Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 816
Filtrar
1.
BMC Surg ; 21(1): 43, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468126

RESUMO

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

2.
Future Med Chem ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427493

RESUMO

Background: Discovery of effective autophagy-initiating kinase ULK1 inhibitors has attracted more and more attention in cancer treatment. Methodology & results: The present study describes the application of a pharmacophore-based virtual screening and structure-based docking approach guided drug design. Compound U-2 exhibited a nanomolar range of IC50 against the ULK1 target. Molecular dynamics simulation was used to assess the quality of docking studies. The determinants of binding affinity were investigated, and a different binding pattern was observed. Subsequently, prediction properties of ADMET (absorption, distribution, metabolism, excretion and toxicity) and hepatotoxicity in vitro studies indicated that U-2 possessed good drug-like properties. Moreover, western blot analysis indicated that the compound inhibited autophagic flux in cells. Conclusion: The present study provides an appropriate guideline for discovering novel ULK1 inhibitors. The novel compound may serve as a good starting point for further development and optimizations.

3.
Future Med Chem ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438471

RESUMO

Casein kinase 1 (CK1) is an extensively expressed serine/threonine kinase family, with six highly conserved isoforms of human CK1. Due to its involvement in many biological processes, CK1 is a promising target for several pathological states, including circadian sleep disorder, neurodegenerative diseases, cancer and inflammation. However, due to the structural similarities between the six CK1 members, the design of CK1 inhibitors is intricate. So far, no effective CK1 inhibitors are reported to reach clinical trials; thus, approaches to obtaining both selective and effective CK1 inhibitors are in great demand. Here we analyze several CK1 inhibitors that provide successful experience for structure-based drug design and rational structure modification, which could provide references for further drug design.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 248: 119261, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33307347

RESUMO

Luminescent polymer dots have showed great potential applications in chemical sensing and bioimaging. Herein, phosphoramidic acid oligomers in aqueous solution can form nanodots (ONDs) with mean diameter of 50 ~ 60 nm. The ONDs display blue fluorescence of excitation-dependence and the fluorescence quantum yields can reach 4.16% to 9.71% under the maximum excitation and emission wavelengths. The steady and dynamic fluorescence quenching experiments by iodide ion show that the luminescence of ONDs originates to charge transfer (CT). The calculation on distribution of HOMO and LUMO of ONDs in monomer and dimer states supports further the CT mechanism, and the separated and localized distribution of HOMO and LUMO provides possible explanation on the excitation wavelength dependent luminescence based on internal and external CT. It is expected that the luminescent ONDS are useful in chemical or biological sensing fields.

5.
Bioorg Med Chem ; 30: 115940, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33340937

RESUMO

In the present work, a novel series of pyridinethiazole bearing benzylpiperidine hybrids were designed and synthesized as dual-target inhibitors of GSK-3ß/AChE. Among them, GD29 was the most promising candidate, with an IC50 value of 0.3 µM for hAChE and an IC50 value of 0.003 µM for hGSK-3ß, respectively. The compounds exhibited good drug-like properties with optimal inhibitory enzyme activities. Moreover, GD29 showed anti-inflammatory properties at micromolar concentrations and displayed interesting neuroprotective profiles in an in vitro model of oxidative stress-induced neuronal death. Notably, the compounds also exhibited good permeability across the blood-brain-barrier (BBB) both in vitro. Central cholinomimetic activity was confirmed using a scopolamine-induced cognition impairment model in Institute of Cancer Research (ICR) mice upon oral administration. The current work identified optimized compounds and explored the therapeutic potential of glycogen synthase kinase 3/cholinesterase inhibition for the treatment of AD.

6.
Int J Biol Macromol ; 166: 1352-1364, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33161083

RESUMO

In recent years, butyrylcholinesterase (BChE) has gradually gained worldwide interests as a novel target for treating Alzheimer's disease (AD). Here, two pharmacophore models were generated using Schrödinger suite and used to virtually screen ChemDiv database, from which three hits were obtained. Among them, 2513-4169 displayed the highest inhibitory activity and selectivity against BChE (eeAChE IC50 > 10 µM, eqBChE IC50 = 3.73 ± 1.90 µM). Molecular dynamic (MD) simulation validated the binding pattern of 2513-4169 in BChE, and it could form a various of receptor-ligand interactions with adjacent residues. In vitro cytotoxicity assay proved the safety of 2513-4169 on diverse neural cell lines. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay performed on SH-SY5Y cells proved the neuroprotective effect of 2513-4169 against toxic Aß1-42. In vivo behavioral study further confirmed the great efficacy of 2513-4169 on reversing Aß1-42-induced cognitive impairment of mice and clearing the toxic Aß1-42 in brains. Moreover, 2513-4169 was proved to be able to cross blood-brain barrier (BBB) through a parallel artificial membrane permeation assay of BBB (PAMPA-BBB). Taken together, 2513-4169 is a promising lead compound for future optimization to discover anti-AD treating agents.

7.
Eur J Med Chem ; 210: 112949, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33097303

RESUMO

Glycogen synthase kinase 3ß (GSK-3ß) is involved in a variety of diseases such as neurodegenerative diseases, bipolar disorder, and diabetes. In this study, a series of heterobifunctional small molecule proteolysis targeting chimera (PROTAC) were designed and synthesized based on E3 ubiquitin ligase cereblon (CRBN). Most of PROTACs displayed good inhibitory activity, with the IC50 values at the double-digits nanomolar levels and moderate protein degradation ability against GSK-3ß. Western-blot data showed compound PG21 can effectively degrade GSK-3ß in a dose-dependent manner, which can induce 44.2% protein degradation at 2.8 µM. Further pharmacological experiments revealed that the ability of PG21 to degrade GSK-3ß is mediated by the ubiquitin-proteasome system (UPS). In addition, PG21 protects against glutamate-induced cell death in HT-22 cells. As the first PROTAC example to degrade GSK-3ß protein, the present study has provided potential candidates for further investigation in the biological function of GSK-3ß protein and its association with diseases.

8.
Eur J Med Chem ; 210: 112960, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33148492

RESUMO

Medicinal plants are well-known in affording clinically useful agents, with rich medicinal values by combining with disease targets through various mechanisms. Plant secondary metabolites as lead compounds lay the foundation for the discovery and development of new drugs in disease treatment. Genus Uncaria from Rubiaceae family is a significant plant source of active alkaloids, with anti-hypertensive, sedative, anti-Alzheimer's disease, anti-drug addiction and anti-inflammatory effects. This review summarizes and discuss the research progress of Uncaria based on alkaloids in the past 15 years, mainly in the past 5 years, including biosynthesis, phytochemistry, pharmacology and structural chemistry. Among, focusing on representative compounds rhynchophylline and isorhynchophylline, the pharmacological activities surrounding the central nervous system and cardiovascular system are described in detail. On the basis of case studies, this article provides a brief overview of the synthesis and analogues of representative compounds types. In summary, this review provides an early basis for further searching for new targets and activities, discussing the mechanisms of pharmacological activity and studying the structure-activity relationships of active molecules.

9.
Sci Total Environ ; 753: 141922, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32896732

RESUMO

Algal productivity in steady-state cultivation systems depends on important factors such as biomass concentration, solids retention time (SRT), and light intensity. Current modeling of algal growth often ignores light distribution in algal cultivation systems and does not consider all these factors simultaneously. We developed a new algal growth model using a first principles approach to incorporate the effect of light intensity on algal growth while simultaneously considering biomass concentration and SRT. We first measured light attenuation (decay) with depth in an indoor algal membrane bioreactor (A-MBR) cultivating Chlorella sp. We then simulated the light decay using a multi-layer approach and correlated the decay with biomass concentration and SRT in model development. The model was calibrated by delineating specific light absorptivity and half-saturation constant to match the algal biomass concentration in the A-MBR operated at a target SRT. We finally applied the model to predict the maximum algal productivity in both indoor and outdoor A-MBRs. The predicted maximum algal productivities in indoor and outdoor A-MBRs were 6.7 g·m-2·d-1 (incident light intensity 5732 lx, SRT approximately 8 d) and 28 g·m-2·d-1 (sunlight intensity 28,660 lx, SRT approximately 4 d), respectively. The model can be extended to include other factors (e.g., water temperature and carbon dioxide bubbling) and such a modeling framework can be applied to full-scale, continuous flow outdoor systems to improve algal productivity.


Assuntos
Chlorella , Biomassa , Reatores Biológicos , Dióxido de Carbono , Temperatura
10.
Talanta ; 221: 121451, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076074

RESUMO

In this paper, a rationally designed aptasensing platform based on Hybridization Chain Reaction (HCR) and G-quadruplex DNAzyme for the fluorescence detection of Carcinoembryonic Antigen (CEA) has been developed. In the presence of target CEA, the aptamer sequence in Aptamer Probe (AP) specifically bound to CEA, resulting in the AP conformation change and thus releasing initiator, which triggered the autonomous cross-opening of Hairpin 1 (H1) and Hairpin 2 (H2) that yielded extended nicked double-stranded DNA via HCR. Upon the addition of hemin, G-rich segments at the end of H1 and H2 self-assembled into the peroxidase-mimicking hemin/G-quadruplex DNAzymes, which catalyzed the hydrogen peroxide-mediated oxidation of thiamine to achieve fluorescence detection of CEA. The HCR product, and the formation and catalytic performance of DNAzyme were characterized by agarose gel electrophoresis, UV-vis spectroscopy and fluorescence spectroscopy, respectively. Under optimal conditions, the fluorescent aptasensor showed a linear relationship ranging from 0.25 to 1.5 nM toward CEA with a detection limit of 0.2 nM. In addition, this aptasensor exhibited high selectivity for CEA without being affected by other interfering proteins, such as IgG, AFP and PSA. Furthermore, this proposed aptasensor was successfully applied to CEA analysis in diluted human serum samples. It is believed that this strategy has a promising potential in biochemical analysis and clinic application.

11.
Talanta ; 221: 121453, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076076

RESUMO

Glycoalkaloids (GAs) are toxic secondary metabolites in potatoes, which are harmful to human body. The storage time has a great influence on the biosynthesis and distribution of GAs. In present study, an imaging mass microscope (iMScope) was used to investigate the distribution and changes of GAs in potato tubers under different storage time (0, 10, 15, 20, 30, 40 and 60 days). We established a growth model with logistic equation to evaluate the growth trends of four major GAs in sprout, periderm and medulla. The results showed that the growth rate and relative contents of four GAs in sprout and periderm were significantly higher than that in medulla. In addition, four GAs also presented different change trends. For dehydrosolanine and α-solanine, rapid growth period of these two GAs in sprout (about at the day 23, similar to these in medulla) was later than which period in periderm (about at the day 17), while rapid growth of dehydrochaconine and α-chaconine appeared at almost the same time (about at the day 20). Based on the biosynthesis and metabolism of GAs, we have made possible explanations for these results. This study is useful for comprehending the metabolism of GAs in different parts and monitoring food safety in potatoes.

12.
Eur Radiol ; 31(1): 403-410, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32743768

RESUMO

OBJECTIVES: Epithelial ovarian cancers (EOC) can be divided into type I and type II according to etiology and prognosis. Accurate subtype differentiation can substantially impact patient management. In this study, we aimed to construct an MR image-based radiomics model to differentiate between type I and type II EOC. METHODS: In this multicenter retrospective study, a total of 294 EOC patients from January 2010 to February 2019 were enrolled. Quantitative MR imaging features were extracted from the following axial sequences: T2WI FS, DWI, ADC, and CE-T1WI. A combined model was constructed based on the combination of these four MR sequences. The diagnostic performance was evaluated by ROC-AUC. In addition, an occlusion test was carried out to identify the most critical region for EOC differentiation. RESULTS: The combined radiomics model exhibited superior diagnostic capability over all four single-parametric radiomics models, both in internal and external validation cohorts (AUC of 0.806 and 0.847, respectively). The occlusion test revealed that the most critical region for differential diagnosis was the border zone between the solid and cystic components, or the less compact areas of solid component on direct visual inspection. CONCLUSIONS: MR image-based radiomics modeling can differentiate between type I and type II EOC and identify the most critical region for differential diagnosis. KEY POINTS: • Combined radiomics models exhibited superior diagnostic capability over all four single-parametric radiomics models, both in internal and external validation cohorts (AUC of 0.834 and 0.847, respectively). • The occlusion test revealed that the most crucial region for differentiating type Ι and type ΙΙ EOC was the border zone between the solid and cystic components, or the less compact areas of solid component on direct visual inspection on T2WI FS. • The light-combined model (constructed by T2WI FS, DWI, and ADC sequences) can be used for patients who are not suitable for contrast agent use.

13.
Eur Radiol ; 31(1): 411-422, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32749583

RESUMO

OBJECTIVE: To construct a MRI radiomics model and help radiologists to improve the assessments of pelvic lymph node metastasis (PLNM) in endometrial cancer (EC) preoperatively. METHODS: During January 2014 and May 2019, 622 EC patients (age 56.6 ± 8.8 years; range 27-85 years) from five different centers (A to E) were divided into training set, validation set 1 (351 cases from center A), and validation set 2 (271 cases from centers B-E). The radiomics features were extracted basing on T2WI, DWI, ADC, and CE-T1WI images, and most related radiomics features were selected using the random forest classifier to build a radiomics model. The ROC curve was used to evaluate the performance of training set and validation sets, radiologists based on MRI findings alone, and with the aid of the radiomics model. The clinical decisive curve (CDC), net reclassification index (NRI), and total integrated discrimination index (IDI) were used to assess the clinical benefit of using the radiomics model. RESULTS: The AUC values were 0.935 for the training set, 0.909 and 0.885 for validation sets 1 and 2, 0.623 and 0.643 for the radiologists 1 and 2 alone, and 0.814 and 0.842 for the radiomics-aided radiologists 1 and 2, respectively. The AUC, CDC, NRI, and IDI showed higher diagnostic performance and clinical net benefits for the radiomics-aided radiologists than for the radiologists alone. CONCLUSIONS: The MRI-based radiomics model could be used to assess the status of pelvic lymph node and help radiologists improve their performance in predicting PLNM in EC. KEY POINTS: • A total of 358 radiomics features were extracted. The 37 most important features were selected using the random forest classifier. • The reclassification measures of discrimination confirmed that the radiomics-aided radiologists performed better than the radiologists alone, with an NRI of 1.26 and an IDI of 0.21 for radiologist 1 and an NRI of 1.37 and an IDI of 0.24 for radiologist 2.

14.
J Clin Endocrinol Metab ; 106(1): e217-e231, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000120

RESUMO

CONTEXT: Postoperative hypercortisolemia mandates further therapy in patients with Cushing's disease (CD). Delayed remission (DR) is defined as not achieving postoperative immediate remission (IR), but having spontaneous remission during long-term follow-up. OBJECTIVE: We aimed to develop and validate machine learning (ML) models for predicting DR in non-IR patients with CD. METHODS: We enrolled 201 CD patients, and randomly divided them into training and test datasets. We then used the recursive feature elimination (RFE) algorithm to select features and applied 5 ML algorithms to construct DR prediction models. We used permutation importance and local interpretable model-agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. RESULTS: Eighty-eight (43.8%) of the 201 CD patients met the criteria for DR. Overall, patients who were younger, had a low body mass index, a Knosp grade of III-IV, and a tumor not found by pathological examination tended to achieve a lower rate of DR. After RFE feature selection, the Adaboost model, which comprised 18 features, had the greatest discriminatory ability, and its predictive ability was significantly better than using Knosp grading and postoperative immediate morning serum cortisol (PoC). The results obtained from permutation importance and LIME algorithms showed that preoperative 24-hour urine free cortisol, PoC, and age were the most important features, and showed the reliability and clinical practicability of the Adaboost model in DC prediction. CONCLUSIONS: Machine learning-based models could serve as an effective noninvasive approach to predicting DR, and could aid in determining individual treatment and follow-up strategies for CD patients.

15.
Phytochemistry ; 181: 112544, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130375

RESUMO

Phytochemical investigation of the roots of Streblus asper Lour. resulted in the isolation of six previously undescribed cardiac glycosides, designated 2'-de-O-methylstrebloside (1), cannogenol-3α-O-ß-D-gluopyranosyl-(1 â†’ 4)-6-deoxy -2,3-dimethoxyl-ß-D-fucopyranoside (2), periplogenin-3-O-α-L-rhamnopyranosyl -(1 â†’ 4)-6-deoxy-ß-D-allopyranoside (3), 5-de-O-hydroxylstrebloside (4), 5ßH-16ß-hydroxylkamaloside (5), and 17S, 21R-21-hydroxylstrebloside (6), and three known analogues (7-9). The structures were elucidated using NMR spectroscopic techniques, mass spectrometry, and comparison of the spectroscopic data with previously reported data. Compound 6 is a novel C-21 hydroxyl cardiac glycoside, its absolute configuration was established from the analysis of computational ECD calculations and NMR spectroscopic data. The effects of the cardiac glycosides on apoptosis and cytotoxicity were examined in human A549 lung cancer cells. All the compounds showed remarkable inhibitory activities, with IC50 values in the range of 0.01-6.08 µM. Furthermore, compound 3 was able to significantly inhibit A549 cell growth proliferation via the induction of apoptosis, due to the activation of caspases-3, -8 and -9 in A549 cells, as revealed by Western blot analysis.


Assuntos
Glicosídeos Cardíacos , Moraceae , Células A549 , Apoptose , Glicosídeos Cardíacos/farmacologia , Glicosídeos/farmacologia
16.
Phytochemistry ; 181: 112577, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33190100

RESUMO

The new concept that Na/K-ATPase acts as a receptor prompted us to look for new ligands from Callicarpa kwangtungensis Chun. Using column chromatography, an undescribed phenethyl alcohol glycoside, callicarpanoside A, and an undescribed benzyl alcohol glycoside, callicarpanoside B, along with twelve known polyphenols were isolated from Callicarpa kwangtungensis Chun. All the isolated compounds were evaluated for their Na/K-ATPase (NKA) inhibitory activities. Using our NKA technology platform-based screening assay protocols, callicarpanoside B was identified as an undescribed Na/K-ATPase agonist. In particular, the newly identified benzyl alcohol glycoside was found to bind NKA and activate the receptor NKA/Src complex, resulting in the activation of protein kinase cascades. These cascades included extracellular signal-regulated kinases and protein kinase C epsilon, as well as NKA α1 endocytosis at nanomolar concentrations. Unlike the class of cardiotonic steroids, callicarpanoside B showed less inhibition of NKA activity and caused less cellular toxicity. Moreover, callicarpanoside B was found to bind NKA at a different site other than the cardiotonic steroids binding site. Thus, we have identified an undescribed NKA α1 agonist that may be used to enhance the physiological processes of NKA α1 signaling.


Assuntos
Callicarpa , Glicosídeos Cardíacos , Glicosídeos Cardíacos/farmacologia , Glicosídeos/farmacologia , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/metabolismo
17.
Entropy (Basel) ; 22(4)2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33286216

RESUMO

It is critically meaningful to accurately predict the ionospheric F2 layer critical frequency (foF2), which greatly limits the efficiency of communications, radar, and navigation systems. This paper introduced the entropy weight method to develop the combination prediction model (CPM) for long-term foF2 at Darwin (12.4° S, 131.5° E) in Australia. The weight coefficient of each individual model in the CPM is determined by using the entropy weight method after completing the simulation of the individual model in the calibration period. We analyzed two sets of data to validate the method used in this study: One set is from 2000 and 2009, which are included in the calibration period (1998-2016), and the other set is outside the calibration cycle (from 1997 and 2017). To examine the performance, the root mean square error (RMSE) of the observed monthly median foF2 value, the proposed CPM, the Union Radio Scientifique Internationale (URSI), and the International Radio Consultative Committee (CCIR) are compared. The yearly RMSE average values calculated from CPM were less than those calculated from URSI and CCIR in 1997, 2000, 2009, and 2017. In 2000 and 2009, the average percentage improvement between CPM and URSI is 9.01%, and the average percentage improvement between CPM and CCIR is 13.04%. Beyond the calibration period, the average percentage improvement between CPM and URSI is 13.2%, and the average percentage improvement between CPM and CCIR is 12.6%. The prediction results demonstrated that the proposed CPM has higher precision of prediction and stability than that of the URSI and CCIR, both within the calibration period and outside the calibration period.

18.
Mol Ther Nucleic Acids ; 22: 1063-1077, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33294293

RESUMO

Emerging evidence indicates that microRNAs play a pivotal role in neural remodeling after spinal cord injury (SCI). This study aimed to investigate the mechanisms of miR-135a-5p in regulating the functional recovery of SCI by impacting its target genes and downstream signaling. The gene transfection assay and luciferase reporter assay confirmed the target relationship between miR-135a-5p and its target genes (specificity protein 1 [SP1] and Rho-associated kinase [ROCK]1/2). By establishing the H2O2-induced injury model, miR-135a-5p transfection was found to inhibit the apoptosis of PC12 cells by downregulating the SP1 gene, which subsequently induced downregulation of pro-apoptotic proteins (Bax, cleaved caspase-3) and upregulation of anti-apoptotic protein Bcl-2. By measuring the neurite lengths of PC12 cells, miR-135a-5p transfection was found to promote axon outgrowth by downregulating the ROCK1/2 gene, which subsequently caused upregulation of phosphate protein kinase B (AKT) and phosphate glycogen synthase kinase 3ß (GSK3ß). Use of the rat SCI models showed that miR-135a-5p could increase the Basso, Beattie, and Bresnahan (BBB) scores, indicating neurological function recovery. In conclusion, the miR-135a-5p-SP1-Bax/Bcl-2/caspase-3 and miR-135a-5p-ROCK-AKT/GSK3ß axes are involved in functional recovery of SCI by regulating neural apoptosis and axon regeneration, respectively, and thus can be promising effective therapeutic strategies in SCI.

19.
Eur J Med Chem ; 211: 113113, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33360799

RESUMO

Stimulator of interferon genes (STING) plays a crucial role in human innate immune system, which is gradually concerned following the emerging immunotherapy. Activated STING induces the production of type I interferons (IFNs) and proinflammatory cytokines through STING-TBK1-IRF3/NF-κB pathway, which could be applied into the treatment of infection, inflammation, and tumorigenesis. Here, we provided a detailed summary of STING from its structure, function and regulation. Especially, we illustrated the canonical or noncanonical cyclic dinucleotides (CDNs) and synthetic small molecules for STING activation or inhibition and their efficacy in related diseases. Importantly, we particularly emphasized the discovery, development and modification of STING agonist or antagonist, attempting to enlighten reader's mind for enriching small molecular modulator of STING. In addition, we summarized biological evaluation methods for the assessment of small molecules activity.

20.
Anal Chem ; 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33377760

RESUMO

The pan-cancer detection and precise visualization of tiny tumors in surgery still face great challenges. As tumors grow aggressively, hypoxia is a common feature of solid tumors and has supplied a general way for detecting tumors. Herein, we report a simple aggregation-induced emission nanoprobe-TPE-4NE-O that can specifically switch on their fluorescence in the presence of cytochrome P450 reductase, a reductase which is overexpressed under hypoxia conditions. The probe can selectively light up the hypoxia cells and has shown enhanced deep tumor penetration via charge conversion both in vitro and in vivo. After being modified with FA-DSPE-PEG, higher tumor uptake can be seen and FA-DSPE/TPE-4NE-O showed specific visualization to the hypoxia cancer cells. Excitingly, much brighter fluorescence was accumulated at the tumors in the FA-DSPE/TPE-4NE-O group, even though the tumor was as small as 2.66 mm. The excellent performance of FA-DSPE/TPE-4NE-O in detecting tiny tumors has made it possible for imaging-guided tumor resection. More importantly, the probe exhibited good biocompatibility with negligible organ damage and eliminated a hemolysis risk. The simple but promising probe has supplied a new strategy for pan-cancer detection and tiny tumor visualization, which have shown great potential in clinical translation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA