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1.
Diabetes and tuberculosis are world’s most deadly epidemics. People suffering from diabetes are susceptible to tuberculosis. Molecular link between the two is largely unknown. It is known that Vitamin A receptor (RXR) heterodimerizes with Vitamin D receptor (VDR) and Peroxisome proliferator-activator receptor-γ (PPARγ) to regulate Tryptophan-aspartate containing coat protein (TACO) expression and fatty acid metabolism respectively, so it would be interesting to check the expression of these genes in diabetes mellitus (DM) patients which might explain the susceptibility of diabetics to tuberculosis. In this study, we checked the expression of RXR, VDR, TACO and Interferon-γ (IFNγ) genes in type-2 DM patients for understanding the link between the two diseases. We observed down regulation of RXR gene and corresponding up regulation of TACO gene expression. We have not observed significant change in expression of VDR and IFNγ genes in type-2 DM patients. Repression of RXR gene could hamper VDR-RXR heterodimer formation and thus would up regulate TACO gene expression which may predispose the type-2 DM patients to tuberculosis. Also, decrease in RXR-PPARγ heterodimer could be involved in DM.  相似文献   

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3.
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   

4.
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   

5.
The objective of this study is to induce experimental diabetes mellitus by streptozotocin in normal adult Wistar rats via comparison of changes in body weight, consumption of food, volume of water, urine and levels of glucose, insulin and C-peptide in serum, between normal and diabetic rats. Intra-venous injection of 60 mg/kg dose of streptozotocin in 250–300 g (75–90 days) adult Wistar rats makes pancreas swell and causes degeneration in Langerhans islet β-cells and induces experimental diabetes mellitus in 2–4 days. For a microscopic study of degeneration of Langerhans islet β-cells of diabetic rats, biopsy from pancreas tissue of diabetic and normal rats, staining and comparison between them, were done. In this process, after collagenase digestion of pancreas, islets were isolated, dissociated and identified by dithizone method and then with enzymatic procedure by DNase and trypsin, the islet cells changed into single cells and β-cells were identified by immune fluorescence method and then assayed by flow-cytometer. Donor tissue in each step of work was prepared from 38 adult male Wistar rats weighted 250–300 g (75–90 days). Transplantation was performed in rats after 2–4 weeks of diabetes induction. In this study, the levels of insulin, C-peptide and glucose in diabetic rats reached to normal range as compared to un-diabetic rats in 20 days after transplantation of islet cells. Transplantation was performed under the cortex of testis as immunoisolated place for islet cells transplantation.  相似文献   

6.
Insulin injection is the main way to combat against insulin-dependent diabetes mellitus effects. Today in some laboratories in the world, the investigators are trying to find some treatments for this disease with insulin-secreting pancreatic islet cells transplantation. Donor tissue in each step of work was prepared from 36 adult male wistar Rats weighted 250–300 grams (75–90 days). Transplantation was done in rats after 2–4 weeks induction of diabetes with 60mg/kg of streptozotocin injection by intravenous method. Encapsulation of pancreatic islet cells allows for transplantation in the absence of immunosuppression. This technique that is called “immunoisolation” is based on the principle that transplanted tissue is protected for the host immune system by an artificial or natural membrane. In this study, the levels of insulin, C-peptide and glucose in diabetic rats have been reached to normal range as compared to un-diabetic rats in 20 days after transplantation of islet cells, so that testis is immunoisolated place for islet cells transplantation. Inside the testis subcutaneously and intrapretoneally implantation of pure islet cells graft, that is a natural immunoisolation method, rapidly and permanently normalized the diabetic state of streptozocin-administered animals.  相似文献   

7.
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   

8.
Label-free isolation of single cells is essential for the growing field of single-cell analysis. Here, we present a device which prints single living cells encapsulated in free-flying picoliter droplets. It combines inkjet printing and impedance flow cytometry. Droplet volume can be controlled in the range of 500 pl–800 pl by piezo actuator displacement. Two sets of parallel facing electrodes in a 50 μm × 55 μm channel are applied to measure the presence and velocity of a single cell in real-time. Polystyrene beads with <5% variation in diameter generated signal variations of 12%–17% coefficients of variation. Single bead efficiency (i.e., printing events with single beads vs. total number of printing events) was 73% ± 11% at a throughput of approximately 9 events/min. Viability of printed HeLa cells and human primary fibroblasts was demonstrated by culturing cells for at least eight days.  相似文献   

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10.
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   

11.
Nonfullerene acceptors are being investigated for use in polymer solar cells (PSCs), with their advantages of extending the absorption range, reducing the energy loss and therefore enhancing the power conversion efficiency (PCE). However, to further boost the PCE, mobilities of these nonfullerene acceptors should be improved. For nonfullerene acceptors, the π–π stacking distance between cofacially stacked molecules significantly affects their mobility. Here, we demonstrate a strategy to increase the mobility of heteroheptacene-based nonfullerene acceptors by reducing their π–π stacking distances via control over the bulkiness of lateral side chains. Incorporation of 2-butyloctyl substituents into the nonfullerene acceptor (M36) leads to an increased mobility with a reduced π–π stacking distance of 3.45 Å. Consequently, M36 affords an enhanced PCE of 16%, which is the highest among all acceptor-donor-acceptor-type nonfullerene acceptors to date. This strategy of control over the bulkiness of side chains on nonfullerene acceptors should aid the development of more efficient PSCs.  相似文献   

12.
Although digital detection of nucleic acids has been achieved by amplification of single templates in uniform microfluidic droplets and widely used for genetic analysis, droplet-based digital detection of proteins has rarely been reported, largely due to the lack of an efficient target amplification method for protein in droplets. Here, we report a key step towards digital detection of proteins using a highly parallel microfluidic droplet approach for single enzyme molecule detection in picoliter droplets via enzyme catalyzed signal amplification. An integrated microfluidic chip was designed for high throughput uniform droplet generation, monolayer droplet collection, incubation, detection, and release. Single β-galatosidase (β-Gal) molecules and the fluorogenic substrate fluorescein di-β-D-galactopyranoside were injected from two separated inlets to form uniform 20 μm droplets in fluorinated oil at a frequency of 6.6 kHz. About 200 000 droplets were captured as a monolayer in a capture well on-chip for subsequent imaging detection. A series of β-Gal solutions at different concentrations were analyzed at the single-molecule level. With no enzyme present, no droplets were found to fluoresce, while brightly fluorescent droplets were observed under single-enzyme molecule conditions. Droplet fluorescence intensity distribution analysis showed that the distribution of enzyme molecules under single-molecule conditions matched well with theoretical prediction, further proving the feasibility of detecting single enzyme molecules in emulsion droplets. Moreover, the population of fluorescent droplets increased as the β-Gal concentration increased. Based on a digital counting method, the measured concentrations of the enzyme were found to match well with input enzyme concentration, establishing the accuracy of the digital detection method for the quantification of β-Gal enzyme molecules. The capability of highly parallel detection of single enzyme molecules in uniform picoliter droplets paves the way to microdroplet based digital detection of proteins.  相似文献   

13.
Induction of diabetes by Streptozotocin in rats   总被引：1，自引：0，他引：1  
The objective of this study is to induce experimental diabetes mellitus by Streptozotocin in normal adult Wistar rats via comparison of changes in body weight, consumption of food and water, volume of urine and levels of glucose, insulin and C-peptide in serum, between normal and diabetic rats. Intra-venous injection of 60mg/kg dose of Streptozotocin in adult wistar rats, makes pancreas swell and at last causes degeneration in Langerhans islet beta cells and induces experimental diabetes mellitus in the 2–4 days. Induction of experimental diabetes mellitus is indeed the first step in the plan of purification of pancreatic Langerhans islet cells of normal rats for transplanting under the testis subcutaneous of experimentally induced diabetic rats. Streptozotocin induces one type of diabetes which is similar to diabetes mellitus with non-ketosis hyperglycemia in some animal species. For induction of experimental diabetes in male adult rats weighted 250–300 grams (75–90 days), 60mg/kg of Streptozotocin was injected intravenously. Three days after degeneration of beta cells, diabetes was induced in all animals. The diabetic and normal animals were kept in the metabolic cages separately and their body weight, consumption of food and water, urine volume, the levels of serum glucose, insulin and C-peptide quantities in all animals were measured and then these quantities were compared. For a microscopic study of degeneration of Langerhans islet beta cells of diabetic rats, sampling from pancreas tissue of diabetic and normal rats, staining and comparison between them, were done. Induction of diabetes with Streptozotocin decreases Nicotinamide-adenine dinucleotide (NAD) in pancreas islet beta cells and causes histopathological effects in beta cells which probably intermediates induction of diabetes. In this study, we used Streptozotocin for our experiments in induction of experimental diabetes mellitus. After Induction of diabetes, consumption of food and water, volume of urine and glucose increased in the diabetic animals in comparison with normal animals, but the weight of body and the volume of insulin and C-peptide decreased in the diabetic animals. Sampling and staining of pancreas tissue of diabetic and normal rats showed that the Langerhans islet beta cells of diabetic rats have been clearly degenerated. In three days, Streptozotocin makes pancreas swell and at last causes degeneration in Langerhans islet beta cells and induces experimental diabetes. It also changes normal metabolism in diabetic rats in comparison with normal rats. Consumption of water and food, volume of urine, serum glucose increases in diabetic animals in comparison with normal rats but the levels of serum insulin, C-peptide and body weight decreases.  相似文献   

14.
Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a substitution of Phe for Leu at position 91 of α1-globin chain, originally described in individual of unknown ethnic background. This article addresses the interaction of Hb Grey Lynn with a non-deletional α+-thalassemia found in Thailand, a hitherto un-described condition. The proband was adult Thai woman referred for investigation of mild anemia with Hb 90 g/L. Hb analyses using low pressure liquid chromatography raised a suspicion of abnormal Hb presence, which was failed to demonstrate by cellulose acetate electrophoresis and capillary electrophoresis. DNA sequencing identified a CTT (Leu) to TTT (Phe) mutation at codon 91 corresponding to the Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1) on α1-globin gene and a C deletion between codons 36 and 37 on α2-globin gene causing α+-thalassemia. As compared to those observed in a compound heterozygote for Hb Grey Lynn / α0-thalassemia reported previously, higher MCV (81.7 fL) and MCH (26.3 pg) values with a lower level of Hb Grey Lynn (19.7%) were observed in the proband. The normochromic normocytic anemia observed could be due to the interaction of Hb Grey Lynn with α+-thalassemia. The two mutations could be identified using PCR-RFLP and allele-specific PCR assays developed.  相似文献   

15.
Methods for assaying lysosomal diseases in dried blood samples are very useful today due to its several advantages related to the stability of samples, its transportation, handled and analysis, and its potential use for newborn screening compared to traditional methods in leucocytes samples. For this reason, it is important to validate these assays before being used in routine laboratory. Because of different in biological markers based on ethnicity, we aimed this study to validation a DBS-based fluorometric assay for measurement of α-l-Iduronidase activity for diagnosis of MPS I patients in Iran. DBS samples were collected from 15 MPS I patients and 60 healthy age matched subjects. Diagnostic value, biological variance and α-l-Iduronidase activity were determined. DBS α-l-Iduronidase activity was significantly higher in male subjects than in female group. Using a cut-off level of 1.08 µmol/spot 20 h, sensitivity and specificity were 100 and 98 %. The linearity of test was proved and we showed that within-run and between run precision were 5.6 and 14.66 %. Measurement of α-l-Iduronidase activity in DBS samples is an accurate test for diagnosis of MPS I and because of its rapid shipping and simplicity to keeping, DBS-based enzyme activity could be considered as a useful diagnostic tool in this disease.  相似文献   

16.
Geophysical observations suggest that the transition zone is wet locally. Continental and oceanic sediment components together with the basaltic and peridotitic components might be transported and accumulated in the transition zone. Low-velocity anomalies at the upper mantle–transition zone boundary might be caused by the existence of dense hydrous magmas. Water can be carried farther into the lower mantle by the slabs. The anomalous Q and shear wave regions locating at the uppermost part of the lower mantle could be caused by the existence of fluid or wet magmas in this region because of the water-solubility contrast between the minerals in the transition zone and those in the lower mantle. δ-H solid solution AlO2H–MgSiO4H2 carries water into the lower mantle. Hydrogen-bond symmetrization exists in high-pressure hydrous phases and thus they are stable at the high pressures of the lower mantle. Thus, the δ-H solid solution in subducting slabs carries water farther into the bottom of the lower mantle. Pyrite FeO2Hx is formed due to a reaction between the core and hydrated slabs. This phase could be a candidate for the anomalous regions at the core–mantle boundary.  相似文献   

17.
Although β-Fe2O3 has a high theoretical solar-to-hydrogen efficiency because of its narrow band gap, the study of β-Fe2O3 photoanodes for water splitting is elusive as a result of their metastable nature. Raman identification of β-Fe2O3 is theoretically and experimentally investigated in this study for the first time, thus clarifying the debate about its Raman spectrum in the literature. Phase transformation of β-Fe2O3 to α-Fe2O3 was found to potentially take place under laser and electron irradiation as well as annealing. Herein, phase transformation of β-Fe2O3 to α-Fe2O3 was inhibited by introduction of Zr doping, and β-Fe2O3 was found to withstand a higher annealing temperature without any phase transformation. The solar water splitting photocurrent of the Zr-doped β-Fe2O3 photoanode was increased by 500% compared to that of the pure β-Fe2O3 photoanode. Additionally, Zr-doped β-Fe2O3 exhibited very good stability during the process of solar water splitting. These results indicate that by improving its thermal stability, metastable β-Fe2O3 film is a promising photoanode for solar water splitting.  相似文献   

18.
糖尿病的治疗目前集中于细胞的替代疗法。供体器官的短缺激发了对如何产生beta细胞的研究。目前，胰岛的扩增，胰岛的异种移植，人胰岛细胞系的开发，干细胞的分化都是热点。干细胞的治疗包括胚胎干细胞和成体干细胞。本文讨论干细胞向胰腺beta细胞分化的各种可能性。  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   

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