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1.
World J Clin Cases ; 9(26): 7909-7916, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34621845

RESUMO

BACKGROUND: Syphilis is a chronic, classic sexually transmitted disease caused by Treponema pallidum, which can invade almost all organs of the body and produce various symptoms and signs. Although there are some cases of colorectal bleeding caused by syphilis, small intestinal bleeding caused by syphilis is still rare. CASE SUMMARY: A 58-year-old man had experienced recurrent abdominal pain and melena for 3 years. Repeated gastroenteroscopy and computed tomography angiography examinations failed to find bleeding lesions. During the same admission, multiple intestinal ulcers were found by capsule endoscopy, and syphilis was also diagnosed. With a history of atrial fibrillation and chronic pancreatitis, he had undergone mitral valve replacement and tricuspid valvuloplasty for valvular heart disease. After anti-syphilis treatment, the melena and abdominal pain disappeared and his hemoglobin gradually increased. It is considered that gastrointestinal bleeding, chronic pancreatitis, atrial fibrillation, and heart valvular disease may have been caused by syphilis. CONCLUSION: This case report found that syphilis can mimic systemic disease and cause intestinal bleeding. In addition, treatment of the disease requires both sexual partners to be treated. Finally, although syphilis is easy to treat, it is more important to consider that bleeding could be caused by syphilis.

2.
Medicine (Baltimore) ; 100(40): e27491, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622882

RESUMO

ABSTRACT: Since lung nodules on computed tomography images can have different shapes, contours, textures or locations and may be attached to neighboring blood vessels or pleural surfaces, accurate segmentation is still challenging. In this study, we propose an accurate segmentation method based on an improved U-Net convolutional network for different types of lung nodules on computed tomography images.The first phase is to segment lung parenchyma and correct the lung contour by applying α-hull algorithm. The second phase is to extract image pairs of patches containing lung nodules in the center and the corresponding ground truth and build an improved U-Net network with introduction of batch normalization.A large number of experiments manifest that segmentation performance of Dice loss has superior results than mean square error and Binary_crossentropy loss. The α-hull algorithm and batch normalization can improve the segmentation performance effectively. Our best result for Dice similar coefficient (0.8623) is also more competitive than other state-of-the-art segmentation algorithms.In order to segment different types of lung nodules accurately, we propose an improved U-Net network, which can improve the segmentation accuracy effectively. Moreover, this work also has practical value in helping radiologists segment lung nodules and diagnose lung cancer.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Redes Neurais de Computação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Humanos , Pulmão/patologia
3.
Oncoimmunology ; 10(1): 1971418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616588

RESUMO

Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m2] plus docetaxel [25 mg/m2] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9-24.5), OS and PFS time ranged from 8.2-28.5 and 4.0-28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c+ dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Docetaxel/uso terapêutico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Humanos , Qualidade de Vida
4.
Food Chem ; 372: 131249, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34634587

RESUMO

Nowadays, computational approaches have drawn more and more attention when exploring the relationship between sweetness and chemical structure instead of traditional experimental tests. In this work, we proposed a novel multi-layer sweetness evaluation system based on machine learning methods. It can be used to evaluate sweet properties of compounds with different chemical spaces and categories, including natural, artificial, carbohydrate, non-carbohydrate, nutritive and non-nutritive ones, suitable for different application scenarios. Furthermore, it provided quantitative predictions of sweetness. In addition, sweetness-related chemical basis and structure transforming rules were obtained by using molecular cloud and matched molecular pair analysis (MMPA) methods. This work systematically improved the data quality, explored the best machine learning algorithm and molecular characterizing strategy, and finally obtained robust models to establish a multi-layer prediction system (available at: https://github.com/ifyoungnet/ChemSweet). We hope that this study could facilitate food scientists with efficient screening and precise development of high-quality sweeteners.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34603476

RESUMO

Background: Cancer has been considered as the leading cause of death in the world. In patients with cancer, up to 80% display a cachectic period after diagnosis. Cachexia is known to have a negative impact on function, treatment tolerance, higher rates of hospitalizations, and mortality. Anorexia is often used as a warning sign of precachexia. Long-term anorexia may lead to malnutrition and, then, accelerate the occurrence of cachexia. A safe and effective treatment, which can both improve appetite and assist nutritional support for precachexia cancer patients shows its particular important role. Methods: A retrospective analysis comparing the different therapeutic effects on precachexia cancer patients with anorexia-malnutrition. We recorded 46 patients with the improved-Sijunzi decoction combined with enteral nutrition emulsion (ISJZ group) and 35 patients with single enteral nutrition emulsion (SEN group). The different therapeutic effects of the two groups were observed by recording indicators before and 2 weeks after treatment, including patient-generated subjective global assessment score, quality of life score, Karnofsky performance status scale, Eastern cooperative oncology group scale standard and traditional Chinese medicine syndrome, daily total dietary intake, red blood cells, hemoglobin, prealbumin, albumin, total protein cholinesterase, C-reactive protein, leukocytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea nitrogen, and creatinine. Results: ISJZ group exhibited prominent improvement of traditional Chinese medicine syndrome (TCMS), nutritional condition, and quality of life compared with the SEN group (QOL: p=0.0001, PG-SGA: p=0.019, dietary intake: p=0.0001, TCMS: p=0.0001). The levels of HGB (p=0.006), PAlb (p=0.001), Alb (p=0.0001), TP (p=0.008), and ChE (p=0.0001) in the ISJZ group were higher than the SEN group after treatment. Moreover, the ratios of CRP/ALB (p=0.028) and CRP/PALB (p=0.005) in the two groups have obvious differences; they were lower for the ISJZ group than the SEN group. Conclusions: Enteral nutrition combined with ISJZ decoction is an effective treatment in precachexia cancer patients for the prevention of cachexia. This treatment therapy can alleviate the inflammatory response, improve malnutrition state, and promote the performance status. Tianjin Medical University Cancer Institute and Hospital approved this study (Trial No. 1913).

6.
Anal Methods ; 13(38): 4361-4369, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494633

RESUMO

Colorimetric tests for at-home health monitoring became popular 50 years ago with the advent of the urinalysis test strips, due to their reduced costs, practicality, and ease of operation. However, developing digital systems that can interface these sensors in an efficient manner remains a challenge. Efforts have been put towards the development of portable optical readout systems, such as smartphones. However, their use in daily settings is still limited by their error-prone nature associated to optical noise from the ambient lighting, and their low sensitivity. Here, a smartphone application (Colourine) to readout colorimetric signals was developed on Android OS and tested on commercial urinalysis test strips for pH, proteins, and glucose detection. The novelty of this approach includes two features: a pre-calibration step where the user is asked to take a photo of the commercial reference chart, and a CIE-RGB-to-HSV color space transformation of the acquired data. These two elements allow the background noise given by environmental lighting to be minimized. The sensors were characterized in the ambient light range 100-400 lx, yielding a reliable output. Readouts were taken from urine strips in buffer solutions of pH (5.0-9.0 units), proteins (0-500 mg dL-1) and glucose (0-1000 mg dL-1), yielding a limit of detection (LOD) of 0.13 units (pH), 7.5 mg dL-1 (proteins) and 22 mg dL-1 (glucose), resulting in an average LOD decrease by about 2.8 fold compared to the visual method.

7.
J Obstet Gynaecol ; : 1-6, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569426

RESUMO

The aim of our study was to compare the efficacy of two dosages of hepatitis B immunoglobulin (HBIG) combined with HBV vaccine (HBVac) to prevent mother-to-child transmission (MTCT) of hepatitis B in HBsAg- and HBeAg-positive mother. We enrolled 331 mother-infant pairs with HBsAg- and HBeAg-positive maternal state from the Women's Hospital School of Medicine of Zhejiang University. Newborns were randomly distributed into two groups according to the dosages of HBIG injection: 100 IU and 200 IU. Newborns from both groups were injected with HBVac in the same doses. We compared the immune outcomes between the two groups and explore the influencing factors of immune outcomes through regression analysis. There was no statistically significant relationship between HBsAg serological transmission of newborns and dosages of HBIG in HBsAg- and HBeAg-positive mother (p > .05). The Logistic regression showed that high DNA load is a risk factor for passive-active immunoprophylaxis failure for both 100 IU and 200 IU group, but higher-dosage HBIG is not necessary for higher-viral-load pregnant women with HBsAg- and HBeAg-positive. In conclusion, combined application of HBVac and a single dose of 100 IU HBIG can achieve the ideal MTCT interruption results for HBsAg- and HBeAg-positive pregnant women.IMPACT STATEMENTWhat is already known on this subject? Passive-active immunoprophylaxis is proved to be effective in preventing mother-to-child transmission of hepatitis B. Hepatitis B vaccine combined with 100 IU or 200 IU immunoglobulin is mostly recommended in China.What do the results of this study add? At present, there is still a lack scientific basis for improving existing strategies and measures to prevent mother-to-child transmission of hepatitis B in China.What are the implications of these findings for clinical practice and/or further research? 100 IU and 200 IU immunoglobulin show equivalent blocking effect, and combined use of hepatitis B vaccine and 100 IU immunoglobulin is more cost-effective.

8.
BMJ Open ; 11(9): e047957, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561257

RESUMO

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) is recognised as a suitable prognostic biomarker in patients with breast cancer. Nevertheless, the efficacy of this biomarker in predicting the pathological complete response (pCR) and survival in patients with breast cancer receiving neoadjuvant chemotherapy (NACT) is still controversial. This meta-analysis aimed to identify the association between baseline NLR and the prognosis of patients with breast cancer treated with NACT. DESIGN: Meta-analysis. DATA SOURCES: Relevant literature published before 1 May 2021 was searched using the Cochrane Library, Embase, PubMed and the Web of Science databases. ELIGIBILITY CRITERIA: All studies involving patients with breast cancer treated with NACT and peripheral blood pretreatment NLR recorded as a dichotomous variable were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted and evaluated OR/HR and its 95% CIs of survival outcomes and clinicopathological parameters. RESULTS: A total of 19 studies were identified. From each study, the impact of NLR on the pCR, OR and HR, with their 95% CIs were extracted and combined using either a random or fixed-effects model. The results indicate that a higher pCR in patients with a low NLR (OR 1.620, 95% CI 1.209 to 2.169, p<0.001). In addition, an elevated NLR predicted lower disease-free survival (HR 2.269, 95% CI 1.557 to 3.307, p<0.001) and overall survival (HR 1.691, 95% CI 1.365 to 2.096, p<0.001) in patients with breast cancer treated with NACT. CONCLUSIONS: NLR is a suitable biomarker for predicting pCR and survival in patients with breast cancer receiving NACT.

9.
Nanoscale ; 13(29): 12466-12474, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477611

RESUMO

The development of optical materials with room temperature phosphorescence (RTP) and white light emission (WLEDs) is highly desirable and remains a challenging task. Herein, a porous metal-organic framework PCN-921 with a high quantum yield (ΦF = 93.6%) was achieved. To make full use of the advantages of the high porosity of PCN-921, we hierarchically encapsulated different guest molecules coronene and rhodamine B (RhB) into the framework. Unsurprisingly, the hybrid material coronene@PCN-921 was obtained after in situ encapsulation of the guest coronene into the framework, and it exhibits obvious RTP behavior with a long phosphorescence lifetime of 62.5 ns. Subsequently, second guest RhB molecules were introduced after soaking in RhB solution and the material RhB@coronene@PCN-921 was achieved. Interestingly, it exhibits white light emission with the CIE coordinates of (0.29, 0.34), and can be used as a high performance WLED lamp. This is the first work on dual-functional hybrid dyes@MOFs with hierarchical guest encapsulation for RTP and white light emission, which suggests the potential applications of MOFs in multifunctional optical devices.

10.
Cell Oncol (Dordr) ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491549

RESUMO

PURPOSE: Treatment-associated upregulation of suppressive checkpoints and a lack of costimulatory signals compromise the antitumor efficacy of oncolytic virus immunotherapy. Therefore, we aimed to identify highly effective therapeutic targets to provide a proof-of-principle for immune checkpoint together with oncolytic virus-mediated viro-immunotherapy for cancer. METHODS: A fusion protein containing both the extracellular domain of programmed death-1 (PD-1) and the poliovirus receptor (PVR) was designed. Next, the corresponding expression fragment was inserted into the genome of a replication-competent adenovirus to generate Ad5sPD1PVR. The infection, expression, replication and oncolysis of Ad5sPD1PVR were investigated in hepatocellular carcinoma (HCC) cell lines. Immune activation and the antitumor efficacy of Ad5sPD1PVR were examined in HCC tumor models including a humanized immunocompetent mouse model. RESULTS: Ad5sPD1PVR effectively infected and replicated in HCC cells and secreted sPD1PVR. In a H22 ascitic HCC mouse model, intraperitoneal injection of Ad5sPD1PVR markedly recruited lymphocytes and activated antitumor immune responses. Ad5sPD1PVR exerted a profound antitumor effect on ascitic HCC. Furthermore, we found that Ad5sPD1PVR-H expressing sPD1PVR of human origin exhibited potent antitumor effects in a HCC humanized mouse model. We also found that CD8+ T cells mediated the antitumor effects and long-term tumor-specific immune surveillance induced by Ad5sPD1PVR. Finally, when combined with fludarabine, the antitumor efficacy of Ad5sPD1PVR was found to be further improved in the ascitic HCC model. CONCLUSIONS: From our data we conclude that the newly designed recombinant Ad5sPD1PVR virus significantly enhances CD8+ T cell-mediated antitumor efficacy with long-term tumor-specific immune surveillance in hepatocellular carcinoma, and that fludarabine is a promising therapeutic partner for Ad5sPD1PVR.

11.
J Mater Chem B ; 9(36): 7447-7460, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551057

RESUMO

Nowadays, cancer is one of the most serious diseases threatening the health of human beings, and imaging-guided photothermal therapy (PTT) is rapidly emerging as a potent oncotherapy strategy due to its unique advantages of high efficiency, noninvasiveness, visualization, and accuracy. In this study, a multifunctional nanoplatform based on gadolinium ion chelated natural anthocyanins (ACNs) is reported, which can be used not only as an excellent photoacoustic/magnetic resonance (PA/MR) dual-modal contrast agent but also for imaging-guided tumor PTT. The nanoparticles obtained have a suitable size, good dispersity, and physiological stability. The excellent biocompatibility and remarkable photothermal effect of the nanoparticles in vitro were demonstrated by CCK-8 assays and co-staining experiments. Moreover, the magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) results obtained in vivo showed that the nanoparticles were ideal dual-modal contrast agents whether given by intravenous or intratumoral injection. After intratumoral injection, the dual-modal PAI/MRI was used for determining the maximum diffusion time of the probe in the tumor site to guide laser treatment, achieving complete tumor elimination without normal tissue injury. Importantly, ACN is a natural compound extracted from black carrots, possessing native biocompatibility and biodegradability, which was further proved by the results of the detailed safety evaluation. Overall, the as-prepared nanoparticles displayed significant tumor diagnosis and treatment effects while mitigating biosafety concerns, and thus this was found to be a promising nanotherapeutic method for cancer treatment.

12.
Dis Markers ; 2021: 5647933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512814

RESUMO

Background: Xp11.2 translocation renal cell carcinoma, a rare malignancy, has a higher prevalence in children than in adults. It is relatively indolent in children but manifests with an aggressive course in adults. Clinical characteristics and prognostic studies for adult patients are scarce due to its rarity. Methods: This retrospective single-center study consecutively enrolled 24 newly diagnosed Xp11.2 translocation RCC adult patients. Clinical presentations were recorded, and baseline laboratory results and follow-up data were collected. Possible risk factors for progression-free survival and overall survival were first scanned with chi-square tests and t-tests to compare patients who suffered from progression or death with who did not. Multivariate Cox regression was further utilized to identify independent risk factors. Results: Twenty-four adult patients (median age 32, range 16-73), with a male-to-female ratio of 1 : 1, was included from April 2010 to March 2020. After follow-up for 35.7 months (+/- months), seven patients died. With univariate analysis, higher C-reactive protein-to-albumin (CRP/Alb) ratio (p = 0.028), higher baseline fibrinogen (p = 0.006), and presence of distant metastasis (p = 0.007) were associated with progression of the disease; higher preoperative fibrinogen (p = 0.014) and distant metastasis (p = 0.020) were associated with death. With multivariate Cox regression, only baseline fibrinogen level (p = 0.001) was identified as an independent risk factor for progression-free survival; meanwhile, fibrinogen level (p = 0.048) and distant metastasis (p = 0.043) were identified as independent risk factors for survival. Conclusions: Overall, relatively high CRP/Alb ratios, fibrinogen, and distant metastasis were associated with a poor prognosis of Xp11.2 tRCC adult patients; among them, only baseline fibrinogen levels independently predicted the progression of Xp11.2 tRCC; thus, it may help to identify patients with worse progression or death risk.

13.
ACS Appl Mater Interfaces ; 13(36): 43323-43332, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469683

RESUMO

Conductive ionic hydrogel fibers and textiles with excellent mechanical properties and chemical stability are requested for flexible and wearable electronic devices, strain sensors, and even artificial skin. However, most of the reported hydrogel fibers are not suitable in complex environments, especially in alkaline solutions and organic solvents due to their poor chemical stability. Herein, we report ionic polyimide hydrogel fibers derived from an organosoluble polyimide salt that can be continuously and rapidly prepared via a facile wet spinning method. Thanks to their ion-rich property and robust skeletal structure, the obtained ionic polyimide hydrogel fibers showed an excellent conductivity of ∼21 mS/cm and outstanding mechanical properties with a tensile strength of 2.5 MPa and breaking elongation of 215%. Furthermore, the as-prepared fibers could be easily woven to form integral textiles, endowing them with good wearable properties. Accordingly, facile strain sensors assembled by polyimide hydrogel fibers show a linear response with high sensitivity and good cycling stability, which have great potential for applications in wearable and flexible strain sensors under diverse complex environments.

14.
PLoS Pathog ; 17(9): e1009901, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34506605

RESUMO

Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.

15.
J Immunol ; 207(5): 1411-1418, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34348973

RESUMO

The receptor for activated C kinase 1 (RACK1) adaptor protein has been implicated in viral infection. However, whether RACK1 promotes in vivo viral infection in mammals remains unknown. Moreover, it remains elusive how RACK1 is engaged in antiviral innate immune signaling. In this study, we report that myeloid RACK1 deficiency does not affect the development and survival of myeloid cells under resting conditions but renders mice less susceptible to viral infection. RACK1-deficient macrophages produce more IFN-α and IFN-ß in response to both RNA and DNA virus infection. In line with this, RACK1 suppresses transcriptional activation of type 1 IFN gene promoters in response to virus infection. Analysis of virus-mediated signaling indicates that RACK1 inhibits the phosphorylation of IRF3/7. Indeed, RACK1 interacts with IRF3/7, which is enhanced after virus infection. Further exploration indicates that virus infection triggers AMPK activation, which in turn phosphorylates RACK1 at Thr50 RACK1 phosphorylation at Thr50 enhances its interaction with IRF3/7 and thereby limits IRF3/7 phosphorylation. Thus, our results confirm that myeloid RACK1 promotes in vivo viral infection and provide insight into the control of type 1 IFN production in response to virus infection.


Assuntos
Proteínas Quinases Ativadas por AMP , Fator Regulador 3 de Interferon , Proteínas Adaptadoras de Transdução de Sinal , Animais , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/metabolismo , Camundongos , Fosforilação , Receptores de Quinase C Ativada , Transdução de Sinais
16.
Int J Pharm ; 607: 120962, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34339812

RESUMO

Drug-excipient compatibility study is the essential basis for excipient selection at the pre-formulation stage. According to the pharmaceutical Quality by Design (QbD) principles, a comprehensive understanding of the ingredients' physicochemical properties and a theoretical evaluation of the interaction risk between the drugs and excipients are required for conducting rational compatibility experimental design. Currently, there is an urgent need to establish an artificial intelligence system for researchers to easily get through the problem because it is very inconvenient and hard to utilize those drug-excipient incompatibility data scattered in scientific literature. Here, we designed a knowledge-driven expert system named PharmDE for drug-excipient incompatibility risk evaluation. PharmDE firstly developed an information-rich database to store incompatibility data, covering 532 data items from 228 selected articles. Then, 60 drug-excipient interaction rules were created based on our knowledge and formulation research experiences. Finally, the expert system was developed by organically integrating the database searching and rule-based incompatibility risk prediction, which resulted in four main functionalities: basic search of incompatibility database, data matching by similarity search, drug incompatibility risk evaluation, and formulation incompatibility risk evaluation. PharmDE is expected to be a useful tool for drug-excipient compatibility study and accelerate drug formulation design. It is now freely available at https://pharmde.computpharm.org.


Assuntos
Química Farmacêutica , Excipientes , Inteligência Artificial , Estabilidade de Medicamentos , Sistemas Especialistas
17.
J Reprod Immunol ; 147: 103360, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34390899

RESUMO

Preterm birth (PTB) is considered to be one of the most frequent causes of neonatal death. Prompt and effective measures to predict adverse fetal outcome following PTB are urgently needed. Placenta macrophages are a critical immune cell population during pregnancy, phenotypically divided into M1 and M2 subsets. An established mouse model of intrauterine inflammation (IUI) was applied. Placenta (labyrinth) and corresponding fetal brain were harvested within 24 hours post injection (hpi). Flow cytometry, Western blot, real-time qPCR, and regular histology were utilized to examine the cytokines, macrophage polarization, and sex-specificity. Placental exposure to LPS led to significantly reduced labyrinth thickness compared to PBS-exposed controls as early as 3 hpi, accompanied by apoptosis and necrosis. Pro-inflammatory M1 markers, Il-1ß, and iNOS, and anti-inflammatory M2 marker Il-10 increased significantly in placentas exposed to IUI. Analysis of flow cytometry revealed that fetal macrophages (Hofbauer cell, HBCs) were mostly M1-like and that maternal inter-labyrinth macrophages (MIM) were M2-like in their features in IUI. Male fetuses displayed significantly decreased M2-like features in HBCs at 3 and 6 hpi, while female fetuses showed significant increase in M2-like features in MIM at 3 and 6 hpi. Furthermore, there was a significant correlation between the frequency of HBCs and corresponding microglial marker expression at 3 and 6 hpi. Placental macrophages demonstrated sex-specific features in response to IUI. Specifically, HBCs may be a potential biomarker for fetal brain injury at preterm birth.

18.
Placenta ; 114: 29-38, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34418752

RESUMO

INTRODUCTION: Children conceived by assisted reproductive technologies have a high risk of suffering from obstetrical complications and long-term health problems, but the related mechanisms are not fully understood. Normal placental function is closely linked with foetal growth and future health. Given the significance of glycogen metabolism in placentas, we investigated the effect of in vitro fertilization (IVF) on glycogen storage in placentas using a mouse model. METHODS: Mouse placentas were collected at E18.5 after natural mating or IVF, and the placental and foetal weights were recorded. The quantitative assay kit and histological staining were used to measure the glycogen content. Additionally, we detected the expression of multiple genes associated with glycogen synthesis/decomposition, glucose transporters, and the phosphorylation of Akt and Gsk3ß. RESULTS: Our findings showed that IVF resulted in a significantly increased mouse placental weight and enlarged junctional area. We found, compared to the control, excessive glycogen was accumulated in IVF placentas. However, we observed that multiple genes involved in glycogen generation (Gsk3b, Phka1, Phkb, Phkg1, and Phkg2) and glycogenolysis (Agl and Pygm) had lower mRNA levels in IVF placentas. Moreover, the expression levels of glycogen synthase, phosphorylase, Glut1, and Glut3 were significantly decreased in IVF placentas. The phosphorylation activities of Akt Ser473 and Gsk3ß Ser9 were inhibited in IVF placentas. DISCUSSION: IVF leads to enlarged mouse placentas with excessive glycogen storage in late pregnancy, and these abnormal changes may be associated with the activation of the Akt-Gsk3ß pathway.

19.
Sci Rep ; 11(1): 17170, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446747

RESUMO

The present study aimed to construct and evaluate a novel experiment-based hypoxia signature to help evaluations of GBM patient status. First, the 426 proteins, which were previously found to be differentially expressed between normal and hypoxia groups in glioblastoma cells with statistical significance, were converted into the corresponding genes, among which 212 genes were found annotated in TCGA. Second, after evaluated by single-variable Cox analysis, 19 different expressed genes (DEGs) with prognostic value were identified. Based on λ value by LASSO, a gene-based survival risk score model, named RiskScore, was built by 7 genes with LASSO coefficient, which were FKBP2, GLO1, IGFBP5, NSUN5, RBMX, TAGLN2 and UBE2V2. Kaplan-Meier (K-M) survival curve analysis and the area under the curve (AUC) were plotted to further estimate the efficacy of this risk score model. Furthermore, the survival curve analysis was also plotted based on the subtypes of age, IDH, radiotherapy and chemotherapy. Meanwhile, immune infiltration, GSVA, GSEA and chemo drug sensitivity of this risk score model were evaluated. Third, the 7 genes expression were evaluated by AUC, overall survival (OS) and IDH subtype in datasets, importantly, also experimentally verified in GBM cell lines exposed to hypoxic or normal oxygen condition, which showed significant higher expression in hypoxia than in normal group. Last, combing the hypoxia RiskScore with clinical and molecular features, a prognostic composite nomogram was generated, showing the good sensitivity and specificity by AUC and OS. Meanwhile, univariate analysis and multivariate analysis were used for performed to identify variables in nomogram that were significant in independently predicting duration of survival. It is a first time that we successfully established and validated an independent prognostic risk model based on hypoxia microenvironment from glioblastoma cells and public database. The 7 key genes may provide potential directions for future biochemical and pharmaco-therapeutic research.

20.
Science ; 373(6557): 918-922, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34413236

RESUMO

Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare, heterozygous single-nucleotide variants in the MX1 gene. MX1 codes for myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase known to control IAV infections in transgenic mice. Most of the MxA variants identified lost the ability to inhibit avian IAVs, including H7N9, in transfected human cell lines. Nearly all of the inactive MxA variants exerted a dominant-negative effect on the antiviral function of wild-type MxA, suggesting an MxA null phenotype in heterozygous carriers. Our study provides genetic evidence for a crucial role of the MX1-based antiviral defense in controlling zoonotic IAV infections in humans.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/genética , Influenza Humana/virologia , Proteínas de Resistência a Myxovirus/genética , Doenças dos Trabalhadores Agrícolas/genética , Doenças dos Trabalhadores Agrícolas/virologia , Animais , Linhagem Celular , Predisposição Genética para Doença , Variação Genética , Heterozigoto , Humanos , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Vírus da Influenza A/fisiologia , Mutação de Sentido Incorreto , Proteínas de Resistência a Myxovirus/química , Proteínas de Resistência a Myxovirus/metabolismo , Aves Domésticas , Zoonoses Virais , Sequenciamento Completo do Genoma
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