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1.
J Environ Manage ; 354: 120395, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367500

RESUMO

Large-scale desertification combatting programs (DCPs) are crucial tools for addressing climate change and improving the ecological environment. Despite existing research having predominantly focused on assessing the ecological benefits of DCPs, the understanding of their impacts on surrounding socioeconomic aspects remains limited, particularly at the household level. To comprehensively evaluate the returns of DCPs, this study chose the representative desertification control area of the Gonghe Basin on the Qinghai-Tibet Plateau as the research region and identified the dual benefits in terms of ecological environment and socioeconomic gains. Firstly, two essential ecosystem services, carbon sequestration (CS) and wind erosion prevention (WEP), were assessed using the MODIS NPP dataset and the RWEQ model from 2001 to 2021. Household surveys were conducted in 36 villages across 14 townships within the Gonghe Basin to gain a deeper understanding of the residents' socioeconomic conditions. Through regression analysis, the study assessed the impact of DCPs on the regional ecological environment and household socioeconomic status. The research findings revealed significant improvements in CS and WEP across a significant portion of the study area from 2001 to 2021. Upon analyzing data from 401 household questionnaires, it was generally perceived by residents in the Gonghe Basin that the implementation of DCPs led to environmental improvements and increased their income levels. Further regression analysis revealed a significant impact of both natural factors and the extent of resident participation in the projects on the ecological environment surrounding the villages and on household socioeconomic aspects. With increased resident engagement in the projects, the likelihood of increased household income and life satisfaction was higher. The diverse array of DCPs implemented in the Gonghe Basin not only improved the regional ecological environment but also stimulated socioeconomic development. In future projects, it is imperative to consider regional characteristics, align ecological effects, ensure the sustainability of livelihoods, and maximize the role of social capital.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Tibet , Mudança Climática , Fatores Socioeconômicos , China
2.
J Cell Biochem ; 124(9): 1249-1258, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37450693

RESUMO

This study aims to investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) administration on tissue repair following acute lung injury (ALI). PMSCs were transplanted intravenously to a mouse model of lipopolysaccharide-induced ALI. The therapeutic effects were determined by evaluating several indicators, including pathology; the wet/dry ratio of the lungs; blood gas analysis; the total protein content, cell numbers, and the activity of myeloperoxidase (MPO) in bronchial alveolar lavage fluid (BALF); and the levels of anti-inflammatory and proinflammatory cytokines in serum and BALF. To investigate the underlying mechanism, PMSC-derived exosomes were used for ALI treatment. Administration of PMSCs improved the degree of lung injury, reduced inflammation, increased the expression levels of anti-inflammatory cytokines, and protected lung function. As expected, the effects of PMSC-derived exosomes in the ALI model were similar to those of PMSCs, both in terms of improved lung function and reduced inflammation. These findings suggest that PMSCs have ameliorating effects on ALI that are potentially mediated via their secreted exosomes.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Camundongos , Animais , Humanos , Células-Tronco Mesenquimais/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos/efeitos adversos , Fatores Imunológicos , Inflamação/metabolismo
3.
BMC Anesthesiol ; 23(1): 88, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944937

RESUMO

STUDY OBJECTIVES: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. METHODS: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. RESULTS: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. CONCLUSIONS: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.


Assuntos
Dexmedetomidina , Delírio do Despertar , Humanos , Qualidade do Sono , Ensaios Clínicos Controlados Aleatórios como Assunto , Delírio do Despertar/tratamento farmacológico
4.
New Phytol ; 234(3): 918-933, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35152419

RESUMO

Wood formation is controlled by transcriptional regulatory networks (TRNs) involving regulatory homeostasis determined by combinations of transcription factor (TF)-DNA and TF-TF interactions. Functions of TF-TF interactions in wood formation are still in the early stages of identification. PtrMYB074 is a woody dicot-specific TF in a TRN for wood formation in Populus trichocarpa. Here, using yeast two-hybrid and bimolecular fluorescence complementation, we conducted a genome-wide screening for PtrMYB074 interactors and identified 54 PtrMYB074-TF pairs. Of these pairs, 53 are novel. We focused on the PtrMYB074-PtrWRKY19 pair, the most highly expressed and xylem-specific interactor, and its direct transregulatory target, PtrbHLH186, the xylem-specific one of the pair's only two direct TF target genes. Using transient and CRISPR-mediated transgenesis in P. trichocarpa coupled with chromatin immunoprecipitation and electrophoretic mobility shift assays, we demonstrated that PtrMYB074 is recruited by PtrWRKY19 and that the PtrMYB074-PtrWRKY19 dimers are required to transactive PtrbHLH186. Overexpressing PtrbHLH186 in P. trichocarpa resulted in retarded plant growth, increased guaiacyl lignin, a higher proportion of smaller stem vessels and strong drought-tolerant phenotypes. Knowledge of the PtrMYB074-PtrWRKY19-PtrbHLH186 regulation may help design genetic controls of optimal growth and wood formation to maximize beneficial wood properties while minimizing negative effects on growth.


Assuntos
Populus , Parede Celular/metabolismo , Dimerização , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ativação Transcricional , Madeira , Xilema/metabolismo
5.
Plant Cell ; 31(3): 602-626, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30755461

RESUMO

Wood remains the world's most abundant and renewable resource for timber and pulp and is an alternative to fossil fuels. Understanding the molecular regulation of wood formation can advance the engineering of wood for more efficient material and energy productions. We integrated a black cottonwood (Populus trichocarpa) wood-forming cell system with quantitative transcriptomics and chromatin binding assays to construct a transcriptional regulatory network (TRN) directed by a key transcription factor (TF), PtrSND1-B1 (secondary wall-associated NAC-domain protein). The network consists of four layers of TF-target gene interactions with quantitative regulatory effects, describing the specificity of how the regulation is transduced through these interactions to activate cell wall genes (effector genes) for wood formation. PtrSND1-B1 directs 57 TF-DNA interactions through 17 TFs transregulating 27 effector genes. Of the 57 interactions, 55 are novel. We tested 42 of these 57 interactions in 30 genotypes of transgenic P. trichocarpa and verified that ∼90% of the tested interactions function in vivo. The TRN reveals common transregulatory targets for distinct TFs, leading to the discovery of nine TF protein complexes (dimers and trimers) implicated in regulating the biosynthesis of specific types of lignin. Our work suggests that wood formation may involve regulatory homeostasis determined by combinations of TF-DNA and TF-TF (protein-protein) regulations.


Assuntos
Cromatina/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Redes Reguladoras de Genes/genética , Populus/genética , Fatores de Transcrição/metabolismo , Parede Celular/metabolismo , Cromatina/genética , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Populus/crescimento & desenvolvimento , Populus/fisiologia , Fatores de Transcrição/genética , Madeira/crescimento & desenvolvimento
8.
Int J Mol Sci ; 16(9): 22960-75, 2015 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-26404260

RESUMO

Gibberellin (GA) is a key signal molecule inducing differentiation of tracheary elements, fibers, and xylogenesis. However the molecular mechanisms underlying the effect of GA on xylem elongation and secondary wall development in tree species remain to be determined. In this study, Betula platyphylla (birch) seeds were treated with 300 ppm GA3 and/or 300 ppm paclobutrazol (PAC), seed germination was recorded, and transverse sections of hypocotyls were stained with toluidine blue; the two-month-old seedlings were treated with 50 µM GA3 and/or 50 µM PAC, transverse sections of seedling stems were stained using phloroglucinol-HCl, and secondary wall biosynthesis related genes expression was analyzed by real-time quantitative PCR. Results indicated that germination percentage, energy and time of seeds, hypocotyl height and seedling fresh weight were enhanced by GA3, and reduced by PAC; the xylem development was wider in GA3-treated plants than in the control; the expression of NAC and MYB transcription factors, CESA, PAL, and GA oxidase was up-regulated during GA3 treatment, suggesting their role in GA3-induced xylem development in the birch. Our results suggest that GA3 induces the expression of secondary wall biosynthesis related genes to trigger xylogenesis in the birch plants.


Assuntos
Betula/crescimento & desenvolvimento , Germinação , Giberelinas/metabolismo , Sementes/crescimento & desenvolvimento , Xilema/crescimento & desenvolvimento , Betula/genética , Betula/metabolismo , Regulação da Expressão Gênica de Plantas , Hipocótilo/genética , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Sementes/genética , Sementes/metabolismo , Xilema/genética , Xilema/metabolismo
9.
IUCrdata ; 9(Pt 1): x240043, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38322035

RESUMO

Single crystals of the inter-metallic phase with composition Ti4Ni2C were serendipitously obtained by high-pressure sinter-ing of a mixture with initial chemical composition Ti2Ni. The Ti4Ni2C phase crystallizes in the Fd m space group and can be considered as a partially filled Ti2Ni structure with the C atom occupying an octa-hedral void. Ti4Ni2C is isotypic with Ti4Ni2O, Nb4Ni2C and Ta4Ni2C, all of which were studied previously by means of powder diffraction.

10.
Cancer Lett ; 593: 216957, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38762192

RESUMO

Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival. The expression of circHIPK2 was observed to be regulated by the transcription factor HOXD10, which was downregulated in colon cancer. Consequently, low circHIPK2 expression promoted colon cancer cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, circHIPK2 sponges miR-373-3p to upregulate the expression of the tumor suppressor RGMA, leading to the activation of BMP/Smad signaling and, ultimately, the inhibition of colon cancer cells, indicating that circHIPK2 inhibits colon cancer cells through the miR-373-3p/RGMA/BMP pathway. These findings revealed a previously unknown regulation, function, and underlying mechanism of circHIPK2 in cancer cells. Hence, circHIPK2 may have a prognostic value and serve as a potential target for colon cancer treatment.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , MicroRNAs , RNA Circular , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Animais , Movimento Celular/genética , Linhagem Celular Tumoral , Transdução de Sinais , Masculino , Camundongos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Feminino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Camundongos Nus , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Camundongos Endogâmicos BALB C , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Transporte
11.
Front Plant Sci ; 15: 1354249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384752

RESUMO

Mangrove forests are colloquially referred to as "Earth's kidneys" and serve many important ecological and commercial functions. Salinity and waterlogging stress are the most important abiotic stressors restricting the growth and development of mangroves. Kandelia obovata (K. obovata) is the greatest latitudinally-distributed salt mangrove species in China.Here, morphology and transcriptomics were used to study the response of K. obovata to salt and waterlogging stress. In addition, weighted gene co-expression network analysis of the combined gene expression and phenotypic datasets was used to identify core salinity- and waterlogging-responsive modules. In this study, we observed that both high salinity and waterlogging significantly inhibited growth and development in K. obovata. Notably, growth was negatively correlated with salt concentration and positively correlated with waterlogging duration, and high salinity was significantly more inhibitive than waterlogging. A total of 7, 591 salt-responsive and 228 waterlogging-responsive differentially expressed genes were identified by RNA sequencing. Long-term salt stress was highly correlated with the measured physiological parameters while long-term waterlogging was poorly correlated with these traits. At the same time, 45 salinity-responsive and 16 waterlogging-responsive core genes were identified. All 61 core genes were mainly involved in metabolic and biosynthesis of secondary metabolites pathways. This study provides valuable insight into the molecular mechanisms of salinity and waterlogging tolerance in K. obovata, as well as a useful genetic resource for the improvement of mangrove stress tolerance using molecular breeding techniques.

12.
IUCrdata ; 8(Pt 10): x230870, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37936593

RESUMO

The inter-metallic phase with composition Al0.88Cu0.94Fe0.18 was synthesized by high-temperature sinter-ing of a mixture with initial chemical composition Al78Cu48Fe13. Al0.88Cu0.94Fe0.18 adopts the CsCl structure type in space-group Pm m. The structure analysis revealed that one site is co-occupied by Al and Cu with a ratio of 0.88 (5):0.12 (5) and the other is co-occupied by Fe and Cu with a ratio of 0.2 (4):0.8 (4). The Al/Cu⋯Fe/Cu separation is 2.5465 (13) Å.

13.
IUCrdata ; 8(Pt 12): x231065, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38313207

RESUMO

Three B2-type inter-metallic AlFe1 - δ phases (0.18 < δ < 0.05) in the Al-Fe binary system were synthesized by smelting and high temperature sinter-ing methods. The exact crystal structure for δ = 0.05 was refined by single-crystal X-ray diffraction. The amount of vacancy defects at the Fe atom sites was obtained by refining the corresponding site occupancy factor, converging to the chemical formula AlFe0.95, with a structure identical to that of ideal AlFe models inferred from powder X-ray or neutron diffraction patterns.

14.
Front Biosci (Landmark Ed) ; 28(4): 72, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37114535

RESUMO

BACKGROUND: Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cell, have been used extensively in clinical trials for the treatment of multiple conditions, including sepsis. However, increasing evidence indicates that ADSCs vanish from tissues within days of administration. Consequently, it would be desirable to establish the mechanisms underlying the fate of ADSCs following transplantation. METHODS: In this study, sepsis serum from mouse models was used to mimic microenvironmental effects. Healthy donor-derived human ADSCs were cultured in vitro in the presence of mouse serum from normal or lipopolysaccharide (LPS)-induced sepsis models for the purposes of discriminant analysis. The effects of sepsis serum on ADSC surface markers and cell differentiation were analyzed by flow cytometry, and the proliferation of ADSCs was assessed using a Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was applied to assess the degree of ADSC differentiation. The effects of sepsis serum on the cytokine release and migration of ADSCs were determined based on ELISA and Transwell assays, respectively, and ADSC senescence was assessed by ß-galactosidase staining and western blotting. Furthermore, we performed metabolic profiling to determine the rates of extracellular acidification and oxidative phosphorylation and the production of adenosine triphosphate and reactive oxygen species. RESULTS: We found that sepsis serum enhanced the cytokine and growth factor secretion and migratory capacities of ADSCs. Moreover, the metabolic pattern of these cells was reprogrammed to a more activated oxidative phosphorylation stage, leading to an increase in osteoblastic differentiation capacity and reductions in adipogenesis and chondrogenesis. CONCLUSIONS: Our findings in this study reveal that a septic microenvironment can regulate the fate of ADSCs.


Assuntos
Tecido Adiposo , Sepse , Humanos , Camundongos , Animais , Proliferação de Células , Células-Tronco , Diferenciação Celular/fisiologia , Citocinas , Células Cultivadas
15.
Mar Pollut Bull ; 196: 115598, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839131

RESUMO

Flooding stress on mangroves is growing continually with rising sea level. In this study, the physiology and transcriptome of the mangrove species Kandelia obovata under flooding stress were analyzed. With increasing inundation time, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), soluble sugar (SS), soluble protein (SP), and proline (Pro) content declined, while peroxidase (POD) and ascorbate peroxidase (APX) activity rose significantly. According to the KEGG pathway enrichment analysis, upregulated differentially expressed genes (DEGs) were enriched in the plant hormone signaling pathway. Furthermore, MYB44 and MYB108 genes from the MYB transcription factor family and RAP2.12, DREB2B, and ERF4 genes from the AP2/ERF family were up-regulated under flooding conditions. A strong correlation was established between the expression levels of 12 DEGs under flooding stress and RNA sequencing data and was verified by qRT-PCR. These results provide new insights into the molecular mechanism of K. obovata in response to flooding stress.


Assuntos
Rhizophoraceae , Rhizophoraceae/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Glutationa/metabolismo , Estresse Fisiológico
16.
Front Plant Sci ; 13: 1045290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388493

RESUMO

Vegetation greenness is one of the main indicators to characterize changes in terrestrial ecosystems. China has implemented a few large-scale ecological restoration programs on the Qinghai-Tibetan Plateau (QTP) to reverse the trend of ecosystem degradation. Although the effectiveness of these programs is beginning to show, the mechanisms of vegetation degradation under climate change and human activities are still controversial. Existing studies have mostly focused on changes in overall vegetation change, with less attention on the drivers of change in different vegetation types. In this study, earth satellite observation records were used to robustly map changes in vegetation greenness on the QTP from 2000 to 2021. The random forest (RF) algorithm was further used to detect the drivers of greenness browning on the QTP as a whole and in seven different vegetation types. The results show that an overall trend of greening in all seven vegetation types on the QTP over a 21-year period. The area of greening was 46.54×104 km2, and browning was 5.32×104 km2, representing a quarter and 2.86% of the natural vegetation area, respectively. The results of the browning driver analysis show that areas with high altitude, reduced annual precipitation, high intensity of human activity, average annual maximum and average annual minimum precipitation of approximately 500 mm are most susceptible to browning on the QTP. For the seven different vegetation types, their top 6 most important browning drivers and the ranking of drivers differed. DEM and precipitation changes are important drivers of browning for seven vegetation types. These results reflect the latest spatial and temporal dynamics of vegetation on the QTP and highlight the common and characteristic browning drivers of vegetation ecosystems. They provide support for understanding the response of different vegetation to natural and human impacts and for further implementation of site-specific restoration measures.

17.
Medicine (Baltimore) ; 101(31): e29941, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945785

RESUMO

We aimed to investigate the safety and efficacy of endoscopic resection for the treatment of gastric gastrointestinal stromal tumors (GISTs) under single-channel gastroscopy and double-channel gastroscopy. We identified 154 patients with GISTs of the stomach who underwent endoscopic resection and were retrospectively analyzed at our hospital between May 2016 and March 2020, including 49 patients by single-channel gastroscopy and 105 patients by double-channel gastroscopy. We observed the clinical efficacy, complications, and safety of endoscopic resection of gastric GISTs, and the data were evaluated retrospectively. All patients underwent endoscopic resection successfully, without conversion to open surgery. In the single-channel gastroscopy group, 7 patients had lesions in the gastric cardia, 17 in the gastric fundus, 20 in the gastric corpus, and 5 in the gastric antrum. In the double-channel gastroscopy group, 13 patients had lesions in the gastric cardia, 34 in the gastric fundus, 46 in the gastric body, 10 in the gastric antrum, 1 in the pylorus, and 1 in the gastric angular incisure. The double-channel gastroscopy group had a shorter operation time than the single-channel gastroscopy group (59.9 ± 34.9 minutes vs 74.8 ± 26.7 minutes; P = .009 and P < .01, respectively), while they also had a lower perforation rate than the single-channel gastroscopy group (34.3% vs 51.0%; P = .048 and P < .05, respectively). No residual or recurrent lesions were discovered in any patients by gastroscopy reexamination. Both single-channel gastroscopy and double-channel gastroscopy can provide safe, effective, feasible endoscopic resection. However, double-channel gastroscopy has some distinct advantages in endoscopic resection.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Tumores do Estroma Gastrointestinal/cirurgia , Gastroscopia , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
18.
Front Mol Biosci ; 8: 624575, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34212001

RESUMO

Radiotherapy (RT) plays an important role in the prognosis of lung adenocarcinoma (LUAD) patients, but the radioresistance (RR) of LUAD is still a challenge that needs to be overcome. The current study aimed to investigate LUAD patients with RR to illuminate the underlying mechanisms. We utilized gene set variation analysis (GSVA) and The Cancer Immunome Atlas (TCIA) database to characterize the differences in biological functions and neoantigen-coding genes between RR and radiosensitive (RS) patients. Weighted Gene co-expression network analysis (WGCNA) was used to explore the relationship between RT-related traits and hub genes in two modules, i.e., RR and RS; two representative hub genes for RR (MZB1 and DERL3) and two for RS (IFI35 and PSMD3) were found to be related to different RT-related traits. Further analysis of the hub genes with the Lung Cancer Explorer (LCE), PanglaoDB and GSVA resources revealed the differences in gene expression levels, cell types and potential functions. On this basis, the Tumor and Immune System Interaction Database (TISIDB) was used to identify the potential association between RR genes and B cell infiltration. Finally, we used the Computational Analysis of Resistance (CARE) database to identify specific gene-associated drugs for RR patients and found that GSK525762A and nilotinib might be promising candidates for RR treatment. Taken together, these results demonstrate that B cells in TME may have a significant impact on the RT and that these two drug candidates, GSK525762A and nilotinib, might be helpful for the treatment of RR patients.

19.
Bioengineered ; 12(1): 7872-7881, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34612779

RESUMO

Restoration of blood supply through medical or surgical intervention is a commonly adopted method for acute myocardial ischemia, but is also a trigger for cardiac ischemia/reperfusion injury. Studies have shown that remifentanil (REM) displays cardioprotective effects. In this study, the effects of REM on HCMEC viability were examined before and after the induction of H/R using Cell Counting Kit-8 assays. Wound healing and Matrigel angiogenesis assays were performed to assess HCMEC migration and angiogenesis, respectively. Commercial kits and western blotting were used to determine the endothelial barrier function of H/R-stimulated HCMECs with or without REM treatment. The expression of PI3K/Akt/hypoxia-inducible factor-1α (HIF-1α) pathway-related proteins was detected by western blotting. After pre-treatment with PI3K/Akt, the effects of REM on H/R-induced HCMEC injury were examined. We found that pre-treatment with REM displayed no impact on HCMEC viability under normal conditions but noticeably improved cell viability following H/R. The migratory abilities and tube-like structure formations of H/R-stimulated HCMECs were both enhanced by REM in a concentration-dependent manner. REM also decreased the permeability of H/R-stimulated HCMECs and upregulated the expression of tight junction proteins. Furthermore REM increased the expression of PI3K/Akt/HIF-1α signaling-related proteins in HCMECs. Inhibition of PI3K/Akt rescued REM-enhanced HCMEC function under H/R condition. Therefore, the present study demonstrated that REM pretreatment ameliorated H/R-induced HCMEC dysfunction by regulating the PI3K/Akt/HIF-1α signaling pathway.


Assuntos
Cardiotônicos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Células Endoteliais , Miocárdio/citologia , Remifentanil/farmacologia , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Korean Circ J ; 50(3): 250-263, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31845557

RESUMO

BACKGROUND AND OBJECTIVES: To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury. METHODS: Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1ß expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis. RESULTS: Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1ß in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484. CONCLUSIONS: MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1ß in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.

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