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1.
Bioengineered ; 13(5): 11844-11855, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35549631

RESUMO

Circular RNAs (circRNAs) are non-coding RNAs with covalent closed-loop structures that are vital in regulating diverse pathological processes. This work is aimed to investigate the role of circ_0120376 in non-small cell lung cancer (NSCLC). Circ_0120376, microRNA (miR)-148b-3p, and centrosomal protein 55 (CEP55) mRNA expression in NSCLC tissues and cells were determined using qRT-PCR. The influences of circ_0120376 and miR-148b-3p on the proliferation of NSCLC cell lines were analyzed by CCK-8 and colony formation assays. Apoptosis was analyzed by flow cytometry. Cell migration and invasion were analyzed using the Transwell experiment. Binding relationships between circ_0120376 and miR-148b-3p and between miR-148b-3p and CEP55 3'UTR were investigated using the dual-luciferase reporter experiment and the RIP experiment. Western blot was conducted to analyze the regulatory effect of circ_0120376 and miR-148b-3p on CEP55 expression. We found that circ_0120376 was markedly overexpressed in NSCLC, and its overexpression was positively associated with increased T stage and lymph node metastasis of the patients. Functional experiments unveiled that circ_0120376 enhanced the proliferation, migration and invasion of NSCLC cells and impeded apoptosis, while knocking down circ_0120376 remarkably suppressed the malignant features of NSCLC cells mentioned above. Circ_0120376 could adsorb miR-148b-3p to reduce miR-148b-3p expression, and circ_0120376 could increase CEP55 expression via adsorbing miR-148b-3p. In summary, circ_0120376 contributes to the malignancy of NSCLC cells through a ceRNA mechanism via regulating miR-148b-3p/CEP55 axis. Circ_0120376 is likely to be a potential diagnostic biomarker and therapeutic target for NSCLC.

2.
J Med Virol ; 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570330

RESUMO

As one of the most rapidly evolving proteins of the genus Betacoronavirus, ORF8's function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by ROS scavenger and ER-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion,we examined the plasma samples of COVID-19 convalescent patients and found that the patients aged 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in five-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of SARS-CoV-2 infection on the human reproductive system. This article is protected by copyright. All rights reserved.

3.
J Alzheimers Dis ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35570485

RESUMO

BACKGROUND: Synaptic abnormalities in synaptic proteins are the initial hallmarks of Alzheimer's disease (AD). The higher level of palmitoylation of synaptic proteins was closely associated with amyloid-ß (Aß) in AD. Cattle encephalon glycoside and ignotin (CEGI) have been shown to act as multitarget neurotrophic agents in APPswe/PS1dE9 (APP/PS1) transgenic AD mice. However, it is not clear whether CEGI can influence Aß deposition or whether it does so by the regulation of protein palmitoylation and expression of synaptic proteins in transgenic AD mice. OBJECTIVE: In this study, we investigated the roles of CEGI in modulating postsynaptic density protein 95 (PSD-95) palmitoylation, Aß pathologies, and expression of synaptic-associated proteins in APP/PS1 mice. METHODS: Five-month-old APP/PS1 mice were treated intraperitoneally with 6.6 mL/kg of CEGI for 6 weeks. At the end of the treatment period, APP/PS1 mice were subjected to Morris water maze to test their cognitive functions. Acyl-biotinyl exchange (ABE) for PSD-95 palmitoylation, immunofluorescent staining for expression of PSD-95, N-methyl-D-aspartic acid receptor subunit 2B (NR2B), and synaptotagmin 1 (SYT1) were assessed in mouse brain sections. RESULTS: CEGI treatment in APP/PS1 mice significantly reduced Aß deposition, relieved memory deficits, and decreased PSD-95 palmitoylation while markedly increasing the expression of PSD-95, NR2B, and SYT1 in the frontal cortex. There was a significant correlation between Aß expression and PSD-95 palmitoylation in APP/PS1 mice. CONCLUSION: Our findings demonstrate that CEGI improved AD-like neuropathology, possibly by inhibiting PSD-95 palmitoylation, improving learning memory, and enhancing expression of synaptic-associated proteins, representing a potential therapy for AD treatment.

4.
ACS Sustain Chem Eng ; 10(6): 2204-2213, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35572496

RESUMO

Carbon nanotubes (CNTs) are promising nanofillers to enhance the mechanical performance of polymers. Through catalytic conversion, waste plastics can be converted into CNTs, which could be an alternative to commercial CNTs (cCNTs). Exploring a practical application of waste-plastic-derived CNTs will largely promote the technology development related to waste plastic management and CNT production. In this work, CNTs produced from plastics, named pCNTs, were applied as fillers to epoxy resin (EP), while commercial CNTs (cCNTs) were used as a reference. The carboxyl groups were effectively inserted on the CNT skeleton by a facile purification and modification. After ultrasonic dispersion, the modified pCNTs (M-pCNTs) were uniformly dispersed and loaded in the EP matrix. Better mechanical properties than EP were attained with a Young's modulus of 3776.9 MPa, a tensile strength of 37.3 MPa, a fracture strain of 6.32%, and a fracture strength of 111.7 MPa with 2 wt % M-pCNT loading. Thus, pCNTs enhanced the toughness of the EP composites and simultaneously retained the stiffness. It was suggested that CNT pull-out and bridging were predominant toughening mechanisms for pCNT/EP composites. Notably, the coated film developed between residual metal in M-pCNTs and EP built a strong interfacial interaction and reinforced the EP composites.

5.
Cancer Cell Int ; 22(1): 181, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524253

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as master regulators for gene expression and thus play a vital role in human tumorigenesis and progression. But the involvement of novel lncRNAs in non-small cell lung cancer (NSCLC) remains largely unelucidated. METHODS: A total of 170 NSCLC and their adjacent non-tumor tissues were enrolled to detect the expression of Lnc-LSAMP-1 by RT-qPCR. The effects of Lnc-LSAMP-1 on cell proliferation, migration, invasion and drug-sensitivity were determined by in vitro and in vivo experiments. The proteins that interact with Lnc-LSAMP-1were confirmed by RNA pull-down assay. RNA-sequencing were used to identify the potential targets of Lnc-LSAMP-1 in NSCLC. RESULTS: We found that Lnc-LSAMP-1 was significantly down-regulated in 170 cases of NSCLC tissues when compared to their adjacent non-cancerous tissues. Loss expression of Lnc-LSAMP-1 was notably correlated with unfavorable prognosis of NSCLC patients. The ectopic expression of Lnc-LSAMP-1 drastically inhibited lung cancer cell proliferation, viability, invasion and migration ability, arrested cell cycle and facilitated apoptosis. Chemotherapy sensitization experiments showed that over-expressed Lnc-LSAMP-1 enhanced the inhibition of cell proliferation induced by TKI. Mechanistically, Lnc-LSAMP-1-LSAMP formed a complex which could protect the degradation of LSAMP gene, and thus exerted crucial roles in NSCLC progression and TKI targeted treatment. CONCLUSIONS: Consequently, our findings highlight the function and prognostic value of Lnc-LSAMP-1 in NSCLC and provide potential novel therapeutic targets and prognostic biomarkers for patients with NSCLC.

6.
Comput Methods Programs Biomed ; 221: 106887, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35597204

RESUMO

BACKGROUND AND OBJECTIVE: Deep learning abdominal multi-organ segmentation provides preoperative guidance for abdominal surgery. However, due to the large volume of 3D CT sequences, the existing methods cannot balance complete semantic features and high-resolution detail information, which leads to uncertain, rough, and inaccurate segmentation, especially in small and irregular organs. In this paper, we propose a two-stage algorithm named multi-dimensional cascaded net (MDCNet) to solve the above problems and segment multi-organs in CT images, including the spleen, kidney, gallbladder, esophagus, liver, stomach, pancreas, and duodenum. METHODS: MDCNet combines the powerful semantic encoder ability of a 3D net and the rich high-resolution information of a 2.5D net. In stage1, a prior-guided shallow-layer-enhanced 3D location net extracts entire semantic features from a downsampled CT volume to perform rough segmentation. Additionally, we use circular inference and parameter Dice loss to alleviate uncertain boundary. The inputs of stage2 are high-resolution slices, which are obtained by the original image and coarse segmentation of stage1. Stage2 offsets the details lost during downsampling, resulting in smooth and accurate refined contours. The 2.5D net from the axial, coronal, and sagittal views also compensates for the missing spatial information of a single view. RESULTS: The experiments on the two datasets both obtained the best performance, particularly a higher Dice on small gallbladders and irregular duodenums, which reached 0.85±0.12 and 0.77±0.07 respectively, increasing by 0.02 and 0.03 compared to the state-of-the-art method. CONCLUSION: Our method can extract all semantic and high-resolution detail information from a large-volume CT image. It reduces the boundary uncertainty while yielding smoother segmentation edges, indicating good clinical application prospects.

7.
Arthritis Rheumatol ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506208

RESUMO

OBJECTIVE: Prevention of osteoarthritis remains important as there are no disease-modifying treatments. A personalized approach has the potential to better target prevention strategies. We used recently identified genetic risk variants from genome-wide association analysis for advanced osteoarthritis to calculate polygenic risk scores (PRSs) for knee and hip osteoarthritis, and assessed PRS performance in an independent population of older community-dwelling adults. METHODS: PRSs were calculated in 12,093 individuals of European genetic descent aged ≥70 years, enrolled into the ASPREE trial. The outcome measure was knee and hip replacement (hospitalisations during the trial and self-reported joint replacements before enrolment). PRSs were considered as continuous (per standard deviation [SD]) and categorical (low-risk [0-20%], medium-risk [21-80%], high-risk [81-100%]) variables. Logistic regression was used to examine associations between PRSs and risk of joint replacement, adjusted for age, sex, body mass index, and socio-economic status. RESULTS: 1422 (11.8%) participants had knee and 1297 (10.7%) had hip replacements. PRSs (per SD) were associated with risk of knee (odds ratio [OR]=1.13, 95% CI 1.07-1.20) and hip (OR=1.23 [1.16-1.30]) replacements. Participants with high PRS had increased risk of knee (OR=1.44 [1.20-1.73]) and hip (OR=1.88 [1.56-2.26]) replacements, compared with low PRS. Associations were stronger for PRSs and hip replacement risk in females than in males. Associations were similar in sensitivity analyses examining joint replacements before and during the trial separately. CONCLUSION: PRSs have the potential to improve prevention of severe knee and hip osteoarthritis by providing a personalized approach and identifying individuals who may benefit from early intervention. This article is protected by copyright. All rights reserved.

8.
Front Cell Dev Biol ; 10: 846864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531099

RESUMO

Glioblastoma (GBM) is one of the most prevalent and aggressive cancers worldwide. The overall survival period of GBM patients is only 15 months even with standard combination therapy. The absence of validated biomarkers for early diagnosis mainly accounts for worse clinical outcomes of GBM patients. Thus, there is an urgent requirement to characterize more biomarkers for the early diagnosis of GBM patients. In addition, the detailed molecular basis during GBM pathogenesis and oncogenesis is not fully understood, highlighting that it is of great significance to elucidate the molecular mechanisms of GBM initiation and development. Recently, accumulated pieces of evidence have revealed the central roles of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of GBM by binding with DNA, RNA, or protein. Targeting those oncogenic lncRNAs in GBM may be promising to develop more effective therapeutics. Furthermore, a better understanding of the biological function and underlying molecular basis of dysregulated lncRNAs in GBM initiation and development will offer new insights into GBM early diagnosis and develop novel treatments for GBM patients. Herein, this review builds on previous studies to summarize the dysregulated lncRNAs in GBM and their unique biological functions during GBM tumorigenesis and progression. In addition, new insights and challenges of lncRNA-based diagnostic and therapeutic potentials for GBM patients were also introduced.

9.
Oxid Med Cell Longev ; 2022: 2590198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535361

RESUMO

The tryptophan residue has a large hydrophobic surface that plays a unique role in the folded protein conformation and functions. Tryptophan modifications are presumably to be readily detected in proteins due to the vulnerability of the indole structure to electrophilic attacks. In this study, we report a systematic identification of sequence variations at tryptophan, termed tryptophan variants, from the proteome of patients with nonsmall cell lung cancer (NSCLC). Using shotgun proteomics and a modified open search algorithm, 25 tryptophan variants on 2481 sites in over 858 proteins were identified. Among these, 6 tryptophan variants are previously identified, 15 are newly annotated, and 4 are still unknown, most of which are involved in the cascade of oxidation in the blood microparticle. Remarkably, Trp313 of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was up-oxidized whereas Trp16 and Trp38 of hemoglobin (HBB) were down-oxidized in NCSLC tissues. The results were further supported by an independent cohort of 103 lung adenocarcinoma samples, reflecting a negative feedback and potential detoxification mechanism against tumor glycolysis and hypoxia. Overall, the study reports a quick approach to explore tryptophan variants at the proteomic scale. Our findings highlight the predominant role of tryptophan oxidation in regulating the redox balance of cancer cells and its potential role as prognostic biomarker for patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Hipóxia , Neoplasias Pulmonares/patologia , Proteoma/metabolismo , Proteômica/métodos , Triptofano
10.
Front Endocrinol (Lausanne) ; 13: 870708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35518924

RESUMO

Purpose: This study aimed to develop a risk prediction of fertilization disorders during the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: A retrospective study was performed with 106,728 fresh embryo IVF/ICSI cycles from 2009 to 2019. Basic characteristics of patients, clinical treatment data, and laboratory parameters were involved. The associations between the selected variables and risks for low fertilization rate (LFR) and total fertilization failure (TFF) were investigated. Ordinal logistic regression and the receiver operating characteristic curves (ROCs) were used to construct and evaluate the prediction models. Results: A total of 97,181 controls, 4,343 LFR and 5,204 TFF cases were involved in this study. The model based on clinical characteristics (the ages of the couples, women's BMI, types of infertility, ART failure history, the diminished ovarian reserve, sperm quality, insemination method, and the number of oocytes retrieved) had an AUC of 0.743 for TFF. The laboratory model showed that primary infertility, ART failure history, minimal-stimulation cycle/natural cycle, numbers of oocyte retrieved < 5, IVF, and Anti-Mullerian hormone (AMH) level < 1.1ng/ml are predictors of TFF, with an AUC of 0.742. Conclusion: We established a clinical and a laboratory prediction model for LFR/TFF. Both of the models showed relatively high AUCs.


Assuntos
Infertilidade , Injeções de Esperma Intracitoplásmicas , Feminino , Fertilização/fisiologia , Fertilização In Vitro/métodos , Humanos , Infertilidade/terapia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodos
11.
Endocrinology ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536227

RESUMO

Obesity has recently been defined as a chronic low-grade inflammatory disease. Obesity-induced inflammation of adipose tissue (AT) is an essential trigger for insulin resistance (IR) and related metabolic diseases. Although the underlying molecular basis of this inflammation has not been fully identified, there is consensus that the recruited and activated macrophages in AT are the most important culprits of AT chronic inflammation. Adipose tissue macrophages (ATMs) are highly plastic and could be polarized from an anti-inflammatory M2 to pro-inflammatory M1 phenotypes upon stimulation by micro-environmental signals from obese AT. Many efforts have been made to elucidate the molecular signaling pathways of macrophage polarization, however, the upstream drivers governing and activating macrophage polarization have rarely been summarized, particularly regulatory messages from the AT micro-environment. In addition to adipocytes, the AT bed also contains a variety of immune cells, stem cells, as well as vascular, neural and lymphatic tissues throughout, which together orchestrate the AT micro-environment. Here, we summarized how the aforesaid neighbors of ATMs in the AT micro-environment send messages to ATMs and thus regulate its phenotype during obesity. Deciphering the biology and polarization of ATMs in the obese environment is expected to provide a precise immunotherapy for adipose inflammation and obesity-related metabolic diseases.

12.
BMC Med Imaging ; 22(1): 82, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501717

RESUMO

BACKGROUND: An accurate preoperative assessment of cervical lymph node metastasis (LNM) is important for choosing an optimal therapeutic strategy for papillary thyroid carcinoma (PTC) patients. This study aimed to develop and validate two ultrasound (US) nomograms for the individual prediction of central and lateral compartment LNM in patients with PTC. METHODS: A total of 720 PTC patients from 3 institutions were enrolled in this study. They were categorized into a primary cohort, an internal validation, and two external validation cohorts. Radiomics features were extracted from conventional US images. LASSO regression was used to select optimized features to construct the radiomics signature. Two nomograms integrating independent clinical variables and radiomics signature were established with multivariate logistic regression. The performance of the nomograms was assessed with regard to discrimination, calibration, and clinical usefulness. RESULTS: The radiomics scores were significantly higher in patients with central/lateral LNM. A radiomics nomogram indicated good discrimination for central compartment LNM, with an area under the curve (AUC) of 0.875 in the training set, the corresponding value in the validation sets were 0.856, 0.870 and 0.870, respectively. Another nomogram for predicting lateral LNM also demonstrated good performance with an AUC of 0.938 and 0.905 in the training and internal validation cohorts, respectively. The AUC for the two external validation cohorts were 0.881 and 0.903, respectively. The clinical utility of the nomograms was confirmed by the decision curve analysis. CONCLUSION: The nomograms proposed here have favorable performance for preoperatively predicting cervical LNM, hold promise for optimizing the personalized treatment, and might greatly facilitate the decision-making in clinical practice.


Assuntos
Linfonodos , Neoplasias da Glândula Tireoide , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/diagnóstico por imagem , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Ultrassonografia
13.
Lancet Glob Health ; 10(6): e820-e830, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35561719

RESUMO

BACKGROUND: Infertility and intimate partner violence (IPV) are of serious concern globally, yet the prevalence of IPV against infertile women has not been quantified at the regional or global level. We aimed to estimate the prevalence of IPV against infertile women and its variation in low-income and middle-income countries (LMICs). METHODS: We did a systematic literature search of 11 databases for articles published between database inception and Sept 30, 2021, and performed meta-analyses to estimate the pooled prevalence and 95% CI of IPV against infertile women in LMICs. We used subgroup analyses and meta-regressions to explore variation in the prevalence by study period (2010 and before vs after 2010), study region (Africa, west Asia, south Asia, and east Asia), type of infertility (primary or secondary), risk of bias (high, moderate, or low), sample size (continuous variable), and measuring tools (the modified Abuse Assessment Screen, the WHO Violence Against Women instrument, or the revised Conflict Tactics Scales). This study is registered with PROSPERO, CRD42021248448. FINDINGS: Of 2661 references identified (2637 via database searches and 24 via secondary searches), 120 full-text articles were reviewed, and we identified 30 relevant studies conducted in nine LMICs between 2000 and 2019. 25 studies met the inclusion criteria for meta-analysis, with a total sample size of 7164 participants. The 12-month prevalence of IPV among infertile women was 36·0% (95% CI 20·4-55·2), compared with a lifetime prevalence of 47·2% (31·7-63·3). The most common type of IPV was psychological violence, with a prevalence of 24·6% (11·3-45·6) over 12 months and 51·5% (38·8-64·0) over a lifetime (slightly higher than the pooled overall rate due to different data sources), respectively; followed by physical violence (11·9% [5·2-25·1] and 20·2% [12·1-31·7]); sexual violence (8·7% [2·6-25·0] and 11·5% [6·1-20·7]); and economic coercion (2·6% [0·4-13·7] and 9·8% [5·7-16·5]). Significant variations of lifetime prevalence estimates were presented by study period (R2=39·46%), region (R2=50·95%), and measuring tools (R2=54·27%). INTERPRETATION: A high prevalence of IPV against infertile women is evident despite heterogeneity across studies. IPV screening, counselling, and structural interventions should be tailored to address this urgent issue at multiple levels of society. FUNDING: China Medical Board and WHO.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35565007

RESUMO

The study on ecosystem health evaluation for restored urban rivers is of specific significance to improving river health and realizing the adaptive management for urban river ecosystems. Based on the health definition of restored urban rivers in North China, this study attempted to set up a system of alternative indicators on ecosystem health assessment, including water quality, water regime, aquatic organism, riparian environment, and physical morphology. Additionally, a set of health assessment system was proposed, including selection of assessment indexes and determination of assessment criteria and health classes. Taking seventeen typical restored urban rivers in Beijing as the assessment target, the said system was applied in assessing urban river health in 2016 and 2019. As the assessment results indicated, in 2016, the health statuses of 29 percent of urban rivers were ordinary, while 71 percent of urban rivers were somewhat inferior. In 2019, the health state of only one urban river reached "good" level. The health statuses of 88 percent of urban rivers were ordinary, and 6 percent were somewhat inferior in terms of comprehensive health index. In 2019, the health states of rivers improved significantly compared with that of 2016, which indicated that most urban rivers saw marked improvement in ecosystem health after ecological restoration. The health assessment system proposed in the paper not only could be applied to regular evaluation of restored urban rivers in the north but also was suitable for a contrastive health-state analysis between different years prior to or after the restoration. In order to carry out adaptive management of water ecology in urban rivers, the measures of ecological restoration could be adjusted based on the regular health assessment and health weakness analysis.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35579686

RESUMO

BACKGROUND: The effects of sevoflurane anesthesia on childhood neurodevelopment and adult brain function have attracted increasing scientific attentions. However, the exact mechanisms underlying hyperphosphorylation of tau protein in sevoflurane induced abnormalities in central nervous system (CNS) development, particularly in the hippocampus, have not been fully determined. METHODS: We utilized molecular biological and behavioral approaches to compare the changes in cognitive function in mice exposed to repeated sevoflurane during the neonatal stage, and to assess whether PP2A-associated tau hyperphosphorylation is involved in sevoflurane induced neonatal neurotoxicity. RESULTS: We reported that mice anesthetized with repeated sevoflurane during the neonatal period caused cognitive dysfunction during the adulthood. More importantly, we found that hyperphosphorylation of tau protein and decreased level of protein phosphatase 2A (PP2A) were detected in the hippocampus of mice after neonatal exposure of sevoflurane. Meanwhile, GSK-3ß activity was found to be increased with repeated sevoflurane exposure, but not for more than 2 weeks. CONCLUSION: Our results suggest that PP2A-associated hyperphosphorylation of tau protein might contribute to sevoflurane induced developmental neurotoxicity. These findings could provide a theoretical basis for the safely usage of sevoflurane in pediatric surgeries, and offer a valuable reference and potential therapeutic targets for the development of neuroprotective drugs.

16.
Front Pharmacol ; 13: 908212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600878

RESUMO

Tonsillectomy is a frequently performed surgical procedure in children, requiring post-operative analgesia. This study evaluated the efficacy and safety of nalbuphine or sufentanil combined with dexmedetomidine for patient-controlled intravenous analgesia (PCIA) after pediatric tonsillectomy adenoidectomy. A total of 400 patients undergoing tonsillectomy with and without adenoidectomy were included in the study. Patients received a PCIA pump (0.5 mg/kg nalbuphine, 2 µg/kg dexmedetomidine and 0.9% sodium chloride to a total volume of 100 ml) for postoperative pain management were classified into Group ND (n = 200). Patients received a PCIA pump (2 µg/kg sufentanil, 2 µg/kg dexmedetomidine and 0.9% sodium chloride to a total volume of 100 ml) for postoperative pain management were classified into Group SD (n = 200). More stable hemodynamic changes were noted in Group ND than Group SD from 1 h to 48 h after operation. At 6, 12, 24, and 48 h after operation, the children in Group ND had higher Ramsay sedation scores than those in Group SD. The times to push the PCIA button in Group ND and Group SD were 2.44 ± 0.74 and 2.62 ± 1.00, showing significant differences (p = 0.041). The VASR scores of children in Group ND were significantly lower within 6, 12, and 24 h than those in Group SD (p < 0.05). The VASC scores of children in Group ND were significantly lower within four time points (2, 6, 12, and 24 h) than those in Group SD (p < 0.05). At 1st day after surgery, the children in Group ND had lower levels of serum ACTH, IL-6, and COR levels than those in Group SD (p < 0.001). The incidence rates of nausea and vomiting, and pruritus were significantly higher in Group SD than Group ND (5.00% vs. 11.00%, p = 0.028; 1.00% vs. 4.50%, p = 0.032). The total incidence rate of adverse reactions was significantly higher in Group SD than Group ND (15.00% vs. 31.00%, p = 0.0001). The study demonstrated that dexmedetomidine added to nalbuphine PCIA enhanced the analgesic effects, attenuated the postoperative pain, and reduced the stress response after pediatric tonsillectomy adenoidectomy.

17.
Environ Int ; 164: 107273, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35526298

RESUMO

Human uptake abundance of microplastics via various pathways, and they accumulate in human liver, kidney, gut and even placenta (especially with a diameter of 1 µm or less). Recent scientific studies have found that exposure to microplastics causes intestinal inflammation and liver metabolic disorder, but it remains largely unknown that whether the damage and inflammation may cause further development of severe diseases. In this study, we discovered one of such potential diseases that may be induced by the exposure to small-sized microplastics (with a diameter of 1 µm) performing a multi-organ and multi-omics study comprising metabolomics and microbiome approaches. Unlike other animal experiments, the dosing strategy was applied in mice according to the daily exposure of the highly exposed population, which was more environmentally relevant and reflective of real-world human exposure. Our studies on the gut-liver axis metabolism have shown that the crosstalk between the gut and liver ultimately leaded to insulin resistance and even diabetes. We proactively verified this hypothesis by measuring the levels of fasting blood glucose and fasting insulin, which were found significantly elevated in the mice with microplastics exposure. These results indicate the urgent need of large-scale cohort evaluation on epidemiology and prognosis of insulin resistance after microplastics exposure in future.


Assuntos
Resistência à Insulina , Microplásticos , Animais , Humanos , Inflamação/metabolismo , Fígado/metabolismo , Camundongos , Plásticos/metabolismo , Poliestirenos/metabolismo
18.
Biosens Bioelectron ; 210: 114347, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35550937

RESUMO

Sensitive and accurate detection of prostate-specific antigen (PSA) is of great significance since it is regarded as a biomarker for prostate diseases. Herein, a facile strategy for the design of highly efficient electrochemiluminescence (ECL) sensor was proposed for PSA assay. Carboxylated graphitic carbon nitride (g-C3N4) nanosheet (CCN) and tris (2, 2'-Bipyridyl) ruthenium (II) (Ru(bpy)32+) encapsulated in silica nanospheres (RuSi NPs) were employed as the donor and acceptor, respectively. CCN and RuSi NPs were covalently bound within one nanocomposite (CCN@RuSi) through the amide bond, which greatly shortened the electron-transfer path. Thus, the resonance energy transfer (RET) efficiency was remarkably increased, providing a high initial ECL intensity for the ECL assay. After the successive introducing of aptamer, PSA, and ferroceneboronic acid (FcBA) on the surface of CCN@RuSi modified electrode, the ECL signal remarkably decreased, which was caused by the steric hindrance of PSA and electron transfer quenching between Fc+ and excited-state Ru(bpy)32+*. Therefore, a highly efficient ECL platform was constructed, which achieved the ultrasensitive detection of PSA with a linear range and a limit of detection of 100 fg/mL - 50 ng/mL and 1.2 fg/mL, respectively. Furthermore, the dual-affinity of the aptamer and FcBA to PSA endowed the sensor with a high selectivity for the determination of PSA in human serum samples. The present work provides an important reference for the integration of RET and quenching strategy in the ECL study with rapid, ultrasensitive, and highly selective detection performances.


Assuntos
Técnicas Biossensoriais , Nanocompostos , Técnicas Eletroquímicas , Transferência de Energia , Humanos , Medições Luminescentes , Masculino , Metalocenos , Antígeno Prostático Específico
19.
Gene ; 832: 146557, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35568338

RESUMO

Plant small-RNAs regulate various biological processes by manipulating the expression of target genes at the transcriptional and post-transcriptional levels. However, little is known about the response and the functional roles of sRNAs, particularly small-interfering RNAs (siRNAs), in the soybean-soybean cyst nematode interaction. In this study, siRNA data from 24 sRNA libraries constructed from SCN-infected and non-SCN-infected resistant and susceptible soybean roots were analysed in silico. A total of 26 novel siRNAs including 17 phasiRNAs and 9 nat-siRNAs, as well as two phasiRNAs that were differentially expressed (DE) in three comparisons, were identified. Then, using qRT-PCR, the expression of majority of siRNAs was found to be downregulated after SCN infection, and the expression patterns of DE siRNAs were confirmed. Further functional annotation analyses revealed that the target genes of these siRNA were highly related to disease resistance, which included the genes coding for the NB-ARC domain, leucine-rich repeats, and Hs1pro-1 homologous proteins. Overall, the present research identified novel siRNAs and annotated their target genes, thereby laying the foundation for deciphering the roles of siRNAs in the soybean-SCN interaction.

20.
Front Physiol ; 13: 857239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514356

RESUMO

RNAi was used to downregulate the expression of insulin-like peptides (ILP2), with air-modulation, and high-concentration CO2 stress, in the larvae of Tribolium castaneum. We assessed the changes in carbohydrate-related content, trehalase activity, and the expression levels of trehalose pathway genes. And pupation, adult emergence, pupation rate, and mortality were assessed. There was a significant change in the expression of ILPs in T. castaneum, at a certain concentration of CO2. ILP2 RNAi did not alter the trehalose content significantly, however, the glycogen and glucose content increased significantly. High-concentration CO2 stress altered the trehalose content and reduced the glycogen and glucose content. The expression levels of TPS and TRE2 were up-regulated by hypoxia/hypercapnia and dsILP2 combination, with the increase of CO2 concentration, other trehalase genes begin to respond successively. ILP2 knockout raised the mortality and reduced the pupation rate and eclosion rate in CO2. Understanding the insulin pathway responses to hypoxic stress induced by a high concentration of CO2 would further elucidate the mechanisms underlying trehalose metabolism in insects.

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