed a strategic diagram to show the state of each research hotspot and the relationship between the various hotspots in this field. Results showed publications on professionalism increased in number year by year as a whole. The USA, including its institutions and authors, maintained the top position worldwide in terms of numbers of publications and citations. Among scholarly journals, Academic Medicine has published more articles and has had higher citations per paper than any other journal. Six research hotspots on professionalism were identified, visualized, and expounded. Of these, the theme of "measurement and evaluation of clinical competence" received the most attention in the field of professionalism. The reporting of quantifiable knowledge on the characteristics and research hotspots of publications could help inform gaps in the field of medical professionalism and provide evidence and guidance for future work for researchers, physicians, and educators. Supplementary Information: The online version contains supplementary material available at 10.1007/s11192-021-03993-0.

17.
J Healthc Eng ; 2021: 5533565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306590

RESUMO

Brain-computer interaction based on motor imagery (MI) is an important brain-computer interface (BCI). Most methods for MI classification are based on electroencephalogram (EEG), and few studies have investigated signal processing based on MI-Functional Near-Infrared Spectroscopy (fNIRS). In addition, there is a need to improve the classification accuracy for MI fNIRS methods. In this study, a deep belief network (DBN) based on a restricted Boltzmann machine (RBM) was used to classify fNIRS signals of flexion and extension imagery involving the left and right arms. fNIRS signals from 16 channels covering the motor cortex area were recorded for each of 10 subjects executing or imagining flexion and extension involving the left and right arms. Oxygenated hemoglobin (HbO) concentration was used as a feature to train two RBMs that were subsequently stacked with an additional softmax regression output layer to construct DBN. We also explored the DBN model classification accuracy for the test dataset from one subject using training dataset from other subjects. The average DBN classification accuracy for flexion and extension movement and imagery involving the left and right arms was 84.35 ± 3.86% and 78.19 ± 3.73%, respectively. For a given DBN model, better classification results are obtained for test datasets for a given subject when the model is trained using dataset from the same subject than when the model is trained using datasets from other subjects. The results show that the DBN algorithm can effectively identify flexion and extension imagery involving the right and left arms using fNIRS. This study is expected to serve as a reference for constructing online MI-BCI systems based on DBN and fNIRS.

18.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 2077-2084, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227295

RESUMO

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.


Assuntos
Curcumina , Escherichia coli , Curcumina/farmacologia , Escherichia coli/genética , Fermentação
19.
Arch Microbiol ; 203(8): 4821-4828, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34212209

RESUMO

Harmful algal blooms have deleterious effects on aquatic ecosystems and human health. The application of algicidal bacteria is a promising and environmentally friendly method of preventing and eradicating harmful algal blooms. In this study, a screen for algicidal agents against harmful algal blooms was used to identify an algicidal bacterial strain (strain O-4) isolated from a Karenia mikimotoi culture. Strain O-4 exhibited a strong inhibitory effect on harmful K. mikimotoi and was identified as Paracoccus homiensis via 16S rRNA gene sequence analysis. This strain killed K. mikimotoi by secreting active algicidal compounds, which were stable at temperatures of -80-121 °C but were sensitive to strongly acidic conditions (pH = 2). The algicidal properties of strain O-4 against K. mikimotoi were cell density- and time-dependent. No significant changes or negative effects were noted for two other Chlorophyta species, which highlighted the specificity of the studied algicidal substance. Finally, single-factor experiments revealed the optimum growth conditions of strain O-4 under different pH and temperature conditions. Therefore, strain O-4 has the potential to be used as a bio-agent for reducing the biomass of harmful K. mikimotoi blooms.

20.
Eur J Med Chem ; 224: 113720, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34332399

RESUMO

Fatty acid-binding protein 4 (FABP4) and fatty acid-binding protein 5 (FABP5) are promising therapeutic targets for the treatment of various metabolic diseases. However, the weak potency, low selectivity over FABP3, or poor pharmacokinetic profiles of currently reported dual FABP4/5 inhibitors impeded further research. Here, we described the characterization of a series of dual FABP4/5 inhibitors with improved metabolic stabilities and physicochemical properties based on our previous studies. Among the compounds, D9 and E1 exhibited good inhibitory activities against FABP4/5 and favorable selectivity over FABP3 in vitro. In cell-based assays, D9 and E1 exerted a decrease of FABP4 secretion, a strong anti-lipolytic effect in mature adipocytes, and suppression of MCP-1 expression in THP-1 macrophages. Moreover, D9 and E1 possessed good metabolic stabilities in mouse hepatic microsomes and acceptable pharmacokinetics profiles in ICR mice. Further in vivo experiments showed that D9 and E1 could potently decrease serum FABP4 levels and ameliorate glucose metabolism disorders in obese diabetic db/db mice. These results demonstrated that D9 and E1 could serve as lead compounds for the development of novel anti-diabetic drugs.

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