ABSTRACT
Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models. The deletion of Dnase1 in mice (Dnase1-/-) caused aberrations in ucfDNA fragmentation, including a 24-fold increase in DNA concentration, and a 3-fold enrichment of long DNA molecules, with a relative decrease of fragments with thymine ends and reduction of jaggedness (i.e., the presence of single-stranded protruding ends). In contrast, such changes were not observed in mice with Dnase1l3 deletion (Dnase1l3-/-). These results suggested that DNASE1 was an important nuclease contributing to the ucfDNA fragmentation. Western blot analysis revealed that the concentration of DNASE1 protein was higher in urine than DNASE1L3. The native-polyacrylamide gel electrophoresis zymogram showed that DNASE1 activity in urine was higher than that in plasma. Furthermore, the proportion of ucfDNA fragment ends within DNase I hypersensitive sites (DHSs) was significantly increased in Dnase1-deficient mice. In humans, patients with bladder cancer had lower proportions of ucfDNA fragment ends within the DHSs when compared with participants without bladder cancer. The area under the curve (AUC) for differentiating patients with and without bladder cancer was 0.83, suggesting the analysis of ucfDNA fragmentation in the DHSs may have potential for bladder cancer detection. This work revealed the intrinsic links between the nucleases in urine and ucfDNA fragmentomics.
Subject(s)
Cell-Free Nucleic Acids , Urinary Bladder Neoplasms , Animals , Cell-Free Nucleic Acids/genetics , DNA/genetics , Deoxyribonuclease I/genetics , Deoxyribonuclease I/metabolism , Endodeoxyribonucleases/genetics , Endonucleases , Humans , Mice , Mice, Knockout , Urinary Bladder Neoplasms/geneticsABSTRACT
BACKGROUND: The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping. METHODS: We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls). RESULTS: For SNPs within 40â kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185â kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls. CONCLUSIONS: The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications.
Subject(s)
Haplotypes , Noninvasive Prenatal Testing , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Humans , Polymerase Chain Reaction/methods , Female , Noninvasive Prenatal Testing/methods , Pregnancy , Pharmacogenomic Testing/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Sequence Analysis, DNA/methods , Thalassemia/genetics , Thalassemia/diagnosisABSTRACT
BACKGROUND: Nuclear-derived cell-free DNA (cfDNA) molecules in blood plasma are nonrandomly fragmented, bearing a wealth of information related to tissues of origin. DNASE1L3 (deoxyribonuclease 1 like 3) is an important player in shaping the fragmentation of nuclear-derived cfDNA molecules, preferentially generating molecules with 5 CC dinucleotide termini (i.e., 5 CC-end motif). However, the fragment end properties of microbial cfDNA and its clinical implication remain to be explored. METHODS: We performed end motif analysis on microbial cfDNA fragments in plasma samples from patients with sepsis. A sequence context-based normalization method was used to minimize the potential biases for end motif analysis. RESULTS: The end motif profiles of microbial cfDNA appeared to resemble that of nuclear cfDNA (Spearman correlation coefficient: 0.82, P value 0.001). The CC-end motif was the most preferred end motif in microbial cfDNA, suggesting that DNASE1L3 might also play a role in the fragmentation of microbe-derived cfDNA in plasma. Of note, differential end motifs were present between microbial cfDNA originating from infection-causing pathogens (enriched at the CC-end) and contaminating microbial DNA potentially derived from reagents or the environment (nearly random). The use of fragment end signatures allowed differentiation between confirmed pathogens and contaminating microbes, with an area under the receiver operating characteristic curve of 0.99. The performance appeared to be superior to conventional analysis based on microbial cfDNA abundance alone. CONCLUSIONS: The use of fragmentomic features could facilitate the differentiation of underlying contaminating microbes from true pathogens in sepsis. This work demonstrates the potential usefulness of microbial cfDNA fragmentomics in metagenomics analysis.
Subject(s)
Cell-Free Nucleic Acids , Sepsis , Humans , DNA/genetics , Sepsis/diagnosis , DNA FragmentationABSTRACT
BACKGROUND/AIMS: The present study aimed to investigate the serum levels of adiponectin (APN) and adiponectin receptor 1 (AdipoR1) in patients with type 2 diabetes mellitus (T2DM) combined with macrovascular complications (MVC), as well as their correlation with clinical parameters. METHODS: A total of 60 T2DM patients were divided into 2 groups according to the presence of MVC: T2DM + MVC group (n=30) and T2DM group (n=30). Additionally, 30 healthy people were selected as control group (NC group). Clinical data and biological parameters were detected and recorded. T test was performed to compare the differences between two groups, and the results were corrected using Bonferroni method. Meanwhile, the correlation analysis and multiple stepwise regression analysis were used to analyze the association of APN and AdipoR1 with clinical factors. RESULTS: The levels of APN and AdipoR1 were significantly decreased in T2DM group and T2DM + MVC group compared with NC group, with the lowest value in T2DM + MVC group (all P<0.01). Serum APN levels were positively correlated with FINS and TG (r = 0.412, 0.316, respectively; both P<0.05), and negatively correlated with SBP, DBP and LDL-C (r = -0.292, -0.383, -0.334, respectively; all P<0.05). Serum levels of AdipoR1 were positively correlated with APN (r = 0.726, P<0.01), and negatively correlated with BMI, SBP, DBP, FBG, TC and LDL-C (r = -0.440, -0.446, -0.374, -0.444, -0.344, -0.709, respectively; all P<0.01). CONCLUSION: Serum levels of APN and AdipoR1 are significantly lower in T2DM group and T2DM + MVC group, showing lowest value in T2DM + MVC group. APN and AdipoR1 levels may influence glucose and lipid metabolism in T2DM patients.
Subject(s)
Adiponectin/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetic Angiopathies/blood , Lipid Metabolism , Receptors, Adiponectin/blood , Female , Humans , Male , Middle AgedABSTRACT
Grain size and weight are two important determinants of grain yield in rice. Although overexpression of sucrose synthase (SUS) genes has led to several improvements on cellulose and starch-based traits in transgenic crops, little is reported about SUS enhancement of hull size and grain weight in rice. In this study, we selected transgenic rice plants that overexpressed OsSUS1-6 genes driven with the maize Ubi promoter. Compared to the controls (wild type and empty vector line), all independent OsSUS homozygous transgenic lines exhibited considerably increased grain yield and grain weights. Using the representative OsSUS3 overexpressed transgenic plants, four independent homozygous lines showed much raised cell numbers for larger hull sizes, consistent with their enhanced primary cell wall cellulose biosynthesis and postponed secondary wall synthesis. Accordingly, the OsSUS3 transgenic lines contained much larger endosperm volume and higher starch levels than those of the controls in the mature grains, leading to increased brown grain weights by 15-19%. Hence, the results have demonstrated that OsSUS overexpression could significantly improve hull size and grain weight by dynamically regulating cell division and starch accumulation in the transgenic rice.
Subject(s)
Cell Division/genetics , Edible Grain , Glucosyltransferases/metabolism , Oryza/genetics , Oryza/metabolism , Starch/metabolism , Cellulose/biosynthesis , Endosperm/genetics , Endosperm/metabolism , Gene Expression Regulation, Plant , Multigene Family , Oryza/classification , Phenotype , Phylogeny , Plants, Genetically ModifiedABSTRACT
Plant lodging resistance is an important integrative agronomic trait of grain yield and quality in crops. Although extensin proteins are tightly associated with plant cell growth and cell wall construction, little has yet been reported about their impacts on plant lodging resistance. In this study, we isolated a novel extensin-like (OsEXTL) gene in rice, and selected transgenic rice plants that expressed OsEXTL under driven with two distinct promoters. Despite different OsEXTL expression levels, two-promoter-driven OsEXTL-transgenic plants, compared to a rice cultivar and an empty vector, exhibited significantly reduced cell elongation in stem internodes, leading to relatively shorter plant heights by 7%-10%. Meanwhile, the OsEXTL-transgenic plants showed remarkably thickened secondary cell walls with higher cellulose levels in the mature plants, resulting in significantly increased detectable mechanical strength (extension and pushing forces) in the mature transgenic plants. Due to reduced plant height and increased plant mechanical strength, the OsEXTL-transgenic plants were detected with largely enhanced lodging resistances in 3 years field experiments, compared to those of the rice cultivar ZH11. In addition, despite relatively short plant heights, the OsEXTL-transgenic plants maintain normal grain yields and biomass production, owing to their increased cellulose levels and thickened cell walls. Hence, this study demonstrates a largely improved lodging resistance in the OsEXTL-transgenic rice plants, and provides insights into novel extensin functions in plant cell growth and development, cell wall network construction and wall structural remodelling.
Subject(s)
Cell Wall/metabolism , Oryza/metabolism , Plant Stems/metabolism , Cell Wall/physiology , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Oryza/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Stems/physiology , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolismABSTRACT
BACKGROUND LncRNA CASC2 has been established to have critical functions in tumorigenesis but, while its involvement in high-glucose-induced chronic renal failure remains unclear. MATERIAL AND METHODS We included patients with type 2 diabetes combined with chronic renal failure, as well as patients with diabetic retinopathy, diabetic ketoacidosis, diabetic foot infections or diabetic cardiomyopathy, and diabetic patients without any obvious complication, as well as healthy controls. Blood samples and renal tissues were obtained from each participant and expression of lncRNA CASC2 in those tissues was detected by qRT-PCR. Diagnostic value of lncRNA CASC2 for type 2 diabetes combined with chronic renal failure was evaluated by ROC curve analysis. All patients were followed up for 5 years and the occurrence of chronic renal failure was recorded. RESULTS Compared with healthy controls, expression of lncRNA CASC2 in serum and renal tissue was specifically downregulated in patients with type 2 diabetes combined with chronic renal failure but not in type 2 diabetic patients combined with other complications. Follow-up showed that patients with low serum level of lncRNA CASC2 had significantly higher incidence of chronic renal failure. CONCLUSIONS lncRNA CASC2 is a reliable diagnostic biomarker for type 2 diabetes combined with chronic renal failure and low serum level of lncRNA CASC2 predicts the occurrence of chronic renal failure in patients with type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Kidney Failure, Chronic/genetics , RNA, Long Noncoding/blood , Tumor Suppressor Proteins/genetics , Adult , Aged , Case-Control Studies , Cell Proliferation/genetics , Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Down-Regulation , Female , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , RNA, Long Noncoding/genetics , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/genetics , Tumor Suppressor Proteins/bloodABSTRACT
Stress is a crucial factor affecting social decision-making. However, its impacts on the behavioral and neural processes of females' unfairness decision-making remain unclear. Combining computational modeling and functional near-infrared spectroscopy (fNIRS), this study attempted to illuminate the neurocomputational signature of unfairness decision-making in females. We also considered the effect of trait stress coping styles. Forty-four healthy young females (20.98 ± 2.89 years) were randomly assigned to the stress group (n = 21) and the control group (n = 23). Acute psychosocial stress was induced by the Trier Social Stress Test (TSST), and participants then completed the one-shot ultimatum game (UG) as responders. The results showed that acute psychosocial stress reduced the adaptability to fairness and lead to more random decision-making responses. Moreover, in the stress group, a high level of negative coping style predicted more deterministic decision. fNIRS results showed that stress led to an increase of oxy-hemoglobin (HbO) peak in the right temporoparietal junction (rTPJ), while decreased the activation of left middle temporal gyrus (lMTG) when presented the moderately unfair (MU) offers. This signified more involvement of the mentalization and the inhibition of moral processing. Moreover, individuals with higher negative coping scores showed more deterministic decision behaviors under stress. Taken together, our study emphasizes the role of acute psychosocial stress in affecting females' unfairness decision-making mechanisms in social interactions, and provides evidences for the "tend and befriend" pattern based on a cognitive neuroscience perspec.
ABSTRACT
A high-voltage (10 kV) electrostatic antisolvent process was used to prepare methotrexate (MTX)-loaded, large, highly-porous poly-L-lactide (PLLA) microspheres. MTX solution in dimethyl sulfoxide (DMSO) and PLLA solution in dichloromethane (DCM) were homogeneously mixed, and then ammonium bicarbonate (AB) aqueous solution was added. The mixed solution was emulsified by ultrasonication with Pluronic F127 (PF127) as an emulsion stabilizer. The emulsion was electrosprayed by the specific high-voltage apparatus and dropped into a 100 mL of ethanol, which acted as an antisolvent for the solute and extracted DMSO and DCM, causing the co-precipitation of PLLA and MTX, thus forming microspheres with AB aqueous micro-droplets uniformly inlaid. The obtained MTX-PLLA microspheres were subsequently lyophilized to obtain large, highly-porous MTX-PLLA microspheres, which exhibited an identifiable spherical shape and a rough surface furnished with open pores, with a mean particle size of 25.0 µm, mass median aerodynamic diameter of 3.1 ± 0.2 µm, fine-particle fraction of 57.1 ± 1.6 %, and porosity of 81.8 %; furthermore, they offered a sustained release of MTX. X-ray diffraction and Fourier transform-infrared spectra revealed that no crystallinity or alteration of chemical structure occurred during the high-voltage electrostatic antisolvent process, which in this study was proved to have great potential for preparing highly-porous drug-loaded polymer microspheres for use in pulmonary drug delivery.
Subject(s)
Drug Carriers/chemical synthesis , Drug Compounding/methods , Methotrexate/administration & dosage , Microspheres , Polyesters/chemistry , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Delivery Systems , Methotrexate/pharmacokinetics , Models, Biological , Particle Size , Polyesters/chemical synthesis , Porosity , Solvents/pharmacology , Spectroscopy, Fourier Transform Infrared , Static Electricity , Surface Properties , X-Ray DiffractionABSTRACT
To investigate sexual dimorphism of serum pigment epithelium-derived factor (PEDF) and its influencing factors in healthy individuals. A total of 162 healthy people (69 males, 93 females) who underwent health examinations in our department were selected. Serum PEDF, estradiol and other metabolic indices were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were calculated to evaluate insulin resistance and ß-cell function, respectively. Subjects were divided intoâ <â 50 years andâ ≥â 50 years groups to explore the sexual dimorphism of serum PEDF in different age groups. We found no statistically significant difference in serum PEDF levels between men and women in total. However, in the group of subjects under 50 years old, men had significantly higher PEDF levels than women (9.32â ±â 2.07 µg/mL vs 8.24â ±â 2.29 µg/mL, Pâ <â .05), and no sex difference was found in theâ ≥â 50 years group. In women, serum PEDF levels were significantly higher in subjects aged 50 years and over than in those younger than 50 years of age (9.56â ±â 3.05 µg/mL vs 8.25â ±â 2.30 µg/mL, Pâ <â .05). In men, there was no significant difference in serum PEDF levels between the 2 age groups. In women, correlation analysis showed that serum PEDF levels were significantly correlated with body mass index, waist circumference, diastolic blood pressure (DBP), 2-h postprandial glucose, fasting and 2-h postprandial insulin, HOMA-ß, HOMA-IR, aminotransferase, triacylglycerol, and estradiol. Elevated triacylglycerol and aminotransferase and decreased estradiol were significant predictors of increased PEDF concentrations in women. There is sexual dimorphism in circulating PEDF levels, which may be related to estrogen status.
Subject(s)
Serpins , Sex Characteristics , Aged , Female , Humans , Male , Middle Aged , Estradiol , Eye Proteins , Insulin Resistance , Serpins/metabolismABSTRACT
OBJECTIVE: Reninoma is a rare benign tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia via hypersecretion of renin, while it is extremely rare that reninoma induced hypertensive crisis with reversible posterior encephalopathy syndrome (RPES). To improve the clinical understanding for this disease, we conducted a case-analysis. METHODS: To analyze the clinical and pathological data of a case of reninoma-induced hypertensive crisis with reversible posterior encephalopathy syndrome, who was admitted to Peking University First Hospital in November, 2007 and follow-up. RESULTS: This was a 16-year old female patient, onset with suddenly spasm with loss of consciousness, while blood pressure stepped up to 210/140 mm Hg (1 mm Hg = 0.133 kPa), and the head magnetic resonance imaging (MRI) revealed "multiple long-T(2) signal", and hypokalemia (2.8 - 3.2 mmol/L), urine protein positive, ultrasound cardiogram revealed left ventricular hypertrophy, laboratory study revealed hyperreninism (38.23 ng·ml(-1)×h(-1), normal range 0.07 - 1.15 ng·ml(-1)×h(-1)) and hyperaldosteronism (660.9 ng/L, normal range 60 - 174 ng/L), abdominal CT-Scan revealed a mass at right kidney, blood pressure achieved safety range and the head MRI was rechecked and revealed "the abnormal long-T(2) signal disappeared". The clinical diagnosis was reninoma induced hypertensive crisis with RPES. The tumor was resected and the pathologic diagnosis was reninoma. The patient remained normotensive in the postoperative period without any medication. CONCLUSIONS: Reninoma represents a rare but surgically curable cause of hypertension, thus the clinical suspicion of it is very important in young patients. If the diagnosis is confirmed, positive treatment must be done immediately to improve the prognosis. The most common cause of RPES is hypertension, and the diagnosis depends on the distinctive head MRI. There is always a good prognosis with the decline of blood pressure rapidly.
Subject(s)
Hypertension/etiology , Hypertensive Encephalopathy/etiology , Kidney Neoplasms/complications , Adolescent , Female , Humans , Hyperaldosteronism/etiology , Kidney Neoplasms/physiopathology , SyndromeABSTRACT
We aimed to explore the association of BMI in pre-pregnant women with metabolic syndrome in pregnancy in advanced maternal age. A total of 229 maternal women and 536 maternal women participated in this study. Pregnancy women underwent a 75 g-oral glucose tolerance test and maternal lipid profile test between 24 and 28 weeks. Data about biological and sociodemographic characteristics were recorded for each case. The metabolic equivalent (Met) was 9.6% in the maternal age ≥35 group, 5.4% in the age 20-34 group (P = 0.027), and 6.7% in all pregnant women. Results also demonstrated that gestational diabetes mellitus (GDM) and MetS were more likely to appear in the maternal age ≥35 years group than the maternal age 20-34 years group (41.5% vs. 30.6%; P = 0.001, 9.6% vs. 5.4%, P = 0.027). Risk for preterm delivery and eclampsia were increased with raised MetS (RR 3.434 and RR 1.800); MetS in women aged ≥35 years had the largest area under the curve (AUC) (AUC 0.925, 95% CI 0.885-0.965), and its optimal cutoff point was ≥24.998 kg/m2, and the optimal cutoff point for total cholesterol (TC) (AUC 0.686, 95% CI 0.571-.802) predicting MetS was ≥4.955 mmol/l. MetS in pregnancy are associated with the occurrence of preterm delivery and eclampsia, and pre-BMI and TC can predict MetS in the maternal age ≥35 group.
Subject(s)
Eclampsia , Metabolic Syndrome , Premature Birth , Body Mass Index , Female , Humans , Infant, Newborn , Lipids , Maternal Age , Metabolic Syndrome/epidemiology , PregnancyABSTRACT
Single-stranded ends of double-stranded DNA (jagged ends) are more abundant in urinary DNA than in plasma DNA. However, the lengths of jagged ends in urinary DNA remained undetermined, as a previous method used for urinary DNA jagged end sequencing analysis (Jag-seq) relied on unmethylation at CpG sites, limiting the resolution. Here, we performed high-resolution Jag-seq analysis using methylation at non-CpG cytosine sites, allowing determination of exact length of jagged ends. The urinary DNA bore longer jagged ends (~26-nt) than plasma DNA (~17-nt). The jagged end length distribution displayed 10-nt periodicities in urinary DNA, which were much less observable in plasma DNA. Amplitude of the 10-nt periodicities increased in patients with renal cell carcinoma. Heparin treatment of urine diminished the 10-nt periodicities. The urinary DNA jagged ends often extended into nucleosomal cores, suggesting potential interactions with histones. This study has thus advanced our knowledge of jagged ends in urine DNA.
ABSTRACT
BACKGROUND: Diabetes is a chronic disease, which may cause various complications. Patients with diabetes are at high risk of bone and joint disorders, such as osteoporosis and bone fractures. In addition, it became widely accepted that diabetes has an important impact on bone metabolism. Metformin is a commonly used and effective first-line treatment for type 2 diabetes. Some glucose-lowering agents have been found to have an effect on bone metabolism. The present study explored if different doses of metformin have an effect on bone mineral density (BMD) and bone metabolism in type 2 diabetes. AIM: To investigate the effects of different doses of metformin on BMD and bone metabolism in elderly male patients with type 2 diabetes mellitus. METHODS: A total of 120 elderly male outpatients with type 2 diabetes mellitus who were admitted to our hospital were included in the study from July 2018 to June 2019. They were randomly assigned to an experimental group and a control group with 60 patients in each group. Patients in the experimental group were given high dose metformin four times a day 0.5 g each time for 12 wk. Patients in the control group were given low dose metformin orally twice a day 0.5 g each time for 12 wk. The changes in bone mineral density and bone metabolism before and after treatment and the efficacy rate of the treatment were compared between the two groups. RESULTS: There was no significant difference in the efficacy rate between the two groups (P > 0.05). Before the treatment, there was no significant difference in BMD and bone metabolism between the two groups (P > 0.05). However, after the treatment, BMD and bone metabolism were improved in the two groups. Moreover, BMD and 25-hydroxyvitamin D were significantly higher in the experimental group than in the control group, and N-terminal/midregion and ß-isomerized C-terminal telopeptides were significantly lower in the experimental group than in the control group (all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). CONCLUSION: Both high and low dose metformin can effectively control the blood glucose levels in elderly male patients with type 2 diabetes mellitus. However, the benefits of high dose metformin in improving BMD and bone metabolism level was more obvious in patients with type 2 diabetes mellitus.
ABSTRACT
Genetic modification of plant cell walls is an effective approach to reduce lignocellulose recalcitrance in biofuel production, but it may affect plant stress response. Hence, it remains a challenge to reduce biomass recalcitrance and simultaneously enhance stress resistance. In this study, the OsSUS3-transgenic plants exhibited increased cell wall polysaccharides deposition and reduced cellulose crystallinity and xylose/arabinose proportion of hemicellulose, resulting in largely enhanced biomass saccharification and bioethanol production. Additionally, strengthening of the cell wall also contributed to plant biotic resistance. Notably, the transgenic plants increased stress-induced callose accumulation, and promoted the activation of innate immunity, leading to greatly improved multiple resistances to the most destructive diseases and a major pest. Hence, this study demonstrates a significant improvement both in bioethanol production and biotic stress resistance by regulating dynamic carbon partitioning for cellulose and callose biosynthesis in OsSUS3-transgenic plants. Meanwhile, it also provides a potential strategy for plant cell wall modification.
ABSTRACT
Monocyte chemotactant protein-1 (MCP-1), a pro-inflammatory cytokine, plays an important role in inflammatory process. In present study, we evaluated the association of MCP-1 gene rs1024611 polymorphism with risk and clinical characteristics of diabetic foot ulcers (DFUs).This study recruited 116 patients with DFUs, 135 patients with diabetes mellitus (DM) without complications (non-DFU), and 149 healthy controls (HCs). MCP-1 gene rs1024611 polymorphism was genotyped by direct sequencing. The expression of MCP-1 was analyzed using quantitative real-time polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assume the association strength.Individuals with rs1024611 AG and GG genotypes exhibited significantly higher susceptibility to DFUs, in the comparison with HCs (AG vs AA, ORâ=â2.364, 95% CIâ=â1.021-5.470; GG vs AA, ORâ=â2.686, 95% CIâ=â1.154-6.255). Meanwhile, G allele was associated with increased DFUs susceptibility (ORâ=â1.457, 95% CIâ=â1.014-2.093). Besides, rs1024611 SNP was slightly correlated with increased DFUs susceptibility in patients with DM. GG genotype of rs1024611 was significantly correlated with higher epidermal thickness and lower dermis thickness in patients with DFUs (Pâ<â.01). Patients with DFU exhibited upregulation of MCP-1 mRNA, and GG genotype was correlated with enhanced MCP-1 expression in DFU and non-DFU groups.Rs1024611 polymorphism was significantly associated with MCP-1 expression and individual susceptibility to DFUs.
Subject(s)
Chemokine CCL2/genetics , Diabetes Mellitus, Type 2/complications , Diabetic Foot/genetics , Aged , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
OBJECTIVE: To study the distribution and intake of vegetable fiber of Chinese rural residents. METHODS: The vegetable fiber content data were come from the datumbase of ecological survey in 65 Chinese counties in 1983. All food data were grouped under eight areas according to Chinese "Eleven-Five" Programming of State Council. Average value, standard deviation and variances analysis were used to evaluate the distribution of dietary fiber content in vegetables. RESULTS: The consumptions of vegetables in different areas were unbalanced. Radish, kidney bean, eggplant, red pepper, pumpkin, radish leaf, rape, Chinese cabbage, common cabbage, Chinese celery, Chinese leek were widely taken in all area of China, while other vegetables were partly taken in the part area of China. The content distributions of dietary fiber and/or its monomer were also unbalanced. There were statistically significant differences of vegetable fiber and/or its monomer contents in radish, kidney bean, red pepper, pumpkin, common cabbage, sweet potato leaf, spinach, and Chinese leek among the part area of China (P < 0.01, P < 0.05). When the vegetable fiber data were used to evaluate its intake of a rural standard person from vegetables in the national survey of nutrition in 1982, 1992 and 2002, the percentage of its intake to AI were respectively 32.7%, 32.2% and 29.7%. CONCLUSION: The consumptions of vegetables, and its fiber and its monomer contents were unbalanced in different areas all over the country.
Subject(s)
Diet Surveys , Diet , Dietary Fiber/administration & dosage , Vegetables/chemistry , China , Food Analysis , Humans , Rural Population , Sampling StudiesABSTRACT
Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 µIU/mLSubject(s)
Hemostasis
, Hypothyroidism/blood
, Hypothyroidism/drug therapy
, Thyroxine/therapeutic use
, Case-Control Studies
, Female
, Humans
, Middle Aged
, Thyrotropin/blood
ABSTRACT
BRCA1-associated protein-1 (BAP1) is an important nuclear-localized deubiquitinating enzyme. Dysregulation of BAP1 has been reported in many types of cancers. However, there are few articles on the role of BAP1 in osteosarcoma (OS) and the molecular mechanisms of BAP1 in OS remain largely unknown. In this study, we examined the expression of BAP1 in the tissue sample from OS patients and healthy control subjects, and then investigated the biological function and molecular mechanisms of BAP1 in OS. We found that BAP1 was significantly reduced in OS patients and OS cell lines. Then we found that BAP1 has a key role in OS cell proliferation, apoptosis, migration, and invasion. Furthermore, we found that BAP1 exerted its influence on the PI3K/Akt signaling pathway and there was physical association between BAP1 and miR-125. In conclusion, our data highlight the important roles of BAP1 in the survival of OS. It may be a potential therapy for OS.