ABSTRACT
Aluminum-activated malate transporters (ALMTs) and slow anion channels (SLACs) are important in various physiological processes in plants, including stomatal regulation, nutrient uptake, and in response to abiotic stress such as aluminum toxicity. To understand their evolutionary history and functional divergence, we conducted phylogenetic and expression analyses of ALMTs and SLACs in green plants. Our findings from phylogenetic studies indicate that ALMTs and SLACs may have originated from green algae and red algae, respectively. The ALMTs of early land plants and charophytes formed a monophyletic clade consisting of three subgroups. A single duplication event of ALMTs was identified in vascular plants and subsequent duplications into six clades occurred in angiosperms, including an identified clade, 1-1. The ALMTs experienced gene number losses in clades 1-1 and 2-1 and expansions in clades 1-2 and 2-2b. Interestingly, the expansion of clade 1-2 was also associated with higher expression levels compared to genes in clades that experienced apparent loss. SLACs first diversified in bryophytes, followed by duplication in vascular plants, giving rise to three distinct clades (I, II, and III), and clade II potentially associated with stomatal control in seed plants. SLACs show losses in clades II and III without substantial expansion in clade I. Additionally, ALMT clade 2-2 and SLAC clade III contain genes specifically expressed in reproductive organs and roots in angiosperms, lycophytes, and mosses, indicating neofunctionalization. In summary, our study demonstrates the evolutionary complexity of ALMTs and SLACs, highlighting their crucial role in the adaptation and diversification of vascular plants.
Subject(s)
Magnoliopsida , Plant Proteins , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Aluminum/metabolism , Plants/genetics , Plants/metabolism , Biological Evolution , Magnoliopsida/genetics , Evolution, MolecularABSTRACT
Despite effective mining environmental regulations, residual metal pollution persists, leading to significant ecological harm and posing substantial risks to human well-being. This study employed multiple-criteria methods to investigate the ecological and health risks caused by metals in multiple environmental media (e.g., arable soil, indoor dust, PM10, homegrown vegetables, and rice) around abandoned mine areas (MA) in central south China. The study also aimed to identify predominant risk factors and the main exposure pathway. The findings revealed that metal levels and risks in the environmental media surrounding the MA were significantly higher than those in the control areas (away from abandoned mines, CA). This indicates that the accumulation of metals in the environmental media surrounding the MA was attributed to the previous mining activities. Variations in metal content were observed among different environmental media in MA, with Cd from mining source being the primary pollutant in arable soil, indoor dust, PM10, and vegetables, while As from agricultural source was the main pollutant in rice. Additionally, the consumption of Cd-contaminated vegetables and As-contaminated rice emerged as the primary routes of health hazards for the local population, leading to significant non-carcinogenic and carcinogenic risks. Consequently, it is imperative for the government and mining companies to promptly establish risk control and remedial strategies for mitigating residual metal levels in multiple environmental media surrounding the MA.
Subject(s)
Mining , China , Risk Assessment , Humans , Metals/analysis , Environmental Monitoring , Dust/analysis , Environmental Exposure/analysis , Environmental Pollutants/analysis , Soil Pollutants/analysis , Vegetables/chemistry , Oryza/chemistryABSTRACT
Patients with anal condyloma acuminatum (CA) are at risk of developing anal cancer which is associated with oncogenic human papillomavirus (HPV) infection. Investigation of anal HPV prevalence and risk factors can provide effective strategies for the prevention of anal cancer. A retrospective study was conducted among 549 patients with anal CA in the Third People's Hospital of Shenzhen between January 2019 and October 2021. HPV prevalence and HIV antibodies were detected by fluorescent PCR and ELISA, respectively. Logistic regression model and structural equation modeling (SEM) were conducted to analyzed the risk factors of oncogenic HPV infection. The overall prevalence of HPV was 96.72%. Both HPV6 (N = 285, 51.91%) and HPV11 (N = 300, 54.64%) were more than half infected and the most frequent Hr-HPV genotype was HPV16 (N = 138, 25.14%). HIV-positive (AOR: 5.02, 95% CI: 2.98-8.60, p < 0.0001) and history of syphilis (AOR: 4.24, 95% CI: 2.31-8.46, p < 0.0001) were independent risk factors statistically associated with oncogenic HPV infection. Ever had anal sex (AOR: 3.40, 95% CI: 1.28-11.81, p = 0.0267) and age 35 years and older (AOR: 2.79, 95% CI: 1.53-5.15, p = 0.0009) were associated with HPV16 and HPV52, respectively. SEM analyses showed that HIV-positive (b = 1.549, p < 0.001) and history of syphilis (b = 1.450, p < 0.001) had significant positive effects on oncogenic HPV infection. Ever had anal sex (b = 1.243, p = 0.025) and Age (b = 0.043, p = 0.002) positively drived HPV16 and HPV52 infection, respectively. Anal CA patients who are HIV-positive, have a history of syphilis, or at least 35 years old should be considered for Hr-HPV, cytology and other anal cancer related tests to reduce the risk of cancer development.
Subject(s)
Anus Neoplasms , Condylomata Acuminata , HIV Infections , HIV Seropositivity , Papillomavirus Infections , Syphilis , Male , Humans , Adult , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Retrospective Studies , HIV Infections/complications , HIV Infections/epidemiology , Homosexuality, Male , Syphilis/complications , Prevalence , Risk Factors , Anal Canal , Condylomata Acuminata/complications , Condylomata Acuminata/epidemiology , Anus Neoplasms/epidemiology , Anus Neoplasms/complications , Papillomaviridae/genetics , Human papillomavirus 16/geneticsABSTRACT
The ectopic expression of cellular retinoic acid binding protein 2 (CRABP2) is associated with various tumorigenesis. However, the effects of CRABP2 on the progression of cervical cancer are still unclear. The current study aimed to investigate the role of CRABP2 in the malignant phenotypes of cervical cancer cells. CRABP2 was artificially regulated in CaSki, SiHa, and C-33A cells. CCK-8 assay and flow cytometry were used to assess the cell proliferation and apoptosis abilities, respectively. Wound healing assay and transwell assay were employed to measure the cell migration and invasion abilities, respectively. The results showed that CRABP2 was highly expressed in cervical carcinoma tissues and cell lines, and its high expression was associated with poor overall survival. Knockdown of CRABP2 promoted the cell apoptosis and inhibited cell proliferation, migration, and invasion in cervical carcinoma cells, whereas CRABP2 overexpression exhibited the opposite results. Mechanically, CRABP2 silencing suppressed the Integrin ß1/FAK/ERK signaling via HuR. Treatment with siITGB1 or a FAK inhibitor PF-562271 or an ERK inhibitor FR180204 reversed the promoting effects of CRABP2 on cell proliferation, migration, and invasion. Moreover, the overexpression of CRABP2 reverted the HPV16 E6/E7 knockdown-induced inhibition of cell proliferation, migration, and invasion in cervical cancer cells. These results suggested that HPV16 E6/E7 promoted the malignant phenotypes of cervical cancer by upregulating the expression of CRABP2. In conclusion, CRABP2, upregulated by HPV E6/E7, promoted the progression of cervical cancer through activating the Integrin ß1/FAK/ERK signaling pathway via HuR.
ABSTRACT
In this work, a sensitive analytical method based on packed-nanofiber solid-phase extraction (PFSPE), after derivatization with trichloroacetic acid and high-performance liquid chromatography with a fluorescence detector (HPLC-FLD), has been established for the determination of aflatoxins (AFs) in milk. Polystyrene polymeric multi-walled carbon nanotube (PS-MWCNT/OH) composite nanofibers were fabricated by electrospinning and used to prepare homemade extraction columns. The extraction efficiency of the HPLC-FLD analysis method was sufficiently investigated and validated. After the implementation of optimal conditions, all of the analytes were separated efficiently and the components of the milk matrix did not disturb the determination. The obtained linear ranges of the calibration curves were 0.2-20 ng/mL for AFTB1 and AFTG2, 0.1-10 ng/mL for AFTB2, and 0.4-40 ng/mL for AFTG1. The recoveries ranged between 80.22% and 96.21%. The relative standard deviations (RSDs) for the intra-day and inter-day results ranged from 2.81-6.43% to 3.42-7.75%, respectively. Generally, 11 mg of sorbent and 200 µL of elution solvent were used to directly extract all of the AFs from the milk matrix. Reported herein is the first utilization of PS-MWCNT/OH-PFSPE HPLC-FLD to simultaneously analyze the occurrence of aflatoxins in milk.
Subject(s)
Aflatoxins , Nanofibers , Animals , Milk , Chromatography, High Pressure Liquid , Solid Phase ExtractionABSTRACT
BACKGROUND: Ultrasound is widely used as a novel non-thermal processing technique to improve protein properties. In recent decades, applying ultrasound-assisted emulsification (UAE) to produce protein-stabilized emulsion has attracted people's attention. Instead of applying ultrasound to treat a single protein solution, UAE treatment refers to the use of sonication to a mixture of protein and oil. The purpose of this study was to compare the different effects of ultrasound treatment on the properties of myofibrillar protein (MP) in the presence or absence of soybean oil. A suitable sonication power was selected based on the change in emulsion properties. RESULTS: 300 W sonication power was selected because of its most effectively decreased emulsion droplet size and increased absolute zeta potential. Sonication more significantly increased the protein carbonyl content and disulfide bonds of the MP-soybean oil sample compared with the MP sample. Due to the presence of oil, ultrasound could unfold more protein molecules, illustrated by a lower α-helix content and intrinsic fluorescence intensity, and a higher surface hydrophobicity. Results of liquid chromatography-tandem mass spectrometry illustrated that sonication enhanced the myosin heavy chain and actin content at the soybean oil interface as well as accelerated the myosin light chain to separate from myosin in the MP-soybean oil system. CONCLUSION: Ultrasound treatment could lead to a higher level of protein oxidation and greater protein molecule exposure in the MP in the presence of oil system than in the oil-free MP system. © 2023 Society of Chemical Industry.
Subject(s)
Soybean Oil , Humans , Soybean Oil/chemistry , Emulsions/chemistry , Protein Carbonylation , Oxidation-Reduction , Hydrophobic and Hydrophilic InteractionsABSTRACT
Human papillomavirus (HPV) is a significant risk factor for head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients have a higher survival rate, which may be related to its unique tumor microenvironment. Exosomes are emerging as a communication tool between tumor cells and the tumor microenvironment, including cancer-associated fibroblasts (CAFs). In this study, 111 clinical samples tissues and public sequencing data were analyzed. Our study found fewer CAFs infiltrated in HPV+ HNSCC, and poor CAF infiltration level was associated with a good prognosis. HPV+ HNSCC cell-derived exosomes can significantly reduce the phenotypic transformation of fibroblasts. miR-9-5p, as a miRNA enriched in HPV+ HNSCC cell-derived exosomes, can be transferred to fibroblasts. miR-9-5p mimic transfection decreased the expression of NOX4 and the level of intracellular reactive oxygen species (ROS), which inhibited the transforming growth factor beta 1(TGF-ß1)-induced increase of αSMA levels. Therefore, these results indicated that HPV+ HNSCC-derived exosomal miR-9-5p inhibits TGF-ß signaling-mediated fibroblast phenotypic transformation through NOX4, which is related to the excellent prognosis of HPV patients.
Subject(s)
Alphapapillomavirus , Exosomes , Head and Neck Neoplasms , MicroRNAs , Papillomavirus Infections , Cell Line, Tumor , Cell Proliferation , Exosomes/genetics , Exosomes/metabolism , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , NADPH Oxidase 4/genetics , NADPH Oxidase 4/metabolism , Papillomaviridae/genetics , Papillomavirus Infections/genetics , Papillomavirus Infections/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , Tumor MicroenvironmentABSTRACT
This study aimed to investigate the correlation between Leishmania infection and dendritic cell infiltration and explore the underlying molecular mechanism how Leishmania infection regulates dendritic cell infiltration. Three datasets, GSE63931, GSE80008 and GSE77528 were combined and their batch effects were removed by Combat function in sva R package. Immune cell infiltrations were estimated using the Microenvironment Cell Populations-counter (MCP-counter) R package. Statistical results were verified by Student's t test. The differential expression of metadherin (MTDH) was identified by Limma R package. The correlation between MTDH expression and dendritic cell infiltration was estimated by Pearson's product moment correlation coefficient. GDS5086 was used to explore MTDH expression pattern in dendritic cells infected with Leishmania. Compared with normal samples, 5 types of immune cells showed differential infiltration in leishmaniasis samples, including T cells, CD8+ T cells, dendritic cells, cytotoxic lymphocytes and B lineage cells. Among these, only DCs were significantly suppressed in leishmaniasis samples. Notably, MTDH expression was differential between leishmaniasis and normal samples. There was a significant correlation between MTDH expression and dendritic cell infiltration. In conclusion, these results demonstrate that Leishmania infection leads to the downregulation of MTDH expression and the suppression of dendritic cell infiltration.
Subject(s)
Cell Adhesion Molecules , Leishmania , Humans , Cell Adhesion Molecules/metabolism , RNA-Binding Proteins , Leishmania/metabolism , Membrane Proteins/metabolism , CD8-Positive T-Lymphocytes/metabolism , Dendritic Cells/metabolismABSTRACT
In this study, keratins were extracted from pig nail waste through the reduction method using L-cysteine as a reductant. Curcumin was successively incorporated in a mixed solution including keratin, gelatin, and glycerin to prepare different kinds of keratin/gelatin/glycerin/curcumin composite films. The morphology of the keratin/ gelatin/glycerin/curcumin composite films were examined using scanning electron microscopy. The structures and the molecular interactions between curcumin, keratin, and pectin were examined using Fourier transform infrared spectroscopy and X-ray diffraction, and the thermal properties were determined through thermogravimetric analysis. The tensile strengths of keratin/gelatin/glycerin/curcumin and keratin/gelatin/curcumin composite films are 13.73 and 12.45 MPa, respectively, and their respective elongations at break are 56.7% and 4.6%. In addition, compared with the control group (no film wrapped on the surface of tomato), the ratio of weight loss of the keratin (7.0%)/gelatin (10%)/glycerin (2.0%)/curcumin (1.0%) experimental groups is 8.76 ± 0.2%, and the hardness value of the tomatoes wrapped with composite films is 11.2 ± 0.39 kg/cm3. Finally, the composite films have a superior antibacterial effect against Staphylococcus aureus and Escherichia coli because of the addition of curcumin. As the concentration of curcumin reaches 1.0%, the antibacterial activity effect of the film is significantly improved. The diameter of the inhibition zone of E. coli is (12.16 ± 0.53) mm, and that of S. aureus is (14.532 ± 0.97) mm. The multifunctional keratin/gelatin/glycerin/curcumin bioactive films have great potential application in the food packaging industry.
Subject(s)
Curcumin , Solanum lycopersicum , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Curcumin/chemistry , Curcumin/pharmacology , Cysteine/pharmacology , Escherichia coli , Food Packaging , Gelatin/chemistry , Gelatin/pharmacology , Glycerol/pharmacology , Keratins/chemistry , Pectins/pharmacology , Reducing Agents/pharmacology , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus , SwineABSTRACT
Human papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV-related HNSCC. In this study, 124 HPV+ and 513 HPV- HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV- HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV- HNSCC sample was detected with single-cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+ CD38+ ) and memory B cells (MS4A1+ CD27+ ) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC.
Subject(s)
Alphapapillomavirus/immunology , B-Lymphocytes/immunology , Carcinoma, Squamous Cell/immunology , Head and Neck Neoplasms/immunology , Squamous Cell Carcinoma of Head and Neck/immunology , Aged , CD4-Positive T-Lymphocytes/immunology , Carcinoma, Squamous Cell/virology , Chemokine CXCL13/immunology , Female , Head and Neck Neoplasms/virology , Humans , Male , Middle Aged , Papillomavirus Infections/immunology , Papillomavirus Infections/virology , Prognosis , Receptors, CXCR5/immunology , Squamous Cell Carcinoma of Head and Neck/virologyABSTRACT
The effect of host immune status on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Here, we report the first case of coronavirus disease 2019 (COVID-19) with human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus coinfection, who showed a persistently negative SARS-CoV-2 RNA test but delayed antibody response in the plasma. This case highlights the influence of HIV-1-induced immune dysfunction on early SARS-CoV-2 clearance.
Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coinfection/immunology , HIV Infections/complications , Hepatitis C/complications , Adult , Antibodies, Viral/immunology , Antibody Formation , COVID-19/blood , COVID-19/diagnosis , COVID-19 Serological Testing , Coinfection/virology , HIV Infections/immunology , HIV-1 , Hepacivirus , Hepatitis C/immunology , Humans , Immunocompromised Host , Male , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray ComputedABSTRACT
Laryngeal squamous cell carcinoma (LSCC) is a highly malignant tumor originated from respiratory system. Although there have been many improvements in therapy until now, reducing the high mortality remains difficult. Understanding the cellular heterogeneity of LSCC could contribute to improve this problem. Single-cell RNA sequencing was applied to dissect the cell composition and molecular characteristics of LSCC tissues. Immunohistochemistry staining of the LSCC tissues was performed to identify the spatial location of tumor cells. Survival analysis of marker genes was executed in The Cancer Genome Atlas to verify the correlation between each cell clusters and patients' prognosis. The LSCC tissue cells were finely grouped into various clusters, including tumor cells, immune cells, epithelial cells, fibroblasts and endothelial cells. Notably, in tumor cells, keratinocyte-like cells were in the core of tumor while malignant proliferating cells were located at the tumor edge. The malignant proliferating cells were correlated with poor prognosis. In summary, this is the first study to delineate a landscape of the LSCC intratumor heterogeneity. Our work might help researchers have a better understanding for tumor progression.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/pathology , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Aged , Carcinoma, Squamous Cell/genetics , Female , Gene Expression Regulation, Neoplastic , Genetic Heterogeneity , Humans , Laryngeal Neoplasms/genetics , Male , Middle Aged , Prognosis , Survival AnalysisABSTRACT
As persistent carcinogenic human papillomavirus (HPV) infection is a prominent driver of cervical cancer, it is essential to explore HPV persistence and its associated factors for cancer screening and prevention. A retrospective cohort study was performed in outpatient women between March 2010 and 2019 in Heilongjiang, northeast China. HPV genotyping was performed by polymerase chain reaction-membrane hybridization. An unconditional logistic regression model was used to analyze the association of factors with persistence. The overall prevalence of HPV at baseline was 27.1%, with a downward trend from 2010 to 2019 (P < .0001). The most commonly observed high- and low-risk HPVs were HPV16 (N = 1094, 5.9%) and HPV11 (N = 596, 3.2%), respectively. The probabilities of 6-month persistence were high for women infected with HPV16 (P = .0001), HPV58 (P = .018), and HPV53 (P = .014), as well as for women with multiple infections (P = .009), and those who were 51 to 60 years old (P = .004) or more than 60 years old (P = .007). The probabilities of 12-month persistence were high for women infected with HPV53 (P = .017) and 51- to 60-year-old women (P = .044). HPV16 is the dominant HPV type in Heilongjiang. An age in the range of 51 to 60 years and infection with HPV53 is associated with HPV infection persistence in the Heilongjiang population.
ABSTRACT
Free fatty acid receptor G protein-coupled receptor 120 (GPR120) is highly expressed in macrophages and was reported to inhibit lipopolysaccharide (LPS)-stimulated cytokine expression. Under inflammation, macrophages exhibit striking functional changes, but changes in GPR120 expression and signaling are not known. In this study, the effects of LPS treatment on macrophage GPR120 expression and activation were investigated. The results showed that LPS inhibited GPR120 expression in mouse macrophage cell line Ana-1 cells. Moreover, LPS treatment inhibited GPR120 expression in mouse alveolar macrophages both in vitro and in vivo. The inhibitory effect of LPS on GPR120 expression was blocked by Toll-like receptor 4 (TLR4) inhibitor TAK242 and p38 mitogen-activated protein kinase inhibitor LY222820, but not by ERK1/2 inhibitor U0126 and c-Jun N-terminal kinase inhibitor SP600125. LPS-induced inhibition of GPR120 expression was not attenuated by GPR120 agonists TUG891 and GW9508. TUG891 inhibited the phagocytosis of alveolar macrophages, and LPS treatment counteracted the effects of TUG891 on phagocytosis. These results indicate that pretreatment with LPS inhibits GPR120 expression and activation in macrophages. It is suggested that LPS-induced inhibition of GPR120 expression is a reaction enhancing the LPS-induced pro-inflammatory response of macrophages.
ABSTRACT
Natamycin is a polyene macrolide antibiotic and widely used as a natural food preservative. Fungal elicitor had positive effects on the natamycin biosynthesis in Streptomyces natalensis HW-2. However, the global gene expression in response to fungal elicitor is not still reported. In the study, RNA-Seq was used to check the change of transcriptome by fungal elicitor in S. natalensis HW-2. The results showed that there were 1265 differential expression genes (DEGs) at 40 h and 2196 DEGs at 80 h. Most of the genes involved in natamycin biosynthesis were upregulated. KEGG pathway analysis showed that fungal elicitor had strong effects on the transcriptional levels of genes related to branch-chained amino acid (BCAA) metabolism. There were 23 upregulated or downregulated DEGs involved in BCAA biosynthesis and degradation at 40 h and 80 h. To confirm whether the improvement of BCAA biosynthesis could produce more natamycin, metabolic engineering was used to homologously overexpress the gene ilvH which encoded the regulatory subunit of acetolactate synthase (ALS) in S. natalensis. The results showed that overexpression of ilvH in S. natalensis HW-2 increased natamycin production to 1.25 g/L in the flask, which was a 32% increase compared with that of the parent strain. Real-time quantitative PCR analysis showed that the transcriptional level of ilvH in mutant strain S. natalensis ZS101 was significantly increased. Acetyl-CoA content was also raised. The results suggested that the fungal elicitor enhanced natamycin biosynthesis by improving precursor supply via BCAA metabolism. This study will open a new avenue for enhancing natamycin production by metabolic engineering and adding fungal elicitor. KEY POINTS: ⢠The fungal elicitor had strong effects on the transcriptional levels of genes related to branch-chained amino acid metabolism by RNA-Seq. ⢠The homologous overexpression of gene ilvH increased natamycin production by 32% and acetyl-CoA content was raised in mutant strain S. natalensis ZS101.
Subject(s)
Amino Acids, Branched-Chain/metabolism , Biosynthetic Pathways/genetics , Fungi/metabolism , Gene Expression Regulation, Bacterial , Natamycin/biosynthesis , Streptomyces/genetics , Anti-Bacterial Agents/biosynthesis , Biosynthetic Pathways/drug effects , Culture Media , Fermentation , Metabolic Engineering , Penicillium chrysogenum/growth & development , Penicillium chrysogenum/metabolism , RNA-Seq , Streptomyces/drug effects , Streptomyces/metabolismABSTRACT
The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
Subject(s)
Adipocytes/metabolism , Fibroblast Growth Factors/metabolism , Leptin/metabolism , 3T3 Cells , Adenylate Kinase , Animals , Down-Regulation , MAP Kinase Signaling System , Mice , Phosphorylation , Signal TransductionABSTRACT
BACKGROUND: Glioma is the primary cancer of the central nervous system, and defining the prognosis of glioma is of great significance in the clinical. The long noncoding RNAs (lncRNAs) emerge as important regulators of pathological processes. This study aimed to identify lncRNAs which could function as potential prognosis biomarkers of glioma. MATERIAL AND METHODS: Glioma RNA-seq data from TCGA and CGGA were analyzed to identify neoplasm grade associated lncRNAs by DEseq. 2R and weighted gene co-expression network analysis. Consensus module genes were analyzed in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway to predict lncRNAs biological functions. Then neutrophil immune estimations were analyzed by Tumor Immune Estimation Resource. Transcrption factors of these lncRNAs were predicted by PROMO. Overall survival and receiver operating characteristic (ROC) analyses were applied to test the accuracy of predicted lncRNAs as the markers of prognosis. RESULTS: We identified four lncRNAs most correlated with both higher neoplasm grade and worse prognosis, including AC064875.2, HOTAIRM1, LINC00908, and RP11-84A19.3. Neutrophil-mediated immunity and cell adhesion junction were considered as the main biological functions of these lncRNAs. In addition, the correlation of these four lncRNAs with glioma prognosis was validated. CONCLUSION: Neutrophil immune infiltration is implicated in higher neoplasm grade and worse prognosis of glioma. AC064875.2, HOTAIRM1, LINC00908, and RP11-84A19.3 may serve as potential prognosis biomarkers of glioma.
Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Genome, Human , Glioma/genetics , Glioma/pathology , RNA, Long Noncoding/genetics , Gene Expression Profiling , Humans , Prognosis , Survival RateABSTRACT
Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a far better prognosis than HPV negative HNSCC. Recent studies suggest that long noncoding RNA (lncRNA) moieties may play a role in HPV associated differential HNSCC prognoses. In this study, we examined differential expression of lncRNAs in HPV+ vs HPV- HNSCC using The Cancer Genome Atlas database. LncRNAs were categorized based on expression level and survival analysis. A group of eight lncRNAs was identified in which altered expression was associated with both HPV infection and better prognosis. Subsequently, genes coexpressed with these lncRNAs in HNSCC cells were sorted into corresponding co-expression modules. The lnc-IL17RA-11 coexpression module exhibited the greatest correlation with HPV infection and radiotherapy efficacy. We identified the lnc-IL17RA-11 transcription factor ER-alpha as the most likely HPV infection associated factor promoting increased lnc-IL17RA-11 levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment among lnc-IL17RA-11 co-expressed genes for functions related to DNA replication and cell proliferation. These observations are consistent with a model in which HPV infection upregulates transcription factor ER-alpha, which increases levels of lnc-IL17RA-11 and coexpressed genes that promote HNSCC cell sensitivity to radiotherapy, thereby improving disease prognosis.
Subject(s)
Papillomavirus Infections/genetics , RNA, Long Noncoding/genetics , Receptors, Interleukin-17/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Ontology , Humans , Male , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Prognosis , Radiation Tolerance/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/virologyABSTRACT
BACKGROUND: The increasing availability of high-throughput sequencing data provides researchers with unprecedented opportunities to investigate viral genetic elements in host genomes that contribute to virus-linked cancers. Almost all of the available computational tools for secondary analysis of sequencing data detect viral infection or genome integration events. However, viral oncogenes expression is likely of importance in carcinoma. We therefore developed a new software, DisV-HPV16, for the evaluation of HPV16 oncogenes expression. RESULTS: HPV16 virus and viral oncogenes expression was detected more rapidly using DisV-HPV16 compared to other software. DisV-HPV16 was proved highly convenient for detecting candidate virus after modification of the reference file. The accuracy of DisV-HPV16 was empirically confirmed in laboratory experiments. DisV-HPV16 exhibited greater reliability than other software. CONCLUSIONS: DisV-HPV16 is a new, dependable software to detect virus and viral oncogenes expression through analysis of RNA sequencing data. Use of DisV-HPV16 can yield deeper, more comprehensive insights into virus infection status and viral and host cell gene expression.
Subject(s)
Human papillomavirus 16/genetics , Oncogene Proteins, Viral/genetics , Software , Base Sequence , Cell Line, Tumor , Genome, Viral , High-Throughput Nucleotide Sequencing , Human papillomavirus 16/isolation & purification , Humans , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , RNA, Viral/chemistry , RNA, Viral/isolation & purification , RNA, Viral/metabolism , Reproducibility of Results , Sequence Analysis, RNAABSTRACT
Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.