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1.
Medicine (Baltimore) ; 101(39): e30920, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181065

RESUMO

The aim of the study was to observe the association between follicle stimulating hormone (FSH) levels and serum lipid profiles in postmenopausal women. A total of 411 healthy postmenopausal women with a mean age of 55 years (range 45-65 years) were enrolled in this study. Data on age, time of last menstrual period, past medical history, use of medications, and smoking status were collected, and body weight, height, and blood pressure were measured. Blood samples were collected to measure the serum concentrations of FSH, luteinizing hormone (LH), estradiol (E2), glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using routine methods. FSH levels were negatively associated with LDL-C, even after adjustment for age, LH, E2, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (OR = 0.185, 95% CI = 0.051-0.669). Although FSH may also be negatively associated with dyslipidemia (P = .06 for trend) and hypercholesterolemia (P = .079 for trend), but no statistical significance was found after adjusting for confounding factors, particularly BMI. All relevant data are within the paper and its Supporting Information files. The results indicated that lower FSH levels might increase the odds of dyslipidemia, especially the risk of LDL-C elevation, which is an important factor that increases the risk of CVD in postmenopausal women.


Assuntos
Dislipidemias , Hormônio Foliculoestimulante , Idoso , HDL-Colesterol , LDL-Colesterol , Estradiol , Feminino , Glucose , Humanos , Hormônio Luteinizante , Pessoa de Meia-Idade , Pós-Menopausa , Triglicerídeos
2.
Front Oncol ; 12: 997306, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185190

RESUMO

Objective: To explore the application values of deep-learning based artificial intelligence (AI) automatic classification system, on the differential diagnosis of non-lactating mastitis (NLM) and malignant breast tumors, via its comparation with traditional ultrasound interpretations and the following interpretation conclusions made by the sonographers with various seniorities. Methods: A total of 707 patients suffering from breast lesions (475 malignant breast tumors and 232 NLM), were selected from the following three medical centers, including Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical University, and the time period was set from April 2020 to September 2021. All selected cases firstly accepted the routine breast ultrasound diagnosis, followed by the interpretations from a senior sonographer with more than 15 years of work experience, and an intermediate-aged sonographer with more than 5 years of work experience, independently. Meanwhile, a third physician also interpreted the same ultrasound images by deep learning-based AI automatic classification system, independent of the interpretation results from the previous two physicians. The kappa test was performed to evaluate the consistency between the conventional ultrasound interpretation results and pathological results interpreted from physicians with different working experiences. Results: In total, 475 cases of malignant breast tumors (512 nodules) and 232 cases of NLM (255 nodules) were pathologically diagnosed. The accuracy, sensitivity, and specificity of conventional ultrasound interpretations vary from different sonographers with different working experiences. The accuracy, sensitivity, and specificity for intermediate-aged sonographers and senior sonographers were 76.92% (590/767), 84.71% (216/255), and 73.95% (374/512) and 87.35% (670/767), 86.27% (220/255), and 87.89% (450/512), respectively (P<0.001). In contrast, if the threshold was set as 0.5, the accuracy, sensitivity, and specificity from deep learning-based AI automatic classification system were 83.00%, 87.20%, and 85.33%, separately, and the area under the curve was 92.6. The results of the kappa consistency test indicated that the diagnosis results from the image interpretations by senior physicians and deep-learning based AI automatic classification system showed high consistency with postoperative pathological diagnosis results, and the kappa values are 0.72 and 0.71, respectively, with the P-value of less than 0.001. In contrast, the consistency between the image interpretation results from intermediate-aged physicians with less working experience, and postoperative pathological diagnosis results, seemed to be relatively lower, with a kappa value of only 0.53 and P-value of less than 0.001. Conclusions: The deep learning-based AI automatic classification system is expected to become a reliable auxiliary way to distinguish NLM and malignant breast tumors due to its high sensitivity, accuracy, and specificity.

3.
Commun Biol ; 5(1): 1055, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36192584

RESUMO

Despite the environmental challenges and nutrient scarcity, the geographically isolated Challenger Deep in Mariana trench, is considered a dynamic hotspot of microbial activity. Hadal viruses are the least explored microorganisms in Challenger Deep, while their taxonomic and functional diversity and ecological impact on deep-sea biogeochemistry are poorly described. Here, we collect 13 sediment cores from slope and bottom-axis sites across the Challenger Deep (down to ~11 kilometers depth), and identify 1,628 previously undescribed viral operational taxonomic units at species level. Community-wide analyses reveals 1,299 viral genera and distinct viral diversity across the trench, which is significantly higher at the bottom-axis vs. slope sites of the trench. 77% of these viral genera have not been previously identified in soils, deep-sea sediments and other oceanic settings. Key prokaryotes involved in hadal carbon and nitrogen cycling are predicted to be potential hosts infected by these viruses. The detected putative auxiliary metabolic genes suggest that viruses at Challenger Deep could modulate the carbohydrate and sulfur metabolisms of their potential hosts, and stabilize host's cell membranes under extreme hydrostatic pressures. Our results shed light on hadal viral metabolic capabilities, contribute to understanding deep sea ecology and on functional adaptions of hadal viruses for future research.


Assuntos
Carbono , Solo , Carboidratos , Nitrogênio , Enxofre
4.
ACS Nano ; 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36190834

RESUMO

The number of patients who benefit from acquired immunotherapy is limited. Stimulator of interferon genes (STING) signal activation is a significant component to enhance innate immunity, which has been used to realize broad-spectrum immunotherapy. Here, M@P@HA nanoparticles, as a STING signal amplifier, are constructed to enhance innate immunotherapy. Briefly, when M@P@HA was targeted into tumor cells, the nanoparticles decomposed with Mn2+ and activated the release of protoporphyrin (PpIX). Under light irradiation, the generated reactive oxygen species disrupt the cellular redox homeostasis to lead cytoplasm leakage of damaged mitochondrial double-stranded (ds) DNA, which is the initiator of the STING signal. Simultaneously, Mn2+ as the immunoregulator could significantly increase the activity of related protein of a STING signal, such as cyclic GMP-AMP synthase (cGAS) and STING, to further amplify the STING signal of tumor cells. Subsequently, the STING signal of tumor-associated macrophages (TAM) is also activated by capturing dsDNA and Mn2+ that escaped from tumor cells, so as to enhance innate immunity. It is found that, by amplifying the STING signal of tumor tissue, M@P@HA could not only activate innate immunity but also cascade to activate CD8+ T cell infiltration even in a tumor with low immunogenicity.

5.
Front Pharmacol ; 13: 967532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188528

RESUMO

Background: Many studies demonstrated that roxadustat (FG-4592) could increase hemoglobin (Hb) levels effectively in anemia patients with chronic kidney disease (CKD). However, its safety remains controversial. This study aims to explore the risk of infection for CKD patients treated with roxadustat, especially focused on sepsis. Methods: We thoroughly searched for the randomized controlled trials (RCTs) comparing treatment with roxadustat versus erythropoiesis stimulating agents (ESAs) or placebo in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, European Union Clinical Trials Register. Both on and not on dialysis anemia patients with CKD were included. Primary outcomes contained the incidence rates of sepsis. Secondary outcomes included infection-related consequences (septic shock and other infection events), general safety outcomes [all-cause mortality, treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)] and iron parameters. Moreover, a trial sequential analysis (TSA) was conducted to assess if the results were supposed to be a robust conclusion. Results: Eighteen RCTs (n = 11,305) were included. Overall, the incidence of sepsis (RR: 2.42, 95% CI [1.50, 3.89], p = 0.0003) and cellulitis (RR: 2.07, 95% CI [1.24, 3.44], p = 0.005) were increased in the roxadustat group compared with placebo group. In non-dialysis-dependent (NDD) CKD patients, the incidence of cellulitis (RR 2.01, 95% CI [1.23, 3.28], p = 0.005) was significantly higher in roxadustat group than that in the ESAs or placebo group. Both groups showed similar results in the incidence of septic shock (RR 1.29, 95% CI [0.86, 1.94], p = 0.22). A significant increased risk of all-cause mortality [risk ratios (RR): 1.15, 95% confidence interval (CI) [1.05, 1.26], p = 0.002] was found in roxadustat treatment, and TSA confirmed the result. Compared with ESAs or placebo, both the incident rates of TEAEs (RR:1.03, 95% CI [1.01, 1.04], p = 0.008) and TESAEs (RR: 1.06, 95% CI [1.02, 1.11], p = 0.002) were significantly increased in roxadustat group. As for iron parameters, changes from baseline (Δ) of hepcidin (MD: -26.46, 95% CI [-39.83, -13.09], p = 0.0001), Δ ferritin and Δ TSAT were remarkably lower in the roxadustat group, while Δ Hb, Δ iron and Δ TIBC increased significantly versus those in ESAs or placebo group. Conclusion: We found evidence that incidence rates of sepsis and cellulitis are higher in roxadustat group compared with placebo. This may be the result of improved iron homeostasis. The risk of all-cause mortality, TEAEs and TESAEs in CKD patients also increased in patients treated with roxadustat. We need more clinical and mechanistic studies to confirm whether roxadustat really causes infection.

6.
Oncogene ; 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192479

RESUMO

Single-cell RNA sequencing (scRNA-seq) is one of the most efficient technologies for human tumor research. However, data analysis is still faced with technical challenges, especially the difficulty in efficiently and accurately discriminating cancer/normal cells in the scRNA-seq expression matrix. If we can address these challenges, we can have a deeper understanding of the intratumoral and intertumoral heterogeneity. In this study, we developed a cancer/normal cell discrimination pipeline called pan-Cancer Seeker (CaSee) devoted to scRNA-seq expression matrix, which is based on the traditional high-quality pan-cancer bulk sequencing data using transfer learning. CaSee is the first tool directly used to discriminate cancer/normal cells in the scRNA-seq expression matrix, with much wider application fields and higher efficiency than copy number variation (CNV) method which requires corresponding reference cells. CaSee is user-friendly and can adapt to a variety of data sources, including but not limited to scRNA tissue sequencing data, scRNA cell line sequencing data, scRNA xenograft cell sequencing data and scRNA circulating tumor cell sequencing data. It is compatible with mainstream sequencing technology platforms, 10× Genomics Chromium, Smart-seq2, and Microwell-seq. Here, CaSee pipeline exhibited excellent performance in the multicenter data evaluation of 11 retrospective cohorts and one independent dataset, with an average discrimination accuracy of 96.69%. In general, the development of a deep-learning based, pan-cancer cell discrimination model, CaSee, to distinguish cancer cells from normal cells will be compelling to researchers working in the genomics, cancer, and single-cell fields.

7.
Int J Endocrinol ; 2022: 9492056, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193283

RESUMO

Background: Ultrasonography (US) is the most common method of identifying thyroid nodules, but US images require an experienced surgeon for identification. Many artificial intelligence (AI) techniques such as computer-aided diagnostic systems (CAD), deep learning (DL), and machine learning (ML) have been used to assist in the diagnosis of thyroid nodules, but whether AI techniques can improve the diagnostic accuracy of thyroid nodules still needs to be explored. Objective: To clarify the accuracy of AI-based thyroid nodule US images for differentiating benign and malignant thyroid nodules. Methods: A search strategy of "subject terms + key words" was used to search PubMed, Cochrane Library, Embase, Web of Science, China Biology Medicine (CBM), and China National Knowledge Infrastructure (CNKI) for studies on AI-assisted diagnosis of thyroid nodules based on US images. The summarized receiver operating characteristic (SROC) curve and the pooled sensitivity and specificity were used to assess the performance of the diagnostic tests. The quality assessment of diagnostics accuracy studies-2 (QUADAS-2) tool was used to assess the methodological quality of the included studies. The Review Manager 5.3 and Stata 15 were used to process the data. Subgroup analysis was based on the integrity of data collection. Results: A total of 25 studies with 17,429 US images of thyroid nodules were included. AI-assisted diagnostic techniques had better diagnostic efficacy in the diagnosis of benign and malignant thyroid nodules: sensitivity 0.88 (95% CI: (0.85-0.90)), specificity 0.81 (95% CI: 0.74-0.86), diagnostic odds ratio (DOR) 30 (95% CI: 19-46). The SROC curve indicated that the area under the curve (AUC) was 0.92 (95% CI: 0.89-0.94). Threshold effect analysis showed a Spearman correlation coefficient: 0.17 < 0.5, suggesting no threshold effect for the included studies. After a meta-regression analysis of 4 different subgroups, the results showed a statistically significant effect of mean age ≥50 years on heterogeneity. Compared with studies with an average age of ≥50 years, AI-assisted diagnostic techniques had higher diagnostic performance in studies with an average age of <50 years (0.89 (95% CI: 0.87-0.92) vs. 0.80 (95% CI: 0.73-0.88)), (0.83 (95% CI: 0.77-0.88) vs. 0.73 (95% CI: 0.60-0.87)). Conclusions: AI-assisted diagnostic techniques had good diagnostic efficacy for thyroid nodules. For the diagnosis of <50 year olds, AI-assisted diagnostic technology was more effective in diagnosis.

8.
Nat Commun ; 13(1): 5845, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195598

RESUMO

Autophagy is crucial for maintaining cellular energy homeostasis and for cells to adapt to nutrient deficiency, and nutrient sensors regulating autophagy have been reported previously. However, the role of eiptranscriptomic modifications such as m6A in the regulation of starvation-induced autophagy is unclear. Here, we show that the m6A reader YTHDF3 is essential for autophagy induction. m6A modification is up-regulated to promote autophagosome formation and lysosomal degradation upon nutrient deficiency. METTL3 depletion leads to a loss of functional m6A modification and inhibits YTHDF3-mediated autophagy flux. YTHDF3 promotes autophagy by recognizing m6A modification sites around the stop codon of FOXO3 mRNA. YTHDF3 also recruits eIF3a and eIF4B to facilitate FOXO3 translation, subsequently initiating autophagy. Overall, our study demonstrates that the epitranscriptome regulator YTHDF3 functions as a nutrient responder, providing a glimpse into the post-transcriptional RNA modifications that regulate metabolic homeostasis.

9.
Discov Oncol ; 13(1): 99, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195696

RESUMO

Immune checkpoint inhibitors (ICIs) are changing all aspects of malignant tumour therapy as an immunotherapy subverter in oncology. However, the current ICIs might induce systemic immune activation in other tissues and organs since they are not tumour-specific, causing the immune system to attack some normal tissues and organs of the human body. The toxicity can also amplify greatly although combined immunotherapy for cancer has increased the curative efficacy. The LC4 peptide was modified to improve its tumour-targeting ability and reduce peripheral immune system activation, which was obtained through phage display peptide library screening and could block the CTLA-4/CD80 interaction. The LC4 peptide as a result, like other ICIs, exerts anti-tumour effects by refreshing T cell function, and also activates the peripheral immune system. We used the PLGLAG peptide as a linker at the C-terminal of LC4 to connect with a tumour-targeting peptide RGD to increase the tumour tissue targeting ability, and obtain LC4-PLG-RGD. Further experiments demonstrated that the anti-tumour LC4-PLG-RGD activity was better than LC4 in vivo, and the ability to activate the peripheral immune system was weakened. In conclusion, LC4-PLG-RGD can increase the ICIs tumour-targeting and reduce excessive peripheral tissue immune activation, thereby reducing the side effects of ICIs, while increasing their anti-tumour efficacy. This study confirmed that enhanced ICI tumour targeting can effectively reduce immune-related adverse reaction occurrence.

10.
Contrast Media Mol Imaging ; 2022: 5054507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105441

RESUMO

In order to investigate the clinical application value of HR-HPV DNA combined with liquid-based cytology in colposcopy of cervical cancer, a retrospective analysis is performed on 428 patients who underwent a cervical pathological examination in our hospital from May 2020 to December 2021. The pathological biopsy results are used as the gold standard to determine whether cervical lesions occurred in patients, and patients with positive gold standard results are included in the study group. The positive rates of liquid-based cytology and HR-HPV DNA are observed and recorded, and the patients with negative gold standard results are used as the control group. The positive rate of HR-HPV DNA and liquid-based cytology will increase with the aggravation of pathological results. The ROC curve shows that HR-HPV DNA combined with liquid-based cytology has high diagnostic efficiency in colposcopy of cervical lesions. It is clearly evident that both liquid-based cytology and HR-HPV DNA tests have certain advantages in the screening of cervical lesions, and the combined detection can further improve the screening value of cervical lesions.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Colposcopia , DNA , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
11.
Ann Transl Med ; 10(16): 902, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111007

RESUMO

Background: Most previous studies have focused on the intrinsic carcinogenic pathways of tumors; however, little is known about the potential role of N6-methyladenosine (m6A) methylation in the tumor immune microenvironment (TIME). To better diagnose and treat acute myeloid leukemia (AML), we sought to examine the correlation between m6A regulatory factors and immune infiltration in cases of AML. At the same time, a prognostic model was constructed to predict the survival of AML. Methods: We extracted data from The Cancer Genome Atlas (TCGA) database, including ribonucleic acid sequencing (RNA-seq) transcriptome data and data on the corresponding clinical characteristics of AML patients. We identified two m6A modification patterns with distinct clinical outcomes and found a significant relationship between them. Simultaneous discovery of distinct m6A clusters associated with the tumor immune microenvironment [immune cell types and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm] are closely related. Next, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to build a predictive model in the 2-m6A regulator TCGA dataset to further explore m6A prognostic features in AML, and perform correlation validation. Results: We identified 2 molecular subtypes (Clusters 1 and 2) by the consistent clustering of significant m6A regulators in AML. Cluster 2 was associated with a higher immune score and obvious immune cell infiltration, and thus patients in Cluster 2 had a poorer prognosis than those in Cluster 1 (P<0.05). Additionally, the 2 m6A-related signatures representing the independent prognostic factors in AML were screened to construct a prognostic risk-score model. We found that patients with low-risk scores had higher immune scores than those with high-risk scores (P<0.05). Conclusions: Our research confirmed that m6A methylation plays an important role in AML. Further provide new directions for the prognosis and treatment of AML.

12.
Sci Rep ; 12(1): 15262, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088485

RESUMO

The di-2-ethylhexyl phthalate (DEHP) degrading strain LMB-7 was isolated from electronic waste soil. According to its biophysical/biochemical characteristics and 16S rRNA gene analysis, the strain was identified as Nocardia asteroides. Optimal pH and temperature for DEHP degradation were 8.0 and 30 °C, respectively, and DEHP removal reached 97.11% after cultivation for 24 h at an initial concentration of 400 mg/L. As degradation intermediates, di-butyl phthalates, mono-2-ethylhexyl phthalate and 2-ethylhexanol could be identified, and it could be confirmed that DEHP was completely degraded by strain LMB-7. To our knowledge, this is a new report of DEHP degradation by a strain of Nocardia asteroides, at rates higher than those reported to date. This finding provides a new way for DEHP elimination from environment.


Assuntos
Dietilexilftalato , Resíduo Eletrônico , Anticorpos Monoclonais , Exotoxinas , Nocardia asteroides/genética , Nocardia asteroides/metabolismo , Ácidos Ftálicos , RNA Ribossômico 16S/genética , Solo
13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(7): 773-776, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36100421

RESUMO

Acute respiratory distress syndrome (ARDS), a common respiratory critical illness with multiple causes, is associated with high mortality. The high degree of heterogeneity may be the reason why it is lack of highly specific and sensitive biological biomarkers. Therefore, it is an urgent need to explore biomarkers, perform phenotypic analysis and establish risk stratification model for diagnosis, prognosis, and treatment of ARDS. Endothelial cells specificity molecular-1 (ESM-1, endocan), is a soluble dermatan sulfate proteoglycan, and be involved in regulating biological behaviors such as cell proliferation, differentiation and migration. Numerous studies have confirmed that ESM-1 is closely related to inflammation, endothelial activation and dysfunction. However, the role of ESM-1 in the initiating and developing process of ARDS is still unclear. To provide a scientific basis for its clinical applications in ARDS, such as early prognosis assessment and timely prevent strategies, this paper focuses on the biological properties and the clinical value of ESM-1 as a potential biomarker for ARDS.


Assuntos
Células Endoteliais , Síndrome do Desconforto Respiratório , Biomarcadores , Estado Terminal , Humanos , Prognóstico
14.
J Asthma Allergy ; 15: 1245-1261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101840

RESUMO

Background: Increased proliferation and hypertrophy of airway smooth muscle cells (ASMCs) contribute substantially to airway remodeling in asthma. Interleukin (IL)-13 regulates ASMC proliferation by increasing Orai1 expression, the pore-forming subunit of store-operated Ca2+ entry (SOCE). The underlying mechanisms of this effect are not fully understood. Methods: Bioinformatic analysis identified an interaction between microRNA 93-5p (miR-93-5p) and long non-coding RNA (lncRNA) H19, and between miR-93-5p and Orai1. RNA interference was used to investigate H19 knockdown on IL-13-induced proliferation and migration of in vitro cultured human bronchial smooth muscle cells (hBSMCs). Functional relevance of H19 in airway inflammation and airway remodeling was investigated in murine models of acute and chronic asthma. Results: IL-13 concentration-dependently increased the expression of H19 and Orai1 and decreased the expression of miR-93-5p in hBSMCs. H19 knockdown partly reversed the effects of IL-13 on the expression of miR-93-5p and Orai1 and attenuated the proliferation and migration of hBSMCs promoted by IL-13. IL-13-promoted expression of Orai1 was attenuated by miR-93-5p mimic and increased by miR-93-5p inhibitor. IL-13-promoted proliferation of hBSMCs was increased by miR-93-5p inhibitor but not affected by miR-93-5p mimic, whereas IL-13-promoted migration of hBSMCs was increased by miR-93-5p inhibitor and attenuated by miR-93-5p mimic. The inhibiting effect of H19 knockdown on IL-13-induced Orai1 expression and the proliferation and migration of hBSMCs was counteracted by miR-93-5p inhibitor but only marginally or not impacted by miR-93-5p mimic. The expression of H19 and Orai1 was higher in the lungs of asthmatic mice than in control mice. In asthmatic mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition and smooth muscle mass in the lungs. Conclusion: H19 may mediate the effects of IL-13 on Orai1 expression by inhibition of miR-93-5p in hBSMCs. H19 may be a therapeutic target for airway inflammation and airway remodeling.

15.
Clin Oral Investig ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053353

RESUMO

OBJECTIVES: To evaluate the long-term therapeutic effect of EASYDO ACTIVATOR, passive ultrasonic irrigation, and needle irrigation in experimental apical periodontitis in rats. MATERIALS AND METHODS: Sprague-Dawley male rats were used to produce periapical lesions. The pulp chambers of the bilaterally first mandibular molars were exposed and left open for 21 days. The rats were divided into four groups according to different irrigation protocols. Seven days after irrigation, the mandibles were removed for micro-CT, histological, and immunohistochemical analysis. Serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme-linked immunosorbent assays (ELISA). Statistical data were analyzed by one-way analysis of variance (ANOVA) with LSD tests. RESULTS: The passive ultrasonic irrigation and EASYDO ACTIVATOR groups had the smallest apical lesions compared to the other groups (P < 0.05), while the needle irrigation group had smaller lesions than the control group (P < 0.05). The EASYDO ACTIVATOR group had less inflammation infiltration compared to the control and needle irrigation groups (P < 0.05). The control and needle irrigation groups had more TNF-α expression compared to the passive ultrasonic irrigation and EASYDO ACTIVATOR groups (P < 0.05). The lowest IL-6 expression was observed in the EASYDO ACTIVATOR group. The EASYDO ACTIVATOR group had the lowest serum level of TNF-α than other groups (P < 0.05). IL-6 expression was significantly lower in the EASYDO ACTIVATOR group in comparison with the control and needle irrigation groups (P < 0.05). CONCLUSIONS: EASYDO ACTIVATOR can significantly reduce the apical lesions and decrease the inflammatory response around the periapical area. CLINICAL RELEVANCE: EASYDO ACTIVATOR is recommended for clinical application.

16.
Carbohydr Polym ; 296: 119892, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36087967

RESUMO

Inspired by the phenol-amine chemistry and biomineralization of insect cuticles, we developed a green and facile strategy for preparing a bio-adhesive with excellent adhesion properties, mildew resistance, and antibacterial activity. This biomimetic strategy incorporates functional catechol-modified ε-polylysine and vanillin via grafting and Schiff base reactions. The biomineralized cellulose nanocrystals were prepared using a cellulose nanocrystal bio-template by regulating the in-situ biomineralization of inorganic nanoparticles, thereby building an optimized organic-inorganic mineralization framework in the polymer. The bonding strength of composite adhesive was significantly improved by multiple cross-linking networks through sacrificial hydrogen bonds, electrostatic interactions, and dynamic covalent bonds. The adhesion strength of the composite adhesive reached 1.13 MPa, which was 151% higher than the pristine adhesive. As a result of the synergistic effect of the catechol component, cationic ε-polylysine, and aldehyde group, the bio-adhesive also exhibited favorable anti-mildew and anti-bacterial properties.


Assuntos
Celulose , Nanopartículas , Adesivos/química , Aminas , Catecóis/química , Celulose/química , Nanopartículas/química , Polilisina
17.
Front Pharmacol ; 13: 962201, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091767

RESUMO

Insulin glargine is a long-acting insulin analog, which plays an important role in the treatment of diabetes mellitus. Biosimilar products of insulin glargine can provide patients with additional safe, high-quality, and potentially cost-effective options for treating diabetes. This article presents a randomized, double-blind, single-dose, two-treatment, four-period, replicate crossover, euglycemic clamp study which was designed to evaluate the PK and PD similarity between the recombinant insulin glargine developed by Wanbang (test) and Lantus® (reference) in healthy volunteers. Subjects received subcutaneous administration of the insulin glargine formulation (0.4 U/kg) on two occasions for the test and reference drug, respectively, and a 20% dextrose solution was infused at variable rate to clamp the blood glucose concentrations at 0.3 mmol/L below the subjects' fasting glucose for 24 h. Taking advantage of the improved sensitivity of the bioanalytical method applied and the solution of the matrix stability problem, the parent insulin glargine was determined in the vast majority of plasma samples using a fully validated UHPLC-MS/MS method. The PK characteristics of the parent insulin glargine were revealed for the first time: after subcutaneous injection, concentrations of the parent insulin glargine increased to a relative high level within 3 h, and then, a relatively flat concentration-time profile lasting for at least 12 h post-dose was observed. For the first time, the pharmacokinetic parameters of the parent insulin glargine were used as endpoints for similarity evaluation, which complied with the regulatory guidance better and made the similarity conclusion more powerful. The ratios of geometric means of all PK and PD endpoints were close to 100.00%. For the PK endpoints (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of the parent insulin glargine and its metabolite M1), the 90% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. For the PD endpoints [AUCGIR(0-24h), GIRmax, AUCGIR(0-12h), and AUCGIR(12-24h)], the 95% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. Based on the above mentioned results, it can be concluded that the PK and PD characteristics of the biosimilar drug developed by Wanbang are similar to those of Lantus.

18.
Front Psychol ; 13: 978144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092063

RESUMO

The outbreak of the COVID-19 epidemic has promoted the popularity of online learning, but has also exposed some problems, such as a lack of interaction, resulting in loneliness. Against this background, students' attitudes toward peer interaction may have become even more important. In order to explore the impact of attitude toward peer interaction on students' mindset including online learning motivation and critical thinking practice that could affect their problem-solving self-efficacy during the COVID-19 pandemic, we developed and administered a questionnaire, receiving 1,596 valid responses. The reliability and validity of the questionnaire were re-tested, and structural equation modeling was applied. It was found that attitude toward peer interaction could positively predict middle school students' online learning motivation and critical thinking. Learning motivation and critical thinking also positively supported problem-solving self-efficacy. It is expected that the results of this study can be a reference for teachers to adopt student-centered online learning in problem solving courses.

19.
Molecules ; 27(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080318

RESUMO

The COVID-19 pandemic continues to impose a huge threat on human health due to rapid viral mutations. Thus, it is imperative to develop more potent antivirals with both prophylactic and treatment functions. In this study, we screened for potential antiviral compounds from Sarcandra glabra (SG) against Cathepsin L and HIV-1 proteases. A FRET assay was applied to investigate the inhibitory effects and UPLC-HRMS was employed to identify and quantify the bioactive components. Furthermore, molecular docking was carried out to get a glimpse of the binding of active compounds to the proteases. Our results showed that the SG extracts (SGW, SG30, SG60, and SG85) inhibited HIV-1 protease with an IC50 of 0.003~0.07 mg/mL and Cathepsin L protease with an IC50 of 0.11~0.26 mg/mL. Fourteen compounds were identified along with eight quantified from the SG extracts. Chlorogenic acid, which presented in high content in the extracts (12.7~15.76 µg/mg), possessed the most potent inhibitory activity against HIV-1 protease (IC50 = 0.026 mg/mL) and Cathepsin L protease (inhibition: 40.8% at 0.01 mg/mL). Thus, SG extracts and the active ingredients could potentially be used to prevent/treat viral infections, including SARS-CoV-2, due to their dual-inhibition functions against viral proteases.


Assuntos
COVID-19 , HIV-1 , Antivirais/química , Antivirais/farmacologia , Catepsina L , HIV-1/metabolismo , Humanos , Simulação de Acoplamento Molecular , Pandemias , Peptídeo Hidrolases , SARS-CoV-2
20.
Molecules ; 27(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080327

RESUMO

The roots of Sophora tonkinensis Gagnep., a traditional Chinese medicine, is known as Shan Dou Gen in the Miao ethnopharmacy. A large number of previous studies have suggested the usage of S. tonkinensis in the folk treatment of lung, stomach, and throat diseases, and the roots of S. tonkinensis have been produced as Chinese patent medicines to treat related diseases. Existing phytochemical works reported more than 300 compounds from different parts and the endophytic fungi of S. tonkinensis. Some of the isolated extracts and monomer compounds from S. tonkinensis have been proved to exhibit diverse biological activities, including anti-tumor, anti-inflammatory, antibacterial, antiviral, and so on. The research progress on the phytochemistry and pharmacological activities of S. tonkinensis have been systematically summarized, which may be useful for its further research.


Assuntos
Sophora , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Fungos , Medicina Tradicional Chinesa , Compostos Fitoquímicos/análise , Raízes de Plantas/química , Sophora/química
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