75 research outputs found
The Role of Dimethyl Sulfoxide (DMSO) in Gene Expression Modulation and Glycosaminoglycan Metabolism in Lysosomal Storage Disorders on an Example of Mucopolysaccharidosis
Obstacles to effective therapies for mucopolysaccharidoses (MPSs) determine the need
for continuous studies in order to enhance therapeutic strategies. Dimethyl sulfoxide (DMSO) is
frequently utilised as a solvent in biological studies, and as a vehicle for drug therapy and the in vivo
administration of water-insoluble substances. In the light of the uncertainty on the mechanisms of
DMSO impact on metabolism of glycosaminoglycans (GAGs) pathologically accumulated in MPSs,
in this work, we made an attempt to investigate and resolve the question of the nature of GAG
level modulation by DMSO, the isoflavone genistein solvent employed previously by our group in
MPS treatment. In this work, we first found the cytotoxic effect of DMSO on human fibroblasts at
concentrations above 3%. Also, our results displayed the potential role of DMSO in the regulation of
biological processes at the transcriptional level, then demonstrated a moderate impact of the solvent
on GAG synthesis. Interestingly, alterations of lysosomal ultrastructure upon DMSO treatment were
visible. As there is growing evidence in the literature that DMSO can affect cellular pathways leading
to numerous changes, it is important to expand our knowledge concerning this issue
Genistein modulates gene activity in psoriatic patients
Despite the impressive advancements in the treatment
of psoriasis over the past two decades, there is still a
need for further improvement. As previously shown in
the literature, genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)
chromen-4-one), naturally occurring plant compound
displays multidirectional action, also in relation to alleviating
psoriasis symptoms. In this work we focused our
attention on genistein impact on expression of genes
when treating moderate-to-severe psoriasis patients.
Testing the effects of this isoflavone on transcript levels
in both skin specimens and peripheral blood cells of four
psoriatic subjects, we found that this compound modulated
activities of genes coding for anti-psoriatic members
and anti-inflammatory mediators of inflammation.
It impairs the activity of certain genes which are overexpressed
in psoriasis, while stimulating the expression of
other transcripts that are repressed in dermatosis
Oxidative stress as an important contributor to the pathogenesis of psoriasis
This review discusses how oxidative stress (OS), an imbalance between oxidants and antioxidants in favor of the oxidants, increased production of reactive oxygen species (ROS)/reactive nitrogen species (RNS), and decreased concentration/activity of antioxidants affect the pathogenesis or cause the enhancement of psoriasis (Ps). Here, we also consider how ROS/RNS-induced stress modulates the activity of transcriptional factors and regulates numerous protein kinase cascades that participate in the regulation of crosstalk between autophagy, apoptosis, and regeneration. Answers to these questions will likely uncover novel strategies for the treatment of Ps. Action in the field will avoid destructive effects of ROS/RNS-mediated OS resulting in cellular dysfunction and cell death. The combination of the fragmentary information on the role of OS can provide evidence to extend the full picture of Ps
Critical factors for the performance of chip array-based electrical detection of DNA for analysis of pathogenic bacteria
Different factors influencing chip array-based electrical detection of DNA for analysis of pathogenic bacteria were examined. Both rehydration of capture probe layer of functionalized chip arrays and efficient hybridization of targets irrespective of their length resulted in signal enhancement when high-ionic phosphate-buffered saline (i.e., 600 mM sodium chloride and 40 mM disodium hydrogen phosphate) was used. Similarly, placement of two adjacent capture and detection probe-binding sites at a terminal part of the target strand resulted in significant signal increase. Moreover, 10-min ultrasonic fragmentation of targets amplified the signals up to twofold for longer DNA strands (i.e., >300 bp). No obvious effects on signals were visible for shorter than 400-bp PCR amplicons subjected to ultrasonication. For DNA strands of all sizes, more than 10 min ultrasonication diminished the specific electrical responses. Our results also demonstrate that target analytes are detected with discrimination against mismatches even for single nucleotide sequence alteration. The mismatch detection appeared in order of ease of recognition as follows: triple random > quintuple middle > triple middle > single middle mismatch. Among the three variants of one-base mismatches, a sequence variation was most remarkable for adenine. On the other hand, no benefits in assay sensitivity were recognized by the use of longer capture probe linkers as the 6-C linker
Effect of silicone on the collagen fibrillogenesis and stability
Collagen, the most abundant protein in mammals, is able to form fibrils, which have central role in tissue repair, fibrosis, and tumor invasion. As a component of skin, tendons, and cartilages, this protein contacts with any implanted materials. An inherent problem associated with implanted prostheses is their propensity to be coated with host proteins shortly after implantation. Also, silicone implants undergoing relatively long periods of contact with blood can lead to formation of thrombi and emboli. In this paper, we demonstrate the existence of interactions between siloxanes and collagen. Low-molecular-weight cyclic siloxane (hexamethylcyclotrisiloxaneâD3) and polydimethylsiloxanes (PDMS) forming linear chains, ranging in viscosity from 20 to 12,000 cSt, were analyzed. We show that D3 as well as short-chain PDMS interact with collagen, resulting in a decrease in fibrillogenesis. However, loss of collagen native structure does not occur because of these interactions. Rather, collagen seems to be sequestered in its native form in an interlayer formed by collagenâsiloxane complexes. On the other hand, silicone molecules with longer chains (i.e., PDMS with viscosity of 1000 and 12,000 cSt, the highest viscosity analyzed here) demonstrate little interaction with this protein and do not seem to affect collagen activity
Lipophagy and lipolysis status in lipid storage and lipid metabolism diseases
This review discusses how lipophagy and cytosolic lipolysis degrade cellular lipids, as well as how these pathway ys communicate, how they affect lipid metabolism and energy homeostasis in cells and how their dysfunction affects the pathogenesis of lipid storage and lipid metabolism diseases. Answers to these questions will likely uncover novel strategies for the treatment of aforementioned human diseases, but, above all, will avoid destructive effects of high concentrations of lipidsâreferred to as lipotoxicityâresulting in cellular dysfunction and cell death
Synthetic genistein derivatives as modulators of glycosaminoglycan synthesis
Background: Mucopolysaccharidoses (MPS) are severe metabolic disorders caused by
26 accumulation of undegraded glycosaminoglycans (GAGs) in lysosomes due to defects in certain
27 lysosomal hydrolases. Substrate reduction therapy (SRT) has been proposed as one of potential
28 treatment procedures of MPS. Importantly, small molecules used in such a therapy might
29 potentially cross the blood-brain barrier (BBB) and improve neurological status of patients, as
30 reported for a natural isoflavone, 5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one,
31 also known as genistein. Although genistein is able to cross BBB to some extent, its delivery to
32 the central nervous system is still relatively poor (below 10% efficiency). Thus, we aimed to
33 develop a set of synthetically modified genistein molecules and characterize physicochemical as
34 well as biological properties of these compounds. Methods: Following parameters were
35 determined for the tested synthetic derivatives of genistein: cytotoxicity, effects on cell
36 proliferation, kinetics of GAG synthesis, effects on epidermal growth factor (EGF) receptorâs
37 tyrosine kinase activity, effects on lysosomal storage, potential ability to cross BBB. Results: We
38 observed that some synthetic derivatives inhibited GAG synthesis similarly to, or more
39 efficiently than, genistein and were able to reduce lysosomal storage in MPS III fibroblasts. The
40 tested compounds were generally of low cytotoxicity and had minor effects on cell proliferation.
41 Moreover, synthetic derivatives of genistein revealed higher lipophilicity (assessed in silico) than
42 the natural isoflavone. Conclusion: Some compounds tested in this study might be promising
43 candidates for further studies on therapeutic agents in MPS types with neurological symptoms
Confirmative electric DNA array-based test for food poisoning Bacillus cereus
Detection of the full set of toxin encoding genes involved in gastrointestinal diseases caused by B. cereus was performed. Eight genes determining the B. cereus pathogenicity, which results in diarrhea or emesis, were simultaneously evaluated on a 16-position electrical chip microarray. The DNA analyte preparation procedure comprising first 5 min of ultrasonic treatment, DNA extraction, and afterwards an additional 10 min sonication, was established as the most effective way of sample processing. No DNA amplification step prior to the analysis was included. The programmed assay was carried out within 30 min, once theDNAanalyte from 108 bacterial cells, corresponding to one agar colony, was subjected to the assay. In general, this work represents a mature analytical way for DNA review. It can be used under conditions that require almost immediate results
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