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BACKGROUND: N6-methyladenosine (m6A) modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its significance, the comprehensive investigation of METTL5, a key m6A methyltransferase, in colorectal cancer (CRC) remains limited. AIM: To investigate the role of METTL5 in CRC. METHODS: We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion. RESULTS: Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth. CONCLUSION: The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.
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A mild and effective strategy for the asymmetric synthesis of C2-quaternary indolin-3-ones from 2-alkynyl arylazides and ketones by gold/chiral amine relay catalysis is described. In this reaction, 2-alkynyl arylazides undergo gold-catalyzed cyclization, nucleophilic attack, and oxidation to form intermediate 2-phenyl-3H-indol-3-ones, followed by an l-proline-catalyzed asymmetric Mannich reaction with ketones, to afford corresponding products in satisfactory yields with excellent enantio- and diastereoselectivities.
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It is of great scientific significance in regulating plantation ecosystem restoration to investigate the effects of the nitrogen (N) deposition and litter manipulation on soil organic carbon components and enzyme activities. A micro-plot experiment was conducted with four nitrogen additions[CK (0 kg·hm-2·a-1, calculated by N), LN (50 kg·hm-2·a-1), MN (100 kg·hm-2·a-1), and HN (200 kg·hm-2·a-1)] and two litter treatments[LR (litter removal) and L (litter retained)] for tropical rubber plantations in western Hainan Island. The soil physico-chemical properties, soil organic carbon components, and enzyme activities in 0-10 cm and 10-20 cm depths were analyzed. The results showed that soil pH significantly decreased with elevated N addition and litter removal. The contents of NO3--N and NH4+-N significantly increased with elevated N addition. Moreover, there was a significant interaction between N addition and litter treatment on the contents of NO3--N and NH4+-N (P < 0.05). Compared to that with L, LR reduced SOC and its component contents; particularly, the largest decrease was in LFOC by 29.0%-81.4% in the 0-10 cm depth and 23.5%-58.4% in 10-20 cm, respectively. The contents of SOC and its components presented a trend of increasing first and then decreasing with elevated N addition irrespective of litter treatment, and those contents were significantly higher at LN than those at HN. There was a significant interaction between N addition and litter treatment on SOC, LFOC (0-10 cm), and HFOC contents. Compared with that under L, PPO activity was significantly reduced at LR under CK and LN but was significantly increased at LR under MN and HN, respectively. Variance analysis showed significant interactive effects between N addition and litter treatment on PPO and CBH (0-10 cm) activities, and the soil enzyme activity (BG, PPO, and CBH) responding to N addition was greater than that to the litter treatment. Pearson correlation analysis showed that SOC content was extremely positively correlated with MBC, POC, LFOC, and HFOC contents. To summarize, litter retained combined with low N deposition played an important synergistic role of improving SOC pool and soil enzyme activities for tropical rubber plantation systems.
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Carbono , Solo , Solo/química , Carbono/análise , Borracha , Ecossistema , Nitrogênio/análise , ChinaRESUMO
Background: Preoperative albumin-bilirubin (ALBI) grade has been proposed and applied in recent years to evaluate the prognosis of liver cancer, but its role in gastric cancer (GC) is still unclear. This research aimed to examine the prognostic value of ALBI grade after gastrectomy among patients with GC complicated with metabolic syndrome (MetS). Methods: There were 628 patients who received radical resection for GC. Laboratory data and short-term results were collected prospectively, and preoperative ALBI grades were calculated from the albumin and bilirubin levels. The appropriate ALBI cutoff value was calculated by receiver operating characteristic (ROC) curve analysis, which we used to put patients into high (>-2.54) and low (≤-2.54) ALBI grade groups. The differences between the short-term complication rates of the two groups were analyzed with the chi-square test. Results: Of the included patients, 133 (21.2%) and 495 (78.8%) had high and low ALBI grades, respectively. A high ALBI grade (P=0.001), body mass index (BMI) ≥25 kg/m2 (P=0.001), and hypertension (P=0.018) were independent risk factors for postoperative complications. In GC patients with and without MetS, the high ALBI subgroup showed more overall complications than the low ALBI subgroup (P=0.028 and P=0.001). Among GC patients with MetS, those with a high ALBI grade showed a higher incidence of serious complications than those with a low ALBI grade (P=0.001); a similar, nonsignificant trend occurred in non-MetS patients (P=0.153). Conclusions: The preoperative ALBI grade is important in the prognosis of GC patients with MetS after gastrectomy. GC patients with MetS can lower their incidence of serious complications by adjusting their preoperative ALBI grade.
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Based on data collected from 2054 saplings of Larix gmelinii forest in 55 fixed plots in 2018-2019 in Cuigang Forestry Station, Daxing'anling area, we classified the stand density index (SDI) into four classes, i.e., Class â (SDI1<1863 plants·hm-2), Class â ¡ (1863 plants·hm-2≤SDI2<2155 plants·hm-2), Class â ¢ (2155 plants·hm-2≤SDI3<2459 plants·hm-2) and Class â £ (SDI4≥2459 plants·hm-2) by using the quartile method. We constructed a dummy variable model and quantile regression model for the height-breast diameter of saplings of L. gmelinii with dummy variable method introduced SDI. The results showed that among the five selected representative non-linear tree height curve models, the Richards model fitted the best, with Ra2, RMSE and MAE of 0.7637, 0.8250 m and 0.5696 m. The dummy variable model including the SDI constructed based on the Richards model showed a 1.3% increase in Ra2 compared with the base model, while RMSE, MAE, and AIC decreased by 2.1%, 1.5%, and 11.2%, respectively. When the quantile τ was 0.5, Ra2 of quantile regression model was the maximum, and RMSE, MAE, AIC was the minimum, being 0.7612, 0.8294 m, 0.5657 m, and -767.19, respectively. Compared with SDI1, sapling height in SDI2-SDI4 was increased by 5.6%, 5.6%, and 11.3%, suggesting reasonable that regulation of stand density was conducive to increase the height growth of saplings in regeneration.
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Larix , Florestas , Árvores , Agricultura Florestal , ChinaRESUMO
BACKGROUND: Whether patients over 85 years old with gastrointestinal cancer should undergo surgery remains controversial. We aimed to describe the changing trends of characteristics to provide more information to decision makers, and strive to find appropriate surgical plan. AIM: To describe the changing trends of characteristics to provide more information to decision makers, and strive to find appropriate surgical plan. METHODS: A total of 218 gastric cancer (GC) patients and 563 colorectal cancer (CRC) patients who underwent surgery between 2001 and 2021 were enrolled in this retrospective analysis. Changes in clinicopathological features, surgical treatments, and survival status were analyzed longitudinally at 5-year intervals. RESULTS: Only 14 GC patients underwent laparoscopic surgery where 219 CRC patients had this procedure. Cardia and esophagogastric junction cancer increased in GC patients, and the proportion of sigmoid colon cancer decreased in CRC patients. Pulmonary infection gradually became the most common postoperative complication, its incidence in period 4 reached 48.79%. However, the incidence of anastomotic leakage decreased from 26.79% to 9.38% (P < 0.01). Additionally, 30-d mortality significantly decreased from 32.14% to 9.01%. Increases were observed in 5-year overall survival (OS) in GC patients from period 1 to period 4 (18.18% vs 33.32%, respectively) and CRC patients (0 vs 36.32%, respectively). Disease-free survival (DFS) also increased in GC and CRC patients (7.14% vs 27.74% and 0 to 36.03%, respectively). The average survival time of GC patients following radial lymphadenectomy was higher than in patients that underwent limited lymphadenectomy (26 vs 22 mo, respectively), the same was seen in CRC patients (44 vs 33 mo, respectively). This advantage was particularly evident in patients with TNM I, but not in patients with TNM II/III period cancer. CONCLUSION: The safety as well as effectiveness of surgery in ultra-elderly patients is increasing. Radical lymphadenectomy has advantages in patients with TNM I gastrointestinal cancer, but not TNM II/III.
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Although the engineering of visible-light-driven photocatalysts with appropriate bandgap structures is beneficial for generating hydrogen (H2), the construction of heterojunctions and energy band matching are extremely challenging. In this study, In2O3@Ni2P (IO@NP) heterojunctions are attained by annealing MIL-68(In) and combining the resulting material with NP via a simple hydrothermal method. Visible-light photocatalysis experiments validate that the optimized IO@NP heterojunction exhibits a dramatically improved H2 release rate of 2485.5 µmol g-1 h-1 of 92.4 times higher than that of IO. Optical characterization reveals that the doping of IO with an NP component promotes the rapid separation of photo-induced carriers and enables the capture of visible light. Moreover, the interfacial effects of the IO@NP heterojunction and synergistic interaction between IO and NP that arises through their close contact mean that plentiful active centers are available to reactants. Notably, eosin Y (EY) acts as a sacrificial photosensitizer and has a significant effect on the rate of H2 generation under visible light irradiation, which is an aspect that needs further improvement. Overall, this study describes a feasible approach for synthesizing promising IO-based heterojunctions for use in practical photocatalysis.
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A targeted defect-induced strategy of metal sites in a porous framework is an efficient avenue to improve the performance of a catalyst. However, achieving such an activation without destroying the ordered framework is a major challenge. Herein, a dielectric barrier discharge plasma can etch the Fe(CN)6 group of the NiFe Prussian blue analogue framework in situ through reactive oxygen species generated in the air. Density functional theory calculations prove that the changed local electronic structure and coordination environment of Fe sites can significantly improve oxygen evolution reaction catalytic properties. The modified NiFe Prussian blue analogue is featured for only 316 mV at a high current density (100 mA cm-2), which is comparable to that of commercial alkaline catalysts. In a solar cell-driven alkaline electrolyzer, the overall electrolysis efficiency is up to 64% under real operation conditions. Over 80 h long-time continuous test under 100 mA cm-2 highlights superior durability. The density functional theory calculations confirm that the formation of OOH* is the rate-determining step over Fe sites, and Fe(CN)6 vacancy and extra oxygen atoms can introduce charge redistribution to the catalyst surface, which finally enhances the oxygen evolution reaction catalytic properties by reducing the overpotential by 0.10 V. Both experimental and theoretical results suggest that plasma treatment strategy is useful for modifying the skeletal material nondestructively at room temperature, which opens up a broad prospect in the field of catalyst production.
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An asymmetric double oxidative [3 + 2] cycloaddition is reported. Oxidation of 3-((2,2,2-trifluoroethyl)amino)indolin-2-ones and ß-aryl-substituted aldehydes simultaneously and subsequent asymmetric cycloaddition in the presence of the chiral amino catalyst generated highly functionalized chiral CF3-containing spiro[pyrrolidin-3,2'-oxindole] with four contiguous stereocenters stereoselectively, which is characterized by directly constructing two C-C bonds from four C(sp3)-H bonds. This new method features mild conditions, broad substrate scope, and excellent functional group compatibility.
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Purpose: It has previously been reported that repeated exposure to hypoxia increases spleen size and haemoglobin (HGB) level and recent reports on the effect apnoea has on spleen size and haematological parameters are contradictory. Therefore, this study aims to evaluate the effect apnoea training has on spleen size and haematological parameters. Methods: The breath-holding (BH) group was comprised of 12 local student-athletes with no BH exercise experience who performed BH jogging and BH jumping rope dynamic apnoea protocols, five times weekly for 8 weeks. The BH event duration was progressively increased as the apnoea tolerance of the athletes improved (20 to 35 s). The same training task was performed by the control group (n = 10) without BH. Spleen sizes were measured with an ultrasound system and a complete blood cell analysis was performed on the median cubital venous blood. Results: Spleen volume in the BH group increased from 109 ± 13 ml to 136 ± 13 ml (p < 0.001), and bulky platelets decreased from 70.50 ± 5.83 to 65.17 ± 5.87 (p = 0.034), but no changes were recorded for erythrocytes (p = 0.914), HGB (p = 0.637), PLTs (p = 0.346) and WBC (p = 0.532). No changes were recorded for the control group regarding spleen size or haematological parameters. Conclusion: Eight weeks of dry dynamic apnoea training increased spleen size and decreased the number of circulating bulky platelets in the athletes who were assessed in this study. However, the baseline RBC counts and HGB levels of the athletes were not altered by the training programme.
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This study constructed the recombinant plasmid of a TonB-dependent receptor from V. parahaemolyticus and evaluated the immunogenicity of the recombinant protein in mice. The TonB-dependent receptor gene (GI: 28901321) was obtained by PCR amplification and cloned into plasmid pET-32a (+). The recombinant plasmids were transformed into Escherichia coli BL21, and the protein expression was induced by isopropyl-ß-d-thiogalactopyranoside (IPTG). The 6 × His-tagged TonB-dependent receptor inclusion bodies were purified by Ni-NTA Agarose column and renatured by gradient urea dialysis. The soluble and inclusion bodies of the TonB-dependent receptor were emulsified with Freund's adjuvant and subcutaneously injected into BALB/c mice. The serum titers with seven V. parahaemolyticus strains, eight Vibrio species, and nine other bacteria were studied by enzyme-linked immunosorbent assay and immunoblotting. The results showed that the serum homogenously bound the target protein in the V. parahaemolyticus cell lysates. The titers against the immunized protein were above 89K, while the titer against whole cells of seven V. parahaemolyticus strains ranged from 4.12K to 12.5K. However, the titers were higher for the soluble TonB-dependent receptor. The serums reacted with E. coli strains but did not cross-react with eight Vibrio species and Photobacterium damselae. These results showed that the TonB-dependent receptor proteins in this study were immunogenic, and the serums showed adequate specificity for V. parahaemolyticus. However, the availability of the TonB-dependent receptor on V. parahaemolyticus cells is probably limited.
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Vibrio parahaemolyticus , Animais , Proteínas de Transporte/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Camundongos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Diálise Renal , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismoRESUMO
BACKGROUND: The present study aims to investigate whether malnutrition defined by the Global Leadership Initiative in Malnutrition (GLIM) criteria using hand-grip strength (HGS) adequately predict postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer in a similar manner to GLIM-defined malnutrition using skeletal muscle index (SMI). METHODS: Patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included in this study. Clinical data were prospectively collected. Malnutrition was diagnosed based on the two-step approach following the GLIM criteria. Skeletal muscle mass was assessed using SMI based on abdominal computed tomography (CT) scans, or assessed using HGS. RESULTS: A total of 1359 patients were included in this study, in which 36.2% of the patients were at risk of malnutrition (Nutritional Risk Screening 2002 scores ≥3). The incidence of malnutrition was 28.2% and 27.5% using SMI and HGS, respectively. There was a high agreement between the two criteria of malnutrition (kappa = 0.863, P < 0.001). Both of the two criteria of malnutrition were independently associated with postoperative complications (SMI-GLIM, P = 0.041; HGS-GLIM, P = 0.023), overall survival (P < 0.001, both), and disease-free survival (P < 0.001, both), with similar odds ratio or hazard ratio after adjusting for the same confounding variables. HGS-GLIM malnutrition (P = 0.046) but not SMI-GLIM malnutrition (P = 0.270) was associated with a higher incidence of severe complications. CONCLUSIONS: GLIM criteria using HGS is a useful tool to diagnose malnutrition and has a similar or even better predictive value for postoperative complications and long-term survival after radical gastrectomy for gastric cancer compared with GLIM criteria using SMI.
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Desnutrição , Neoplasias Gástricas , Gastrectomia/efeitos adversos , Força da Mão , Humanos , Liderança , Desnutrição/epidemiologia , Avaliação Nutricional , Estado Nutricional , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Traumatic brain edema occurs commonly brain injury, and most manifests as pericontusional edema of brain contusions. On the basis of evidence-based medicine, apart from recommending craniotomy and mannitol, there are few particularly effective measures to prevent and treat traumatic brain edema. It is uncertain whether an early complementary acupuncture treatment would improve long-term outcomes of patients with traumatic brain edema. The aim of this study is to assess the efficacy and the safety of early complementary acupuncture for patients with traumatic brain edema. METHODS: This study is an actively accruing, single-center, single-blinded, 2-arm, randomized controlled trial. Patients with traumatic brain injury, a Glasgow Coma Scale score of 6â¼12, and brain edema on computed tomography scan will be divided into 2 groups on the basis of stratified block randomization. All patients will receive conventional treatment, and the study group will undergo additional acupuncture therapy (start within 72âhours after the injury) once a day for 28âdays. The primary outcome is the dichotomized Glasgow Outcome Score at 6âmonths and 12âmonths after injury, and the secondary outcomes are the Glasgow Coma Scale, the volume of traumatic brain edema, the serum levels of C-reactive protein and interleukin-6, and the Modified Barthel Index. DISCUSSION: This study will provide data regarding the efficacy of early complementary acupuncture for traumatic brain edema. If the study yields positive results, its findings may offer insights into a valuable complementary option of acupuncture for traumatic brain edema that could provide pilot evidence for large, randomized, controlled trials.Trial registration: This trial has been published in the Chinese Clinical Trial Register, http://www.chictr.org.cn/edit.aspx?pid=141208&htm=4 (Identifier: ChiCTR2100053794, registered on December 3, 2021).
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Acupuntura , Edema Encefálico/terapia , Lesões Encefálicas Traumáticas/complicações , Terapia por Acupuntura/métodos , Adolescente , Adulto , Idoso , Edema Encefálico/etiologia , Lesões Encefálicas Traumáticas/terapia , Humanos , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients. METHODS: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses. RESULTS: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]. CONCLUSIONS: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery.
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Neoplasias Colorretais , Desnutrição , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Humanos , Liderança , Desnutrição/complicações , Avaliação Nutricional , Estado Nutricional , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: To investigate the expression of glucocorticoid receptor (GR) in the PCa tissue and its correlation with the clinicopathological characteristics and prognosis of PCa. METHODS: Using immunohistochemical staining, we determined the expression of GR in the PCa tissue and analyzed its correlation with the clininicopathological features and prognosis of the malignancy. RESULTS: The positive expression of GR in the PCa tissue was 64%, of which the strongly positive rate was 34.7%. The GR expression was positively correlated with preoperative androgen-deprivation therapy (ADT) (χ2 = 22.307, P < 0.01), Gleason grades (χ2 = 16.534, P = 0.002) and clinical stages of the tumor (χ2 = 9.969, P = 0.041). Kaplan-Meier analysis showed that the GR expression was correlated not with the overall survival (P = 0.156), but with the PSA progression-free survival rate of the PCa patients (P = 0.042), with a shorter PSA progression-free survival time in those with a higher GR expression. Multivariate COX regression analysis revealed that the expression of GR was not an independent prognostic factor for PSA progression-free survival of the PCa patients. CONCLUSION: The expression of GR is related with preoperative ADT, and closely with the biological behavior of the malignancy and treatment resistance of the patients. GR is expected to be a new effective therapeutic target and a prognostic biomarker for PCa.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Receptores de Glucocorticoides/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Relevância Clínica , PrognósticoRESUMO
BACKGROUND: Sarcopenia and cachexia are two predictors of adverse clinical outcomes, but they are partly overlapping. We aimed to compare the characteristics and prognostic value of cachexia and sarcopenia in patients after gastrectomy. METHODS: From 2014 to 2019, a total of 1215 gastric cancer patients were enrolled. Cachexia and sarcopenia were diagnosed according to the most recent consensus definitions. Baseline characteristics and clinical outcomes were compared between the two groups. Risk factors of survival were evaluated by Cox regression analysis. RESULTS: Of all patients, 26.5% were diagnosed with cachexia and 19.8% were diagnosed with sarcopenia. Sarcopenia was more prevalent in elderly patients, while cachexia was prone to occur in patients with TMN stage III. Survival curves showed that sarcopenia had adverse effects in patients with TMN stage I and II-III, while cachexia was only associated with poor survival at stages II-III. For the entire cohort, both cachexia and sarcopenia were adverse factors for prognosis. However, for stage I patients, sarcopenia was an independent predictor for overall survival (OS) (HR = 4.939, P < 0.001) and disease-free survival (DFS) (HR = 4.256, P < 0.001), but not cachexia; for stage II-III patients, cachexia was an independent predictor for OS (HR = 1.538, P < 0.001) and DFS (HR = 1.473, P = 0.001), but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different clinical characteristics and prognostic values. For patients with early stage gastric cancer, detection for sarcopenia was more meaningful than cachexia. However, the prognostic significance of cachexia exceeded sarcopenia in advanced cancer.
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Sarcopenia , Neoplasias Gástricas , Idoso , Caquexia/complicações , Gastrectomia/efeitos adversos , Humanos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcopenia/complicações , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgiaRESUMO
This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (control (CT)) or 0·5 % CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 d. CLA treatment had no significant influence on development, egg quality and fertility of breeder hens but darkened the egg yolks in shade and increased yolk sac mass compared with the CT group. Addition of CLA resulted in increased body mass and liver mass and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum TAG and total cholesterol levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in the liver of chick offspring, accompanied by the decreased hepatic TAG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC and sterol regulatory element-binding protein-1c) and induced the expression of genes related to ß-oxidative (CPT1, AMP-activated protein kinase and PPARα) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased the incorporation of CLA in the liver of chick offspring, which further regulate hepatic lipid metabolism.
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Ácidos Linoleicos Conjugados , Animais , Galinhas/metabolismo , Dieta/veterinária , Ácido Graxo Sintases/metabolismo , Feminino , Ácidos Linoleicos Conjugados/metabolismo , Ácidos Linoleicos Conjugados/farmacologia , Metabolismo dos Lipídeos , Fígado/metabolismoRESUMO
Aberrant variations in angiogenesis have been observed in tumor tissues with abnormal stiffness of extracellular matrix (ECM). However, it remains largely unclear how ECM stiffness influences tumor angiogenesis. Numerous studies have reported that vascular endothelial growth factor-A (VEGF-A) released from tumor cells plays crucial roles in angiogenesis. Hence, we demonstrated the role of ECM stiffness in VEGF-A release from neuroblastoma (NB) cells and the underlying mechanisms. Based on 17 NB clinical samples, a negative correlation was observed between the length of blood vessels and stiffness of NB tissues. In vitro, an ECM stiffness of 30 kPa repressed the secretion of VEGF165 from NB cells which subsequently inhibited the tube formation of human umbilical vein endothelial cells (HUVECs). Knocked down VEGF165 in NB cells or blocked VEGF165 with neutralizing antibodies both repressed the tube formation of HUVECs. Specifically, 30 kPa ECM stiffness repressed the expression and nuclear accumulation of Yes-associated protein (YAP) to regulate the expression of Serine/Arginine Splicing Factor 1 (SRSF1) via Runt-related transcription factor 2 (RUNX2), which may then subsequently induce the expression and secretion of VEGF165 in NB tumor cells. Through implantation of 3D col-Tgels with different stiffness into nude mice, the inhibitory effect of 30 kPa on NB angiogenesis was confirmed in vivo. Furthermore, we found that the inhibitory effect of 30 kPa stiffness on NB angiogenesis was reversed by YAP overexpression, suggesting the important role of YAP in NB angiogenesis regulated by ECM stiffness. Overall, our work not only showed a regulatory effect of ECM stiffness on NB angiogenesis, but also revealed a new signaling axis, YAP-RUNX2-SRSF1, that mediates angiogenesis by regulating the expression and secretion of VEGF165 from NB cells. ECM stiffness and the potential molecules revealed in the present study may be new therapeutic targets for NB angiogenesis.
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Proteínas de Ciclo Celular/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Neovascularização Patológica/metabolismo , Neuroblastoma , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Matriz Extracelular , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Nus , Neovascularização Patológica/genética , Neuroblastoma/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
PURPOSE: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma. MATERIALS AND METHODS: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect. RESULTS: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group (p < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them. CONCLUSIONS: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Benzilaminas , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CXCL12 , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Ciclamos , Desoxicitidina/análogos & derivados , Humanos , Invasividade Neoplásica , Receptores CXCR4/genética , GencitabinaRESUMO
OBJECTIVE: The present study aims to determine the correlations between Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition and body composition and functional parameters, and to comprehensively analyze the predictive value of GLIM-defined malnutrition for postoperative outcomes in the context of detailed measurement of body composition and functional parameters in elderly patients who underwent radical gastrectomy for gastric cancer. METHODS: Elderly patients (aged ≥65 years) who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index (SMI), skeletal muscle density (SMD), subcutaneous fat area (SFA), and visceral fat area (VFA) were analyzed using abdominal computed tomography (CT) images. Handgrip strength and 6-m gait speed were measured. RESULTS: A total of 597 elderly patients were included in this study, in which 45.7% were at risk of malnutrition identified using Nutritional Risk Screening 2002 (NRS 2002), and 34.5% were diagnosed with malnutrition. Patients with malnutrition had lower SMI, SMD, SFA, VFA, lower handgrip strength and gait speed. Low handgrip strength and age ≥80 years were independent risk factors for postoperative complications, rather than GLIM-defined malnutrition. GLIM-defined malnutrition was independently associated with overall survival and disease-free survival after adjusting to the body composition and functional parameters in the multivariate analyses. CONCLUSIONS: GLIM-defined malnutrition was a better predictive factor than single parameters of body composition or physical function for survival in elderly gastric cancer patients. Handgrip strength can be used as a supportive measure to further improve the definition of malnutrition.