RESUMEN
The gut microbiota and cancer have been demonstrated to be closely related. However, few studies have explored the bronchoalveolar lavage fluid (BALF) microbiota in patients with lung cancer (LC), specifically the microbiota related to progression-free survival (PFS) in LC. A total of 216 BALF samples were collected including 166 LC and 50 benign pulmonary disease (N-LC) samples, and further sequenced using 16S rRNA amplicon sequencing. Enrolled LC patients were followed up, the therapeutic efficacy was assessed, and PFS was calculated. The associated clinical and microbiota sequencing data were deeply analysed. Distinct differences in the microbial profiles were evident in the lower airways of patients with LC and N-LC, which was also found between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A combined random forest model was built to distinguish NSCLC from SCLC and reached area under curves (AUCs) of 0.919 (95% CI 86.69-97.1%) and 0.893 (95% CI 79.39-99.29%) in the training and test groups, respectively. The lower alpha diversity of the BALF microbiota in NSCLC patients was significantly associated with reduced PFS, although this link was not observed in SCLC. Specifically, NSCLC with a higher abundance of f_Lachnospiraceae, s_Prevotella nigrescens and f_[Mogibacteriaceae] achieved longer PFS. The enrichment of o_Streptophyta and g_Prevotella was observed in SCLC with worse PFS. This study provided a detailed description of the characteristics of BALF microbiota in patients with NSCLC and SCLC simultaneously and provided insights into the role of the diagnosis and prognosis evaluation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00135-9.
RESUMEN
Lymphatic metastasis is related to an unsatisfactory prognosis in pancreatic cancer. Sphingosine kinase 1 (SPHK1) is an oncogene in cancer. However, the potential effect of SPHK1 on the lymphangiogenesis of pancreatic cancer is little known. In this study, the expression level and role of SPHK1 in pancreatic cancer were evaluated to explore the underlying mechanism involved. The expression of SPHK1 and the lymphatic vessel density (LVD) in pancreatic cancer patient tissue were investigated by immunohistochemistry. The role of SPHK1 in lymphangiogenesis was verified in vitro. Elevated expression of SPHK1 was strongly related to high LVD in pancreatic cancer patient tissue. Silencing of SPHK1 in pancreatic cancer cells observably inhibited lymphangiogenesis. Furthermore, the downregulation of SPHK1 markedly attenuated the phosphorylation of extracellular signal-regulated kinase in lymphatic endothelial cells. This study revealed that SPHK1 might play a crucial role in pancreatic cancer lymphangiogenesis.
RESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive respiratory disorder characterized by poor prognosis, often presenting with acute exacerbation. The primary cause of death associated with IPF is acute exacerbation of IPF (AE-IPF). However, the pathophysiology of acute exacerbation has not been clearly elucidated yet. This study aims to investigate the underlying pathophysiological molecular mechanism in a mouse AE-PF model. C57BL/6J mice were intratracheally administered bleomycin (BLM, 5 mg/kg) to induce pulmonary fibrosis. After 14 days, lipopolysaccharide (LPS, 2 mg/kg) was injected via the trachea route. Histological assessments, including H&E and Masson staining, as well as inflammatory indicators, were included to evaluate the induction of AE-PF by BLM and LPS in mice. Transcriptomic profiling of pulmonary tissues identified CSF3 as one of the top 10 upregulated DEGs in AE-PF mice. Indeed, administration of exogenous CSF3 protein exacerbated AE-PF in mice. Mechanistically, CSF3 disrupted alveolar epithelial barrier integrity and permeability by regulating specialized cell adhesion complexes such as tight junctions (TJs) and adherens junctions (AJs) via PI3K/p-Akt/Snail pathway, contributing to the aggravation of AE-PF in mice. Moreover, the discovery of elevated sera CSF3 indicated a notable increase in IPF patients during the exacerbation of the disease. Pearson correlation analysis in IPF patients revealed significant positive associations between CSF3 levels and KL-6 levels, LDH levels, CRP levels, respectively. These results provide mechanistic insights into the role of CSF3 in exacerbating of lung fibrotic disease and indicate monitoring CSF3 levels may aid in early clinical decisions for alternative therapy in the management of rapidly progressing IPF.
Asunto(s)
Bleomicina , Fibrosis Pulmonar Idiopática , Ratones Endogámicos C57BL , Animales , Humanos , Ratones , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/inducido químicamente , Masculino , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Transducción de Señal , Persona de Mediana Edad , Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/patología , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción de la Familia Snail/genética , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Poly(vinyl chloride) (PVC) is widely used in various fields and requires the use of thermal stabilizers to enhance its thermal stability during processing because of its poor thermal stability. Layered double hydroxides (LDHs) are widely considered to be one kind of highly efficient and environmentally friendly PVC thermal stabilizer. To investigate the thermal stabilizing process of layered double hydroxides (LDHs) in PVC resin, PVC and MgAl-LDHs powders with different interlayer anions (CO32-, Cl-, and NO3-) were physically mixed and aged at 180 °C. The structure of LDHs at different aging times was studied using XRD, SEM, and FT-IR. The results show that the thermal stabilizing process of LDHs on PVC mainly has three stages. In the first stage, the layers of LDHs undergo a reaction with HCl, which is released during the thermal decomposition of PVC. Subsequently, the ion exchange process occurs between Cl- and interlayer CO32-, resulting in the formation of MgAl-Cl-LDHs. Finally, the layers of MgAl-Cl-LDHs react with HCl slowly. During the thermal stabilizing process of MgAl-Cl-LDHs, the peak intensity of XRD reduces slightly, and no new XRD peak emerges. It indicates that only the first step happens for MgAl-Cl-LDHs. The TG-DTA analysis of LDHs indicates that the interaction of LDHs with different interlayer anions has the following order: NO3- < CO32- < Cl-, according to the early coloring in the thermal aging test of PVC composites. The results of the thermal aging tests suggest that LDHs with a weak interaction between interlayer anions and layers can enhance the early stability of PVC significantly. Furthermore, the thermal aging test demonstrates that LDHs with high HCl absorption capacities exhibit superior long-term stabilizing effects on PVC resin. This finding provides a valuable hint for designing an LDHs/PVC resin with a novel structure and excellent thermal stability.
RESUMEN
Amur honeysuckle (Lonicera maackii) is a widely used medicinal plant of the Caprifoliaceae family that produces chlorogenic acid. Research on this plant mainly focuses on its ornamental value and medicinal compounds, but a reference genome sequence and molecular resources for accelerated breeding are currently lacking. Herein, nanopore sequencing and high-throughput chromosome conformation capture (Hi-C) allowed a chromosome-level genome assembly of L. maackii (2n = 18). A global view of the gene regulatory network involved in the biosynthesis of chlorogenic acid and the dynamics of fruit coloration in L. maackii was established through metabolite profiling and transcriptome analyses. Moreover, we identified the genes encoding hydroxycinnamoyl-CoA quinate transferase (LmHQT) and hydroxycinnamoyl-CoA shikimic/quinate transferase (LmHCT), which localized to the cytosol and nucleus. Heterologous overexpression of these genes in Nicotiana benthamiana leaves resulted in elevated chlorogenic acid contents. Importantly, HPLC analyses revealed that LmHCT and LmHQTs recombinant proteins modulate the accumulation of chlorogenic acid (CGA) using quinic acid and caffeoyl CoA as substrates, highlighting the importance of LmHQT and LmHCT in CGA biosynthesis. These results confirmed that LmHQTs and LmHCT catalyze the biosynthesis of CGA in vitro. The genomic data presented in this study will offer a valuable resource for the elucidation of CGA biosynthesis and facilitating selective molecular breeding.
Asunto(s)
Ácido Clorogénico , Lonicera , Ácido Clorogénico/metabolismo , Lonicera/genética , Lonicera/metabolismo , Ácido Quínico/metabolismo , Fitomejoramiento , Mapeo CromosómicoRESUMEN
As an important part of acid fracturing technology for the carbonate reservoir, the performance of the acid system directly affects the stimulation effect. In view of the current problems of an acid fluid system in an ultrahigh-temperature carbonate reservoir, such as fast acid-rock reaction, short effective action distance, and difficulty maintaining the conductivity of acid etching fractures, an experimental study on the self-generated organic acid system was carried out. The results showed that acetic anhydride and ethyl acetate, which had a strong acid generating ability, were suitable for the parent acid types of self-generated organic acids. Preferably, the peak temperature of 25% acetic anhydride is 160 °C, while the peak temperature of 30% ethyl acetate is 180 °C. The acid-rock reaction kinetics experiment shows that the order of activation energy is ethyl acetate > acetic anhydride > cross-linked acid. The reaction rate is arranged as follows: ethyl acetate < acetic anhydride ⪠cross-linked acid. The self-generated organic acid of ethyl acetate has the largest activation energy, the smallest reaction rate, and the best retarding effect. Acetic anhydride forms a strong nonuniform pitting morphology on the surface of the rock plate, with an initial conductivity of 225.4 µm2·cm. Ethyl acetate forms an uneven pitting morphology, and the initial conductivity is 53.1 µm2·cm. However, the ability of acid etching fracture formed by ethyl acetate to maintain fracture conductivity is stronger than that of acetic anhydride. Ethyl acetate is more suitable for a deep ultrahigh-temperature carbonate reservoir.
RESUMEN
As a typical feature of a reservoir, heterogeneity is the main reason for low oil recovery and the poor effect of acidizing measures. Diversion is the main measure to improve the acidizing effect. Over the years, technological progress has mainly focused on the material development of diverting agents. In this study, the diverting effect and influencing factors for a viscous fluid were systematically studied by the heterogeneous dual-core flooding experiment. The results are as follows: First, increasing the displacement pressure in heterogeneous reservoirs can improve the diverting effect, which is consistent with maximum differential pressure and injection rate (MADPIR) theory, but the diverting effect is weak. The injection pressure difference is increased by 50 times, and the diverting effect is improved by 16.27% at most. Second, taking a viscous fluid as the stimulation fluid can partially realize the diversion for heterogeneous reservoir and further improve the acidizing effect, and the breaking through PV can be improved by 78% at most. Using a viscous fluid as a diverting agent can achieve 100% balanced acid injection. Third, compared with a viscoelastic surfactant, a relatively uniform and stable polymer solution as the diverting agent has the possibility to completely block the low-permeability layer. So, a 5% viscoelastic surfactant as the diverting agent is more suitable for acidizing. Finally, any diverter injected into the formation will enter all layers. The conclusion that the diverting agent only enters the high-permeability layer but not the low-permeability layer is not tenable. Diverting acidizing is only effective for near-well zones, which is difficult to fundamentally solve the seepage problem of heterogeneous reservoirs.
RESUMEN
We enrolled 264 patients with papillary thyroid carcinoma (PTC). We performed immunohistochemical detection of p16 and determined the degree of interstitial fibrosis (IF). The expression of p16 was associated with pathological tumor-node-metastasis (pTNM) stage and age (p < 0.05). The cancer-specific survival (CSS) was longer in p16-negative patients (195.73 vs. 181.78 months, p = 0.007). p16 was significantly related to the degree of IF (r = 0.130, p = 0.035). PTC patients with no or mild fibrosis tended to have a larger tumor (p = 0.045). The degree of fibrosis was related to the proportion of papillary structure components (p = 0.025). Univariate and multivariate survival analyses showed that relapse-free survival (RFS) was longer in patients with moderate/severe IF (p < 0.05). In summary, p16 was correlated with prognosis and IF of PTC. Patients with moderate/severe IF tend to have better prognosis in RFS.
Asunto(s)
Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/diagnóstico , Carcinoma Papilar/patología , Neoplasias de la Tiroides/patología , Recurrencia Local de Neoplasia , Pronóstico , FibrosisRESUMEN
Hydraulic fracturing and acid fracturing are very effective stimulation technologies and are widely used in unconventional reservoir development. Fracture height, as an essential parameter to describe the geometric size of a fracture, is not only the input parameter of two-dimensional fracturing models but also the output parameter of three-dimensional fracturing models. Accurate prediction of fracture height growth can effectively avoid some risks. For example, petroleum reservoirs produce a large amount of formation water because wrong fracture height prediction leads to the connection between the oil or gas reservoir and the water layer. Although some fracture height prediction models were developed, few models considered the effects of the plastic zone, induced stress, and heterogeneous multilayer formation and its interaction. Therefore, considering the influence of many factors, an improved fracture-equilibrium-height model was developed in this study. The successive over-relaxation iteration method and the displacement discontinuity method were used to solve the model. We investigated the effects of the geological and engineering factors on fracture height growth by using the model, and some important conclusions were obtained. The higher the fracture height, the larger the plastic zone size, and the more obvious its influence on fracture height propagation. High overlying or underlying in situ stress and fracture toughness and low fluid density played a positive role in limiting the growth of the fracture height. Induced stress caused by fracture 1 could not only inhibit the height growth of fracture 2 but also promote its growth. The model established in this paper could be coupled to a fracturing simulator to provide a more reliable fracture height prediction.
RESUMEN
As an important part of the acid fracturing process of carbonate reservoir, the performance of acid fracturing working fluid directly affects the stimulation effect of oil wells. In this paper, formaldehyde (agent A) and ammonium chloride (agent B) were used as the matrix. Several aldehydes with different volume ratios were prepared. The acid ratio with the highest acid yield was selected by the sodium hydroxide titration experiment. The results show that when the volume ratio of agent A to agent B is 1:1.3, the acid production capacity is the strongest. The pH values at several time points in the process of acid reaction were measured by a pen pH meter. The relationship curve between acid production capacity and time was obtained. The acid production capacity increased with time. It tends to be stable after a certain time. The experiment of acid rock reaction kinetics shows that the reaction rate between acid and rock decreases with the extension of time. The reaction time can reach 6 h. The reaction rate of autogenic acid under different temperatures and concentrations ranges from 6.61 × 10-7 to 9.49 × 10-7 mol/(s·cm2) within 6 h. Therefore, it indicates that the reaction time between autogenic acid and carbonate rock is long and the reaction rate is low. It is beneficial to improve the acid treatment effect of the carbonate reservoir. The conductivity experiments show that at different temperatures, with the increase of sealing pressure, the etching ability of autogenic acid decreases. The etching effect is better at 338 K. After etching, the permeability and conductivity of the rock slab of 5 MPa closure pressure are 227 D and 72.62 D·cm, respectively. To sum up, this autogenic acid is an effective working fluid in the acid fracturing process of the carbonate reservoir. It can obviously reduce the reaction rate of acid rock and has certain conductivity.
RESUMEN
Combined small-cell lung cancer (C-SCLC) is a relatively rare subtype of SCLC and is defined by the combination of SCLC and any elements of non-small-cell lung carcinoma. Anlotinib is a novel oral multitarget tyrosine kinase inhibitor that led to significant improvements in progression-free survival and overall survival in third-line therapy of advanced SCLC in the ALTER1202 study. Antiangiogenic therapy with anlotinib in C-SCLC has not previously been reported. An 80-year-old man was admitted with a 20-day history of blood-stained sputum. Chest computed tomography revealed a soft mass (45 × 43 mm) in the right upper lobe and a mediastinal lymph node and additional lung lesions in the homo lung. Pathology confirmed C-SCLC after an ultrasound-guided percutaneous puncture biopsy of the right lung tumor. The elderly patient was given anlotinib monotherapy at a dose of 10 mg/day on days 1-14 of a 21-day cycle after providing informed consent, and the outcome was assessed as continued partial response. As of the last follow-up evaluation, the patient's progression-free survival was more than 7 months, and the treatment showed satisfactory safety. Our findings provide direct evidence of the efficacy of anlotinib in an elderly patient with C-SCLC. More studies are needed to confirm our observations.
RESUMEN
BACKGROUND: Systemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)-35 and IL-37 have been identified as novel immune-modulating cytokines with anti-inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL-35 and IL-37 in patients with OSA, and to investigate their associations with the severity of OSA. METHODS: A total of 97 patients, including 67 cases of OSA and 30 age- and gender-matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL-35, IL-37, and pro-inflammatory cytokine IL-1ß levels were examined by ELISA. RESULTS: Compared with those in the control subjects, serum IL-35, IL-37, and IL-1ß levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity-dependent increase in serum IL-35 and IL-37 levels was observed in patients with OSA. IL-35 and IL-37 levels were positively correlated with the apnea-hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = -0.461 and -0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = -0.616 and -0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL-35 or IL-37 and IL-1ß levels (all p < 0.001). CONCLUSION: The serum levels of IL-35 and IL-37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL-35 and IL-37 may have a protective role in OSA by counteracting inflammatory responses.
Asunto(s)
Biomarcadores/sangre , Interleucina-1/sangre , Interleucina-1beta/sangre , Interleucinas/sangre , Apnea Obstructiva del Sueño/diagnóstico , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Pronóstico , Apnea Obstructiva del Sueño/sangreRESUMEN
In this study, five fats (hydrogenated palm kernel oil, HPKO-A and HPKO-B; refined vegetable oils, RVO-A and RVO-B; transesterification oil, TO) were used to prepare whipping creams. HPKO-A and RVO-A which rich in lauric and myristic acids facilitated the formation of small crystals and dense crystal network, while higher stearic acid content of HPKO-B formed large spherical crystals. The richness in palmitic acid (RVO-B and TO) and oleic acid (TO) led to the formation of weak crystal network. Higher partial coalescence was correlated to higher collision frequency of fat globules and crystal connection, therefore, the overruns, firmness and stability of creams prepared by HPKO-A and RVO-A were higher than those of HPKO-B and RVO-B. The least stability of cream prepared by TO was related to the weak crystal networks. In summary, higher lauric and myristic acids content resulted in dense crystal networks, promoting partial coalescence and improving the cream quality.
Asunto(s)
Ácidos Grasos/química , Análisis de los Alimentos/métodos , Aceites de Plantas/química , Cristalización , Emulsiones/química , Aceite de Palma/química , Temperatura de TransiciónRESUMEN
PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may cause pulmonary diseases, and periostin plays an important role on the development of pulmonary diseases. In addition, periostin and pro-inflammatory cytokine TNF-α can regulate each other in vivo. This study aimed to observe the changes of serum periostin and TNF-α levels in patients with OSAHS compared with healthy volunteers and to investigate their correlation. METHODS: A convenience sample of 67 patients with OSAHS in our hospital from December 2018 to December 2019 was selected and categorized into mild, moderate, and severe groups according to apnea-hypopnea index by polysomnography. In addition, 21 healthy volunteers were selected as the control group. Serum levels of periostin and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Results were analyzed using the SPSS software. RESULTS: Both serum periostin and TNF-α levels in all the three OSAHS groups were higher than those of the control group and increased with severity of OSAHS. The severe group had significantly higher serum periostin and TNF-α levels than the mild and moderate groups (p < 0.05). For patients with OSAHS, serum periostin and TNF-α levels positively correlated with the apnea-hypopnea index (AHI) (p < 0.01) and negatively correlated with the lowest saturation oxygen (LSaO2) and mean saturation oxygen (MSaO2) (both p < 0.01). In addition, there was a positive correlation between serum periostin and TNF-α levels in patients with OSAHS (p < 0.001). CONCLUSIONS: Serum periostin and TNF-α levels were significantly increased in patients with OSAHS and may serve as a potential biomarker for severity of OSAHS. These findings suggest that it may be fruitful to study the role of periostin and TNF-α in OSAHS-induced pulmonary diseases.
Asunto(s)
Moléculas de Adhesión Celular/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Factor de Necrosis Tumoral alfa/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Tetracentron sinense is an endemic and endangered deciduous tree. It belongs to the Trochodendrales, one of four early diverging lineages of eudicots known for having vesselless secondary wood. Sequencing and resequencing of the T. sinense genome will help us understand eudicot evolution, the genetic basis of tracheary element development, and the genetic diversity of this relict species. RESULTS: Here, we report a chromosome-scale assembly of the T. sinense genome. We assemble the 1.07 Gb genome sequence into 24 chromosomes and annotate 32,690 protein-coding genes. Phylogenomic analyses verify that the Trochodendrales and core eudicots are sister lineages and showed that two whole-genome duplications occurred in the Trochodendrales approximately 82 and 59 million years ago. Synteny analyses suggest that the γ event, resulting in paleohexaploidy, may have only happened in core eudicots. Interestingly, we find that vessel elements are present in T. sinense, which has two orthologs of AtVND7, the master regulator of vessel formation. T. sinense also has several key genes regulated by or regulating TsVND7.2 and their regulatory relationship resembles that in Arabidopsis thaliana. Resequencing and population genomics reveals high levels of genetic diversity of T. sinense and identifies four refugia in China. CONCLUSIONS: The T. sinense genome provides a unique reference for inferring the early evolution of eudicots and the mechanisms underlying vessel element formation. Population genomics analysis of T. sinense reveals its genetic diversity and geographic structure with implications for conservation.
Asunto(s)
Evolución Molecular , Genoma de Planta , Genoma , Magnoliopsida/genética , Arabidopsis/genética , Secuencia de Bases , China , Variación Genética , Filogenia , Proteínas de Plantas/genética , Análisis de Secuencia , Sintenía , Factores de Transcripción/genética , XilemaRESUMEN
BACKGROUND: Emerging evidence has suggested that dysbiosis of the lung microbiota may be associated with the development of lung diseases. However, the interplay between the lung microbiome and lung cancer remains unclear. The aim of the present study was to evaluate and compare differences in taxonomic and derived functional profiles in the lung microbiota between lung cancer and benign pulmonary diseases. METHODS: Bronchoalveolar lavage fluid (BALF) samples were collected from 32 patients with lung cancer and 22 patients with benign pulmonary diseases, and further analyzed by 16S rRNA amplicon sequencing. The obtained sequence data were deeply analyzed by bioinformatics methods. RESULTS: A significant differentiation trend was observed between the lung cancer and control groups based on principal coordinate analysis (PCoA), while richness and evenness in the lung microbiome of lung cancer patients generally resembled those of patients with benign pulmonary diseases. Phylum TM7 and six genera (c:TM7-3, Capnocytophaga, Sediminibacterium, Gemmiger, Blautia and Oscillospira) were enriched in the lung cancer group compared with the control group (adjust P<0.05). The area under the curve (AUC) combining the microbiome with clinical tumor markers to predict lung cancer was 84.52% (95% CI: 74.06-94.97%). In addition, predicted KEGG pathways showed that the functional differences in metabolic pathways of microbiome varied with groups. CONCLUSIONS: The results indicated that differences existed in the lung microbiome of patients with lung cancer and those with benign pulmonary diseases, and some certain bacteria may have potential to predict lung cancer, though future larger-sample studies are required to validate this supposition.
RESUMEN
BACKGROUND Acute kidney injury (AKI) caused by sepsis is a very dangerous clinical complication. This study explored the effects of calcitonin gene-related peptides (CGRP) on AKI and its mechanisms. MATERIAL AND METHODS We cultured renal proximal tubular epithelial cells (HK-2 cells) and induced AKI models using LPS. Recombinant human CGRP was used to stimulate HK-2 cells and we detected markers of kidney injury (KIM-1 and NGAL) to determine the protective effect of CGRP on HK-2 cells. In addition, we constructed Sirt1-overexpressing lentivirus and small interfering RNA to increase or decrease Sirt1 expression in HK-2 cells to verify that CGRP protects HK-2 cells by regulating Sirt1. RESULTS After CGRP stimulation of HK-2 cells, LPS-induced HK-2 cell damage was significantly ameliorated, showing a decrease in the expression of KIM-1, NGAL, and inflammatory factors. In addition, Sirt1 was significantly increased in CGRP-stimulated HK-2 cells. After transfection of HK-2 cells with Lenti-Sirt1, inflammation and damage of HK-2 cells were both reduced, indicating that Sirt1 has a protective effect on HK-2 cells and can mediate the protective effect of CGRP on HK-2 cells. Therefore, the protective effect of CGRP on HK-2 cells was also attenuated after reducing Sirt1 in HK-2 cells. Finally, we used CGRP to treat LPS-induced mice and verified the protective effect of CGRP on mouse AKI. CONCLUSIONS CGRP has a significant anti-inflammatory effect. In the treatment of AKI, CGRP can increase the expression of Sirt1 to exert an anti-inflammatory effect and has a good protective effect on LPS-induced HK-2 cells.
Asunto(s)
Lesión Renal Aguda/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Sirtuina 1/metabolismo , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Calcitonina/metabolismo , Péptido Relacionado con Gen de Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/farmacología , Línea Celular , Citocinas/metabolismo , Células Epiteliales/metabolismo , Expresión Génica , Humanos , Inflamación/metabolismo , Riñón/metabolismo , Túbulos Renales Proximales/metabolismo , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteínas Recombinantes/farmacología , Sepsis/metabolismo , Transducción de Señal/efectos de los fármacos , Sirtuina 1/genéticaRESUMEN
A multi-strand composite welding wire was applied to join high nitrogen austenitic stainless steel, and microstructures and mechanical properties were investigated. The electrical signals demonstrate that the welding process using a multi-strand composite welding wire is highly stable. The welded joints are composed of columnar austenite and dendritic ferrite and welded joints obtained under high heat input and cooling rate have a noticeable coarse-grained heat-affected zone and larger columnar austenite in weld seam. Compared with welded joints obtained under the high heat input and cooling rate, welded joints have the higher fractions of deformed grains, high angle grain boundaries, Schmid factor, and lower dislocation density under the low heat input and cooling rate, which indicate a lower tensile strength and higher yield strength. The rotated Goss (GRD) ({110}ã1 1 ¯ 0ã) orientation of a thin plate and the cube (C) ({001}ã100ã) orientation of a thick plate are obvious after welding, but the S ({123}ã63 4 ¯ ã) orientation at 65° sections of Euler's space is weak. The δ-ferrite was studied based on the primary ferrite solidification mode. It was observed that low heat input and a high cooling rate results in an increase of δ-ferrite, and a high dislocation density was obtained in grain boundaries of δ-ferrite. M23C6 precipitates due to a low cooling rate and heat input in the weld seam and deteriorates the elongation of welded joints. The engineering Stress-strain curves also show the low elongation and tensile strength of welded joints under low heat input and cooling rate, which is mainly caused by the high fraction of δ-ferrite and the precipitation of M23C6.
RESUMEN
Oil and gas exploration and development extends from medium-low temperatures to high and ultra-high temperatures with the development of the oil and gas industry. High-temperature deep carbonate reservoir acid fracturing has introduced more stringent requirements, a slower chemical reaction rate and excellent dissolution performance of acid systems, which means that the acid system should still have a certain dissolution ability above 135 °C. A novel water-soluble encapsulated acid (EA), dual controlled by hydrogen ion concentration and temperature, was developed to exploit ultra-high-temperature carbonate reservoirs. The encapsulating material was insoluble and isolated the internal solid acid at high H+ ion concentrations and low temperatures, but the solid acid was released as the encapsulating material was dissolved at low H+ ion concentrations and high temperatures. This unique performance was characterized by ESEM, TGA, FTIR, NMR, mechanical performance, solubility, etching performance, and etching fracture conductivity. All the scientific results show that this EA can be applied as a long-distance etching acid controlled by H+ ion concentration and temperature, without the need for a thickener and emulsifier to reduce the reaction between the rock and the acid near the wellbore. The test results demonstrated that the solid acid had good thermal stability at 135 °C, the encapsulation material was almost insoluble in high acid concentrations (>14%) at any temperature, and the solid acid began to release when the concentration of hydrochloric acid was less than 14% and the temperature was higher than 95 °C. The rock etching and dissolution behavior was better than that of HCl with the same concentration and the etching fracture conductivity was improved by supplementing the consumption of H+ ions when etching rock. The encapsulating material is completely dissolved after acid fracturing, avoiding reservoir damage by the residue. The described EA is a promising approach for application in acid fracturing of carbonate reservoirs at ultra-high temperature (>135 °C).