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1.
Neural Regen Res ; 18(1): 194-199, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35799542

RESUMO

DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

2.
Oncol Lett ; 25(1): 3, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36419756

RESUMO

Tumor protein p53 (TP53) is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), an event that has been associated with a poor prognosis. Therefore, availability of an accurate prognostic signature would be beneficial for improving therapeutic efficacy and patient prognosis. In the present study, HCC genetic mutation data, transcriptomic data and clinical data were downloaded from The Cancer Genome Atlas database to screen for specific TP53-associated signatures based on differentially expressed genes. Subsequently, the predictive value of any signatures found for the overall survival (OS) and the immune response were investigated, followed by validation in clinical specimens. The present study revealed 270 mutant genes, of which 28% were TP53 mutations. In addition, 81 upregulated genes and 27 downregulated genes were identified. Enrichment analysis revealed that mutant TP53 was particularly enriched for pathways associated with the cell cycle and cell metabolism, and whilst clustered, most enriched for terms associated with metabolic processes and the immune response. The alcohol dehydrogenase 4 (ADH4) gene was selected using univariate and multivariate Cox regression analysis. A nomogram was constructed to validate this prognostic signature. Patients in the low-ADH4 expression group displayed significantly worse OS time regardless of the TP53 mutation status compared with the high-ADH4 expression group. In addition, a higher degree of B-cell infiltration was observed in the low-ADH4 expression group, revealing differential immune microenvironments. Subsequently, ADH4 expression and the prognostic prediction values were validated further in clinical HCC samples by IHC assay, Risk score, OS analysis and ROC analysis. To conclude, these data suggest that the TP53-associated immune-metabolic signature is a specific and independent prognostic biomarker for patients with HCC that will help to facilitate novel immunotherapy development.

3.
Sci Total Environ ; 857(Pt 1): 159303, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36228789

RESUMO

BACKGROUND: Accumulating evidence have investigated the effects of nighttime light exposure on sleep problems. Nevertheless, the evidence of the relationship between light at night (LAN) and sleep problems remains scarce and inconsistent. OBJECTIVE: Conducted a systematic review and meta-analysis based on observational studies to examine the association between LAN exposure and sleep problems among human subjects. METHODS: We systematically searched three databases (PubMed, Web of Science, and Embase) to identify potentially eligible studies through May 25, 2022. The risk of bias and the quality of the generated evidence were assessed by two authors using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) risk of bias rating tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline. Random-effects model was applied to synthesize the risk estimates across eligible studies. The heterogeneity of included studies was quantified by the statistics of I2. RESULTS: A total of 7 cross-sectional studies comprising 577,932 participants were included. Individuals with higher levels of LAN exposure were associated with a 22 % (Summary Odds Ratio, SOR: 1.22, 95 %CI: 1.13-1.33) increased prevalence of sleep problems. The pooled effect size of indoor LAN exposure (SOR: 1.74, 95%CI: 1.27-2.37) associated with sleep problems was significantly higher than outdoor LAN exposure (SOR: 1.19, 95%CI: 1.11-1.29; P = 0.022). Additionally, dose-response analysis demonstrated that LAN intensity threshold exceeding 5.8 nW/cm2/sr (SOR: 1.04, 95%CI: 1.01-1.07) had a significant effect on sleep problems and the prevalence of sleep problems was increasing with increase in LAN intensity. CONCLUSIONS: Overall, our findings support the detrimental effects of LAN exposure on sleep. Maintaining bedroom darkness at night may be a feasible measure to reduce the prevalence of sleep problems. Future longitudinal studies with more advanced LAN assessment methods are required to move the field forward.


Assuntos
Redes Locais , Transtornos do Sono-Vigília , Humanos , Estudos Transversais , Sono , Escuridão , Luz , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia
4.
J Proteomics ; 271: 104768, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36336261

RESUMO

Liver fibrosis (LF), commonly associated with chronic liver diseases, is a major public health problem worldwide. Protein phosphorylation is not only an important form of protein modification in organisms but also the most important mechanism to regulate and control the activity and function of proteins, affecting the occurrence and development of many diseases. However, comprehensive phosphoproteomic profiling in LF has not been fully elucidated. In this study, data-independent acquisition (DIA) was used to analyse the phosphoproteomics of mice with LF. A total of 553 phosphopeptides (representing 440 phosphoproteins) had significant phosphorylation levels. Among these phosphoproteins, 49 were upregulated and 401 were downregulated, and 5 phosphoserine (P-Ser) motifs and 2 phosphothreonine (P-Thr) motifs were conserved in LF. GO and KEGG pathway enrichment analyses identified 769 significant GO terms and 49 significant KEGG pathways. Four phosphorylated proteins were selected for parallel reaction monitoring (PRM) verification, and the results were consistent with DIA data. Together, there were significantly different phosphoproteomic profiles in LF, suggesting that protein phosphorylation was related to the occurrence and progression of LF, which could pave the way for further investigation into the related regulatory mechanisms. SIGNIFICANCE: LF is a necessary stage in the development of chronic liver disease to liver cirrhosis and has attracted wide attention. To the best of our knowledge, there are few reports on the phosphorylated proteomics of LF. In this study, DIA and PRM techniques were used to study the liver tissue of mice induced by CCl4. The results showed that phosphorylation had a significant effect on the activity and function of proteins, and the PRM results were consistent with the trend observed in DIA analysis. This study will help to better reveal the relationship of phosphorylated proteins in LF and lay a foundation for further study of related regulatory mechanisms.


Assuntos
Fosfopeptídeos , Proteômica , Animais , Camundongos , Fosfopeptídeos/análise , Proteômica/métodos , Espectrometria de Massas/métodos , Fosfoproteínas/análise , Fosforilação , Cirrose Hepática
5.
Oxid Med Cell Longev ; 2022: 5064494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338340

RESUMO

Excessive generation of reactive oxygen species (ROS) has great impacts on MSU crystal-induced inflammation. Drp1-dependent mitochondrial fission is closely associated with mitochondrial ROS levels. However, whether Drp1 signaling contributes to MSU crystal-induced inflammation remains unclear. Mice bone marrow-derived macrophages (BMDMs) were primed with LPS and then stimulated with MSU suspensions for 12 h. The protein levels associated with mitochondrial dynamics, oxidative stress, and mitophagy were detected by Western blot. BMDMs were loaded with MitoTracker Green probe to detect mitochondrial morphology. To measure mitochondrial reactive oxygen species (ROS) and total ROS levels, cells were loaded, respectively, with MitoSOX and DHE probes. The effects of Mito-TEMPO, an antioxidant that targets the mitochondria or DRP1 inhibitor (Mdivi-1) on MSU crystal-induced peritonitis and arthritis mouse models, were evaluated. Our study revealed that MSU crystal stimulation resulted in elevation of mitochondrial fragmentation of BMDMs. Treatment with Mito-TEMPO or Drp1 knockdown significantly ameliorated the mitochondrial damage induced by MSU crystals. BMDMs exposure to MSU crystals increased the expression of auto/mitophagy marker proteins and promoted the fusion of mitophagosomes with lysosomes, leading to accumulation of mitolysosomes. Drp1 knockdown alleviated defective mitophagy and activation of the NLRP3 inflammasome in MSU crystal-treated BMDMs. This study indicates that there is crosstalk between mitochondrial ROS and Drp1 signaling in MSU crystal-induced inflammation. Drp1 signaling is involved in MSU crystal-induced mitochondrial damage, impaired mitophagy and NLRP3 inflammasome activation.


Assuntos
Inflamassomos , Mitofagia , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Dinaminas/metabolismo , Dinâmica Mitocondrial , Inflamação
6.
Front Plant Sci ; 13: 1001740, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340399

RESUMO

Carbonization of agricultural and forestry wastes is the main use of biochar application in agriculture. In this study, the effects of biochar on the physical and chemical properties of soil and diversity in rhizosphere microorganisms, leaf nutrients and fruit quality of acid red soil in "Shatangju" (Citrus reticulate cv.) orchard were studied using organic wastes and small-scale carbonization furnaces from orchards were used to produce biochar. The results showed that the finished rate of biochar produced from the organic wastes in the orchard was approximately 37%, and the carbon content of the finished product was as high as 80%. The results suggested that the biochar produced in the orchard could meet the annual consumption of the orchard. Applying biochar can improve the physical and chemical properties of acid soil in the "Shatangju" orchard by enhancing the availability of various mineral nutrients such as nitrogen, phosphorus, potassium, calcium, magnesium and boron. The species and quantity of root and rhizosphere microbial communities (fungi, bacteria and archaea) increased, and the dominant bacterial group changed, manifested in the increase in microbial diversity. Biochar directly affected the soil pH value and increased the soil organic carbon content, which may be the main reason for the change in microbial diversity in the soil and rhizosphere of "Shatangju" in the orchard and pot tests. The fruit quality of each treatment group with biochar was also better than that of the control group and improved fruit coloring. In the pure soil test, whether or not chemical fertilizer was applied, 3% biochar amendments can provide a suitable pH value for "Shatangju" growth and are relatively stable. Regardless of whether or not fertilizer was applied, 1.5%-3% biochar improved the soil in the pot test. In the field, the biochar at a rate of 2.4 kg/plant to 3.6 kg/plant, respectively, was the best in improving soil physical and chemical properties, foliar nutrition and fruit quality. Therefore, the amount of biochar added in the open environment (if the garden) can be slightly adjusted according to the results of the closed environment test (pure soil test and pot test). In this experiment, we explored the self-recycling of organic carbon, mainly through the preparation of a simple small-scale biochar furnace suitable for the use by orchards, and selected the appropriate amount of biochar to improve the physical and chemical conditions of "Shatangju" orchard soil and increase fruit quality.

7.
J Clin Oncol ; : JCO2201214, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346962

RESUMO

PURPOSE: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS: Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19-/CD22+, one CD19-/CD22-, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients (P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION: CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36425259

RESUMO

This study aimed to investigate the molecular mechanisms of microRNA-146a (miR-146a) on gingival mesenchymal stem cells (MSCs). Gingival MSCs were isolated from the gingiva tissues of patients with periodontal disease to reveal the function of miR-146a in regulating osteoblast differentiation. miR-146a inhibits osteoblast differentiation by inhibiting phosphorylated cyclic-AMP response binding (CREB) protein translocation into the nucleus and ultimately attenuating runt-related transcription factor 2 (Runx2) expression. Furthermore, silencing miR-146a promotes the proliferation of gingival MSCs. Of note, targeted inhibition of miR-146a also inhibited LPS-induced inflammatory response and promoted the proliferation of gingival MSCs via CREB/Runx2 axis. MiR-146a is a key negative regulator of gingival MSCs proliferation and osteogenic differentiation, and targeting to reduce the miR-146a expression is essential for bone formation signaling. Therefore, we propose that miR-146a is a useful therapeutic target for the development of bone anabolic strategies.

9.
Front Oncol ; 12: 945143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419885

RESUMO

Background: Circular RNAs (circRNAs) are receiving increasing attention as novel biomarkers. Our goal was to investigate the diagnostic, clinicopathological, and prognostic utility of circRNAs in prostate cancer (PCa). Methods: Relevant literature was searched in PubMed, Web of Science, and EMBASE. Sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (NLR), positive likelihood ratio (PLR), and the area under the curve (AUC) were calculated to evaluate the diagnostic accuracy of circRNA expression. circRNAs' clinical, pathological, and prognostic value was examined using pooled odds ratios (ORs) and hazard ratios (HRs). Results: This meta-analysis included 23 studies, with 5 for diagnosis, 16 for clinicopathological parameters, and 10 for prognosis. For diagnostic value, the pooled sensitivity, pooled specificity, PLR, NLR, DOR, and AUC were 0.82, 0.62, 2.17, 0.29, 7.37, and 0.81, respectively. Upregulation of carcinogenic circRNAs was associated with poor clinical parameters (Gleason score: OR = 0.222, 95% CI: 0.145-0.340; T classification: OR = 0.274, 95% CI: 0.175-0.430; lymph node metastasis: OR = 0.353, 95% CI: 0.175-0.716; tumor size: OR = 0.226, 95% CI: 0.099-0.518) and could predict poor survival outcomes (HR = 2.408, 95% CI: 1.559-3.720, p < 0.001). Conversely, downregulation of tumor-suppressor circRNAs was also associated with poor clinical parameters (Gleason score: OR = 1.689, 95% CI: 1.144-2.493; T classification: OR = 2.586, 95% CI: 1.779-3.762) and worse prognosis (HR = 1.739, 95% CI: 1.147-2.576, p = 0.006). Conclusion: Our results showed that circRNAs might be useful biomarkers for the diagnosis and prognosis of PCa. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021284785.

10.
PeerJ ; 10: e14394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36415861

RESUMO

Context: Scutellaria baicalensis Georgi (SBG) may relieve bone cancer pain (BCP) by regulating cell proliferation, angiogenesis, and apoptosis. Objective: The mechanism of SBG in the treatment of BCP remains to be further explored. Methods: The active compounds and targets of SBG were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction databases. BCP-related targets were screened from NCBI and GeneCards databases. Additionally, Cytoscape software was applied to construct network diagrams, and OmicShare platform was used to enrich Gene Ontology (GO) and pathways. Finally, the verification of active compounds and core targets was performed based on quantitative real-time PCR (qRT-PCR). Results: Interestingly, we identified baicalein and wogonin as the main active components of SBG. A total of 41 SBG targets, including VEGFA, IL6, MAPK3, JUN and TNF, were obtained in the treatment of BCP. In addition, pathways in cancer may be an essential way of SBG in the treatment of BCP. Experimental verification had shown that baicalein and wogonin were significantly related to BCP core targets. Conclusions: The active components of SBG have been clarified, and the mechanism of the active components in treating BCP has been predicted and verified, which provides an experimental and theoretical basis for the in-depth elucidation of the pharmacodynamics material basis and mechanism of SBG.

11.
BMC Complement Med Ther ; 22(1): 299, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401273

RESUMO

BACKGROUND: Shengjing capsule (SJC) is a traditional Chinese medicine (TCM) and has gained widespread clinical application for the treatment of male infertility (MI). However, the pharmacological mechanism of SJC against MI remains vague to date. METHOD: The active ingredients of SJC and their targets were identified from the database, and MI-related genes were retrieved from several databases. Protein-protein interaction (PPI) data were obtained to construct the PPI networks. The candidate targets of SJC against MI were identified through topological analysis of the PPI network. Functional enrichment analysis of candidate targets was performed, and the key target genes were identified from the gene-pathway network. RESULTS: We identified 154 active ingredients and 314 human targets of SJC, as well as 564 MI-related genes. Eight pharmacological network diagrams illustrating the interactions among herbs, active ingredients, targets, and pathways, were constructed. The four dominating network maps included a compound-target network of SJC, a compound-anti-MI targets network, a candidate targets PPI network, a pathway-gene network, and a drug-key compounds-hub targets-pathways network. Systematic analysis indicated that the targets of SJC in the treatment of MI mainly involved RPS6, MAPK1, MAPK3, MDM2, and DDX5. Pathway enrichment analysis showed that SJC had the potential to impact multiple biological pathways, such as cancer-related pathways, viral/bacterial infection-related pathways, and signal transduction-related pathways. CONCLUSION: Our results preliminarily revealed the pharmacological basis and molecular mechanism SJC in treating MI, but further experimental research is required to verify these findings.


Assuntos
Medicamentos de Ervas Chinesas , Infertilidade Masculina , Humanos , Masculino , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Infertilidade Masculina/tratamento farmacológico , RNA Helicases DEAD-box
12.
PeerJ ; 10: e14345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405021

RESUMO

Background: Cardiopulmonary resuscitation (CPR) skills may decay over time after conventional instructor-led BLS training. The Resuscitation Quality Improvement® (RQI®) program, unlike a conventional basic life support (BLS) course, is implemented through mastery learning and low-dose, high-frequency training strategies to improve CPR competence. We facilitated the RQI program to compare the performance of novices vs those with previous BLS training experience before RQI implementation and to obtain their confidence and attitude of the RQI program. Methods: A single-center observational study was conducted from May 9, 2021 to June 25, 2021 in an emergency department of a tertiary hospital. The performance assessment data of both trainees with a previous training experience in conventional BLS course (BLS group) and the novice ones with no prior experience with any BLS training (Non-BLS group) was collected by RQI cart and other outcome variables were rated by online questionnaire. Outcome measurements included chest compression and ventilation in both adult-sized and infant-sized manikins. Results: A total of 149 participants were enrolled. Among them, 103 participants were in BLS group and 46 participants in Non-BLS group. Post RQI training, all the trainees achieved a passing score of 75 or more, and obtained an improvement in CPR performance. The number of attempts to pass RQI for compression and ventilation practice was lower in the BLS group in both adult and infant training sessions (P < 0.05). Although the BLS group had a poor baseline, it had fewer trials and the same learning outcomes, and the BLS group had better self-confidence. Trainees were well adapted to the innovative training modality, and satisfaction among all of the participants was high. Only the respondents for non-instructor led training, the satisfaction was low in both groups (72.8% in BLS group vs 65.2% in No-BLS group, strongly agreed). Conclusion: Among novices, RQI can provide excellent CPR core skills performance. But for those who had previous BLS training experience, it was able to enhance the efficiency of the skills training with less time consumption. Most trainees obtained good confidence and satisfaction with RQI program, which might be an option for the broad prevalence of BLS training in China.

13.
Front Physiol ; 13: 986422, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407002

RESUMO

Lung transplantation is the preferred treatment method for patients with end-stage pulmonary disease. However, several factors hinder the progress of lung transplantation, including donor shortages, candidate selection, and various postoperative complications. Electrical impedance tomography (EIT) is a functional imaging tool that can be used to evaluate pulmonary ventilation and perfusion at the bedside. Among patients after lung transplantation, monitoring the graft's pulmonary function is one of the most concerning issues. The feasible application of EIT in lung transplantation has been reported over the past few years, and this technique has gained increasing interest from multidisciplinary researchers. Nevertheless, physicians still lack knowledge concerning the potential applications of EIT in lung transplantation. We present an updated review of EIT in lung transplantation donors and recipients over the past few years, and discuss the potential use of ventilation- and perfusion-monitoring-based EIT in lung transplantation.

14.
Front Public Health ; 10: 1019198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408017

RESUMO

Background: Understanding multidrug-resistant tuberculosis (MDR-TB) transmission patterns is crucial for controlling the disease. We aimed to identify high-risk populations and geographic settings of MDR-TB transmission. Methods: We conducted a population-based retrospective study of MDR-TB patients in Beijing from 2018 to 2020, and assessed MDR-TB recent transmission using whole-genome sequencing of isolates. Geospatial analysis was conducted with kernel density estimation. We combined TransPhylo software with epidemiological investigation data to construct transmission networks. Logistic regression analysis was utilized to identify risk factors for recent transmission. Results: We included 241 MDR-TB patients, of which 146 (60.58%) were available for genomic analysis. Drug resistance prediction showed that resistance to fluoroquinolones (FQs) was as high as 39.74% among new cases. 36 (24.66%) of the 146 MDR strains were grouped into 12 genome clusters, suggesting recent transmission of MDR strains. 44.82% (13/29) of the clustered patients lived in the same residential community, adjacent residential community or the same street as other cases. The inferred transmission chain found a total of 6 transmission events in 3 clusters; of these, 4 transmission events occurred in residential areas and nearby public places. Logistic regression analysis revealed that being aged 25-34 years-old was a risk factor for recent transmission. Conclusions: The recent transmission of MDR-TB in Beijing is severe, and residential areas are common sites of transmission; high levels of FQs drug resistance suggest that FQs should be used with caution unless resistance can be ruled out by laboratory testing.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Adulto , Pequim/epidemiologia , Estudos Retrospectivos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/genética , Genômica
15.
Cell Rep ; 41(6): 111592, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351383

RESUMO

Steady-state extramedullary hematopoiesis during adulthood is an emerging field of great interest. The meninges contain both innate and adaptive immune cells, which provide immunosurveillance of the central nervous system (CNS). Hematopoietic progenitors that give rise to meningeal immune cells remain elusive. Here, we report that steady-state meninges of adult mice host hematopoietic stem cells (HSCs), as defined by long-term, efficient, multi-lineage reconstitution and self-renewal capacity in the meninges, blood, spleen, and bone marrow of sublethally irradiated adult recipients. HSCs lodge in the meninges after birth with local expression of pro-hematopoietic niche factors. Meningeal HSCs are locally maintained in homeostasis and get replenished from the blood only when the resident pool is reduced. With a tissue-specific expression profile, meningeal HSCs can provide the CNS with a constant supply of leukocytes more adapted to local microenvironment.


Assuntos
Hematopoese , Células-Tronco Hematopoéticas , Camundongos , Animais , Células-Tronco Hematopoéticas/metabolismo , Hematopoese/fisiologia , Medula Óssea , Baço , Meninges , Camundongos Endogâmicos C57BL
16.
Ying Yong Sheng Tai Xue Bao ; 33(11): 3075-3086, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36384842

RESUMO

Guizhou Province is a test area of ecological civilization in China, and one of the most typical areas of karst landform development in the world. Exploring the change of ecosystem service value and its spatial correlation distribution characteristics with landscape pattern is conducive to formulating ecological environment improvement and protection measures according to local conditions. We analyzed the spatial and temporal variations of landscape pattern and ecosystem services in Guizhou Province from 2005 to 2018 and constructed a geographically weighted regression model to explore the spatial changes of their correlation coefficients. The results showed that the transfer of landscape types in Guizhou Province from 2005 to 2018 mainly occurred in the five landscapes of construction land, forest, water, grassland, and cropland. The landscape fragmentation and diversity increased. The value of ecosystem services was increasing year by year. Forests were the main contributors to the value of ecosystem services in Guizhou Province, with regulation services as the main ecosystem services. For high-value landscape types, the increase of diversity and the reduction of fragmentation were conducive to the increases of ecosystem service value. In the area with concentrated low-value landscape types, it showed the opposite effect. The direction of landscape transfer and the spatial distribution of diversity and fragmentation of different landscape types should be adjusted according to the characteristics of ecological environment in different regions of Guizhou Province, to realize the increases of ecosystem service value.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Conservação dos Recursos Naturais/métodos , Florestas , China , Água
17.
Stat Med ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36412978

RESUMO

Many real data analyses involve two-sample comparisons in location or in distribution. Most existing methods focus on problems where observations are independently and identically distributed in each group. However, in some applications the observed data are not identically distributed but associated with some unobserved parameters which are identically distributed. To address this challenge, we propose a novel two-sample testing procedure as a combination of the g $$ g $$ -modeling density estimation introduced by Efron and the two-sample Kolmogorov-Smirnov test. We also propose efficient bootstrap algorithms to estimate the statistical significance for such tests. We demonstrate the utility of the proposed approach with two biostatistical applications: the analysis of surgical nodes data with binomial model and differential expression analysis of single-cell RNA sequencing data with zero-inflated Poisson model.

18.
Proteomics ; : e2200176, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36413357

RESUMO

It is challenging to study regulatory genetic variants as gene expression is affected by both genetic polymorphisms and non-genetic regulators. The mRNA allele-specific expression (ASE) assay has been increasingly used for the study of cis-acting regulatory variants because cis-acting variants affect gene expression in an allele-specific manner. However, poor correlations between mRNA and protein expressions were observed for many genes, highlighting the importance of studying gene expression regulation at the protein level. In the present study, we conducted a proof-of-concept study to utilize a recently developed allele-specific protein expression (ASPE) assay to identify the cis-acting regulatory variants of CES1 using a large set of human liver samples. The CES1 gene encodes for carboxylesterase 1 (CES1), the most abundant hepatic hydrolase in humans. Two cis-acting regulatory variants were found to be significantly associated with CES1 ASPE, CES1 protein expression, and its catalytic activity on enalapril hydrolysis in human livers. Compared to conventional gene expression-based approaches, ASPE demonstrated an improved statistical power to detect regulatory variants with small effect sizes since allelic protein expression ratios are less prone to the influence of non-genetic regulators (e.g., diseases and inducers). This study suggests that the ASPE approach is a powerful tool for identifying cis-regulatory variants. This article is protected by copyright. All rights reserved.

19.
Asian J Surg ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36376184

RESUMO

OBJECTIVE: Positive resection margin indicates worse prognosis. The present study identified the independent risk factors of R1 resection in pancreaticoduodenectomy (PD) and distal pancreatosplenectomy (DP) for patients with pancreatic ductal adenocarcinoma (PDAC). METHOD: Consecutive patients who were operated from 1st December 2017 to 30th December 2018 were analyzed retrospectively. A standardized pathological examination with digital whole-mount slide images (DWMSIs) was utilized for evaluation of resection margin status. R1 was defined as microscopic tumor infiltration within 1 mm to the resection margin. The potential risk factors of R1 resection for PD and DP were analyzed separately by univariate and multivariate logistic regression analyses. RESULTS: For the 192 patients who underwent PD, and the 87 patients who underwent DP, the R1 resection rates were 31.8% and 35.6%, respectively. Univariate analysis on risk factors of R1 resection for PD were tumor location, lymphovascular invasion, N staging, and TNM staging; while those for DP were T staging and TNM staging. Multivariate logistic regression analysis showed the location of tumor in the neck and uncinate process, and N1/2 staging were independent risk factors of R1 resection for PD; while those for DP were T3 staging. CONCLUSIONS: The clarification of the risk factors of R1 resection might clearly make surgeons take reasonable decisions on surgical strategies for different surgical procedures in patients with PDAC, so as to obtain the first attempt of R0 resection.

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