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1.
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease which is characterized by dysregulation of various cytokines propagating the inflammatory processes that is responsible for tissue damage. Tumor necrosis factor alpha (TNF-α) is one of the most important immunoregulatory cytokines that has been implicated in the different autoimmune diseases including SLE. Two hundred and two patients with SLE and 318 controls were included in the study. The TNF-α gene promoter region (from − 250 to − 1000 base pairs) was analyzed by direct Sanger’s DNA sequencing method to find promoter variants associated with South Indian SLE patients. We have analyzed six TNF-α genetic polymorphisms including, − 863C/A (rs1800630), − 857C/T (rs1799724), − 806C/T (rs4248158), − 646G/A (rs4248160), − 572A/C (rs4248161) and − 308G/A (rs1800629) in both SLE patients and controls. We did not find association of TNF-α gene promoter SNPs with SLE patients. However, the − 863A (rs1800630) allele showed association with lupus nephritis phenotype in patients with SLE (OR: 1.62, 95%CI 1.04–2.53, P = 0.034). We found serum TNF-α level was significantly elevated in SLE cases as compared to control and found no association with any of the polymorphisms. The haplotype analysis revealed a significant protective association between the wild TNF-α alleles at positions − 863C, − 857C, − 806C, − 646G, − 572A and − 308G (CCCGAG) haplotype with lupus nephritis phenotype (OR 0.53, 95% CI 0.35–0.82, P = 0.004). Additionally, the TNF-α − 863 C/A (rs1800630) polymorphism and HLA-DRB1*07 haplotype showed significant differences between SLE patients and controls (OR 4.79, 95% CI 1.73–13.29, P = 0.0009). In conclusion, TNF-α − 863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-α − 863 C/A promoter polymorphism giving supportive evidence for the tight linkage disequilibrium between TNF-α promoter SNPs and MHC class II DRB1 alleles.  相似文献   

2.
Severe hemolytic anemia in β-thalassemia major and β-thalassemias/HbE (β-TM) patients requires giving blood transfusions. Chronic blood transfusions lead to iron overload consequence with organs damage and risk of alloantibody-formation. This study evaluates the prevalence of red cell alloimmunization and estimates the risk of alloantibody-formation in chronic transfusion-dependent β-TM patients. This cross sectional study was conducted on 143 β-TM patients receiving regular transfusions. We tried to determine the frequency, types and factors influencing red cell alloimmunization in these transfusion-dependent β-TM patients. Median age of 25 (17.5 %) alloantibody-formation β-TM patients was 19.0 years (inter quartile 15.5–24.0 years). The alloantibodies were Anti-Rh (E) (13.1 %), Anti-Rh (D) (0.7 %). Thirty-four patients (23.8 %) of the sample had splenectomies of which 10 (29.4 %) had alloantibody-formation. The interval from first transfusion to antibody development varied from 1.5 to 14 years. Alloantibody-formation correlated with splenectomy and splenectomy correlated with number of transfusion (p < 0.005). In multiple logistic regression used to estimate the risk of alloantibodies formation with splenectomy; OR and 95 % CI were 2.88 (1.07–7.80), p = 0.037 after adjusting for other co-variates. The rate of red cell alloimmunization was 17.5 % and splenectomy associated with increased alloantibody-formation in these transfusion-dependent β-TM patients.  相似文献   

3.
Deterministic lateral displacement (DLD) is a microfluidic size-based particle separation or filter technology with applications in cell separation and enrichment. Currently, there are no cost-effective manufacturing methods for this promising microfluidic technology. In this fabrication paper, however, we develop a simple, yet robust protocol for thermoplastic DLD devices using regulatory-approved materials and biocompatible methods. The final standalone device allowed for volumetric flow rates of 660 μl min−1 while reducing the manufacturing time to <1 h. Optical profilometry and image analysis were employed to assess manufacturing accuracy and precision; the average replicated post height was 0.48% less than the average post height on the master mold and the average replicated array pitch was 1.1% less than the original design with replicated posts heights of 62.1 ± 5.1 μm (mean ± 6 standard deviations) and replicated array pitches of 35.6 ± 0.31 μm.  相似文献   

4.
Genetic sequence and hyper-methylation profile information from the promoter regions of tumor suppressor genes are important for cancer disease investigation. Since hyper-methylated DNA (hm-DNA) is typically present in ultra-low concentrations in biological samples, such as stool, urine, and saliva, sample enrichment and amplification is typically required before detection. We present a rapid microfluidic solid phase extraction (μSPE) system for the capture and elution of low concentrations of hm-DNA (≤1 ng ml−1), based on a protein-DNA capture surface, into small volumes using a passive microfluidic lab-on-a-chip platform. All assay steps have been qualitatively characterized using a real-time surface plasmon resonance (SPR) biosensor, and quantitatively characterized using fluorescence spectroscopy. The hm-DNA capture/elution process requires less than 5 min with an efficiency of 71% using a 25 μl elution volume and 92% efficiency using a 100 μl elution volume.  相似文献   

5.
End stage renal disease (ESRD) patients on hemodialysis (HD) have an increased oxidative stress, with a high risk of atherosclerosis and other co-morbid conditions. Recent studies have suggested that myeloperoxidase (MPO)—mediated oxidative stress may play a role in the pathogenesis of cardiovascular complications in dialysis patients. Furthermore, dialysis treatment ‘per se’ can aggravate oxidative stress. Hence this study was designed to determine whether HD leads to an alteration in the plasma levels of MPO and malondialdehyde (MDA), a marker of oxidative stress in ESRD patients on maintenance HD. To study the effect of HD, plasma MPO and MDA were determined before and after HD in forty ESRD patients (24 men and 16 women, age between 8 and 71 years, median being 40.5 years) on maintenance HD. Plasma MPO and MDA were assayed by spectrophotometric methods. Haematological and other biochemical parameters were obtained from patients’ case records. Plasma MPO and MDA levels were significantly higher after HD when compared with pre-dialysis levels (p < 0.05). There was no correlation between MPO and MDA (r = 0.184, p = 0.10) and other biochemical parameters (p > 0.05). However, there was a significant correlation between MPO and MDA with haemodialysis vintage (p < 0.05). In univariate regression analysis duration of HD (β = 1.470, p = 0.045, β = 0.388, p = 0.013), was independently associated with MPO and MDA. Although HD is indispensable for survival of patients with ESRD, it is fraught with undesirable side-effects, such as an increase in the plasma MPO and MDA levels. The elevated levels of MPO contribute to the increased oxidative stress as free radicals are produced by the reaction catalyzed by it.  相似文献   

6.
The main objective of this study is to evaluate the anti-hypertrophic potential of the aqueous extract of Enicostemma littorale (E. littorale) against isoproterenol induced cardiac hypertrophic rat models (male albino Wistar rats) through biochemical investigations. Aqueous extract of E. littorale known for various beneficial properties was administered (100 mg/kg, 12 days, oral) to isoproterenol (ISO) induced cardiac hypertrophic rats (low ISO—60 mg/kg, 12 days and high ISO—100 mg/kg, 12 days, subcutaneous) and were compared with group that was treated with the reference drug, Losartan (10 mg kg, administered for 12 days, oral). The anti-hypertrophic effect of E. littorale was evaluated by analysing the morphometric indices of the heart, ECG tracings, changes in blood biochemical parameters viz., serum glucose, serum total protein, serum albumin, lipid profile, cardiac specific enzymes (SGOT, SGPT and LDH) and histopathological examination of the heart tissue. The results fundamentally revealed that the plant extract efficiently ameliorated cardiac hypertrophy induced by ISO injected in experimental rats. The outcomes of biochemical investigations of this study highlighted the association between the hypertrophic β-adrenergic receptor signalling (β-AR) and the 5′ AMP-activated protein kinase (AMPK)—peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) axis in the metabolism of cardiac fibrosis and hypertrophy. This β-AR/AMPK-PGC1α signalling stem can serve as a key target in ameliorating cardiac hypertrophy through focus on its principal regulators. To add, we also propose that the glycoside, swertiamarin present in this plant with the reported anti-fibrotic potential in liver can be further isolated and evaluated for its anti-hypertrophic potential to treat cardiac hypertrophy.  相似文献   

7.
Activated carbon fabrics (ACF) mask prevents the absorption of lead and reduce its adverse effects of human health. Aim of this study to know the blood lead level and its effects on heme biosynthesis and hematological parameters after using 2 months activated carbon fabric mask of battery manufacturing workers (BMW). Blood lead level, heme biosynthesis and hematological parameters were measured by using standard method. Blood lead level (P < 0.001, − 13.5%) was significantly decreased, activated δ-aminolevulinic acid dehydratase (P < 0.001, 11.97%) and non-activated δ- aminolevulinic acid dehydratase (P < 0.001, 23.17%) enzyme activity were significantly increased, however, the ratio of activated to Non-activated δ- ALAD (P < 0.001, − 10.13%) was significantly decreased, urinary excretion of δ- aminolevulinic acid (P < 0.001, − 10.49%) and porphobilinogen (P < 0.001, − 7.38%) were significantly decreased after using 2 months ACF mask as compared to before using mask of BMW. Hematological parameters i.e Hb (P < 0.05, 13.42%), PCV (P < 0.05, 7.23%), MCV (P < 0.05, 1.9%) were significantly increased and total WBC count (P < 0.05, − 5.18%) was significantly decreased after using 2 months ACF mask as compared to before using mask of BMW. Two months using ACF mask reduces the blood lead level and improves the δ-ALDH activity and hematological parameters, decreases the urinary excretion of δ-ALA, PBG of battery manufacturing workers. Therefore, the regular using of ACF mask is beneficial to prevent the lead absorption and its adverse effects on human health.  相似文献   

8.
For the first time, we report on the preliminary evaluation of gold coated optical fibers (GCOFs) as three-dimensional (3D) electrodes for a membraneless glucose/O2 enzymatic biofuel cell. Two off-the-shelf 125 μm diameter GCOFs were integrated into a 3D microfluidic chip fabricated via rapid prototyping. Using soluble enzymes and a 10 mM glucose solution flowing at an average velocity of 16 mm s−1 along 3 mm long GCOFs, the maximum power density reached 30.0 ± 0.1 μW cm−2 at a current density of 160.6 ± 0.3 μA cm−2. Bundles composed of multiple GCOFs could further enhance these first results while serving as substrates for enzyme immobilization.  相似文献   

9.
Separation and sorting of biological entities (viruses, bacteria, and cells) is a critical step in any microfluidic lab-on-a-chip device. Acoustofluidics platforms have demonstrated their ability to use physical characteristics of cells to perform label-free separation. Bandpass-type sorting methods of medium-sized entities from a mixture have been presented using acoustic techniques; however, they require multiple transducers, lack support for various target populations, can be sensitive to flow variations, or have not been verified for continuous flow sorting of biological cells. To our knowledge, this paper presents the first acoustic bandpass method that overcomes all these limitations and presents an inherently reconfigurable technique with a single transducer pair for stable continuous flow sorting of blood cells. The sorting method is first demonstrated for polystyrene particles of sizes 6, 10, and 14.5 μm in diameter with measured purity and efficiency coefficients above 75 ± 6% and 85 ± 9%, respectively. The sorting strategy was further validated in the separation of red blood cells from white blood cells and 1 μm polystyrene particles with 78 ± 8% efficiency and 74 ± 6% purity, respectively, at a flow rate of at least 1 μl/min, enabling to process finger prick blood samples within minutes.  相似文献   

10.
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11.
As a non-invasive therapeutic method without penetration-depth limitation, magnetic hyperthermia therapy (MHT) under alternating magnetic field (AMF) is a clinically promising thermal therapy. However, the poor heating conversion efficiency and lack of stimulus–response obstruct the clinical application of magnetofluid-mediated MHT. Here, we develop a ferrimagnetic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane) (mPEG-b-PHEP) copolymer micelle loaded with hydrophobic iron oxide nanocubes and emodin (denoted as EMM). Besides an enhanced magnetic resonance (MR) contrast ability (r2 = 271 mM−1 s−1) due to the high magnetization, the specific absorption rate (2518 W/g at 35 kA/m) and intrinsic loss power (6.5 nHm2/kg) of EMM are dozens of times higher than the clinically available iron oxide nanoagents (Feridex and Resovist), indicating the high heating conversion efficiency. Furthermore, this composite micelle with a flowable core exhibits a rapid response to magnetic hyperthermia, leading to an AMF-activated supersensitive drug release. With the high magnetic response, thermal sensitivity and magnetic targeting, this supersensitive ferrimagnetic nanocomposite realizes an above 70% tumor cell killing effect at an extremely low dosage (10 μg Fe/mL), and the tumors on mice are completely eliminated after the combined MHT–chemotherapy.  相似文献   

12.
Charmonium is a bound state of a charmed quark and a charmed antiquark, and a charmoniumlike state is a resonant structure that contains a charmed quark and antiquark pair but has properties that are incompatible with a conventional charmonium state. While operating at center-of-mass energies from 2 to 5 GeV, the BESIII experiment can access a wide mass range of charmonium and charmoniumlike states, and has contributed significantly in this field. We review BESIII results involving conventional charmonium states, including the first observation of the M1 transition ψ(2S) → γηc(2S) and the discovery of the ψ2(3823) state; and report on studies of charmoniumlike states, including the discoveries of the Zc(3900) and Zc(4020) tetraquark candidates, the resolution of the fine structure of the Y(4260) state, the discovery of the new production process e+e− → γX(3872) and the uncovering of strong evidence for the commonality among the X(3872), Y(4260) and Zc(3900) states. The prospects for further research at BESIII and proposed future facilities are also presented.  相似文献   

13.
Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the US and other parts of the world. There are conflicting reports on the serum levels of testosterone and 17β-estradiol (E2) in benign prostatic hyperplasia (BPH) and prostate cancer. This study was designed to evaluate the serum concentrations of these hormones in patients with these disorders. Serum levels of prostate specific antigen (PSA), total testosterone and estradiol were determined in 228 subjects comprising of 116 subjects with BPH, 62 subjects with prostate cancer (CaP) and 50 age-matched apparently healthy controls, using ELISA methods. PSA levels were significantly elevated (p < 0.05) in BPH subjects than controls, while there was no significant difference (p > 0.05) in testosterone and estradiol levels of these subjects. PSA and estradiol levels were significantly higher (p < 0.05) in CaP subjects than in controls, while there was no observed significant difference (p > 0.05) in testosterone levels. CaP subjects had significantly raised PSA, testosterone, and estradiol levels than BPH subjects. The mean molar ratio of testosterone: E2 was lowest among CaP patients (134:1) and highest among controls (166:1). Significant positive correlation between PSA and 17β-estradiol was observed in prostate disorders (BPH and CaP patients: r = 0.347; p = 0.000). Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = −0.221, p = 0.049) and control subjects (r = −0.490, p = 0.000). No significant correlation existed between testosterone and PSA in CaP patients (r = 0.051, p = 0.693). Correlations between age and estradiol in both BPH and CaP were not significant (p > 0.05). This study has shown that, there was a significant increase in serum estradiol in CaP subjects, while the testosterone levels in both BPH and CaP subjects were not different from those of controls.  相似文献   

14.
Sustained high levels of circulating catecholamines are reported to induce cardiotoxicity. Isoproterenol (ISP), a synthetic catecholamine has been widely employed to induce myocardial injury, though the role of inflammation and apoptosis is not well established. This study was designed to investigate the underlying mechanism of oxidative damage, inflammatory signaling, cell death in ISP induced myocardial infarction in rats. Wistar albino rats were divided in two groups: group I (sham control) and group II (ischemic control). ISP (85 mg/kg, s.c.) was administered at an interval of 24 h to group II for two consecutive days. On day third, after 48 h of the first injection of ISP, blood was collected from retro orbital plexus of rat eyes to estimate the biochemical parameters. Glutathione (GSH) and superoxide dismutase (SOD) were measured for antioxidant status. Similarly, malondialdehyde (MDA) was measured as an index of lipid peroxidation. Cardiac markers (SGOT, CK-MB, TropI and LDH) and pro-inflammatory cytokines (IL-6, CRP and TNF-α) were also estimated in ISP-induced rats. At the end of experiments animals were sacrificed for histopathological studies. GSH and SOD showed significant decrease after ISP challenge as compared to sham (control) group (p < 0.01) while MDA level, increased significantly (p < 0.01). ISP, also increased the level of cardiac markers and markers of inflammation significantly (p < 0.01), which was further verified by histopathological studies of the heart tissues. The study confirmed that ISP causes detrimental changes in the myocardium by altering cardiac and inflammatory markers, which leads to severe necrosis. The deleterious effects produced by ISP substantiate its suitability as a novel animal model for evaluation of cardioprotective agents/drugs.  相似文献   

15.
The majority of available cardiomyocyte markers are intercellular proteins, limiting our ability to enrich live cardiomyocytes from heterogeneous cell preparations in the absence of genetic labeling. Here, we describe enrichment of live cardiomyocytes from the hearts of adult mice in a label-free microfluidic approach. The separation device consisted of a vertical column (15 mm long, 700 μm diameter), placed between permanent magnets resulting in a field strength of 1.23 T. To concentrate the field at the column wall, the column was wrapped with 69 μm diameter nickel wire. Before passing the cells through the column, the cardiomyocytes in the cell suspension had been rendered paramagnetic by treatment of the adult mouse heart cell preparation with sodium nitrite (2.5 mM) for 20 min on ice. The cell suspension was loaded into the vertical column from the top and upon settling, the non-myocytes were removed by the upward flow from the column. The cardiomyocytes were then collected from the column by applying a higher flow rate (144 μl/min). We found that by applying a separation flow rate of 4.2 μl/min in the first step, we can enrich live adult cardiomyocytes to 93% ± 2% in a label-free manner. The cardiomyocytes maintained viability immediately after separation and upon 24 h in culture.  相似文献   

16.
The misfolding of amyloid-β (Aβ) peptides from the natural unfolded state to β-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer''s disease (AD). Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro. However, soluble Aβ oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so far. Here we show that Au23(CR)14 (a new Au nanocluster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfolded β-sheets. Furthermore, the cytotoxicity of Aβ40 fibrils when dissolved by Au23(CR)14 is fully abolished. More importantly, Au23(CR)14 is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice. In addition, Au23(CR)14 has good biocompatibility and infiltration ability across the blood–brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines.  相似文献   

17.
Recent years have witnessed a strong trend towards analysis of single-cells. To access and handle single-cells, many new tools are needed and have partly been developed. Here, we present an improved version of a single-cell printer which is able to deliver individual single cells and beads encapsulated in free-flying picoliter droplets at a single-bead efficiency of 96% and with a throughput of more than 10 beads per minute. By integration of acoustophoretic focusing, the cells could be focused in x and y direction. This way, the cells were lined-up in front of a 40 μm nozzle, where they were analyzed individually by an optical system prior to printing. In agreement with acoustic simulations, the focusing of 10 μm beads and Raji cells has been achieved with an efficiency of 99% (beads) and 86% (Raji cells) to a 40 μm wide center region in the 1 mm wide microfluidic channel. This enabled improved optical analysis and reduced bead losses. The loss of beads that ended up in the waste (because printing them as single beads arrangements could not be ensured) was reduced from 52% ± 6% to 28% ± 1%. The piezoelectric transducer employed for cell focusing could be positioned on an outer part of the device, which proves the acoustophoretic focusing to be versatile and adaptable.  相似文献   

18.
This article describes a fabrication process for the generation of a leak proof paper based microfluidic device and a new design strategy for convenient incorporation of externally prepared test zones. Briefly, a negative photolithographic method was used to prepare the device with a partial photoresist layer on the rear of the device to block the leakage of sample. Microscopy and Field Emission Scanning Electron Microscopy data validated the formation of the photoresist layer. The partial layer of photoresist on the device channel limits sample volume to 7 ± 0.2 μl as compared to devices without the partial photoresist layer which requires a larger sample volume of 10 ± 0.1 μl. The design prototype with a customized external test zone exploits the channel protrusions on the UV exposed photoresist treated paper to bridge the externally applied test zone to the sample and absorbent zones. The partially laminated device with an external test zone has a comparatively low wicking speed of 1.8 ± 0.9 mm/min compared to the completely laminated device with an inbuilt test zone (3.3 ± 1.2 mm/min) which extends the reaction time between the analyte and reagents. The efficacy of the prepared device was studied with colorimetric assays for the non-specific detection of protein by tetrabromophenol blue, acid/base with phenolphthalein indicator, and specific detection of proteins using the HRP-DAB chemistry. The prepared device has the potential for leak proof detection of analyte, requires low sample volume, involves reduced cost of production (∼$0.03, excluding reagent and lamination cost), and enables the integration of customized test zones.  相似文献   

19.
We developed a microfluidic device to culture cellular spheroids of controlled sizes and suitable for live cell imaging by selective plane illumination microscopy (SPIM). We cocultured human umbilical vein endothelial cells (HUVECs) within the spheroids formed by hepatocellular carcinoma cells, and studied the distributions of the HUVECs over time. We observed that the migration of HUVECs depended on the size of spheroids. In the spheroids of ∼200 μm diameters, HUVECs migrated outwards to the edges within 48 h; while in the spheroids of ∼250 μm diameters, there was no outward migration of the HUVECs up to 72 h. In addition, we studied the effects of pro-angiogenic factors, namely, vascular endothelial growth factor (VEGF) and fibroblast growth factor (β-FGF), on the migration of HUVECs in the carcinoma cell spheroid. The outward migration of HUVECs in 200 μm spheroids was hindered by the treatment with VEGF and β-FGF. Moreover, some of the HUVECs formed hollow lumen within 72 h under VEGF and β-FGF treatment. The combination of SPIM and microfluidic devices gives high resolution in both spatial and temporal domains. The observation of HUVECs in spheroids provides us insight on tumor vascularization, an ideal disease model for drug screening and fundamental studies.  相似文献   

20.
Cancer vaccines have exhibited immense potential in cancer treatment. Through activating the host''s immune system, vaccines stimulate extensive functional T cells to eliminate cancer. However, the therapeutic efficacy of cancer vaccines is limited by their inferior lymph node delivery and inadequate uptake of dendritic cells. Herein, we propose an in situ phase transitional strategy on vaccine manufacturing to maximally enhance lymph node drainage while ensuring adequate dendritic cell uptake. The phase transitional vaccines, with dynamic size modulation property, retain a small size (24.4 ± 3.1 nm) during lymph node draining then transform into larger particles (483.0 ± 41.6 nm) on-site by external signal input. Results show that this strategy induced rapid and robust immune response in a mouse melanoma tumor model. Furthermore, a stronger humoral immune response was observed in mice when immunized with MHC-II restricted antigen, which demonstrated that lymph node-targeted cancer vaccine delivery could be effectively manipulated through dynamic size modulation.  相似文献   

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