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1.
Bioengineered ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606406

RESUMO

Our study aimed to explore potential new diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) to find new target molecules involved in the progression of OSCC. Potential novel biomarkers of OSCC were identified using a protein microarray assay. Compared with the healthy control group, there were five proteins (I309, GDF15, AXL, MMP3, and CTACK) in the serum of in situ oral cancer group. However, there were four differentially expressed proteins (MCSF, I309, MMP3, and CTACK) in the serum of the OSCC group. Receiver operating characteristic (ROC) curve analysis results suggested that these six proteins (I309, GDF15, AXL, MMP3, CTACK, and MCSF) had diagnostic value for OSCC. Based on The Cancer Genome Atlas (TCGA) database, we found that only GDF15 expression was associated with the prognosis of OSCC. Subsequently, we verified the expression levels of six proteins in HSC-3 and HaCaT cells, and the results showed that the level of these six proteins was significantly higher in HSC-3 cells than in normal HaCaT cells. Similarly, in the OSCC nude mouse model, the expression levels of these proteins were significantly upregulated in OSCC tumor tissue compared to the normal tissue. GDF-15, MMP-3, AXL, MCSF, I309, and CTACK may be used as biomarkers for OSCC diagnosis and provide a novel study direction for the treatment of OSCC.

2.
Appl Opt ; 60(21): 6140-6146, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613278

RESUMO

The laser-induced fluorescence (LIF) technique, which has been widely used for food testing, can be combined with various algorithms to classify and recognize different kinds of honey. This paper proposes the Kolmogorov-Smirnov test-Gaussian mixture model (KS-GMM) algorithm, which is coupled with the LIF technique to realize accurate classification and recognition of different types of pure honey. The experiments are designed and carried out to obtain a set of LIF spectrum data from various honey and syrup samples. The proposed KS-GMM algorithm is applied for classification and recognition, with GMM, k-nearest neighbor (kNN), and decision tree algorithms as cross-validation methods. By comparing recognition results of training sets containing different amounts of data, it is found that the KS-GMM algorithm exhibits a maximum recognition accuracy of 96.52%. The research results prove that the KS-GMM algorithm outperforms, to the best of our knowledge, the other three algorithms in classifying and recognizing the honey types.

3.
Aging (Albany NY) ; 13(17): 21483-21496, 2021 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511433

RESUMO

2,5-dimethyl celecoxib (DMC), a close derivative of celecoxib, has also been reported to have anticancer effects. However, the effects and underlying molecular mechanisms of DMC with respect to nasopharyngeal carcinoma are still largely unknown. In this study, we present that DMC has displayed anticancer potency in nasopharyngeal carcinoma in vitro and in vivo. Mechanistically, we found DMC induced apoptosis and autophagy for anticancer therapy against nasopharyngeal carcinoma. Furthermore, DMC-induced autophagy could remarkably attenuate after the treatment of reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) and c-Jun N-terminal kinase (JNK) inhibitor SP600125 (SP). Taken together, these results suggested DMC induced apoptosis and autophagic death via activation of ROS/JNK axis in NPC cells, which providing us new insights into developing potential therapeutic agents for nasopharyngeal carcinoma patients.

4.
Mikrochim Acta ; 188(10): 356, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585287

RESUMO

Two high-sensitivity competitive immune-nanoplatforms based on the inner filter effect (IFE-IN) and magnetic separation (MS-IN) with a positive readout were developed to rapidly detect imidacloprid (IMI) using gold nanoparticles (AuNPs). For IFE-IN, IMI competes with AuNPs-labeled IMI antigens (IMI-BSA-AuNPs) to bind with anti-IMI monoclonal antibody (mAb)-conjugated NaYF4:Yb,Er upconversion nanoparticles, which changes the fluorescence signal at excitation/emission wavelength of 980/544 nm. For MS-IN, the immunocomplex of IMI-BSA-AuNPs and magnetic-nanoparticles-labeled mAb (mAb-MNPs) dissociates in the presence of IMI, and the optical density of IMI-BSA-AuNPs at 525 nm increases with the IMI concentration after magnetic separation. Under the optimal conditions, the IMI concentration producing a 50% saturation of the signal (SC50) and linear range (SC10- SC90) were found to be 4.30 ng mL-1 and 0.47 - 21.37 ng mL-1 for IFE-IN, while 1.21 ng mL-1 and 0.07 - 10.21 ng mL-1 for MS-IN, respectively. Both IFE-IN and MS-IN achieved excellent accuracy for the detection of IMI in different matrices. The quantities of IMI in apple samples detected by IFE-IN and MS-IN were consistent with the high-performance liquid chromatography results. For IFE-IN, analyte competes with AuNPs-labeled-antigen to bind with the mAb-conjugated-UCNPs, which changes the fluorescence signal at 544 nm. For MS-IN, the immunocomplex of AuNPs-labeled-antigen and mAb-conjugated-MNPs dissociates in the presence of analyte, and the optical density of AuNPs-labeled-antigen at 525 nm increases with increasing analyte concentration after separation.

5.
J Am Chem Soc ; 143(37): 15073-15083, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34520194

RESUMO

Proteolysis targeting chimeras (PROTACs) represent a new class of promising therapeutic modalities. PROTACs hijack E3 ligases and the ubiquitin-proteasome system (UPS), leading to selective degradation of the target proteins. However, only a very limited number of E3 ligases have been leveraged to generate effective PROTACs. Herein, we report that the KEAP1 E3 ligase can be harnessed for targeted protein degradation utilizing a highly selective, noncovalent small-molecule KEAP1 binder. We generated a proof-of-concept PROTAC, MS83, by linking the KEAP1 ligand to a BRD4/3/2 binder. MS83 effectively reduces protein levels of BRD4 and BRD3, but not BRD2, in cells in a concentration-, time-, KEAP1- and UPS-dependent manner. Interestingly, MS83 degrades BRD4/3 more durably than the CRBN-recruiting PROTAC dBET1 in MDA-MB-468 cells and selectively degrades BRD4 short isoform over long isoform in MDA-MB-231 cells. It also displays improved antiproliferative activity than dBET1. Overall, our study expands the limited toolbox for targeted protein degradation.

6.
Fish Shellfish Immunol ; 118: 396-404, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34571156

RESUMO

Heat shock protein 40 (Hsp40), a member of Heat shock proteins (Hsps) family, plays a crucial role in regulation of cell proliferation, survival and apoptosis in mammals. In this study, Hsp40, EcHsp40, was identified from Epinephelus coioides, an economically important marine-cultured fish in China and Southeast Asian counties. The full length of EcHsp40 was 2236 bp in length containing a 1026 bp open reading frame (ORF) encoding 341 amino acids, with a molecular mass of 37.88 kDa and a theoretical pI of 9.09. EcHsp40 has two conserved domains DnaJ and DnaJ_C. EcHsp40 mRNA was detected in all tissues examined, and the expression was significantly up-regulated response to challenged with Vibrio alginolyticus or Singapore grouper iridovirus (SGIV), one of the important pathogens of marine fish. EcHsp40 was distributed in both the cytoplasm and nucleus, over-expression of EcHsp40 can inhibit the activity of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), significantly promote SGIV-induced apoptosis, intracellular caspase-3 activity and viral replication, suggesting that the EcHsp40 may play an important role in pathogenic stimulation.

7.
ACS Appl Mater Interfaces ; 13(39): 46866-46874, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34559512

RESUMO

Transparent material has been widely used in product design and has seen a large increase in its use. In this paper, a kind of aesthetically decorative 5 GHz Wi-Fi dielectric resonator antenna (DRA) of aluminum oxynitride (AlON) transparent ceramic has been designed. High-quality-factor AlON transparent dielectric ceramics were fabricated by presintering at 1780 °C and further cold isostatic pressing (CIP) under a 200 MPa argon atmosphere. For a 9.0 mm thick specimen, the in-line light transmittance reached 83%. Optimum dielectric constant (εr = 9.32), quality factor (Qf = 47 960) and temperature coefficient (TCF = -51.7 ppm/°C) was achieved in the AlON transparent ceramic by cold isostatic pressing. As a result, the proposed aesthetically decorative DRA can achieve an impedance bandwidth of 32% (4.48-6.19 GHz), a high radiation efficiency of 85%, and a low cross-polarization discrimination (XPD) of -30 dB. To achieve a broad bandwidth, the proposed antenna was excited in its dominant TE111x mode and higher-order TE113x mode. The proposed antenna is thus an excellent candidate for an indoor decoration Wi-Fi antenna.

8.
Front Physiol ; 12: 666449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539422

RESUMO

Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE-/- mice induced by high-fat diet (HFD). Furthermore, we investigated the effects of HLJDD on macrophage polarization in oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 cells. For in vivo assay, compared with the model group, HLJDD ameliorated lipid metabolism, with significantly decreased levels of serum triglyceride, total cholesterol (CHOL), and lipid density lipoprotein. HLJDD suppressed serum tumor necrosis factor α (TNF-α) and IL-1ß levels with increased serum IL-10 level, and inhibited mRNA level of NLRP3 inflammasome in carotid tissues. HLJDD enhanced carotid lesion stability by decreasing macrophage infiltration together with increased expression of collagen fibers and α-SMA. Moreover, HLJDD inhibited M1 macrophage polarization, which decreased the expression and mRNA levels of M1 markers [inducible nitric oxide synthase (iNOS) and CD86]. HLJDD enhanced alternatively activated macrophage (M2) activation, which increased the expression and mRNA levels of M2 markers (Arg-1 and CD163). For in vitro assay, HLJDD inhibited foam cell formation in RAW264.7 macrophages disturbed by ox-LDL. Besides, groups with ox-LDL plus HLJDD drug had a lower expression of CD86 and mRNA levels of iNOS, CD86, and IL-1ß, but higher expression of CD163 and mRNA levels of Arg-1, CD163, and IL-10 than ox-LDL group. Collectively, our results revealed that HLJDD alleviated atherosclerosis and promoted plaque stability by suppressing M1 polarization and enhancing M2 polarization.

9.
J Org Chem ; 86(17): 11987-11997, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34374284

RESUMO

A cheap iron-catalyzed C-C bond cleavage/thiolation and selenylation of cycloalkyl hydroperoxides are presented. This redox-neutral protocol provides efficient access to diverse distal keto-functionalized thioethers and selenium compounds. Remarkably, only some amounts of disulfides are required for this transformation.


Assuntos
Peróxido de Hidrogênio , Ferro , Catálise , Dissulfetos , Sulfetos
10.
Mol Biol Rep ; 48(8): 6075-6083, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34374892

RESUMO

BACKGROUND: Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. METHODS AND RESULTS: DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. CONCLUSIONS: Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

11.
J Med Chem ; 64(16): 12273-12285, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34378936

RESUMO

Molecular glues and proteolysis targeting chimeras (PROTACs) are promising new therapeutic modalities. However, the lack of specificity for molecular glue- or PROTAC-mediated proteolysis in cancer cells versus normal cells raises potential toxicity concerns that will likely limit their clinical applications. Here, we developed a general strategy to deliver immunomodulatory imide drug (IMiD)-based molecular glues and PROTACs to folate receptor α (FOLR1)-positive cancer cells. Specifically, we designed a folate-caged pomalidomide prodrug, FA-S2-POMA, by incorporating a folate group as a caging and guiding element and validated its degradation effect on its neo-substrates in FOLR1-positive cancer cells in a FOLR1-dependent manner. We also developed a folate-caged pomalidomide-based anaplastic lymphoma kinase (ALK) PROTAC, FA-S2-MS4048, which effectively degraded ALK fusion proteins in cancer cells, again in a FOLR1-dependent manner. This novel approach provides a generalizable platform for the targeted delivery of IMiD-based molecular glues and PROTACs to FOLR1-expressing cancer cells with the potential to ameliorate toxicity.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34453606

RESUMO

PURPOSE: To estimate the clinical characteristics of retinal arterial macroaneurysms (RAM) and evaluate the prognosis of different interventions. METHODS: This study is a meta-analysis. The databases PubMed, EMBASE, and Ovid from inception to January 2021 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated by means of Freeman-Tukey variant of arcsine square transformation. RESULTS: Sixty-nine studies involving 1332 patients were finally included. The pooling results indicated that 91% (95% CI [88 ~ 94%]) of the RAM patients were over sixty, 73% (95% CI [68 ~ 77%]) were female, and 73% (95% CI [66 ~ 79%]) have hypertension. By observation, the RAM closure rate was 64% (95% CI [39 ~ 86%]), the visual acuity (VA) improved in 55% (95% CI [40 ~ 71%]) of the patients, and the VA of 64% (95% CI [54 ~ 74%]) hemorrhagic versus 27% (95% CI [15 ~ 41%]) exudative patients improved significantly. By laser, the closure rate was 96% (95% CI [87 ~ 100%]), the VA improved in 73% (95% CI [65 ~ 80%]) of the patients, and the VA of 66% (95% CI [47 ~ 84%]) hemorrhagic versus 35% (95% CI [23 ~ 47%]) exudative patients improved significantly. By anti-VEGF, the closure rate was 98% (95% CI [93 ~ 100%]), the VA improved in 90% (95% CI [74 ~ 100%]) of the patients, and the VA of 58% (95% CI [18 ~ 94%]) hemorrhagic versus 67% (95% CI [31 ~ 96%]) exudative patients improved significantly. CONCLUSION: RAM are most commonly seen in the elderly with a marked female predominance and a strong association with hypertension. Patients receiving laser or anti-VEGF treatments get higher closure rate and better visual prognosis than those with observation alone. Hemorrhagic RAM have a better visual prognosis by observation or laser treatment, while exudative RAM have a better visual prognosis by anti-VEGF treatment.

13.
Anal Chem ; 93(34): 11800-11808, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34415158

RESUMO

Phage-borne peptides and antibody fragments isolated from phage display libraries have proven to be versatile and valuable reagents for immunoassay development. Due to the lack of convenient and mild-condition methods for the labeling of the phage particles, isolated peptide/protein affinity ligands are commonly removed from the viral particles and conjugated to protein tracers or nanoparticles for analytical use. This abolishes the advantage of isolating ready-to-use affinity binders and creates the risk of affecting the polypeptide activity. To circumvent this problem, we optimized the phage display system to produce phage particles that express the affinity binder on pIII and a polyglycine short peptide fused to pVIII that allows the covalent attachment of tracer molecules employing sortase A. Using a llama heavy chain only variable domain (VHH) against the herbicide 2,4-D on pIII as the model, we showed that the phage can be extensively decorated with a rhodamine-LPETGG peptide conjugate or the protein nanoluciferase (Nluc) equipped with a C-terminal LPETGG peptide. The maximum labeling amounts of rhodamine-LPETGG and Nluc-LPETGG were 1238 ± 63 and 102 ± 16 per phage, respectively. The Nluc-labeled dual display phage was employed to develop a phage bioluminescent immunoassay (P-BLEIA) for the detection of 2,4-D. The limit of detection and 50% inhibition concentration of P-BLEIA were 0.491 and 2.15 ng mL-1, respectively, which represent 16-fold and 8-fold improvement compared to the phage enzyme-linked immunosorbent assay. In addition, the P-BLEIA showed good accuracy for the detection of 2,4-D in spiked samples.


Assuntos
Bacteriófagos , Ensaio de Imunoadsorção Enzimática , Imunoensaio , Fragmentos de Imunoglobulinas , Biblioteca de Peptídeos
14.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21259384

RESUMO

BackgroundWomen and gender-diverse individuals face disproportionate socioeconomic burden during COVID-19. We compared mental health symptom changes since pre-COVID-19 by sex or gender. MethodsWe searched MEDLINE, PsycINFO, CINAHL, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, medRxiv, and Open Science Framework December 31, 2019 to March 22, 2021 for studies that reported mental health outcomes prior to and during COVID-19 by sex or gender. We conducted restricted maximum-likelihood random-effects meta-analyses. ResultsAll 11 included studies (9 unique cohorts) compared females or women to males or men; none included gender-diverse individuals. Continuous symptom change differences were not statistically significant for depression (standardized mean difference [SMD]= 0.15, 95% CI - 0.09 to 0.39; 3 studies, 4,159 participants; I2=77%) and stress (SMD= -0.09, 95% CI -0.21 to 0.02; 3 studies, 1,217 participants; I2=0%), but anxiety (SMD= 0.14, 95% CI 0.01 to 0.26; 3 studies, 4,028 participants; I2=34%) and general mental health (SMD= 0.15, 95% CI 0.12 to 0.18; 2 studies, 15,590 participants; I2=0%) worsened more among females or women than males or men. There were no significant differences in changes in proportion above a cut-off: anxiety (difference= 0.00, 95% CI -0.01 to 0.02; 2 studies, 6,684 participants; I2=0%), depression (difference= 0.12, 95% CI -0.04 to 0.28; 1 study, 217 participants), general mental health (difference= -0.03, 95% CI -0.09 to 0.04; 3 studies, 18,985 participants; I2=94%), stress (difference= 0.04, 95% CI -0.11 to 0.18; 1 study, 217 participants). InterpretationMental health outcomes did not differ or were somewhat worse among women than men.

15.
Front Pharmacol ; 12: 700373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305608

RESUMO

Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and subsequent destruction of adjacent articular cartilage and bone. In our previous work we showed that phosphatase and tension homolog deleted on chromosome 10 (PTEN) contributes to the activation of fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA), but the underlying mechanism is not unknown. In this study, we show that PTEN is downregulated while DNA methyltransferase (DNMT)1 is upregulated in FLS from RA patients and a rat model of AIA. DNA methylation of PTEN was increased by administration of tumor necrosis factor (TNF)-α in FLS of RA patients, as determined by chromatin immunoprecipitation and methylation-specific PCR. Treatment with the methylation inhibitor 5-azacytidine suppressed cytokine and chemokine release and FLS activation in vitro and alleviated paw swelling in vivo. PTEN overexpression reduced inflammation and activation of FLS via protein kinase B (AKT) signaling in RA, and intra-articular injection of PTEN-expressing adenovirus into the knee of AIA rats markedly reduced inflammation and paw swelling. Thus, PTEN methylation promotes the inflammation and activation of FLS in the pathogenesis of RA. These findings provide insight into the molecular basis of articular cartilage destruction in RA, and indicate that therapeutic strategies that prevent PTEN methylation may an effective treatment.

16.
Neurobiol Stress ; 15: 100358, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34195305

RESUMO

Adult-born dentate granule cells (aDGCs) at 4-6 weeks of age are particularly excitable but subsequently develop the quiet properties of mature cells. Most existing studies have focused on the hyperactivity of 4-6-week-old aDGCs or neurogenesis, which confers stress resilience or buffers stress responses. However, the function of the quiet property of new mature aDGCs remains unclear. Here we used a retrovirus expressing cre recombinase in combination with an associated-adenovirus to specifically interfere with the activity of new mature aDGCs, and estimated anxiety-like behaviors by the open-field test and elevated plus maze test, antidepressant-like behaviors by the tail suspension test, and spatial memory by the Barnes maze test. We found that sustained hyperactivity of 6-8-week-old, but not 8-10-week-old, aDGCs induced anxiety-like behaviors, and suppression of the activity of 6-8-week-old aDGCs disturbed spatial memory. Meanwhile, sustained hyperactivity of 6-8-week-old aDGCs induced activation of mature dentate gyrus (DG) neurons and inhibition of immature aDGCs. Additionally, the mice showing anxiety-like behaviors induced by chronic mild immobilization stress exhibited increased activity in 6-8-week-old aDGCs. Furthermore, the sustained hyperactivity of mature DG neurons also induced anxiety-like behaviors and decreased the activity of immature aDGCs. Our results combined show that the excitation of 6-8-week-old new mature aDGCs, which prohibits them from normally entering the resting state, determines anxiety-like behavior, while the maintenance of normal excitation ability of 6-8-week-old new mature aDGCs confers memory. Our results suggests that strategies aimed at inhibiting unusual hyperactive new mature aDGCs at a restricted time window may protect against stress-related psychiatric disorders, such as anxiety and depression.

17.
Front Pharmacol ; 12: 705325, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262463

RESUMO

Patients with Crohn's disease (CD) are inclined to have platelet hyperactivity and an increased risk of intestinal micro-thrombosis. However, the mechanisms underlying platelet hyperactivity in CD are not well understood. We investigated the assembly of platelet NLRP3 inflammasome in patients with active CD and its correlation with platelet hyperactivity. In this study, Real-time PCR and western blotting analyses uncovered that ASC, NLRP3, and active caspase-1 were significantly upregulated in platelets from patients with active CD compared with healthy subjects. As revealed by flow cytometry (FCM) and ELISA analyses, the levels of interleukin-1ß in both serum and isolated platelets were elevated in patients with active CD. Co-immunoprecipitation and immunofluorescence experiments revealed an increased assembly of NLRP3 inflammasome in platelets from patients with active CD. In addition, higher levels of intracellular reactive oxygen species (ROS) were observed in these platelets by FCM. Furthermore, elevated levels of platelet P-selectin exposure and fibrinogen binding were demonstrated in patients with active CD by FCM. They were positively correlated with the protein levels of NLRP3 inflammasome components. Collectively, our results indicate that the ROS-NLRP3 inflammasome-interleukin-1ß axis may contribute to platelet hyperactivity in active CD.

18.
J Am Chem Soc ; 143(23): 8902-8910, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34100597

RESUMO

Transcription factors (TFs) represent a major class of therapeutic targets for the treatment of human diseases including cancer. Although the biological functions and even crystal structures of many TFs have been clearly elucidated, there is still no viable approach to target the majority of TFs, thus rendering them undruggable for decades. PROTACs (proteolysis targeting chimeras) emerge as a powerful class of therapeutic modalities, which rely on induced protein-protein interactions between the proteins of interest (POIs) and E3 ubiquitin ligases to aid the degradation of POIs by the ubiquitin-proteasome system (UPS). Here, we report the development of a platform termed TF-PROTAC, which links an DNA oligonucleotide to an E3 ligase ligand via a click reaction, to selectively degrade the TF of interest. The selectivity of these TF-PROTACs depends on the DNA oligonucleotides utilized that can be specific to the TFs of interest. We have developed two series of VHL-based TF-PROTACs, NF-κB-PROTAC (dNF-κB) and E2F-PROTAC (dE2F), which effectively degrade endogenous p65 and E2F1 proteins in cells, respectively, and subsequently display superior antiproliferative effects in cells. Collectively, our results suggest that TF-PROTACs provide a generalizable platform to achieve selective degradation of TFs and a universal strategy for targeting most "undruggable" TFs.

19.
Front Plant Sci ; 12: 609876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093601

RESUMO

In recent years, the unmanned aerial vehicle (UAV) remote sensing system has been rapidly developed and applied in accurate estimation of crop parameters and yield at farm scale. To develop the major contribution of UAV multispectral images in predicting winter wheat leaf area index (LAI), chlorophyll content (called soil and plant analyzer development [SPAD]), and yield under different water treatments (low water level, medium water level, and high water level), vegetation indices (VIs) originating from UAV multispectral images were used during key winter wheat growth stages. The estimation performances of the models (linear regression, quadratic polynomial regression, and exponential and multiple linear regression models) on the basis of VIs were compared to get the optimal prediction method of crop parameters and yield. Results showed that LAI and SPAD derived from VIs both had high correlations compared with measured data, with determination coefficients of 0.911 and 0.812 (multivariable regression [MLR] model, normalized difference VI [NDVI], soil adjusted VI [SAVI], enhanced VI [EVI], and difference VI [DVI]), 0.899 and 0.87 (quadratic polynomial regression, NDVI), and 0.749 and 0.829 (quadratic polynomial regression, NDVI) under low, medium, and high water levels, respectively. The LAI and SPAD derived from VIs had better potential in estimating winter wheat yield by using multivariable linear regressions, compared to the estimation yield based on VIs directly derived from UAV multispectral images alone by using linear regression, quadratic polynomial regression, and exponential models. When crop parameters (LAI and SPAD) in the flowering period were adopted to estimate yield by using multiple linear regressions, a high correlation of 0.807 was found, while the accuracy was over 87%. Importing LAI and SPAD obtained from UAV multispectral imagery based on VIs into the yield estimation model could significantly enhance the estimation performance. This study indicates that the multivariable linear regression could accurately estimate winter wheat LAI, SPAD, and yield under different water treatments, which has a certain reference value for the popularization and application of UAV remote sensing in precision agriculture.

20.
Front Endocrinol (Lausanne) ; 12: 668073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122342

RESUMO

The uterine endometrium, which lines the mammalian uterus, is essential for embryo implantation. This lining undergoes significant changes during sexual and menstrual cycles. The endometrium is also associated with hormone-related diseases such as endometriosis and endometrial cancer. Circular RNAs (circRNAs) play a role in various biological processes. Recent studies have determined that circRNAs function in both normal and pathological endometrial environments. Here, we review high-throughput studies pertaining to circRNAs as well as individual circRNAs active in the endometrium, in order to explore the myriad functions of circRNAs in the endometrium and mechanisms underlying these functions, from panoramic and individual perspectives. Owing to their abundant expression, stability, and small size, circRNAs have displayed potential usefulness as diagnostic markers and treatment targets for endometrial-related diseases. Therefore, the specific role of circRNAs in the endometrium warrants systematic investigation in the future.

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