ABSTRACT
In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells, which, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.
Subject(s)
Macrophages, Peritoneal , Macrophages , Humans , Mice , Animals , Mice, Inbred C57BL , Macrophages/metabolism , Macrophages, Peritoneal/metabolism , Cell Differentiation , Dendritic CellsABSTRACT
The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunologic Memory/immunology , Lymph Nodes/immunology , Melanoma, Experimental/immunology , Melanoma/immunology , Skin Neoplasms/immunology , Animals , Humans , Mice , Vitiligo , Melanoma, Cutaneous MalignantABSTRACT
The ketocarotenoid fucoxanthin and its derivatives can absorb blue-green light enriched in marine environments. Fucoxanthin is widely adopted by phytoplankton species as a main light-harvesting pigment, in contrast to land plants that primarily employ chlorophylls. Despite its supreme abundance in the oceans, the last steps of fucoxanthin biosynthesis have remained elusive. Here, we identified the carotenoid isomerase-like protein CRTISO5 as the diatom fucoxanthin synthase that is related to the carotenoid cis-trans isomerase CRTISO from land plants but harbors unexpected enzymatic activity. A crtiso5 knockout mutant in the model diatom Phaeodactylum tricornutum completely lacked fucoxanthin and accumulated the acetylenic carotenoid phaneroxanthin. Recombinant CRTISO5 converted phaneroxanthin into fucoxanthin in vitro by hydrating its carbon-carbon triple bond, instead of functioning as an isomerase. Molecular docking and mutational analyses revealed residues essential for this activity. Furthermore, a photophysiological characterization of the crtiso5 mutant revealed a major structural and functional role of fucoxanthin in photosynthetic pigment-protein complexes of diatoms. As CRTISO5 hydrates an internal alkyne physiologically, the enzyme has unique potential for biocatalytic applications. The discovery of CRTISO5 illustrates how neofunctionalization leads to major diversification events in evolution of photosynthetic mechanisms and the prominent brown coloration of most marine photosynthetic eukaryotes.
Subject(s)
Diatoms , Xanthophylls , Molecular Docking Simulation , Xanthophylls/metabolism , Carotenoids/metabolism , Chlorophyll/metabolism , Diatoms/genetics , Diatoms/metabolismABSTRACT
Recent global marine lipidomic analysis reveals a strong relationship between ocean temperature and phytoplanktonic abundance of omega-3 long-chain polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential for human nutrition and primarily sourced from phytoplankton in marine food webs. In phytoplanktonic organisms, EPA may play a major role in regulating the phase transition temperature of membranes, while the function of DHA remains unexplored. In the oleaginous diatom Phaeodactylum tricornutum, DHA is distributed mainly on extraplastidial phospholipids, which is very different from the EPA enriched in thylakoid lipids. Here, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9-mediated knockout of delta-5 elongase (ptELO5a), which encodes a delta-5 elongase (ELO5) catalyzing the elongation of EPA to synthesize DHA, led to a substantial interruption of DHA synthesis in P. tricornutum. The ptELO5a mutants showed some alterations in transcriptome and glycerolipidomes, including membrane lipids and triacylglycerols under normal temperature (22 °C), and were more sensitive to elevated temperature (28 °C) than wild type. We conclude that PtELO5a-mediated synthesis of small amounts of DHA has indispensable functions in regulating membrane lipids, indirectly contributing to storage lipid accumulation, and maintaining thermomorphogenesis in P. tricornutum. This study also highlights the significance of DHA synthesis and lipid composition for environmental adaptation of P. tricornutum.
Subject(s)
Diatoms , Docosahexaenoic Acids , Diatoms/genetics , Diatoms/metabolism , Docosahexaenoic Acids/metabolism , Fatty Acid Elongases/genetics , Fatty Acid Elongases/metabolism , Gene Knockout Techniques , Thermotolerance/genetics , Lipid Metabolism/geneticsABSTRACT
Fucoxanthin, a natural carotenoid that has substantial pharmaceutical value due to its anticancer, antioxidant, antiobesity, and antidiabetic properties, is biosynthesized from glyceraldehyde-3-phosphate (G3P) via a series of enzymatic reactions. However, our understanding of the transcriptional mechanisms involved in fucoxanthin biosynthesis remains limited. Using reverse genetics, the med8 mutant was identified based on its phenotype of reduced fucoxanthin content, and the biological functions of MED8 in fucoxanthin synthesis were characterized using approaches such as gene expression, protein subcellular localization, protein-protein interaction and chromatin immunoprecipitation assay. Gene-editing mutants of MED8 exhibited decreased fucoxanthin content as well as reduced expression levels of six key genes involved in fucoxanthin synthesis, namely DXS, PSY1, ZDS-like, CRTISO5, ZEP1, and ZEP3, when compared to the wild-type (WT) strain. Furthermore, we showed that MED8 interacts with HSF3, and genetic analysis revealed their shared involvement in the genetic pathway governing fucoxanthin synthesis. Additionally, HSF3 was required for MED8 association with the promoters of the six fucoxanthin synthesis genes. In conclusion, MED8 and HSF3 are involved in fucoxanthin synthesis by modulating the expression of the fucoxanthin synthesis genes. Our results increase the understanding of the molecular regulation mechanisms underlying fucoxanthin synthesis in the diatom P. tricornutum.
Subject(s)
Diatoms , Heat Shock Transcription Factors/metabolism , Diatoms/genetics , Diatoms/metabolism , Xanthophylls/metabolism , Carotenoids/metabolismABSTRACT
Long-lived memory CD8+ T cells play important roles in tumor immunity. Studies over the past two decades have identified four subsets of memory CD8+ T cells - central, effector, stem-like, and tissue resident memory - that either circulate through blood, lymphoid and peripheral organs, or reside in tissues where cancers develop. In this article, we will review studies from both pre-clinical mouse models and human patients to summarize the phenotype, distribution and unique features of each memory subset, and highlight specific roles of each subset in anti-tumor immunity. Moreover, we will discuss how stem-cell like and resident memory CD8+ T cell subsets relate to exhausted tumor-infiltrating lymphocytes (TIL) populations. These studies reveal how memory CD8+ T cell subsets together orchestrate durable immunity to cancer.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunologic Memory , Neoplasms/immunology , Animals , CD8-Positive T-Lymphocytes/metabolism , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/therapy , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Tumor Microenvironment/immunologyABSTRACT
In addition to being important primary productive forces in marine ecosystems, diatoms are also rich in bioactive substances such as triacylglycerol and fucoxanthin. However, little is known about the transcriptional mechanisms underlying the biosynthesis of these substances. In this study, we found that the heat shock transcription factor PtHSF1 positively regulated the synthesis of triacylglycerol and fucoxanthin in Phaeodactylum tricornutum. Overexpression of PtHSF1 could increase the contents of triacylglycerol and fucoxanthin and upregulate key enzyme genes involved in the triacylglycerol and fucoxanthin biosynthesis pathways. On the other hand, gene silencing of PtHSF1 reduced the contents of triacylglycerol and fucoxanthin and the expression of the key enzyme genes involved in the triacylglycerol and fucoxanthin biosynthesis pathways. Further biochemical analysis revealed that PtHSF1 upregulated glycerol-2-phosphate acyltransferase 3 (GPAT3) and 1-deoxy-d-xylulose 5-phosphate synthase (DXS) by directly binding to their promoters, while genetic analysis demonstrated that PtHSF1 acted upstream of GPAT3 and DXS to regulate triacylglycerol and fucoxanthin synthesis. Therefore, in addition to elucidating the regulation mechanisms underlying PtHSF1-mediated triacylglycerol and fucoxanthin synthesis, this study also provided a candidate target for metabolic engineering of triacylglycerol and fucoxanthin in P. tricornutum.
Subject(s)
Acyltransferases , Diatoms , Triglycerides/metabolism , Heat Shock Transcription Factors/metabolism , Acyltransferases/metabolism , Diatoms/genetics , Diatoms/metabolism , EcosystemABSTRACT
BACKGROUND: Pectus excavatum (PE) is the most common disease of chest wall deformity, with an incidence of 1 in 300-400 births. Nuss procedure has proved to be the best surgical treatment method and has been widely used after clinical use for 30 years. We aimed to review the clinical data of pectus excavatum (PE) of thoracoscopic Nuss procedure adopted the Modified bar bending method of the six-point seven-section type, and compare it with the traditional curved bar bending method to explore the clinical application effect. METHODS: Forty-six cases of clinical data were summarized of children with PE who adopted the treatment of the Modified bar bending method of the six-point seven-section type from January 2019 to December 2021, and 51 cases were compared of PE children who adopted the treatment of traditional curved bar bending method from January 2016 to December 2018, including the data of age, gender, preoperative symptoms, symmetry, Haller index, operation time, bar bending time, intraoperative bleeding, postoperative complications, bar migration, postoperative effect evaluation, etc. RESULTS: The Procedure duration (P = 0.008), bar bending time (P < 0.001), and duration of postoperative pain (P < 0.001) were reduced significantly, and the incidence of bar migration after surgery was reduced as well by the modified bar bending method. There was no difference compared with traditional Nuss produce, like the incidence of evaluation of postoperative effects (Excellent, P = 0.93; Good, P = 0.80; Medium, P = 1.00; Poor, P = 1.00), bar migration (P = 1.00), postoperative complications (P = 1.00), Clavien- Dindo classification of surgical complications (I = 0.165; II = 1.00; IIIa = 1.00; IIIb = 1.00; VI = 1.00; V = 1.00), operative safety, and operative validity. CONCLUSION: Modified bar bending method of the six-point seven-section type, which is a kind of surgical method worth applying and popularizing, and the advantages of minimally procedure duration, bar bending time, and duration of postoperative pain, compared with the traditional bar bending method.
Subject(s)
Funnel Chest , Thoracic Wall , Child , Humans , Funnel Chest/surgery , Retrospective Studies , Pain, Postoperative , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
It is attractive to explore practical approaches to optimize the photodegraded NO property of TiO2. Herein, a typicalZ-shaped heterojunction C-TiO2/rGO composed of carbon-doped TiO2and reductive graphene oxide (rGO) was constructed to optimize the NO removal efficiency through anin situone-pot hydrothermal process with glucose as reductant and dopant. The C-TiO2/rGO (0.11%) composite displays a remarkable NO removal performance of 40.6% under visible light illumination. It was found that the C-TiO2nanoparticles were tightly attached to the rGO sheets and had strong interactions with rGO, which induced a positive impact on not only the light absorption and photo-generated charge separation but also the NO adsorption and reactive oxygen species formation, resulting in boosted photodegrade NO activity. As to the photodegrade NO process over the C-TiO2/rGO, the HOâ¢and O2â¢-were the dominant radicals, of which the O2â¢-radical originated from the interactions between C-TiO2and rGO. We proposed aZ-scheme mechanism to illuminate the advanced photocatalytic activity of C-TiO2/rGO. This work affords an approach to developing effective photocatalysts in the NO purification field.
ABSTRACT
BACKGROUND: Lipoleiomyoma is a rare, benign variant of the commonplace uterine leiomyoma. Unlike leiomyoma, these tumors are composed of smooth muscle cells admixed with mature adipose tissue. While rare, they are most frequently identified in the uterus, but even more infrequently have been described in extrauterine locations. CASE PRESENTATION: We describe a case report of a 45-year-old woman with a history of in vitro fertilization pregnancy presenting 6 years later with abdominal distention and weight loss found to have a 30-cm intra-abdominal lipoleiomyoma. While cross-sectional imaging can narrow the differential diagnosis, histopathological analysis with stains positive for smooth muscle actin, desmin, and estrogen receptor, but negative for HMB-45 confirms the diagnosis of lipoleiomyoma. The large encapsulated tumor was resected en bloc. The patients post-operative course was uneventful and her symptoms resolved. CONCLUSIONS: Lipoleiomyoma should be considered on the differential diagnosis in a woman with a large intra-abdominal mass. While considered benign, resection should be considered if the mass is symptomatic, and the diagnosis is unclear or there is a concern for malignancy.
Subject(s)
Leiomyoma , Lipoma , Uterine Neoplasms , Female , Humans , Leiomyoma/diagnostic imaging , Leiomyoma/surgery , Menopause , Middle Aged , Pregnancy , PrognosisABSTRACT
The groundwater is an important route of human exposure to kinds of contaminants. This study was carried out to investigate the occurrence and spatial distribution of groundwater arsenic in the Jinghui irrigation district in Shaanxi Province, China. The water contamination was assessed for drinking purposes by comparing it to national guidelines, and the impacts of arsenic on human health were quantified using the health risk assessment model recommended by the USEPA. The results show that the concentration of groundwater arsenic ranges from 0.0012 to 0.0190â¯mg/L (average 0.0054â¯mg/L), and 2.58% of groundwater exceed the national guidelines of 0.01â¯mg/L for drinking. The carcinogenic risk of arsenic affecting adults has reached 3.50â¯×â¯10-4, significantly exceeding the national guideline (1.00â¯×â¯10-4.) The health risks resulting from oral exposure are higher than those of dermal exposure. The carcinogenic risk for adults is higher than that for children, while the non-carcinogenic risk for children is higher than that for adults. The area ratio of the carcinogenic risk is 42.82%, and the area of the non-carcinogenic risk is 69.19%. Groundwater arsenic mainly originates from the discharge of industrial wastewater and the slowly release of natural sediments. The results of this study can help to set up suitable management strategies to guarantee water supply and health safety for local residents.
Subject(s)
Arsenic , Drinking Water , Groundwater , Water Pollutants, Chemical , Adult , Child , China , Environmental Monitoring , Humans , Risk AssessmentABSTRACT
The main aim of this study was to compare and evaluate the performance of fractal dimension as input data in the landslide susceptibility mapping of the Baota District, Yan'an City, China. First, a total of 632 points, including 316 landslide points and 316 non-landslide points, were located in the landslide inventory map. All points were divided into two parts according to the ratio of 70%:30%, with 70% (442) of the points used as the training dataset to train the models, and the remaining, namely the validation dataset, applied for validation. Second, 13 predisposing factors, including slope aspect, slope angle, altitude, lithology, mean annual precipitation (MAP), distance to rivers, distance to faults, distance to roads, normalized differential vegetation index (NDVI), topographic wetness index (TWI), plan curvature, profile curvature, and terrain roughness index (TRI), were selected. Then, the original numerical data, box-counting dimension, and correlation dimension corresponding to each predisposing factor were calculated to generate the input data and build three classification models, namely the kernel logistic regression model (KLR), kernel logistic regression based on box-counting dimension model (KLRbox-counting), and the kernel logistic regression based on correlation dimension model (KLRcorrelation). Next, the statistical indexes and the receiver operating characteristic (ROC) curve were employed to evaluate the models' performance. Finally, the KLRcorrelation model had the highest area under the curve (AUC) values of 0.8984 and 0.9224, obtained by the training and validation datasets, respectively, indicating that the fractal dimension can be used as the input data for landslide susceptibility mapping with a better effect.
ABSTRACT
Although hypotheses have been proposed and developed to interpret the origins and functions of introns, substantial controversies remain about the mechanism of intron evolution. The availability of introns in the intermediate state is quite helpful for resolving this debate. In this study, a new strain of diatom (denominated as DB21-1) was isolated and identified as Olifantiella sp., which possesses multiple types of 18S rDNAs (obtained from genomic DNA; lengths ranged from 2,056 bp to 2,988 bp). Based on alignments between 18S rDNAs and 18S rRNA (obtained from cDNA; 1,783 bp), seven intron insertion sites (IISs) located in the 18S rDNA were identified, each of which displayed the polymorphism of intron presence/absence. Specific primers around each IIS were designed to amplify the introns and the results indicated that introns in the same IIS varied in lengths, while terminal sequences were conserved. Our study showed that the process of intron loss happens via a series of successive steps, and each step could derive corresponding introns under intermediate states. Moreover, these results indicate that the mechanism of genomic deletion that occurs at DNA level can also lead to exact intron loss.
Subject(s)
Diatoms/genetics , Introns/genetics , Polymorphism, Genetic , DNA, Algal/analysis , Phylogeny , RNA, Algal/analysis , RNA, Ribosomal, 18S/analysis , Sequence AlignmentABSTRACT
The parameters of water contents, oxidation-reduction potential, organic matter, total phosphorus, total nitrogen and heavy metals concentrations of mercury (Hg), cadmium (Cd), lead (Pb), arsenic (As), chromium (Cr), copper (Cu) and zinc (Zn) in surface sediment and their vertical distribution incore sediments of the Heer river were investigated. Evaluation of nutrients and heavy metals in the Heer River sediments was done by pollution index and potential ecological risk index (PERI) method, respectively. Environmental dredging depth was calculated. The parameters pH, water content, total nitrogen (TN), and organic matter (OM) as well as heavy metals decline with the increased depth. Nutrients of TN, total phosphorus (TP), OM, and heavy metals Cd, Cu, and Pb were classified into the same group and there were significant positive correlations according to the principal component analysis and Pearson correlation, implying that they have a common origin. The results of high pollution index value of OM, TP, and TN of surface sediment obtained from this research showed that the Heer River was in serious nutrient pollution. The contributions of individual metals to the potential ecological risk were in the following order: Cd > Cu > Ni > Cr > Zn > As > Pb. Cd presented serious ecological risk and contributed most to the sediments of the Heer River. The ecological risk (RI) was at a considerable high risk level, and therefore, the environmental dredging depth of the Heer River is 94 cm for the purpose of reducing heavy metal contamination of the Heer River.
Subject(s)
Environmental Monitoring , Geologic Sediments/chemistry , Rivers/chemistry , Water Pollutants, Chemical/analysis , Arsenic/analysis , Cadmium/analysis , China , Chromium/analysis , Ecology , Environmental Pollution/analysis , Mercury/analysis , Metals, Heavy/analysis , Nitrogen/analysis , Phosphorus/analysis , Risk Assessment , Zinc/analysisABSTRACT
Mining is considered to be one of the most significant sources of environmental pollution with regard to heavy metals. Mineral mining causes large quantities of mercury, cadmium, and other elements to be released into the environment and naturally poses a serious threat to environment. This paper will analyze the pollution status of agricultural soil caused by the mining of heavy metals in various mining areas in the Xunyang County in the Shaanxi Province of China, an area in famous for its resource mining. Equally, it will look at the potential ecological risk assessment process that is used to analyze the ecological risks of mining heavy metals in agricultural soil located in the surrounding areas. Based on the soil investigation, As pose a moderate ecological risk on the Au mining area. In addition, the Hg metals pose a significantly high potential ecological risk and Cd metals pose a considerable potential ecological risk on the Hg mining area. In the Pb-Zn mining area, a significantly high potential ecological risk was mainly posed by Cd. These results suggest that many heavy metals pose a high potential ecological risk on the agricultural soil in these three mining areas in the Xunyang County, and may cause elevated heavy metal contents in crops, eventually jeopardizing the health of local residents who consume food grown in polluted soil.
Subject(s)
Metals, Heavy/analysis , Soil Pollutants/analysis , Agriculture , China , Crops, Agricultural , Environmental Monitoring/methods , Environmental Pollution/analysis , Mining , Risk AssessmentABSTRACT
BACKGROUND: Maize was grown on compound soils constituted from mixtures of soft rock and sand at different ratios, and water use efficiency (WUE), nitrogen use efficiency (NUE) and fertilizer nitrogen use efficiency (FNUE) were quantified. The data were used to assist in designing strategies for optimizing water and nitrogen management practices for maize on the substrates used. Maize was sown in composite soil prepared at three ratios of soft rock and sand (1:1, 1:2 and 1:5 v/v) in Mu Us Sandy Land, Yuyang district, Yulin city, China. Yields, amount of drainage, nitrogen (N) leaching, WUE and NUE were calculated. Then a water and nitrogen management model (WNMM) was calibrated and validated. RESULTS: No significant difference in evapotranspiration of maize was found among compound soils with soft rock/sand ratios of 1:1, 1:2 and 1:5, while water drainage increased significantly with increasing soft rock/sand ratio. WUE increased to 1.30 kg m-3 in compound soil with 1:2 soft rock/sand ratio. Nitrogen leaching and ammonia volatilization were the main reason for nitrogen loss, and N reduction mainly relied on crop uptake. NUE and FNUE could reach 33.1 and 24.9 kg kg-1 N respectively. Water drainage and nitrogen leaching occurred mostly during heavy rainfall or irrigation. Through a scenario analysis of different rainfall types, water and fertilizer management systems were formulated each year. CONCLUSION: This study shows that soft rock plays a key role in improving the WUE, NUE and FNUE of maize. © 2016 Society of Chemical Industry.
Subject(s)
Nitrogen/metabolism , Soil/chemistry , Water/metabolism , Zea mays/growth & development , Zea mays/metabolism , Agriculture , China , Fertilizers/analysis , Nitrogen/analysis , Water/analysis , Zea mays/chemistryABSTRACT
BACKGROUND: Asthma is a common chronic airway disorder associated with significant morbidity and mortality. OBJECTIVE: Current study aims at investigating the correlation between four vitamin D receptor (VDR) gene polymorphisms and asthma susceptibility by conducting a meta-analysis. METHODS: PubMed, EBSCO, Ovid, Wiley, Web of Science, Wanfang, CNKI and VIP databases were searched using combinations of keywords relating to VDR and asthma. The published studies were filtered using our stringent inclusion and exclusion criteria, and the resultant high-quality data from final selected studies were analyzed using Stata 12.0 software. RESULTS: A total of 77 studies were initially retrieved, and after further selection, 9 studies were eligible in current analysis. The selected studies contained 2,116 patients with asthma and 1,884 healthy controls. Our results demonstrated that rs2228570, rs7975232 and rs731236 in both allele models and dominant models, and rs3782905 in allele model in the VDR gene were linked with a high risk of asthma. No significant association between VDR gene rs3782905 in dominant model and risk of asthma was detected. CONCLUSIONS: This meta-analysis provides convincing evidence that rs2228570, rs7975232, rs731236 and rs3782905 gene polymorphisms in VDR are associated with increased susceptibility to asthma, indicating VDR polymorphisms could be developed as biomarkers for asthma susceptibility.
Subject(s)
Asthma/genetics , Genetic Predisposition to Disease , Receptors, Calcitriol/genetics , Humans , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
BACKGROUND: The aim of this study was to examine the associations between the single-nucleotide polymorphisms (SNPs) of interleukin-17 (IL-17), including rs763780 (7488A/G), rs2275913 (-197G/A), and rs8193036 (-737C/T), and asthma susceptibility in an Asian population. MATERIAL/METHODS: From Oct 2013 to Dec 2014, 125 asthma patients enrolled in our hospital were selected as the case group. Another 132 healthy controls undergoing physical examinations in our hospital were enrolled as the control group. The genotype frequencies of IL-17 rs763780, rs2275913 and rs8193036 SNPs were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comprehensive Meta-analysis 2.0 (CMA 2.0) software was applied for meta-analysis. RESULTS: Our results demonstrated that asthma patients presented with higher frequencies of GA genotype in rs2275913 and TT genotype in rs8193036 of IL-17 than healthy controls (both P<0.001). The genotype frequencies of IL-17 rs763780 between the asthma patients and healthy controls exhibited no significant differences (P>0.05). The comparisons on the rs2275913 and rs8193036 frequencies between the asthma patients and healthy controls were statistically significant in both allele and addictive models (all P<0.05). The frequency of IL-17 rs763780 between the asthma patients and healthy controls were statistically different in allele models (P<0.05), but not in addictive models (P>0.05). The overall results of our case-control study were further confirmed by meta-analysis. CONCLUSIONS: Our results revealed that, in an Asian population, IL-17 rs763780, rs2275913, and rs8193036 SNPs may be associated with asthma susceptibility, and GA genotype in rs2275913 and TT genotype in rs8193036 of IL-17 may contribute to increased risk of asthma in Asians.
Subject(s)
Asian People/genetics , Asthma/genetics , Genetic Predisposition to Disease , Interleukin-17/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Case-Control Studies , Female , Gene Frequency , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Matrix metalloproteinase 7 (MMP-7) promotes tumor invasion and metastasis in several cancers. However, its role in lung cancer progression is understudied. In this study, we investigated the correlation between MMP-7 expression and lung cancer pathology. METHODS: We searched the databases PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, China BioMedicine (CBM) and China National Knowledge Infrastructure (CNKI) for scientific literature relevant to MMP-7 and lung cancer. Carefully selected studies were pooled and ORs with 95% CI were calculated. Subgroup analyses and publication bias were analyzed to understand the retrieved data in greater detail. Version 12.0 STATA software was used for statistical analysis. RESULTS: We retrieved a total of 121 studies through database searches. Finally, 14 cohort studies satisfied our inclusion/exclusion criteria, and these 14 studies, published between 2004 and 2012, were selected for meta-analysis to understand the influence of MMP-7 expression in lung cancer progression. Our results showed consistent differences in MMP-7 expression when comparisons were made between TNM I-II versus III-IV (OR = 1.82, 95% CI: 1.19 to 2.78, P = 0.006); histologic grade 1 to 2 versus 3 to 4 (OR = 1.67, 95% CI: 1.14 to 2.42, P = 0.008); and lymph node-negative versus lymph node-positive samples (OR = 2.81, 95% CI: 1.73 to 4.58, P <0.001), with significantly higher MMP-7 expression levels found in the more advanced stages. Subgroup analysis showed that age was not the factor influencing the associations between histologic grade, LN metastasis and MMP-7 expression in lung cancer patients, as both under 60 and over 60 age groups showed strong correlations (all P <0.05). However, when TNM staging was analyzed for its association with MMP-7 expression, only patients under age 60 showed a statistically significant correlation. CONCLUSIONS: Our meta-analysis results revealed that MMP-7 overexpression is associated with advanced TNM and histological grades, and is linked to aggressive LN metastasis in lung cancer patients; thus MMP-7 is a useful biomarker to assess the disease status in lung cancers.
Subject(s)
Adenocarcinoma/enzymology , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/enzymology , Lung Neoplasms/enzymology , Matrix Metalloproteinase 7/metabolism , Adenocarcinoma/secondary , Adenocarcinoma of Lung , Carcinoma, Squamous Cell/secondary , Humans , Immunoenzyme Techniques , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lymphatic MetastasisABSTRACT
BACKGROUND: This study detected osteopontin (OPN) and matrix metalloproteinase-7 (MMP-7) expressions to explore the roles of OPN and MMP-7 in the occurrence, progression, and prognosis of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective study was conducted on NSCLC tissues (n = 152; case group) and adjacent nonneoplastic lung parenchyma (adjacent to tumor >5 cm; n = 152; control group) collected from 152 NSCLC patients. The protein expressions of OPN and MMP-7 were detected by immunohistochemistry. OPN and MMP-7 messenger RNA (mRNA) expressions were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The protein and mRNA expressions of OPN and MMP-7 in NSCLC tissues were evidently higher than those in adjacent nonneoplastic lung parenchyma (all P < 0.05). OPN protein and mRNA expression were associated with the degree of differentiation, tumor node metastasis (TNM) staging, and lymph node metastasis in NSCLC (all P < 0.05). MMP-7 protein expression was associated with TNM staging and lymph node metastasis (both P < 0.05) while MMP-7 mRNA expression was associated with the degree of differentiation, TNM staging, and lymph node metastasis (all P < 0.05). A significantly positive relativity was revealed between OPN expression and MMP-7 expression (protein: r = 0.789, P < 0.001; mRNA: r = 0.377, P < 0.001). Lymph node metastasis, TNM staging, OPN, and MMP-7 protein expressions were independent risk factors for the prognosis of NSCLC (all P < 0.05). CONCLUSION: High MMP-7 and OPN protein expressions are closely related to the occurrence, progression, and prognosis of NSCLC, and can be served as unfavorable prognostic factors for NSCLC.