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1.
Biol Trace Elem Res ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34993909

RESUMO

Preeclampsia (PE) is a pregnancy-specific disorder, which is one of the leading causes of maternal, fetal, and neonatal death, particularly in developing countries. Arsenic (As), which is commonly found in soil and groundwater, has been associated with various complications of pregnancy, such as spontaneous abortion, hypertension, and stillbirth. Hence, the study was used to explore the relationship between PE and blood concentration of As in this study. Blood concentration of As during pregnancy was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results shown that the mean blood concentration of As was gradually increased from the control group to the severe PE group (P < 0.0001). Elevated blood concentration of As was associated with the prevalence of PE (OR = 12.81, 95% CI: 2.43-67.39 and 27.55, 1.75-433.43 for middle and high vs. low). Furthermore, elevated blood concentration of As was associated with the severity of PE. Additionally, we observed that blood concentration of As was associated with the hypoproteinemia (P = 0.001, rs = 0.37). Blood concentration of As was negatively corelated with the mean corpuscular volume (MCV) (P = 0.040, rs = - 0.23) and positively corelated with the mean corpuscular hemoglobin concentration (MCHC) (P = 0.044, rs = 0.23). Overall, our results indicated that the blood concentration of As can significantly predict the occurrence of PE. Additionally, we provided evidence that blood concentration of As may affect the occurrence of hypoproteinemia. These findings may provide some ideas for the prevention of PE and pregnancy complications.

2.
J Biomed Inform ; : 103984, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007754

RESUMO

OBJECTIVE: Social determinants of health (SDOH) are non-medical factors that can profoundly impact patient health outcomes. However, SDOH are rarely available in structured electronic health record (EHR) data such as diagnosis codes, and more commonly found in unstructured narrative clinical notes. Hence, identifying social context from unstructured EHR data has become increasingly important. Yet, previous work on using natural language processing to automate extraction of SDOH from text (a) usually focuses on an ad hoc selection of SDOH, and (b) does not use the latest advances in deep learning. Our objective was to advance automatic extraction of SDOH from clinical text by (a) systematically creating a set of SDOH based on standard biomedical and psychiatric ontologies, and (b) training state-of-the-art deep neural networks to extract mentions of these SDOH from clinical notes. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC-III) database. The corpus comprised 3,504 social related sentences from 2,670 clinical notes. METHODS: We developed a framework for automated classification of multiple SDOH categories. Our dataset comprised narrative clinical notes under the "Social Work" category in the MIMIC-III Clinical Database. Using standard terminologies, SNOMED-CT and DSM-IV, we systematically curated a set of 13 SDOH categories and created annotation guidelines for these. After manually annotating the 3,504 sentences, we developed and tested three deep neural network (DNN) architectures - convolutional neural network (CNN), long short-term memory (LSTM) network, and the Bidirectional Encoder Representations from Transformers (BERT) - for automated detection of eight SDOH categories. We also compared these DNNs to three baselines models: (1) cTAKES, as well as (2) L2-regularized logistic regression and (3) random forests on bags-of-words. Model evaluation metrics included micro- and macro- F1, and area under the receiver operating characteristic curve (AUC). RESULTS: All three DNN models accurately classified all SDOH categories (minimum micro-F1 =.632, minimum macro-AUC=.854). Compared to the CNN and LSTM, BERT performed best in most key metrics (micro-F1 = 0.690, macro-AUC=0.907). The BERT model most effectively identified the "occupational" category (F1=.774, AUC=.965) and least effectively identified the "non-SDOH" category (F=.491, AUC=.788). BERT outperformed cTAKES in distinguishing social vs non-social sentences (BERT F1 = .87 vs. cTAKES F1=.06), and outperformed logistic regression (micro-F1=0.649, macro-AUC=0.696) and random forest (micro-F1=0.502, macro-AUC=0.523) trained on bag-of-words. CONCLUSIONS: Our study framework with DNN models demonstrated improved performance for efficiently identifying a systematic range of SDOH categories from clinical notes in the EHR. Improved identification of patient SDOH may further improve healthcare outcomes.

3.
Pharmacol Res ; 175: 106020, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34896249

RESUMO

Obesity associated with low-grade chronic inflammation and intestinal dysbiosis is considered as a worldwide public health crisis. In the meanwhile, different probiotics have demonstrated beneficial effects on this condition, thus increasing the interest in the development of probiotic treatments. In this context, the aim of this study is to investigate the anti-obesity effects of potential probiotic Lactobacillus acidophilus isolated from the porcine gut. Then, it is found that L. acidophilus reduces body weight, fat mass, inflammation and insulin resistance in mice fed with a high-fat diet (HFD), accompanied by activation in brown adipose tissue (BAT) as well as improvements of energy, glucose and lipid metabolism. Besides, our data indicate that L. acidophilus not only reverses HFD-induced gut dysbiosis, as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin bearing Gram-negative bacteria levels, but also maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the TLR4 / NF- κB signaling pathway. In addition, the results of microbiome phenotype prediction by BugBase and bacterial functional potential prediction using PICRUSt show that L. acidophilus treatment improves the gut microbiota functions involving metabolism, immune response, and pathopoiesia. Furthermore, the anti-obesity effect is transmissible via horizontal faeces transfer from L. acidophilus-treated mice to HFD-fed mice. According to our data, it is seen that L. acidophilus could be a good candidate for probiotic of ameliorating obesity and associated diseases such as hyperlipidemia, nonalcoholic fatty liver diseases, and insulin resistance through its anti-inflammatory properties and alleviation of endothelial dysfunction and gut dysbiosis.

4.
Dev Comp Immunol ; 128: 104333, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34914929

RESUMO

Galectins belong to the ß-galactoside binding protein family, which have conserved carbohydrate-recognition domains (CRDs) and participate in innate and acquired immunity in animals. In this study, two galectin genes were cloned from Onychostoma macrolepis, OmGal-3 (galectin-3) and OmGal-9 (galectin-9). The open reading frames (ORFs) of OmGal-3 and OmGal-9 contain 732 and 978 base pairs, encoding 243 and 325 amino acids, respectively. OmGal-3 contains a C-terminal CRD, but OmGal-9 contains an N-terminal CRD and a C-terminal CRD. Two galectins were expressed at varying levels in all tissues examined, with the liver showing the highest expression. The relative gene expression levels of OmGal-3 and OmGal-9 following Aeromonas hydrophila infection were significantly up-regulated in the liver and spleen, and OmGal-9 had a greater increase than OmGal-3. The recombinant OmGal-3 and OmGal-9 proteins (rOmGal-3 and rOmGal-9) were authenticated and verified by SDS-PAGE and western blotting. ROmGal-3 and rOmGal-9 agglutinated all tested bacteria, including 3 g-positive bacteria (Aeromonas hydrophila, Escherichia coli, and Vibrio parahaemolyticus) and 3 g-negative bacteria (Streptococcus agalactiae, Staphylococcus aureus, and Bacillus cereus) in vivo without Ca2+. ROmGal-3 showed strong binding both to gram-positive and gram-negative bacteria and OmGal-9 had a stronger binding activity against gram-positive bacteria. Furthermore, rOmGal-3 and rOmGal-9 exhibited dose-dependent binding capability to two classic pathogens associated molecular pattern (LPS and PGN) and two sugars (d-lactose and d-galactose), and rOmGal-3 has better binding activity at lower concentrations in LPS and PGN than rOmGal-3. The integrated analyses indicate that the two galectins probably play an important role in innate immune defense by binding to bacterial cells via the CRD domain against pathogen infection.

5.
Front Oncol ; 11: 758917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868972

RESUMO

Background: This study aimed to characterize the bacterial microbiota in the oral cavity (OC), throat, trachea, and distal alveoli of patients with primary malignant tracheal tumors (PMTT), including squamous cell carcinoma (SCC) and salivary gland carcinoma patients (SGC), for comparison with a matched non-malignant tracheal tumor (NMTT) group. Methods: Patients with pathological diagnosis of PMTT and NMTT were included in this study. Saliva, throat swab (TS), trachea protected specimen brush (PSB), and bronchoalveolar lavage fluid (BALF) samples were collected for 16S rRNA gene sequencing. The composition, diversity, and distribution of the microbiota were compared among biogeographic sampling sites and patient groups. The relationship between the genera-level taxon abundance and tracheal tumor types was also investigated to screen for candidate biomarkers. Findings: The most represented phyla in the four sites were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. In SCC patients, the relative abundance of Bacteroidetes and Firmicutes gradually decreased with increasing depth into the respiratory tract, while the relative abundance of Proteobacteria gradually increased. Bacterial communities at the four biogeographic sites formed two distinct clusters, with OC and TS samples comprising one cluster and PSB and BALF samples comprising the other group. Principal coordinate analysis showed that trachea microbiota in SCC patients were distinct from that of SGC or NMTT patients. In the trachea, AUCs generated by Prevotella and Alloprevotella showed that the abundance of these genera could distinguish SCC patients from both NMTT and SGC patients. Interpretation: The structure of respiratory tract microbiota in PMTT patients is related to tumor type. Certain bacteria could potentially serve as markers of SCC, although verification with large-sample studies is necessary.

6.
Molecules ; 26(24)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34946685

RESUMO

Ghrelin is a 28-residue peptide hormone produced by stomach P/D1 cells located in oxyntic glands of the fundus mucosa. Post-translational octanoylation of its Ser-3 residue, catalyzed by MBOAT4 (aka ghrelin O-acyl transferase (GOAT)), is essential for the binding of the hormone to its receptor in target tissues. Physiological roles of acyl ghrelin include the regulation of food intake, growth hormone secretion from the pituitary, and inhibition of insulin secretion from the pancreas. Here, we describe a medicinal chemistry campaign that led to the identification of small lipopeptidomimetics that inhibit GOAT in vitro. These molecules compete directly for substrate binding. We further describe the synthesis of heterocyclic inhibitors that compete at the acyl coenzyme A binding site.

7.
Ann Transl Med ; 9(17): 1369, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733921

RESUMO

Background: Long non-coding RNAs (lncRNAs) have recently been found to be vital regulators of various cancers, including colorectal cancer (CRC). It has been previously reported that the dysregulated expression of lncRNA Five prime to Xist (FTX) is involved in carcinogenesis. However, the role of lncRNA FTX in the progression of CRC is still unclear. Methods: Fluorescence in situ hybridization (FISH) was used to detect the expression of lncRNA FTX and miR-214-5p in CRC tissues. Cell Counting Kit-8 assay, transwell assay, wound-healing assay, and proliferation assay were used to explore the function of lncRNA FTX in CRC cells. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and luciferase reporter assay were used to confirm the relationship between lncRNA FTX and miR-214-5p-jagged canonical Notch ligand 1 (JAG1). We further explored the role of lncRNA FTX in vivo using xenograft tumor assay. Results: lncRNA FTX was found to be upregulated in CRC tissues by FISH. The downregulation of endogenous lncRNA FTX expression inhibited CRC cell proliferation, migration, and invasion. Mechanistically, lncRNA FTX sequestered miR-214-5p and thus released its repression on JAG1, driving the malignant progression of CRC. Conclusions: These findings give rise to a new perspective, the lncRNA FTX-miR-214-5p-JAG1 regulatory axis, in exploring the cancer-promoting mechanism of lncRNA FTX in CRC.

8.
Cancer Sci ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741373

RESUMO

Recent studies have reported that MLST8 is upregulated in many malignant tumors. Nevertheless, the underlying molecular mechanism is still unclear. The aim of this work was to investigate how MLST8 contributes to the development and progression of clear cell renal cell carcinoma (ccRCC). MLST8 is an oncogenic protein in the TCGA database and ccRCC clinical specimens. We also ascertain that MLST8 interacts with FBXW7, which was universally regarded as an E3 ubiquitin ligase. MLST8 can be degraded and ubiquitinated by tumor suppressor FBXW7. FBXW7 recognizes a consensus motif (T/S) PXX (S/T/D/E) of MLST8 and triggers MLST8 degradation via the ubiquitin-proteasome pathway. Strikingly, the activated cyclin dependent kinase 1 (CDK1) kinase engages in the MLST8 phosphorylation required for FBXW7-mediated degradation. In vitro, we further prove that MLST8 is an essential mediator of FBXW7 inactivation-induced tumor growth, migration, and invasion. Furthermore, the MLST8 and FBXW7 proteins are negatively correlated in human renal cancer specimens. Our findings suggest that MLST8 is a putative oncogene that functions via interaction with FBXW7, and inhibition MLST8 could be a potential future target in ccRCC treatment.

9.
Curr Neuropharmacol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34766896

RESUMO

There are various differences in the response to different antipsychotics and antioxidant defense system (ADS) by sex. Previous studies have shown that several ADS enzymes are closely related to the treatment response of patients with antipsychotics-naïve first-episode (ANFE) schizophrenia. Therefore, the main goal of this study was to assess the sex difference in the relationship between changes in ADS enzyme activities and risperidone response. The plasma activities of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and total antioxidant status (TAS) were measured in 218 patients and 152 healthy controls. Patients were treated with risperidone for 3 months, and we measured PANSS for psychopathological symptoms and ADS biomarkers at baseline and at the end of 3 months of treatment. We compared sex-specific group differences between 50 non-responders and 168 responders at baseline and at the end of the three months of treatment. We found that female patients responded better to risperidone treatment than male patients. At baseline and 3-month follow-up, there were no significant sex differences in TAS levels and three ADS enzyme activities. Interestingly, only in female patients, after 12 weeks of risperidone treatment, the GPx activity of responders was higher than that of non-responders. These results indicate that after treatment with risperidone, changes in GPx activity were associated with treatment response, suggesting that changes in GPx may be a predictor of response to risperidone treatment in female patients with ANFE schizophrenia.

10.
Front Pharmacol ; 12: 735196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603051

RESUMO

Background: Accumulating studies have shown that the pathophysiology of schizophrenia may be associated with aberrant lysophospolipid metabolism in the early stage of brain development. Recent evidence demonstrates that antipsychotic medication can regulate the phospholipase activity. However, it remains unclear whether lysophospolipid is associated with the therapeutic response to antipsychotic medication in schizophrenia. This study aimed to investigate the influence of olanzapine monotherapy on lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) and the association between symptom improvement and changes of LPC and LPE levels during treatment in antipsychotic-naïve first-episode (ANFE) patients. Materials and Methods: The psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). 25 ANFE patients were treated with olanzapine for 1 mo. The levels of LPC and LPE were determined and psychotic symptoms were assessed at baseline and at 1-mo follow-up. Results: Relative to baseline, the psychotic symptoms were significantly reduced after olanzapine treatment, except for negative symptoms. Moreover, the levels of most LPC and LPE increased after treatment. Interestingly, increased LPC(18:3) and LPC(20:2) levels were positively associated with the reduction rates of PANSS positive subscore. In addition, baseline levels of LPE(20:5), LPE(18:3) and LPE(22:5) were predictors for the reduction of positive symptoms. Conclusion: Our study reveals that the levels of lysophospolipid are associated with the improvement of positive symptoms, indicating that LPC may be a potential therapeutic target for olanzapine in schizophrenia. Moreover, baseline LPE levels were predictive biomarkers for the therapeutic response to olanzapine in the early stage of treatment in ANFE patients.

11.
Artigo em Chinês | MEDLINE | ID: mdl-34628805

RESUMO

The diagnostic criteria for "Vestibular Migraine of Childhood", "Probable Vestibular Migraine of Childhood" and "Recurrent Vertigo of Childhood" is put forth by the Committee for the Classification of Vestibular Disorders of the Bárány Society and the Migraine Classification subgroup of the International Headache Society at the beginning of 2021. It provides directions for the diagnosis and treatment of these syndromes to international community of pediatricians, otolaryngologists, neurologists, neurosurgeons, neuro-otologists physiotherapists, neurophysiologists, and audiologists. The paper concludes the current situation and research progress of diagnosis and treatment of children vertigo diseases.


Assuntos
Transtornos de Enxaqueca , Doenças Vestibulares , Criança , Consenso , Tontura , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/terapia , Vertigem/diagnóstico , Vertigem/terapia , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/terapia
12.
Am J Transl Res ; 13(9): 10536-10544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650724

RESUMO

OBJECTIVE: To assess the computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) fusion imaging technique features in cervical cancer staging and lymph node metastasis. METHODS: A total of 196 cervical cancer patients undergoing CT, MRI, PET/CT, and PET/MRI preoperatively were enrolled. The diagnostic accuracy and detection rates for paracervical invasion were evaluated on the basis of the International Federation of Gynecology and Obstetrics (FIGO) staging classification for cervical cancer. The diagnostic efficacy of each examination modality for determining lymph node metastasis was evaluated using surgical pathology as a reference. The CT and MRI imaging features of lymph node metastasis were compared. RESULTS: PET/MRI had a higher diagnostic accuracy for cervical cancer (94.90%) than PET/CT, MRI, and CT (83.67%, 75.51%, and 69.39%) (P < 0.05). PET/MRI showed a higher detection rate of vaginal invasion, uterine invasion, bladder invasion, and cervical invasion than PET/CT, MRI, and CT (P < 0.05). The metastasis group showed higher maximum long and short axis diameters and axial ratios than the non-metastasis group (P < 0.05). The metastasis group had higher wash-in rates (WIR), maximum relative enhancements (MRE), wash-out ratios (WOR), and apparent diffusion coefficients (ADC), and lower times to peak (TTP) than the non-metastasis group (P < 0.05). The sensitivity (94.74%), specificity (93.33%), and accuracy (93.88%) of PET/MRI in the diagnosis of cervical cancer lymph node metastasis were higher than the sensitivity, specificity, and accuracy of PET/CT, MRI and CT (P < 0.05). CONCLUSION: CT, MRI, PET/CT and PET/MRI can be used effectively in the diagnosis of cervical cancer staging and lymph node metastasis, among which PET/MRI has a higher diagnostic sensitivity, specificity, and accuracy and is helpful in clinical diagnosis and treatment.

13.
Curr Neuropharmacol ; 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34544343

RESUMO

Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities. The activities of plasma superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls. Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities and MDA levels were measured at baseline and during follow-up. Compared with healthy controls, the patients showed higher activities of SOD and CAT, but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with bodyweight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparison between WG group and non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up. These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.

15.
Chem Asian J ; 16(20): 3230-3235, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34411460

RESUMO

Transition metal@Nx Cy -graphene (TM@Nx Cy -GR) materials have been widely used as redox reaction catalysts in the field of fuel cells due to their low cost and high performance. In the present work, we systematically investigate the effect of different metal and defect types on the electro-magnetic properties of TM@Nx Cy -GR materials using first principles calculations. Our simulations show that TM@N3 -GR (the minimum defect size) and TM@N7 -GR (the maximum defect size) materials always possess metallic property regardless the metal type. However, doping different TM can regulate the medium defects (TM@N2 C2 -GR-I and TM@N2 C2 -GR-II) among metallicity, half-metallicity and semi-conductivity. In addition, we found that different TM and defect type largely affects the magnetic moment. The spin density and projected density of state calculations show that the net charges of the defect structure are mainly located near the hole, and the magnetic regulation comes from the coupling of TM-d orbital with carbon (nitrogen)-s(p) orbitals. The present study provides abundant valuable information for the TM@Nx Cy -GR materials designs and applicants in the future.

16.
Drug Des Devel Ther ; 15: 3475-3486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413632

RESUMO

Purpose: Non-small cell lung cancer (NSCLC) therapy faces the barriers including drug resistance. A transferrin-functionalized protein-lipid hybrid nanoparticle (PLHN) was designed loading both cisplatin (CIS) and docetaxel (DTX) for the lung cancer treatment. Methods: CIS and DTX were loaded into the hybrid nanoparticle and then decorated with transferrin (Tf). The Tf-functionalized protein-lipid hybrid nanoparticle (Tf-CIS/DTX-PLHN) was investigated by determining the release behavior, cytotoxicity in vitro, and anticancer efficiency in vivo. Results: Tf-CIS/DTX-PLHN showed a nano-size of 189.5 ± 5.9 nm, and a surface tested to be -16.9 ± 2.1 mV. Tf-CIS/DTX-PLHN exhibited obviously better antitumor ability in vitro and in vivo compared with the non Tf contained CIS and DTX co-loaded lipid nanoparticles (CIS/DTX-LN), single drug loaded nanoparticles, and free drugs. Conclusion: Since remarkable enhanced efficiency of Tf and synergistic effect of the drugs, it could inhibit the lung tumor growth and help with the lung cancer treatment.

17.
J Mech Behav Biomed Mater ; 123: 104789, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34450418

RESUMO

As expected from the material design, a novel shell-core-like structural TiNb/NiTi composite possessing both decent biocompatibility and large near-linear-elastic deformation behavior (namely as near-linear elasticity accompanied by high elastic strain limit) was prepared successfully by a hot pack-rolling combined with cold rolling procedure. Non-cytotoxic TiNb outer shell obstructs the NiTi inner core from cells and provides the decent biocompatibility of TiNb/NiTi composite. Large near-linear-elastic deformation behavior for this TiNb/NiTi composite has been confirmed to be associated with intrinsic elastic deformation, two types of reversible stress-induced martensitic transformations (i.e. ß↔α'' and B2↔B19' transformations) occurring in a homogeneous manner, together with the (001) compound twin in B19' martensitic plates. Our study provides a new design approach for developing NiTi-based composites with both decent biocompatibility and large near-linear-elastic deformation behavior for biomedical or engineering applications.


Assuntos
Titânio , Elasticidade , Teste de Materiais
18.
Front Microbiol ; 12: 679805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248893

RESUMO

The excessive use of antibiotics speeds up the dissemination and aggregation of antibiotic resistance genes (ARGs) in the environment. The ARGs have been regarded as a contaminant of serious environmental threats on a global scale. The constant increase in aquaculture production has led to extensive use of antibiotics as a means to prevent and treat bacterial infections; there is a universal concern about the environmental risk of ARGs in the aquaculture environment. In this study, a survey was conducted to evaluate the abundance and distributions of 10 ARGs, bacterial community, and environmental factors in sediment samples from aquatic farms distributed in Anhui (AP1, AP2, and AP3), Fujian (FP1, FP2, and FP3), Guangxi (GP1, GP2, and GP3), Hainan (HP1, HP2, and HP3), and Shaanxi (SP1, SP2, and SP3) Province in China. The results showed that the relative abundance of total ARGs was higher in AP1, AP2, AP3, FP3, GP3, HP1, HP2, and HP3 than that in FP1, FP2, GP1, GP2, SP1, SP2, and SP3. The sul1 and tetW genes of all sediment samples had the highest abundance. The class 1 integron (intl1) was detected in all samples, and the result of Pearson correlation analysis showed that the intl1 has a positive correlation with the sul1, sul2, sul3, bla OXA, qnrS, tetM, tetQ, and tetW genes. Correlation analysis of the bacterial community diversity and environmental factors showed that the Ca2+ concentration has a negative correlation with richness and diversity of the bacterial community in these samples. Of the identified bacterial community, Proteobacteria, Firmicutes, Chloroflexi, and Bacteroidota were the predominant phyla in these samples. Redundancy analysis showed that environmental factors (TN, TP, Cl-, and Ca2+) have a positive correlation with the bacterial community (AP1, GP1, GP2, GP3, SP1, SP2, and SP3), and the abundance of ARGs (sul1, tetW, qnrS, and intl1) has a positive correlation with the bacterial community (AP2, AP3, HP1, HP2, and HP3). Based on the network analysis, the ARGs (sul1, sul2, bla CMY, bla OXA, qnrS, tetW, tetQ, tetM, and intl1) were found to co-occur with bacterial taxa from the phyla Chloroflexi, Euryarchaeota, Firmicutes, Halobacterota, and Proteobacteria. In conclusion, this study provides an important reference for understanding the environmental risk associated with aquaculture activities in China.

19.
Future Oncol ; 17(30): 4027-4040, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34278818

RESUMO

The present meta-analysis was performed to evaluate the efficacy of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients. A systematic literature search was conducted of online databases prior to February 21, 2021. Eleven articles involving 8429 patients were included. The pooled hazard ratio for overall survival (OS) of RFA versus SBRT was 0.79 (p < 0.001). Statistically significant differences were found in the 1-, 2-, 3-, 4- and 5-year pooled OS and freedom from local progression (FFLP) rates between the two groups, favoring the RFA arms. However, the pooled local control (LC) rates were higher in the SBRT arm. RFA provided better OS and FFLP for treating HCC, while SBRT achieved superior LC. PROSPERO registration number: CRD42020207877.

20.
Eur J Med Chem ; 223: 113645, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34217059

RESUMO

Protein degradation is a promising strategy for drug development. Proteolysis-targeting chimeras (PROTACs) hijacking the E3 ligase cereblon (CRBN) exhibit enormous potential and universal degradation performance due to the small molecular weight of CRBN ligands. In this study, the CRBN-recruiting PROTACs were explored on the degradation of oncogenic fusion protein BCR-ABL, which drives the pathogenesis of chronic myeloid leukemia (CML). A series of novel PROTACs were synthesized by conjugating BCR-ABL inhibitor dasatinib to the CRBN ligand including pomalidomide and lenalidomide, and the extensive structure-activity relationship (SAR) studies were performed focusing on optimization of linker parameters. Therein, we uncovered that pomalidomide-based degrader 17 (SIAIS056), possessing sulfur-substituted carbon chain linker, exhibits the most potent degradative activity in vitro and favorable pharmacokinetics in vivo. Besides, degrader 17 also degrades a variety of clinically relevant resistance-conferring mutations of BCR-ABL. Furthermore, degrader 17 induces significant tumor regression against K562 xenograft tumors. Our study indicates that 17 as an efficacious BCR-ABL degrader warrants intensive investigation for the future treatment of BCR-ABL+ leukemia.


Assuntos
Desenho de Fármacos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Ubiquitina-Proteína Ligases/química , Animais , Proliferação de Células/efeitos dos fármacos , Dasatinibe/farmacologia , Proteínas de Fusão bcr-abl/metabolismo , Meia-Vida , Humanos , Células K562 , Lenalidomida/química , Lenalidomida/metabolismo , Ligantes , Camundongos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteólise , Relação Estrutura-Atividade , Talidomida/análogos & derivados , Talidomida/química , Talidomida/metabolismo , Transplante Heterólogo , Ubiquitina-Proteína Ligases/metabolismo
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