ABSTRACT
BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.
Subject(s)
Atherosclerosis , Foam Cells , Humans , Mice , Animals , Foam Cells/metabolism , Proprotein Convertase 9/metabolism , Macrophages/metabolism , Atherosclerosis/pathology , Lipoproteins, LDL/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolismABSTRACT
Scaling up superconducting nanowire single-photon detectors (SNSPDs) into a large array for imaging applications is the current pursuit. Although various readout architectures have been proposed, they cannot resolve multiple-photon detections (MPDs) currently, which limits the operation of the SNSPD arrays at high photon flux. In this study, we focused on the readout ambiguity of a superconducting nanowire single-photon imager applying time-of-flight multiplexing readout. The results showed that image distortion depended on both the incident photon flux and the imaging object. By extracting multiple-photon detections on idle pixels, which were virtual because of the incorrect mapping from the ambiguous readout, a correction method was proposed. An improvement factor of 1.3~9.3 at a photon flux of µ = 5 photon/pulse was obtained, which indicated that joint development of the pixel design and restoration algorithm could compensate for the readout ambiguity and increase the dynamic range.
ABSTRACT
A superconducting nanowire single-photon imager (SNSPI) uses a time-multiplexing method to reduce the readout complexity. However, due to the serial connection, the nanowire should be uniform so that a common bias can set all segments of the nanowire to their maximum detection efficiency, which becomes more challenging as the scalability (i.e., the length of the nanowire) increases. Here, we have developed a 64-pixel SNSPI based on amorphous Mo80Si20 film, which yielded a uniform nanowire and slow transmission line. Adjacent detectors were separated by delay lines, giving an imaging field of 270 µm × 240 µm. Benefiting from the high kinetic inductance of Mo80Si20 films, the delay line gave a phase velocity as low as 4.6 µm/ps. The positions of all pixels can be read out with a negligible electrical cross talk of 0.02% by using cryogenic amplifiers. The timing jitter was 100.8 ps. Saturated internal quantum efficiency was observed at a wavelength of 1550â nm. These results demonstrate that amorphous film is a promising material for achieving SNSPIs with large scalability and high efficiency.
ABSTRACT
Osteoarthritis (OA) is the most common arthritis with a rapidly increasing prevalence. Disease progression is irreversible, and there is no curative therapy available. During OA onset, abnormal mechanical loading leads to excessive osteoclastogenesis and bone resorption in subchondral bone, causing a rapid subchondral bone turnover, cyst formation, sclerosis, and finally, articular cartilage degeneration. Moreover, osteoclast-mediated angiogenesis and sensory innervation in subchondral bone result in abnormal vascularization and OA pain. The traditional Chinese medicine Panax notoginseng (PN; Sanqi) has long been used in treatment of bone diseases including osteoporosis, bone fracture, and OA. In this study we established two-dimensional/bone marrow mononuclear cell/cell membrane chromatography/time of flight mass spectrometry (2D/BMMC/CMC/TOFMS) technique and discovered that diterbutyl phthalate (DP) was the active constituent in PN inhibiting osteoclastogenesis. Then we explored the therapeutic effect of DP in an OA mouse model with anterior cruciate ligament transaction (ACLT). After ACLT was conducted, the mice received DP (5 mg·kg-1·d-1, ip) for 8 weeks. Whole knee joint tissues of the right limb were harvested at weeks 2, 4, and 8 for analysis. We showed that DP administration impeded overactivated osteoclastogenesis in subchondral bone and ameliorated articular cartilage deterioration. DP administration blunted aberrant H-type vessel formation in subchondral bone marrow and alleviated OA pain assessed in Von Frey test and thermal plantar test. In RANKL-induced RAW264.7 cells in vitro, DP (20 µM) retarded osteoclastogenesis by suppressing osteoclast fusion through inhibition of the ERK/c-fos/NFATc1 pathway. DP treatment also downregulated the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of the vacuolar (H+) ATPase V0 domain (Atp6v0d2) in the cells. In conclusion, we demonstrate that DP prevents OA progression by inhibiting abnormal osteoclastogenesis and associated angiogenesis and neurogenesis in subchondral bone.
Subject(s)
Osteoarthritis , Osteoclasts , Animals , Anterior Cruciate Ligament/metabolism , Mice , NFATC Transcription Factors/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/etiology , Osteoarthritis/metabolism , Osteoclasts/metabolism , Pain/metabolism , Phthalic AcidsABSTRACT
As an important ecological barrier for the North China Plain, research on the spatial variations of soil nutrients in the southern foot of the Taihang Mountains is of great significance for the forestry ecological construction in this rocky mountainous area. With the typical slopes (the artificial forestland and the natural wild slope) of the southern foot of the Taihang Mountains as the research objects, we used the grid method to arrange sampling points, and combined classical statistics, geostatistics and constrained sorting methods to analyze the spatial variations of soil nutrients. The results showed that: 1) soil total carbon (TC) contents were 6.80-57.05 g·kg-1, and the total nitrogen (TN) contents were 0.74-3.93 g·kg-1. The coefficients of variation of both soil TC and TN were 25.0%-52.8%, belonging to the moderate degree of variation, which were caused by the combination of random and structural factors. The spatial aggregation of soil nutrients decreased with increasing lag distances. 2) The contents of soil nutrients had increasing trends from the top to the bottom of the slopes, with high nutrient values appearing at the bottom of the slopes. 3) The soil bulk density, gravel content, vegetation coverage, and soil water content were the main factors affecting the spatial variability of soil TC and TN on the southern foot of the Taihang Mountains. 4) Soil water content was the main factor affecting soil nutrients at the natural wild slope, but not at the artificial forestland.
Subject(s)
Nitrogen , Soil , Carbon/analysis , China , Forests , Nitrogen/analysisABSTRACT
AIMS: Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin-ASK1 pathway, not the classical calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis. METHODS AND RESULTS: Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages. CONCLUSION: Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.
Subject(s)
Atherosclerosis , MicroRNAs , Animals , Atherosclerosis/genetics , Foam Cells , Humans , Leukocytes, Mononuclear , Mice , MicroRNAs/genetics , NFATC Transcription Factors/genetics , Proprotein Convertase 9ABSTRACT
BACKGROUND: Feature extraction from photoplethysmography (PPG) signals is an essential step to analyze vascular and hemodynamic information. Different morphologies of PPG waveforms from different measurement sites appear. Various phenomena of missing or ambiguous features exist, which limit subsequent signal processing. METHODS: The reasons that cause missing or ambiguous features of finger and wrist PPG pulses are analyzed based on the concept of component waves from pulse decomposition. Then, a systematic approach for missing-feature imputation and ambiguous-feature resolution is proposed. RESULTS: From the experimental results, with the imputation and ambiguity resolution technique, features from 35,036 (98.7%) of 35,502 finger PPG cycles and 36307 (99.1%) of 36,652 wrist PPG cycles can be successfully identified. The extracted features became more stable and the standard deviations of their distributions were reduced. Furthermore, significant correlations up to 0.92 were shown between the finger and wrist PPG waveforms regarding the positions and widths of the third to fifth component waves. CONCLUSION: The proposed missing-feature imputation and ambiguous-feature resolution solve the problems encountered during PPG feature extraction and expand the feature availability for further processing. More intrinsic properties of finger and wrist PPG are revealed. The coherence between the finger and wrist PPG waveforms enhances the applicability of the wrist PPG.
Subject(s)
Photoplethysmography , Wrist , Fingers , Heart Rate , Signal Processing, Computer-AssistedABSTRACT
Chloride (Cl-) homeostasis is of great significance in cardiovascular system. Serum Cl- level is inversely associated with the mortality of patients with heart failure. Considering the importance of angiogenesis in the progress of heart failure, this study aims to investigate whether and how reduced intracellular Cl- concentration ([Cl-]i) affects angiogenesis. Human umbilical endothelial cells (HUVECs) were treated with normal Cl- medium or low Cl- medium. We showed that reduction of [Cl-]i (from 33.2 to 16.18 mM) inhibited HUVEC proliferation, migration, cytoskeleton reorganization, tube formation, and subsequently suppressed angiogenesis under basal condition, and VEGF stimulation or hypoxia treatment. Moreover, VEGF-induced NADPH-mediated reactive oxygen species (ROS) generation and VEGFR2 axis activation were markedly attenuated in low Cl- medium. We revealed that lowering [Cl-]i inhibited the expression of the membrane-bound catalytic subunits of NADPH, i.e., p22phox and Nox2, and blunted the translocation of cytosolic regulatory subunits p47phox and p67phox, thereby restricting NADPH oxidase complex formation and activation. Furthermore, reduced [Cl-]i enhanced ROS-associated protein tyrosine phosphatase 1B (PTP1B) activity and increased the interaction of VEGFR2 and PTP1B. Pharmacological inhibition of PTP1B reversed the effect of lowering [Cl-]i on VEGFR2 phosphorylation and angiogenesis. In mouse hind limb ischemia model, blockade of Cl- efflux using Cl- channel inhibitors DIDS or DCPIB (10 mg/kg, i.m., every other day for 2 weeks) significantly enhanced blood flow recovery and new capillaries formation. In conclusion, decrease of [Cl-]i suppresses angiogenesis via inhibiting oxidase stress-mediated VEGFR2 signaling activation by preventing NADPH oxidase complex formation and promoting VEGFR2/PTP1B association, suggesting that modulation of [Cl-]i may be a novel therapeutic avenue for the treatment of angiogenic dysfunction-associated diseases.
Subject(s)
Chlorides/metabolism , Neovascularization, Physiologic/physiology , Oxidative Stress/physiology , Vascular Endothelial Growth Factor Receptor-2/metabolism , Actin Cytoskeleton/physiology , Animals , Cell Movement/physiology , Cell Proliferation/physiology , Hindlimb/blood supply , Human Umbilical Vein Endothelial Cells , Humans , Ischemia/metabolism , Mice, Inbred C57BL , NADPH Oxidase 2/metabolism , NADPH Oxidases/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Combining organic fertilizer with chemical fertilizer may affect the microbial processes related to nitrous oxide (N2O) emissions under different degrees of soil salinization. A mild saline soil (S1; electrical conductivity (EC) 0.46 dS·m-1) and moderate saline soil (S2; EC 1.07 dS·m-1) in the Hetao irrigation district of Inner Mongolia were selected. Under equal N rates, the study involved five treatments:U1 (240 kg·hm-2 of chemical fertilizer), U3O1 (180 kg·hm-2 of chemical fertilizer+60 kg·hm-2 of organic fertilizer), U1O1 (120 kg·hm-2 of chemical fertilizer+120 kg·hm-2 of organic fertilizer), U1O3 (60 kg·hm-2 of chemical fertilizer+180 kg·hm-2 of organic fertilizer), and O1 (240 kg·hm-2 of organic fertilizer). In addition, a blank control treatment (CK) was employed to investigate the effects of different fertilization treatments on the N2O emissions from the two saline soils. The results showed that the total N2O emissions from the S2 soil in the same treatment were between 11.86% and 47.23% higher than those from the S1 soil (P<0.05). the dynamic trend of the soil N2O fluxes among the different treatments were similar. The peak N2O emissions occurred after fertilization, and the N2O cumulative emission fluxes accounted for nearly 60% of the emissions during the entire growth period. The proper application of organic fertilizer could significantly reduce the soil N2O emission; the S1 and S2 saline soils treated with U1O1 and O1, respectively, had the lowest N2O emissions, whereby there were significant reductions of 33.62% and 28.51% in comparison to the U1 treatment (P<0.05). Moreover, higher maize yields could be obtained and the N2O flux was significantly positively correlated with the NH4+-N content (P<0.01) but negatively correlated with the NO3--N content. The results demonstrated that nitrification was the main way to produce N2O in the studied salinized maize farmland, and that the addition of organic fertilizer could reduce the N2O production by decreasing the soil NH4+-N content. Based on the changes in the corn yield and a reduction in the greenhouse effect, suitable organic and inorganic fertilizer management models for the Hetao irrigation area were the mild saline soil:120 kg·hm-2 of urea +120 kg·hm-2 of organic fertilizer), and the moderate saline soil:240 kg·hm-2 of organic fertilizer.
Subject(s)
Fertilizers , Soil , Agriculture , China , Fertilizers/analysis , Nitrogen , Nitrous Oxide/analysisABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease, and the mechanisms underpinning its pathogenesis have not been completely established. Transmembrane member 16A (TMEM16A), a component of the Ca2+-activated chloride channel (CaCC), has recently been implicated in metabolic events. Herein, TMEM16A is shown to be responsible for CaCC activation in hepatocytes and is increased in liver tissues of mice and patients with NAFLD. Hepatocyte-specific ablation of TMEM16A in mice ameliorates high-fat diet-induced obesity, hepatic glucose metabolic disorder, steatosis, insulin resistance, and inflammation. In contrast, hepatocyte-specific TMEM16A transgenic mice exhibit the opposite phenotype. Mechanistically, hepatocyte TMEM16A interacts with vesicle-associated membrane protein 3 (VAMP3) to induce its degradation, suppressing the formation of the VAMP3/syntaxin 4 and VAMP3/synaptosome-associated protein 23 complexes. This leads to the impairment of hepatic glucose transporter 2 (GLUT2) translocation and glucose uptake. Notably, VAMP3 overexpression restrains the functions of hepatocyte TMEM16A in blocking GLUT2 translocation and promoting lipid deposition, insulin resistance, and inflammation. In contrast, VAMP3 knockdown reverses the beneficial effects of TMEM16A downregulation. This study demonstrates a role for TMEM16A in NAFLD and suggests that inhibition of hepatic TMEM16A or disruption of TMEM16A/VAMP3 interaction may provide a new potential therapeutic strategy for NAFLD.
ABSTRACT
BACKGROUND: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5- dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism. METHODS: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema. RESULTS: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of 1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1ß and 6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase- 2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production. CONCLUSION: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives, especially compound 7, represent potential value for antiinflammatory drug development.
Subject(s)
Anti-Inflammatory Agents , Cinnamates , Lipoxygenase Inhibitors , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arachidonate 5-Lipoxygenase/metabolism , Arachidonic Acid , Calcimycin/pharmacology , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Cinnamates/chemical synthesis , Cinnamates/pharmacology , Cinnamates/therapeutic use , Cyclooxygenase 2/metabolism , Cytokines/genetics , Cytokines/immunology , Dinoprostone/metabolism , Ear/pathology , Edema/chemically induced , Edema/drug therapy , Edema/immunology , Edema/pathology , Female , Lipopolysaccharides , Lipoxygenase Inhibitors/chemical synthesis , Lipoxygenase Inhibitors/pharmacology , Lipoxygenase Inhibitors/therapeutic use , Mice, Inbred BALB C , Peroxidase/immunology , RNA, Messenger/metabolism , Rats , Tetradecanoylphorbol AcetateABSTRACT
Denitrification-decomposition (DNDC) model can estimate the emission fluxes of soil trace gases such as carbon dioxide (CO2), methane (CH4) , and nitrous oxide (N2O) via the coupling of the denitrification and decomposition processes driven by soil environmental factors. At present, DNDC model is one of the most successful models in the world in simulating the terrestrial biogeochemical cycles. This paper mainly reviewed the development process of the DNDC model, its structure, model validation, and sensitive factor analysis, and summarized the hot fields in the applications of the model.
Subject(s)
Greenhouse Effect , Methane/analysis , Models, Theoretical , Soil Pollutants/analysis , Carbon Dioxide/analysis , Denitrification , Gases/analysis , Nitrous Oxide/analysis , Soil/chemistryABSTRACT
Contents and density of soil organic carbon (SOC) in soil profiles and dissolved organic carbon (DOC) of soil solution in different soil depths in wetland, soybean and paddy field reclaimed from the wetland around Xingkai Lake were determined to investigate how reclamation of wetland for soybean and rice farming impacts vertical distribution of SOC and retention of DOC. SOC contents in 0-40 cm soil layers were significantly influenced. SOC contents in 0-10, 10-20, 20-30 and 30-40 cm soil layers in soybean and paddy field were 79.07% and 82.01%, 79.01% and 82.28%, 79.86% and 92.90%, 37.49% and 78.05% respectively lower than those in wetland. Before and after reclamation, SOC contents in soil layers deeper than 40 cm were not significantly different. SOC densities in soybean and paddy field were 25.50% and 47.35% respectively lower than those in wetland. However, either in wetland or farm land, most of the SOC storage in 0-100 cm soil layer was stored in 0-50 cm soil layer. The relationships between SOC content and soil depth in wetland and two farm lands all could be described by exponential functions; cultivation did not change the variation of SOC content with soil depth. The retention of DOC was more obvious for soybean farming than wetland and rice farming, and that was roughly the same for wetland as rice farming.
Subject(s)
Carbon/analysis , Organic Chemicals/analysis , Soil/chemistry , Wetlands , Agriculture/methods , Lakes , Oryza/growth & development , Solubility , Glycine max/growth & developmentABSTRACT
OBJECTIVE: To analyze Helicobacter pylori infection in the gastric mucosa of patients with HIV/AIDS in different clinical stages. METHODS: This study involved 170 patients with HIV/AIDS and 34 HIV-negative patients. All the patients underwent upper endoscopy and antral gastric biopsy to determine the status of Helicobacter pylori infection using aniline red staining and rapid urease test. The patients with HIV/AIDS were stratified based on CD4(+)T lymphocyte counts and clinical setting into asymptomatic HIV infection (A1, A2) group, symptomatic HIV infection (B1, B2) group and AIDS (A3, B3, C1-3) group. RESULTS: The prevalence of Helicobacter pylori infection in HIV/AIDS patients was 16.5% (28/170), and in the 3 groups classified, the infection rates were 23.4% (11/47), 14.0% (8/57), and 13.6% (9/66), respectively; the infection rate was 47.1% (16/34) in the control group. Helicobacter pylori infection rate in the gastric mucosa of the patients with HIV/AIDS in different clinical stages was significantly lower than that of the control group (P<0.05); the infection rates in symptomatic HIV-infected (B1, B2) group and AIDS (A3, B3, C1-3) group were significantly lower than that in asymptomatic HIV-infected (A1, A2) group (P<0.05). CONCLUSION: The low Helicobacter pylori infection rate in HIV/AIDS patients may result from severe immunodeficiency in the gastric mucosa.
Subject(s)
Acquired Immunodeficiency Syndrome/microbiology , Gastric Mucosa/microbiology , HIV Infections/microbiology , Helicobacter Infections/epidemiology , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/pathology , Acquired Immunodeficiency Syndrome/pathology , Adult , Female , Gastroscopy , HIV Infections/pathology , Helicobacter Infections/pathology , Helicobacter pylori , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) encompasses a histopathological spectrum of clinical conditions such as simple fatty liver (steatosis), nonalcoholic steatohepatitis (NASH), and a variant that has degrees of fibrosis. Tumor Necrosis Factor-alpha (TNF-alphalpha) is considered essential for NAFLD. Therefore, we investigated the correlation between TNF-alphalpha gene promoter polymorphism and NAFLD in this human study. PATIENTS AND METHODS: The TNF-alpha gene polymorphisms at position -238 and -308 were analyzed in 189 Chinese patients with NAFLD and 138 healthy controls by using polymerase chain reaction and restriction fragment length polymorphism assay. The serum levels of TNF-alpha in both patient and control groups were measured by ELISA. The associations of TNF-alpha polymorphism and serum TNF-alpha, and/or insulin resistance, and/or clinical features were analyzed. RESULTS: The carrier frequencies of TNF-alpha gene polymorphism with G/A mutation at -238 were significantly higher in the patients with NAFLD than those in the control subjects (p < 0.05). However, there were no significant differences between the NAFLD patients and control subjects in the polymorphisms at -308 (p > 0.05). In addition, the serum level of TNF-alpha was markedly higher in the patients with NAFLD than in the control subjects (p < 0.05). There were significant associations between TNF-alpha gene polymorphism in the -238 A allele and increased serum TNF-alpha, insulin resistance, as well as increased body mass index in the NAFLD patients. CONCLUSIONS: The results indicate that the TNF-alpha gene polymorphism at position -238 is associated with susceptibility of nonalcoholic Fatty Liver Disease in a Chinese population.
Subject(s)
Fatty Liver/genetics , Promoter Regions, Genetic , Tumor Necrosis Factor-alpha/genetics , Asian People , Female , Heterozygote , Humans , Male , Middle Aged , Polymorphism, Genetic , Tumor Necrosis Factor-alpha/bloodABSTRACT
OBJECTIVE: To investigate the relationship among serum leptin, homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI) and dyslipidema in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Eighty-two patients with NAFLD were divided into mild, moderate and severe NAFLD groups according histological examination results of the liver. Twenty healthy volunteers were chosen as the normal control (NC) group. Fasting insulin, glucose, leptin and lipid levels were measured in the 82 patients with NAFLD and the BMI calculated. IR index of the patients was calculated according to the HOMA method. RESULTS: Leptin, HOMA-IR index, BMI and dyslipidemia showed significant differences between NAFLD and NC groups (P<0.05 or 0.01). Leptin and HOMA-IR index increased with the exacerbation of NAFLD, both of which were positively correlated with the severity of NAFLD. CONCLUSION: Increased leptin level, HOMA-IR, BMI and dyslipidemia can be important risk factors of NAFLD, and serum leptin level and HOMA-IR are positively correlated with the severity of NAFLD.
Subject(s)
Fatty Liver/blood , Insulin Resistance , Leptin/blood , Adult , Aged , Body Mass Index , Dyslipidemias/complications , Fatty Liver/etiology , Female , Humans , Male , Middle Aged , Risk FactorsABSTRACT
OBJECTIVE: To investigate the appropriate ratio of liquid/powder and use of radiopaque agent in EH composite material for percutaneous vertebroplasty (PVP). METHODS: (1) EH composite material was divided into 6 groups. The material without contrast with the liquid/powder ratios 8:9, 8:8, and 8:7 was classifieds as groups I, II, and III; and the EH composite material with the liquid/powder ratios 8:9, 8:8, and 8:7 and with the addition of 20% barium sulfate by weight was classified as the groups IV, V, and VI. The curing temperature was measured. The bone cement of different groups was made into cylinders to be X-rayed to observe the opacity. Universal tester was used to examine the strength and stiffness. (2) The vertebrae (T8 approximately L5) were isolated from the cadaver of an elder female patient with osteoporosis. Universal tester was used to examine the strength and stiffness of the vertebral bodies (VBs). Osteoporotic vertebral compression fracture (OVCF) model was made. PVP procedure was mimicked by puncturing through the bilateral pedicle of vertebral arch into the anterior 1/3 of the vertebral bodies and the EH composite materials of the groups II and V were injected into the VBs Then the temperatures of the geometric center (CT) and spinal canal posterior wall (PT) of the VBs were measured in a water bath with the temperature of 37 degrees C. Twenty-four hours later the vertebrae underwent X-ray examination to observe the opacity and underwent examination of strength and stiffness with universal tester. RESULTS: (1) The sticking periods (?) of the groups IV, V, and VI were significantly longer than those of the corresponding groups I, II, and III respectively by about 60 s, and the highest temperature of the groups IV, V, and VI were significantly lower than those of the corresponding groups I, II, and III respectively. Addition1 of barium sulfate increased the opacity of the bone cement, but did nor significantly influence the strength of the bone cement. The properties of the group V was the best. (2) The bone cement was easy to be injected into the VBs. The peak PT was not beyond 50 degrees C. After the injection of the bone cement of the groups II, the strength and stiffness of the VB were (1501.6 +/- 5.0) N/mm and (285.6 +/-) N/mm, both significantly higher than those before the injection [(547.5 +/- 3.1) N/mm and (104.1 +/- 1.3) N/mm]; and after the injection of the bone cement of the groups V, the strength and stiffness of the VB were (1355.0 +/- 4.5) N/mm and (257.7 +/- 1.9), both significantly higher than those before the injection [(543.8 +/- 2.7) N/mm and (103.4 +/- 1.1) N/mm]. The opacity of the VBs injected with the bone cement of the group V was better than those injected with the bone cement of the group II. CONCLUSION: The EH (8/8) with 20% barium sulfate is a proper and effective filling material for the treatment of OVCF.