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2.
Artigo em Inglês | MEDLINE | ID: mdl-32003604

RESUMO

The gastrointestinal system is arguably one of the most complicated developmental systems in a multicellular organism as it carries out at least four major functions - digestion of food, absorption of nutrients, excretion of hormones, and defense against pathogens1. Anatomically the fetal gut has a tubular structure with an outer layer of smooth muscle derived from lateral splanchnic mesoderm and an inner lining of epithelium derived from the definitive endoderm. During morphogenesis of the gut tube, the definitive endoderm transforms into a primitive gut tube with a foregut, midgut, and hindgut. During the course of further development, the midgut gives rise to the small and proximal large intestine and the hindgut gives rise to the distal large intestine and rectum2. The small intestine is subdivided into three parts: duodenum, jejunum, and ileum, whereas the large intestine is subdivided in to the cecum, colon, and rectum3.

3.
Crit Rev Oncol Hematol ; 147: 102893, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32065969

RESUMO

The present study aimed to evaluate the effect of liver metastases on the efficacy from the combination of PD-1/PD-L1 inhibitor with chemotherapy as first-line treatment in lung cancer using the meta-analysis. A total of 8 randomized controlled trials (RCTs) were included. In patients without liver metastases, PD-1/PD-L1 inhibitor plus chemotherapy could decrease the risk of progression by 40% and risk of death by 29% (HR = 0.60; 95%CI,0.55- 0.65 and HR = 0.71;95%CI,0.58-0.90 respectively). In patients with liver metastases, PD-1/PD-L1 inhibitor plus chemotherapy could decrease the risk of progression by 31% and risk of death by 21% (HR = 0.69;95%CI,0.58-0.81; and HR = 0.79; 95%CI,0.62-0.80, respectively). The pooled ratios of PFS-HRs and OS- HRs reported in lung cancer patients with liver metastases versus those without liver metastases were 1.11 (95%CI, 0.92-1.34) and 1.03 (95%CI, 0.80-1.35), respectively, suggesting that lung cancer patients with and without liver metastases could obtain comparable efficacy.

4.
Am J Trop Med Hyg ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32043453

RESUMO

In tropical areas of developing countries, the interactions among parasitic diseases such as soil-transmitted helminths (STHs) and malaria, and glucose-6-phosphate dehydrogenase deficiency (G6PDd), are complex. Here, we investigated their interactions and impact on anemia in school students residing in a conflict zone of northeast Myanmar. A cross-sectional survey was conducted between July and December 2015 in two schools located along the China-Myanmar border. Stool samples from the schoolchildren were analyzed for STH infections, whereas finger-prick blood samples were analyzed for G6PDd, hemoglobin concentrations, and Plasmodium infections. Among 988 enrolled children, Plasmodium vivax, Plasmodium falciparum, hookworm, Ascaris lumbricoides, and Trichuris trichiura infections occurred in 3.3%, 0.8%, 31.5%, 1.2%, and 0.3%, respectively. Glucose-6-phosphate dehydrogenase deficiency was present in 16.9% of the children, and there was a very high prevalence of anemia (73%). Anthropometric measures performed on all children showed that 50% of the children were stunted and 25% wasted. Moderate to severe anemia was associated with STH infections, stunting, and wasting. In addition, children had increasing odds of anemia with increasing burden of infections. This study revealed a high prevalence of G6PDd, STHs, and anemia in schools located in a conflict zone. In areas where malnutrition and STH infections are rampant, testing for both glucose-6-phosphate dehydrogenase and anemia should be considered before treating vivax malaria with 8-aminoquinolines.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31983674

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) has shown effectiveness in terms of reducing the hospital stay and cost. However, the benefit of ERAS in patients undergoing hepatectomy for benign liver lesions is still unclear. METHODS: ERAS was implemented in our center since March 1st, 2018. From September 2016 to February 2018, 109 patients were enrolled into the control group, and from March 2018 to June 2019, 124 patients were enrolled into the ERAS group. All the indicators related to operation, liver functions, and postoperative outcomes were included in the analysis. RESULTS: The clinicopathologic baselines were similar in these two groups. A significantly higher proportion of patients underwent laparoscopic surgery in the ERAS group. On the whole, intraoperative blood loss (100.00 mL vs. 200.00 mL, P < 0.001), blood transfusion (3.23% vs. 10.09%, P = 0.033), total bilirubin (17.10 µmol/L vs. 21.00 µmol/L, P = 0.041), D-dimer (2.08 µg/mL vs. 2.57 µg/mL, P = 0.031), postoperative hospital stay (5.00 d vs. 6.00 d, P < 0.001), and postoperative morbidity (16.13% vs. 32.11%, P = 0.008) were significantly shorter or less in the ERAS group than those in the control group. After stratified by operation methods, ERAS group showed significantly shorter postoperative hospital stay in both open and laparoscopic operation (both P < 0.001). In patients underwent open surgery, ERAS group demonstrated significantly shorter operative duration (131.76 ± 8.75 min vs. 160.73 ± 7.23 min, P = 0.016), less intraoperative blood loss (200.00 mL vs. 450.00 mL, P = 0.008) and less postoperative morbidity (16.00% vs. 44.44%, P = 0.040). CONCLUSIONS: ERAS program may be safe and effective for the patients underwent hepatectomy, especially open surgery, for benign liver lesions.

6.
Talanta ; 209: 120552, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892096

RESUMO

Currently, the nanocomposites based on silicon nanoparticles (SiNPs) are usually limited to a single therapeutic modality, and the design of the SiNPs nanohybrids with multi-modal synergistic therapeutic functions is still worth being explored to achieve more effective treatment. Herein, we used mesoporous silica nanoparticle (MSN) as a nanoplatform, SiNPs and the photosensitizer 5,10,15,20-tetrakis (1-methyl 4-pyridinio) porphyrin tetra (p-toluenesulfonate) (TMPyP) were first embedded in the MSN and was further modified with folic acid (FA) to obtain the mesoporous silica nanocomposite (MSN@SiNPs@TMPyP-FA) for targeted two-photon-excited fluorescence imaging-guided photodynamic therapy (PDT) and chemotherapy. The embedded TMPyP could generate singlet oxygen to perform PDT under light irradiation, meanwhile the anticancer drugs doxorubicin (DOX) could be loaded for chemotherapy. Moreover, due to the two-photon excited fluorescence of SiNPs, the nanocomposite successfully achieved targeted two-photon fluorescence cellular imaging at the near-infrared (NIR) laser excitation, which could effectively avoid the interference of biological auto-fluorescence. And in vitro cytotoxicity assays revealed that the synergistic therapy combining PDT and chemotherapy exhibited high therapeutic efficacy for cancer cells.

7.
J Exp Med ; 217(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31922531

RESUMO

In this issue of JEM, Wang et al. (https://doi.org/10.1084/jem.20191130), using a single-cell RNA-seq approach, establish an atlas of human colon, rectum, and ileum epithelial cells. Their study reveals that different regions have specialized nutrient absorption preferences, microbe defenses, and endocrine function. They also identify new markers for a variety of cell types.

8.
Aging (Albany NY) ; 12(2): 1610-1623, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980591

RESUMO

It has been widely reported that advanced maternal age impairs oocyte quality. To date, various molecules have been discovered to be involved in this process. However, prevention of fertility issues associated with maternal age is still a challenge. In the present study, we find that both in vitro supplement and in vivo administration of melatonin are capable of alleviating the meiotic phenotypes of aged oocytes, specifically the spindle/chromosome disorganization and aneuploidy generation. Furthermore, we identify SIRT2 as a critical effector mediating the effects of melatonin on meiotic structure in old oocytes. Candidate screening shows that SIRT2-controlled deacetylation of histone H4K16 is essential for maintaining the meiotic apparatus in oocytes. Importantly, non-acetylatable-mimetic mutant H4K16R partially rescues the meiotic deficits in oocytes from reproductive aged mice. In contrast, overexpression of acetylation-mimetic mutant H4K16Q abolishes the beneficial effects of melatonin on the meiotic phenotypes in aged oocytes. To sum up, our data uncover that melatonin alleviates advanced maternal aged-associated meiotic defects in oocytes through the SIRT2-depenendet H4K16 deacetylation pathway.

9.
World J Surg ; 44(1): 171-178, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31552458

RESUMO

BACKGROUND: Although a greater depth of tumor invasion is correlated with a poorer prognosis in esophageal squamous cell carcinoma (ESCC), it remains controversial whether T2 ESCC should be subclassified by circular and longitudinal muscle invasion. We conducted a multicenter retrospective study to evaluate the relationship between the depth of invasion and long-term outcome and to identify the clinical significance of subclassifying T2 ESCC. METHODS: Patients with T2 ESCC who underwent esophagectomy at two different institutes between January 2009 and December 2017 were analyzed retrospectively. ESCC with circular and longitudinal muscle invasion was defined as T2 circular and T2 longitudinal ESCC, respectively. Survival outcomes and risk factors for lymph node metastasis (LNM) were evaluated by univariate and multivariate analyses. In addition, data from stage T1b ESCC cases during the same period were retrieved for use as a comparison cohort to evaluate the prognostic significance of the T2 substage. RESULTS: A total of 536 T2 ESCC patients were eligible, and 192 (36%) patients developed LNM. No significant difference was found in general characteristics between the T2 circular and T2 longitudinal ESCC groups (n = 219 and n = 317, P > 0.05), except for tumor location (P = 0.02). The T2 substage was not significantly correlated with survival on univariate or multivariate analysis (P = 0.30 and P = 0.34, respectively). Multivariate analysis also indicated that the T2 substage was not an independent risk factor for LNM (P = 0.15). When patients with stage T1b ESCC were considered, their survival time was significantly different from that of patients with T2 circular and T2 longitudinal disease (P = 0.01). CONCLUSIONS: The depth of tumor invasion into the circular and longitudinal muscle layers in T2 ESCC does not affect the prognosis or risk of LNM.

10.
Toxicol In Vitro ; 63: 104747, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31838184

RESUMO

Cinnabar, a mercury-containing mineral medicine, has been used as an ingredient in Traditional Chinese Medicines for treatment of various diseases for thousands of years and is still widely used today. The toxicity of cinnabar is much less than other mercury-containing compounds. This study aimed to evaluate the possible role of oligopeptide transporter1 (PEPT1) in intestinal uptake of cinnabar. Thus, the Caco-2 cell model was employed to investigate the differential transport levels and the probable transporter involved in the transport of cinnabar, mercury sulfide (HgS) and mercury chloride (HgCl2). Cells were incubated with the same molar concentration of cinnabar, HgS or HgCl2 and then the inorganic mercury content of apical (AP), cellular and basolateral (BL) side of the cell was measured by ultra-high liquid chromatography-inductively coupled plasma mass spectrometry (UPLC-ICP/MS) after the treatment, respectively. Their transportation levels were also investigated when pH was changed to 5.5 in AP side to define the role of the H+ dependent transporter. Effects of cinnabar, HgS or HgCl2 on transporter mRNA and protein expression levels were assayed by RT-PCR and Western-blot method, respectively. The possible transporter involved in the transport was examined by siRNA silencing and chemical inhibition. The results showed that the levels of inorganic mercury in the BL side for cinnabar and HgS were 49.39% and 30.41% of that in HgCl2 group. The transport levels of cinnabar and HgCl2 were significantly increased when the pH was changed to 5.5 on the AP side as compared with the control group (pH 7.4). Cinnabar significantly decreased the mRNA and protein expression of PEPT1. Transport levels of cinnabar were significantly decreased by PEPT1-siRNA and chemical inhibition of PEPT1. The present study demonstrates that PEPT1 may be an important transporter in the entry of cinnabar into the intestinal epithelium, and intestinal transport levels of cinnabar and HgS was lower than that of HgCl2.

11.
Proc Natl Acad Sci U S A ; 117(1): 464-471, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31852821

RESUMO

Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor (AdoR) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A (Adgf-A) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation.

12.
Pac Symp Biocomput ; 25: 659-670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31797636

RESUMO

Phenome-wide association studies (PheWAS) allow agnostic investigation of common genetic variants in relation to a variety of phenotypes but preserving the power of PheWAS requires careful phenotypic quality control (QC) procedures. While QC of genetic data is well-defined, no established QC practices exist for multi-phenotypic data. Manually imposing sample size restrictions, identifying variable types/distributions, and locating problems such as missing data or outliers is arduous in large, multivariate datasets. In this paper, we perform two PheWAS on epidemiological data and, utilizing the novel software CLARITE (CLeaning to Analysis: Reproducibility-based Interface for Traits and Exposures), showcase a transparent and replicable phenome QC pipeline which we believe is a necessity for the field. Using data from the Ludwigshafen Risk and Cardiovascular (LURIC) Health Study we ran two PheWAS, one on cardiac-related diseases and the other on polyunsaturated fatty acids levels. These phenotypes underwent a stringent quality control screen and were regressed on a genome-wide sample of single nucleotide polymorphisms (SNPs). Seven SNPs were significant in association with dihomo-γ-linolenic acid, of which five were within fatty acid desaturases FADS1 and FADS2. PheWAS is a useful tool to elucidate the genetic architecture of complex disease phenotypes within a single experimental framework. However, to reduce computational and multiple-comparisons burden, careful assessment of phenotype quality and removal of low-quality data is prudent. Herein we perform two PheWAS while applying a detailed phenotype QC process, for which we provide a replicable pipeline that is modifiable for application to other large datasets with heterogenous phenotypes. As investigation of complex traits continues beyond traditional genome wide association studies (GWAS), such QC considerations and tools such as CLARITE are crucial to the in the analysis of non-genetic big data such as clinical measurements, lifestyle habits, and polygenic traits.

13.
Onco Targets Ther ; 12: 8947-8954, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802904

RESUMO

Purpose: Increasing evidence suggests that lysyl oxidase-like 2 (LOXL2) contributes to tumor progression. However, the role of LOXL2 in cervical cancer still remains unclear. Patients and methods: We used the TCGA database to analyze the expression of LOXL2 in cervical cancer and its role on survival. The effects of LOXL2 on cervical cancer metastasis and EMT were verified by transwell and wound healing assay. Western blot assay was used to detect the effect of LOXL2 on EMT-related gene expression. In addition, we used animal experiments to observe the role of LOXL2 on tumor genesis and metastasis in cervical cancer. Results: Here we found that LOXL2 participates in epithelial-mesenchymal transition-related cervical cancer progression. LOXL2 ablation in cervical cancer cells inhibited cell metastatic ability, whereas LOXL2 overexpression promoted cell metastasis. In addition, more clinical data from TCGA revealed that LOXL2 is closely related to the prognosis and is highly expressed in highly malignant and metastatic cervical tumors. Conclusion: Taken together, our findings established a pathophysiologic role and new function for LOXL2 in cervical cancer metastasis.

14.
Med Sci Monit ; 25: 8204-8212, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674342

RESUMO

BACKGROUND Nanotechnology is one of the most productive approaches for specifically delivering drug payloads to the region of interest to decrease nonspecific distribution and unwanted toxicities. MATERIAL AND METHODS We prepared glycol chitosan stearate self-assembled nanoparticles loaded with methotrexate (MTX) for NF-kappaB targeting in treatment of rheumatoid arthritis (RA). The nanoparticles were prepared using hydrophobic modification of glycol chitosan (GC) with steric acid (SA) and was characterized using IR. The efficiency of nanoparticles after their physiochemical characterization was measured in vitro and by in vivo studies in mice. RESULTS The nanoparticles thus prepared were spherical in shape, 235 nm in diameter, and had negative zeta potential. The entrapment efficiency of MTX-GC-SA was more than 70%. The in vitro higher uptake of MTX-GC-SA in murine macrophage cells (RAW 264.7) was confirmed using confocal microscopy and FACS analysis. Systemic administration of MTX-GC-SA into collagen-induced arthritis (CIA) mice resulted in high accumulation in inflamed joints. The MTX-GS-SA revealed significantly better therapeutic efficacy against CIA mice compared to free MTX. CONCLUSIONS These findings highlight the potential of using this MTX-GC-SA nanoparticle formulation in suppressing inflammatory arthritis for effective treatment of RA.

15.
Animals (Basel) ; 9(11)2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31717851

RESUMO

The small intestine plays an important role for animals to digest and absorb nutrients. The epithelial lining of the intestine develops from the embryonic endoderm of the embryo. The mature intestinal epithelium is composed of different types of functional epithelial cells that are derived from stem cells, which are located in the crypts. Chickens have been widely used as an animal model for researching vertebrate embryonic development. However, little is known about the molecular basis of development and differentiation within the chicken small intestinal epithelium. This review introduces processes of development and growth in the chicken gut, and compares the cellular characteristics and signaling pathways between chicken and mammals, including Notch and Wnt signaling that control the differentiation in the small intestinal epithelium. There is evidence that the chicken intestinal epithelium has a distinct cellular architecture and proliferation zone compared to mammals. The establishment of an in vitro cell culture model for chickens will provide a novel tool to explore molecular regulation of the chicken intestinal development and differentiation.

16.
Adv Sci (Weinh) ; 6(21): 1901430, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31728288

RESUMO

Tumor-associated macrophages (TAMs) constitute over 50% of the number of cells within the tumor, playing a major role in tumor progression and invasion. Remodeling the tumor immune microenvironment by modulating TAM polarization has been emerging as a new and promising therapeutic strategy. However, the high interstitial fluid pressure and dense extracellular matrix lead to insufficient penetration of nanosized therapies. To overcome this dilemma, an acid-triggered size-changeable nanoparticle (aptamer/acid sensitive linker crosslinked DGL/zoledronic acid, i.e., Apt@(DGL-ZA) n NPs) with effective tumor distribution, extravasation, and penetration is designed. Dendrigraft poly-L-lysines (DGLs) which can induce tumor autophagy as mimics of natural abnormal proteins are crosslinked via a mild-acid-responsive linker (1,6-bis(4-formylbenzoyloxy) hexane). Long circulation property and tumor penetration are achieved simultaneously by catching DGLs in neutral pH while releasing them in the tumor's pH, like dandelion seeds in midair. The macrophage conditioning agent zoledronic acid (ZA) is loaded on DGLs by the charge attraction. A Tenascin-C targeting aptamer (GBI-10) is modified onto (DGL-ZA) n NPs for a tumor-homing effect. Apt@(DGL-ZA) n NPs show both enhanced penetration in in vitro 3D triple negative breast cancer spheroids and in vivo tumor tissues. Effective macrophage regulation, enhanced tumor autophagy, and excellent in vivo antitumor efficacy are achieved, suggesting this tactic as a significant antitumor strategy.

17.
Anim Sci J ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729108

RESUMO

Magnolol rich in Magnolia officinalis is a bioactive polyphenolic compound. The aim of this study was to clarify the effects of magnolol additive (MA) on carcass and meat quality, biochemical characteristics and antioxidative capacity of Linwu ducks, by comparing it to that of antibiotic additive (colistin sulphate, CS). A total of 275 49-d-old ducks were randomly assigned to 5 groups with 5 cages of 11 ducks each and fed by the diets supplemented with 0, 100, 200 and 300 mg of MA/kg and 30 mg of CS/kg for 3 weeks, respectively. The results revealed that MA administration not only increased dressed percentage (calculated as a percentage of live weight), percentage of breast muscle, leg muscle and lean meat (calculated as a percentage of eviscerated weight), but also remarkably increased a*45 min and pH45 min of leg muscle. Moreover, MA administration decreased the percentage of abdominal fat (calculated as a percentage of eviscerated weight), 45-min cooking loss, water loss rate of leg muscle, 45-min cooking loss and drip loss of breast muscle at 24 hr and 48 hr. Furthermore, MA administration enhanced the activities of superoxide dismutase and catalase in serum or liver, serum total antioxidant capacity and hepatic reduced glutathione concentration significantly, compared with the basal diet or CS group (p < .05). On the other hand, triglyceride, total cholesterol, aspartate aminotransferase, malondialdehyde, protein carbonyl and 8-hydroxy-2'-deoxyguanosine contents in serum and liver were significantly increased in Linwu ducks fed with CS, compared with MA groups (p < .05). Taken together, these data demonstrated that magnolol could effectively improve the carcass and meat quality of Linwu ducks by regulating the in vivo antioxidant status and would be a potential candidate to replace antibiotic.

18.
Front Nutr ; 6: 151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616670

RESUMO

Dietary protein sources have the potential to affect the colon microbiome of piglets that will subsequently have a large impact on metabolic capabilities and hindgut health. This study explored the effects of different protein sources on the growth performance, diarrhea rate, apparent ileal digestibility (AID) of crude protein (CP), colonic mucin chemotypes, colonic microbiome, and microbial metabolites of piglets. Twenty-four piglets were randomly divided into four groups that received isoenergetic and isonitrogenous diets containing either Palbio 50 RD (P50), Soyppt-50% (S50), concentrated degossypolized cottonseed protein (CDCP), or fish meal (FM) as the sole protein source. The experimental diets did not affect the estimated daily gain (EDG), but P50 increased fecal score compared with S50 and CDCP. CDCP increased, but P50 reduced AID of CP in comparison to FM and S50. S50 and CDCP increased the amount of mixed neutral-acidic mucins relative to P50. Venn analysis identified unique OTUs in the P50 (13), CDCP (74), FM (39), and S50 (31) groups. The protein sources did not change the colonic bacterial richness or diversity. High Escherichia abundance in the P50 and FM, great abundant of Lactobacillus in the CDCP, and high Gemmiger abundance in the S50 were found. The CDCP tended to elevate valeric acid and branched chain fatty acid (BCFA) concentrations compared with the other diets. The P50 and FM groups had greater ammonia nitrogen and methylamine contents than the S50 and CDCP groups. There was a positive correlation between the Escherichia and ammonia nitrogen, the Lactobacillus and short chain fatty acid (SCFA), and a negative correlation between the Gemmige and BCFA. These findings suggested short-term feeding of different protein sources did not affect the piglets' growth, but P50 increased the diarrhea rate. Potential pathogenic bacteria and detrimental metabolites appeared in the colons of piglets fed P50 and FM, whereas, beneficial effects were conferred upon piglets fed CDCP and S50, thus indicating that available plant proteins (cotton seed, soy) added to the diets of piglets enhanced colon health by reducing protein fermentation.

19.
Cancer Manag Res ; 11: 8111-8123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564971

RESUMO

Purpose: Lung cancer is one of the most life-threatening cancer worldwide with poor prognosis attributed to the lack of early diagnosis and proper therapy. The estrogen-related receptor alpha (ERRα) is a multifunctional protein not limited to bind ligands and has been reported to be associated with numerous cancers. This study aimed to investigate the potential role of ERRα in lung cancer and to provide a novel perspective for lung cancer early diagnosis, targeted therapy, and prognosis assessment. Methods: The correlation between ERRα mRNA expression and survival time of the online clinical data about lung cancer was analyzed by using Kaplan-Meier (KM) plotter. A mouse model of lung adenocarcinoma (LUAD) was constructed to detect the expression level of ERRα in tumor tissues. ERRα-knockdown LUAD cells were generated and the impacts of ERRα on cell proliferation, invasion, and metastasis were further analyzed. Cancerous and paracancerous tissues were collected to semi-quantitative the levels of ERRα in LUAD clinical samples (n=88), combined with clinical information for prognostic analysis. Results: The KM plotter analysis suggested that ERRα is correlated with poor prognosis in LUAD (n=720) rather than in lung squamous cell carcinoma (LSCC) (n=524). ERRα is also upregulated in tumor tissues obtained from LUAD model mice. Quantitative analysis suggested an abnormal elevation of ERRα in LUAD cells rather than in LSCC cells. The results demonstrated that downregulation of ERRα impairs proliferation, invasion and migration abilities (P<0.01). The prognostic analysis showed that the overexpressed ERRα in LUAD was positively correlated with low survival rates (HR=1.597). The results indicate that the death risk of ERRα high expression is 1.597 times higher than ERRα low level in LUAD patients. Conclusion: In summary, our findings suggest that ERRα is a potential aggressive factor of LUAD which implies poor prognosis.

20.
Food Funct ; 10(10): 6417-6428, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31517363

RESUMO

Protein fermentation has an adverse effect on colonic health; high-quality proteins and reducing the protein level (protein restriction) can effectively decrease the amount of proteins flowing into the colon for microbial protein fermentation. The study is aimed at determining the effects of different protein sources on colonic microbial composition and barrier function in nursery pigs with a low protein diet. A total of 264 weaned pigs were randomly divided into 4 dietary groups and each group had 6 pens with 11 pigs. Four low protein, amino acid (AA)-supplemented diets containing either 4% Palbio 50 RD (P50), Soyppt-50% (S50), concentrated degossypolized cottonseed protein (CDCP), or fish meal (FM) were prepared, and all the diets had similar digestible energy (DE), crude protein content (CP, about 18%), and equal amount of standardized ileal digestible (SID) lysine, methionine, tryptophan, and threonine. After 28 days of feeding trial, CDCP decreased the Desulfovibrio abundance but increased the Parabacteroides abundance. S50 elevated the Bacteroides and CF231 abundance. P50 and FM reduced the Clostridium and Ruminococcus abundance. CDCP upregulated the Occludin mRNA expression and tended to increase the amount of mixed neutral-acidic mucins in the colon. FM and CDCP declined the serum DAO and endotoxin contents. S50 and CDCP decreased the levels of serum IL-1α, and P50 lowered the serum IL-8 content. We concluded that plant protein (CDCP and S50) had advantages over animal protein (P50 and FM) in maintaining the colonic health via the regulation of colonic microbiota and barrier function.

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