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1.
Transl Lung Cancer Res ; 11(4): 523-542, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529784

RESUMO

Background: Macrophages are critical players in regulating innate and adaptive immunity in the tumor microenvironment (TME). The prognostic value of macrophages and their heterogeneous phenotypes in non-small cell lung cancer (NSCLC) is still uncertain. Methods: Surgically-resected samples of 681 NSCLC cases were stained by multiplex immunofluorescence to examine macrophage phenotypes as well as the expression levels of program death-ligand 1 (PD-L1) on them in both tumor nest and tumor stroma, including pan-macrophage (CD68+), M1 (CD68+CD163-), and M2 macrophages (CD68+CD163+). Various other immune cell markers, including CD4, CD8, CD20, CD38, CD66B, FOXP3, and CD133, were also evaluated. Machine learning algorithm by Random Forest (RF) model was utilized to screen the robust prognostic markers and construct the CD68-based immune-related risk score (IRRS) for predicting disease-free survival (DFS). Results: The expression levels of CD68 were moderately correlated with the levels of PD-L1 (P<0.001), CD133 (P<0.001), and CD8 (P<0.001). Higher levels of CD68 (OR 1.03, 95% CI: 1.01-1.05, P<0.001) as well as M1 macrophage (OR 1.04, 95% CI: 1.01-1.06, P<0.001) indicated shorter DFS. Despite without statiscial significance, intratumoral M2 macrophage (OR 1.05, 95% CI: 0.99-1.10, P=0.081) was also associated with worse DFS. IRRS incorporating three intratumoral CD68-related markers and four intrastromal markers was constructed and validated to predict recurrence (high-risk group vs. low-risk group: OR 2.52, 95% CI: 1.89-3.38, P<0.001). The IRRS model showed good accuracy [area under the curve (AUC) =0.670, 0.709, 0.695, 0.718 for 1-, 3-, 5-year, and overall DFS survival, respectively] and the predictive performance was better than the single-marker model (area under the curve 0.718 vs. 0.500-0.654). A nomogram based on clinical characteristics and IRRS for relapse prediction was then established and exhibited better performance than the tumor-node-metastasis (TNM) classification and IRRS system (C-index 0.76 vs. 0.69 vs. 0.60, 0.74 vs. 0.67 vs. 0.60, 0.81 vs. 0.74 vs. 0.60 of the entire, training, testing cohort, respectively). Conclusions: Our study suggested close interactions between CD68 and other immune markers in TME, demonstrating the prognostic value of CD68 in relapse prediction in resectable NSCLC.

2.
Molecules ; 27(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458741

RESUMO

In this paper, the syntheses of twelve asymmetric curcumin analogs using Pabon's method are reported. Generally, the previously reported yields of asymmetric curcuminoids, such as 9a (53%), 9c (38%), and 9k (38%), have been moderate or low. Herein, we propose that the low yields were due to the presence of water and n-BuNH2 in the reaction media. To prove this formulated hypothesis, we have demonstrated that the yields can be improved by adding molecular sieves (MS) (4 Å) to the reaction mixture, thus reducing the interference of water. Therefore, improved yields (41-76%) were obtained, except for 9b (36.7%), 9g (34%), and 9l (39.5%). Furthermore, compounds 9b, 9d, 9e, 9f, 9g, 9h, 9i, 9j, and 9l are reported herein for the first time. The structures of these synthetic compounds were determined by spectroscopic and mass spectrometry analyses. The free radical scavenging ability of these synthetic asymmetric curcuminoids was evaluated and compared to that of the positive control butylated hydroxytoluene (BHT). Among the synthesized asymmetric curcuminoids, compounds 9a (IC50 = 37.57 ± 0.89 µM) and 9e (IC50 = 37.17 ± 1.76 µM) possessed effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, and compounds 9h (IC50 = 11.36 ± 0.65 µM) and 9i (IC50 = 10.91 ± 0.77 µM) displayed potent 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging abilities comparable to that of curcumin (IC50 = 10.14 ± 1.04 µM). Furthermore, all the synthetic asymmetric curcuminoids were more active than BHT.


Assuntos
Antioxidantes , Curcumina , Antioxidantes/química , Hidroxitolueno Butilado/química , Curcumina/química , Diarileptanoides , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Água
3.
World J Pediatr ; 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35364799

RESUMO

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. With the gradual expansion of the incidence of JIA in the population, the pathogenesis and treatment of JIA were further explored and analyzed, and JIA has achieved some success in drug therapy. DATA SOURCES: A systemic literature search was conducted on PubMed, Cochrane Library, EMBASE, ISI Web of Science, the US National Institutes of Health Ongoing Trials Register, and the EU Clinical Trials Register. Through the searching of clinical trials of JIA in recent years, we summarized the progress of the clinical treatment of JIA. RESULTS: The main treatment drugs for JIA include non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs and biological agents. So far, a variety of biological agents targeting the cytokines and receptors involved in its pathogenesis have been gradually approved for JIA in many countries. The application of biological agents in JIA showed good efficacy and safety, bringing unprecedented experience to children and adolescents with JIA. CONCLUSIONS: The potential and advantages of biologic agents in the treatment of JIA are significant, and the application of biologic agents in the treatment of JIA will be more and more common.

4.
RSC Adv ; 12(13): 7911-7921, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35424765

RESUMO

Acetylcholinesterase (AChE) has been demonstrated as a crucial enzyme in the development and treatment of Alzheimer's disease (AD). The present work reported the preparation of high fluorescence emission, water-soluble, non-conjugated polymer dots (NCPDs) via Schiff base reaction, and its self-assembly between hyperbranched poly(ethylenimine) (PEI) and pyrogallol in aqueous solutions. A one-pot method was introduced, which made the preparation process of the NCPDs more convenient, energy-efficient, and environmentally friendly. The mechanism of the inherent fluorescence of NCPDs and its fluorescence properties were investigated. This study, for the first time, explored the application of NCPDs to a nanoquencher biosensing system, discovering the reversible quenching effect of MnO2 nanosheets for NCPDs. Furthermore, the quenching mechanism of MnO2 for NCPDs was demonstrated to be an inner filter effect (IFE). The NCPDs-MnO2 biosensing system showed a broader detection range from 12.3 to 3675 U L-1 for AChE and the limit of detection (LOD) was as low as 4.9 U L-1. The sensing system has been applied to screen AChE inhibitors, and the result of the positive drug was highly consistent with previous studies. The established method showed a promising prospect in screening for leading compounds in new drug discoveries for AD.

5.
J Mater Chem B ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451446

RESUMO

The design and fabrication of nanoplatforms with both nuclear medical imaging and therapeutic functions remain challenging in current precision nanomedicine. Herein, we report the design of a novel nanoplatform based on glucose-modified dendrimer-entrapped gold nanoparticles (Au DENPs) labeled with radionuclide 68Ga and incorporated with cytosine-guanine (CpG) oligonucleotide for positron emission tomography (PET)/computed tomography (CT) dual-mode imaging and immunotherapy of tumors. In this study, generation 5 poly(amidoamine) (PAMAM) dendrimers were first modified to have 8.2 DOTA and 7.3 polyethylene glycol with the other end functionalized with 2-amino-2-deoxy-D-glucose (DG) for each dendrimer, entrapped with Au NPs, and then radiolabeled with 68Ga through the DOTA chelation. The synthesized DG-Au DENPs have good cytocompatibility, targeting specificity toward cancer cells expressing glucose transporters, and the ability to be labeled by 68Ga with great labeling efficiency (≥85%) and stability (≥95%). After being loaded with CpG, the formed DG-Au DENPs/CpG polyplexes were proven to be used for tumor dual-mode PET/CT imaging and immunotherapy by effectively maturing dendritic cells to initiate a T cell-based antitumor immune response in vivo. Compared with the DG-free polyplexes, the developed DG-Au DENPs/CpG polyplexes show a much more sensitive imaging effect and better inhibition effect of tumors. These findings demonstrate a unique design of 68Ga-labeled DG-Au DENPs, a promising theranostic nanoplatform that may be extended to tackle different tumor types.

6.
ACS Appl Mater Interfaces ; 14(17): 20257-20267, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35451814

RESUMO

Thermodynamically induced tensile stress in the perovskite film will lead to the formation of atomic vacancies, seriously destroying the photovoltaic efficiency stability of the perovskite solar cells (PSCs). Among them, cations and halide anions vacancies are unavoidable; these point vacancies are considered to be a major source of the ionic migration and perovskite degradation at the crystal boundary and surface of the perovskite films. Here, we use choline bromide to modify the perovskite film by occupying the atomic defects in the CsPbBr3 perovskite film. The results show that the zwitterion quaternary ammonium ions and bromide ions in choline bromide can simultaneously occupy the Cs+ cation and Br- anions vacancies in the perovskite film by the ionic bonding effect, for which the defect-state density on the surface of the perovskite film can be significantly reduced, leading to the effective enhancement of carrier lifetime. In addition, the residual stress at the crystal boundary can be effectively reduced by lowering the Young's modulus in the CsPbBr3 perovskite film. As a result, the optimized device achieves a photoelectric conversion efficiency (PCE) of 9.06% with an increase of 41.1% compared to the control device with a PCE of 6.42%. Most importantly, the newborn thermal stress due to thermal expansion during heat working conditions can be transferred from the polycrystalline perovskite to the carbon layer by the matched Young's modulus, thus resulting in improved stability perovskite film under environmental conditions. The work provides new insights for preparing high-quality perovskite films with low defect-state density and residual stress.

7.
BMJ Open ; 12(4): e052180, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35450891

RESUMO

INTRODUCTION: Primary postoperative ileus is one of the principal factors affecting in-hospital recovery after colorectal surgery. Research on the relationship between anaesthetic depth and perioperative outcomes has been attracting growing attention. However, the impact of anaesthetic depth on the recovery of gastrointestinal function after surgery is unclear. We aimed to conduct a single-centre, prospective, randomised, controlled trial to explore the effect of anaesthetic depth on primary postoperative ileus after laparoscopic colorectal surgery. METHODS AND ANALYSIS: In this single-centre, prospective, patient-blinded and assessor-blinded, parallel, randomised, controlled trial, a total of 854 American Society of Anesthesiologists physical status I-III patients, aged between 18 and 65 years and scheduled for laparoscopic colorectal surgery lasting ≥2 hours, will be randomly assigned to deep anaesthesia group (Bispectral Index (BIS) 30-40) or light anaesthesia group (BIS 45-55). The primary outcome is primary postoperative ileus during the hospital stay. Secondary outcomes were time to gastrointestinal function recovery, another defined postoperative ileus, 15-item quality of recovery score, length of postoperative stay, postoperative 30-day complications and serum concentrations of intestinal fatty acid-binding protein at 6 hours after surgery. ETHICS AND DISSEMINATION: The protocol was approved by Medical Ethics Committee of Nanfang Hospital, Southern Medical University (Approval number: NFEC-2018-107) prior to recruitment. All participants will provide written informed consent before randomisation. Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR1800018725.


Assuntos
Anestésicos , Cirurgia Colorretal , Íleus , Laparoscopia , Adolescente , Adulto , Idoso , Cirurgia Colorretal/efeitos adversos , Humanos , Íleus/etiologia , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Dados Preliminares , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
8.
Sci Total Environ ; 835: 155460, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35472342

RESUMO

A new diffusive gradients in thin films technique (HR-MPTS DGT) with mercapto-functionalized attapulgite in a binding gel was developed for simultaneous two-dimensional (2-D) chemical imaging of AsIII, CrIII and SbIII selectively at the submillimeter scale, combined with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis. The HR-MPTS DGT exhibited selective accumulation of AsIII, SbIII and CrIII (> 97%), yet negligible accumulation of AsV, SbV and CrVI (< 2%). Accumulation of AsIII, CrIII and SbIII on the binding gel had a linear relationship (R2 > 0.99) with the corresponding standardized laser ablation signals, proving the feasibility of LA-ICP-MS analysis. Analysis for AsIII, CrIII and SbIII was provided with favorable analytical precision (relative standard deviation <10%). With the purpose of evaluating the dynamics of AsIII, CrIII, SbIII and O2 in the rooting zone, a hybrid sensor, which comprises the HR-MPTS gel overlying an O2 planar optode, was deployed in rhizosphere sediments. Results showed that the consumption of both AsIII and SbIII due to the oxidation extended ~4.48 mm into the sediments, which was consistent with the extension length of the oxidized sediment layers around the roots created by O2 leakage.

9.
Front Microbiol ; 13: 855988, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401464

RESUMO

Microbial infections cause significant morbidity and mortality in neonates. Metagenomic next-generation sequencing is a hypothesis-free and culture-free test that enables broad identification of pathogens and antimicrobial resistance genes directly from clinical samples within 24 h. In this study, we used mNGS for etiological diagnosis and monitoring the efficacy of antibiotic treatment in a cohort of neonatal patients with severe infections. The median age was 19.5 (3-52) days, median gestational age was 37.96 (31-40+3) weeks, and the median birth weight was 3,261 (1,300-4,300) g. The types of infectious diseases included pneumonia, sepsis, and meningitis. mNGS reported microbial findings in all cases, which led to changes in antibiotic treatment. These included cases of Mycobacterium tuberculosis, Legionella pneumophila, and Bacillus cereus. Eight of ten infants recovered after antibiotic adjustment and showed normal development during follow-up. On the other hand, neurological retardation was seen in two infants with meningitis. mNGS enabled etiological diagnosis and guided antibiotic therapy when all conventional methods failed to discover the culprit. It has the potential to cut down the overall cost and burden of disease management in neonatal infections.

10.
Cell ; 185(10): 1646-1660.e18, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35447073

RESUMO

Incomplete lineage sorting (ILS) makes ancestral genetic polymorphisms persist during rapid speciation events, inducing incongruences between gene trees and species trees. ILS has complicated phylogenetic inference in many lineages, including hominids. However, we lack empirical evidence that ILS leads to incongruent phenotypic variation. Here, we performed phylogenomic analyses to show that the South American monito del monte is the sister lineage of all Australian marsupials, although over 31% of its genome is closer to the Diprotodontia than to other Australian groups due to ILS during ancient radiation. Pervasive conflicting phylogenetic signals across the whole genome are consistent with some of the morphological variation among extant marsupials. We detected hundreds of genes that experienced stochastic fixation during ILS, encoding the same amino acids in non-sister species. Using functional experiments, we confirm how ILS may have directly contributed to hemiplasy in morphological traits that were established during rapid marsupial speciation ca. 60 mya.

11.
Sci Total Environ ; : 154575, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35302015

RESUMO

The sources and composition of dissolved organic matter (DOM) in rivers are critical to water quality and aquatic ecosystems. Studies on detailed composition of organic matter in rivers in the farming-pastoral ecotone are relatively limited in the research community. To better understand the characteristics and dynamics of DOM, Yang River in North China was selected as the study area because of its profound influences on the farming-pastoral ecotone nearby. A combination of fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) techniques revealed that the DOM composition of Yang River is driven by land use. DOM in Yang River is predominantly imported from allochthonous inputs, together with agricultural runoff, pastureland, and urban sewage, causing a comprehensive impact on DOM. In detail, DOM associated with cropland inputs was dominated by lignin-like species, with higher nitrogen content. In comparison, DOM related to grassland is more diverse and susceptible to degradation. An increase in urban areas led to an increase in sulfur-containing compounds, while their oxygen, nitrogen, and aromaticity contents were significantly lower than those in cropland. Interestingly, urban-influenced lignin-like compounds may be associated with the effluents from the pulp and paper mill. Additionally, synthetic surfactants from the lower section of the river were also structurally identified by tandem mass spectrometry. Overall, this study could provide valuable insights into the DOM sources and their transformation dynamics at a molecular level, which could be an indicator for riverine water quality management and be applied to other farming-pastoral ecotones straightforward.

12.
World J Pediatr Congenit Heart Surg ; 13(2): 155-165, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35238702

RESUMO

Background: Infective endocarditis (IE) is one of the major complications following pulmonary valve replacement (PVR). This analysis hopes to evaluate the incidence, outcomes and possible risk factors of IE associated with trans-catheter and surgical placement of a bovine jugular vein (BJV) graft in the pulmonary position. Methods: In this single-center retrospective study, all records of trans-catheter and surgical PVR from 3/2010 to 12/2019 were reviewed. IE was defined as positive blood cultures, with vegetations seen on echocardiography or sudden increase in peak gradient across the valve or vegetations confirmed at time of valve replacement. Poor dental hygiene:1.dental procedures without S.B.E prophylaxis AND/OR 2.one or more dental cavities, caries, dental abscess. Results: 165 patients had PVR with BJV:107 trans-catheter and 63 surgical. 7%(12/170) of PVRs developed IE(catheter:n = 10, surgery:n = 2) at a median time from valve placement of 38 months. The incidence of IE in the catheter group:3-per-100patient-years and in surgical group:1-per-100patient-years. Multivariate cox regression showed that poor dental hygiene was significantly associated with IE [HR(95% CI):16.9(4.35-66.2)](p value <.001). Kaplan-Meier curves showed a significant difference in freedom from IE between patients with poor and appropriate dental hygiene (p value<.001). Conclusions: There is a 7% incidence of IE with the use of BJV grafts in the pulmonary position at mid-term follow-up. Though the rate in catheter placed BJV seems 3x higher than surgically placed ones, their cohorts are quite different making this comparison flawed. Poor dental hygiene is a strong predictor for post-operative IE and offers a significant opportunity for lowering the rate of infective endocarditis.


Assuntos
Endocardite Bacteriana , Endocardite , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Valva Pulmonar , Animais , Bovinos , Endocardite/etiologia , Endocardite/cirurgia , Endocardite Bacteriana/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Desenho de Prótese , Valva Pulmonar/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
13.
J Gastrointest Oncol ; 13(1): 221-230, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284117

RESUMO

Background: Surgery is an effective treatment for improving the survival rate of patients with colorectal cancer liver metastases (CRLM). However, accurately determining the resection margin of liver lesions during surgery remains challenging. Therefore, this study aimed to evaluate the sensitivity and predictive value of intraoperative contrast-enhanced ultrasound (CE-IOUS) in CRLM patients undergoing surgery. Methods: We performed a literature search of the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases using the following search terms: metastatic liver cancer, colorectal cancer, sensitivity, contrast-enhanced intraoperative ultrasound, CE-IOUS, colorectal liver metastases, and CRLM. The search period was set from the date of establishment of the database to September 2021. Quality assessment of diagnostic accuracy studies 2 (QUADAS-2) recommended by the Cochrane Collaboration was used to assess the methodological quality of the included studies, and network meta-analysis was performed using Stata 15.0 software. Results: A total of 10 articles met the inclusion criteria. The meta-analysis results showed that the overall sensitivity and specificity of CE-IOUS were 0.96 [95% confidence interval (CI), 0.95-0.97] and 0.75 (95% CI, 0.70-0.80), respectively. The overall sensitivity and specificity of IOUS were 0.84 (95% CI, 0.82-0.86) and 0.82 (95% CI, 0.77-0.87), respectively. The area under the summary receiving operating characteristic (SROC) curves (AUCs) of CE-IOUS and IOUS were 0.9753 and 0.8590, respectively. The odds ratio (OR) and 95% CI of CE-IOUS changed the surgical margin were 0.205 and 0.071-0.465, P=0.000, the difference was statistically significant. Discussion: Based on the results of this meta-analysis, CE-IOUS improved the sensitivity and predictive value of CRLM detection compared with IOUS, and is more suitable for intraoperative planning of surgical margins. At present, it is the most sensitive imaging method available, and is recommended for use during liver resection to provide doctors with more reliable information during surgery.

14.
PeerJ ; 10: e13098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35291482

RESUMO

Background: In high-dimensional survival genomic data, identifying cancer-related genes is a challenging and important subject in the field of bioinformatics. In recent years, many feature screening approaches for survival outcomes with high-dimensional survival genomic data have been developed; however, few studies have systematically compared these methods. The primary purpose of this article is to conduct a series of simulation studies for systematic comparison; the second purpose of this article is to use these feature screening methods to further establish a more accurate prediction model for patient survival based on the survival genomic datasets of The Cancer Genome Atlas (TCGA). Results: Simulation studies prove that network-adjusted feature screening measurement performs well and outperforms existing popular univariate independent feature screening methods. In the application of real data, we show that the proposed network-adjusted feature screening approach leads to more accurate survival prediction than alternative methods that do not account for gene-gene dependency information. We also use TCGA clinical survival genetic data to identify biomarkers associated with clinical survival outcomes in patients with various cancers including esophageal, pancreatic, head and neck squamous cell, lung, and breast invasive carcinomas. Conclusions: These applications reveal advantages of the new proposed network-adjusted feature selection method over alternative methods that do not consider gene-gene dependency information. We also identify cancer-related genes that are almost detected in the literature. As a result, the network-based screening method is reliable and credible.

15.
Microbiome ; 10(1): 38, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241180

RESUMO

BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury. RESULTS: Intestinal I/R-sensitive (Sen) and intestinal I/R-resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. CONCLUSION: The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice. Video Abstract.


Assuntos
Traumatismo por Reperfusão , Receptor 2 Toll-Like , Animais , Humanos , Interleucina-10 , Isquemia , Lactobacillus , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/tratamento farmacológico
16.
Arch Pharm (Weinheim) ; 355(5): e2100448, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35174890

RESUMO

We synthesized multiple cinnamils and quinoxalines to evaluate their anticancer activity. Cinnamils were used as precursors for quinoxalines via condensation with 1,2-diaminobenzene. Among the 26 synthesized compounds reported in this article, we found that cinnamil 3l exhibited its inhibitory effect with an IC50 value of 1.45 ± 0.98 µM, significantly higher than doxorubicin (8.5 ± 0.85 µM) against pancreatic cancer cells (PANC-1). Additionally, cinnamil 3l (IC50 10.98 ± 3.63 µM) showed less cytotoxicity than doxorubicin to Hs68 cells (0.92 ± 1.11 µM). The colony formation assay demonstrated that 3l obviously decreased the PANC-1 cell viability, and Western blot assays confirmed that 3l markedly induced apoptosis of PANC-1 cells through Bax, Bcl-2, and caspase 3 signaling cascades. These results demonstrate that cinnamil 3l has great potential to be further developed as a promising chemotherapeutic agent for pancreatic cancer.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias Pancreáticas/tratamento farmacológico , Quinoxalinas/farmacologia , Relação Estrutura-Atividade
17.
Mol Immunol ; 144: 49-57, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35189399

RESUMO

OBJECTIVE: Graves' disease (GD) is one of the most common autoimmune conditions, but the mechanisms underlying the associated induction of autoimmunity are not known. We explored the role of peripheral lymphocyte subpopulations in disease pathogenesis. METHODS: In total, 32 patients and 40 age- and sex-matched healthy controls were recruited in this study. Peripheral levels of T, B, NK, CD4+ T, CD8+ T, Th1, Th2, Th17, and Treg cells were measured using flow cytometry. For all patients, we compared all lymphocyte subpopulations between GD patients and healthy controls. Changes in patient lymphocyte subsets were compared before and after treatment. RESULTS: The absolute numbers of circulating Th17 cells (0.45 ± 1.16, p > 0.05) between GD patients and healthy controls were not significantly different. However, the percentage of Th17 cells was significantly increased (0.25 ± 0.11, p < 0.05). The absolute numbers and percentages of circulating Tregs in GD patients were significantly decreased compared with those in healthy participants (11.61 ± 2.75, p < 0.05). There was a significant difference in Treg absolute numbers between the untreated and drug-treated groups. Furthermore, we found that the Treg percentage in untreated patients (mean=4.78) was not significantly different from that in the drug-treated group (mean=4.81). In addition, circulating Treg absolute numbers in GD patients with exophthalmos were significantly lower than those in GD patients without exophthalmos (9.96 ± 4.16, p < 0.05). A similar trend was observed in GD patients with weight loss (11.97 ± 3.28, p < 0.05). CONCLUSION: GD pathogenesis was associated with a lower Treg population and an increased Th17/Treg ratio (T helper cell 17/ regulatory T cells). Th17 cells in this study were not related to the disease. Furthermore, anti-thyroid drug therapy improved immune-mediated system disorders. Finally, we found lower absolute numbers of circulating Tregs in GD patients with certain positive signs, such as exophthalmos and/or weight loss. Thus, immune changes are correlated with partial clinical manifestations.


Assuntos
Doença de Graves , Linfócitos T Reguladores , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Humanos , Contagem de Linfócitos , Células Th17 , Perda de Peso
18.
Transpl Immunol ; 71: 101556, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35202801

RESUMO

The unclear mechanism that ischemia-reperfusion injury (IRI) contributes to the development of primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) remains a major issue in lung transplantation. Differentially expressed PGD-related genes and CLAD-related genes during IRI (IRI-PGD common genes and IRI-CLAD common genes) were identified using GEO datasets (GSE127003, GSE8021, GSE9102) and GeneCards datasets. Enrichment analysis and four network analyses, namely, protein-protein interaction, microRNA (miRNA)-gene, transcription factor (TF)-gene, and drug-gene networks, were then performed. Moreover, GSE161520 was analyzed to identify the differentially expressed core miRNAs during IRI in rats. Finally, Pearson correlation analysis and ROC analysis were performed. Eight IRI-PGD common genes (IL6, TNF, IL1A, IL1B, CSF3, CXCL8, SERPINE1, and PADI4) and 10 IRI-CLAD common genes (IL1A, ICAM1, CCL20, CCL2, IL1B, TNF, PADI4, CXCL8, GZMB, and IL6) were identified. Enrichment analysis showed that both IRI-PGD and IRI-CLAD common genes were significantly enriched in "AGE-RAGE signaling pathway in diabetic complication" and "IL-17 signaling pathway". Among the core miRNAs, miR-1-3p and miR-335 were differentially expressed in IRI rats. Among core TFs, CEBPB expression had a significant negative correlation with P/F ratio (r = -0.33, P = 0.021). In the reperfused lung allografts, the strongest positive correlation was exhibited between PADI4 expression and neutrophil proportion (r = 0.76, P < 0.001), and the strongest negative correlation was between PADI4 expression and M2 macrophage proportion (r = -0.74, P < 0.001). In lung allografts of PGD recipients, IL6 expression correlated with activated dendritic cells proportion (r = 0.86, P < 0.01), and IL1B expression correlated with the neutrophils proportion(r = 0.84, P < 0.01). In whole blood of CLAD recipients, GZMB expression correlated with activated CD4+ memory T cells proportion (r = 0.76, P < 0.001).Our study provides the novel insights into the molecular mechanisms by which IRI contributes to PGD and CLAD and potential targets for therapeutic intervention.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Pulmão , MicroRNAs , Disfunção Primária do Enxerto , Traumatismo por Reperfusão , Aloenxertos/metabolismo , Animais , Interleucina-6 , Pulmão/metabolismo , MicroRNAs/genética , Disfunção Primária do Enxerto/genética , Ratos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Transcriptoma
19.
Hum Vaccin Immunother ; 18(1): 2029257, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35175866

RESUMO

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks (P = .007), 25.40% increased for times of washing hands (P = .01), and 20.90% increased for times of wearing gloves (P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , China/epidemiologia , Comportamentos Relacionados com a Saúde , Pessoal de Saúde , Humanos , SARS-CoV-2 , Vacinação
20.
Sci Rep ; 12(1): 2856, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190606

RESUMO

The SQUAMOSA promoter-binding protein-like (SPL) family play a key role in guiding the switch of plant growth from juvenile to adult phases. Populus euphratica Oliv. exhibit typical heterophylly, and is therefore an ideal model for studying leaf shape development. To investigate the role and regulated networks of SPLs in the morphogenesis of P. euphratica heteromorphic leaves. In this study, 33 P. euphratica SPL (PeuSPL) genes were identified from P. euphratica genome and transcriptome data. Phylogenetic analysis depicted the classification of these SPL genes into two subgroups. The expression profiles and regulatory networks of P. euphratica SPL genes analysis displayed that major P. euphratica SPL family members gradually increases from linear to broad-ovate leaves, and they were involved in the morphogenesis regulation, stress response, transition from vegetative to reproductive growth, photoperiod, and photosynthesis etc. 14 circRNAs, and 33 lncRNAs can promote the expression of 12 of the P. euphratica SPLs by co-decoying miR156 in heteromorphic leaf morphogenesis. However, it was found that the effect of PeuSPL2-4 and PeuSPL9 in leaf shape development was contrasting to their homologous genes of Arabidopsis. Therefore, it was suggested that the SPL family were evolutionarily conserved for regulation growth, but were varies in different plant for regulation of the organ development.


Assuntos
Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Genes de Plantas/genética , Morfogênese/genética , Folhas de Planta/genética , Populus/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fotossíntese/genética , Filogenia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Populus/crescimento & desenvolvimento , Populus/fisiologia , RNA Circular/fisiologia , RNA Longo não Codificante/fisiologia , RNA de Plantas/fisiologia
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