Electropolymerized neutral red, thionine, and aniline were used as part of hybrid nanocomposite conductive polymers, to create an amperometric reagent-less biosensor for glucose determination. The ...structure of the obtained polymers was studied using infrared (IR) spectroscopy and scanning electron microscopy. Electrochemical characteristics were studied by cyclic voltammetry and impedance spectroscopy. It was shown that, from the point of view of both the rate of electron transfer to the electrode, and the rate of interaction with the active center of glucose oxidase (GOx), the most promising is a new nanocomposite based on poly(neutral red) (pNR) and thermally expanded graphite (TEG). The sensor based on the created nanocomposite material is characterized by a sensitivity of 1000 ± 200 nA × dm
/mmol; the lower limit of the determined glucose concentrations is 0.006 mmol/L. The glucose biosensor based on this nanocomposite was characterized by a high correlation (R
= 0.9828) with the results of determining the glucose content in human blood using the standard method. Statistical analysis did not reveal any deviations of the results obtained using this biosensor and the reference method. Therefore, the developed biosensor can be used as an alternative to the standard analysis method and as a prototype for creating sensitive and accurate glucometers, as well as biosensors to assess other metabolites.
We have investigated the properties of a several bioelectrodes based on the immobilization of Gluconobacter oxydans bacterial cells on carbon superfine materials (CFMs). We use three types of CFMs ...(as adopted by the working classification CFM 1-3). All bioelectrodes was formed by covering the surface of the CFM via suspension of bacteria in a chitosan gel. The properties of samples are evaluated by measuring the physiological state of the bacteria immobilized: (a) recording the intensity of cellular respiration, (b) for measuring the charge transport characteristics of electrode (bioelectrocatalysis), and (c) by measuring the electrode impedance. Measurements (b) and (c) are made on two and three-electrode circuits in the oxidation of ethanol in the presence of 2,6-dichlorophenol electron transport mediator. For CFMs 1 and 2 the electron transport by the oxidation of the substrate is not registered, while for CFM 3 the current generation occurs. The resistance of CFM 3 bioelectrode is below the resistance of CFMs 1 and 2 both before (39.6 kΩ/cm2 for CFM 3, 630 Ω/cm2 for CFM 2, and 1329 Ω/cm2 for CFM 1) and after the addition of the substrate (2.9 kΩ/cm2 for CFM 3, 45 kΩ/cm2 for CFM 2, and 58 kΩ/cm2 for CFM 1). The bioelectrode made of CFM 3 has a capacitance of 196 μF/cm2-greater than two orders of magnitude of the bioelectrode capacity of CFMs 1 and 2 (0.51 and 0.58 μF/cm2, respectively). It is important to further study the properties of the CFM class of materials, which are promising as the basis of mechanically flexible electrodes with controlled parameters.
Inflammatory gastrointestinal (GI) diseases and malignancies are associated with growing morbidity and cancer-related mortality worldwide. GI tumor and inflammatory cells contain activated ...sphingolipid-metabolizing enzymes, including sphingosine kinase 1 (SphK1) and SphK2, that generate sphingosine-1-phosphate (S1P), a highly bioactive compound. Many inflammatory responses, including lymphocyte trafficking, are directed by circulatory S1P, present in high concentrations in both the plasma and the lymph of cancer patients. High fat and sugar diet, disbalanced intestinal flora, and obesity have recently been linked to activation of inflammation and SphK/S1P/S1P receptor (S1PR) signaling in various GI pathologies, including cancer. SphK1 overexpression and activation facilitate and enhance the development and progression of esophageal, gastric, and colon cancers. SphK/S1P axis, a mediator of inflammation in the tumor microenvironment, has recently been defined as a target for the treatment of GI disease states, including inflammatory bowel disease and colitis. Several SphK1 inhibitors and S1PR antagonists have been developed as novel anti-inflammatory and anticancer agents. In this review, we analyze the mechanisms of SphK/S1P signaling in GI tissues and critically appraise recent studies on the role of SphK/S1P/S1PR in inflammatory GI disorders and cancers. The potential role of SphK/S1PR inhibitors in the prevention and treatment of inflammation-mediated GI diseases, including GI cancer, is also evaluated.
Nanotechnology for Alzheimer Disease Leszek, Jerzy; Md Ashraf, Ghulam; Tse, Wai Hei ...
Current Alzheimer research,
01/2017, Letnik:
14, Številka:
11
Journal Article
Recenzirano
Alzheimer disease (AD) typically affects behavior, memory and thinking. The change in brain have been reported to begin approx. 10-20 years before the appearance of actual symptoms and diagnosis of ...AD. An early stage diagnosis and treatment of this lethal disease is the prime challenge, which is mainly halted by the lack of validated biomarkers.
Recent nanotechnological advancements have the potential to offer large scale effective diagnostic and therapeutic options. Targeted drug (e.g. Rivastigmine) delivery with the help of nanoparticles (NPs) in the range of 1-100 nm diameters can effectively cross the blood brain barrier with minimized side effects. Moreover, biocompatible nanomaterials with increased magnetic and optical properties can act as excellent alternative agents for an early diagnosis. With the high volume of research coming in support of the effective usage of NP based drug delivery in critical environment of CNS, it is quite likely that this approach can end up providing remarkable breakthroughs in early stage diagnosis and therapy of AD.
In the current review, we have presented a comprehensive outlook on the current challenges in diagnosis and therapy of AD, with an emphasis on the effective options provided by biocompatible NPs as imaging contrast agents and drug carriers.
Structural and mechanical characterization of electron beam additive manufactured stainless steel samples has been carried out. The XRD measured austenite and ferrite lattice parameters showed their ...sensitivity to the heat input value, which was related to the chromium atom redistribution. The ferrite content depended on the heat input too. Optimal heat input level has been detected, which allowed obtaining the tensile strength higher than that of the base stainless steel. Residual strain levels in the as-deposited metal and fusion line zone have been measured using the X-ray sin
2
ψ method. The highest tensile residual strain was determined in a fusion line zone between the first as-deposited layer and a substrate. The microstructure of the first fusion line zone contained deformation twins and entangled dislocations generated by plastic flow under thermal expansion-contraction cycles.
Rpn13 is a proteasome ubiquitin receptor that has emerged as a therapeutic target for human cancers. Its ubiquitin-binding activity is confined to an N-terminal Pru (pleckstrin-like receptor for ...ubiquitin) domain that also docks it into the proteasome, while its C-terminal DEUBAD (DEUBiquitinase ADaptor) domain recruits deubiquitinating enzyme Uch37 to the proteasome. Bis-benzylidine piperidone derivatives that were found to bind covalently to Rpn13 C88 caused the accumulation of polyubiquitinated proteins as well as ER stress-related apoptosis in various cancer cell lines, including bortezomib-resistant multiple myeloma lines. We find that a 38-amino acid peptide derived from the C-terminus of proteasome PC repeat protein hRpn2/PSMD1 binds to hRpn13 Pru domain with 12 nM affinity. By using NMR, we identify the hRpn13-interacting amino acids in this hRpn2 fragment, some of which are conserved among eukaryotes. Importantly, we find the hRpn2-derived peptide to immunoprecipitate endogenous Rpn13 from 293T cells, and to displace it from the proteasome. These findings indicate that this region of hRpn2 is the primary binding site for hRpn13 in the proteasome. Moreover, the hRpn2-derived peptide was no longer able to interact with endogenous hRpn13 when a strictly conserved phenylalanine (F948 in humans) was replaced with arginine or a stop codon, or when Y950 and I951 were substituted with aspartic acid. Finally, over-expression of the hRpn2-derived peptide leads to an increased presence of ubiquitinated proteins in 293T cells. We propose that this hRpn2-derived peptide could be used to develop peptide-based strategies that specifically target hRpn13 function in the proteasome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Extracellular vesicles in cancer nanomedicine Tarasov, Vadim V.; Svistunov, Andrey A.; Chubarev, Vladimir N. ...
Seminars in cancer biology,
February 2021, 2021-02-00, 20210201, Letnik:
69
Journal Article
Recenzirano
To date, a lot of nanotechnological optitions are available for targeted drug delivery. Extracellular vesicles (EVs) are membrane structures that cells use for storage, transport, communication, and ...signaling. Recent research has focused on EVs as natural nanoparticles for drug delivery. This review sheds light on the application of EVs in cancer therapy, such as targeted chemotherapy, gene therapy, and vaccine development. Aspects of biogenesis, isolation, targeting, and loading of EVs are discussed in detail.
Ras proteins have been reported to play key role in oncologic diseases. Ras proteins are associated with cellular membranes for its carcinogenic activities through post-translational modifications, ...including farnesylation. Farnesyltransferase is responsible for a type of Ras membrane targeting, which leads to cancer origin and progression. Inhibitors of farnesyltransferase have been developed as novel anticancer agents. In this review, the role of farnesyltransferase in cancer progression and development has been discussed. Further, the current status of development of farnesyltransferase inhibitors for cancer prevention and treatment has also been reviewed.
Radiocarbon-dated pollen and diatom records from Lake Kotokel in southern Siberia help to reconstruct the environmental history of the area since ~
47
kyr BP. Pollen spectra composition and ...reconstructed biome scores suggest predominance of a tundra–steppe vegetation and variable woody cover (5–20%) between ~
47 and 30
kyr BP, indicating generally a harsh and unstable climate during this interval, conventionally regarded as the interstadial within the last glacial. The short-term climate amelioration episodes in the glacial part of the records are marked by the peaks in taiga and corresponding minima in steppe biome scores and appear synchronously with the hemispheric temperature and precipitation changes recorded in the Greenland ice cores and Chinese stalagmites. Transition to full glacial environments occurred between 32 and 30
kyr BP. The interval at ~
30–24
kyr BP was probably the driest and coldest of the whole record, as indicated by highest scores for steppe biome, woody coverage <
5%, absence of diatoms and reduced size of the lake. A slight amelioration of the regional climate at ~
24–22
kyr BP was followed by a shorter than the previous and less pronounced deterioration phase. The late-glacial (~
17–11.65
kyr BP) is marked by a gradual increase in tree/shrub pollen percentages and re-appearance of diatoms. After 14.7
kyr BP the climate became warmer and wetter than ever during ~
47–14.7
kyr BP, resulting in the deepening of the lake and increase in the woody coverage to 20–30% ~
14.5–14
kyr and ~
13.3–12.8
kyr BP. These two intervals correspond to the Meiendorf and Allerød interstadials, which until now were interpreted as part of the undifferentiated Bølling/Allerød interstadial complex in the Lake Baikal region. The increase in tundra biome scores and pronounced change in the diatom composition allow (for the first time) the unambiguous identification of the Younger Dryas (YD) in the Lake Baikal region at ~
12.7–11.65
kyr BP, in agreement with the formal definition and dating of the YD based on the Greenland NGRIP ice core records. The maximal spread of the taiga communities in the region is associated with a warmer and wetter climate than the present prior to ~
7
kyr BP. This was followed by a wide spread of Scots pine, indicating the onset of modern environments.
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