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1.
Front Neurosci ; 16: 874768, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573317

RESUMO

Friedreich's ataxia (FRDA) is an autosomal recessive disease caused by an intronic guanine-adenine-adenine (GAA) triplet expansion in the frataxin (FXN) gene, which leads to reduced expression of full-length frataxin (1-210) also known as isoform 1. Full-length frataxin has a mitochondrial targeting sequence, which facilitates its translocation into mitochondria where it is processed through cleavage at G41-L42 and K80-S81 by mitochondrial processing (MPP) to release mitochondrial mature frataxin (81-210). Alternative splicing of FXN also leads to expression of N-terminally acetylated extra-mitochondrial frataxin (76-210) named isoform E because it was discovered in erythrocytes. Frataxin isoforms are undetectable in serum or plasma, and originally whole blood could not be used as a biomarker in brief therapeutic trials because it is present in erythrocytes, which have a half-life of 115-days and so frataxin levels would remain unaltered. Therefore, an assay was developed for analyzing frataxin in platelets, which have a half-life of only 10-days. However, our discovery that isoform E is only present in erythrocytes, whereas, mature frataxin is present primarily in short-lived peripheral blood mononuclear cells (PBMCs), granulocytes, and platelets, meant that both proteins could be quantified in whole blood samples. We now report a quantitative assay for frataxin proteoforms in whole blood from healthy controls and FRDA patients. The assay is based on stable isotope dilution coupled with immunoprecipitation (IP) and two-dimensional-nano-ultrahigh performance liquid chromatography/parallel reaction monitoring/high resolution mass spectrometry (2D-nano-UHPLC-PRM/HRMS). The lower limit of quantification was 0.5 ng/mL for each proteoform and the assays had 100% sensitivity and specificity for discriminating between healthy controls (n = 11) and FRDA cases (N = 100 in year-1, N = 22 in year-2,3). The mean levels of mature frataxin in whole blood from healthy controls and homozygous FRDA patients were significantly different (p < 0.0001) at 7.5 ± 1.5 ng/mL and 2.1 ± 1.2 ng/mL, respectively. The mean levels of isoform E in whole blood from healthy controls and homozygous FRDA patients were significantly different (p < 0.0001) at 26.8 ± 4.1 ng/mL and 4.7 ± 3.3 ng/mL, respectively. The mean levels of total frataxin in whole blood from healthy controls and homozygous FRDA patients were significantly different (p < 0.0001) at 34.2 ± 4.3 ng/mL and 6.8 ± 4.0 ng/mL, respectively. The assay will make it possible to rigorously monitor the natural history of the disease and explore the potential role of isoform E in etiology of the disease. It will also facilitate the assessment of therapeutic interventions (including gene therapy approaches) that attempt to increase frataxin protein expression as a treatment for this devastating disease.

2.
Psychiatry Res ; 313: 114616, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35576626

RESUMO

Although many studies have been conducted on the relationship between cognitive functioning, psychopathological symptoms, and global functioning in patients with schizophrenia, these studies frequently suffer from a lack of control for confounding variables, high attrition rates, and a lack of cognitive domains completed at each assessment point. The purpose of this study is to select patients with untreated first-episode schizophrenia to investigate the relationship between psychopathological symptoms, cognitive functioning, and global functioning. A total of 117 untreated first-episode schizophrenia patients were evaluated using the global assessment functions (GAF), the Positive And Negative Syndrome Scale (PANSS), the MATRICS Consensus Cognitive Battery (MCCB), and some social and role functional parameters. The GAF, PANSS, and MCCB scores of 117 patients were significantly lower than normal. Multiple stepwise linear regression analysis revealed that the negative symptom factor, positive symptom factor, excitation-hostility factor, and attention/vigilance were all independent factors influencing global functioning. Our findings show that the negative symptom factor, the positive symptom factor, the excitement hostility factor, and attention/vigilante are all independent risk factors for GAF in first-episode schizophrenia. The negative symptom factor had the most noticeable effect among these influencing factors, followed by the positive symptom factor, the excitement hostility factor, and attention/vigilance in that order.

3.
Eur J Pharmacol ; 923: 174951, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405114

RESUMO

Itaconate (ItA), a byproduct of the Krebs cycle, has recently emerged as an anti-inflammatory metabolite for inhibiting the overactive immune response. In addition to its immunomodulatory and antimicrobial effects, ItA may have other therapeutic avenues. Herein, the effect of ItA on aging was explored in order to better establish the therapeutic potential of this promising metabolite. ItA extended the lifespan and enhanced the stress resistance of Caenorhabditis elegans (C. elegans), even at the doses of 0.01 and 0.1 µM. Moreover, the lifespan extension effect of ItA was pronounced even for the aged worms (days 7 and 9 post adult stage). Furthermore, ItA was found to extend the healthy longevity of C. elegans in a mitochondria-dependent manner. ItA protected the mitochondrial integrity, increased ATP content, and decreased the reactive oxygen species (ROS) in C. elegans. Mechanistic investigations showed that ItA specifically activated the mitochondrial unfolded protein response (UPRmt) in worms and significantly increased the expression of activating transcription factor associated with stress-1 (ATFS-1) that senses mitochondrial stress and communicates with the nucleus during the UPRmt. ItA extended the lifespan of C. elegans in an ATFS-1-dependent manner. In summary, this study elucidates the molecular mechanism by which ItA extends the healthy lifespan and highlights the importance of mitochondrial integrity in the intervention of aging.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Longevidade , Succinatos , Fatores de Transcrição/metabolismo , Resposta a Proteínas não Dobradas
4.
Biomed Pharmacother ; 150: 113005, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35483189

RESUMO

Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.

5.
Bioact Mater ; 18: 91-103, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387173

RESUMO

Thromboembolism is the leading cause of cardiovascular mortality. Currently, for the lack of targeting, short half-life, low bioavailability and high bleeding risk of the classical thrombolytic drugs, pharmacological thrombolysis is usually a slow process based on micro-pumping. In addition, frequently monitoring and regulating coagulation functions are also required during (and after) the process of thrombolysis. To address these issues, a targeted thrombolytic and anticoagulation nanoplatform (UCATS-UK) is developed based on upconversion nanoparticles (UCNPs) that can convert 808 or 980 nm near-infrared (NIR) light into UV/blue light. This nanoplatform can target and enrich in the thrombus site. Synergistic thrombolysis and anticoagulation therapy thus could be realized through the controlled release of urokinase (UK) and nitric oxide (NO). Both in vitro and in vivo experiments have confirmed the excellent thrombolytic and anticoagulative capabilities of this multifunctional nanoplatform. Combined with the unique fluorescent imaging capability of UCNPs, this work is expected to contribute to the development of clinical thrombolysis therapy towards an integrated system of imaging, diagnosis and treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35449813

RESUMO

Liver cirrhosis is a common chronic disease in China. The effect of modified Xianglian Pingwei powder plus Western medicine in the treatment of liver cirrhosis and positive small intestinal bacterial overgrowth is promising. Totally, 100 patients with liver cirrhosis and positive intestinal bacterial overgrowth in Cangzhou Central Hospital from February 2020 to February 2021 were enrolled and randomized via the random number table method at a ratio of 1 : 1 into the study group and control group. The control group received glutathione and levofloxacin hydrochloride, and the study group received Xianglian Pingwei powder plus glutathione and levofloxacin hydrochloride. The traditional Chinese medicine (TCM) syndrome scores, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels of the two groups were decreased after treatment with lower results in the study group. Xianglian Pingwei powder plus glutathione and levofloxacin hydrochloride was associated with a significantly lower positive rate of small intestine bacterial growth, serum endotoxin level, and peripheral blood toll-like receptor 2 (TLR2) and TRL4 levels versus glutathione and levofloxacin hydrochloride. The combined medication achieved a higher efficacy (90.00%) versus glutathione and levofloxacin hydrochloride (66.00%). The two groups experienced similar safety. Xianglian Pingwei powder plus glutathione and levofloxacin hydrochloride achieved significant benefits of clinical efficacy with a high safety profile in patients with liver cirrhosis versus glutathione and levofloxacin hydrochloride.

7.
Clin Transl Med ; 12(4): e817, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35474296

RESUMO

BACKGROUND: Extrachromosomal circular deoxyribonucleic acid (eccDNA) is evolving as a valuable biomarker, while little is known about its presence in urine. METHODS: Here, we report the discovery and analysis of urinary cell-free eccDNAs (ucf-eccDNAs) in healthy controls and patients with advanced chronic kidney disease (CKD) by Circle-Seq. RESULTS: Millions of unique ucf-eccDNAs were identified and comprehensively characterised. The ucf-eccDNAs are GC-rich. Most ucf-eccDNAs are less than 1000 bp and are enriched in four pronounced peaks at 207, 358, 553 and 732 bp. Analysis of the genomic distribution of ucf-eccDNAs shows that eccDNAs are found on all chromosomes but enriched on chromosomes 17, 19 and 20 with a high density of protein-coding genes, CpG islands, short interspersed transposable elements (SINEs) and simple repeat elements. Analysis of eccDNA junction sequences further suggests that microhomology and palindromic repeats might be involved in eccDNA formation. The ucf-eccDNAs in CKD patients are significantly higher than those in healthy controls. Moreover, eccDNA with miRNA genes is highly enriched in CKD ucf-eccDNA. CONCLUSIONS: This work discovers and provides the first deep characterisation of ucf-eccDNAs and suggests ucf-eccDNA as a valuable noninnvasive biomarker for urogenital disorder diagnosis and monitoring.


Assuntos
DNA Circular , Insuficiência Renal Crônica , Biomarcadores , DNA , DNA Circular/genética , Feminino , Genômica , Humanos , Masculino , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética
8.
Chemosphere ; 301: 134628, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35447213

RESUMO

In the context of carbon peak, neutrality, and circular agricultural economy, the use of renewable resources from agricultural processing for plant cultivation still needs to be explored to clarify material flow and its ecological effects. Paddy-upland rotation is an effective agricultural strategy to improve soil quality. This study evaluated the effects of biogas slurry application against those of chemical fertilisers in these two typical Chinese cropping soils. The application of biogas slurry increased total carbon content in paddy soil by 73.4%, and that in upland soil by 65.8%. Conversely, application of chemical fertiliser reduced total carbon in both soil types. There were significant positive correlations between total carbon and Zn, Cu, and Pb in rice husks grown in paddy soil (R2 = 0.95, 0.996, 0.95; p < 0.05). The content of amylose in biogas slurry treatment of paddy soil increased by 35.9%, while that in upland soil decreased by 19.2%. After biogas slurry was applied, the contents of fulvic acid- and humic acid-like substances in paddy soil average increased by 40.9% and 45.6%, while the contents of protein-like components were enhanced by 46.8% in upland soil. This result was consistent with predictions of microbial community function. Microorganisms in paddy soil generally preferred carbon fixation, while those in upland soil preferred hydrocarbon degradation and chemoheterotrophy. Understanding the changes in soil carbon stock and microbial function after biogas slurry application will contribute to sustainable agricultural development and food security.

9.
Eur J Neurol ; 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363940

RESUMO

BACKGROUND: Short-term exposure to ambient air pollution has been linked to increased risk of stroke mortality, but its adverse effects on mortality from specific types of stroke including ischemic stroke and hemorrhagic stroke remain poorly understood. METHODS: Using the China National Mortality Surveillance System, we conducted a time-stratified case-crossover study among 412,567 stroke deaths in Jiangsu province, China during 2015-2019. Residential daily PM2.5 , PM10 , SO2 , NO2 , CO, and O3 exposure concentrations were extracted from the ChinaHighAirPollutants dataset for each subject. Conditional logistic regression models were performed to conduct exposure-response analyses. RESULTS: Each 10 µg/m3 increase of PM2.5 , PM10 , SO2 , NO2 , CO, and O3 was respectively associated with a 1.44%, 0.93%, 5.55%, 2.90%, 0.148%, and 0.54% increase in odds of mortality from ischemic stroke, which was significantly stronger than that from hemorrhagic stroke (percent change in odds: 0.74%, 0.51%, 3.11%, 1.15%, 0.090%, and 0.10%). The excess fraction of ischemic stroke mortality associated with PM2.5 , PM10 , SO2 , NO2 , CO, and O3 exposure was 6.90%, 6.48%, 8.21%, 8.61%, 9.67%, and 4.76%, respectively, which was also significantly higher than that of hemorrhagic stroke mortality (excess fraction: 3.49%, 3.48%, 4.69%, 3.48%, 5.86%, and 0.88%). These differences in adverse effects generally remained across sex, age, and season. CONCLUSIONS: Short-term exposure to ambient air pollution was significantly associated with increased risk of both ischemic and hemorrhagic stroke mortality and posed considerable excess mortality. Our results suggest that air pollution exposure may lead to substantially greater adverse effects on mortality from ischemic stroke than that from hemorrhagic stroke.

10.
J Neurol ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35486214

RESUMO

BACKGROUND: There is increasing evidence for the role of inflammation in the pathogenesis of mitochondrial diseases (MDs). However, the mechanisms underlying mutation-induced inflammation in MD remain elusive. Our previous study suggested that mitophagy is impaired in the skeletal muscle of those with MD, likely causing mitochondrial DNA (mtDNA) release and thereby triggering inflammation. We here aimed to decipher the role of the cGAS-STING pathway in inflammatory process in MDs. METHODS: We investigated the levels of circulating cell-free mtDNA (ccf-mtDNA) in the serum of 104 patients with MDs. Immunofluorescence was performed in skeletal muscles in MDs and control. Biochemical analysis of muscle biopsies was conducted with western blot to detect cGAS, STING, TBK1, IRF3 and phosphorylated IRF3 (p-IRF3). RT-qPCR was performed to detect the downstream genes of type I interferon in skeletal muscles. Furthermore, a protein microarray was used to examine the cytokine levels in the serum of patients with MDs. RESULTS: We found that ccf-mtDNA levels were significantly increased in those with MDs compared to the controls. Consistently, the immunofluorescent results showed that cytosolic dsDNA levels were increased in the muscle samples of MD patients. Biochemical analysis of muscle biopsies showed that cGAS, IRF3, and TBK1 protein levels were significantly increased in those with MDs, indicating that there was activation of the cGAS-STING pathway. RT-qPCR showed that downstream genes of type I interferon were upregulated in muscle samples of MDs. Protein microarray results showed that a total of six cytokines associated with the cGAS-STING pathway were significantly increased in MD patients (fold change > 1.2, p value < 0.05). CONCLUSIONS: These findings suggest that increases in ccf-mtDNA levels is associated with the activation of the cGAS-STING pathway, thereby triggering inflammation in MDs.

11.
Cells ; 11(7)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35406630

RESUMO

Hepatocarcinogenesis is frequently accompanied by substantial metabolic reprogramming to maximize the growth and proliferation of cancer cells. In this study, we carried out a comprehensive study of metabolomics and lipidomics profiles combined with gene expression analysis to characterize the metabolic reprogramming in hepatocellular carcinoma (HCC). Compared with adjacent noncancerous liver tissue, the enhanced aerobic glycolysis and de novo lipogenesis (DNL) and the repressed urea cycle were underscored in HCC tissue. Furthermore, multiscale embedded correlation analysis was performed to construct differential correlation networks and reveal pathologically relevant molecule modules. The obtained hub nodes were further screened according to the maximum biochemical diversity and the least intraclass correlation. Finally, a panel of ornithine, FFA 18:1, PC O-32:1 and TG (18:1_17:1_18:2) was generated to achieve the prognostic risk stratification of HCC patients (p < 0.001 by log-rank test). Altogether, our findings suggest that the metabolic dysfunctions of HCC detected via metabolomics and lipidomics would contribute to a better understanding of clinical relevance of hepatic metabolic reprogramming and provide potential sources for the identification of therapeutic targets and the discovery of biomarkers.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Humanos , Lipogênese , Neoplasias Hepáticas/patologia , Metabolômica
12.
Front Public Health ; 10: 783153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35400054

RESUMO

Objective: To assess the incidence, risk factors, and clinical characteristics of perinatal stroke in Beijing. Methods: This multicenter prospective study included all the live births from 17 representative maternal delivery hospitals in Beijing from March 1, 2019 to February 29, 2020. Neonates with a stroke were assigned to the study group. Clinical data, including general information, clinical manifestations, and risk factors, were collected. Up until 18 months after birth, neonates were routinely assessed according to the Ages and Stages Questionnaire (ASQ) and/or the Bayley scale. Statistical analysis was done using the chi-squared, t-tests, and logistic regression analysis using SPSS version 26.0. Outcomes: In total, 27 cases were identified and the incidence of perinatal stroke in Beijing was 1/2,660 live births, including 1/5,985 for ischemic stroke and 1/4,788 for hemorrhagic stroke. Seventeen cases (62.96%) of acute symptomatic stroke and convulsions within 72 h (10 cases, 37.04%) were the most common presentations. Ten patients showed no neurological symptoms and were found to have had a stroke through routine cranial ultrasonography after being hospitalized for non-neurological diseases. The risk factors include primiparity, placental or uterine abruption/acute chorioamnionitis, intrauterine distress, asphyxia, and severe infection. In the study group, 11.1% (3/27) of patients had adverse neurodevelopmental outcomes. The patients in the study group had lower scores for the ASQ than those in the control group in the communication, gross, and fine motor dimensions. Conclusion: The incidence of perinatal stroke in Beijing was consistent with that in other countries. Routine neuroimaging of infants with risk factors may enable identification of asymptomatic strokes in more patients. Patients who have suffered from a stroke may have neurological sequelae; therefore, early detection, treatment, and regular follow-ups are beneficial for improving their recovery outcomes.


Assuntos
Placenta , Acidente Vascular Cerebral , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Gravidez , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
13.
Mol Genet Genomic Med ; 10(5): e1918, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35266334

RESUMO

BACKGROUND: Neurodevelopmental disorders, a group of early-onset neurological disorders with significant clinical and genetic heterogeneity, remain a diagnostic challenge for clinical genetic evaluation. Therefore, we assessed the diagnostic yield by combining standard phenotypes and whole-exome sequencing in families with these disorders that were "not yet diagnosed" by the traditional testing methods. METHODS: Using a standardized vocabulary of phenotypic abnormalities from human phenotype ontology (HPO), we performed deep phenotyping for 45 "not yet diagnosed" pedigrees to characterize multiple clinical features extracted from Chinese electronic medical records (EMRs). By matching HPO terms with known human diseases and phenotypes from model organisms, together with whole-exome sequencing data, we prioritized candidate mutations/genes. We made probable genetic diagnoses for the families. RESULTS: We obtained a diagnostic yield of 29% (13 out of 45) with probably genetic diagnosis, of which compound heterozygosity and de novo mutations accounted for 77% (10/13) of the diagnosis. Of note, these pedigrees are accompanied by a more significant number of non-neurological features. CONCLUSIONS: Deep phenotyping and whole-exome sequencing improve the etiological evaluation for neurodevelopmental disorders in the clinical setting.


Assuntos
Transtornos do Neurodesenvolvimento , Humanos , Mutação , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Linhagem , Fenótipo , Sequenciamento Completo do Exoma/métodos
14.
Mol Cell ; 82(9): 1660-1677.e10, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35320754

RESUMO

Tumor-infiltrating myeloid cells (TIMs) are crucial cell populations involved in tumor immune escape, and their functions are regulated by multiple epigenetic mechanisms. The precise regulation mode of RNA N6-methyladenosine (m6A) modification in controlling TIM function is still poorly understood. Our study revealed that the increased expression of methyltransferase-like 3 (METTL3) in TIMs was correlated with the poor prognosis of colon cancer patients, and myeloid deficiency of METTL3 attenuated tumor growth in mice. METTL3 mediated m6A modification on Jak1 mRNA in TIMs, the m6A-YTHDF1 axis enhanced JAK1 protein translation efficiency and subsequent phosphorylation of STAT3. Lactate accumulated in tumor microenvironment potently induced METTL3 upregulation in TIMs via H3K18 lactylation. Interestingly, we identified two lactylation modification sites in the zinc-finger domain of METTL3, which was essential for METTL3 to capture target RNA. Our results emphasize the importance of lactylation-driven METTL3-mediated RNA m6A modification for promoting the immunosuppressive capacity of TIMs.


Assuntos
Metiltransferases , Neoplasias , Adenosina/metabolismo , Animais , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Células Mieloides/metabolismo , RNA , Microambiente Tumoral
15.
Stem Cell Rev Rep ; 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35230645

RESUMO

Partial bladder outlet obstruction (pBOO) often results in bladder tissue inflammation and remodeling. As human urine-derived stem cells (USCs) have demonstrated therapeutic benefits, we used a rat model to investigate the effect of USCs on bladder function and explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing. Eighteen rats were assigned to a sham surgery group, pBOO group, and pBOO+USC group (six biweekly treatments). Routine urodynamic monitoring, analysis of detrusor muscle strips, and pathophysiology assessments were conducted. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis. After USC treatment, elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity were found. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs was reversed by USC treatment. Two large nodes (miR-142 and miR-9a) were identified in the miRNA-gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions. This is the first study to demonstrate the protective effect of USCs on bladder function and remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35262886

RESUMO

Typical non-parametric frontier analysis based on material balance principle (MBP) is superior for measuring agricultural economic-environmental trade-offs when considering the flow of materials, but fails to incorporate the serious health effects caused by excessive use of pesticides. Here, using MBP-based data envelopment analysis, we measure the economic-environmental-health performances and trade-offs of agricultural production in China during 2006-2016. Evaluation results indicate that (i) the average agricultural sector would be able to produce current output with 16.3% fewer inputs; (ii) 17 million tons CO2 reduction potentials (9.6% of total emissions in 2016) could be realized through technical efficiency promotion without damaging environmental, health, and economic performances; (iii) synergistic effects on agricultural performance promotion exist in 12 regions indicating that the improvement of technical efficiency and the adjustment of input mix would simultaneously lead to 0.2-74.3% reductions on costs and pollutions; and (iv) improving cost efficiency in 18 regions and improving pollution efficiency in another 11 regions would be the most beneficial strategies for their agricultural sectors which would lead to additional reductions on total (economic, environmental, and health) costs by 10.3-22.5%.

17.
Lasers Med Sci ; 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35286527

RESUMO

The objective of this study was to evaluate the effect of Er:YAG laser irrigation on the push-out bond strength of fiber posts to the root dentine. Sixty extracted human mandibular first premolars were collected and decoronated. The residual roots received endodontic treatment. The treated roots were randomly divided into three groups according to different irrigation protocols: group LAI (Er:YAG laser-activated irrigation), group PUI (passive ultrasonic irrigation, positive control), and group CSI (conventional syringe irrigation, negative control) (n = 20). Each group was divided into two subgroups, either total-etching modes or self-etching modes (n = 10). After fiber post restoration, all roots were sectioned into seven 1.0-mm-thick slices. The slices received a push-out test by a universal test machine. The resin tag on the segments' bonding interfaces was observed by scanning electron microscope. There were significant differences in the effects of the irrigation method, bonding modes, and root regions on the push-out bond strength among the groups (p < 0.05). The specimens with Er:YAG laser-activated irrigation and self-etching mode showed significantly the highest bonding strength (p < 0.001). The lengths and densities of resin tags in group PUI or group LAI with self-etching modes were longer than those in group CSI with total-etching modes. The laser-activated irrigation with self-etching modes improved the bond strength of fiber post to root dentine compared to the passive ultrasonic irrigation or conventional syringe irrigation with total or self-etching modes.

18.
Transl Neurosci ; 13(1): 30-37, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35273811

RESUMO

Backgound: Low-density lipoprotein (LDL) cholesterol can lead to the occurrence of atherosclerotic plaques, but patients with normal LDL still have atherosclerotic plaques in clinical practice. With the proposal of LDL subclass, this experiment investigated the relationship between the LDL content of different subclasses and the stability of carotid plaques. Methods: Plaque stability was suggested by carotid ultrasound results. 37 patients with stable plaques were classified into one group and 41 patients with unstable plaques were classified into another group. The data of age, glycosylated hemoglobin (Ghb), and homocysteine (Hcy) were collected. The contents of LDL subclasses were measured by LIPOPRINT system. The data of total cholesterol (TC), LDL cholesterol, and triglyceride (TG) were collected. The plaque stability was assessed by carotid artery color Doppler ultrasound and the intima-media thickness (IMT) was measured. Results: The levels of LDL-1 subclass 19.00 (13.00, 27.50) and LDL-2 subclass (21.62 ± 7.24) in the stable plaque group were higher than those in the unstable plaque group (p < 0.05). The levels of LDL-3 subclass (12.24 ± 4.58), LDL-4 subclass 5.00 (2.00, 9.00), and sd-LDL 0 (0.00, 3.00) in the unstable plaque group were higher than those in the stable plaque group (p < 0.05). LDL-1 subclass (adjusted OR = 0.923 and p < 0.05), and LDL-3 subclass (adjusted OR = 1.176 and p < 0.05) were independent risk factors for plaque stability. Conclusion: Elevated LDL1 is associated with stable plaques whereas LDL3 was found associated with unstable plaques.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35270225

RESUMO

BACKGROUND: Evidence of the effectiveness of intervention against extreme heat remains unclear, especially among children, one of the vulnerable populations. This study aimed to evaluate the effectiveness of a primary school-based intervention program against heatwave and climate change in China to provide evidence for development of policies for adaptation to climate change. METHODS: Two primary schools in Dongtai City, Jiangsu Province, China, were randomly selected as intervention and control schools (CTR registration number: ChiCTR2200056005). Health education was conducted at the intervention school to raise students' awareness and capability to respond to extreme heat during May to September in 2017. Knowledge, attitude, and practice (KAP) of students and their parents at both schools were investigated by questionnaire surveys before and after intervention. The changes in KAP scores after intervention were evaluated using multivariable difference-in-difference (DID) analysis, controlling for age, sex, etc. Results: The scores of knowledge, attitude, and practice of students and their parents increased by 19.9% (95%CI: 16.3%, 23.6%) and 22.5% (95%CI: 17.8%, 27.1%); 9.60% (95%CI: 5.35%, 13.9%) and 7.22% (95%CI: 0.96%, 13.5%); and 9.94% (95%CI: 8.26%, 18.3%) and 5.22% (95%CI: 0.73%, 9.71%), respectively, after intervention. The KAP score changes of boys were slightly higher than those of girls. Older students had higher score changes than younger students. For parents, the higher the education level, the greater the score change, and change in scores was greater in females than in males. All the health education activities in the program were significantly correlated with the changes in KAP scores of primary school students after intervention, especially those curricula with interesting activities and experiential learning approaches. CONCLUSIONS: Heat and health education program in primary school was an effective approach to improve cognition and behavior for both students and their parents to better adapt to heatwaves and climate change. The successful experience can be generalized to respond to the increasing extreme weather/climate events in the context of climate change, such as heatwaves, and other emergent occasions or public health education, such as the control and prevention of COVID-19.


Assuntos
COVID-19 , Conhecimentos, Atitudes e Prática em Saúde , Criança , China , Feminino , Humanos , Masculino , SARS-CoV-2 , Instituições Acadêmicas
20.
Brain Behav Immun ; 102: 237-250, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35245678

RESUMO

Recent studies have reported that complement-related proteins modulate brain development through regulating synapse processes in the cortex. CSMD3 belongs to a group of putative complement control proteins. However, its role in the central nervous system and synaptogenesis remains largely unknown. Here we report that CSMD3 deleterious mutations occur frequently in patients with neurodevelopmental disorders (NDDs). Csmd3 is predominantly expressed in cortical neurons of the developing cortex. In mice, Csmd3 disruption induced retarded development and NDD-related behaviors. Csmd3 deficiency impaired synaptogenesis and neurogenesis, allowing fewer neurons reaching the cortical plate. Csmd3 deficiency also induced perturbed functional networks in the developing cortex, involving a number of downregulated synapse-associated genes that influence early synaptic organization and upregulated genes related to immune activity. Our study provides mechanistic insights into the endogenous regulation of complement-related proteins in synaptic development and supports the pathological role of CSMD3 in NDDs.


Assuntos
Transtornos do Neurodesenvolvimento , Neurogênese , Animais , Humanos , Camundongos , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Sinapses/metabolismo
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