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1.
Artigo em Inglês | MEDLINE | ID: mdl-34653517

RESUMO

BACKGROUND: Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear. OBJECTIVE: This study aims to identify a key cellular player of air pollutant-induced asthma exacerbation and development. METHODS: We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite (HDM) and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry, RNA seq analysis. The roles of Sialic acid-binding, Ig-like lectin F (SiglecF)+ neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies. RESULTS: We show here that DEP exposure induces a unique population of lung granulocytes that co-express Ly-6G and sialic acid-binding, Ig-like lectin (Siglec)-F. These cells differ phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEP induces the local release of adenosine 5'-​triphosphate (ATP), which is a damage-associated molecular pattern (DAMP) signal. ATP promotes the expression of SiglecF on neutrophils, and these SiglecF+ neutrophils worsen type 2 and 3 airway inflammation by producing high levels of cysteinyl leukotrienes and neutrophil extracellular traps. We also found Siglec8 (which corresponds to murine SiglecF) expressing neutrophils and in the patients with asthma-COPD overlap (ACO). CONCLUSION: SiglecF+ neutrophil is a novel and critical player in airway inflammation and targeting the populations could reverse or ameliorate asthma.

2.
Thorax ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593614

RESUMO

BACKGROUND: Smoking has been considered an important risk factor for idiopathic pulmonary fibrosis (IPF) incidence. However, there are no population-based large-scale studies demonstrating the effects of smoking on the development of IPF. We aimed to evaluate the effect of smoking on IPF development using a nationwide population-based cohort. METHODS: Using the Korean National Health Information Database, we enrolled individuals who had participated in the health check-up service between 2009 and 2012. Participants having a prior diagnosis of IPF were excluded. The history of smoking status and quantity was collected by a questionnaire. We identified all cases of incident IPF through 2016 on the basis of ICD-10 codes for IPF and medical claims. Cox proportional hazards models were used to calculate the adjusted HR (aHR) of the development of IPF. RESULTS: A total of 25 113 individuals (0.11%) with incident IPF were identified out of 23 242 836 participants registered in the database. The risk of IPF was significantly higher in current and former smokers than in never smokers, with an aHR of 1.66 (95% CI 1.61 to 1.72) and 1.42 (95% CI 1.37 to 1.48), respectively. Current smokers had a higher risk of IPF than former smokers (aHR 1.17, 95% CI 1.13 to 1.21). The risk of IPF development increased as the smoking intensity and duration increased. CONCLUSION: Smoking significantly increased the risk of IPF development. Current smokers had a higher risk of IPF than former smokers. A dose-response relationship was observed between smoking and the development of IPF.

3.
Sleep Med ; 87: 143-150, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34607112

RESUMO

BACKGROUND: We aimed to assess mortality in chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and overlap syndrome, and evaluate which polysomnographic indices-apnea-hypopnea index (AHI) or hypoxemic load measurements-better predict mortality within 10 years. METHODS: Adults with symptoms suggestive of sleep apnea and airway disease who underwent both polysomnography and spirometry plus bronchodilator response tests between 2000 and 2018 were included and divided into four groups according to presence of COPD and moderate-to-severe OSA (AHI ≥15/h). We estimated mortality using a Cox model adjusted for demographic/anthropometric covariates and comorbidities; this was called clinical model. To evaluate prognostic performance, we compared the concordance index (C-index) between clinical model and extended models, which incorporated one of polysomnographic indices-AHI, sleep time spent with SpO2 < 90% (TS90), and mean and lowest SpO2. RESULTS: Among 355 participants, patients with COPD alone (57/355, 16.1%) and COPD-OSA overlap syndrome (37/355, 10.4%) had increased all-cause mortality than those who had neither disease (152/355, 42.8%) (adjusted HR, 2.98 and 3.19, respectively). The C-indices of extended models with TS90 (%) and mean SpO2 were significantly higher than that of clinical model (0.765 vs. 0.737 and 0.756 vs. 0.737, respectively; all P < 0.05); however, the C-index of extended model with AHI was not (0.739 vs. 0.737; P = 0.15). CONCLUSIONS: In this cohort with symptoms of sleep apnea and airway disease, patients with overlap syndrome had increased mortality, but not higher than in those with COPD alone. The measurement of hypoxemic load, not AHI, better predicted mortality.

4.
Pharmgenomics Pers Med ; 14: 1291-1302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629889

RESUMO

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have represented the prototype of targeted therapy in NSCLC. Patients with EGFR-mutant lung adenocarcinoma extract an extraordinary clinical benefit from EGFR-TKIs. However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. We investigated whether genetic variants in miRNA binding sites are associated with the clinical outcome of EGFR-TKIs in lung adenocarcinoma patients. Methods: One hundred SNPs at miRNA binding sites in cancer-related genes were selected for the analysis using the crosslinking, ligation and sequencing of hybrids (CLASH) and CancerGenes database. qRT-PCR and luciferase assays were conducted to evaluate the functional relevance of the SNPs. Results: NUP62 rs9523A>G were significantly associated with worse response to EGFR-TKIs, overall survival (OS), and progression-free survival (PFS). The other three SNPs (DVL2 rs2074216G>A, ARF1 rs11541557G>T, and UHRF1 rs2261988C>A) were significantly associated with worse OS and PFS. The rs9523A>G was significantly associated with decreased NUP62 expression in tumor tissues. In addition, a significantly decreased luciferase activity was noted in NUP62 rs9523 G allele compared to A allele. Conclusion: Genetic variants in miRNA binding sites, especially NUP62 rs9523A>G, may be useful in predicting the clinical outcomes of EGFR-mutant lung adenocarcinoma patients treated with EGFR-TKIs.

5.
J Infect Chemother ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34627705

RESUMO

INTRODUCTION: Patients with aspiration pneumonia (AP) exhibit higher mortality than those with non-AP. However, data regarding predictors of short-term prognosis in patients with community-acquired AP are limited. METHODS: Patients hospitalized with community-acquired pneumonia (CAP) were retrospectively classified into aspiration pneumonia (AP) and non-AP groups. The AP patients were further divided into nonsurvivors and survivors by 30-day mortality, and various clinical variables were compared between the groups. RESULTS: Of 1249 CAP patients, 254 (20.3%) were classified into the AP group, of whom 76 patients (29.9%) died within 30 days. CURB-65, pneumonia severity index (PSI), and Infectious Diseases Society of America/American Thoracic Society criteria for severe CAP (SCAP) showed only modest prognostic performance for the prediction of 30-day mortality (c-statistics, 0.635, 0.647, and 0.681, respectively). Along with the PSI and SCAP, Eastern Cooperative Oncology Group performance status (ECOG-PS) and blood biomarkers, including, N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and albumin, were independent predictors of 30-day mortality. In models based on clinical prediction rules, including CURB-65, PSI, and SCAP, the addition of ECOG-PS further improved their c-statistics compared to the clinical prediction rules alone. In the four combinations based on SCAP, ECOG-PS, and two blood biomarkers (NT-proBNP and albumin), the c-statistics further increased to reach approximately 0.8. CONCLUSIONS: CURB-65, PSI, and SCAP exhibited only modest discriminatory power in predicting the 30-day mortality of patients with community-acquired AP. The addition of performance status and blood biomarkers, including NT-proBNP and albumin, further increased prognostic performance, showing good predictive accuracy in the SCAP-based model.

6.
Mol Oncol ; 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34605158

RESUMO

Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression. We investigated whether variants in BET genes are associated with survival outcomes for lung cancer. To do this, the associations between 77 variants in BET family genes and survival outcomes were analyzed in 773 non-small-cell lung cancer (NSCLC) patients who underwent surgery (349 and 424 patients in the discovery and validation cohorts, respectively). We found that six variants were significantly associated with overall survival (OS) in the discovery cohort, and one variant (rs2506711C>T) was replicated in the validation cohort. BRD3 rs2506711C>T is located in the repressed area and has a strong linkage disequilibrium with rs2427964C>T in the promoter region. BRD3 rs2427964C>T was significantly associated with worse OS in the discovery cohort, validation cohort, and combined analysis. In a luciferase assay, promoter activity in the BRD3 rs2427964 T allele was significantly higher than that in the BRD3 rs2427964 C allele, which selectively bound with the transcriptional repressor SIN3A. Knockdown of BRD3 with BRD3-specific siRNA decreased the proliferation and migration of lung cancer cells while also increasing the rate of apoptosis. These results suggest that BRD3 rs2427964C>T increases BRD3 expression through increased promoter activity, which is associated with poor prognosis for lung cancer.

7.
Nat Commun ; 12(1): 6112, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671051

RESUMO

Stroke profoundly disrupts cortical excitability which impedes recovery, but how it affects the function of specific inhibitory interneurons, or subpopulations therein, is poorly understood. Interneurons expressing vasoactive intestinal peptide (VIP) represent an intriguing stroke target because they can regulate cortical excitability through disinhibition. Here we chemogenetically augmented VIP interneuron excitability in a murine model of photothrombotic stroke and show that it enhances somatosensory responses and improves recovery of paw function. Using longitudinal calcium imaging, we discovered that stroke primarily disrupts the fidelity (fraction of responsive trials) and predictability of sensory responses within a subset of highly active VIP neurons. Partial recovery of responses occurred largely within these active neurons and was not accompanied by the recruitment of minimally active neurons. Importantly, chemogenetic stimulation preserved sensory response fidelity and predictability in highly active neurons. These findings provide a new depth of understanding into how stroke and prospective therapies (chemogenetics), can influence subpopulations of inhibitory interneurons.

8.
Mol Cells ; 44(9): 658-669, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34588321

RESUMO

Enhancers have been conventionally perceived as cis-acting elements that provide binding sites for trans-acting factors. However, recent studies have shown that enhancers are transcribed and that these transcripts, called enhancer RNAs (eRNAs), have a regulatory function. Here, we identified putative eRNAs by profiling and determining the overlap between noncoding RNA expression loci and eRNA-associated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCC-derived noncoding RNAs, 74 overlapped with the eRNA loci defined by the FANTOM consortium, and 65 were located in the proximal regions of genes differentially expressed between normal and tumor tissues in TCGA dataset. Interestingly, knockdown of two selected putative eRNAs, THUMPD3-AS1 and LINC01572, led to downregulation of their target mRNAs and to a reduction in the proliferation and migration of HCC cells. Additionally, the expression of these two noncoding RNAs and target mRNAs was elevated in tumor samples in the TCGA dataset, and high expression was associated with poor survival of patients. Collectively, our study suggests that noncoding RNAs such as THUMPD3-AS1 and LINC01572 (i.e., putative eRNAs) can promote the transcription of genes involved in cell proliferation and differentiation and that the dysregulation of these noncoding RNAs can cause cancers such as HCC.

9.
Int J Mol Sci ; 22(18)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34576317

RESUMO

Gintonin, a novel compound of ginseng, is a ligand of the lysophosphatidic acid (LPA) receptor. The in vitro and in vivo skin wound healing effects of gintonin remain unknown. Therefore, the objective of this study was to investigate the effects of gintonin on wound healing-linked responses, especially migration and proliferation, in skin keratinocytes HaCaT. In this study, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, Boyden chamber migration assay, scratch wound healing assay, and Western blot assay were performed. A tail wound mouse model was used for the in vivo test. Gintonin increased proliferation, migration, and scratch closure in HaCaT cells. It also increased the release of vascular endothelial growth factor (VEGF) in HaCaT cells. However, these increases, induced by gintonin, were markedly blocked by treatment with Ki16425, an LPA inhibitor, PD98059, an ERK inhibitor, 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester), a calcium chelator, and U73122, a PLC inhibitor. The VEGF receptor inhibitor axitinib also attenuated gintonin-enhanced HaCaT cell proliferation. Gintonin increased the phosphorylation of AKT and ERK1/2 in HaCaT cells. In addition, gintonin improved tail wound healing in mice. These results indicate that gintonin may promote wound healing through LPA receptor activation and/or VEGF release-mediated downstream signaling pathways. Thus, gintonin could be a beneficial substance to facilitate skin wound healing.

10.
Microorganisms ; 9(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34576812

RESUMO

MALDI TOF MS-based microbial identification significantly lowers the operational costs because of minimal requirements of substrates and reagents for extraction. Therefore, it has been widely used in varied applications such as clinical, food, military, and ecological research. However, the MALDI TOF MS method is laced with many challenges including its limitation of the reference spectrum. This review briefly introduces the background of MALDI TOF MS technology, including sample preparation and workflow. We have primarily discussed the application of MALDI TOF MS in the identification of microorganisms. Furthermore, we have discussed the current trends for bioaerosol detection using MALDI TOF MS and the limitations and challenges involved, and finally the approaches to overcome these challenges.

11.
J Steroid Biochem Mol Biol ; 214: 105994, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481040

RESUMO

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that are capable of blocking or mimicking the action of bioidentical hormones. Obesogenic EDCs, commonly called obesogens, play an important role in adipogenesis. This study was carried out to determine the effects of select obesogens and their alternatives on adipogenesis in 3T3-L1 cells under dexamethasone (DEX)-free conditions. Preadipocytes were treated with a cocktail of 3-isobutyl-1-methylxanthine (IBMX) and insulin to which an obesogen (viz., bisphenol A (BPA) or its analogs BPS and BPF; dioctyl terephthalate; tris (2-ethylhexyl) trimellitate; or various parabens) had been added. A mixture containing IBMX, insulin, and DEX, which constitute the typical hormonal cocktail required for adipocyte differentiation, was used as the control against which the other groups were measured. The obesogens and the PBA analogs all had evident adipogenic effects under DEX-free conditions, as was determined by estimating the lipid accumulation levels in the cells using Oil Red O staining. Furthermore, the expression of adipogenic transcription factors (CCAAT/enhancer-binding protein-alpha, peroxisome proliferator-activated receptor-gamma, and adipocyte protein 2) was induced by 20 µM of BPA, BPS, or BPF at both the mRNA and protein levels, as determined through reverse transcription-polymerase chain reaction and western blot assays. Taken together, the results reveal that adipocyte differentiation can be induced by obesogens and their alternatives in the absence of DEX.

12.
PLoS One ; 16(9): e0257356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506598

RESUMO

Oral lichen planus (OLP) is one of the most prevalent oral mucosal diseases, but there is no cure for OLP yet. The aim of this study was to gain insights into the role of barrier dysfunction and infection in OLP pathogenesis through analysis of transcriptome datasets available in public databases. Two transcriptome datasets were downloaded from the Gene Expression Omnibus database and analyzed as whole and as partial sets after removing outliers. Differentially expressed genes (DEGs) upregulated in the dataset of OLP versus healthy epithelium were significantly enriched in epidermal development, keratinocyte differentiation, keratinization, responses to bacterial infection, and innate immune response. In contrast, the upregulated DEGs in the dataset of the mucosa predominantly reflected chemotaxis of immune cells and inflammatory/immune responses. Forty-three DEGs overlapping in the two datasets were identified after removing outliers from each dataset. The overlapping DEGs included genes associated with hyperkeratosis (upregulated LCE3E and TMEM45A), wound healing (upregulated KRT17, IL36G, TNC, and TGFBI), barrier defects (downregulated FRAS1 and BCL11A), and response to infection (upregulated IL36G, ADAP2, DFNA5, RFTN1, LITAF, and TMEM173). Immunohistochemical examination of IL-36γ, a protein encoded by one of the DEGs IL36G, in control (n = 7) and OLP (n = 25) tissues confirmed the increased expression of IL-36γ in OLP. Collectively, we identified gene signatures associated with hyperkeratosis, wound healing, barrier defects, and response to infection in OLP. IL-36γ, a cytokine involved in both wound repair and antimicrobial defense, may be a possible therapeutic target in OLP.

13.
Front Bioeng Biotechnol ; 9: 713860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368107

RESUMO

Paris polyphylla var. yunnanensis is a kind of biomass resource, which has important medicinal and economical values with a huge market. This review article aims to summarize the recent development of biomass P. polyphylla var. yunnanensis. The genetic diversity and chemical components of biomass P. polyphylla var. yunnanensis were reviewed based on the literature. Both the genetic diversity and genetic structure of biomass P. polyphylla var. yunnanensis were compared by using molecular marker technologies. All the extraction processes, harvest time, and drying methods on the chemical components were summarized in detail. The differences of arbuscular mycorrhizal fungi on the infection rate, diosgenin content, microorganisms, enzyme activities, rhizospheric environment, and endogenous hormones were discussed. This review article is beneficial for the applications of biomass P. polyphylla var. yunnanensis as a biomass resource in the biomedical field.

15.
Sci Total Environ ; 799: 149303, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34358748

RESUMO

In situ moorings were conducted at salt marsh and bare flat to reveal the environmental disturbance of sedimentary processes in the intertidal flat. Spartina alterniflora (Spartina), an invasive species, grew up to 156 cm in the Ganghwa tidal flat from June to November 2019. This rapid growth has resulted in the dense salt marsh, which complicated hydrodynamics and associated sediment processes. Stems and leaves could effectively trap fine-grained sediments (17.24-20.42 µm) at the bed, increasing the differences in bed elevation between the two sites to up to 5.11 cm. The cohesive sediments accumulated in Spartina communities were resuspended differently by stem-scale turbulence generated from the disturbance of stems and leaves, depending on wind forcing and vegetation conditions. The vegetated sediments, under low wind speeds (<4 m s-1), were hardly resuspended in the water column, compared to those in the bare flat, resulting in sedimentation. Under high wind speeds (>6 m s-1), stem-scale turbulence was sufficiently strengthened to surpass the sedimentation of suspended sediments; thus, it resuspended additional bed sediments without a loss of the trapped sediment, unlike in the bare flat. The flocculation of suspended sediments in Spartina communities was mainly controlled by stem-scale turbulence. The flocs were confined to a size of 40 µm (settling velocity: 0.17 mm s-1) and developed an approaching spherical shape. After the cut-off of Spartina, a favorable condition for the flocs to grow by 57 µm (settling velocity: 0.23 mm s-1) was established with decrease in stem-scale turbulence. These larger flocs were able to develop into a ramified spherical structure. Despite diminishment of stem-scale turbulence, the disturbed sediments were outflowed, resulting in an abrupt decrease in bed elevation (0.12 cm day-1). The results suggest that the sediment accumulated in Spartina communities remained erodible due to frequent disturbances without sufficient consolidation.


Assuntos
Sedimentos Geológicos , Áreas Alagadas , Espécies Introduzidas , Poaceae
16.
Sci Rep ; 11(1): 16091, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373514

RESUMO

Cold atmospheric plasma (CAP) has been incorporated into various fields, including promotion of cutaneous wound healing. Atopic dermatitis (AD) is a chronic cutaneous condition characterized by inflammation-induced skin wounds and impaired skin barrier function. To investigate whether CAP may improve AD using an animal model. Dermatophagoides farinae extracts (DFE)-induced murine models of AD were used in this study. The plasma-treated group received a total of 6 CAP treatments during 2 weeks, while the control group did not receive any treatment. Differences in dermatitis severity, transepidermal water loss (TEWL), serum level of immunoglobulin (Ig) E and epidermal thickness were evaluated in both groups. The dermatitis severity was significantly improved by CAP treatment. TEWL was lower in the plasma-treated group compared with the non-treated control group. Serum Ig E dropped significantly after treatment with CAP. Difference in epidermal thickness of the ear skin was not significant between the plasma-treated and non-treated groups. Localized treatment of AD with CAP decreases dermatitis severity, TEWL, and serum Ig E level. These results show CAP's potentials as a novel therapeutic modality for AD.

17.
Sci Rep ; 11(1): 16692, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404834

RESUMO

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10-8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10-6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10-6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

18.
Proc (Bayl Univ Med Cent) ; 34(5): 566-570, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34456474

RESUMO

This retrospective study examined clinical parameters associated with amantadine treatment of psychiatric symptoms in children. A total of 297 pediatric patients were prescribed amantadine and met study criteria to assess clinical responses and medication outcomes. More than 62% of patients experienced clinically significant symptom control and 83% achieved at least maintenance symptom control, while 11% discontinued amantadine for nonresponse and 6% stopped amantadine because of side effects. Among patients previously receiving other psychotropic medication, 42% and 28% of patients fully discontinued second- or third-generation antipsychotics or antidepressants, respectively. Patients responsive to amantadine who discontinued or reduced antipsychotic dose experienced a significant reduction in body mass index. Amantadine appears be an efficacious and safe alternative for treatment of a broad set of psychiatric symptoms in children and adolescents. Specifically, it may serve as an effective adjunct to stimulants for attention deficit/hyperactivity disorder-related symptoms and appears to be a safer alternative to second- or third-generation antipsychotics.

19.
Surg Endosc ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341907

RESUMO

BACKGROUND: The posterior retroperitoneoscopic approach (PRA) has been under attention as a method for resection of paraganglioma (PGL) for the past few years. However, only a few studies have explored the effectiveness and safety of the PRA for aortocaval and infrarenal PGL resection. METHODS: We designed this retrospective study to investigate the safety and effectiveness of the PRA for aortocaval and infrarenal PGL resection in a single center. We retrospectively reviewed the medical records of patients who underwent PRA for PGL resection at our medical center from January 2006 to March 2021. Eight patients were enrolled, of whom six had aortocaval PGL. We investigated the surgical outcomes of enrolled patients. RESULTS: The locations of the tumors in relation to the renal vein were: suprarenal in two (25.0%) patients, at the renal vein level in three (37.5%) patients, and infrarenal in three (37.5%) patients. The mean operative time of the enrolled patients was 101.5 ± 39.1 min. The mean postoperative stay was 3.5 ± 1.5 days, and the estimated blood loss was 31.3 ± 51.4 ml. There was one minor complication (chyle leakage), and two hypotensive events occurred during the surgery. Focusing on the results of the renal vein level and infrarenal PGL resection, the mean operative time, mean postoperative stay, and estimated blood loss of the patients were 109.2 ± 41.3 min, 3.5 ± 1.8 days, and 41.7 ± 56.4 ml, respectively. CONCLUSION: The PRA for aortocaval and infrarenal PGL resection is feasible and safe. Additional data analysis and long-term follow-up are needed in the future.

20.
J Med Chem ; 64(17): 12525-12536, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34435786

RESUMO

Distinguishing compounds' agonistic or antagonistic behavior would be of great utility for the rational discovery of selective modulators. We synthesized truncated nucleoside derivatives and discovered 6c (Ki = 2.40 nM) as a potent human A3 adenosine receptor (hA3AR) agonist, and subtle chemical modification induced a shift from antagonist to agonist. We elucidated this shift by developing new hA3AR homology models that consider the pharmacological profiles of the ligands. Taken together with molecular dynamics (MD) simulation and three-dimensional (3D) structural network analysis of the receptor-ligand complex, the results indicated that the hydrogen bonding with Thr943.36 and His2727.43 could make a stable interaction between the 3'-amino group with TM3 and TM7, and the corresponding induced-fit effects may play important roles in rendering the agonistic effect. Our results provide a more precise understanding of the compounds' actions at the atomic level and a rationale for the design of new drugs with specific pharmacological profiles.

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