Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 402
Filtrar
1.
Adv Wound Care (New Rochelle) ; 11(1): 19-27, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33554730

RESUMO

Objective: MiRNAs are important regulators of inflammation and wound healing. However, the mechanisms through which miRNAs regulate wound healing under normal and diabetic conditions are poorly understood. We aimed to determine the effects of miR-146a on the pathogenesis of wound healing in normal and streptozotocin (STZ)-induced diabetic mice. Approach: Wild-type (WT) and miR-146a knockout (KO) mice were induced to develop diabetes with STZ. Next, skin and corneal wounds were produced and measured. Percent wound closure and histology were evaluated. Inflammation at wound sites was analyzed using flow cytometry, reverse-transcription PCR, and western blot. Results: Healing of wounded skin was significantly delayed in miR-146a KO compared with WT mice. However, corneal epithelial wound healing did not differ significantly in the mice with normal blood glucose, whereas corneal and skin wound healing was significantly delayed in KO mice with diabetes. Neutrophil infiltration increased in skin wounds of KO compared with normal mice. The potential mechanisms were associated with dysregulated interleukin 1ß, tumor necrosis factor alpha (TNF-α), IRAK1 (interleukin-1 receptor-associated kinase 1), TRAF6 (TNF receptor-associated factor 6), and nuclear factor kappa B (NF-κB) signaling induced by miR-146a KO. Innovation: Skin wound healing was delayed in miR-146a KO mice and enhanced inflammatory responses were mediated by the NF-κB signaling pathway. Conclusions: Deficiency in miR-146a delayed skin wound healing by enhancing inflammatory responses in normal and diabetic mice. Therefore, miR-146a may be a potential target for modulation to accelerate skin wound healing.

2.
Molecules ; 26(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34834078

RESUMO

Photocatalytic degradation, as an emerging method to control environmental pollution, is considered one of the most promising environmental purification technologies. As Tibet is a region with some of the strongest solar radiation in China and even in the world, it is extremely rich in solar energy resources, which is ideal for applying photocatalytic technology to its ecological environment protection and governance. In this study, Na2Ti3O7 nanobelts were prepared via a hydrothermal method and converted to TiO2∙xH2O ion exchange, which was followed by high-temperature calcination to prepare TiO2(B) nanobelts ("B" in TiO2(B) means "Bronze phase"). A simple in situ method was used to generate Ag3PO4 particles on the surface of the TiO2 nanobelts to construct a Ag3PO4/TiO2(B) heterojunction composite photocatalyst. By generating Ag3PO4 nanoparticles on the surface of the TiO2(B) nanobelts to construct heterojunctions, the light absorption range of the photocatalyst was successfully extended from UV (ultraviolet) to the visible region. Furthermore, the recombination of photogenerated electron-hole pairs in the catalyst was inhibited by the construction of the heterojunctions, thus greatly enhancing its light quantum efficiency. Therefore, the prepared Ag3PO4/TiO2(B) heterojunction composite photocatalyst greatly outperformed the TiO2(B) nanobelt in terms of photocatalytic degradation.

3.
J Healthc Eng ; 2021: 5222745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820077

RESUMO

The report of bradycardia caused by propofol is increasing. In the experiment, we investigated the chronotropic function of propofol and the underlying mechanism. Rabbits of both sexes were randomly divided into 4 groups: propofol 5 mg/kg group, 10 mg/kg group, 15 mg/kg group, and sham group. Heart rate and frequency of vagal efferent discharge were recorded before the injection and 0, 0.5, 1, 2, and 10 min after the injection through intravenous mode. Then, their hearts were removed, and sinoatrial nodes were dissected. The action potentials of the sinus node pacemaker cells were recorded by the intracellular glass microelectrode technique, and the sinoatrial (SA) node was exposed to propofol 1, 3, 5, and 10 µM respectively. The action potentials were recorded after the sinoatrial nodes were exposed to each concentration of propofol for 15 min. Our results show that the heart rate significantly decreased, and the vagal efferent discharge was significantly increased at 0, 0.5, 1, and 2 min after the injection, respectively. Besides, as the dose increases, the magnitude of change shows a dose-dependent manner. Propofol exerts a negative chronotropic action on sinoatrial node pacemaker cells. The drug significantly decreased APA, VDD, RPF, and prolonged APD90 in a concentration-dependent manner. These effects may be the main mechanism of propofol-induced bradycardia in clinical study.

4.
Talanta ; : 123069, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34836637

RESUMO

Characterization of alkaloids and new compound discovery become increasing challenging for Gelsemium elegans Benth. (G. elegans), due to the lack of an effective separation method. In this study, we developed a new online heart-cutting + comprehensive (HC) RPLC × RPLC system with pH difference, which was coupled to a mass detector to realize the separation and characterization of alkaloids from G. elegans. 18 Gelsemium standards were used to construct the RPLC × RPLC system with pH difference (pH 3 and 11), and good orthogonality (correlation coefficient 0.3) was obtained. A heart-cutting valve was introduced into the traditional online comprehensive RPLC × RPLC system to remove principal components and improve detection of minor components. The online HC RPLC × RPLC system achieved good resolving power (effective peak capacity 687) in condition of optimized practical factors, like the first- and second-dimension flow rates, modulation period and elution gradient et al. Finally, a total of 256 alkaloids were grouped and tentatively identified, among which 156 were unreported, including a new alkaloid type in G. elegans and many dimeric indole alkaloids, which was an important supplement to the study on chemical constituents of G. elegans.

5.
Phytochemistry ; 194: 113015, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34798412

RESUMO

A phytochemical investigation on chemical constituents from the rhizomes of Menispermum dauricum DC. identified eight undescribed dimeric alkaloids with structurally diverse monomeric isoquinoline. Alkaloid structures were elucidated by a combination of spectroscopic data analyses and time-dependent density functional theory (TDDFT) ECD calculation. The isolates were evaluated for inhibitory effect on dopamine D1 receptor and compound 1 exhibited potent D1 receptor antagonistic activity with an IC50 value of 8.4 ± 2.0 µM.

6.
Front Oncol ; 11: 666017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737942

RESUMO

Nanozymes, a new generation of enzyme mimics, have recently attracted great attention. Nanozymes could catalyze chemical reactions as biological enzymes under physiologically mild conditions with higher-efficiency catalytic activities. Moreover, nanozymes could overcome the shortcomings of natural enzymes, such as easy inactivation, high cost, and low yield. With the development of more and more smart and multi-functional nanosystems, nanozymes display great achievement in tumor biology. In this review, we outline the recent advances of nanozymes in tumor and tumor microenvironment diagnosis, therapy, and theranostics.

7.
Adv Mater ; : e2107836, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719819

RESUMO

Metal-organic frameworks (MOFs) with controllable shapes and sizes show a great potential in Li-S batteries. However, neither the relationship between shapes and specific capacity nor the influence of MOF particle size on cyclic stability have been fully established yet. Herein, MIL-96-Al with various shapes, forming hexagonal platelet crystals (HPC), hexagonal bipyramidal crystals (HBC), and hexagonal prismatic bipyramidal crystals (HPBC) were successfully prepared via co-solvent methods. Density functional theory (DFT) calculations demonstrate that the HBC shape with highly exposed (101) planes can effectively adsorb lithium polysulfides (LPS) during the charge/discharge process. By changing the relative proportion of the co-solvents, HBC samples with different particle sizes were prepared. When these MIL-96-Al crystals were used as sulfur host materials, it was found that those with the smaller size of HBC shape deliver the higher initial capacity. These investigations establish that different crystal planes have different adsorption abilities for LPS, and that the MOF particle size should be considered for a suitable sulfur host. More broadly, this work provides a strategy for designing sulfur hosts in Li-S batteries. This article is protected by copyright. All rights reserved.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34610781

RESUMO

AIM AND OBJECTIVES: The Gochnatia decora (Kurz) A. L. Cabrera is a rare woody plant belonging to the family of Asteraceae. The bark of this plant is used in Chinese folk medicine to treat cough and pneumonia. However, the effective substance related to its efficacy remains unknown. This study aims to evaluate the potential anti-inflammatory activities of the chemicals isolated from this plant using a model of LPS-induced RAW264.7 cells. MATERIAL AND METHODS: Chemical constituents were isolated from the stems and leaves of G. decora by a series of chromatographic separation methods and identified by spectral analysis techniques. The model of inflammation in vitro was established by treatment of 1 µM LPS on RAW264.7 cells. The influence of tested compounds on inflammatory factor production, including NO, TNF-α, IL-1ß, IL-6, IL-17, were determined by ELISA. The mechanisms involved were studied by western blot analysis. RESULTS: Two known ent-kaurane diterpenes (1 and 2), identified as ent-17-hydroxy-15-oxokauran-19-oic acid (1) and ent-15α-hydroxy-16-kauran-19-oic acid (2), were isolated from the stems and leaves of G. decora. The bioassay showed both of them produced significant inhibition of LPS-induced release of NO, TNF-α, IL-1ß, IL-6, IL-17, iNOS, and COX-2 expression. Western blot analysis showed that these same 2 chemicals blocked LPS-induced phosphorylation of NF-κB. CONCLUSIONS: Compounds 1 and 2 were obtained from the genus Gochnatia. These compounds demonstrated useful anti-inflammatory activities in the model of LPS-induced RAW264.7 cells. A potential action mechanism may be correlation of the NF-κB pathway.

9.
Cancer Cell Int ; 21(1): 526, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627254

RESUMO

BACKGROUND: The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. METHODS: We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. RESULTS: In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. CONCLUSIONS: Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1606-1609, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627448

RESUMO

OBJECTIVE: To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT. RESULTS: The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment(P<0.01); the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ(P<0.01). The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD(P<0.05). CONCLUSION: ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Proteínas Sanguíneas , Doença Crônica , Humanos , Transplante Homólogo , Quinases Associadas a rho
11.
Front Oncol ; 11: 724435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552875

RESUMO

Background: The prognosis of acute myeloid leukemia (AML) with a normal karyotype is highly heterogonous, and the current risk stratification is still insufficient to differentiate patients from high-risk to standard-risk. Changes in some genetic profiles may contribute to the poor prognosis of AML. Although the prognostic value of G protein subunit alpha 15 (GNA15) in AML has been reported based on the GEO (Gene Expression Omnibus) database, the prognostic significance of GNA15 has not been verified in clinical samples. The biological functions of GNA15 in AML development remain open to investigation. This study explored the clinical significance, biological effects and molecular mechanism of GNA15 in AML. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of GNA15 in blasts of bone marrow specimens from 154 newly diagnosed adult AML patients and 26 healthy volunteers. AML cell lines, Kasumi-1 and SKNO-1, were used for lentiviral transfection. Cell Counting Kit-8 (CCK8) and colony formation assays were used to determine cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The relevant signaling pathways were evaluated by Western blot. The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Xenograft tumor mouse model was used for in vivo experiments. Results: The expression of GNA15 in adult AML was significantly higher than that in healthy individuals. Subjects with high GNA15 expression showed lower overall survival and relapse-free survival in adult AML with normal karyotype. High GNA15 expression was independently correlated with a worse prognosis in multivariate analysis. Knockdown of GNA15 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. GNA15-knockdown induced down-regulation of p-P38 MAPK and its downstream p-MAPKAPK2 and p-CREB. Rescue assays confirmed that P38 MAPK signaling pathway was involved in the inhibition of proliferation mediated by GNA15 knockdown. Conclusions: In summary, GNA15 was highly expressed in adult AML, and high GNA15 expression was independently correlated with a worse prognosis in adult AML with normal karyotype. Knockdown of GNA15 inhibited the proliferation of AML regulated by the P38 MAPK signaling pathway. Therefore, GNA15 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

12.
Mater Sci Eng C Mater Biol Appl ; 129: 112422, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579930

RESUMO

An in-situ formed hemostatic hydrogel (GelMA/OD/Borax) was prepared for the emergency wound hemostasis and anti-inflammation applications. Gelatin was chosen as the backbone and modified with methacrylic anhydride (MA) to synthesize GelMA, which showed the admirable UV light activatable polymerizing ability. Aldehyde groups, which cross-linked with the -NH2 on the tissue surface and afforded the tissue adhesion, were produced by oxidizing the o-hydroxyl groups of dextran. Further, the sodium tetraborate formed dynamic boric acid ester bonds with the oxidized dextran (OD). With this triple-network structure, the as-prepared hydrogel presented excellent hemostatic capacity and surmounted a high blood pressure of 165 mmHg, which is higher than the threshold systolic blood pressure of healthy adults (i.e., 120 mmHg). The mechanical property, morphology, biocompatibility and degradation of the hydrogel were character Borax, the hydrogel successfully blocked the bleeding and accelerated the wound healing. This research provides a new modality for the design of a multifunctional hemostatic hydrogel for effective hemostasis and wound healing.


Assuntos
Hemostáticos , Hidrogéis , Adesivos/farmacologia , Hemostasia , Hemostáticos/farmacologia , Humanos , Hidrogéis/farmacologia , Cicatrização
13.
Animals (Basel) ; 11(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34573452

RESUMO

The current study was designed to investigate the chemical composition, rumen degradation characteristics, and feeding value of three roughages commonly used in Asia as ruminant feed, including Chinese rye grass (CRG), barley grass (BG), and naked oat straw (NO). Four Holstein Friesian cows equipped with permanent rumen fistulas were chosen for experimental trials in the current study. The nylon bag method was carried out to measure the crude protein (CP), acid detergent fiber (ADF), ruminal degradability of dry matter (DM), and neutral detergent fiber (NDF). Our analysis revealed that the contents of CP in the CRG (9.0%) and BG (8.9%) were higher than in the NO (5.94%). The contents of NDF in the CRG (64.97%) and NO (63.83%) were lower than in the BG (67.33%), and the content of ADF in the CRG (37.03%) was lower than in the BG (37.93%) and NO (38.28%). The ED values of DM in the NO and CRG were significantly higher (p < 0.001) than in the BG. The effective degradability (ED) values of NDF were the highest in the CRG and lowest in the NO (p < 0.001). In addition, the ED values of ADF were the highest in the CRG and lowest in the BG (p < 0.001). The ED value of CP in the CRG was significantly higher than that in the BG and NO (p < 0.001). The estimated total digestible nutrients (TDN) (54.56%) and DM degradation rate (DDM) (60.06%) of the CRG were higher than those of BG and NO. In addition, the expected DM intake (DMI), estimated relative feed value (RFV), and estimated relative feed quality (RFQ) of the BG were lower than those of the CRG and NO. Altogether, based on our findings, we concluded that the nutritional quality, feeding value and effective rumen degradation rate of CRG were better than of BG and NO.

14.
Clin Neurol Neurosurg ; 209: 106863, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34474332

RESUMO

OBJECTIVE: The predictive roles of copeptin and insulin-like growth factor-1 (IGF-1) in aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. We aimed to define the relationship between copeptin and IGF-1 levels and functional outcome as well as quality of life (QoL) after aSAH. METHODS: Patients with aSAH were prospectively enrolled in a tertiary university hospital. Controls were sex- and age-matched healthy subjects. Plasma concentrations of copeptin and IGF-1 were measured on admission. Demographics and clinical, radiological and laboratory characteristics of the patients were collected. Favorable functional outcome was defined as modified Rankins≤2, and QoL was evaluated by the 36-Item Short Form Health Survey (SF-36) 1 year after aSAH. Uni- and multivariable analyses were performed. RESULTS: One hundred eighteen patients were eligible, with 122 healthy controls were included in this study. Plasma copeptin levels were significantly higher and plasma IGF-1 was lower in patients than in controls. Both copeptin (adjusted HR 4.143 [1.120-15.328], p = 0.033) and IGF-1 levels (adjusted HR 0.089 [0.013-0.602], p = 0.013) were positively associated with 1-year mortality, while only single copeptin and IGF-1 concentrations were independent predictors of poor functional outcome and QoL, respectively. CONCLUSIONS: Plasma copeptin and IGF-1 levels are abnormal in patients with acute aSAH, and this may reliably predict long-term mortality, functional outcome and QoL.

15.
Neurol Res ; : 1-10, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34431446

RESUMO

To systematically compare 27 ICH models with regard to mortality and functional outcome at 1-month, 3-month and 1-year after ICH. The validation cohort was derived from the Beijing Registration of Intracerebral Hemorrhage. Poor functional outcome was defined as modified Rankin Scale score (mRS) ≥3 at 1-month, 3-month and 1-year after ICH, respectively. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration. A total number of 1575 patients were included. The mean age was 57.2 ± 14.3 and 67.2% were male. The median NIHSS score on admission was 11 (IQR: 3-21). For predicting mortality at 3-month after ICH, AUROC of 27 ICH models ranged from 0.604 to 0.856. In pairwise comparison, the ICH-FOS (0.856, 95%CI = 0.835-0.878, P < 0.001) showed statistically better discrimination than other models for mortality at 3-month after ICH (all P < 0.05). For predicting poor functional outcome (mRS≥3) at 3-month after ICH, AUROC of 27 ICH models ranged from 0.602 to 0.880. In pairwise comparison with other prediction models, the ICH-FOS was superior in predicting poor functional outcome at 3-month after ICH (all P < 0.001). The ICH-FOS showed the largest Cox and Snell R-square. Similar results were verified for mortality and poor functional outcome at 1-month and 1-year after ICH. Several risk models are externally validated to be effective for risk stratification and outcome prediction after ICH, especially the ICH-FOS, which would be useful tools for personalized care and clinical trial in ICH.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1129-1135, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362492

RESUMO

OBJECTIVE: To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells. METHODS: The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA. RESULTS: The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle. CONCLUSION: Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.


Assuntos
Proteínas de Ciclo Celular , Leucemia , Proteína Quinase CDC2 , Proteínas de Ciclo Celular/genética , Proliferação de Células , Humanos , Mitose , Fosforilação , Proteínas Proto-Oncogênicas/genética
17.
Front Oncol ; 11: 694933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367978

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor and is insensitive to radiotherapy and chemotherapy, as it is highly correlated with its complex tumor microenvironment (TME). A comprehensive description of PDAC's immune microenvironment at the pathological level has not been reported, thus limiting its treatment. Previous studies have shown that large-section histopathology (LSH) can reveal the complete structure and margin of the tumor on a single slice and effectively reflect intratumoral heterogeneity. LSH, as opposed to classic small-section histopathology (SSH), can also be used to explore the infiltration state of immune cells in different regions. In the current study, EnVision immunohistochemical staining was used to explore the panoramic distribution of CD4-, CD8-, CD15-, CD20-, and CD56 (surface markers of helper T cells, cytotoxic T cells, neutrophils, B cells, and NK cells, respectively)-positive cells in 102 pairs of paraffin wax-embedded PDAC samples (LSH vs SSH) for the first time. These indicators were then analyzed, and correlations of clinicopathological characteristics with clinical prognoses were analyzed. The findings of this study show that LSH can effectively indicate more immune cells than SSH. Upregulated CD4, CD8, CD20, and CD56 or downregulated CD15 was correlated with a good prognosis in PDAC patients. However, analysis of SSH showed that only upregulated CD4 and CD8 can be used as indicators of a good prognosis. Multivariate Cox regression analysis showed that 7 variables, namely, pTNM stage (P=0.002), PDL1 expression (P=0.001), CDX2 expression (P=0.008), DPC4 expression (P=0.004), CD4 expression in LSH (P<0.001), CD8 expression in LSH (P=0.010) and CD15 expression in LSH (P=0.031), were significantly correlated with the prognosis of PDAC patients. The findings of this study indicate that LSH is an effective tool for a panoramic assessment of the immune microenvironment in pancreatic cancer patients.

18.
J Ethnopharmacol ; 280: 114488, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358653

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has a long history in the prevention and treatment of pandemics. The TCM formula Lung Cleansing and Detoxifying Decoction (LCDD), also known as Qing Fei Pai Du Decoction, has been demonstrated effective against Coronavirus Disease 2019 (COVID-19). AIM OF THE STUDY: This work aimed to elucidate the active ingredients, targets and pathway mechanism of LCDD related to suppression of inflammatory, immunity regulation and relaxation of airway smooth muscle for the treatment of COVID-19. MATERIALS AND METHODS: Mining chemical ingredients reported in LCDD, 144 compounds covering all herbs were selected and screened against inflammatory-, immunity- and respiratory-related GPCRs including GPR35, H1, CB2, B2, M3 and ß2-adrenoceptor receptor using a label-free integrative pharmacology method. Further, all active compounds were detected using liquid chromatography-tandem mass spectrometry, and an herb-compound-target network based on potency and content of compounds was constructed to elucidate the multi-target and synergistic effect. RESULTS: Thirteen compounds were identified as GPR35 agonists, including licochalcone B, isoliquiritigenin, etc. Licochalcone B, isoliquiritigenin and alisol A exhibited bradykinin receptor B2 antagonism activities. Atractyline and shogaol showed as a cannabinoid receptor CB2 agonist and a histamine receptor H1 antagonist, respectively. Tectorigenin and aristofone acted as muscarinic receptor M3 antagonists, while synephrine, ephedrine and pseudoephedrine were ß2-adrenoceptor agonists. Pathway deconvolution assays suggested activation of GPR35 triggered PI3K, MEK, JNK pathways and EGFR transactivation, and the activation of ß2-adrenoceptor mediated MEK and Ca2+. The herb-compound-target network analysis found that some compounds such as licochalcone B acted on multiple targets, and multiple components interacted with the same target such as GPR35, reflecting the synergistic mechanism of Chinese medicine. At the same time, some low-abundance compounds displayed high target activity, meaning its important role in LCDD for anti-COVID-19. CONCLUSIONS: This study elucidates the active ingredients, targets and pathways of LCDD. This is useful for elucidating multitarget synergistic action for its clinical therapeutic efficacy.


Assuntos
Técnicas Biossensoriais/métodos , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Linhagem Celular Tumoral , Chalconas/farmacologia , Cricetulus , Medicamentos de Ervas Chinesas/análise , Efedrina/farmacologia , Células HEK293 , Humanos , Imunidade/efeitos dos fármacos , Inflamação/metabolismo , Pneumopatias/metabolismo , Músculo Liso/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Respiração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
19.
J Sep Sci ; 44(18): 3441-3449, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291571

RESUMO

Plant-derived alkaloids are bioactive natural ingredients, but their contents are relatively low in plants. Therefore, the efficient enrichment of alkaloids is a prerequisite for purification and further pharmacological research. In this study, an efficient and simple strategy for enrichment of steroidal alkaloids in Fritillaria was developed for the first time based on the fluorinated reverse-phase stationary phase (FC8HL). Superior selectivity between alkaloids and non-alkaloids was achieved in a non-aqueous system, and a simple solvent system containing low-content additives was applied to elute alkaloids. Key parameters that affected the elution were investigated, including different types of buffer salts and optimized concentrations. The optimized elution system was then applied to selectively enrich alkaloids from five species of Fritillaria. Its practicability was further demonstrated by enrichment of alkaloids from Fritillaria cirrhosa D.Don at a preparative level. This developed method has great potential for other types of hydrophobic alkaloids.

20.
Biotechnol Biofuels ; 14(1): 155, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229745

RESUMO

BACKGROUND: Saccharomyces cerevisiae is widely used in traditional brewing and modern fermentation industries to produce biofuels, chemicals and other bioproducts, but challenged by various harsh industrial conditions, such as hyperosmotic, thermal and ethanol stresses. Thus, its stress tolerance enhancement has been attracting broad interests. Recently, CRISPR/Cas-based genome editing technology offers unprecedented tools to explore genetic modifications and performance improvement of S. cerevisiae. RESULTS: Here, we presented that the Target-AID (activation-induced cytidine deaminase) base editor of enabling C-to-T substitutions could be harnessed to generate in situ nucleotide changes on the S. cerevisiae genome, thereby introducing protein point mutations in cells. The general transcription factor gene SPT15 was targeted, and total 36 mutants with diversified stress tolerances were obtained. Among them, the 18 tolerant mutants against hyperosmotic, thermal and ethanol stresses showed more than 1.5-fold increases of fermentation capacities. These mutations were mainly enriched at the N-terminal region and the convex surface of the saddle-shaped structure of Spt15. Comparative transcriptome analysis of three most stress-tolerant (A140G, P169A and R238K) and two most stress-sensitive (S118L and L214V) mutants revealed common and distinctive impacted global transcription reprogramming and transcriptional regulatory hubs in response to stresses, and these five amino acid changes had different effects on the interactions of Spt15 with DNA and other proteins in the RNA Polymerase II transcription machinery according to protein structure alignment analysis. CONCLUSIONS: Taken together, our results demonstrated that the Target-AID base editor provided a powerful tool for targeted in situ mutagenesis in S. cerevisiae and more potential targets of Spt15 residues for enhancing yeast stress tolerance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...