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1.
Acta Pharmacol Sin ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060777

RESUMO

G protein-coupled receptors (GPCRs) play important roles in human physiology. GPCRs are involved in immunoregulation including regulation of the inflammatory response. Chemotaxis of phagocytes and lymphocytes is mediated to a great extent by the GPCRs for chemoattractants including myriads of chemokines. Accumulation and activation of phagocytes at the site of inflammation contribute to local inflammatory response. A handful of GPCRs have been found to transduce anti-inflammatory signals that promote resolution of inflammation. These GPCRs interact with selected metabolites of arachdonic acid, such as lipoxins, and of omega-3 essential fatty acids, such as resolvins and protectins. Despite mounting evidence for the in vivo functions of these anti-inflammatory and pro-resolving ligands paired with their respective GPCRs, the underlying signaling mechanisms have not been fully delineated. The present review summarizes what we have learned about these GPCRs, their structures and signaling pathways and the prospect of targeting these receptors for novel anti-inflammatory therapies.

2.
ACS Sens ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052655

RESUMO

Aflatoxin B1 (AFB1), one of the most toxic mycotoxins, poses great health risks. Rapid and sensitive detection of AFB1 is important for food safety, environment monitoring, and health risk assessment. We report here the development of a simple and reusable electrochemical aptasensor for rapid and sensitive detection of AFB1. Main improvements were achieved through engineering an aptamer containing a short stem-loop structure and enhancing the binding affinity at a lower temperature. The DNA aptamer with a methylene blue (MB) label at one end was immobilized on a gold electrode. Upon AFB1 binding, the aptamer folded into a stem-loop structure and brought MB close to the electrode surface, resulting in increases in electric current. The aptamer having a shorter stem (2-4 bp) underwent a larger conformation change upon target binding. The sensors built with the aptamer containing a 2 bp stem generated much higher signal-on responses to AFB1 at 4 °C than at room temperature (25 °C). The improvements resulted in a detection limit of 6 pM, enabling the determination of trace AFB1 in a complex sample matrix. This study demonstrates that low temperature greatly enhances the performance of aptamer electrochemical sensors. This aptasensor is simple to construct and readily regenerated by washing with deionized water for reuse. This aptasensor strategy could be applied to the development of an electrochemical aptasensor for other targets.

3.
Cancer Med ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040485

RESUMO

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol(RES)in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES-mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial-mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1474-1479, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067940

RESUMO

OBJECTIVE: To investigate the value of fluorescence in situ hybridization (FISH) in the diagnosis and prognosis evaluation of patients with chronic lymphocytic leukemia (CLL). METHODS: Ninty-three patients with newly diagnosed CLL were tested by five probes including RB1 (13q14.1), D13S25 (13q14.3), p53(17p13.1), ATM( 11q22.3) and CSP12, while conventional cytogenetics (CC) was used for karyotype analysis. Then the correlation of the molecular cytogenetic abnormalities with the clinical Binet stages, Rai stages and the other related laboratory examinations was analyzed. RESULTS: The detection rate of chromosome abnormality in 93 patients was 79.6%, out of which detection rate of 13q (13q- was the highest and accounted for 45.2%), followed by trisomy 12 (+12) 26.9%, p53 deletion (17p-) 19.4% and ATM deletion (11p-) 17.2%. There were 27 cases (29.0%) with 2 or more abnormalities, including 13 cases with 13q-/17q-, 5 with 13q-/11q-, and 4 with 13q-/+12. Compared with CC test results, the positive rate of FISH detection was significantly higher (χ2=32.127, P<0.01). There was no significant correlation between FISH results and Rai stages (P>0.05), meanwhile 17p- highly correlated with later stage of the Binet stages (P=0.012). The molecular cytogenetic abnormalities significantly correlated with age, absolute value of peripheral lymphocyte count and CD38 expression level (P>0.05). The incidence of 13q- in female (65.4%) was statistically significantly higher than that in male (37.3%) (P=0.015). The unmutated IGHV rate of CLL patients with a 17p- was significantly higher than that in patients without this genetic abnormality (P=0.013). The expression of CD38 was detected among 29.0% of the patients, which significantly correlated with Binet stages (P=0.027) and unmutated IGHV (P=0.006). CONCLUSION: FISH can greatly increase the detection rate of molecular cytogenetic abnormalities in CLL patients, which, as a powerful supplement to the conventional cytogenetics, can be applied for the clinical staging and prognosis evaluation of CLL patients.

5.
Zhongguo Fei Ai Za Zhi ; 23(10): 837-844, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33070512

RESUMO

BACKGROUND: Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumor-associated macrophages (TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1 (PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients' prognosis of non-small cell lung cancer (NSCLC). METHODS: Clinico-pathological data and surgical specimens of 92 patients with NSCLC were collected, and immunohistochemistry was used to stain the expression of TAMs, tumor neo-vessels and PD-L1 on tumor tissue and peri-tumor tissues. The inverted microscopy was used to take pictures and Image-pro Plus 6.0 software was used for quantitative analysis. The clinicopathological characteristics and overall survival (OS) were analyzed. RESULTS: The median OS of 92 NSCLC cases was 22.5 month. The expression of TAMs, tumor neo-vessels and PD-L1 in tumor tissue and peri-tumor tissues were not statistically significant (P>0.05). According to the cutoff of above key three components in tumor microenvironment, all the cases could be classified into high, middle and low expression groups. The survival analysis demonstrated that the OS in high expression group of TAMs (P=0.016) and PD-L1 (P=0.002) was shorter than the other two groups, respectively, with statistical significance. The OS in high tumor neo vessels group was shorter than the other two groups. However, there was no statistical significance between these three group (P=0.626). Combined with above the three components, all the cases could be classified into low, middle and high density groups. The survival analysis demonstrated that the median OS of combined high density group was shorter than the other two groups (P=0.001). Multivariate analysis by Cox regression indicated that pathological type, TAMs and PD-L1 expression were the independent prognostic factors. CONCLUSIONS: The key components of TAMs and PD-L1 in tumor microenvironment are closely related to the prognosis of NSCLC patients.

6.
Thorac Cancer ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975378

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death worldwide. The family of glutathione peroxidase (GPX), an important antioxidant enzyme in human tissues, has been discovered to play a key role in the development of cancers. GPX8 is the most promising molecule of the family in a therapeutic strategy against a variety of cancers. The main purpose of this study was to examine and analyze the function and clinical value of GPX8 in NSCLC. METHODS: Immunohistochemistry (IHC), western blot analysis and quantitative real-time polymerase chain reaction (qPCR) were used to assess GPX8 expression and its clinical significance in NSCLC. A series of cell biology experiments and bioinformatic analysis tools were further used to study the function of GPX8. RESULTS: GPX8 expression in tumor tissues was much higher than that in normal lung tissues. High expression of GPX8 in NSCLC was correlated with a worse clinical outcome and prognosis. Furthermore, GPX8 could inhibit the apoptosis of tumor cells and promote its migration and invasion. CONCLUSIONS: Our results conclusively demonstrated that GPX8 could affect the oncogenesis and prognosis of NSCLC via regulating epithelial characteristics. The study also illustrated that GPX8 could serve as a prognostic predictor and potential therapeutic target for NSCLC.

7.
J Environ Sci (China) ; 97: 19-24, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32933735

RESUMO

Bisphenol A (BPA) is one of the environmental endocrine disruptors (EDCs), and BPA contamination in environment can cause high risks to human health. Rapid determination of BPA on sites is in high demand in environmental analysis. Taking advantage of aptamers as affinity ligands and fluorescence anisotropy (FA) analysis, we developed a simple and rapid FA assay for BPA by employing a single tetramethylrhodamine (TMR) labeled short 35-mer DNA aptamer against BPA. The assay is based on the BPA-binding induced conformation change of TMR-labeled aptamer and alteration of interaction between TMR and guanine bases, resulting in change of FA signals. We screened the FA change of aptamer probes having TMR label on a specific site of the aptamer upon BPA addition. The aptamer with a TMR label on the 22nd T base showed large FA-decreasing response to BPA and maintained good binding affinity to BPA. By using this TMR-labeled aptamer, we achieved FA detection of BPA with a detection limit of 0.5 µmol/L under the optimized conditions. This assay was selective towards BPA and enabled the detection of BPA spiked in tap water sample, showing the potential applications on water samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Compostos Benzidrílicos , Polarização de Fluorescência , Humanos , Limite de Detecção , Fenóis
8.
Medicine (Baltimore) ; 99(37): e22063, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925740

RESUMO

RATIONALE: Wandering spleen (WS) is a rare clinical entity characterized by splenic hypermobility caused by absent or abnormal laxity of the suspensory ligaments, which fix the spleen in its normal position. Due to abnormal attachment, the spleen is predisposed to torsion and a series of complications. Pediatric WS is mostly reported in children aged <10 years, especially among infants aged <1 year; it is uncommon among toddlers between 1 and 3 years. To the authors' knowledge, only seven cases of WS have been described previously. Herein, we present the case of a 3-year-old toddler with WS and splenic torsion. PATIENT CONCERNS: A 3-year-old boy was presented to the pediatric emergency room with a 2-day history of abdominal pain and vomiting. The ultrasonographic examination revealed a mass in the left upper abdomen cavity and absence of spleen in its normal position. Computed tomography showed an enlarged displaced spleen occupying the left abdomen cavity with an elongated splenic vascular pedicle (whirl sign), suggesting splenic torsion. DIAGNOSES: The patient was diagnosed that had WS and splenomegaly, with or without complications due to splenic torsion. INTERVENTIONS: The patient underwent emergency laparotomy and splenectomy due to nonviability after detorsion. OUTCOMES: The postoperative course was uneventful, and the patient was discharged on the 7th day postoperatively without complications. The patient had favorable outcome over a 1-year follow-up. LESSONS: Herein, we reported the case of a toddler with WS with splenic torsion. Moreover, after reviewing relevant studies in literature, we presented our findings on the diagnosis and treatment of toddlers with WS. Toddlers with WS are characterized by acute abdominal pain, unclear history description, examination restrictions, and high rates of life-threatening complications. High level of suspicion, careful physical examination, detailed history collection, and objective investigation are crucial in the management of toddlers with WS.


Assuntos
Esplenopatias/diagnóstico por imagem , Esplenopatias/etiologia , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/etiologia , Baço Flutuante/complicações , Baço Flutuante/diagnóstico por imagem , Abdome Agudo/etiologia , Pré-Escolar , Humanos , Masculino , Esplenectomia , Esplenopatias/cirurgia , Tomografia Computadorizada por Raios X , Anormalidade Torcional/cirurgia , Ultrassonografia , Vômito/etiologia
9.
J Craniofac Surg ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32969923

RESUMO

OBJECTIVE: Patients with classic trigeminal neuralgia (CTN) have abnormalities in white matter integrity of the corpus callosum (CC). However, in CTN patients, it is unclear whether the CC substructure region is affected to varying degrees. MATERIAL AND METHODS: A total of 22 patients with CTN and 22 healthy controls (HC) with matching age, gender, and education were selected. All subjects underwent 3.0 T magnetic resonance diffusion tensor imaging and high resolution T1-weighted imaging. The CC was reconstructed by DTI technology, which was divided into three substructure regions: genu, body, and splenium. Group differences in multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were compared between CTN patients and HC, and correlations between the white matter change and disease duration and VAS in CTN patients were assessed. RESULTS: Compared with HC group, CTN patients had extensive damage to the CC white matter. The FA of the genu (P = 0.04) and body (P = 001) parts decreased, while RD (P = 0.003; P = 0.02) and MD (P = 0.002; P = 0.04) increased. In addition, the authors observed that the disease duration and VAS of CTN patients were negatively correlated with FA. CONCLUSION: The corpus callosum substructure region has extensive damage in chronic pain, and the selective microstructural integrity damage was particularly manifested by changes in axons and myelin sheath in the genu and body of corpus callosum.

10.
Biomaterials ; 257: 120226, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32736256

RESUMO

The regeneration of smooth muscle with physiological functions has been a key challenge in vascular tissue engineering. Hyaluronan (HA), as a major component of the extracellular matrix, plays a vital role in regulating tissue injury and repair. In this study, a biomimetic vascular graft was prepared by co-electrospinning of synthetic degradable polymers and native ECM components including collagen type-I as well as low and high molecular weight HA (LMW HA and HMW HA). Upon implantation in the rat abdominal aorta, the grafts exhibited sustained HA release that effectively enhanced the regeneration of vascular smooth muscle. Besides, LMW HA loaded vascular grafts demonstrated rapid endothelialization compared to the other groups. More importantly, HA-loaded poly(L-lactide-co-caprolactone) grafts demonstrated an optimal vascular media layer accompanied by well-organized elastin fibers after long-term implantation (6 months), and they maintained potent physiological function up to 1/3 that of the native artery. In contrast, inadequate smooth muscle regeneration was observed in poly(ε-caprolactone) grafts due to slow degradation restricting the regeneration. The mechanism was further investigated and explained by the HA-induced migration of smooth muscle cell (SMC) via CD44-mediated signaling. Besides, low molecular weight HA can promote the migration of vascular progenitor cells that further differentiate into SMCs. These results highlight the importance of HA in the regeneration of functional vascular smooth muscle, and provide a new insight into the fabrication of tissue engineering vascular grafts (TEVGs) via combining rapidly degradable polymers and bioactive ECM components that hold great translational potential.

11.
J Cereb Blood Flow Metab ; : 271678X20948612, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787543

RESUMO

In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two critical systems contribute to post-CA outcome remains largely unknown. Using a mouse model of CA and cardiopulmonary resuscitation (CA/CPR), we demonstrate that CA/CPR induced neuroinflammation in the brain, in particular, a marked increase in pro-inflammatory cytokines, which subsequently activated the hypothalamic-pituitary-adrenal (HPA) axis. Importantly, this activation was associated with a severe immunosuppression phenotype after CA. The phenotype was characterized by a striking reduction in size of lymphoid organs accompanied by a massive loss of immune cells and reduced immune function of splenic lymphocytes. The mechanistic link between post-CA immunosuppression and the HPA axis was substantiated, as we discovered that glucocorticoid treatment, which mimics effects of the activated HPA axis, exacerbated post-CA immunosuppression, while RU486 treatment, which suppresses its effects, significantly mitigated lymphopenia and lymphoid organ atrophy and improved CA outcome. Taken together, targeting the HPA axis could be a viable immunomodulatory therapeutic to preserve immune homeostasis after CA/CPR and thus improve prognosis of post-resuscitation CA patients.

12.
Dalton Trans ; 49(32): 11192-11200, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32748922

RESUMO

Photodynamic therapy (PDT) has been widely used in conjunction with molecular oxygen to cause cancer cell death. Hypoxia, the inherent property in solid tumors, is the obstacle during the process of PDT. It is urgent to develop PDT photosensitizers independent of the oxygen concentration. Herein, triphenylamine-modified Ru(ii) complexes have been used as photosensitizers to produce superoxide anions (O2-˙) and hydroxyl radicals (˙OH) through a type I photochemical process. Ru(ii) complexes with triphenylamine can provide a possibility to drive the reactive oxygen species production through low oxidation potential and good light-harvesting abilities. The investigation on light-mediated radical production showed that Ru4 could produce abundant ˙OH and O2-˙ compared to Ru1-Ru3 under hypoxic environments owing to the strong absorption. These radicals exhibit potent toxicity, which can damage the neighbouring biomolecules and cause the apoptosis of cancer cells. The PDT effect was evaluated in vitro under hypoxia, suggesting that Ru4 could maintain excellent performance in inducing a sharp decrease in the activity of cancer cells.

13.
J BUON ; 25(3): 1430-1435, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32862586

RESUMO

PURPOSE: To explore the associations of computed tomography (CT) features with tumor-node-metastasis (TNM) stage and pathology of patients with rectal cancer and their significance in the evaluation of efficacy and prognosis. METHODS: A total of 83 rectal cancer patients who were operated in our hospital were collected. CT examination was performed before operation, and pathological examination was conducted after operation. The influence of CT stage on the prognosis of patients with rectal cancer was assessed. RESULTS: Postoperative pathological examination showed that there were 15 cases in T1-T2, 41 cases in T3 and 27 cases in T4. The results of CT examination showed that there were 15 cases in T1-T2, 40 cases in T3 and 28 cases in T4, and the sensitivity was 93.18%. It can be seen that the results in the two examinations were similar. The postoperative pathological examination revealed that lymph node metastasis occurred in 57 cases, and the main metastatic sites were the left and right pelvic cavity, near the intestine and iliac vessels. CT also confirmed that 22 cases had no lymph node metastasis, 4 of which were pathologically diagnosed with lymph node hyperplasia after operation. The consistency of results in the two examinations was lower. The survival rate of patients with stage A, B, C and D rectal cancer was 85.33%, 63.44%, 36.12% and 11.14%, respectively. CONCLUSIONS: CT scan plays an important role in the preoperative staging of rectal cancer, which is helpful for judging the tumor site and infiltration, and highly accurate for T1-T2 lesions, but has limitations for lymph node metastasis. CT scan also has great value for distant metastasis, and contributes to the development of clinical therapeutic regimens for patients with rectal cancer in different stages. CT stage has an influence on the prognosis and patient survival.

14.
J Thorac Dis ; 12(7): 3602-3610, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32802439

RESUMO

Background: Airway-gastric fistulas (AGFs) are rare but life-threatening complications after esophagectomy for esophageal cancer. Their effective and reasonable management is challenging and still controversial. This study reports the classification and management strategies of post-esophagectomy AGF based on a retrospective analysis of 26 cases in two large volume centers in China. Methods: Between January 2000 and December 2017, 6,316 consecutive patients with esophageal carcinoma underwent esophagectomy. AGF was verified in 26 patients. The patients with AGF were divided into two types based on the anatomic characteristics of the fistula. Type I was characterized by the presence of fistula orifices in digestive tract that were higher than those in the airway and were treated with conservative management. Type II had both fistula orifices located on the same horizontal plane and were treated with surgical management. Pearson Chi-Square (R software) was used to compare mortality rates. Results: From January 2000 and December 2017, 26 cases occurred AGF in 6,316 consecutive patients with esophageal carcinoma underwent esophagectomy and the incidence of AGF was 0.4%. Ten of 12 patients with type I AGF survived. Nine of 14 patients with type II AGF died. There was a significantly difference in the mortality rates between patients with AGF type I and II, which was 16.7% (2/12) and 64.3% (9/14) (χ2=6.003, P=0.014), respectively. Conclusions: AGF may be classified into two types according to the anatomic characteristics. Type I patients may be cured by conservative management and type II patients, require surgical intervention with pedicled tissues flap wrapping of the airway.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32840291

RESUMO

Skin epidermal stem cells (EpSCs) play an important role in wound healing. Quercetin is a phytoestrogen reported to accelerate skin wound healing, but its effect on EpSCs is unknown. In this study, we investigated the effect of quercetin on human EpSC proliferation and explored the underlying mechanisms. We found that quercetin at 0.1~1 µM significantly promoted EpSC proliferation and increased the number of cells in S phase. The pro-proliferative effect of quercetin on EpSCs was confirmed in cultured human skin tissue. Mechanistic studies showed that quercetin significantly upregulated the expressions of ß-catenin, c-Myc, and cyclins A2 and E1. Inhibitor for ß-catenin or c-Myc significantly inhibited quercetin-induced EpSC proliferation. The ß-catenin inhibitor XAV-939 suppressed quercetin-induced expressions of ß-catenin, c-Myc, and cyclins A2 and E1. The c-Myc inhibitor 10058-F4 inhibited the upregulation of c-Myc and cyclin A2 by quercetin. Pretreatment of EpSCs with estrogen receptor (ER) antagonist ICI182780, but not the G protein-coupled ER1 antagonist G15, reversed quercetin-induced cell proliferation and upregulation of ß-catenin, c-Myc, and cyclin A2. Collectively, these results indicate that quercetin promotes EpSC proliferation through ER-mediated activation of ß-catenin/c-Myc/cyclinA2 signaling pathway and ER-independent upregulation of cyclin E1 and that quercetin may accelerate skin wound healing through promoting EpSC proliferation. As EpSCs are used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering, quercetin is a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering.

16.
Food Chem ; 338: 127820, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32827899

RESUMO

Lactoferrin (LF), a bioactive multifunctional protein of the transferrin family, is found mainly in the secretions of all mammals, especially in milk. In the present study, a hybridoma cell (LF8) secreting IgG against bovine LF was screened, and the purified LF8 mAb showed high specificity and affinity to bovine LF. The linear range of ic-ELISA to detect LF was 9.76 ~ 625 ng/mL, with a limit of detection (LOD) of 0.01 ng/mL. The average recovery of intra- and inter-assay were (104.45 ± 4.12)% and (107.13 ± 4.72)%, respectively. The LOD of colloidal gold- and AuNFs-based strip by naked eye were 9.7 and 2.4 ng/mL, respectively, and the detection time was less than 10 min without any samples pretreatment and expensive equipment. The developed ELISA and lateral flow immunosensors based on specific IgG could be used directly for rapid detection of the bovine LF content in cow milk samples.

17.
Mediators Inflamm ; 2020: 4694090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733165

RESUMO

Background: The aim of our study was to investigate whether serum cholinesterase (ChE) levels were associated with inflammatory bowel disease (IBD). Materials and Methods: We conducted a retrospective case-control study to clarify the relationship between serum ChE levels and IBD that included 142 patients with ulcerative colitis (UC), 60 patients with Crohn's disease (CD), and 264 healthy controls (HCs). We used ROC curves to evaluate the diagnostic value of serum ChE levels for IBD. Results: Substantially lower serum ChE levels were detected in patients with UC than in HCs (6376 U/L versus 8418 U/L, P < 0.001) and in patients with CD than in HCs (5181 U/L versus 8418 U/L, P < 0.001). Additionally, patients with CD displayed significantly lower serum ChE levels than patients with UC (5181 U/L versus 6376 U/L, P < 0.01). We also found that there was a negative association between serum ChE levels and the Crohn's Disease Activity Index (CDAI) score of patients with CD (P = 0.011) and the Simple Clinical Colitis Activity Index (SCCAI) score of patients with UC (P = 0.018). The area under the curve (AUC) for serum ChE for the diagnosis of IBD was 0.826, and the AUCs of serum ChE for the diagnosis of CD and UC were 0.890 and 0.800, respectively. Conclusions: Serum ChE levels have important clinical significance in the diagnosis and assessment of clinical activity in patients with IBD, and the cholinergic anti-inflammatory pathway may provide new ideas for targeted treatment of IBD.

18.
Biosens Bioelectron ; 167: 112478, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810704

RESUMO

Aptamer electrochemical sensors using immobilized aptamers with redox tag rely on the target binding-induced changes of current signal on electrode, offering advantages in operation convenience, no separation, rapidity, and sensitivity. Usually, the redox tag is placed on aptamer terminal, however, sometimes the terminal label may be insensitive to target-binding and fail to generate sensitive responses. The redox tag methylene blue (MB) labeled on different sites of aptamer may experience distinct changes in local environment, distance to electrode, or interactions with aptamer bases during affinity binding, which affect the current signal. Thus, it is possible to construct aptamer electrochemical sensors with sensitive and significant responses to targets by screening a series of sites (e.g., internal thymine T) of the aptamer and placing MB tag on a specific site of the aptamer. With this strategy, we successfully fabricated an electrochemical sensor on gold electrode for rapid, reagentless, and sensitive detection of aflatoxin B1 (AFB1), an important mycotoxin causing great health risks, by using a 26-mer DNA aptamer with MB on an internal T site (e.g., 18th T) and a thiol moiety at 5' terminal. This sensor generated remarkable signal-on responses to AFB1, allowed a detection limit of 6 pM, and enabled detection of AFB1 in wine, milk and corn flour samples. This sensor can be well regenerated by rinsing with deionized water and reused, and shows good stability. This sensor and the demonstrated strategy are promising in wide applications.

19.
ACS Appl Mater Interfaces ; 12(38): 43073-43082, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32851841

RESUMO

Using temporal dimension in optical multiplexing is a promising method to increase the security of data encryption. However, adjusting the fluorescence lifetime of light-emitting material often results in inevitable changes in their fluorescence spectra, which is unfavorable for confidential information protection. Here, we report the preparation of various perovskite quantum dot/polymer nanospheres (PQD/polymer) with tunable and long fluorescence lifetimes but identical fluorescence spectra, which are ideal multidimensional data encryption materials. This new data encryption strategy utilizes the water sensitivity of perovskite and achieves spatial dimension encryption of information using different water stabilities between uncoated perovskite quantum dots and PQD/polymer. The fluorescence lifetime of PQD/polymer is used as the coding element to achieve temporal dimension data encryption, and the data are decrypted by fluorescence lifetime imaging microscopy and time-gated luminescence imaging techniques. This study shows the potential of PQD/polymer as a new class of materials for advanced data encryption.

20.
J Am Soc Nephrol ; 31(10): 2292-2311, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32769144

RESUMO

BACKGROUND: Progressive fibrosis is the underlying pathophysiological process of CKD, and targeted prevention or reversal of the profibrotic cell phenotype is an important goal in developing therapeutics for CKD. Nanoparticles offer new ways to deliver antifibrotic therapies to damaged tissues and resident cells to limit manifestation of the profibrotic phenotype. METHODS: We focused on delivering plasmid DNA expressing bone morphogenetic protein 7 (BMP7) or hepatocyte growth factor (HGF)-NK1 (HGF/NK1) by encapsulation within chitosan nanoparticles coated with hyaluronan, to safely administer multifunctional nanoparticles containing the plasmid DNA to the kidneys for localized and sustained expression of antifibrotic factors. We characterized and evaluated nanoparticles in vitro for biocompatibility and antifibrotic function. To assess antifibrotic activity in vivo, we used noninvasive delivery to unilateral ureteral obstruction mouse models of CKD. RESULTS: Synthesis of hyaluronan-coated chitosan nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI resulted in consistently sized nanoparticles, which-following endocytosis driven by CD44+ cells-promoted cellular growth and inhibited fibrotic gene expression in vitro. Intravenous tail injection of these nanoparticles resulted in approximately 40%-45% of gene uptake in kidneys in vivo. The nanoparticles attenuated the development of fibrosis and rescued renal function in unilateral ureteral obstruction mouse models of CKD. Gene delivery of BMP7 reversed the progression of fibrosis and regenerated tubules, whereas delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition. CONCLUSIONS: Nanoparticle delivery of HGF/NK1 conveyed potent antifibrotic and proregenerative effects. Overall, this research provided the proof of concept on which to base future investigations for enhanced targeting and transfection of therapeutic genes to kidney tissues, and an avenue toward treatment of CKD.

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